October 21, 2013 - TransCelerate - Pharmaceutical … Portola; Receptos; Tekmira; XenoPort, et...

Cover Story

TransCelerate Up to Speed — Theprecompetitive biopharma consortiumhas hit key milestones on its initiatives toincrease the speed and quality of clinicaltrials, enable head-to-head studies andimprove comparability of data.

Strategy

MedImmune’s Warheads — Astra-Zeneca’s latest duo of deals, with Spirogenand ADC Therapeutics, gives the pharma’sMedImmune unit all the tools it needs tobuild out in the antibody-drug conjugatespace./A6

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By Tim FulmerSenior Writer

In its first year, the industry’s precom-petitive experiment TransCelerateBioPharma Inc. has hit key milestonesin all five of its initial projects aimed atimproving the speed and quality of clinicaltrials. The biopharma consortium also hasincreased its membership to 18 compa-nies from 10, and could announce its nextset of projects this year.

TransCelerate was founded last yearafter a group of pharma R&D heads con-cluded that precompetitive collabora-tion was best way to solve clinical trialbottlenecks. The hope was that the re-sulting efficiencies would speed up drugdevelopment and lower costs for allmembers.

So far, TransCelerate has launched anetwork to facilitate member companyaccess to comparator drugs for clinicaltrials, which should ensure rapid availabil-ity of high-quality drugs for head-to-headstudies.

The consortium also has designed andis preparing to launch an online portalthat will allow companies and clinical trialinvestigators to exchange trial data andprotocols through a single platform, po-

Product Discovery & Development

TransCelerate up to speed

BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS OCTOBER 21, 2013 PAGE A2 OF 22

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Product Discovery & Development,from previous page

This Week in SciBX

Revving up cGAS — UT Southwestern researchers have confirmed the role of cyclicGMP-AMP signaling in the innate immune system, making a case for developing adjuvantsthat agonize the pathway or antagonists of the pathway to treat autoimmune conditions.SciBX Table of Contents, A4.

tentially speeding up investigator and siteselection.

TransCelerate has also published whitepapers and guidelines on trial and datastandards, most of which are available tomembers and non-members alike via theconsortium’s website (see Featured Links,A22).

A white paper on standards for risk-based monitoring (RBM) of clinical trialsshould help companies direct resourcesto the prospective identification and miti-gation of risks to patient safety and dataquality, while promoting centralized moni-toring of the most important parts of agiven trial in place of cumbersome com-prehensive on-site visits.

The remaining initiatives on theconsortium’s initial list include clinicaltrial site qualification and good clinicalpractice (GCP) training, and clinical trialdata standards. The group has publishedminimum criteria for GCP training of clini-cal site investigators and staff, and haspublished standards for collecting andsharing efficacy data from asthma trials.

“A major advance by itself is just thefact that the pharmas taking part inTransCelerate successfully worked togetherin the first place,” CEO Dalvir Gill toldBioCentury.

“We’ve shown that we’re not gettingbogged down in excessive bureaucracyand instead have created a functioninginfrastructure like any working company.On top of that, we’ve generated concreteoutputs for all of our initiatives,” he said.

TransCelerate hasn’t said what it wantsto tackle next, or whether its projects willget more challenging. When it was foundedin August 2012, the members prioritizedprojects they considered most amenableto short-term fixes (see BioCentury, Oct. 1,2012).

NetworkingIn August, TransCelerate announced

it had reached a key milestone by settingup a network for obtaining comparator

drugs and co-therapies for use in clinicaltrials and completing the first deal underthe network. The network allows partici-pating member companies to purchaseapproved drugs directly from each otherfor clinical trials, ensuring an adequateand timely supply.

Terry Walsh, head of the comparatornetwork initiative at TransCelerate andhead of comparator strategy and planningat GlaxoSmithKline plc, told BioCen-tury it was rare for companies to getcomparator drugs directly from each oth-er except under one-off agreements.

Instead, he said, companies frequentlyturn to wholesalers and third-party dis-tributors to purchase the needed drugs onthe open market. According to TransCel-erate, this practice is inefficient, leads touncertainty about obtaining the necessaryquantity of drugs and can result in supplyinterruptions.

In July, several members of TransCel-erate signed a master service agreementthat commits them to offer each other asecure and rapid supply of drugs for clin-ical trials. Walsh declined to say whichcompanies had signed the agreement.

Cutting out wholesalers could savecost and time, Walsh said, “and we shouldget a better idea of how those savingsmaterialize moving forward.”

However, reducing costs was neverthe driving objective. “Ensuring qualityproduct for trials has been the main goal,”he said.

“Companies in the network cannotcherry-pick drugs to exclude from theagreement,” Walsh noted. “If you’re amember of the network, your entire port-

folio of marketed drugs is made availableto other member companies for use ascomparators in their clinical trials.”

The network ensures that drugs comewith stability and regulatory data thatpromote correct storage and handlingprocesses, reducing waste. It also providesdetailed demand data to the supplyingcompany, which can help improve supplychain planning and avoid shortages.

Discussions are ongoing about widen-ing the scope of the agreement to includecompounds that are still in development,Walsh said.

Milestones for 2014 include standard-izing methods for bulk commercial supplyof drugs directly from companies in thenetwork rather than supply based on smallallotments in bottles and vials, as well asdeveloping methods for the manufactureand supply of placebos.

Through the portalAnother major milestone during

TransCelerate’s first year was the designof a single online platform that will allowcompanies and investigators to share dataand documents associated with clinicaltrials. The fully tested first release of theplatform will go live next year.

A cross-industry portal will make iteasier for companies and investigators todeliver content and services to one an-other than if they dealt with one anotherthrough their individual sites, Jacalyn Kentof Eli Lilly and Co. told BioCentury.

Kent is director of clinical develop-ment information and optimization at Lilly.

The initiative originally focused ondeveloping a simple log-on interface foreach investigator and company, but hasexpanded to include regulators and toallow all three stakeholder groups to shareclinical trial data and protocols.

“What was initially envisioned as sim-ply a common computer interface or log-on portal for drug companies and clinicaltrial investigators has, over the course ofthe year, transitioned into less of a portaland into more of an overarching IT plat-form for TransCelerate companies, inves-tigators and regulators to exchange avariety of clinical trial data,” Kent said.

The platform creates a one-stop shopfor information on investigators and com-panies instead of requiring them to usemultiple systems to get the same informa-tion.

For companies, centralizing informa-tion on investigators — such as qualifica-tions, relevant experience and contact

“We’ve shown that we’renot getting bogged down inexcessive bureaucracy and

instead have created afunctioning infrastructure

like any working company.”

Dalvir Gill, TransCelerate


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information — will speed up the process of identifying appropri-ate investigators and staff for trials, said Kent.

Investigators will be able to access an “integrated to-do list”that tracks all of their current activity in any trials being run bymember companies.

The platform has common file exchange capabilities forregulatory documents, GCP training modules and other elec-tronic publications.

Firewalls allow companies to control what data are madeaccessible to whom.

“Now that we’ve designed it, we’re in the process of selectinga vendor for the software interface of the portal as well as a placewhere we can physically house it. After we make those selectionsby the first quarter of next year, we will then release the portalat an undisclosed time later in 2014,” said Kent.

She said TransCelerate also expects to release updatedversions of the platform in 2015.

Risk-based monitoringThe risk-based monitoring (RBM) initiative hit its two main

milestones. One was to publish a white paper on an RBMmethodology; the other was starting the first pilot study of themethodology.

The RBM approach should enable sponsors to focus re-sources on activities that will have the greatest impact on patientsafety and data integrity in clinical trials.

FDA regulations require sponsors to monitor the conduct ofclinical trials to ensure patient safety and data integrity. Accord-ing to the agency, monitoring includes communicating with theclinical investigator and study site staff; reviewing site processes,procedures and records; and verifying the accuracy of data

submitted to the sponsor.The regulations do not specify how sponsors should accom-

plish this.According to a survey conducted by FDA’s Clinical Trials

Transformation Initiative (CTTI), the predominant method forcompanies running “major efficacy” trials has been on-site visitsconducted every four to eight weeks to evaluate study conductand review data for each enrolled subject.

According to the survey, non-industry sponsors such asacademic centers and government agencies typically monitortrial sites less frequently.

If patient safety and/or data integrity issues are identifiedduring on-site visits, the monitor may propose ways to addressthe risks while the trial is ongoing.

Instead of relying on comprehensive on-site visits, risk-basedmonitoring focuses on sites, processes and data elements that aremost crucial to a given study or that present the greatest risks topatient safety or data integrity.

The concept is not new. ICH guidelines published in 1996and 2011 advise sponsors to consider the objective, design,complexity, size, and endpoints of a trial to determine the extentand nature of monitoring that is necessary.

In August, FDA released guidance that said risk-based ap-proaches “are more likely than routine visits to all clinical sitesand 100% data verification to ensure subject protection andoverall study quality.”

The guidance notes that some aspects of monitoring may beadequately or even better served by centralized, or remote,monitoring procedures enabled by technologies such as elec-tronic data capture and electronic records.

“We expect that the pharmaceutical and device industrieswill, for the foreseeable future, continue to use some amount ofon-site monitoring, but we anticipate decreased use of on-sitemonitoring with evolving monitoring methods and technological


TransCelerate’s progress reportAbout a year after its founding, the not-for-profit pharma consortium TransCelerate Biopharma Inc. has not only reached the first-year milestonesit set for its five clinical trial initiatives, it also has additional milestones in place for 2014 and 2015. Over the same period, TransCelerate has expandedfrom 10 pharma members to 18. Darker shading below denotes milestones that have been met.

Initiatives Milestones 2012 2013 2014 2015

Standards for risk-based Publish white paper describing RBM methodology Junemonitoring of clinical Start and run first pilot studies of RBM methodology 2013trials (RBM) Start additional pilot studies 2014

Standards for clinical site Standardize good clinical practices (GCP) training protocols Junequalification and training Design and implement investigator curriculum vitae (CV) template June(SQT) Design and implement clinical site profile questionnaire form June

Design and implement additional forms and training guidance 2014

Standards for clinical Publish standards for first disease area - asthma Septefficacy data Select metadata repository for standards June

Put repository online 1Q14Publish standards for other disease areas 2014

Common investigator and Design version 1 of platform/portal 2013company site portal Select software and hardware vendors for platform 1Q14

Release version 1 of platform 2014Release subsequent versions of platform 2015

Comparator drug network Master service agreement (MSA) signed by TransCelerate members AugBulk commercial supply of drugs 2014Manufacture placebo versions of comparator drugs 2014


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capabilities,” the guidance said.While FDA’s guidance describes principles for risk-based

monitoring, the TransCelerate position paper provides moredetailed recommendations for creating and implementing a risk-based monitoring plan, such as recommending tools and meth-ods for identifying, analyzing and monitoring risks, includingdetermining what triggers should result in increased monitoringactivity.

TransCelerate’s RBM methodology recommends targetingon-site monitoring to activities that cannot be assessed remotely.

After TransCelerate published its RBM approach, “we thenbegan testing that methodology in pilot studies of clinical trialprotocols,” said initiative lead Rehbar Tayyabkhan.

Tayyabkhan is executive director of global clinical develop-ment at Bristol-Myers Squibb Co.

In the pilot, TransCelerate members submitted risk-monitor-ing plans and protocols for trials to FDA to solicit feedback onhow well the RBM approach could identify risks.

So far, nine plans from seven TransCelerate member compa-nies have been submitted to FDA for feedback, Tayyabkhan said.

Additional publications are planned for 2014, includinglessons learned from the pilot studies, he said.

Data standardsTransCelerate’s clinical data standards initiative aims to

identify the most commonly collected data in a specific diseasearea and develop a universal terminology for describing andcategorizing those data in study reports. Doing so shouldfacilitate comparison of clinical data for different products.

In September, TransCelerate published a draft documentdescribing standards for collecting and reporting data fromclinical trials in adult asthma.

For each disease included in the initiative, TransCelerateforms a project team consisting of member companies that workin that particular disease. The team then develops standards onhow efficacy data are collected, transmitted and shared betweencompanies, CROs, clinicians and regulators.

The standards do not prescribe what data should be collectedfor a given disease. “It does state that if you collect such-and-suchdata, these are the agreed upon standards for collecting, report-ing and sharing it,” said David Jordan, who leads the initiative.

The clinical data standards initiative “addresses the underly-ing issue of how to compare clinical trial efficacy data acrosscompanies and products,” he said.

Jordan was divisional VP of statistics and data management atAbbott Laboratories and is now a consultant to globalpharmaceutical R&D at AbbVie Inc.

The asthma draft describes how to categorize and recordmedical history data in case study reports, how to conductcommonly used tests including peak flow, spirometry and airwayresponsiveness, and how to record the resulting data.

It also discusses methods for collecting specimens that can beused to measure biomarkers and provides examples for report-ing biomarker results in study reports.

The document describes various methods of assessing andrecording symptoms and measures of quality of life.

It also describes how to measure and record common adverseevents that are of special interest for asthma, such as respiratory


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ANALYSIS

COVER STORYRevving up cGASUniversity of Texas Southwestern Medical Center re-searchers have confirmed the role of cyclic GMP-AMPsignaling in the innate immune system, making a case fordeveloping adjuvants that agonize the pathway or antago-nists of the pathway to treat autoimmune conditions.

TRANSLATIONAL NOTESClinical takeoff for new epigenetic targetsNext year is expected to be a banner year for next-generation epigenetics companies, with key clinical dataexpected for next-generation drugs and first-generationcandidates. Big biotech and pharma companies that carvedup the space in recent years might have clinical data evensooner.

TARGETS & MECHANISMSHER2’s outside helpAn international team has found that neurokinin 1 sub-stance P receptor, a known player in nausea, pain andinflammation, enhances HER2 signaling in breast cancer.The findings argue for combining antagonists against bothreceptors to treat cancer.

sFGFR for achondroplasiaFrench researchers have designed a decoy version offibroblast growth factor receptor 3 that increased bonelength and decreased achondroplasia-associated compli-cations in mice compared with vehicle. The molecule has alonger half-life than other clinical dwarfism candidatesfocused on correcting abnormal signaling by the receptor.

THE DISTILLERYThis week in therapeuticsProtecting against visceral Leishmaniasis with an HbR-based vaccine; improving smoking cessation with asazetidine A derivative; treating retinopathy with ANG1;and more…

This week in techniquesIn vitro generation of branched polyketides using bacterialpolyketide synthase; MMP2-activated, chemotherapeuticnanocarriers for targeted drug delivery; 2-aminoadipic acidas a predictive marker for type 2 diabetes; and more…


infections, sinusitis and anaphylaxis.The asthma user guide was developed

under the Coalition for Accelerating Stan-dards and Therapies (CFAST) initiative.CFAST is a collaboration between theCritical Path Institute (C-Path) andthe Clinical Data Interchange Stan-dards Consortium (CDISC), a non-profitorganization that is establishing standardsto support the acquisition, exchange, sub-mission and archive of clinical researchdata and metadata.

According to Jordan, TransCeleratewill continue to work with CDISC nextyear to develop similar standards for mul-tiple sclerosis (MS), HCV, as well as car-diovascular endpoint data and QT stud-ies.

Qualification and trainingAnother milestone for TransCelerate

was the standardization in June of GCPtraining across all of the consortium’smember companies under the site qualifi-cation and training (SQT) standards ini-tiative.

SQT is intended to eliminate inefficien-cies that arise from each drug companyasking for the same qualifications andtraining information from clinical trial sitesbut asking for it in different ways andformats, Katarina Hugeneck told BioCen-tury.

“We wanted to figure out a way tosimplify that interaction for both clinicaltrial site personnel and staff as well as fordrug companies,” added Sue McHale.

Hugeneck and McHale are leads on theinitiative. Hugeneck is a consultant inbusiness process, study specific instruc-tion at Lilly. McHale is global projectdelivery director of R&D/global medicinesdevelopment at AstraZeneca plc.

The GCP training standards allow clini-cal trial investigators and staff personnelto complete a common training program

that is recognized by all TransCeleratemember companies, making it unneces-sary for staff to train and separately qualifyfor each company’s trials.

In addition to standardizing GCP clini-cal site training, the initiative has createdstandardized templates for clinical trialinvestigator CVs and clinical trial siteprofiles.

Next milestones include developingadditional standards for investigator sitepersonnel training, said Hugeneck.

Next stepsGill said discussions are ongoing within

TransCelerate about kicking off new ini-tiatives in 2014. He declined to providedetails.

Gi l l a lso told BioCentury thatTransCelerate is open to adding moremembers and that the board approved thelatest member — UCB Group’s UCBPharma S.A. subsidiary — on Sept. 30.

The 10 founding members are AbbVie,AstraZeneca, Boehringer IngelheimGmbH, BMS, Lilly, GSK, Johnson &Johnson , Pfizer Inc. , Roche andSanofi.

The seven members added over thepast year are Astellas Pharma Inc.,Biogen Idec Inc., Braeburn Pharma-ceuticals S.p.r.l., Cubist Pharmaceu-ticals Inc., Merck KGaA’s EMD SeronoInc. unit, Forest Laboratories Inc.’s

Forest Research Institute and Onyx Phar-maceuticals Inc.

Onyx was acquired by Amgen Inc.last month. Gill told BioCentury he couldnot yet say whether Amgen might join theconsortium or Onyx will drop out as aresult of the acquisition.

COMPANIES AND INSTITUTIONS MENTIONEDAbbott Laboratories (NYSE:ABT), AbbottPark, Ill.AbbVie Inc. (NYSE:ABBV), Chicago, Ill.Amgen Inc. (NASDAQ:AMGN), ThousandOaks, Calif.Astellas Pharma Inc. (Tokyo:4503), Tokyo,JapanAstraZeneca plc (LSE:AZN; NYSE:AZN),London, U.K.Biogen Idec Inc. (NASDAQ:BIIB), Weston,Mass.Boehringer Ingelheim GmbH, Ingelheim,GermanyBraeburn Pharmaceuticals S.p.r. l . ,Princeton, N.J.Bristol-Myers Squibb Co. (NYSE:BMY),New York, N.Y.Clinical Data Interchange StandardsConsortium (CDISC), Round Rock, TexasCritical Path Institute (C-Path), Tucson,Ariz.Cubist Pharmaceuticals Inc. (NASDAQ:CBST), Lexington, Mass.Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.Forest Laboratories Inc. (NYSE:FRX), NewYork, N.Y.GlaxoSmithKline plc (LSE:GSK; NYSE:GSK),London, U.K.Johnson & Johnson (NYSE:JNJ) , NewBrunswick, N.J.Merck KGaA (Xetra:MRK), Darmstadt, Ger-manyPfizer Inc. (NYSE:PFE), New York, N.Y.Roche (SIX:ROG; OTCQX:RHHBY), Basel,SwitzerlandSanofi (Euronext:SAN; NYSE:SNY), Paris,FranceTransCelerate BioPharma Inc., Philadel-phia, Pa.UCB Group (Euronext:UCB), Brussels, Bel-gium

“If you’re a member of thenetwork, your entire port-folio of marketed drugs ismade available to othermember companies foruse as comparators in

their clinical trials.”

Terry Walsh, TransCelerateand GlaxoSmithKline


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By Stephen HansenSenior Writer

AstraZeneca plc’s latest pair of deals— the acquisition of Spirogen Ltd. and apartnership with ADC TherapeuticsS.a.r.l. — gives the pharma’s MedIm-mune LLC biologics unit all the tools itneeds for antibody-drug conjugates.

ADCs are one of MedImmune’s twoprimary focus areas in cancer. The otherarea, immunotherapy, was the driver ofMedImmune’s acquisition of AmplimmuneInc. for $225 million up front and up to$275 million in milestones.

That deal closed Oct. 7, giving MedIm-mune a pipeline of cancer immunomodu-lators, including AMP-514, a mAb againstPD-1 receptor (PDCD1; PD-1; CD279)that is in preclinical development for can-cer (see BioCentury, Sept. 9).

Eight days later MedImmune announcedthe two ADC deals.

MedImmune will acquire partner Spiro-gen for $200 million in cash up front plusup to $240 million in milestones.

The AZ unit also partnered with ADCTherapeutics to co-develop two undis-closed preclinical ADC programs. MedIm-mune will make a $20 million investmentin ADC, which also will receive an undis-closed upfront payment and is eligible formilestones.

ADC Therapeutics has a license toSpirogen’s ADC technology under a 2012deal.

MedImmune is not new to the ADCspace, though it has not been as visible asother big biotech and pharma players thathave been taking licenses to ADC technol-ogies (see BioCentury, Aug. 19, & Dec. 20,2010).

MedImmune is developing moxetumo-mab pasudotox, a legacy program fromCambridge Antibody Technology Groupplc, which AstraZeneca acquired in 2006.The molecule is an ADC that consists of amurine anti-CD22 antibody variable frag-ment fused to PE38, a fragment ofPseudomonas exotoxin A.

Moxetumomab pasudotox movedstraight into Phase III testing to treat hairycell leukemia (HCL) in May after a Phase Itrial in 48 patients showed an 88% overallresponse rate, said Ed Bradley, SVP andhead of MedImmune’s oncology innova-tive medicines unit (iMed).

The company, which hopes to submit

Strategy

MedImmune’s warheads

a BLA in 2017, would not disclose whetherit has requested breakthrough designa-tion from FDA.

MedImmune also had a 2005 deal touse ADC technology from Seattle Ge-netics Inc. that was expanded in 2007,but the deal has since been terminated.

According to EVP Bahi ja Ja l la l ,MedImmune has an undisclosed numberof ADC programs in preclinical testing.Details on the technologies used to de-velop those molecules have not been dis-closed.

MedImmune, founded as an antibodydiscovery and development company, hasbeen developing a site-specific conjuga-tion approach to improve the homogene-ity of its ADC products.

The company also has internally devel-oped a toxin warhead and linker technol-ogy.

3-way innovationJallal said the addition of Spirogen

strengthens MedImmune’s arsenal of ADCwarheads and linker chemistries.

Rather than license the technology,Jallal said MedImmune acquired the com-pany for its integrated approach to thecomponents of an ADC — the antibody,linker and warhead.

It is “important to innovate in all thesespaces, and that is not as straightforwardto do if you are going to do it just througha license,” she said.

As of June 30, MedImmune had dis-closed eight mAbs in Phase I or Phase IItesting for cancer. Jallal said some couldbe amenable to development as ADCs.

Spirogen’s main assets are its pyr-rolobenzodiazepine (PBD) warheads, butthe company also has linker and conjuga-

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“Spirogen provides a suiteof warheads and a widerange of different linkersand conjugation chemis-tries, so that gives you a

great tool kit.”

Chris Martin, Spirogen


Strategy,from previous page

Reopening the U.S. government is one thing. Funding NIH and FDA isanother.

During the shutdown both Democrats and Republicans raised choruses ofwarnings about the dire consequences of closing NIH’s campus and fur-loughing FDA staff. But everyone knows both agencies still will be crying outfor money.

If austerity is here to stay, what’s the right answer for taxpayers, scientistsand patients? The newest edition of BioCentury This Week television asks:

• Dr. Howard Garrison, Deputy Executive Director for Policy at theFederation of American Societies for Experimental Biology (FASEB)

• Kevin Wilson, Director of Public Policy at the American Society forCell Biology (ASCB)

• Steven Grossman, Deputy Executive Director at the Alliance for aStronger FDA

And, BioCentury’s Affordable Care Update is joined by Dan Mendelson, CEOof Avalere Health.

This week’s topic: The healthcare exchanges are off to a rocky start. Is itsimply embarrassing, or will it be fatal?

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tion technologies.“Spirogen provides a suite of warheads

and a wide range of different linkers andconjugation chemistries, so that gives youa great tool kit,” CEO Chris Martin toldBioCentury.

According to Martin, the PBD pay-loads are two to four times more potentthan other cytotoxic agents used in ADCs.The PBDs also have a different mechanismof action in that they cross-link DNAinside the cancer cell.

As a result, the PBDs are not affectedby cancer cell resistance machinery. “Thismeans that head-to-head with other tox-ins, ADCs armed with PBDs tend to be

very active,” he said.The potency of PBDs should translate

into better efficacy, particularly in resis-tant tumors or against targets that areexpressed at low levels.

While targets like HER2 are highlyexpressed and internalized, which is idealfor ADCs, others can be more difficult forconventional ADCs because the targetantigen may have a low copy count orhave a slow rate of internalization.

Spirogen’s linkers also give MedImmuneflexibility in developing ADCs dependingon the target and desired pharmacokinet-ics, Martin said.

He said Spirogen’s linkers either canbe cleaved by a specific enzyme or be non-cleavable, in which case the PBD is re-leased via degradation of the mAb.

In addition, Spirogen has developedlinkers using undisclosed substrates. Dif-ferent substrates determine which com-partment of the cancer cell the linker iscleaved in and the PBD released.

Martin said the company also has link-er technology that effectively turns thePBD warhead into a prodrug. “It inhibitsthe activity while the linker is in place, butwhen the linker is inside the cell it releasesthe potent drug,” he said.

Besides ADC Therapeutics, at leastfour other companies have licensed Spiro-gen’s ADC technology: the GenentechInc. unit of Roche, Seattle Genetics, Abl-ynx N.V. and PolyTherics Ltd.

Spirogen’s existing licensing deals arenot part of the acquisition and will betransferred to a holding company 75%owned by private equity firm Auven Ther-apeutics (formerly Celtic Therapeutics).Both Spirogen and ADC are Auven port-folio companies.

Common causeMeanwhile, Jallal said the partnership

with ADC Therapeutics made sense giventhat ADC and Spirogen had already beenworking together. “It made sense for us toalign all of our common interests anddevelop a framework that incorporatedboth Spirogen and ADC Therapeutics,”she said.

Jallal noted that MedImmune and ADCTherapeutics have not yet selected whichtwo of the latter’s 10 preclinical programswill be included in the deal. ADC Thera-peutics has not disclosed targets or indi-cations for any of its programs.

The two chosen programs will be dis-closed after they enter clinical develop-ment. ADC Therapeutics has an option toco-promote one of the programs in theU.S.

COMPANIES AND INSTITUTIONS MENTIONEDAblynx N.V. (Euronext:ABLX), Ghent, Bel-giumADC Therapeutics S.a.r.l., Lausanne, Swit-zerlandAstraZeneca plc (LSE:AZN; NYSE:AZN),London, U.K.Genentech Inc., South San Francisco, Calif.MedImmune LLC, Gaithersburg, Md.PolyTherics Ltd., London, U.K.Roche (SIX:ROG; OTCQX:RHHBY), Basel,SwitzerlandSeattle Genetics Inc. (NASDAQ:SGEN),Bothell, Wash.U.S. Food and Drug Administration (FDA),Silver Spring, Md.


By Tim FulmerSenior Writer

Hemera Bioscience Inc. is design-ing its MAC-based gene therapy to helptreat dry and wet age-related maculardegeneration more safely than other thera-pies targeting the complement pathway inocular diseases. It also may offer moreconvenient dosing and treat a wider vari-ety of AMD types than marketed inject-able VEGF inhibitors.

Both the wet and dry forms of AMD arecharacterized by over-activation of thecomplement cascade. While the cascadeplays a key role in maintaining the homeo-stasis of eye supporting tissue and inhelping the innate immune system re-spond to infection, over-activation of thecascade in the retina is associated withchronic pro-inflammatory damage that canlead to blindness.

Given the large number of molecularactors in the complement cascade, the chal-lenge has been identifying a target that canbe inhibited to reduce unwanted back-of-the-eye inflammation without impairing thenormal function of the cascade.

Hemera’s adeno-associated viral (AAV)vector-based gene therapy is designed toinhibit the complement cascade’s mem-brane attack complex (MAC), the mostdownstream component of the cascade,which directly damages cell membranes.The product delivers the gene encodingthe CD59 protein, a naturally occurringinhibitor of MAC.

At least two lines of evidence suggestMAC contributes to AMD pathology andprogression, co-founder Rajendra Kumar-Singh told BioCentury.

“First, MAC expression is elevated inabout 60-70% patients with dry and wetAMD. Second, in a subpopulation of Japa-nese people, a genetic polymorphism inone of the components of MAC leads todysfunction of the complex and higherprotection against developing AMD com-pared with the overall Japanese popula-tion,” he said. “Those data led us topropose that delivering an inhibitor ofMAC directly to the eye could help treatdry and wet AMD.”

Kumar-Singh is associate professor of


Hemera: Special sauce in AMD

ophthalmology at the Tufts UniversitySchool of Medicine.

Hemera developed a gene therapy thatdelivers the gene encoding a soluble re-combinant form of human CD59 viaintravitreal injection.

The company chose the gene therapyapproach at the outset “because we wanteda therapy that you could deliver once andstill have long-lasting effects, as opposedto a small molecule or antibody that wouldpresumably require multiple injections totreat this chronic condition,” said Kumar-Singh.

In 2011, Kumar-Singh and colleaguespublished in PLoS One that both sub-retinal and intravitreal delivery of the genetherapy protected mouse models of laser-induced wet AMD.

Kumar-Singh said the MAC-based genetherapy could have advantages over anti-VEGF antibodies as well as compoundstargeting the complement pathway.

He noted patients receiving anti-VEGFbiologics typically require regular injec-tions that can lead to discomfort andinflammation.

The two biologics approved for AMDare Lucentis ranibizumab from Roche’sGenentech Inc. unit and Novartis AGand Eylea aflibercept from RegeneronPharmaceuticals Inc. and Bayer AG.

In addition, because the VEGF inhibi-tors target only excess blood vessel growth,they are effective only against wet AMD. Incontrast, by hitting a mechanism upstreamof blood vessel growth, the MAC-basedgene therapy could be effective againstboth the dry and wet forms of the disease,said Kumar-Singh.

Hemera’s gene therapy also could haveadvantages over other products hittingthe complement cascade.

At least five companies have antibod-ies or small molecules in development thattarget the complement cascade to treatAMD, three of which are in Phase IItesting. All hit components sitting up-stream of MAC, including complement 3(C3), complement 5 (C5), complementfactor D (CFD) and complement factor H(CFH).

The potential advantage of hitting MACover those upstream targets is that itcould be safer, said Kumar-Singh. “You’regoing after only the most downstreamdamaging component of the cascade andthus leaving the rest of the cascade intactto play its normal role in the immunesystem and tissue homeostasis,” he said.

In March, Hemera raised $3.8 millionfrom Fireman Capital Partners and undis-closed investors.

The company is conducting toxicologystudies. Kumar-Singh declined to disclosedetails on a clinical development timeline.

COMPANIES AND INSTITUTIONS MENTIONEDBayer AG (Xetra:BAYN), Leverkusen, Ger-manyGenentech Inc., South San Francisco, Calif.Hemera Biosciences Inc., Boston, Mass.Novartis AG (NYSE:NVS; SIX:NOVN), Basel,SwitzerlandRegeneron Pharmaceuticals Inc.(NASDAQ:REGN), Tarrytown, N.Y.Roche (SIX:ROG; OTCQX:RHHBY), Basel,SwitzerlandTufts University School of Medicine, Bos-ton, Mass.

Hemera Biosciences Inc.

Boston, Mass.Technology: Gene therapy targetingthe complement pathwayDisease focus: OphthalmicClinical status: PreclinicalFounded: 2010 by Rajendra Kumar-Singh, Jay Duker, Adam Rogers, EliasReichelUniversity collaborators: Tufts Uni-versityCorporate partners: NoneNumber of employees: UndisclosedFunds raised: $3.8 millionInvestors: Fireman Capital Partners;undisclosed other investorsCEO: NonePatents: 1 issued in the U.S. and EUcovering the use of MAC-based genetherapy to treat ophthalmic diseases

Stay Alert with BioCentury:A Custom Publications Alert Service

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By Emily Cukier-MeisnerSenior Writer

Adenium Biotech ApS is develop-ing derivatives of arenicin-3 to create asafer antibiotic than colistin to treat infec-tions caused by multidrug-resistant Gram-negative pathogens.

Colistin is a broad-spectrum Gram-negative antibacterial first introduced in1952. It was replaced by safer antibacteri-als in the 1970s due to its nephrotoxicityand neurotoxicity, yet it saw a resurgencein the late 1990s as the last line of defenseagainst multidrug-resistant Gram-negativepathogens.

Arenicin-3 originally was identified atNovozymes A/S from a screen of morethan 500 organisms that looked for novelantimicrobial peptides with broad Gram-negative activity. It is found in the marinelugworm Arenicola marina.

Because arenicin-3 binds promiscu-ously to human proteins, Novozymes gen-erated variant libraries and screened themfor reduced protein binding and equal orbetter activity against Gram-negativepathogens.

Novozymes spun out Adenium in 2011to develop the resulting hits, while theparent company focused on bioethanol.

“Every generation we introduce a newantibiotic, with enough exposure to enoughpopulation, the bacteria will ‘crack thecode’ and become resistant. So what isvery important is not only that we developnew antibiotics, but that they have a clear,novel mode of action,” said CEO PeterNordkild.

“We have the same efficacy or betterthan colistin, but we don’t have the sideeffects, and there’s no cross-resistancebetween bacteria that are resistant tocolistin,” he said.

Both colistin and arenicins initially as-sociate with the negatively charged outermembrane of Gram-negative bacteria.Colistin then induces cell death bypermeabilizing the membrane throughmechanisms that are not well understood,but requires a component called “Lipid A”for entry.

In contrast, arenicins disrupt both theouter and inner bacterial membranes with-

Adenium Biotech ApS

Copenhagen, DenmarkTechnology: Peptides based on arenicinto treat Gram-negative bacterial infec-tionsDisease focus: InfectiousClinical status: PreclinicalFounded: 2011 by Peter NordkildUniversity collaborators: NoneCorporate partners: NoneNumber of employees: 2Funds raised: $9.5 millionInvestors: Novo Seeds, Sunstone Capi-talCEO: Peter NordkildPatents: 2 issued covering composi-tion of matter and use of arenicin-3variants


Adenium: Lugworms vs. superbugs

out relying on the presence of a particularreceptor.

Arenicins also may interfere with bac-terial protein synthesis, although Nordkildsaid it is not yet known whether thatmechanism occurs if membrane disrup-tion is blocked.

Arenicins also may be less susceptibleto resistance than other antibiotic targets.Nordkild said unpublished data showAdenium’s AA139 and AA230 have aspontaneous frequency of resistance forselect isolates of Escherichia coli, Klebsiellapneumoniae, Pseudomonas aeruginosa andAcinetobacter baumannii that is five to sixorders of magnitude less than penicillin.

Across panels containing 55-120multidrug-resistant strains for each of thosebacteria, AA230 inhibited 90% of thespecies in each panel at concentrations of0.5-4 µg/mL. AA139 did so at 1-8 µg/mL,and colistin at 0.25-8 µg/mL.

Arenicins also have demonstrated bet-ter activity than colistin in at least oneanimal model. In mice with pneumonia,aerosolized AA139 or AA230 reduced bac-terial load after 48 hours by more than 104,compared to a 101.75 reduction for colistindosed equally by weight. Nordkild said a

load reduction of at least 103 defines abactericidal rather than bacteriostatic agent.

Nordkild said arenicins have a widetherapeutic window, as the half-maximaleffective dose (ED50) and no observedadverse effect level in mice and minipigsdiffer by a factor of 25-150.

Nordkild said histamine release is themost likely side effect and should be man-ageable in a hospital setting.

This month Adenium selected AA139as the clinical candidate because it had amore favorable pharmacokinetic profilethan AA230. The company plans to sub-mit a U.S. IND in 4Q14.

Adenium will develop the peptide in anIV formulation to treat urinary tract infec-tions (UTIs) and an aerosol nebulizedformulation for hospital-acquired and ven-tilator-acquired pneumonia.

Nordkild said UTIs and HAP/VAP arethe two largest indications in which themultidrug resistant Gram-negative bacte-ria specified by the Generating AntibioticsIncentives Now (GAIN) Act predominate.

GAIN gives additional market exclu-sivity and Priority Review to qualifiedinfectious disease products (QIDPs), in-cluding those that target pathogens speci-fied by FDA. In July the agency publisheddraft guidance on how to streamline clini-cal trials of pathogen-focused antibacteri-als, as required by GAIN (see BioCentury,Nov. 19, 2012).

Nordkild said the company is fundedthrough the IND submission, and plans totap current and two new investors for a$20 million series A round in 1Q14 to lastthrough a Phase II proof-of-concept trial.

Adenium hopes to license the com-pound or be acquired by Phase II comple-tion in 2Q17.

Novozymes does not hold any rights toAdenium’s IP or programs, nor does ithold equity in the company.

COMPANIES AND INSTITUTIONS MENTIONEDAdenium Biotech ApS, Copenhagen, Den-markNovozymes A/S (CSE:NZYM B), Bagsvaerd,DenmarkU.S. Food and Drug Administration (FDA),Silver Spring, Md.

BioCentury Extra: Online every business day.


By Erin McCallisterSenior Editor

A decision by the Centers for Medicare & MedicaidServices to require coverage with evidence development forbeta amyloid imaging agents means that Medicare patients willprobably have to wait at least a few more years to receive EliLilly and Co.’s marketed Amyvid florbetapir outside a clinicaltrial.

On Sept. 27, CMS issued a final decision to limit reimburse-ment of beta amyloid imaging to one scan per Medicare patientwith dementia or neurodegenerative dis-eases enrolled in clinical trials under itscoverage with evidence development (CED)policy.

CMS said it would cover the technol-ogy as long as the patients are enrolled ina clinical trial to develop new AD treat-ments, preventative agents or prognostictools; or to resolve “clinically difficultdifferential diagnoses.”

However, the trials must be reviewedand approved by CMS and must evaluatethe impact of an FDA-approved imagingagent on health outcomes, including survival, the avoidance offutile treatment or tests, or improving or slowing the decline ofquality of life.

Qualifying trials also can assess whether there are specificsubpopulations, patient characteristics or differential diagnosesthat are predictive of improved health outcomes in patientswhose management is guided by PET imaging, or if the use of betaamyloid imaging to enrich the enrollment of new compounds forAD leads to improved health outcomes.

Amyvid, an imaging agent labeled with fluorine 18 (F-18) thatbinds to amyloid plaques, is the only FDA-approved betaamyloid imaging agent.

General Electric Co.’s [18F]-flutemetamol is under reviewin the U.S. and Europe with an FDA decision expected this year.The PDUFA date is not disclosed.

Reviewing the evidenceAmyvid was approved in April 2012 to estimate beta amyloid

neuritic plaque density in patients with cognitive impairmentwho are being evaluated for AD and other causes of cognitivedecline. Approval was based on the Phase III A07 trial in whichAmyvid met the co-primary endpoint of a significant correlationwith cortical amyloid burden as measured by histopathologyduring autopsy (p<0.0001).

However, a PET scan using Amyvid is not intended as anabsolute diagnosis.

“If a scan is negative, this is consistent with not havingAlzheimer’s and allows the physician to move on to otherdiagnoses,” said Dan Skovronsky, CEO of Avid Radiopharma-ceuticals & VP of Tailored Therapeutics at Lilly.

Following a positive scan, the physician may order additionaltests to confirm a diagnosis of AD.

Regulation

Limiting amyloid accessIn June 2012, Lilly sent a letter to CMS asking the agency to

include beta amyloid PET imaging for cognitive impairment in itsnational coverage determinations (NCDs) for PET imaging.

CMS started its review of Amyvid in October 2012 and inJanuary held a meeting of its Medicare Evidence Development &Coverage Advisory Committee (MEDCAC) to review the avail-able evidence for beta amyloid imaging.

Because no published data show that PET imaging of betaamyloid in the brain changes health outcomes in patients whodisplay early symptoms of cognitive dysfunction, most panel

members voted that there was littleevidence to support the use of PET tochange patient management (see BioCenturyFeb. 4).

CMS issued a preliminary decision inJuly to limit reimbursement of beta amy-loid PET imaging to patients enrolled inclinical trials, and opened a 30-day publiccomment period.

CMS received 202 comments, with themajority opposed to the agency’s prelimi-nary decision to limit access to beta amy-loid imaging.

Among the commenters were the Society of NuclearMedicine and Molecular Imaging (SNMMI) and theAlzheimer’s Association, which published a joint guidance inJanuary on the appropriate use of amyloid PET imaging.

SNMMI said it disagreed with the agency’s statement thatevidence is not adequate to conclude that PET imaging improvesmeaningful health outcomes in Medicare beneficiaries who dis-play signs and symptoms of AD.

However, the organization did not cite any supportive datarelated to the efficacy of beta amyloid imaging on healthoutcomes or treatment management.

Both SNMMI and the Alzheimer’s Association noted that theirappropriate use criteria defined the specific subgroups of pa-tients who could benefit from PET imaging.

According to the criteria, amyloid imaging is appropriate forthree groups of patients. The first is patients with persistent orprogressive unexplained mild cognitive impairment. The secondis patients satisfying core clinical criteria for possible AD becauseof unclear clinical presentation defined as either an atypicalclinical course or an etiologically mixed presentation.

The third is patients with progressive dementia and early ageof onset (<65 years of age).

The joint guidance also notes that amyloid imaging is inap-propriate for patients with core clinical criteria for probable ADwith typical age of onset; to determine dementia severity; orwhen used based solely on a positive family history of dementiaor presence of apolipoprotein E (ApoE) epsilon 4.

The guidance also states that amyloid imaging is inappropri-ate for patients with a cognitive complaint that is unconfirmed onclinical examination; when used in lieu of genotyping for sus-pected autosomal mutation carriers; in asymptomatic individu-als; or for nonmedical use.

Nonetheless, CMS was not swayed.See next page

“The persuasivenessof expert opinion isconstrained by the

available evidence.”

Centers for Medicare &Medicaid Services


“The persuasiveness of expert opinionis constrained by the available evidence,”the agency wrote in its final decisionmemo. “Depending on the evidence, ex-pert opinion may vary from conjectural toconclusive.”

The memo added: “Furthermore, wealso recognize the expertise of anotherrelevant expert consensus panel that weconvened on January 30, 2013 — the MEDCAC.”

Four members of the 12-person MEDCAC panel were neu-rologists.

CMS acknowledged that the clinical trial data published forAmyvid were “promising” to support the exclusion of AD and toenrich clinical trials on the basis of biological factors.

But the agency said “the data are insufficient to conclude thatthe use of positron emission tomography (PET) amyloid-betaimaging is reasonable and necessary for the diagnosis or treat-ment” for Medicare benef ic iar ies with dementia orneurodegenerative disease.

CMS taketh awayUp until the final decision memo, local and regional Medicare

carriers could and did reimburse for Amyvid scans on a case-by-case basis.

Now, Skovronsky said, the CMS decision limits local andregional carriers’ coverage to clinical trials, which is burden-some.

“Unfortunately the way that CED is designed, you can’t starttrials until you have agreement with CMS. It’s not to say that Lillydoesn’t have trials; we do, but they were not designed to answerthe specific questions asked by CMS,” he said.

In an emailed statement to BioCentury after the final decision,CMS said that ongoing trials of FDA-approved beta amyloidagents “may or may not qualify under the CED policy.”

“To make this determination, we would need to see theprotocol of the ongoing trial to make sure it addresses theresearch questions and meets the criteria outlined in our CEDfinal decision memo,” the agency added.

Lilly has Phase II and Phase III trials of Amyvid that Medicarebeneficiaries could enroll in, but because they were not ap-proved by CMS and do not measure the endpoints included inthe CED, new patients would not receive reimbursement for thetest.

Additionally, Lilly is running a Phase IV study to determinehow Amyvid changes patient management and to evaluate theassociation between scan status and cognitive decline. Theestimated completion date is December 2014.

Once it analyzes those data, Lilly said it may ask CMS toreconsider.

“Depending on the data, it might bepossible to reopen the discussion withCMS, but it is too soon to say for sure,”Skovronsky told BioCentury.

In the meantime, Lilly believes that theCED places undue burden on patients andlimits access.

“Patients will have to go to a clinicaltrials site, be consented to participate inthe trial and this might add burden to thepatient simply because they are partici-pating in a trial that might require fre-

quent follow-up visits. A second factor is that it will be limited interms of where patients can participate and the trial may not beavailable in all areas,” he added.

Lilly wouldn’t say just how long it would take before new trialscould get started, but “this will be a lot more time,” Skovronskysaid.

CMS would not comment on the details of any trials thatmight be submitted under the CED or how long they would needto be. It did say in the final decision memo that they could be“short-term” trials that measure the effect of the imaging agenton treatment management or longer trials with outcome deter-mined by postmortem analysis.

Skovronsky said patient and physician groups like theAlzheimer’s Association are working on a plan to address theconcerns raised within the CED through a potential registry trial.

“While there are no plans finalized yet, discussions arebeginning, and we are really encouraged by the leadership rolethat Alzheimer’s Association is taking. We are eagerly waiting tosee how that develops,” he said.

“One of the key starting points is to understand where theopportunities are and the best way forward as a community,”said Eric Dozier, senior director of the Alzheimer’s businessdivision at Lilly.

Skovronsky wouldn’t give specifics but said the majority ofpatients eligible for Amyvid are covered by Medicare. “To a largeextent, this is the population that would benefit the most fromAmyvid. There are people who have AD or cognitive impairmentat earlier ages, but the bulk of patients are covered by Medicare.”

Lilly gained Amyvid in its 2010 acquisition of AvidRadiopharmaceuticals Inc. The pharma doesn’t break out Amyvidsales.

GE declined BioCentury’s request for an interview.

COMPANIES AND INSTITUTIONS MENTIONEDAlzheimer’s Association, Chicago, Ill.Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.General Electric Co. (NYSE:GE), Fairfield, Conn.Society of Nuclear Medicine and Molecular Imaging (SNMMI),Reston, Va.U.S. Centers for Medicare & Medicaid Services (CMS), Baltimore,Md.U.S. Food and Drug Administration (FDA), Silver Spring, Md.

Regulation,from previous page “It’s not to say that Lilly

doesn’t have trials; we do,but they were not designed

to answer the specificquestions asked by CMS.”

Daniel Skovronsky, Eli Lilly

BioCentury makes people thinkThere is only one journal — BioCentury, the Bernstein Report on BioBusinessTM — that is recognized by key decision makers asthe best source of perspective, interpretation and analysis for top managers and investors in the biotech community.


Earnings on deckAt least 18 biotechs and pharmas are slated to report earnings this week. Alexion Pharmaceuticals Inc. (NASDAQ:ALXN), Celgene Corp.(NASDAQ:CELG), The Medicines Co. (NASDAQ:MDCO) and Shire plc (LSE:SHP; NASDAQ:SHPG) are all expected to report double-digit EPS growthon revenue increases of 10% or more. Revenues for Alexion, which markets Soliris eculizumab for rare blood disorders, are expected to jump 34%to $395.3 million. Celgene’s top line is expected to increase 15% to $1.6 billion. Medicines Co., which markets drugs for acute and intensive care settings,is expected to post a 27% increase in revenues to $173.9 million. And revenues for specialty biopharma Shire are expected to climb 11% to $1.2 billion.3Q13 EPS for Cubist Pharmaceuticals Inc. (NASDAQ:CBST) is expected to fall 36% despite a 13% increase in revenues to $268.6 million. In April, thebiotech provided 2013 R&D expense guidance of $400-$420 million. Cubist reported $277.7 million in R&D expenses in 2012. Cubist markets the antibioticCubicin daptomycin. 3Q13 EPS for Eli Lilly and Co. (NYSE:LLY) is expected to increase 30% on a 6% revenue increase. In July, the company completeda $1.5 billion share repurchase program. (A) Fiscal 2Q; (B) Spun out of Abbott Laboratories (NYSE:ABT) at the start of 2013

Pre/ 3Q13post EPS 3Q12 Expected

Company Date mkt est EPS chg

Illumina Inc. (NASDAQ:ILMN) 10/21 Post $0.40 $0.41 -2%

Forest Laboratories Inc. (NYSE:FRX) (A) 10/22 Pre $0.15 $0.15 0%

Novartis AG (NYSE:NVS; SIX:NOVN) 10/22 Pre $1.31 $1.34 -2%

Waters Corp. (NYSE:WAT) 10/22 Pre $1.23 $1.18 4%

Amgen Inc. (NASDAQ:AMGN) 10/22 Post $1.78 $1.67 7%

Cubist Pharmaceuticals Inc. (NASDAQ:CBST) 10/22 Post $0.35 $0.55 -36%

Sigma-Aldrich Corp. (NASDAQ:SIAL) 10/22 Post $1.00 $0.94 6%

Eli Lilly and Co. (NYSE:LLY) 10/23 Pre $1.03 $0.79 30%

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) 10/23 Pre $0.90 $0.85 6%

The Medicines Co. (NASDAQ:MDCO) 10/23 Pre $0.21 $0.17 24%

Thermo Fisher Scientific Inc. (NYSE:TMO) 10/23 Pre $1.28 $1.19 8%

Bristol-Myers Squibb Co. (NYSE:BMY) 10/23 Post $0.44 $0.41 7%

Alexion Pharmaceuticals Inc. (NASDAQ:ALXN) 10/24 Pre $0.79 $0.60 32%

Celgene Corp. (NASDAQ:CELG) 10/24 Pre $1.54 $1.29 19%

Shire plc (LSE:SHP; NASDAQ:SHPG) 10/24 Pre $1.65 $1.36 21%

BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) 10/24 Post -$0.30 -$0.04 NA

AbbVie Inc. (NYSE:ABBV) (B) 10/25 Pre $0.78 NA NA

UCB Group (Euronext:UCB) 10/25 NA NA NA NA

Ebb & Flow

Turkey trotBy Michael Flanagan,

Stephen Hansen & Samantha McGirrStaff Writers

Even with the traditional post-Thanksgiving break fast ap-proaching, buysiders say there is still plenty of demand to supportcompanies in the IPO queue. But timing will be increasingly tight forthose that haven’t filed publicly by the end of this week.

The number of biotechs in the queue grew to 23 last week asthree new names were added and one — ADMA BiologicsInc. (NASDAQ:ADMA) — slipped out the door. The antibodyplay raised $28.5 million on the OTC Bulletin Board on Thurs-day.

Among the dozen buysiders who spoke with BioCentury, thenear-unanimous consensus was that demand is still strong asgeneralist and momentum investors continue to chase returns —even after more than 40 life science IPOs have priced this year.

“It is hard to know how long this window will last, and we allknow that at some point it will close. But it has been a great year,

and at least for the moment, the aftermarket performancescontinue to look good,” said Joep Muijrers of LSP-Life SciencesPartners.

The interest from generalists can be a double-edged sword,noted Muijrers, as a major blowup could send them all runningfor the hills. “But so far demand continues to look strong,” hesaid.

One thing that is clear: VCs will make sure there is noshortage of supply as long as there is demand for new biotechpaper.

Buysiders unanimously said the pace of “test the waters”meetings with private biotechs has not slackened, suggesting thatthey — along with the bulge bracket banks underwriting manyof the new deals — do not believe the end is nigh.

Indeed, six of the eight new filings over the past two weekshave a bulge bracket bank as the lead underwriter.

They will need to move fast if they want to get the deals doneSee next page


Ebb & Flow,from previous page

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this year.“Based on folks

we have talked to,nearly every com-pany working on adeal is trying to getit done beforeThanksgiving,” saidValence Fund’s EricRoberts.

“ It is usual lytough to get peopleto make speculativebets after Novem-ber, but some deals might slip through in December onlybecause it is such a hot market,” he added.

Immunotherapy top upCancer vaccine company immatics biotechnologies

GmbH may have raised its last private financing round, asinvestors gave it enough cash to submit regulatory applicationsfor lead program IMA901.

Last week, immatics raised €12 million ($16.3 million) in thefirst tranche of a €34 million ($46.1 million) series D round.CEO Paul Higham told BioCentury the additional cash willfinance the company beyond 2015, when final Phase III data areexpected for IMA901 in renal cell carcinoma (RCC). The fundswill support regulatory submissions in the U.S. and Europe forthe vaccine containing tumor-associated peptides (TUMAPs).

If the Phase III data are positive, Higham said immatics wouldseek a large cancer-focused commercial partner for IMA901.And if all goes to plan, immatics may not require another venturefinancing, he said.

A 2010 series Cround of €53.8 mil-lion ($70.5 million)that would havecovered the PhaseIII trial to the in-terim data readout,which is expectedin 1H14. At thetime, investors de-cided immatics

would have to go it alone in Phase III because prospective pharmapartners viewed cancer immunotherapy as too risky (see BioCentury,Sept. 27, 2010).

“That has really changed,” Higham noted. “The environmentfor cancer immunotherapy has improved significantly. It is reallyquite different from even 18 months ago, where big pharma wereon a much more cautious footing.”

He added: “We’ve seen companies who in the past weresaying immunotherapy was too high risk and they weren’tinterested, those companies are now saying they’ve made adecision and it is part of their future.”

Higham noted much of the interest has come with the successof other immunotherapies that modulate the immune system likeIMA901 — such as melanoma drug Yervoy ipilimumab from

“It is usually tough to getpeople to make speculative

bets after November butsome deals might slipthrough in December

only because it is sucha hot market.”

Eric Roberts, Valence Fund

See next page

“The environment forcancer immunotherapy

has improvedsignificantly.”

Paul Higham, immatics


Take advantage of BioCentury Extra.


Bristol-Myers Squibb Co. (NYSE:BMY) — and the clinicalsuccess of other checkpoint inhibitors like programmed celldeath 1 ligand 1 (CD274 molecule; PD-L1; B7-H1).

He said there could be significant synergy between cancervaccines like IMA901, which promote tumor-directed T cells,and checkpoint inhibitors that prevent immune resistance at thesite of the tumor.

“That is the way to go in my view,” Higham said.Existing investors participated in the series D round: dievini

Hopp BioTech; Wellington Partners; MIG Funds; AT Impf;Grazia Equity; EMBL Ventures; SB Asset Management; KfW;National Technology Enterprises; Merifin Capital; Beacon Hill;and PB Invest.

Consolation prizeWhile Alex Denner’s campaign to derail Otsuka Pharma-

ceutical Co. Ltd.’s takeout of Astex Pharmaceuticals Inc. fellshort, his hedge fund still made $1.1 million on its two-monthinvestment.

Sarissa CapitalManagement be-gan taking a posi-tion in Astex inmid-August, andhad purchased459,387 shares at$5.13-$6.61 by the close of Sept. 3, the day before media reportsof a potential bid from Otsuka.

On Sept. 5, Astex agreed to a cash offer of $8.50 per share, or$866 million, representing a 27% premium to Astex’s close on Sept.3.

Both companies’ boards unanimously approved the deal,which was structured as a tender offer. A majority of shareholdersneeded to tender their shares by Oct. 10 to complete the deal.

Believing Otsuka’s offer undervalued Astex, Denner bought3.9 million shares at $8.49, raising Sarissa’s stake to 5%.

He then began lobbying publicly against the deal.Denner told Bloomberg on Sept. 11 the price was “exception-

ally low” based on Astex’s pipeline. On Oct. 2 he issued a publicletter recommending fellow shareholders not tender their shares.

In the letter, Denner said Astex did not contact all potentialbidders and called the timing “inexplicable” given near-termreadouts for SGI-110, a second-generation version of cancer drugDacogen decitabine.

In August, Astex said SGI-110 led to an overall remission rateof 25% in 67 evaluable acute myelogenous leukemia (AML) patients.Additional data are expected in December and next year.

Astex responded with an open letter of its own on Oct. 2, saying“33 pharmaceutical companies were contacted to gauge theirinterest,” but only Otsuka submitted a final proposal.

Last week, Denner told BioCentury his primary goal was todelay the deal to give new bidders more time to emerge.

“A lot of people said they were thinking the same way wewere; and we came close. But they got 52%, which was justenough” for the deal to go through, he said. “In the end we mademoney, so it wasn’t a huge deal.”

All told, Sarissa paid $36 million for its Astex stake. At the$8.50 takeout price, the firm will receive $37.1 million.

Sarissa’s other biotech investment is a 2% stake, as of July 23,in Vivus Inc. (NASDAQ:VVUS). Denner sits on the obesitycompany’s board.

The firm also participated in a September $7.5 million privateround by hematology company Emmaus Life Sciences Inc.

Cashing in on ConformationsBiodesy Inc. has yet to commercialize its system for protein

structure analysis, but a trio of investors are betting the platform’slow cost and simplicity will eventually allow for scalability andcustomizability.

Last week, Biodesy raised $15 million in a series A round led by5AM Ventures. Pfizer Venture Investments and Roche VentureFund also participated. All are new investors.

Biodesy is developing its second-harmonic generation (SHG)technology, which enables real-time, high throughput measure-ment of protein conformational changes with subangstrom resolu-tion.

5AM’s Andrew Schwab, who joined Biodesy’s board, said theVC was drawn to the straightforward technology.

“The key differentiator is that it’s a fairly simple and robustassay,” he said. “Typical binding assays are not very good atdetecting conformational changes. And technology for detectingstructural changes is much more laborious and expensive than theSHG technology.”

Greg Yap, who was named CEO last week, said the real-timeaspect of SHG technology allows researchers to confirm not onlywhether a compound binds a target protein, but also that it inducesthe correct conformational change.

Yap was formerly healthcare entrepreneur-in-residence at Gen-eral Electric Co. (NYSE:GE). Prior to that, he oversaw the

cancer assay portfo-lio at Ventana Medi-cal Systems, a unit ofRoche (SIX:ROG;OTCQX:RHHBY).

The SHG plat-form has high po-tent ia l for highthroughput screen-

ing of allosteric modulators, according to Yap.“For allosteric modulators, you need an assay that can

distinguish between molecules sticking somewhere on a proteinand those that cause the proper functional change,” he said.

In the near term, Biodesy plans to partner with pharmas andacademic institutions to refine the platform and develop itscustomer base.

According to Yap, Biodesy entered its first partnership withan undisclosed pharma prior to the series A close.

The company’s long-term goal is to be a supplier of instru-ments, reagents and assays.

Yap said Biodesy has not set a timeline for a commerciallaunch. But he expects the series A to be “more than sufficient”to get the SHG technology to market as well as develop additionalapplications for specific types of drug discovery.

Schwab said the Biodesy investment came from the $200million 5AM Ventures III L.P. fund.

In an SEC filing last week, 5AM disclosed plans to raise up to$240 million for its fourth fund. Schwab declined to comment.

“In the end we made money,so it wasn’t a huge deal.”

Alex Denner, Sarissa

“The key differentiator isthat it’s a fairly simple and

robust assay.”

Andrew Schwab, 5AM Ventures

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Regulatory milestonesAlimera Science Inc. (NASDAQ:ALIM) fell $0.23 to $2.48

on Friday after FDA issued a complete response letter for anNDA for Iluvien fluocinolone acetonide intravitreal implant totreat diabetic macular edema. Alimera said FDA requested anadditional clinical trial plus at least 12 months of follow-up.Al imera has r ights to I luvien from pSivida Corp.(NASDAQ:PSDV; ASX:PVA), which lost $0.93 (24%) to $2.87on Friday. In Australia, the stock was down A$0.52 (12%) toA$3.84.

Alimera said it will meet with FDA’s Dermatologic andOphthalmic Drug Advisory Committee in January for advice.The complete response letter is the third from FDA for Iluvien.

Alimera lost $0.89 (26%) on the week. pSivida fell $1.74(38%). In Australia, the stock lost A$1.15 (23%).

AMAG Pharmaceuticals Inc. (NASDAQ:AMAG) gained$1.68 to $21.53 last week after FDA extended the PDUFA dateby three months for an sNDA for Feraheme ferumoxytol. Thenew date is Jan. 21; it was Oct. 21. Ferahemeis under review to expand its indication toinclude the treatment of all adult patientswith iron deficiency anemia who have failedor could not tolerate oral iron treatment(see Analyst Picks, A18).

The product is approved to treat irondeficiency anemia in adult patients withchronic kidney disease (CKD).

Amarin Corp. plc (NASDAQ:AMRN)fell $3.61 to $2.01 on Thursday afterFDA’s Endocrinologic and Metabolic DrugsAdvisory Committee voted 9-2 against ex-panding the label of Vascepa icosapentethyl. Amarin is seeking approval forVascepa to treat high triglycerides in pa-tients with mixed dyslipidemia in combina-tion with statins. The committee votedagainst approval prior to the completion ofAmarin’s REDUCE-IT cardiovascular out-comes trial. Data are not expected until atleast 2016 (see “Analyst Picks,” A18).

The sNDA has a Dec. 20 PDUFA date.Amarin already markets Vascepa in theU.S. as an adjunct to diet to reduce triglyc-eride levels in adults with severehypertriglyceridemia.

Amarin finished the week down $3.06(60%) to $2.03.

Ariad Pharmaceuticals Inc.(NASDAQ:ARIA) fell $1.83 (41%) to $2.67on Friday after discontinuing the confirma-tory Phase III EPIC trial of Iclusig ponatinibin newly diagnosed leukemia patients dueto arterial thrombotic events observed inpatients treated with the drug. Earlier thismonth, FDA placed a partial clinical holdon all trials of Iclusig (see Analyst Picks,A18).

The drug is approved for patients withchronic myelogenous leukemia (CML) or

Philadelphia-chromosome positive (Ph+) acute lymphoblasticleukemia (ALL) who are resistant to or intolerant of priortreatment with tyrosine kinase inhibitors (TKIs). Ariad said itexpects FDA to narrow the label for Iclusig to patients who havefailed other therapies.

Ariad lost $1.59 (37%) on the week.Ironwood Pharmaceuticals Inc. (NASDAQ:IRWD) was

off $0.18 to $10.70 last week after Germany’s Federal JointCommittee (G-BA) said in a final benefit assessment that Constellalinaclotide has “no additional benefit” over comparators to treatirritable bowel syndrome with constipation (IBS-C). AlmirallS.A. (Madrid:ALM) has European rights to Constella fromIronwood.

MannKind Corp. (NASDAQ:MNKD) added $0.17 to $5.28last week after resubmitting an NDA to FDA for Afrezza toimprove glycemic control in Type I and II diabetics. Theresubmission includes data from two additional trials that wererequested by FDA in a 2011 complete response letter, theagency’s second for the dry power formulation of insulin plus aninhaler.

Medivation Inc. (NASDAQ:MDVN) was down $0.15 to$50.82 last week after the U.K.’s NICE issued draft guidance

recommending use of Xtandi enzalutamideto treat hormone-relapsed, metastaticprostate cancer in men whose disease hasprogressed on or after docetaxel therapy.The recommendation is contingent onpartner Astellas Pharma Inc. (To-kyo:4503) providing Xtandi at an undis-closed discount under a patient accessscheme. Comments are due Nov. 8.

The European Commission approvedXtandi to treat metastatic castration-re-sistant prostate cancer (CRPC) in June.

ThromboGenics N.V. (Euronext:THR) was down €0.41 to €18.67 lastweek after G-BA said in a final benefitassessment that vitreomacular traction(VMT) drug Jetrea ocriplasmin provides“significant” additional benefit vs. watch-ful waiting in mild disease but “no addi-tional benefit” in severe disease. Throm-boGenics and partner Novartis AG(NYSE:NVS; SIX:NOVN) will now negoti-ate a price for Jetrea with Germany’sStatutory Health Insurance Funds Associ-ation (GKV-Spitzenverband).

UCB Group (Euronext:UCB) rose€1 to €46.76 on Friday after FDA ex-panded the label of Cimzia certolizumabpegol to include treatment of adults withactive ankylosing spondylitis, but issued acomplete response letter for active axialspondyloarthritis. UCB had been seekingto expand Cimzia’s label to include treat-ment of active axial spondyloarthritis,including patients with ankylosing spondyli-tis.

Cimzia is approved in the U.S. foractive psoriatic arthritis, rheumatoid ar-thritis (RA) and Crohn’s disease.

UCB gained €1.65 on the week.Source: BCIQ: BioCentury Online Intelligence

Money Raised in 2013Last week, the biotech industry raised $286million, bringing to $30 billion the total raisedyear-to-date. In 2012, a total of $36.3 billionwas raised, including $19.9 billion in debt, $6.3billion in follow-ons, $2.8 billion in PIPEs andother equity, $1.1 billion in IPOs, and $6.2billion in venture capital. Totals include over-allotments and warrants, and are rounded tothe nearest millions.

Source: BCIQ: BioCentury Online Intelligence



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Vanda Pharmaceuticals Inc. (NASDAQ:VNDA) lost $1.89(19%) to $7.83 last week after FDA said a panel will meet on Nov.14 to discuss an NDA for Vanda’s Hetlioz tasimelteon (VEC-162)to treat non-24-hour sleep wake disorder in totally blind pa-tients. The NDA is under Priority Review with a Jan. 31 PDUFAdate. Vanda previously said FDA had set a tentative date for acommittee to discuss Hetlioz.

Clinical milestonesCoronado Biosciences Inc. (NASAQ:CNDO) fell $3.86

(67%) to $1.91 last Monday after its Trichuris suis ova (TSO)missed the primary endpoint in a Phase II TRUST-I trial to treatCrohn’s disease (see B18).

Partner Dr. Falk Pharma GmbH is evaluating TSO forCrohn’s in the Phase II TRUST-II trial, with data expected thisquarter. Coronado said it will analyze data from both trials todetermine next steps for TSO.

Coronado lost $3.99 (69%) to $1.78 on the week.Keryx Biopharmaceuticals Inc. (NASDAQ:KERX) closed

up $1.73 (20%) to $10.49 on Wednesday on the release of anabstract showing that Zerenex ferric citrate met the primaryendpoint in a Phase II trial to treat hyperphosphatemia in non-dialysis dependent patients with chronic kidney disease (CKD).The data are slated to be presented at the American Society ofNephrology meeting in November (see B20).

Earlier this month, FDA accepted for review an NDA forZerenex to treat hyperphosphatemia in CKD patients on dialy-sis. Keryx said it expects to receive the PDUFA date in the nextfew weeks.

Keryx continued to rise to finish the week up $1.92 (21%) to$11.26.

Medivir AB (SSE:MVIR B) was up SEK5.50 to SEK106.50 onFriday after presenting data from an open-label Phase III trialevaluating simeprevir (TMC435) in patients with HCV genotype1 infection co-infected with HIV-1. Simeprevir plus peginterferonand ribavirin led to a sustained virologic response (SVR) 12weeks after the end of treatment, the primary endpoint, in 74%of patients (see B20).

Last month, Japan’s Ministry of Health, Labor and Welfare(MHLW) approved simeprevir as Sovriad to treat HCV genotype1 infection. Simeprevir is under Priority Review in the U.S. withan undisclosed PDUFA date; a six-month Priority Review wouldplace the PDUFA date in November.

Johnson & Johnson (NYSE:JNJ) has ex-Nordic rights todevelop and commercialize simeprevir from Medivir.

Medivir gained SEK4.75 on the week.Regeneron Pharmaceuticals Inc. (NASDAQ:REGN)

gained $17.22 to $307.65 on Wednesday after it and partnerSanofi (Euronext:SAN; NYSE:SNY) said subcutaneousalirocumab (REGN727) met the primary endpoint in the PhaseIII ODYSSEY MONO trial to treat primary hypercholesterolemia(see B22).

The data are the first from the 12-trial Phase III ODYSSEYprogram evaluating alirocumab as monotherapy and in combina-tion with other lipid-lowering agents. Data from additionalODYSSEY trials are expected next year.

Regeneron gave back some of its gains to finish the week up$13.26 to $303.56.

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Amgen Inc. (NASDAQ:AMGN), which is developing com-petitor hyperlipidemia compound AMG 145, gained $4.03 to$114.92 last week. AMG 145 is in Phase III testing, with dataexpected in 1Q14.

Ebb & FlowAblynx N.V. (Euronext:ABLX) was up €0.07 to €7.58 on

Friday after granting Eddingpharm Inc. exclusive, Chineserights to develop and commercialize ALX-0141, which is inPhase I testing to treat postmenopausal osteoporosis. Ablynx willreceive €2 million ($2.7 million) up front and is eligible forundisclosed milestones, plus tiered double-digit royalties. ALX-0141 is a nanobody against receptor activator of NF-kappa Bligand (RANKL).

Ablynx was up €0.25 on the week.Look for Actelion Ltd. (SIX:ATLN) to move this week. After

market close on Friday, FDA approved Opsumit macitentan totreat PAH. Actelion plans to launch Opsumit next month. Lastweek, Actelion was up CHF1.05 to CHF64.60 after saying it is ontrack to meet its goal of double-digit core earnings growth in2013. Sales rose 4% to CHF1.3 billion ($1.5 billion), including a3% increase in sales of pulmonary arterial hypertension (PAH)drug Tracleer bosentan to CHF1.14 billion ($1.3 billion) (see EPSWatch, A20).

ADMA Biologics Inc. (OTCQB:ADMA) was up $0.03 to$8.53 in its first week of trading after raising $28.5 million in anIPO on the OTC Bulletin Board. ADMA sold 3.4 million sharesat $8.50, which values the company at $78.4 million. Last month,ADMA said it planned to sell 2.7 million shares at $8.50-$9.50.

ADMA’s RI-002 is in Phase III testing to treat primaryimmunodeficiency disease, with preliminary data expected in4Q14 and a BLA submission slated for 1H15. RI-002 is a humanplasma-derived, polyclonal IV Ig that has standardized high levelsof antibodies against respiratory syncytial virus (RSV).

Immunotherapy company Advaxis Inc. (NASDAQ:ADXS)was off $1.95 (34%) to $3.75 in its first week of trading onNASDAQ after raising $23 million through the sale of 5.8 millionshares at $4 in a follow-on. The follow-on includes five-yearwarrants to purchase 2.9 million shares at $5. Advaxis ceasedtrading on OTCQB. The company subsequently sold the $3.5million overallotment, bringing the total raised to $26.5 million.

Anacor Pharmaceuticals Inc. (NASDAQ:ANAC) gained$3.06 (28%) to $13.83 on Friday after announcing that anarbitrator awarded the company $100 million in damages in acontract dispute with Valeant Pharmaceuticals Interna-tional Inc. (TSX:VRX; NYSE:VRX). The dispute covers a 2004deal between Anacor and Dow Pharmaceutical Sciences Inc.,under which Dow was providing services to help Anacor developits topical antifungal agent tavaborole. Valeant — which isdeveloping efinaconazole, a competitor to tavaborole — ac-quired Dow in 2008 (see B7).

An NDA for tavaborole is under FDA review for onychomy-cosis, with a July 29, 2014, PDUFA date.

Anacor gained $2.72 (24%) on the week.Mirati Therapeutics Inc. (NASDAQ:MRTX) added $0.80

to $17.80 last week after saying it plans to sell 3 million sharesin a follow-on. Mirati proposed to raise up to $57.5 million in theoffering on Oct. 2, when its share price was $18.48. The

company’s mocetinostat is in Phase II testing for myelodysplasticsyndromes (MDS), with a Phase III trial slated for 2H14.

Paladin Labs Inc. (TSX:PLB) was up C$0.67 to C$63.55 onFriday after an FDA panel voted that the company had ad-equately demonstrated the safety and efficacy of Impavidomiltefosine to treat visceral, cutaneous and mucosal leishmania-sis. The company is seeking approval for Impavido for all threeforms of the disease. The compound is under Priority Review,with a Dec. 19 PDUFA date.

Paladin acquired Impavido from Aeterna Zentaris Inc.(TSX:AEZ; NASDAQ:AEZS) in 2008. Aeterna was off C$0.02 toC$1.48 on Friday, while the stock was off $0.03 to $1.43 onNASDAQ.

Paladin gained C$0.84 on the week. Aeterna lost C$0.03 onthe week. On NASDAQ, the stock was off $0.03.

Portola Pharmaceuticals Inc. (NASDAQ:PTLA) added$1.14 to $23.75 last week after raising $105.9 million throughthe sale of 4.5 million shares at $23.75 in a follow-on. Portola firstproposed to raise up to $100 million in the offering last week,when its share price was $26.74. Company shareholders alsosold 1.9 million shares at $23.75 in a concurrent secondaryoffering.

Portola’s betrixaban is in Phase III testing for prevention ofvenous thromboembolism (VTE) in high-risk acutely medically illpatients.

Receptos Inc. (NASDAQ:RCPT) jumped $6.22 (23%) to$33.22 on Wednesday on rumors that Celgene Corp.(NASDAQ:CELG) and Teva Pharmaceutical Industries Ltd.(NYSE:TEVA) are making bids to acquire Receptos for more than$700 million. Celgene and Teva said they do not comment onrumors. Receptos could not be reached for comment.

Receptos’ most advanced product is RPC1063, a selectivesphingosine 1-phosphate receptor 1 (S1PR1; S1P1; EDG1)agonist that is in a Phase II/III trial to treat relapsing multiplesclerosis (MS). Data from the Phase II portion are expected inmid-2014. Receptos finished the week up $5.71 (20%) to $33.91.

Celgene was up $7.38 to $160.55 on the week, while Tevalost $1.04 to $40.

Stallergenes S.A. (Euronext:GENP) gained €0.30 to €58.80and DBV Technologies (Euronext:DBV) was up €0.76 (10%)to €8.60 on Friday after partnering to develop and commercial-ize a birch allergy product using DBV’s Viaskin skin patchtechnology and birch pollen allergen from Stallergenes.Stallergenes will have development and commercialization rights.DBV is eligible for up to €145 million ($196.7 million) inmilestones, plus royalties (see B5).

Stallergenes was up €1.33 on the week. DBV rose €0.85(11%).

Stemline Therapeutics Inc. (NASDAQ:STML) closed off$2.79 to $35.20 on Friday after proposing to raise $90 millionin a follow-on. Next year, Stemline plans to start a Phase IIb trialof SL-401 to treat blastic plasmacytoid dendritic cell neoplasmand a Phase III trial in third-line acute myelogenous leukemia(AML). SL-401 is an IL-3 receptor targeting agent.

Stemline lost $2.06 on the week.RNAi company Tekmira Pharmaceuticals Corp.

(TSX:TKM; NASDAQ:TKMR) added C$0.48 to C$9.32 andgained $0.47 to $9.01 on NASDAQ on Friday after raising $30million through the sale of 3.8 million shares at $8 in a follow-on. Tekmira proposed the offering late Wednesday, when itsshare price on NASDAQ was $8.82.

Tekmira’s lead internal candidate is TKM-PKL1, which is in


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Phase I/II testing to treat advanced gastrointestinal neuroendo-crine tumors and adrenocortical carcinoma, with data expectedin mid-2014. TKM-PLK1 comprises short interfering RNA (siRNA)targeting polo-like kinase 1 (PLK1; STPK13) formulated with thecompany’s lipid nanoparticle (LNP) technology.

Tekmira lost C$0.56 on the week. On NASDAQ, the stockwas off $0.65.

XenoPort Inc. (NASDAQ:XNPT) rose $0.27 to $5.89 lastweek after investor Clinton Group Inc. called for the resignationof XenoPort CEO Ronald Barrett and a shift in the company’sfocus away from commercializing Horizant gabapentin enacarbiland toward developing XP23829. XP23829 is in Phase I testingfor relapsing-remitting multiple sclerosis (RRMS) and in preclini-cal development for psoriasis.

Clinton said Horizant — approved in the U.S. to treat restlessleg syndrome (RLS) and to manage postherpetic neuralgia (PHN)— “will never be the commercial success we all wish it were.”

Clinton Group, which has a 2.7% stake in XenoPort, also saidthe fair value of XenoPort is $13-$16 per share and that theshares are undervalued due to a lack of confidence in thebiotech’s management.

CorrectionsAriad Pharmaceuticals Inc. (NASDAQ:ARIA), Cambridge,Mass.

Business: CancerOn Oct. 9, Chairman and CEO Harvey Berger said Ariad’s

Phase III EPIC trial of Iclusig ponatinib in newly diagnosed CMLpatients was likely to have been expanded, but the companydid not say how many additional patients would have beenrequired.

The Oct. 14 BioCentury misstated Berger’s title andmischaracterized the planned expansion of EPIC and thetiming of the interim data. On Oct. 18, Ariad discontinuedthe Phase III EPIC study after updated data from the pivotalPhase II PACE trial showed longer use of Iclusig was associ-ated with increased risk of treatment-emergent serious arte-rial thrombotic events. The interim analysis is no longerplanned.

Separately, an investigator-run Phase II study in 80 newlydiagnosed CML patients is testing a 30 mg dose of Iclusig ina cohort of those patients. Data from that trial are expectedat the American Society of Hematology (ASH) meeting inDecember.

The Oct. 14 BioCentury misstated the number of patientsreceiving the 30 mg dose and when data were expected.

Endocyte Inc. (NASDAQ:ECYT), West Lafayette, Ind.Business: Cancer

Endocyte reported that a DSMB recommended continuingthe vintafolide plus docetaxel and the docetaxel monotherapyarms in the Phase IIb TARGET trial to treat second-line non-small cell lung cancer (NSCLC). The Oct. 14 edition of BioCenturyomitted the information.

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Try the searchable BioCentury Archives.

Analyst picks & changesWk 10/118

Company Bank Analyst Coverage Opinion chg cls

AMAG Pharmaceuticals Inc. Baird Christopher Raymond Upgrade Outperform 8% $21.53 (NASDAQ:AMAG) (from neutral)

Raymond also raised his target to $26 from $25 after FDA extended the PDUFA date by three months for an sNDA for anemia drug Ferahemeferumoxytol. He said applications with three-month PDUFA extensions have a “decent” record of gaining FDA approval. The new date is Jan. 21,2014. The sNDA seeks to expand Feraheme’s indication to all adult patients with iron deficiency anemia who have failed or could not tolerate oraliron treatment. Feraheme is approved to treat iron deficiency anemia in adult patients with chronic kidney disease (CKD).

Amarin Corp. plc Canaccord Ritu Baral Downgrade Hold (from buy) -60% $2.03

(NASDAQ:AMRN) H.C. Wainwright Andrew Fein Downgrade Neutral (from buy)

Baral also lowered her target to $3 from $10 after FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 9-2 against expanding the label ofthe company’s Vascepa icosapent ethyl to adults with high triglycerides with mixed dyslipidemia. Baral estimates a 15% chance of approval by the Dec. 20PDUFA date. The committee voted against approval prior to the completion of Amarin’s REDUCE-IT cardiovascular outcomes trial, which are not expecteduntil at least 2016 (see B12). Amarin markets Vascepa in the U.S. as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia

Fein also lowered his target to $2.50 from $10 on the panel vote.

Ariad Pharmaceuticals Inc. JPMorgan Cory Kasimov Downgrade Neutral (from -37% $2.67(NASDAQ:ARIA) overweight)

Kasimov also removed his $12 target after Ariad discontinued the confirmatory Phase III EPIC trial evaluating Iclusig ponatinib in newly diagnosedchronic myelogenous leukemia (CML) patients based on safety data from the trial (see B24). Earlier this month, FDA placed a partial clinical hold ontrials of the compound after data from the pivotal Phase II PACE trial showed longer use of Iclusig was associated with increased risk of treatment-emergent serious arterial thrombotic events. Kasimov said doctors will likely reserve Iclusig for use as salvage therapy in patients with the T3151variant of BCR-ABL tyrosine kinase. He expects Ariad will have to start another confirmatory trial to satisfy FDA accelerated approval requirements.Iclusig is approved to treat CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) that is resistant or intolerant toprior treatment with tyrosine kinase inhibitors (TKIs).


Analyst Picks & Changes,from previous page

Wk 10/118Company Bank Analyst Coverage Opinion chg cls

Coronado Biosciences Inc. Canaccord Salveen Richter Downgrade Hold (from buy) -69% $1.78

(NASDAQ:CNDO) MLV Graig Suvannavejh Downgrade Hold (from buy)

Roth Capital Joseph Pantginis Downgrade Neutral (from buy)Partners

Wedbush Christopher Marai Downgrade Neutral (fromoutperform)

Richter also lowered her target to $2 from $18 after Coronado’s Trichuris suis ova (TSO) missed the primary endpoint in the Phase II TRUST-I trial totreat Crohn’s disease (see B18). While Coronado observed activity in patients with severe Crohn’s, Richter now “questions” the TSO platform, sayingTRUST-1 was critical in validating the approach. TSO comprises ova from T. suis, a porcine helminth. The ova act as a natural immunomodulator toregulate T cells and inflammatory cytokines following colonization of the host intestinal tract. TSO is also in investigator-initiated Phase II trials totreat ulcerative colitis, multiple sclerosis (MS), autism and psoriasis, for which data are expected this quarter.

Suvannavejh also lowered his target to $2 from $15 and removed all TSO-related revenue from his model, noting the “relatively limitedinformation” for the platform’s potential in severe patients.

Pantginis also lowered his target to $2 from $24 on the TSO results.

Marai also lowered his target to $3 from $13 and now views CNDO-109 as the primary value driver for Coronado. CNDO-109, a cell therapy thatactivates natural killer (NK) cells, is in Phase I/II testing for acute myelogenous leukemia (AML). Marai expects Coronado to begin Phase IIb testingwith CNDO-109 next year.

Exact Sciences Corp. Wedbush Zarak Khurshid Upgrade Outperform (from(NASDAQ:EXAS) neutral) 12% $11.26

Khurshid upgraded and maintained his $12 target ahead of an anticipated FDA approval of Cologuard in early 2014 and a national reimbursementcoverage decision within 90 days of approval. Cologuard is under parallel review by FDA and the Centers for Medicare & Medicaid Services toscreen for colorectal cancer. He estimates $234M in 2016 sales for the non-invasive stool DNA test that uses a multiplexed quantitative Invader assayfor the simultaneous detection of methylated and unmethylated sequences in the promoter region of the vimentin (VIM) gene.

Geron Corp. (NASDAQ:GERN) MLV George Zavoico New B u y 39% $4.28

Zavoico initiated coverage with a $6.50 target ahead of data from an investigator-sponsored Phase II trial of imetelstat (GRN163L) in myelofibrosis(MF) to be presented at the American Society of Hematology (ASH) meeting in December. He said imetelstat showed “promising signs of durableefficacy” in another Phase II trial for essential thrombocythemia data and expects the MF trial to confirm the product’s disease-modifying effect.Zavoico believes imetelstat could become the preferred front-line treatment for MF over Jakafi ruxolitinib from Incyte Corp. (NASDAQ:INCY). Heestimates $1.6B in 2019 sales of imetelstat, an oligonucleotide that competitively inhibits telomerase activity, in MF.

Vivus Inc. (NASDAQ:VVUS) Piper Jaffray Charles Duncan Downgrade Neutral (from -13% $9.79overweight)

Duncan also lowered his target to $11 from $14, saying competition for Qsymia phentermine/topiramate will become “more onerous.” WhileDuncan remains positive on additional reimbursement and a possible commercial partnership in 2014, he said Vivus has “the yeoman’s task” ofdriving acceptance of the pharmacologic treatment of obesity amongst doctors and payers. Duncan also noted that Vivus management shared anestimated 108,000 Qsymia prescriptions of 3Q13, which fell short of IMS Health’s prediction of 120,000.

Waters Corp. (NYSE:WAT) Mizuho Peter Lawson Downgrade Neutral (from buy) 2% $106.48

Lawson downgraded, noting that the tool supplier’s share price is approaching his target of $110. He said he finds it difficult to increase his targetdue to weak end-market sentiment based on his pharmaceutical and diagnostic surveys. Lawson said his surveys revealed “near-term choppiness”around the pharmaceutical end-market, which represents about 55% of Water’s revenues.

BioCenturyCompany IndexOctober 21, 2013

Abbott A4Ablynx A7, A17Actelion A17ADC Therap A6Adenium A9ADMA Biologics A12, A17Advaxis A17Aeterna Zentaris A17

Alimera A15Almirall A15Alzheimer’s Assoc A10AMAG Pharma A15Amarin A15Amgen A5Anacor A17Ariad A15Astellas A5, A15AstraZeneca A5, A6Biodesy A14Biogen Idec A5

Boehringer Ingelheim A5Braeburn Pharma A5Bristol-Myers A14Bristol-Myers Squibb A4Celgene A17Ctrs for Medicare & Medicaid ServA10Clinical Data Interchange A5Coronado Bio A16Critical Path Inst A5Cubist A5DBV Technologies A17

Dr. Falk Pharma A16Eddingpharm A17Eli Lilly A2, A10Emmaus Life Sci A14FDA A6, A9, A10Forest Labs A5Genentech A7, A8GE A14GlaxoSmithKline A2Hemera Bio A8immatics A13Ironwood Pharma A15

See page A22


EPS watchAt least six biotechs and pharmas reported earnings last week. Sales of new products helped big pharmas Johnson & Johnson (NYSE:JNJ) and Roche(SIX:ROG; OTCQX:RHHBY) beat the Street’s revenue estimates. For instance, J&J reported a 73% increase in sales of Zytiga abiraterone to $464 millionin 3Q13. The drug was approved for metastatic castration-resistant prostate cancer (CRPC) in the U.S. and EU in 2011. The label was expanded tochemotherapy-naïve patients in the U.S. in 2012 and in the EU earlier this year. J&J added $6.1 billion to its market cap last week. In its 3Q13 update,Roche CEO Severin Schwan highlighted uptake of breast cancer drugs Perjeta pertuzumab and Kadcyla ado-trastuzumab emtansine. Perjeta sales in 3Qwere CHF78 million ($86 million), while sales of Kadcyla were CHF73 million ($80 million). Perjeta was launched in the U.S. in 2012 and in the EU inMarch, and Kadcyla was launched in the U.S. in February. Kadcyla uses antibody-drug conjugate technology from ImmunoGen Inc. (NASDAQ:IMGN).Roche added $2.8 billion to its market cap last week, while shares of ImmunoGen were up 4% on the week. Abbott Laboratories (NYSE:ABT) tackedon more than $5 billion to its valuation after beating the Street’s revenue and earnings expectations. The company also increased its quarterly dividendby 57% to $0.22 per share. Molecular diagnostic company Cepheid Inc. (NASDAQ:CPHD) closed up 10% on the week after outperforming the Streetand raising its 2013 revenue and non-GAAP EPS guidance. Mcap in $M

3Q13 3Q13 GrowthEPS EPS from 10/18 Wk % Mcap 10/18

Company est actual Outcome 3Q12 cls chg chg chg Mcap

Abbott Laboratories $0.51 $0.55 Beat by $0.04 31% $37.29 $3.53 10% $5,471.5 $57,799.5(NYSE:ABT)

3Q13 worldwide sales were up 4% to $5.37B. The Street was expecting $5.39B. 3Q13 sales from established pharmaceuticals came in at $1.2B, up0.6% from 3Q12. Medical device sales were up 4% to $1.3B, while diagnostics sales were up 11% to $1.1B. Sales in emerging markets were $2.2B,up 8%. Percentage changes for sales figures exclude the impact from currency exchange rates. SG&A fell 10% to $1.7B. The pharma spun out itsresearch-based pharmaceutical business AbbVie Inc. (NYSE:ABBV) at the start of this year. Abbott reiterated 2013 EPS guidance of $1.98-$2.04.

Actelion Ltd. (SIX:ATLN) NA NA NA NA CHF64.60 CHF1.05 2% $138.9 $8,547.0

Core EPS for the nine months ended Sept. 30 was CHF3.60, up 21% from CHF3.09 in the same period last year. Total product sales for the firstnine months were up 4% to CHF1.3B ($1.5B). Sales of Tracleer bosentan for pulmonary arterial hypertension (PAH) were up 3% to CHF1.1B ($1.3B),while sales of the company’s other PAH drug, Ventavis iloprost, fell 2% to CHF83M ($91.3M). Core R&D expenses dropped by 12% to CHF251M($276M) as a result of last year’s cost saving initiative. Actelion reiterated that it expects double-digit core earnings growth in 2013, “at least at thesame level” of earnings growth in 2014, and at least single-digit growth in 2015. Percent changes are based on local currencies.

Baxter International Inc. $1.19 $1.19 Met 4% $66.00 $0.00 0% $0.0 $35,838.0(NYSE:BAX)

3Q13 net sales were up 9% to $3.77B from $3.5B. The Street was expecting $3.81B. Baxter BioScience revenues, which include plasma-basedtherapies and vaccines, were $1.6B, up 6% from 3Q12. Revenues for the company’s Medical Products business, which manufactures products usedin the delivery of fluids and drugs to patients, were up 10% to $2.2B. 3Q13 R&D expenses were unchanged at $290M. Baxter expects 3Q13 EPS of$1.24-$1.26.

Cepheid Inc. -$0.12 -$0.02 Beat by $0.10 NA $40.67 $3.72 10% $251.4 $2,748.2(NASDAQ:CPHD)

The company reported a loss per share of $0.32 in 3Q12. 3Q13 total revenue for the molecular diagnostic company increased 24% to $100.1Mfrom $81M in 3Q12, and beat the Street’s estimate of $93.9M. Clinical reagent sales increased 36% to $74.4M. The company raised its 2013 revenueguidance to $389M-$391M from $380-$385M and its non-GAAP EPS guidance to $0.22-$0.24 from $0.18-$0.21.

Johnson & Johnson $1.32 $1.36 Beat by $0.04 9% $91.63 $2.18 2% $6,104.0 $256,564.0(NYSE:JNJ)

3Q13 sales increased 5% to $17.6B from $17.1B. The Street was expecting $17.4B. Pharmaceutical sales were $7B in 3Q13, up 11% from $6.4B. 3Q13sales of autoimmune drug Remicade infliximab came in at $1.7B, up 7% from 3Q12. Sales of prostate cancer drug Zytiga abiraterone, which J&Jobtained from its 2009 acquisition of Cougar Biotechnology Inc., increased by 73% to $464M. Selling, marketing and administrative expensesincreased by 2% to $5.3B in 3Q13. Percentage changes for sales figures exclude the impact from currency exchange rates. The company increasedits 2013 guidance for EPS excluding special items to $5.44-$5.49 from $5.40-$5.47.

Roche (SIX:ROG; NA NA NA NA CHF241.10 CHF2.50 1% $2,833.2 $229,328.6OTCQX:RHHBY)

The pharma did not provide earnings figures for the quarter or the nine months ended Sept. 30. 3Q13 sales grew 8% to CHF11.6B ($12.7B) fromCHF11.3B in 3Q12. The Street was expecting CHF11.5B. 3Q13 sales of cancer drug MabThera/Rituxan rituximab rose 12% to CHF1.8B ($2B), whileAvastin bevacizumab was up 14% to CHF1.6B ($1.8B) and sales of Herceptin trastuzumab were up 7% to CHF1.5B ($1.7B). The pharma recordedCHF78M ($86M) in worldwide 3Q13 sales of breast cancer drug Perjeta pertuzumab. 3Q13 sales of Kadcyla ado-trastuzumab emtansine wereCHF73M ($80M). U.S. sales were up 12% and included a sales reserve release in the third quarter of CHF184M ($202M) related to a provision inthe U.S. healthcare reform law. Sales in China were up 23%. The pharma reiterated its expectation that 2013 sales will increase in line with 2012 salesgrowth. 2012 sales increased 4% to CHF45.5B ($49.7B). All percent changes assume constant currency.

‘It’s the BioCentury’TM


BioCentury tracks 622 issues that report prices and volume daily. TheBioCentury 100 is a subset used to monitor price and volume trends.

BioCentury 100 Price & Volume TrendCumulative weekly performance of 100 bioscience stocks. 12-week period.Line shows Price Level change (Left scale. Index base=1000 on May 10,1996). Bars show cumulative volume in millions (right scale).

Price GainsStocks with greatest % price increase in the week ended Oct. 18.(Priced above $2; 5,000 minimum share volume)Company Ticker $Close $Chg %Chg Vol(00)Geron GERN 4.280 1.200 39% 361134Aastrom1 ASTM 5.200 1.110 27% 15332PeptiDream 4587 ¥14290 ¥3050 27% 51643Anacor ANAC 13.830 2.720 24% 34827GNI Group 2160 ¥548 ¥100 22% 259040Keryx KERX 11.260 1.921 21% 300912Receptos RCPT 33.910 5.710 20% 20882Novogen2 NVGN 4.650 0.770 20% 868009Genfit ALGFT €11.310 €1.860 20% 54385Aratana PETX 28.040 4.550 19% 11049Senomyx SNMX 4.200 0.680 19% 6634Halozyme HALO 12.050 1.950 19% 115780Trovagene TROV 8.300 1.300 19% 9700

Price DeclinesStocks with greatest % price decline (criteria as above).Company Ticker $Close $Chg %Chg Vol(00)Amarin3 AMRN 2.030 -3.060 -60% 1610385pSivida4 PSDV 2.870 -1.740 -38% 104827Ariad ARIA 2.670 -1.590 -37% 1351457Advaxis ADXS 3.750 -1.950 -34% 23036Alimera Sciences ALIM 2.480 -0.890 -26% 19621Vanda VNDA 7.830 -1.885 -19% 41599Immunomedics IMMU 4.475 -0.935 -17% 81111Prosensa RNA 4.290 -0.800 -16% 19256Onconova Therap ONTX 20.680 -3.300 -14% 9657

Volume GainsGreatest changes in volume above 5,000 shares.Company Ticker Vol(00) %Chg $Close $ChgSilence Therapeutics SLN 8743 1873% 255p -15pPortola PTLA 70257 1440% 23.750 1.140Novogen2 NVGN 868009 1335% 4.650 0.770Advaxis ADXS 23036 1125% 3.750 -1.950D. Western 4576 193435 314% ¥1160 -¥179Sequenom SQNM 305599 277% 2.420 -0.180Bind Therapeutics BIND 8331 245% 15.000 -0.310Response Bio5 RBM 226 224% C$2.10 -C$0.050Receptos RCPT 20882 223% 33.910 5.710

BioCentury 100 Advance-Decline TrendBC100 BC100 BC100

Week Price Stocks Gaining Stocks Decliningended level gaining vol. (00) declining vol. (00)

Sep 20 4349.18 59 5131580 39 2619537Sep 27 4385.38 51 3647598 48 3257319Oct 04 4447.20 52 5397319 46 4233189Oct 11 4214.86 20 1751917 80 9706436Oct 18 4322.17 66 5421463 32 6163352

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and 19 years of industry analysis and reportingbehind your data solutions needs

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BioCentury London IndexWeekly change in the combined market capitalization for 14 biosciencestocks listed on the LSE or AIM, 12-week period. Index base =1000 onMay 10, 1996.

Oct 18

1 Reverse split shares 1-for-20 on 10/16. Price and volume adjusted toreflect split.2 Includes volume from Australian Stock Exchange with converted ADSs(1ADS = 25 shares)3 Volume figure is of ADSs (1ADS = 1 share)4 Includes volume from ASX5 Includes volume from Toronto Stock Exchange and OTCBB


Featured links this week

Links to the following documents reside online on the BioCentury onBioBusiness page of www.biocentury.com.

Biosimilars

Letter from California Gov. Jerry Brown to the California StateSenate saying Brown supports allowing biosimilars to be substi-tuted for biologics once FDA has determined they are inter-changeable but that the physician notification requirement of abill that would have allowed substitution of a biosimilar only ifFDA declared the biosimilar interchangeable for the specific useis “premature” (see BioCentury Extra, Monday, Oct. 14).

Cancer

Paper published in The Lancet on the economic burden of canceracross the EU.

Clinical trials

White paper from TransCelerate BioPharma Inc. and CDISCon standards for asthma clinical data and guidelines fromTransCelerate for site qualification and training (see Cover Story).

HCV

FDA revised draft guidance recommending the use of sustainedvirologic response (SVR) at 12 weeks after the end of treatmentas the primary endpoint in registration trials of chronic HCVtherapies (see BioCentury Extra, Wednesday, Oct. 16).

Orphan drugs

Summary of actions taken at the Oct. 8-10 meeting of EMA’sCommittee for Orphan Medicinal Products (COMP).

Product documentation

— Bosulif: Germany’s Federal Joint Committee (G-BA) finalbenefit assessment concluding that Bosulif bosutinib has an“unquantifiable” additional benefit for adults with chronic,accelerated or blast phase Philadelphia chromosome-positive(Ph+) chronic myelogenous leukemia (CML); from Pfizer Inc.(NYSE:PFE) (see BioCentury Extra, Thursday, Oct. 17).— Constella: Germany’s Federal Joint Committee (G-BA) finalbenefit assessment concluding that Constella linaclotide has “noadditional benefit” for irritable bowel syndrome with constipa-tion (IBS-C) vs. a change in diet and symptom-specific treatment,

G-BA’s requested comparator; from Almirall S.A. (Madrid:ALM)and Ironwood Pharmaceuticals Inc. (NASDAQ:IRWD) (seeBioCentury Extra, Thursday, Oct. 17).— Giotrif: EMA’s CHMP EPAR for Giotrif afatinib to treat locallyadvanced or metastatic non-small cell lung cancer (NSCLC) withactivating EGFR mutations in patients who are EGFR tyrosinekinase inhibitor (TKI)-naïve; from Boehringer IngelheimGmbH.— Impavido: Briefing documents for the Oct. 18 meeting ofFDA’s Anti-Infective Drugs Advisory Committee, which voted15-1, 14-2 and 13-3 that the safety and efficacy of Impavidomiltefosine to treat visceral, cutaneous and mucosal leishmania-sis, respectively, were adequately demonstrated; from PaladinLabs Inc. (TSX:PLB) (see BioCentury Extra, Friday, Oct. 18).— Incresync: EMA’s CHMP EPAR for Incresync alogliptin/pioglitazone to treat Type II diabetics who are uncontrolled onexisting therapies; from Furiex Pharmaceuticals Inc.(NASDAQ:FURX) and Takeda Pharmaceutical Co. Ltd.(Tokyo:4502).— Jetrea: Germany’s Federal Joint Committee (G-BA) finalbenefit assessment concluding that Jetrea ocriplasmin provides“significant” additional benefit vs. watchful waiting invitreomacular traction (VMT) patients with mild symptoms,which includes mild to moderate visual impairment; fromThromboGenics N.V. (Euronext:THR) (see BioCentury Extra,Thursday, Oct. 17).— Pixuvri: The U.K.’s NICE draft guidance recommendingagainst Pixuvri pixantrone to treat multiply relapsed or refrac-tory aggressive non-Hodgkin’s B cell lymphoma; from CellTherapeutics Inc. (NASDAQ:CTIC; Milan:CTIC).— Vascepa: Briefing documents for the Oct. 16 meeting of FDA’sEndocrinologic and Metabolic Drugs Advisory Committee,which voted 9-2 against expanding the label of Vascepaicosapent ethyl to include treatment of patients with mixeddyslipidemia in combination with statins prior to the comple-tion of Amarin’s REDUCE-IT cardiovascular outcomes trial;from Amarin Corp. plc (NASDAQ:AMRN) (see BioCenturyExtra, Wednesday, Oct. 16).— Vipidia: EMA’s CHMP EPAR for Vipidia alogliptin to treat TypeII diabetes in patients who are uncontrolled on existing therapies;from Furiex Pharmaceuticals Inc. (NASDAQ:FURX) and Take-da Pharmaceutical Co. Ltd. (Tokyo:4502).

J&J A5, A16Keryx A16MannKind A15MedImmune A6Medivation A15Medivir A16

Company Index,from page A19

Merck KGaA A5Mirati Therap A17Novartis A8, A15Novozymes A9Otsuka A14Paladin A17Pfizer A5PolyTherics A7Portola Pharma A17

Receptos A17Regeneron A8, A16Roche A5, A7, A8, A14Sanofi A5, A16Seattle Genetics A6Society of Nuclear Medicine andMolecular Imaging A10Stallergenes A17Stemline Therap A17

Tekmira A17Teva A17ThromboGenics A15TransCelerate BioPharma A1Tufts U A8UCB Group A5Valeant A17Vanda A16XenoPort A18

All press releases, news announcements and story inquiries should be submitted to ournews room at [email protected]. Editorial announcements emailed to the Editor-in-Chief

and/or the Publisher may not receive immediate attention and potential stories will be delayed.

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BioCenturyBioBusiness for the week ended October 18

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Using BioCentury Week in Review

You can read Week in Reviewonline every Monday atwww.biocentury.com

And you can set your own filters tocustomize your personal summary of the

week's corporate, clinical and financial news.BioCentury Week in Review is a com-

prehensive compendium of business newsfor management and investors in biosciencecompanies. It is organized into three depart-ments: Company News, Clinical News andFinancial News.

The index on this page lists all the com-panies covered this week. The news itemsin each department are organized alphabeti-cally by company. When more than onecompany is listed, the biotech company isshown first. Each brief is labeled with one ormore applicable business categories fromthe following list:

ADMET; Agbio/Environmental; Antibod-ies; Autoimmune; Bioinformatics; Bioman-ufacturing; Biopharmaceuticals; Biosimilars;Cancer; Cardiovascular; Chemistry; Combi-natorial biology; Computational chemistry/biology; Dental; Dermatology; Diagnostic;Drug delivery; Endocrine/Metabolic; Finance;Functional genomics; Gastrointestinal;Gene/Cell therapy; Generics; Genitouri-nary; Genomics; Hematology; Hepatic; Highthroughput screening; Infectious; Inflamma-tion; Microarrays; Microfluidics; Musculosk-eletal; Neurology; Nutraceuticals; Oph-thalmic; Other; Pharmaceuticals; Pharmaco-genetics; Proteomics; Pulmonary; Renal;Supply/Service; Transplant; Veterinary

WWWWWEEKEEKEEKEEKEEK INININININ R R R R REVIEWEVIEWEVIEWEVIEWEVIEW

Volume 21 • Number 40 • Page B1 of 29

WEEK OF OCTOBER 21, 2013

COMPANY NEWS

Deals (Page B2)

Ablynx (Euronext:ABLX)/EddingpharmADC /Spirogen/AstraZeneca (LSE:AZN;

NYSE:AZN)AmpliPhi Bio (Pink:APHB)/U of Glasgow/U of

LeicesterAstraZeneca (LSE:AZN; NYSE:AZN)/NRPBAstraZeneca (LSE:AZN; NYSE:AZN)/Wyss

Inst for Biologically Inspired Engineering atHarvard U

Berg Pharma/Icahn School of Med at Mt SinaiBiocartis/Hospital del MarBiogen Idec (NASDAQ:BIIB)/Isis (NASDAQ:

ISIS)BioInvent (SSE:BINV)/Sysmex (Tokyo:6869)/

Bayer (Xetra:BAYN)/RWTH Aachen UBioTime (NYSE-M:BTX)/Wistar InstBoston U/Medical Res CouncilCanterbury Labs/Hygeia Therap/Histogen/Stra-

tus Media Group (OTCQB:SMDI)Cel-Sci (NYSE-M:CVM)/Ergomed Clin ResCharleston Labs/Stanford UDance Biopharm/Harmony Asset (HKSE:428;

TSX:HAR)DBV (Euronext:DBV)/Stallergenes (Euronext:

GENP)Endo Health Sol (NASDAQ:ENDP)/MersanaEvotec (Xetra:EVT)/Boehringer IngelheimGalapagos (Euronext:GLPG; Pink:GLPYY)/

Genentech/Roche (SIX:ROG; OTCQX:RHHBY)

Galderma/Nuvo Research (TSX:NRI)Gold NanoTech/Shenzhen Chipscreen Bio.Heptares/MorphoSys (Xetra:MOR;

Pink:MPSYF)Hybrigenics (Euronext:ALHYG)/ImaxioInform Genomics/Tesaro (NASDAQ:TSRO)IntegraGen (Euronext:ALINT)/Assist Publique

- Hopitaux de Paris/Cntr Ntnl de la Recher-che Scientifique/INSERM/Paris Descartes U

Isis (NASDAQ:ISIS)/GlaxoSmithKline (LSE:GSK; NYSE:GSK)

Ixico/Phytopharm (LSE:PYM)JDRFMRM Proteomics/Jain Fndtn/PROOFOpen Monoclonal Tech/SymphogenPolyTherics/Tube Pharma

Rexahn (NYSE-M:RNN)/Ohio State USherrington /Sorrento (OTCQB:SRNED)Taris /AstraZeneca (LSE:AZN; NYSE:AZN)

Sales & Marketing (Page B7)

Cynvenio BioQuest Diagnostics (NYSE:DGX)

Other News (Page B7)

Anacor Pharma (NASDAQ:ANAC)/Valeant

(TSX:VRX; NYSE:VRX)AMAG Pharma (NASDAQ:AMAG)/SilverstrandBayer (Xetra:BAYN)/Natco (BSE:NATCO;

NSE:NATCOPHARM)Bioceros/4SC (Xetra:VSC)/Genedata/HorizonBiondVax (Tel Aviv :BNDX)/Isconova

(SSE:ISCO)/Retroscreen (LSE:RVG)/Seek/MHRA/Ntnl Cntr for Epidemiology/Nor-wegian Inst of Public Health/Robert KochInst/Statens Serum Inst/U of Gothenburg/Uof Groningen/UMCG

Cleveland BioLabs (NASDAQ:CBLI)/Ministryof Industry and Trade of the Russian Fed

Dainippon (Tokyo:4506; Osaka:4506)Genetic AllianceKymab/Regeneron (NASDASQ:REGN)NosopharmNovartis(NYSE:NVS; SIX:NOVN)QR Pharma/U of CaliforniaRoche (SIX:ROG; OTCQX:RHHBY)Savient (NASDAQ:SVNT)/US WorldMedsXenoPort (NASDAQ:XNPT)

Management Tracks (Page B10)

ADC TherapAkebia TherapAmgen (NASDAQ:AMGN)Angiotech PharmaAqualis (OSE:AQUA)BiodesyCyVekEvotec (Xetra:EVT)Genetic Tech (ASX:GTG; NASDAQ:GENE)G1 TherapInVivo Therap (OTCBB:NVIV)Iroko PharmaJ&J (NYSE:JNJ)MedacOsmotica PharmaSage TherapSimcere Pharma (NYSE:SCR)Syndax PharmaZS Pharma

CLINICAL NEWS

Regulatory (Page B11)

Actelion (SIX:ATLN)/Nippon Shinyaku (To-kyo:4516; Osaka:4516)

BioCentury Week in Review OCTOBER 21, 2013 PAGE B2 OF 29

COMPANY NEWS/Deals, Sales & Marketing, Other News, Management Tracks

Regulatory,from previous page

See next page

DEALS

Ablynx N.V. (Euronext:ABLX), Ghent, BelgiumEddingpharm Inc., Shanghai, ChinaBusiness: Musculoskeletal

Ablynx granted Eddingpharm exclusive, Chinese rights to developand commercialize ALX-0141, which has completed a Phase I trial totreat bone loss-related disorders. Ablynx will receive EUR 2 million($2.7 million) up front and is eligible for undisclosed milestones andtiered double-digit royalties. Eddingpharm will be responsible forclinical development, registration and commercialization in China.Ablynx will have rights to data generated by Eddingpharm. ALX-0141 isa nanobody against receptor activator of NF-kappa B ligand (RANKL).Dechert advised Ablynx, which declined to provide details. Eddingpharmcould not be reached in time for publication.

ADC Therapeutics S.a.r.l., Lausanne, SwitzerlandSpirogen Ltd., London, U.K.AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.Business: Cancer

AstraZeneca’s MedImmune LLC biologics unit partnered with ADCTherapeutics to co-develop two of the biotech’s undisclosed preclini-cal antibody-drug conjugate (ADC) cancer programs. ADC Therapeu-tics will receive an undisclosed upfront payment and is eligible forundisclosed development milestones. The biotech also has an optionto co-promote one of the programs in the U.S. MedImmune and ADCTherapeutics will share costs and profits. Private equity firm AuvenTherapeutics (formerly Celtic Therapeutics), which launched ADCTherapeutics last year, expects the two programs to enter clinicaltesting in 12-18 months. MedImmune and Auven each are making a $20million equity investment in ADC Therapeutics, and MedImmune’sBahija Jallal will join ADC’s board.

MedImmune also acquired Spirogen, which was majority owned byAuven, and its preclinical assets for $200 million in cash up front, plusup to $240 million in milestones. Spirogen’s existing licensing agree-ments and associated revenue streams are excluded from the acquisi-tion and have been transferred to a holding company 75% owned byAuven. MedImmune said SG2000 and related IP are part of the Spirogenacquisition, but Auven retains an option to acquire the product afterPhase II testing under a 2009 deal. The small molecule pyrrolobenzo-

Alimera (NASDAQ:ALIM)/pSivida (NASDAQ:PSDV; ASX:PVA)

Almirall (Madrid:ALM)/Ironwood (NASDAQ:IRWD)/Astellas (Tokyo:4503)/Forest Labs(NYSE:FRX)/AstraZeneca (LSE:ANZ;NYSE:AZN)

Amarin (NASDAQ:AMRN)Antares (NASDAQ:ATRS)/UmanApeiron BioBiogen Idec (NASDAQ:BIIB)/Genentech/

Roche (SIX:ROG; OTCQX:RHHBY)Boehringer IngelheimBTG (LSE:BTG)/Sanofi (Euronext:SAN;

NYSE:SNY)Cell Therap (NASDAQ:CTIC; Milan:CTIC)China Ntnl Pharma GroupChugai Pharma (Tokyo:4519)/Roche (SIX:ROG;

OTCQX:RHHBY)Genmab (CSE:GEN; OTCBB:GMXAY)/

GlaxoSmithKline (LSE:GSK; NYSE:GSK)Gilead (NASDAQ:GILD)/J&J (NYSE:JNJ)Iroko/Medicure (TSX-V:MPH; Pink:MCUJF)/

Merck(NYSE:MRK)MannKind (NASDAQ:MNKD)Medivation (NASDAQ:MDVN)/Astellas

(Tokyo:4503)Merck (NYSE:MRK)NewBridge Pharma/UCB (Euronext:UCB)/

Astellas (Tokyo:4503)Novo Nordisk (CSE:NVO; NYSE:NVO)NovoterisPaladin Labs (TSX:PLB)Pfizer (NYSE:PFE)3SBio/AMAG Pharma (NASDAQ:AMAG)/

Takeda (Tokyo:4502)

ThromboGenics (Euronext:THR)Vanda Pharma (NASDAQ:VNDA)/Bristol-

Myers Squibb (NYSE:BMY)

Clinical Results (Page B16)

Acacia PharmaAllaChemAnergisAriad Pharma (NASDAQ:ARIA)AstraZeneca (LSE:AZN; NYSE:AZN)BHV Pharma Inc., Research Triangle Park, N.C.Kissei Pharma (Tokyo:4547)CircassiaCoronado Bio (NASDAQ:CNDO)/Dr. Falk

PharmaCosmo (SIX:COPN)/Santarus (NASDAQ:SNTS)/

Dr. Falk PharmaEnanta Pharma (NASDAQ:ENTA)/AbbVie

(NYSE:ABBV)EsteveGenentech/Roche (SIX:ROG; OTCQX:RHHBY)Keryx (NASDAQ:KERX)/Panion & BF Bio/

Japan Tobacco (Tokyo:2914; Osaka:2914)/Torii (Tokyo:4551)

Medivir (SSE:MVIR B)Medivir AB (SSE:MVIR B)J&J (NYSE:JNJ)Merck (NYSE:MRK)Merck KGaA (Xetra:MRK)/Bristol-Myers

Squibb (NYSE:BMY)/Eli Lilly (NYSE:LLY)Novartis (NYSE:NVS; SIX:NOVN)Regeneron (NASDAQ:REGN)/Sanof i

(Euronext:SAN; NYSE:SNY)Sanofi (Euronext:SAN; NYSE:SNY)Synta (NASDAQ:SNTA)Taisho (Tokyo:4581)Takeda (Tokyo:4502)/GlaxoSmithKline (LSE:

GSK; NYSE:GSK)

Tekmira Pharma (TSX:TKM; NASDAQ:TKMR)

Clinical Status (Page B24)

Alkermes (NASDAQ:ALKS)Ariad Pharma (NASDAQ:ARIA)Arrowhead Res (NASDAQ:ARWR)AtterocorBioMarin (NASDAQ:BMRN)/Catalyst

(NASDAQ:CPRX)/Jazz (NASDAQ:JAZZ)CeltaxsysChugai (Tokyo:4519)/Daiichi (Tokyo:4568;

Osaka:4568)/Roche (SIX:ROG; OTCQX:RHHBY)

D-Pharm (Tel Aviv:DPRM)Dynavax Tech (NASDAQ:DVAX)/AstraZeneca

(LSE:AZN; NYSE:AZN)Genentech/Chugai Pharma (Tokyo:4519)/

Roche (SIX:ROG; OTCQX:RHHBY)H. Lundbeck (CSE:LUN)/Otsuka PharmaHanmi Pharma (KOSDAQ:128940)Insmed (NASDAQ:INSM)PledPharma (SSE:PLED)Portola Pharma (NASDAQ:PTLA)Promedior

FINANCIAL NEWS

Completed Offerings (Page B27)

ADMA Biologics (OTCQB:ADMA)Advaxis (NASDAQ:ADXS)Alliance Pharma (LSE:APH)BiodesyGalectin Therap (NASDAQ:GALT)G1 TherapHybrigenics (Euronext:ALHYG)immatics biotechnologies

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Deals,from previous page

Completed Offerings,from previous page

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diazepine (PBD) dimer is in Phase I/II testing for leukemia. The holdingcompany will also retain rights under previous agreements between theGenentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY, Basel,Switzerland) and Seattle Genetics Inc. (NASDAQ:SGEN, Bothell, Wash.).

Auven launched ADC Therapeutics to develop and commercializea pipeline of 10 preclinical ADC programs using Spirogen’s PBD payloadand linker technologies. Spirogen’s synthetic PBD dimers crosslinkDNA and interfere with DNA processes, including transcription andreplication. Lazard Freres advised Spirogen and ADC Therapeutics.

AmpliPhi Biosciences Corp. (Pink:APHB), Richmond, Va.University of Glasgow, Glasgow, U.K.University of Leicester, Leicester, U.K.Business: Infectious

AmpliPhi will provide undisclosed funding to a team at the Univer-sity of Leicester for preclinical studies of bacteriophage products totreat antibiotic-resistant Clostridium difficile infections. The bacterioph-age therapies will be evaluated for efficacy through in vivo studies, whichAmpliPhi will fund, at the University of Glasgow. The University ofGlasgow will receive research funding on a fee-for-service basis.AmpliPhi will license the patents, materials and know-how related tophages discovered by the team at the University of Leicester that havebeen shown to be effective against clinically relevant strains of C. difficile.Additionally, rights, title and interest to any IP developed under thisdeal will belong to AmpliPhi. The company will also have exclusiverights to background IP from the University of Leicester, which iseligible for milestones and royalties.

AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.National Research Program for Biopharmaceuticals (NRPB),Taipei, TaiwanBusiness: Pharmaceuticals

AstraZeneca partnered with the NRPB to make available to re-searchers in Taiwan an undisclosed set of about 20 small molecules andbiologics developed and selected by AstraZeneca. Academic institutesin Taiwan may submit research proposals for additional preclinical andclinical studies of small molecules and biologics developed byAstraZeneca that, if approved, will be funded by the NRPB. The partnerssaid that areas of high interest include cardiovascular, metabolic,respiratory, inflammation, autoimmune, infection and neurosciencediseases and cancer. AstraZeneca declined to disclose financial details,and the NRPB could not be reached.

AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.Wyss Institute for Biologically Inspired Engineering at HarvardUniversity, Boston, Mass.Business: ADMET

AstraZeneca and the institute partnered to develop and validateanimal-cell versions of the institute’s Organs-on-Chips for preclinicaldrug safety testing. Organs-on-Chips, which are composed of a clear,flexible polymer and contain hollow microfluidic channels lined withhuman cells, allow researchers to recreate the physiological andmechanical functions of the organ. The partners said the animal versionscould be a potential alternative to animal testing. The deal has an initialone-year term. The partners declined to disclose details.

Berg Pharma LLC, Boston, Mass.Icahn School of Medicine at Mount Sinai, New York, N.Y.Business: Pharmaceuticals, Diagnostic

Berg and the medical school partnered to discover and developbiologics and small molecules for cancer and CNS and endocrinedisorders. Over the five-year deal, the partners will use Berg’s Inter-rogative Biology platform in combination with Mount Sinai’s expertisein big data, advanced analytics and biological network modeling. Bergsaid the partners will collaboratively decide which candidates toadvance to clinical testing and that development responsibilities will bedetermined on a case-by-case basis. The partnership also aims todevelop diagnostic tools to improve pharmacovigilance, disease diag-nosis and markers of therapeutic efficacy.

Berg’s Interrogative Biology platform integrates molecular datadirectly from a patient with clinical and demographic information tolearn predictive patterns. Berg declined to disclose details, and themedical school could not be reached.

Biocartis S.A., Lausanne, SwitzerlandHospital del Mar, Barcelona, SpainBusiness: Diagnostic

Hospital del Mar granted Biocartis a license to the S492R mutationon the EGFR gene for developing a colon cancer test. The partners saidthe mutation can help identify patients who are resistant to cetuximabwhile remaining sensitive to panitumumab. The partners declined todisclose details.

Amgen Inc. (NASDAQ:AMGN, Thousand Oaks, Calif.) and TakedaPharmaceutical Co. Ltd. (Tokyo:4502, Osaka, Japan) marketpanitumumab as Vectibix. ImClone Systems Inc., a subsidiary of Eli Lillyand Co. (NYSE:LLY, Indianapolis, Ind.), Bristol-Myers Squibb Co.

Portola Pharma (NASDAQ:PTLA)Rexahn Pharma (NYSE-M:RNN)Sage TherapSeragon PharmaSofie BioTekmira (TSX:TKM; NASDAQ:TKMR)Theravectys

Proposed Offerings (Page B28)

EgaletOxford Immunotec GlobalPlethora Solutions (LSE:PLE)Stemline Therap (NASDAQ:STML)

TetraLogic PharmaVerona Pharma (LSE:VRP)

Amended Offerings (Page B28)

Aerie PharmaCancer Genetics (NASDAQ:CGIX)Mirati Therap (NASDAQ:MRTX)RelypsaRuthigenVeracyte

Other Financial News (Page B29)

Aastrom Bio (NASDAQ:ASTM)Amgen (NASDAQ:AMGN)Cambridge InnovationChimerix (NASDAQ:CMRX)

5AM VenturesGuided Therap (OTCBB:GTHP)iBio (NYSE-M:IBIO)MacroGenics (NASDAQ:MGNX)Mithril Cap MgmtNeptune Tech & Bio (NASDAQ:NEPT;

TSX:NTB)Sage TherapSQI Diagnostics (TSX-V:SQD)Vaccinogen (OTCQB:VGEN)Versant VenturesZalicus (NASDAQ:ZLCS)

BioCentury Extra:Online every business day.


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(NYSE:BMY, New York, N.Y.) and Merck KGaA (Xetra:MRK, Darmstadt,Germany) market cetuximab as Erbitux.

Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.Isis Pharmaceuticals Inc. (NASDAQ:ISIS), Carlsbad, Calif.Business: Musculoskeletal

Isis received a $10 million milestone payment from Biogen undera June 2012 deal to develop and commercialize an antisense drugcandidate targeting dystrophia myotonica-protein kinase (DMPK; DM1)to treat myotonic dystrophy type 1. The milestone was triggered byselection of ISIS-DMPKRx to advance to clinical testing, which Isis plansto begin next year. Biogen has through completion of the Phase II trialto exercise its option. Isis is responsible for discovery and develop-ment of ISIS-DMPKRx through Phase II and is eligible for up to $59million in development milestones prior to exercise of the option. IfBiogen Idec exercises the option, Isis would be eligible for an additional$200 million in a license fee and regulatory milestones, plus double-digit royalties (see BioCentury, July 2, 2012).

BioInvent International AB (SSE:BINV), Lund, SwedenSysmex Corp. (Tokyo:6869), Kobe, JapanBayer AG (Xetra:BAYN), Leverkusen, GermanyRWTH Aachen University, Aachen, GermanyBusiness: Bioinformatics, Antibodies, Pharmacogenetics

Bayer’s Bayer Technology Services GmbH subsidiary and the uni-versity partnered to form the Joint Research Center on ComputationalBiomedicine to develop new methods in computer-based modeling ofcomplex biological processes. Bayer said areas of research include re-engineering of drug action networks from high throughput data, clas-sification of disease states in cancer patients and monitoring of labexperiments in cell cultures. Bayer will contribute funding and adviceto the center, but said there will be no exchange of scientists betweenthe pharma and the university. The center, which is part of the ResearchCluster for Modeling and Simulation and the Faculty of Medicine at theuniversity, will be headed by professor Andreas Schuppert. The univer-sity declined to comment.

Separately, Bayer and BioInvent expanded a 2008 deal to allow Bayerbroader access to BioInvent’s discovery and development technologyplatform. BioInvent will receive an undisclosed license fee to cover newprojects and is eligible for milestones and royalties. In 2008, Bayerreceived a non-exclusive license to BioInvent’s n-CoDeR antibodylibrary to discover up to 14 human mAbs in all disease areas. Bayer saidtwo undisclosed projects resulting from the 2008 deal are in earlyclinical development. Bayer declined to disclose details, and BioInventcould not be reached (see BioCentury, March 17, 2008).

Bayer’s Bayer HealthCare AG unit also partnered with Sysmex’sSysmex Inostics GmbH subsidiary. Sysmex will use its BEAMing tech-nology to develop a blood-based companion diagnostic for Bayer’scancer treatments. BEAMing technology can detect circulating tumorDNA in blood samples. The companies declined to disclose details.

BioTime Inc. (NYSE-M:BTX), Alameda, Calif.Wistar Institute, Philadelphia, Pa.Business: Diagnostic

BioTime’s OncoCyte Corp. subsidiary partnered with the instituteto develop lung cancer diagnostic products. Wistar investigators areconducting a clinical trial to assess gene expression patterns in bloodcells of patients with malignant and non-malignant lung disease. OncoCytescientists will analyze blood samples obtained from patients in the trialto determine levels of tumor-associated proteins using its PanC-Dx

cancer diagnostic. OncoCyte will have an option to exclusively licenseany inventions, discoveries or technology developed by the institute orby OncoCyte using the institute’s technology during the collaborativeresearch.

Boston University, Boston, Mass.Medical Research Council, London, U.K.Business: Cardiovascular, Inflammation

MRC Technology, the U.K.’s Medical Research Council’s technol-ogy transfer organization, partnered with the university to develop ahumanized antibody against IL-16 to treat inflammatory diseases andischemic reperfusion injury. The university developed the antibody, andMRC humanized it. MRC will perform further engineering and X-raystructural analysis, and the university will test and validate the com-pound in vitro and in vivo. The development project is funded in partthrough a Biomedical Catalyst grant of £577,000 ($921,815). Thepartners could not be reached for details.

Canterbury Laboratories LLC, Holden, Mass.Hygeia Therapeutics Inc., Holden, Mass.Histogen Inc., San Diego, Calif.Stratus Media Group Inc. (OTCQB:SMDI), Los Angeles, Calif.Business: Dermatology, Gene/Cell therapy, Transplant

Stratus announced that it will merge with Hygeia and its spinout,Canterbury. The resulting company will remain publicly traded and becalled Restorgenex Corp., which plans to build an anti-aging skincarebrand for women over 45 years. Sol Barer, formerly chairman and CEOof Celgene Corp. (NASDAQ:CELG, Summit, N.J.), will become chair-man of Restorgenex, effective Nov. 1. Isaac Blech will become vice-chairman, effective Nov. 1. Yael Schwartz, founder and CEO of Canter-bury and Hygeia, will join Restorgenex’s board. She will also serve aspresident of the Canterbury and Hygeia divisions. The companies arefinalizing closing conditions for the deal.

Stratus also announced it has signed a letter of intent to merge withHistogen to “expand its entrance into the biotechnology industry.” Theboards of both companies have approved the LOI and the companies arecompleting a formal merger agreement. Gail Naughton, president, CEOand chairman of Histogen, will become CEO of Restorgenex, which willbe headquartered in San Diego. The deal is subject to the approval ofHistogen’s shareholders.

Histogen’s lead product, Hair Stimulating Complex (HSC), is inPhase I/II testing to treat alopecia. The product is a formulation ofwingless-type (Wnt) proteins and growth factors. Histogen said thatCanterbury and Hygeia are part of Histogen’s due diligence process andthat Stratus’ merger with Hygeia and Canterbury will not impact theHistogen/Stratus deal. Histogen declined to disclose its financial per-formance. Stratus reported $71,667 in revenue for the six monthsended June 30.

Cel-Sci Corp. (NYSE-M:CVM), Vienna, Va.Ergomed Clinical Research Ltd., Guilford, U.K.Business: Cancer

The partners expanded an April deal for development of Cel-Sci’sMultikine. Under the expanded deal, CRO Ergomed will assume 50% ofthe clinical and regulatory costs, up to $3 million, of developingMultikine to treat HPV/HIV co-infected women with cervical dysplasiain exchange for a single-digit percentage of any net income in theindication. The partners must jointly agree to the co-developmentprogram prior to implementation. Multikine has completed a Phase Itrial in the indication.

Under the April deal, Ergomed is already contributing up to $10million towards an ongoing Phase III trial of Multikine as a first-line


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treatment of advanced squamous cell carcinoma of the head and neck(SCCHN). Ergomed is eligible for a single-digit percentage of milestoneand royalty payments up to a specified, undisclosed amount. Multikine,a combination of cytokines, has Orphan Drug designation in the U.S. totreat SCCHN (see BioCentury, April 29).

Charleston Laboratories Inc., Charleston, S.C.Stanford University, Stanford, Calif.Business: Gastrointestinal, Neurology

Charleston Labs partnered with the anesthesiology, pain andperioperative medicine department of Stanford’s School of Medicine toevaluate anti-emetic effects on opioid-induced hyperalgesia and physi-cal dependence to prevent opiate withdrawal in patients on chronicopiates. Stanford is responsible for designing and performing experi-ments and analyzing and publishing results. Charleston Labs could notbe reached.

Dance Biopharm Inc., San Francisco, Calif.Harmony Asset Ltd. (HKSE:428; TSX:HAR), Hong Kong, ChinaBusiness: Endocrine/Metabolic

Dance and Harmony formed a JV to develop and commercializeDance’s Adagio inhaled insulin in China and other Asian countries,excluding Japan. Harmony, which will have majority ownership of the JV,will be responsible for the “majority” of the development expenses inmost of the regions and will receive ownership “commensurate with thelevel of expenses paid.” The JV will be governed by a board of directorscomprised of an even number of representatives from each company.Adagio completed the German Phase I/II Samba 01 trial evaluating Adagioin Type I diabetics. The partners declined to disclose details.

DBV Technologies (Euronext:DBV), Bagneux, FranceStallergenes S.A. (Euronext:GENP), Antony, FranceBusiness: Inflammation, Drug delivery

Stallergenes and DBV will develop and commercialize a birch allergyproduct using DBV’s Viaskin skin patch technology and birch pollenallergen from Stallergenes. DBV will conduct and Stallergenes will fundpreclinical work. Stallergenes will then have full development andcommercialization rights. DBV is eligible for up to €145 million ($196.7million) in milestones, plus royalties. Stallergenes also acquired a 2%equity stake in DBV.

Stallergenes and DBV first partnered in May to develop immuno-therapies for respiratory allergies. Under that deal, the partners aresigning separate agreements for selected aeroallergens to determinethe terms of development and commercialization (see BioCentury, May20).

Endo Health Solutions Inc. (NASDAQ:ENDP), Chadds Ford, Pa.Mersana Therapeutics Inc., Cambridge, Mass.Business: Cancer

Mersana received an undisclosed milestone payment from Endounder a 2012 deal to develop antibody-drug conjugates (ADCs) usingMersana’s Fleximer polymer technology and antibodies from Endo. Thepayment was triggered by an undisclosed preclinical event. Endo said thepreclinical ADC has the potential to treat various cancers. Mersana isresponsible for creating the ADCs, while Endo will be responsible fordevelopment, manufacturing and commercialization. Mersana declinedto disclose details, and Endo could not be reached (see BioCentury, March12, 2012).

Evotec AG (Xetra:EVT), Hamburg, GermanyBoehringer Ingelheim GmbH, Ingelheim, GermanyBusiness: Cancer

Evotec received a €4 million ($5.4 million) milestone payment fromBoehringer under an amended 2004 deal to jointly identify and developsmall molecules against GPCRs and other target classes. The paymentwas triggered by the transitioning of an undisclosed oncology moleculeto preclinical development. This is the twentieth milestone paymentEvotec has received under the deal, which was amended in 2009 toinclude cancer targets (see BioCentury, Nov. 16, 2009).

Galapagos N.V. (Euronext:GLPG; Pink:GLPYY), Mechelen, BelgiumGenentech Inc., South San Francisco, Calif.Roche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandBusiness: Chemistry

Galapagos’ Argenta Discovery Ltd. drug discovery service divisionand Roche’s Genentech unit extended their 2005 deal for three yearsto 2016. This is the fourth extension. The companies are collaboratingto discover compounds against undisclosed targets from Genentech.Galapagos’ BioFocus service division is providing additional drugdiscovery services for Genentech under a 2010 expansion (see BioCentury,Sept. 20, 2010).

Galderma S.A., Lausanne, SwitzerlandNuvo Research Inc. (TSX:NRI), Mississauga, OntarioBusiness: Neurology

Nuvo Research will receive a $2 million milestone payment earlynext year from Galderma under an amended 2008 deal granting Galdermaexclusive, worldwide rights to Pliaglis lidocaine/tetracaine from ZarsPharma Inc., which Nuvo acquired in 2011. The payment was triggeredby Brazilian approval of Pliaglis, which Galderma expects to launch inBrazil next year. The product is a phase-changing topical formulationof lidocaine and tetracaine to produce local anesthesia on intact skinin adults prior to superficial dermatological procedures.

Pliaglis is also approved in 16 European countries and Argentina.FDA approved Pliaglis for the indication in 2006, but Galderma volun-tarily removed the product from the market in 2008 due to issues withthe contract manufacturer. Galderma launched Pliaglis in the U.S. inMarch (see BioCentury, April 8).

Gold NanoTech Inc., Taipei, TaiwanShenzhen Chipscreen Biosciences Ltd., Shenzhen, ChinaBusiness: Cancer

Shenzhen Chipscreen granted Gold NanoTech’s GNT Biotech andMedicals Corp. subsidiary exclusive rights to develop and commercial-ize Chidamide in Taiwan. The small molecule histone deacetylase(HDAC) inhibitor is in Phase II testing for peripheral T cell lymphoma(PTCL), cutaneous T cell lymphoma (CTCL) and non-small cell lungcancer (NSCLC). GNT said it will develop and commercialize Chidamideprimarily in PTCL and NSCLC. Huya Bioscience International LLC (SanDiego, Calif.) has exclusive rights from Shenzhen Chipscreen to thecompound outside of China and Taiwan. Shenzhen Chipscreen declinedto disclose financial details, and GNT could not be reached.

Heptares Therapeutics Ltd., Welwyn Garden City, U.K.MorphoSys AG (Xetra:MOR; Pink:MPSYF), Martinsried, GermanyBusiness: Antibodies

Heptares received an undisclosed milestone payment fromMorphoSys under a February deal to discover and develop antibodiestargeting GPCRs. The milestone is the first Heptares has receivedunder the deal and was triggered by the generation of a stabilized formof the first GPCR target selected by MorphoSys, which will enable its




use as an antigen against which antibodies can be produced (seeBioCentury, Feb. 18).

Under the deal, Heptares is generating stabilized receptors usingits StaR technology for a set of GPCR targets selected by MorphoSys,which will then use its Ylanthia antibody library to develop therapeuticcandidates. The Ylanthia library contains over 100 billion human anti-bodies. Ylanthia uses 36 fixed, naturally-occurring heavy and light chainframework combinations.

Hybrigenics S.A. (Euronext:ALHYG), Paris, FranceImaxio S.A., Saint-Beauzire, FranceBusiness: Genomics

Hybrigenics acquired Imaxio’s genomics unit based in the BiopoleClermont-Limagne biotechnology park (Clermont-Ferrard, France).The unit performs fee-for-service studies extracting and sequencingDNA or RNA. Hybrigenics said the unit is certified by Agilent Technolo-gies Inc. (NYSE:A, Santa Clara, Calif.) to perform Agilent’s SureSelecttarget enrichment, comparative genomic hybridization and microRNAmicroarrays technologies. The unit also operates as a next-generationsequencing and genotyping platform for Illumina Inc. (NASDAQ:ILMN,San Diego, Calif.). Imaxio said it will now focus on its immunology R&Dbusiness. The partners declined to disclose financial details.

Inform Genomics Inc., Boston, Mass.Tesaro Inc. (NASDAQ:TSRO), Waltham, Mass.Business: Bioinformatics, Genomics

Tesaro will use Inform Genomics’ bioinformatics and genomicplatforms to evaluate the risk of chemotherapy-induced nausea andvomiting (CINV) in patients who receive “certain” moderatelyemetogenic chemotherapy regimens and standard antiemetic therapywithout a neurokinin 1 (NK1) substance P receptor (TACR1) antago-nist. Inform Genomics and Tesaro declined to disclose details.

Tesaro is developing rolapitant, a NK1 TACR1 antagonist, forCINV. An oral formulation is in Phase III testing and an IV formulationis in Phase I testing. Tesaro has exclusive, worldwide rights to rolapitantfrom Opko Health Inc. (NYSE:OPK; Tel Aviv:OPK, Miami, Fla.) (seeBioCentury, Oct. 7).

IntegraGen S.A. (Euronext:ALINT), Evry, FranceAssistance Publique - Hopitaux de Paris, Paris, FranceCentre National de la Recherche Scientifique, Paris, FranceInstitut National de la Sante et de la Recherche Medicale(INSERM), Paris, FranceParis Descartes University, Paris, FranceBusiness: Diagnostic

IntegraGen received exclusive, worldwide rights from the hospital,institutes and university for IP covering use of the oncology biomarkerhsa-miR-31-3p. The company said expression of the biomarker hasshown to be a predictor of progression-free survival (PFS) inpatients with metastatic colorectal cancer (mCRC) treated with anti-EGFR therapy. The company did not provide comment in time forpublication.

Isis Pharmaceuticals Inc. (NASDAQ:ISIS), Carlsbad, Calif.GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.Business: Infectious

Isis received two milestone payments totaling $7 million fromGlaxoSmithKline under a 2010 deal to discover and develop up to sixtherapeutics using Isis’ antisense technology against rare and seriousdiseases, including infectious diseases. The milestones were triggered

by the advancement towards IND-enabling toxicity studies of the ISIS-GSK3Rx program to treat viral infection. The product is an antisenseinhibitor against an undisclosed target. Isis, which said it is eligible toreceive additional milestones as ISIS-GSK3Rx advances, plus double-digit royalties, will develop ISIS-GSK3Rx to Phase II proof of concept,after which GSK has the exclusive option to license the program fordevelopment and commercialization. Isis declined to disclose details,and GSK could not be reached (see BioCentury, April 5, 2010).

Ixico plc, London, U.K.Phytopharm plc (LSE:PYM), Godmanchester, U.K.Business: Neurology, Diagnostic

Phytopharm completed its reverse merger with medical imagingcompany Ixico Ltd. Phytopharm shareholder owns about 45% and IxicoLtd. shareholders own about 55% of the resulting company, which isrenamed Ixico plc (see BioCentury, Oct. 7).

Juvenile Diabetes Research Foundation International (JDRF),New York, N.Y.Business: Endocrine/Metabolic

The not-for-profit and PureTech Ventures launched T1D Innova-tions (Boston, Mass.) to create and fund companies developing thera-pies for Type I diabetes. JDRF committed $5 million to the newco andsaid the goal is to secure up to an additional $25 million from otherinvestors, including not-for-profits and strategic investors. PureTechdid not contribute funding but received an undisclosed equity stake inT1D Innovations. The VC firm will select the investments and launch upto 10 companies, contingent on T1D Innovations raising $30 million,with the first company to be launched in six months to a year.

In connection with the debut of T1D Innovations, PureTech alsolaunched its Valley of Life initiative, in which the VC firm is aiming topartner with not-for-profits to invest with strategic and financialinvestors. T1D Innovations is the first output of the initiative.

MRM Proteomics Inc., Vancouver, B.C.Jain Foundation, Seattle, Wash.The Centre of Excellence for the Prevention of Organ Failure(PROOF), Vancouver, B.C.Business: Musculoskeletal

The not-for-profit PROOF Centre and MRM Proteomics partneredwith the Jain Foundation to identify blood-based biomarkers of diseasein individuals with limb-girdle muscular dystrophy 2B or Miyoshimyopathy. Jain said it is the sole funder and that MRM and PROOF willinitially receive a third of the undisclosed amount of funding and will beeligible for the remaining amount in milestone payments. Jain said it willidentify patients through its patient registry and participate throughoutthe collaboration, MRM Proteomics will perform mass spectrometryand PROOF will conduct clinical and data analysis. The partners willcompare blood samples from patients with samples from healthy, ageand gender-matched controls and test and validate differences inproteins and nucleic acids in the blood that reflect differences in musclefunction as possible biomarkers. Jain will have rights to the resultingdata.

Open Monoclonal Technology Inc., Palo Alto, Calif.Symphogen A/S, Copenhagen, DenmarkBusiness: Antibodies

Symphogen received access to Open Monoclonal Technology’sgenetically engineered animals OmniRat and OmniMouse. Symphogenwill use its Symplex B cell-based antibody discovery technology toidentify candidates against undisclosed targets using the animal plat-forms. Symphogen will pay Open Monoclonal Technology undisclosed

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annual access fees, and the biotech will be eligible for undisclosedmilestones, plus royalties for each product derived from the mAbplatforms. Symphogen could not be reached for details.

PolyTherics Ltd., London, U.K.Tube Pharmaceuticals GmbH, Vienna, AustriaBusiness: Cancer

PolyTherics and Tube partnered to develop antibody-drug conju-gates (ADCs) to treat cancer using PolyTherics’ ThioBridge conjuga-tion technology and Tube’s cytotoxic synthetic tubulin binding agentscalled cytolysins. The companies will produce reagents to link antibod-ies to cytolysins. The partners plan to conduct feasibility studiesevaluating ThioBridge with a cytolysin for companies supplying antibod-ies, or the partners will supply the conjugate for companies to developin-house. The partners also plan to conduct preclinical testing of ADCcandidates that PolyTherics acquired through its July merger withAntitope Ltd. and then partner the compounds. The partners will sharerevenues arising from licensing deals but declined to disclose financialterms (see BioCentury, Aug. 5).

Rexahn Pharmaceuticals Inc. (NYSE-M:RNN), Rockville, Md.The Ohio State University, Columbus, OhioBusiness: Drug delivery

Rexahn received an exclusive license to lipid-coated albuminnanoparticle (LCAN) drug delivery technology from the university’sOhio State Innovation Foundation. According to Rexahn, preclinicalstudies showed that the technology demonstrated the ability to deliveroligonucleotide compounds into tumors, which can result in improvedsafety and efficacy. Rexahn plans to develop RX-0201-nano using thetechnology. The product is a nanoliposomal protein kinase B (PKB;PKBA; AKT; AKT1) inhibitor. Rexahn could not be reached for details.

Sherrington Pharmaceuticals Inc., New York, N.Y.Sorrento Therapeutics Inc. (OTCQB:SRNED), San Diego, Calif.Business: Neurology

Sorrento acquired Sherrington for 200,000 Sorrento shares in adeal that valued Sherrington at $1.6 million based on Sorrento’s closeof $7.80 on Oct. 9, before the deal was announced. Sorrento will gainSherrington’s Resiniferatoxin, a selective agonist of transient receptorpotential vanilloid 1 (TRPV1; VR1) that is in an NIH-sponsored PhaseI/II trial to treat chronic pain in end-stage cancer patients.

Sorrento said Resiniferatoxin would fit into its products to treatcancer patients. Sorrento is developing Cynvilog in the U.S. to treatmetastatic breast cancer (mBC) and non-small cell lung cancer (NSCLC).The injectable nanoparticle formulation of paclitaxel is in Phase IItesting and is being developed under section 505(b)(2) of the Food,Drug and Cosmetic Act, which allows sponsors to reference data onsafety and efficacy from the scientific literature or from previouslyapproved products. The product is approved in South Korea to treatNSCLC and mBC. In September, Sorrento acquired exclusive, U.S.rights through the acquisition of Igdrasol Inc., which received rightsfrom Samyang Corp. (KSE:000070, Seoul, South Korea) under a 2012deal.

Taris Biomedical Inc., Lexington, Mass.AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.Business: Cancer

Taris and AstraZeneca partnered to evaluate bladder cancer thera-pies using Taris’ bladder delivery technology with undisclosed geneti-cally targeted compounds from AstraZeneca. The pharma will have an

exclusive option to license products resulting from the deal. Taris’technology is inserted into the bladder by a physician using standardprocedures and without general anesthesia. The system providescontinuous local delivery to the bladder for days to weeks. Thecompanies did not disclose financial terms.

SALES & MARKETING

Cynvenio Biosystems Inc., Westlake Village, Calif.Business: Diagnostic

Cynvenio launched worldwide its ClearID monitoring program forearly detection of breast cancer recurrence. The program, which usesblood samples that are analyzed at the company’s CLIA-certifiedlaboratory, first detects the level of potential tumor cells in the bloodusing the ClearID SCORE test. If the level is greater than 15 cells/mL,the ClearID SEQ test is used to analyze 50 oncogenes in the cells. Thecompany then generates a genomic report detailing the types ofmutations, available therapies and open clinical trials. The programincludes four blood tests, which are recommended quarterly. Cynveniosaid the cost would be comparable to other genomic tests in theoncology field.

Quest Diagnostics Inc. (NYSE:DGX), Madison, N.J.Business: Diagnostic

Quest launched BRCAvantage, a suite of four laboratory-developedgenetic tests that identify breast cancer 1 early onset (BRCA1) andBRCA2 mutations, which are associated with increased risk of inher-ited breast and ovarian cancers. The tests use next-generation sequenc-ing and multiplex ligation dependent probe amplification. As part of thelaunch, Quest will also provide access to third-party genetic counselorsto clinicians and patients. Quest said the list price for the four tests isa total of about $2,500.

OTHER NEWS

AMAG Pharmaceuticals Inc. (NASDAQ:AMAG), Lexington, Mass.Silverstrand Investments, location undisclosedBusiness: Hematology

The U.S. Supreme Court will not review an appeal of a case involvinganemia drug Feraheme ferumoxytol. In a February ruling on SilverstrandInvestments, et al. v. AMAG Pharmaceuticals, et al. the First Circuit Courtof Appeals affirmed in part a decision by the U.S. District Court for theDistrict of Massachusetts siding with investor Silverstrand that AMAGfailed to disclose serious adverse events associated with Feraheme ina January 2010 offering prospectus. The 23 adverse events occurred inthe six months between FDA approval of Feraheme in July 2009 to treatiron deficiency anemia in patients with chronic kidney disease (CKD)and AMAG’s $173.7 million follow-on in January 2010, in whichSilverstrand participated. The First Circuit denied a petition for rehear-ing the case in March. AMAG filed its petition for a writ of certiorarito the Supreme Court in June. AMAG said it does not comment onpending litigation (see BioCentury, July 6, 2009 & Jan. 25, 2010).

AMAG reported 1H13 U.S. net product sales of $33 million forFeraheme, an IV iron replacement therapeutic. Feraheme is underreview by FDA to expand its indication to include the treatment of alladult patients with iron deficiency anemia who have failed or could nottolerate oral iron treatment. Last week, FDA extended the PDUFA datefor the sNDA by three months to Jan. 21, 2014, from Oct. 21.

Anacor Pharmaceuticals Inc. (NASDAQ:ANAC), Palo Alto, Calif.Valeant Pharmaceuticals International Inc. (TSX:VRX; NYSE:VRX),Montreal, Quebec


Business: InfectiousAn arbitrator awarded Anacor $100 million in damages as part of

a contract dispute with Valeant. The dispute covers a 2004 deal betweenAnacor and Dow Pharmaceutical Sciences Inc., under which Dow wasproviding services to help Anacor develop its topical antifungal agenttavaborole. Valeant — which is developing eflinaconazole, a competi-tor to tavaborole — acquired Dow Pharmaceutical in 2008. Anacor wasseeking damages of at least $215 million plus injunctive relief. Thecompany said it expects a court to confirm the damages award beforeyear end. At June 30, Anacor had $45.8 million in cash.

An NDA for tavaborole is under FDA review for onychomycosis,with a July 29, 2014, PDUFA date. In May, Valeant would not launchefinaconazole until after the September arbitration hearing. Later thatmonth, the company received a complete response letter from FDA forJublia efinaconazole to treat onychomycosis. Earlier this month, HealthCanada approved Jublia for the indication. Valeant has worldwidecommercialization rights, excluding Japan, China, Taiwan and SouthKorea, to the topical triazole antifungal from Kaken Pharmaceutical Co.Ltd. (Tokyo, Japan) (see BioCentury, May 20 & June 3).

Bayer AG (Xetra:BAYN), Leverkusen, GermanyNatco Pharma Ltd. (BSE:NATCO; NSE:NATCOPHARM), Hyderabad,IndiaBusiness: Cancer, Generics

Bayer said it is pursuing in the Mumbai High Court a case againstNatco’s compulsory license in India to manufacture and market ageneric version of Bayer’s Nexavar sorafenib for kidney and livercancer. The court is a level below India’s Supreme Court. The pharmadeclined to disclose details, and Natco could not be reached.

In March, India’s Intellectual Property Appellate Board (IPAB)upheld a 2012 decision granting Natco the compulsory license. Bayerwas appealing the license, which the Indian Patent Office granted lastMarch because Bayer did not make Nexavar available to the public at a“reasonably affordable price.” In September, IPAB rejected a petitionfrom Bayer for a stay of the order granting the compulsory license whilethe appeal was pending (see BioCentury, March 19, 2012; Sept. 24, 2012& March 5, 2013).

The pharma’s Indian patent covering Nexavar expires in 2021. Bayerand Onyx Pharmaceuticals Inc. (NASDAQ:ONXX, South San Francisco,Calif.) have a worldwide co-development agreement for Nexavaroutside of Japan, where Bayer owns rights. Nexavar is an inhibitor ofCRAF (RAF1) and multiple receptor tyrosine kinases.

Bioceros B.V., Utrecht, the Netherlands4SC AG (Xetra:VSC), Planegg-Martinsried, GermanyGenedata AG, Basel, SwitzerlandHorizon Discovery Ltd., Cambridge, U.K.Business: Cardiovascular, Genomics, Gene/Cell therapy

The CV genes-at-target consortium led by German Heart CenterMunich (Munich, Germany) received a €5.8 million ($7.8 million) grantfrom the EU’s Framework Programme 7 (FP7) to evaluate genomic riskloci for coronary artery disease (CAD) and stroke in in vitro and in vivosettings and determine whether any are suitable targets for therapeu-tics. The consortium includes the biotechs and bio IT company ClinicalGene Networks AB (Stockholm, Sweden), CRO European ScreeningPort(Hamburg, Germany), German Heart Center Munich (Munich, Ger-many), Ludwig Maximilian University of Munich (Munich, Germany),Oxford University (Oxford, U.K.), University Medical Center Utrecht(Utrecht, the Netherlands), the University of Leicester (Leicester,

U.K.) and the University of Luebeck (Luebeck, Germany).Horizon will work with Leicester University to engineer the

candidate genomic risk loci into human cell lines using Horizon’sGenesis genome editing platform. The consortium will then carry outmolecular profiling of the cell lines, including analysis of locus-specificand global gene expression, to determine which SNP variations predis-pose individuals to cardiovascular disease. UMC Utrecht, 4SC, Biocerosand European Screening Port will identify lead molecules against anytarget loci chosen by the consortium.

BiondVax Pharmaceuticals Ltd. (Tel Aviv:BNDX), Ness Ziona,IsraelIsconova AB (SSE:ISCO), Uppsala, SwedenRetroscreen Virology Group plc (LSE:RVG), London, U.K.Seek Ltd., London, U.K.Medicines and Healthcare products Regulatory Agency (MHRA),London, U.K.National Center for Epidemiology, Budapest, HungaryNorwegian Institute of Public Health, Oslo, NorwayRobert Koch Institute, Berlin, GermanyStatens Serum Institut, Copenhagen, DenmarkUniversity of Gothenburg, Gothenburg, SwedenUniversity of Groningen, Groningen, the NetherlandsUniversity Medical Center Groningen (UMCG), Groningen, theNetherlandsBusiness: Infectious

The Universal Influenza Vaccines Secured (UNISEC) consortium willreceive a €6 million ($8.1 million) grant from EU’s FrameworkProgramme 7 (FP7) to develop a universal influenza vaccine. UNISECcomprises the four companies, the five institutes and the three univer-sities. The University of Groningen, which is coordinating the consor-tium, will receive €1.5 million ($2 million) from the grant. UMCG willreceive €500,000 ($678,651). BiondVax said it will receive about€550,000 ($746,516) and will be responsible for defining technical andimmunological criteria for the vaccine. UNISEC will conduct two clinicaltrials, one of which will be sponsored by BiondVax and evaluate itsuniversal flu vaccine (M-001). The vaccine has completed two Phase IItrials and consists of nine conserved linear epitopes taken in triplicatefrom hemagglutinin (HA), nucleoprotein (NP) and matrix proteins ofthe influenza virus.

Cleveland BioLabs Inc. (NASDAQ:CBLI), Buffalo, N.Y.Ministry of Industry and Trade of the Russian Federation, Mos-cow, RussiaBusiness: Cancer

Cleveland BioLabs said its Russian subsidiary, BioLab 612 LLC,entered into a three-year contract worth RUB149 million ($4.6 million)with the ministry to develop the biotech’s Entolimod (CBLB502) forcolorectal cancer (CRC). Entolimod is in preclinical testing for CRC,with Phase Ib testing slated to start mid-2014. The contract requiresthat BioLab 612 attract matching in-kind funds to the project. Clevelandsaid it plans to satisfy the requirement by contributing Eurasian patentsto BioLab 612.

Entolimod, a radioprotectant derivative of the toll-like receptor 5(TLR5) agonist flagellin, is also in Phase I testing to treat solid tumors.Cleveland is also developing the compound as a medical radiationcountermeasure and to treat acute radiation syndrome (ARS) underFDA’s Animal Rule, which allows marketing approval to be grantedbased on efficacy in relevant animal models and an acceptable safety riskprofile in humans. The compound has Fast Track and Orphan Drugdesignations in the U.S. to prevent death following total body irradia-tion during or after radiation disaster.

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Other News,from previous page


Dainippon Sumitomo Pharma Co. Ltd. (Tokyo:4506; Osaka:4506),Osaka, JapanBusiness: Cancer

Dainippon launched Boston Biomedical Pharma Inc. to focus on thecommercialization of cancer therapies, including Dainippon’s BBI608. Theproduct, a small molecule targeting cancer stem cells, is in Phase III testingto treat colorectal cancer. Dainippon expects to launch the product inFY15, which ends March 31, 2016. Dainippon gained the compoundthrough its 2012 acquisition of Boston Biomedical Inc. The subsidiary isheadquartered in Cambridge, Mass. (see BioCentury, April 30, 2012).

Dainippon said the subsidiary would also be responsible for com-mercializing future cancer compounds, including BBI503, an oral smallmolecule that target cancer stem cells, and WT2725, a Wilms tumor 1(WT1) peptide cancer vaccine. The compounds are in Phase I testing.

Genetic Alliance, Washington, D.C.Business: Other

Genetic Alliance issued a request for proposals to offer its crowd-sourced Platform for Engaging Everyone Responsibly (PEER). GeneticAlliance will offer a customized, organization-branded installation ofPEER to up to nine disease and/or condition advocacy organizations(DAOs) that have not yet experienced a public meeting under PDUFAV, which requires FDA to hold at least 20 public meetings over a five-year span to prospectively inform benefit-risk assessments. The PEERinstallation will allow a DAO to collect patient perspectives on acondition’s severity and current unmet medical needs. Genetic Alliance’sgoal is to provide FDA with data to help determine benefit-riskconsiderations for patient-focused drug development and regulatoryreview process. Patients will chose with whom to share their data.

Eligible indications include alpha-1 antitrypsin deficiency, breastcancer, chronic Chagas disease, female sexual dysfunction, heritablebleeding disorders, idiopathic pulmonary fibrosis, sickle cell disease,irritable bowel syndrome (IBS), gastroparesis, gastroesophageal refluxdisease (GERD), neurological manifestations of inborn errors ofmetabolism Parkinson’s disease (PD), Huntington’s disease and pulmo-nary arterial hypertension.

Kymab Ltd., Cambridge, U.K.Regeneron Pharmaceuticals Inc. (NASDASQ:REGN), Tarrytown,N.Y.Business: Antibodies

Kymab said it notified the English Court that it will defend againstclaims by Regeneron that Kymab has infringed Regeneron’s Europeanpatent EP1360287 covering methods of modifying eukaryotic cells.Kymab said it will defend based on the grounds of non-infringement andinvalidity of the patent. Kymab, which declined to disclose details, isfocused on discovering and developing fully human mAbs using itsKymouse transgenic antibody platform. Regeneron, which filed theclaim on Sept. 25, said it expects Kymab to file its defense andcounterclaim in about mid-November.

Nosopharm S.A.S., Nimes, FranceBusiness: Infectious

Antibiotics company Nosopharm received a €870,000 ($1.2 mil-lion) grant from the French government under the Odilorhabdin:Preclinical optimization and study to combat antibiotic resistance(OOPERA) project. Nosopharm’s NOSO-95 is an Odilorhabdin anti-biotic derived from an entopathogenic bacterium of the Xenorhabdusgenus. NOSO-95 is in preclinical testing to treat multidrug-resistanthospital-acquired infections, including those caused by Gram-negative

bacteria. The company said the grant will fund preclinical developmentup to clinical testing. Nosopharm said it has used part of the funding toincrease headcount by three to seven.

Novartis AG (NYSE:NVS; SIX:NOVN), Basel, SwitzerlandBusiness: Cardiovascular

An interim report released by Japan’s Ministry of Health, Labor andWelfare (MHLW) found that Novartis may have violated Japanese lawby promoting hypertension drug Diovan valsartan as a treatment forreducing stroke risk, according to a Bloomberg article. Bloomberg saidthe report indicated there may not have been sufficient evidence for theclaim, as the data came from trials now under investigation. In Septem-ber, The Lancet retracted data published in 2007 from the Japanese PhaseIV Jikei Heart Study of Diovan to treat hypertension or other cardio-vascular disease after an internal investigation by the Jikei UniversitySchool of Medicine (Tokyo, Japan) found data manipulation and a conflictof interest. According to Bloomberg, MHLW’s report concluded thatthe “government should conduct an on-site inspection and take sternaction” against the pharma. Novartis in a statement said that it is“committed to working cooperatively with the MHLW” to addressconcerns related to Diovan advertising and has taken steps includingimplementing new operating procedures and mandatory employeetraining. Novartis reported worldwide net sales of $1.8 billion in 1H13for the small molecule angiotensin II receptor (type AT1) antagonist(see BioCentury, Aug. 12).

Business: MusculoskeletalThe U.S. Supreme Court refused to rehear an appeals court ruling

that upheld that Novartis is responsible for punitive damages afterfailing to adequately warn about the risks of Zometa zoledronic andAredia pamidronate. In Fussman v. Novartis Pharmaceuticals Corp., theU.S. District Court for the District of North Carolina ruled in 2010 thatNovartis intentionally concealed the risk of osteonecrosis of the jawbone with the drugs and awarded $287,000 in compensatory and$861,000 in punitive damages. Plaintiff Herbert Fussman’s wife sufferedosteonecrosis of the jaw bone, which led to her death, after receivingZometa and Aredia. Novartis appealed the ruling in the U.S. AppealsCourt for the Fourth Circuit arguing that a private citizen cannot suea pharmaceutical manufacturer in a state court for punitive damagesover a drug that received FDA approval. The appeals court affirmed thedistrict court ruling. Zometa and Aredia are bisphosphonates thatinhibit bone resorption to treat bone complications caused by cancer.

QR Pharma Inc., Berwyn, Pa.University of California, Los Angeles, Calif.Business: Neurology

QR Pharma and the university received a $3 million grant from theU.S. Army to test Posiphen in rat models to treat traumatic brain injury(TBI). The partners will continue to conduct preclinical studies of theamyloid precursor protein (APP) translation inhibitor in models ofconcussion and blunt head trauma, two forms of TBI. QR Pharma saidit discovered the compound inhibits the synthesis of tau and alpha-synuclein along with APP while developing Posiphen for Alzheimer’sdisease (AD). The company also said the grant is based on the compound’sinhibitory effect on tau in rodents and humans. QR Pharma has exclu-sive, worldwide rights to Posiphen from TorreyPines TherapeuticsInc., which merged with Raptor Pharmaceutical Corp. (NASDAQ:RPTP,Novato, Calif.) in 2009.

Roche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandBusiness: Cancer, Autoimmune

Over the next five years, Roche will invest CHF800 million ($879.2See next page



& Flom LLP and Cole, Schotz, Meisel, Forman & Leonard P.A. are thebiotech’s legal advisors, and Lazard is its financial advisor. Savientmarkets Krystexxa, a pegylated urate oxidase (uricase), to treat gout.

XenoPort Inc. (NASDAQ:XNPT), Santa Clara, Calif.Business: Autoimmune, Neurology

XenoPort investor Clinton Group Inc. said the biotech’s CEORonald Barrett should resign and called for a shift in the company’s focusto XP23829, which is in Phase I testing for relapsing-remitting multiplesclerosis (RRMS) and in preclinical testing for psoriasis. In a letter toBarrett, Clinton Group said XenoPort’s Horizant gabapentin enacarbil— which is approved in the U.S. to treat restless legs syndrome (RLS)and to manage postherpetic neuralgia (PHN) — “will never be thecommercial success we all wish it were.” The activist investor saidXenoPort should use its remaining cash to advance XP23829 in theclinic, which could “garner a significantly improved partnering deal” ora sale of XenoPort. The investor said XP23829 — an oral prodrug ofmonomethyl fumarate (MMF) that induces and activates the nuclearfactor (erythroid-derived 2)-like 2 (NRF2) pathway — “presents amassive commercial opportunity.” At June 30, XenoPort had $93.4million in cash and a six-month operating loss of $47.8 million.

Clinton Group — which has a 2.7% stake in XenoPort — also saidit believes the fair value of XenoPort is $13-$16 per share and that theshares are undervalued due to a lack of confidence in the biotech’smanagement. XenoPort said in a statement that it appreciates stock-holder input and will continue to review all aspects of the company’sbusiness. XenoPort closed Friday at $5.89.

XenoPort reacquired U.S. commercialization rights for Horizantfrom former partner GlaxoSmithKline plc (LSE:GSK; NYSE:GSK, Lon-don, U.K.) and reintroduced the drug in the U.S. in June. GSK reported$4.4 million in U.S. Horizant sales for the first nine months of 2012.Clinton Group said “it is nearly unprecedented for a drug re-launch toachieve significantly different commercial results” (see BioCentury, Nov.12, 2012).

MANAGEMENT TRACKS

Boards of Directors

ADC Therapeutics S.a.r.l., Lausanne, SwitzerlandBusiness: CancerAppointed: Bahija Jallal, EVP of the MedImmune LLC biologics unit ofAstraZeneca plc

Amgen Inc. (NASDAQ:AMGN), Thousand Oaks, Calif.Business: BiopharmaceuticalsAppointed: Greg Garland

Biodesy Inc., Burlingame, Calif.Business: Proteomics, Supply/Service, Computational chemistry/biol-ogyAppointed: William Burkoth, senior director of Pfizer Ventures; andAndrew Schwab, managing partner of 5AM Ventures

G1 Therapeutics Inc., Chapel Hill, N.C.Business: HematologyAppointed: Michael Gutch, managing director at MedImmune Ventures;and Ron Laufer, senior managing director at MedImmune

Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J.Business: PharmaceuticalsAppointed: Mark McClellan, a senior fellow and director of the Initia-

million) to increase production capabilities for its biologics, includingcancer drugs Perjeta pertuzumab and Kadcyla ado-trastuzumabemtansine and autoimmune drug Actemra/RoActemra tocilizumab. Theinvestment will be spread across sites in Penzberg, Germany; Basel,Switzerland; Vacaville, Calif.; and Oceanside, Calif. The pharma said itwill invest about CHF260 million ($285.7 million) in the U.S. sites,which will create about 250 jobs; about CHF350 million ($384.7million) in the Germany site, which will create about 200 jobs; and aboutCHF190 million ($208.8 million) in a new antibody-drug conjugate(ADC) production facility in Basel, which will create 50 jobs. Roche saidit has 39 investigational biologics in its pipeline, including eight ADCsin clinical development.

Perjeta, a humanized mAb HER dimerization inhibitor that preventsHER2 from binding to other HER receptors (HER1/EGF; HER3 andHER4), is approved in the U.S. and EU for treatment-naïve patients withHER2-positive metastatic breast cancer in combination with Herceptintrastuzumab and docetaxel and in Japan to treat HER2-positive inop-erable or recurrent breast cancer. This month, FDA granted acceler-ated approval to Perjeta from Roche’s Genentech Inc. unit for neoadjuvantbreast cancer. Genentech markets Herceptin in the U.S., while Rochemarkets it elsewhere. Chugai, which is majority owned by Roche, hasJapanese rights from the pharma to the product (see BioCentury, Oct. 7).

Kadcyla, a humanized mAb against HER2 linked to the DM1 cytotoxicagent from ImmunoGen Inc. (NASDAQ:IMGN, Waltham, Mass.), isunder review in the EU to treat HER2-positive, unresectable locallyadvanced or metastatic breast cancer in patients who previouslyreceived Herceptin and a taxane. FDA approved Kadcyla for theindication in February. Genentech has rights to use ImmunoGen’s TAPantibody-conjugate technology under a 2000 deal. Chugai has Japaneserights to the product (see BioCentury, May 8, 2000 & Feb. 25, 2013).

In June, the European Commission approved IV tocilizumab asRoActemra in combination with methotrexate or as monotherapy totreat polyarticular juvenile idiopathic arthritis (JIA) in children at least twoyears old who have responded inadequately to previous therapy withmethotrexate. The product is approved in the U.S., where it is known asActemra, for polyarticular JIA in children at least two years old. IVtocilizumab is approved in the U.S. and EU to treat moderate to severerheumatoid arthritis and systemic JIA in children at least two years old.Actemra, a humanized mAb against IL-6 receptor, has Orphan Drugstatus in the U.S. for polyarticular JIA (see BioCentury, June 17).

In February, Chugai and Roche said FDA accepted for review a BLAfrom Genentech for subcutaneous Actemra to treat moderate to severeRA. The PDUFA date is this month. Roche also submitted a regulatoryapplication to EMA for the product last December. Chugai co-developedthe product and markets it in Japan (see BioCentury, March 4).

Savient Pharmaceuticals Inc. (NASDAQ:SVNT), Bridgewater, N.J.US WorldMeds LLC, Louisville, Ky.Business: Endocrine/Metabolic

Savient filed for Chapter 11 bankruptcy in the U.S. Bankruptcy Courtfor the District of Delaware. Savient also entered into an acquisitionagreement with neurology company US WorldMeds and its subsidiarySloan Holdings C.V. whereby Sloan will acquire substantially all ofSavient’s assets, including Krystexxa pegloticase, for about $55 million.The court will supervise an asset auction. WorldMeds and Sloan are the“stalking horse,” or initial bidders, which entitles the companies to abreak-up fee of $1.7 million and expense reimbursement up to $750,000if the court approves a higher bid. Savient anticipates conducting theauction and closing the sale by year end. Skadden, Arps, Slate, Meagher


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tive on Value and Innovation in Health Care at the Brookings Institutionand formerly FDA commissioner and CMS administrator

Sage Therapeutics Inc., Cambridge, Mass.Business: NeurologyAppointed: Robert Nelsen, co-founder and managing director at ArchVentures

Management

Akebia Therapeutics Inc., Cincinnati, OhioBusiness: Hematology, CardiovascularHired: Jason Amello as SVP, CFO and treasurer, formerly EVP, CFO andtreasurer of Ziopharm Oncology Inc.

Angiotech Pharmaceuticals Inc., Vancouver, B.C.Business: Autoimmune, Cardiovascular, DermatologyTransitioned: Thomas Bailey to a director from president and CEO; andVictor Diaz to president and COO from EVP of global manufacturing andsupply chain management

Aqualis ASA (OSE:AQUA), Oslo, NorwayBusiness: Drug delivery, Cancer, InfectiousTransitioned: Ole Eriksen to healthcare CBO from COO

Biodesy Inc., Burlingame, Calif.Business: Proteomics, Supply/Service, Computational chemistry/biologyHired: Greg Yap as CEO and a director, formerly healthcare entrepre-neur-in-residence at General Electric Co.

CyVek Inc., Wallingford, Conn.Business: DiagnosticHired: Bill Dubiel as chief commercial officer, formerly VP of sales atRoche’s Roche Tissue Diagnostics unit

Evotec AG (Xetra:EVT), Hamburg, GermanyBusiness: Neurology, Endocrine/Metabolic, AutoimmuneHired: Thomas Hanke as EVP and head of immunology and inflammation,effective Nov. 1, formerly director of biopharmaceuticals innovationsourcing at Novo Nordisk A/S

Genetic Technologies Ltd. (ASX:GTG; NASDAQ:GENE), Fitzroy,AustraliaBusiness: DiagnosticTransitioned: Alison Mew to three-month health-related leave fromCEO; Tom Howitt becomes acting CEO while remaining CFO

InVivo Therapeutics Holdings Corp. (OTCBB:NVIV), Cambridge,Mass.Business: NeurologyHired: Lou Vaickus as interim CMO, while remaining president of aktaPharmaceutical Development LLC; he replaces Eric Woodard, whoremains a consultant and member of the scientific advisory board

Iroko Pharmaceuticals LLC, Philadelphia, Pa.Business: Cardiovascular, Autoimmune, InfectiousHired: Jyrki Mattila as CBO of Iroko’s iCeutica Inc. subsidiary, formerlypresident and CEO of LZ Therapeutics Inc.

Medac GmbH, Wedel, GermanyBusiness: Cancer, Autoimmune, DiagnosticHired: Terri Shoemaker, a director, as president and CEO ofMedac’s Medac Pharma Inc. subsidiary, formerly VP of sales atInterMune Inc.

Osmotica Pharmaceutical Corp., Wilmington, N.C.Business: Neurology, Drug deliveryHired: Kenneth Gayron as VP and CFO, formerly VP and treasurer atSensus USA Inc.

Simcere Pharmaceutical Group (NYSE:SCR), Nanjing, ChinaBusiness: Cancer, GenericsHired: Zang Jingwu as CSO

Syndax Pharmaceuticals Inc., Waltham, Mass.Business: CancerHired: Steven Fruchtman as CMO, formerly CMO of Spectrum Pharma-ceuticals Inc.

ZS Pharma Inc., Fort Worth, TexasBusiness: Renal, HepaticHired: Todd Creech as CFO, formerly VP of business development andCFO of SARcode Bioscience Inc., which Shire plc acquired

Management Tracks,from previous page

CLINICAL NEWS

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Clinical activities and selected announcements for the week ended October 18.

REGULATORY

Actelion Ltd. (SIX:ATLN), Allschwil, SwitzerlandNippon Shinyaku Co. Ltd. (Tokyo:4516; Osaka:4516), Kyoto, JapanProduct: Opsumit macitentan (formerly Actelion-1, ACT-064992)Business: Cardiovascular

FDA approved Opsumit macitentan from Actelion to treat pulmo-nary arterial hypertension (PAH). The company said it has not yetdetermined the price for the product, which it plans to launch in the U.S.next month. The tissue-targeting endothelin receptor antagonist is alsounder review in Europe for the indication, with a decision expected in

early 2014. Nippon has rights to co-develop and co-commercialize theproduct in Japan (see BioCentury, Feb. 22, 2010).

Alimera Sciences Inc. (NASDAQ:ALIM), Alpharetta, Ga.pSivida Corp. (NASDAQ:PSDV; ASX:PVA), Watertown, Mass.Product: Iluvien fluocinolone acetonide intravitreal implant (formerlyMedidur FA)Business: Ophthalmic

FDA issued a complete response letter for an NDA from Alimerafor Iluvien fluocinolone acetonide intravitreal implant to treat diabeticmacular edema (DME). According to the company, FDA identifiedconcerns with the benefit-risk and safety profiles of Iluvien and re-

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quested an additional clinical trial plus at least 12 months of follow-up.The company said it will meet with FDA’s Dermatologic and OphthalmicDrug Advisory Committee in January for advice on addressing theagency’s concerns and on whether a patient population can be identifiedin which the benefits of Iluvien outweigh its risks.

The complete response letter is the third from FDA for Iluvien. Inits previous November 2011 letter, the agency asked for 2 additionalclinical trials due to “significant” risks of adverse events in the PhaseIII FAME trials. Based on a meeting with FDA, Alimera did not conductthe trials and resubmitted the NDA with additional analysis of the FAMEtrials. The company also had narrowed the indication of the NDA to thesubgroup of patients with chronic DME, for which Iluvien is alreadyapproved in Austria, Portugal, the U.K., France and Germany. Previ-ously, Alimera had been seeking approval of Iluvien for all DME patients.Alimera has rights to the injectable insert delivering fluocinoloneacetonide (FA) to the retina from pSivida.

Almirall S.A. (Madrid:ALM), Barcelona, SpainIronwood Pharmaceuticals Inc. (NASDAQ:IRWD), Cambridge, Mass.Astellas Pharma Inc. (Tokyo:4503), Tokyo, JapanForest Laboratories Inc. (NYSE:FRX), New York, N.Y.AstraZeneca plc (LSE:ANZ; NYSE:AZN), London, U.K.Product: Constella (Linzess) linaclotide (ASP0456)Business: Gastrointestinal

Germany’s Federal Joint Committee (G-BA) issued a final benefitassessment for Constella linaclotide from Almirall that said Constellahas “no additional benefit” for irritable bowel syndrome with consti-pation (IBS-C) vs. a change in diet and symptom-specific treatment, G-BA’s requested comparator. The decision is in line with an Augustpreliminary assessment from Germany’s Institute for Quality andEfficiency in Healthcare (IQWiG) (see BioCentury, Aug. 5). Drugs that donot have an additional benefit are added to the reference pricing system,which gives a similar base price to therapeutically comparable drugs. Ifthere is no reference, companies negotiate a price no higher than thatof the lowest-cost alternative in the indication.

Almirall has exclusive rights to linaclotide from Ironwood inEurope and the Commonwealth of Independent States (CIS), andAstellas has exclusive rights from Ironwood to develop and commer-cialize linaclotide in Japan, Indonesia, Korea, the Philippines, Taiwanand Thailand. In October 2012, Ironwood partnered with AstraZenecato co-develop and co-commercialize linaclotide in China (see BioCentury,Oct. 29, 2012).

Amarin Corp. plc (NASDAQ:AMRN), Dublin, IrelandProduct: Vascepa icosapent ethyl (formerly Miraxion, AMR101)Business: Endocrine/Metabolic

FDA’s Endocrinologic and Metabolic Drugs Advisory Committeevoted 9-2 against expanding the label of Amarin’s Vascepa icosapentethyl to include treatment of patients with mixed dyslipidemia incombination with statins prior to the completion of Amarin’s REDUCE-IT cardiovascular outcomes trial. Data from REDUCE-IT are not ex-pected until at least 2016.

Amarin is seeking approval for Vascepa to treat high triglycerides— defined as triglyceride levels ≥200 mg/dL and <500 mg/dL — inpatients with mixed dyslipidemia and congenital heart disease (CHD)or CHD risk equivalents. The company defines CHD risk equivalentsas comprising other clinical forms of atherosclerotic disease, diabetesor multiple risk factors that confer a 10-year risk for CHD of >20%. ThesNDA has a Dec. 20 PDUFA date. Amarin already markets the >96%pure ethyl ester of eicosapentaenoic acid (ethyl-EPA) in the U.S. as an

adjunct to diet to reduce triglyceride levels in adults with severehypertriglyceridemia, defined as triglyceride levels of ≥500 mg/dL.

Antares Pharma Inc. (NASDAQ:ATRS), Ewing, N.J.Uman Pharma Inc., Candiac, QuebecProduct: Otrexup (Vibex MTX)Business: Autoimmune

FDA approved an NDA from Antares for Otrexup to deliversubcutaneous methotrexate to treat adults with rheumatoid arthritisor psoriasis and children with polyarticular juvenile idiopathic arthritis.Specifically, Otrexup is indicated in adults with severe active RA whohave an inadequate response or intolerance to first-line therapy or withsevere recalcitrant, disabling psoriasis who have an inadequate re-sponse to other therapies. The company expects to launch the productearly next year. Otrexup is a self-injectable formulation of methotrex-ate delivered using Antares’ Vibex autoinjector technology. Uman hasrights to Otrexup in Canada from Antares under a 2010 deal (seeBioCentury, May 10, 2010).

Apeiron Biologics AG, Vienna, AustriaProduct: Ch14.18 (APN311)Business: Cancer

Apeiron partnered with Idis Ltd. (Weybridge, U.K) to launch amanaged access program this quarter in undisclosed countries toprovide access to APN311 to treat patients with high-risk neuroblas-toma. The chimeric mAb against GD2 is in Phase III testing. Apeironplans to submit regulatory applications in the U.S. and EU next year. In2011, the Children’s Cancer Research Institute (Vienna, Austria) andthe European Neuroblastoma Research Network (SIOPEN) grantedApeiron exclusive, worldwide rights to develop and commercialize theproduct (see BioCentury, June 27, 2011). Paladin Labs Inc. (TSX:PLB,Montreal, Quebec) has exclusive rights from Apeiron to commercializeAPN311 in Canada and sub-Saharan Africa (see BioCentury, Jan. 21).

Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.Genentech Inc., South San Francisco, Calif.Roche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandProduct: MabThera (Rituxan) rituximab (R105, RG105)Business: Inflammation

The U.K.’s NICE issued a preliminary appraisal recommendingMabThera rituximab from Roche in combination with glucocorticoidsto induce remission in adults with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis, also known as severely active granulo-matosis with polyangiitis and microscopic polyangiitis. NICE onlyrecommends MabThera if further cyclophosphamide treatment wouldexceed the maximum cumulative cyclophosphamide dose. The commit-tee said the most plausible incremental cost-effectiveness ratios (ICERs)for MabThera in patients with ANCA-associated vasculitis who can havecyclophosphamide was £12,100 (19,331) per quality-adjusted life year(QALY) gained for the comparison of 2 courses of cyclophosphamidefollowed by 1 course of MabThera with 2 courses of cyclophosphamide.Comments are due Oct. 24, with a second appraisal committee meetingscheduled for Nov. 27. Final guidance is expected in March 2014.

The draft reverses a preliminary appraisal issued in July (see BioCentury,July 29). Roche submitted clarification on the definition of severedisease and of the subgroup of people for whom avoiding cyclophos-phamide treatment is desirable. The pharma also submitted 18-monthfollow-up data from the Phase II/III RAVE trial with MabThera and arevised economic model, which represents the management of severeANCA-associated vasculitis in the U.K., including current comparatorsand routine clinical practice. Roche did not submit a patient accessscheme.


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The chimeric mAb against CD20 antigen is approved in the EU forthe indication and to treat non-Hodgkin’s lymphoma (NHL), chroniclymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL) andrheumatoid arthritis (RA). Biogen Idec and Roche’s Genentech unit co-market rituximab as Rituxan in the U.S., while Roche markets it asMabThera elsewhere. In Japan, rituximab is co-marketed as Rituxan byChugai Pharmaceutical Co. Ltd. (Tokyo:4519, Tokyo, Japan), which ismajority owned by Roche, and Zenyaku Kogyo Co. Ltd. (Tokyo, Japan).

Boehringer Ingelheim GmbH, Ingelheim, GermanyProduct: Nintedanib (Vargatef) (BIBF 1120)Business: Cancer

Boehringer submitted an MAA to EMA for nintedanib in combina-tion with docetaxel for second-line treatment of advanced, metastaticor recurrent non-small cell lung cancer (NSCLC) of adenocarcinomahistology. Nintedanib is also in Phase III testing for ovarian cancer andidiopathic pulmonary fibrosis (IPF). The compound is a small moleculeinhibitor of multiple pro-angiogenic kinases including VEGF, plateletderived growth factor receptor (PDGFR) and fibroblast growth factor(FGF) receptor. It has Fast Track designation in the U.S. for IPF.

Product: Striverdi Respimat olodaterol (BI 1744)Business: Pulmonary

Boehringer said the U.K., Denmark and Iceland approved StriverdiRespimat olodaterol as maintenance treatment for chronic obstructivepulmonary disease (COPD). The MAA was approved under the EU’sdecentralized procedure, with the Netherlands acting as the referencemember state. Boehringer submitted the MAA in May. The long-actingbeta 2 agonist (LABA) is already approved in Canada and Russia.

Last month, Boehringer disclosed that it received a completeresponse letter from FDA in March in which the agency cited issues withcGMP inspections at its Ingelheim production site, but did not questionthe efficacy and safety data for the product. Boehringer said it “cannotspeculate” on a timeline for resubmitting the NDA (see BioCentury, Sept.16).

BTG plc (LSE:BTG), London, U.K.Sanofi (Euronext:SAN; NYSE:SNY), Paris, FranceProduct: Lemtrada alemtuzumab (Campath, MabCampath)Business: Autoimmune

FDA’s Peripheral and Central Nervous System Drugs AdvisoryCommittee will meet on Nov. 13 to discuss an sBLA for Lemtradaalemtuzumab from the Sanofi’s Genzyme Corp. unit to treat relapsingmultiple sclerosis (MS). The PDUFA date is in 4Q13, but the exact dateis not disclosed (see BioCentury, Feb. 4). Sanofi acquired Genzyme in 2011for about $20.1 billion plus a $14 contingent value right that includes$1 for FDA approval of the humanized mAb against CD52 and up to $12upon the achievement of sales thresholds. The European Commissionapproved Lemtrada last month (see BioCentury, Sept. 23).

Last year, Genzyme withdrew MabCampath/Campath alemtuzumabfrom the European and U.S. market to treat B cell chronic lymphocyticleukemia (CLL) to prepare for commercialization of the drug for MS.The product has Fast Track designation in the U.S. to treat relapsing-remitting MS. Genzyme has worldwide rights to Lemtrada from BayerAG (Xetra:BAYN, Leverkusen, Germany), which has an option to co-promote Lemtrada for MS and retains full rights in solid organ transplantindications. The product is partnered with BTG, which owns the IP andis eligible for undisclosed royalties in all approved indications (seeBioCentury, April 6, 2009 & June 8, 2009).

Cell Therapeutics Inc. (NASDAQ:CTIC; Milan:CTIC), Seattle, Wash.Product: Pixuvri pixantroneBusiness: Cancer

The U.K.’s NICE issued draft guidance recommending against Pixuvripixantrone from Cell Therapeutics to treat multiply relapsed orrefractory aggressive non-Hodgkin’s B cell lymphoma — its approvedindication. The guidance follows the company’s submission of a patientaccess scheme to make the drug more cost-effective for the NHS. NICEsaid there was still insufficient evidence to show that Pixuvri is moreeffective than current NHS treatments. The guidance reiterates a Julyfinal appraisal determination (FAD) that was withdrawn after CellTherapeutics submitted the patient access scheme (see BioCentury, July15).

NICE had noted that the supporting Phase III PIX301 trial failed torecruit the planned number of patients and had a primary endpoint ofcomplete response rather than overall survival (OS) or progression-free survival (PFS). The European Commission granted conditionalapproval last May for the aza-anthracenedione DNA intercalating agentthat inhibits topoisomerase II (TOP2) (see BioCentury, May 14, 2012).

China National Pharmaceutical Group Corp. (Sinopharm),Beijing, ChinaProduct: SA 14-14-2Business: Infectious

China National’s China National Biotec Group Co. Ltd. subsidiarysaid the World Health Organization (WHO) awarded prequalificationto its SA 14-14-2 vaccine to prevent Japanese encephalitis (JE). ChinaNational Biotec said the live, attenuated vaccine is now eligible forpurchase by United Nations agencies. The product is already availablein 11 countries, including India, Nepal, Cambodia, Sri Lanka and NorthKorea.

Chugai Pharmaceutical Co. Ltd. (Tokyo:4519), Tokyo, JapanRoche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandProduct: Pegasys peginterferon alfa-2a (RG442)Business: Infectious

The U.K.’s NICE issued a final appraisal determination (FAD)recommending the use of Pegasys peginterferon alfa-2a from Roche andViraferonPeg peginterferon alfa-2b from Merck & Co. Inc. (NYSE:MRK,Whitehouse Station, N.J.) both in combination with ribavirin to treatchronic HCV infection in children. The FAD is in line with a Julypreliminary appraisal, which said that the drugs were more effective andless costly than best supportive care, but the comparison between the2 drugs was “not robust enough” for NICE to recommend 1 treatmentover the other (see BioCentury, July 22). Final guidance is expected nextmonth.

Merck markets ViraferonPeg and Rebetol ribavirin in the U.K. totreat HCV infection in patients ages ≥3 years who do not have hepaticdecompensation and have not previously received treatment. Rochemarkets Pegasys and Copegus ribavirin to treat HCV infection inpatients ages ≥5 years who have not previously received treatment.Chugai, which is majority owned by Roche, markets Pegasys, a pegylatedrecombinant interferon (IFN) alfa-2a, in Japan.

Genmab A/S (CSE:GEN; OTCBB:GMXAY), Copenhagen, DenmarkGlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.Product: Arzerra ofatumumab (HuMax-CD20)Business: Cancer

GlaxoSmithKline and partner Genmab said GSK submitted an sBLAto FDA seeking to expand the label for Arzerra ofatumumab to includefirst-line treatment of chronic lymphocytic leukemia (CLL). The sBLAcovers the use of Arzerra in combination with an alkylator-based


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therapy in treatment-naïve patients considered inappropriate forfludarabine-based therapy. Earlier this month, GSK submitted an appli-cation to EMA seeking to include the first-line indication on Arzerra’sEuropean label (see BioCentury, Oct. 7).

Last month, FDA granted breakthrough designation to the humanmAb against CD20 for previously untreated CLL in combination withchlorambucil chemotherapy in patients considered inappropriate forfludarabine-based therapy (see BioCentury, Sept. 16). GSK already mar-kets Arzerra in the U.S. and EU to treat CLL refractory to fludarabineand alemtuzumab. The pharma has worldwide co-development andcommercialization rights to Arzerra from Genmab.

Gilead Sciences Inc. (NASDAQ:GILD), Foster City, Calif.Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J.Product: Darunavir/cobicistatBusiness: Infectious

Johnson & Johnson’s Janssen-Cilag International N.V. unit submit-ted an MAA to EMA for darunavir/cobicistat to treat HIV-1 infection inadults in combination with other HIV-1 drugs. In 2011, Gilead and J&Jpartnered to develop and commercialize a fixed-dose HIV treatmentcombining J&J’s marketed Prezista darunavir and Gilead’s cobicistat. J&Jis responsible for formulation, manufacturing, registration and com-mercialization of the product, and Gilead is eligible for royalties (seeBioCentury, July 4, 2011).

Last month, the European Commission approved Tybost cobicistat asa pharmacokinetic enhancer of protease inhibitors atazanavir and Prezistaas part of antiretroviral combination therapy to treat HIV-1 infection inadults (see BioCentury, Sept. 30). In April, FDA issued a complete responseletter for cobicistat, an inhibitor of cytochrome P450 family 3 subfamily A(CYP3A; CYP3), as a boosting agent for HIV treatment with proteaseinhibitors (see BioCentury, May 6). Bristol-Myers Squibb Co. (NYSE:BMY,New York, N.Y.) markets Reyataz atazanavir.

Iroko Pharmaceuticals LLC, Philadelphia, Pa.Product: Lower dose submicron diclofenac (Nanoformulateddiclofenac, Zorvolex)Business: Neurology

FDA approved an NDA for Zorvolex submicron diclofenac to treatmild to moderate acute pain in adults. The company plans to launch theproduct in 1Q14. The NDA was approved under section 505(b)(2) ofthe Food, Drug and Cosmetic Act, which allows sponsors to referencedata on safety and efficacy from the scientific literature or frompreviously approved products. The nanoformulation of the NSAIDdiclofenac uses SoluMatrix nanoformulation technology from iCeuticaInc., which Iroko acquired.

Iroko Pharmaceuticals LLC, Philadelphia, Pa.Medicure Inc. (TSX-V:MPH; Pink:MCUJF), Winnipeg, ManitobaMerck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.Product: Aggrastat tirofibanBusiness: Cardiovascular

FDA approved an sNDA from Medicure to expand the label ofAggrastat tirofiban to include a high-dose regimen consisting of an initialbolus of 25 µg/kg Aggrastat and then continued at 0.15 µg/kg/min. Theregimen is now the recommended dosing for patients with non-STsegment elevation acute coronary syndrome (NSTE-ACS). The non-peptide GPIIb/IIIa (CD41/CD61) antagonist is already marketed in theU.S. in combination with heparin to treat acute coronary syndrome(ACS), including patients who are to be managed medically and thoseundergoing percutaneous transluminal angioplasty (PTCA) or

atherectomy, at a recommended dose of 0.4 µg/kg/min for 30 minutesand then 0.1 µg/kg/min. Medicure has U.S. rights to the product, whileIroko has rights elsewhere from Merck.

MannKind Corp. (NASDAQ:MNKD), Valencia, Calif.Product: Afrezza (formerly Afresa)Business: Endocrine/Metabolic

MannKind resubmitted an NDA to FDA for Afrezza to improveglycemic control in Type I and II diabetics. The resubmission includesdata from 2 additional trials that were requested by FDA in a 2011complete response letter, the agency’s second for the dry powderformulation of insulin plus an inhaler (see BioCentury, Aug. 19). Theresubmission does not require a user fee, and MannKind said it doesnot expect the government shutdown to affect the PDUFA timing forAfrezza. FDA has said it would continue to accept submissions that donot require fees during the shutdown. The agency issued the firstcomplete response letter in March 2010 (see BioCentury, March 22, 2010& Jan. 24, 2011).

Medivation Inc. (NASDAQ:MDVN), San Francisco, Calif.Astellas Pharma Inc. (Tokyo:4503), Tokyo, JapanProduct: Xtandi enzalutamide (formerly MDV3100)Business: Cancer

NICE issued draft guidance recommending Xtandi enzalutamidefrom Astellas to treat hormone-relapsed, metastatic prostate cancerin men whose disease has progressed on or after docetaxel therapy.The recommendation is contingent upon the partners providing Xtandiunder an undisclosed patient access scheme. The committee said thatthe available incremental cost-effectiveness ratio (ICER) for Xtandicompared to Zytiga abiraterone acetate “are associated with somedegree of uncertainty,” but concluded that the ICER would remain below£30,000 ($48,144) per quality-adjusted life year (QALY) gained. Com-ments are due Nov. 6, with a second appraisal committee meetingscheduled for Nov. 20.

In June, the European Commission approved an MAA for Xtandi totreat metastatic castration-resistant prostate cancer (CRPC) in menwhose disease has progressed on or after docetaxel therapy. Xtandi is alsoapproved in the U.S., Canada and South Korea to treat metastatic CRPC.Medivation and Astellas partnered to develop and commercialize the oralandrogen receptor antagonist in 2009 (see BioCentury, Nov. 2, 2009).

Merck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.Product: ViraferonPeg peginterferon alfa-2bBusiness: Infectious

The U.K.’s NICE issued a final appraisal determination (FAD)recommending the use of Pegasys peginterferon alfa-2a from Roche(SIX:ROG; OTCQX:RHHBY, Basel, Switzerland) and ViraferonPegpeginterferon alfa-2b from Merck both in combination with ribavirin totreat chronic HCV infection in children. The FAD is in line with apreliminary appraisal issued in July which said that the drugs were moreeffective and less costly than best supportive care, but the comparisonbetween the 2 drugs was “not robust enough” for NICE to recommend1 treatment over the other (see BioCentury, July 22). Final guidance isexpected in November.

Merck markets ViraferonPeg and Rebetol ribavirin in the U.K. totreat HCV infection in patients ≥3 years who do not have hepaticdecompensation and have not previously received treatment. Rochemarkets Pegasys and Copegus ribavirin to treat HCV infection inpatients ≥5 years who have not previously received treatment. ChugaiPharmaceutical Co. Ltd. (Tokyo:4519, Tokyo, Japan), which is majorityowned by Roche, markets Pegasys, a pegylated recombinant interferon(IFN) alfa-2a, in Japan.


to treat visceral, cutaneous and mucosal leishmaniasis, respectively. Thecompany is seeking approval for Impavido for all 3 forms of the disease.The compound has a Dec. 19 PDUFA date. Paladin gained thealkylphosphocholine analog that inhibits CTP phosphocholine cytidylyltransferase from Aeterna Zentaris Inc. (TSX:AEZ; NASDAQ:AEZS, Que-bec City, Quebec) in 2008. The product is already approved for leishma-niasis in Europe, India and Central and South America.

Panelists generally agreed that oral Impavido could offer a usefulalternative to IV standard-of-care amphotericin B. Several panelists wantedthe label to specify particular species of leishmaniasis and geographicalregions, depending on the form of the disease being treated and where thePhase III trials were run. Paladin is asking for a label that specifies differentleishmaniasis species in each of the 3 forms of the disease.

Paladin said it is eligible for a Priority Review voucher if FDAapproves Impavido. The transferrable voucher entitles the bearer topriority FDA review for another drug.

Pfizer Inc. (NYSE:PFE), New York, N.Y.Product: Bosulif bosutinib (SKI-606, PF-5208763, PF-05208763)Business: Cancer

Germany’s Federal Joint Committee (G-BA) said Orphan drugBosulif bosutinib from Pfizer has an “unquantifiable” additional benefitfor adults with chronic, accelerated or blast phase Philadelphia chro-mosome-positive (Ph+) chronic myelogenous leukemia (CML) — theindication for which the drug has conditional approval in the EU. Thedrug is indicated for patients previously treated with ≥1 tyrosine kinaseinhibitor (TKI) and for whom imatinib, nilotinib and dasatinib are notconsidered appropriate treatment options. Under drug pricing lawAMNOG, the additional benefit of Orphan products is regarded ashaving been demonstrated by marketing authorization, though G-BAstill determines the extent of the additional benefit. Pfizer will nownegotiate a price for Bosulif with Germany’s Statutory Health InsuranceFunds Association (GKV-Spitzenverband) (see BioCentury, Aug. 12). FDAgranted full approval to the dual inhibitor of BCR-ABL and Src kinasein September (see BioCentury, Sept. 10, 2012 & April 1, 2013). Bosulif hasOrphan Drug status in the U.S. and Europe to treat CML.

Novartis AG (NYSE:NVS; SIX:NOVN, Basel, Switzerland) marketsTasigna nilotinib and Glivec imatinib. Bristol-Myers Squibb Co.(NYSE:BMY, New York, N.Y.) and Otsuka Pharmaceutical Co. Ltd.(Tokyo, Japan) market Sprycel dasatinib.

3SBio Inc., Shenyang, ChinaAMAG Pharmaceuticals Inc. (NASDAQ:AMAG), Lexington, Mass.Takeda Pharmaceutical Co. Ltd. (Tokyo:4502), Osaka, JapanProduct: Feraheme ferumoxytolBusiness: Hematology

AMAG said FDA extended the PDUFA date by 3 months for an sNDAto expand the indication of Feraheme ferumoxytol to include the treat-ment of all adult patients with iron deficiency anemia who have failed orcould not tolerate oral iron treatment. The new date is Jan. 21, 2014; itwas Oct. 21. The IV iron replacement therapy is approved to treat irondeficiency anemia in adult patients with chronic kidney disease (CKD).

In September, AMAG disclosed in an 8-K that it received notificationfrom FDA that the agency identified undisclosed “deficiencies” in theFeraheme sNDA that prevented the agency from discussing potentiallabeling or postmarket requirements by its Sept. 23 target date (seeBioCentury, Sept. 30).

Takeda has rights from AMAG to market ferumoxytol in Europe,Canada, Turkey, India and Asia-Pacific, excluding Japan, China andTaiwan, under an amended 2010 deal (see BioCentury, July 9, 2012). InJune, Takeda submitted a Type II variation application to expand theEuropean label of Rienso ferumoxytol to include all adult patients with

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NewBridge Pharmaceuticals Ltd., Dubai, UAEUCB Group (Euronext:UCB), Brussels, BelgiumAstellas Pharma Inc. (Tokyo:4503), Tokyo, JapanProduct: Cimzia certolizumab pegolBusiness: Autoimmune

FDA expanded the label of Cimzia certolizumab pegol from UCB toinclude treatment of adults with active ankylosing spondylitis, but theagency issued a complete response letter for active axial spondyloar-thritis. UCB had been seeking to expand Cimzia’s label to includetreatment of active axial spondyloarthritis, including patients withankylosing spondylitis. In July, FDA’s Arthritis Advisory Committeevoted 7-6, with 1 abstension, in favor of the label expansion (seeBioCentury, July 29). According to FDA briefing documents for thatmeeting, ankylosing spondylitis is a “well-characterized, chronic andprogressive form” of axial spondyloarthritis. There are currently noapproved drugs in the U.S. for axial spondyloarthritis. UCB declined todisclose the details of the complete response letter.

Cimzia is approved in the U.S. for active psoriatic arthritis, rheuma-toid arthritis (RA) and Crohn’s disease and in the EU for RA. Last month,EMA’s CHMP issued a positive opinion recommending extendingCimzia’s label to include treatment of severe active axialspondyloarthritis comprising ankylosing spondylitis and axialspondyloarthritis without radiographic evidence of ankylosing spondyli-tis (see BioCentury, Sept. 30).

In January 2012, UCB partnered with Astellas to co-develop and co-commercialize Cimzia in Japan. Last November, UCB granted NewBridgeexclusive rights to develop and commercialize the pegylated humanizedantibody fragment against tumor necrosis factor (TNF) alpha in severalMiddle East and African countries (see BioCentury, Feb. 6, 2012 & March 4,2013).

Novo Nordisk A/S (CSE:NVO; NYSE:NVO), Bagsvaerd, DenmarkProduct: Novoeight turoctocog alfa (recombinant FVIII) (NN7008)Business: Hematology

FDA approved a BLA from Novo Nordisk for Novoeight turoctocogalfa to treat hemophilia A in adults and children. The third-generationrecombinant Factor Vlll (rFVIII) is approved to control and preventbleeding, for perioperative management and for routine prophylacticuse to prevent or reduce bleeding episodes. Novo Nordisk said it plansto launch the product in the U.S. in April 2015 after undisclosed third-party patents expire.

Last month, EMA’s CHMP issued a positive opinion recommendingapproval for the product to prevent and treat bleeding in patients withhemophilia A. The company has also submitted regulatory applicationsin Japan, Australia and Switzerland (see BioCentury, Sept. 30).

Novoteris LLC, Garden Grove, Calif.Product: Inhaled nitric oxide (10102-43-9)Business: Pulmonary

Novoteris said FDA granted Orphan Drug designation to its inhalednitric oxide to treat cystic fibrosis (CF). The company plans to startPhase II testing next year.

Paladin Labs Inc. (TSX:PLB), Montreal, QuebecProduct: Impavido miltefosineBusiness: Infectious

FDA’s Anti-Infective Drugs Advisory Committee was unfazed by FDAreviewers’ concerns over trial inconsistencies and resistance to Impavidomiltefosine from Paladin. The panel voted 15-1, 14-2 and 13-3 that thecompany had adequately demonstrated the safety and efficacy of Impavido


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iron deficiency anemia who have a history of unsatisfactory oral irontherapy or in whom oral iron cannot be used. 3SBio has rights in China.

ThromboGenics N.V. (Euronext:THR), Leuven, BelgiumProduct: Jetrea ocriplasmin (formerly Microplasmin)Business: Ophthalmic

Germany’s Federal Joint Committee (G-BA) issued a final benefitassessment for Jetrea ocriplasmin from ThromboGenics that saidJetrea provides “significant” additional benefit vs. watchful waiting invitreomacular traction (VMT) patients with mild symptoms, whichincludes mild to moderate visual impairment. G-BA said the product has“no additional benefit” in VMT patients with severe symptoms becauseThromboGenics did not provide data for the population. In an Augustpreliminary assessment, Germany’s Institute for Quality and Efficiencyin Healthcare (IQWiG) said Jetrea has “major” benefit in VMT patientswith mild visual impairment and “significant” benefit in patients withmoderate visual impairment (see BioCentury, Aug. 5).

The Alcon Inc. ophthalmic unit of Novartis AG (NYSE:NVS;SIX:NOVN, Basel, Switzerland) has ex-U.S. commercialization rights toJetrea. Novartis and ThromboGenics will now negotiate a price forJetrea with Germany’s Statutory Health Insurance Funds Association(GKV-Spitzenverband). The injectable recombinant microplasmin, atruncated form of the natural human protein plasmin, is approved inEurope to treat VMT, including when associated with a macular hole of≤400 µm in diameter (see BioCentury, March 18).

Vanda Pharmaceuticals Inc. (NASDAQ:VNDA), Washington, D.C.Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.Product: Hetlioz tasimelteon (VEC-162)Business: Neurology

FDA’s Peripheral and Central Nervous System Drugs Advisory Com-mittee will meet on Nov. 14 to discuss Hetlioz tasimelteon from Vandato treat non-24-hour sleep wake disorder in totally blind patients. TheNDA is under Priority Review, with a PDUFA date of Jan. 31, 2014. Vandapreviously said FDA had set a tentative date for a committee to discussHetlioz. The product has Orphan Drug designation in the U.S. and EU totreat non-24-hour sleep wake disorder in blind patients without lightperception. Vanda has exclusive, worldwide rights to the melatonin MT1and MT2 receptor agonist from Bristol-Myers Squibb.

CLINICAL RESULTS

Acacia Pharma Ltd., Cambridge, U.K.Product: APD515Business: OtherMolecular target: Muscarinic receptorDescription: Oromucosal formulation of an undisclosed marketedmuscarinic agonistIndication: Treat xerostomia (dry mouth) in advanced cancer patientsEndpoint: Symptoms of mouth dryness at day 7; oral comfort, difficultyspeaking and swallowing, and patient-reported outcomesStatus: Phase II dataMilestone: NA

A double-blind, crossover, U.K. and Danish Phase II trial in 32 advancedcancer patients with persistent dry mouth showed that 20 mg APD515given 4 times daily met the primary endpoint of reducing symptoms of drymouth at day 7 as measured by subjective scoring of mouth dryness on a100 mm visual analog scale (VAS) vs. placebo. Specifically, the mean VASscore for mouth dryness was 26.01 points after treatment with APD515vs. 43.52 points after treatment with placebo (p=0.0005), with a score of

0 points representing no dryness and a score of 100 points representingthe worst dryness possible. APD515 also significantly improved subjectivescores for oral comfort, difficulty speaking and difficulty swallowing vs.placebo. There were no significant differences in the number of adverseevents between treatment groups. Acacia said it plans to optimize APD515in preparation for Phase III testing in an advanced cancer population, butdeclined to disclose details.

AllaChem LLC, Hallandale Beach, Fla.Product: AV4025Business: InfectiousMolecular target: HCV NS5A proteinDescription: HCV NS5A inhibitorIndication: Treat chronic HCV infectionEndpoint: Safety and pharmacokineticsStatus: Phase I dataMilestone: Start Phase Ib/IIa (1Q14)

A double-blind, placebo-controlled Phase I trial in 30 healthy volun-teers showed that single doses of 10, 20 and 40 mg oral AV4025 were welltolerated with no serious adverse events reported. Data were presentedat the Viral Hepatitis: Epidemiology, Diagnostics, Treatment and Prophy-laxis meeting in Moscow. In 1Q14, AllaChem plans to start a Phase Ib/IIatrial with AV4025 in patients with HCV infection.

Anergis S.A., Epalinges, SwitzerlandProduct: AllerTBusiness: InflammationMolecular target: NADescription: Birch pollen allergy vaccine containing contiguous over-lapping (COP) peptides derived from birch pollenIndication: Desensitization for moderate to severe allergies to birchpollenEndpoint: Combined Rhinoconjunctivitis Symptom and Medication Score(RSMS); Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ),rhinoconjunctivitis symptom score, immunological markers and safetyStatus: Additional Phase IIb dataMilestone: Start Phase III (2014)

Additional data from the double-blind, European Phase IIb AN004Ttrial in 240 patients with moderate to severe birch pollen allergyshowed that 50 and 100 µg doses of subcutaneous AllerT each led toa 20-fold increase in allergen-specific IgG4 levels from baseline to 4weeks after treatment and prior to the 2013 birch pollen season, whileIgG4 levels were unchanged for placebo (p<0.0001 for both). Addition-ally, elevated IgG4 levels were sustained for both doses of AllerT duringthe 2013 birch pollen season, while IgG4 levels remained unchanged forplacebo. Patients received 5 subcutaneous injections of AllerT orplacebo over a 2-month period as a pre-seasonal treatment.

Last month, Anergis reported that 50 µg subcutaneous AllerT metthe primary endpoint of reducing combined RSMS scores during the2013 birch pollen season vs. placebo, but the 100 µg dose of AllerTmissed the endpoint. Both doses of AllerT met the secondary end-points of improving total Mini-RQLQ scores and rhinoconjunctivitissymptom scores vs. placebo (see BioCentury, Sept. 16). Anergis plans tostart Phase III testing with AllerT in 2014.

Ariad Pharmaceuticals Inc. (NASDAQ:ARIA), Cambridge, Mass.Product: AP26113Business: CancerMolecular target: Anaplastic lymphoma kinase (ALK); Epidermal growthfactor receptor (EGFR)Description: Dual inhibitor of anaplastic lymphoma kinase (ALK) andEGFR


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Clinical Results,from previous page

Indication: Treat non-small cell lung cancer (NSCLC)Endpoint: Maximum tolerated dose (MTD), dose-limiting toxicities(DLTs), safety, pharmacokinetics, preliminary antitumor activity ac-cording to RECIST criteria and CT scans; recommended Phase II doseStatus: Interim Phase II dataMilestone: NA

Interim data from 26 patients in the Phase II portion of an open-label,international Phase I/II trial showed that once-daily 180 mg oral AP26113,the recommended Phase II dose, led to early-onset pulmonary symp-toms after the first dose in 3 patients. To lessen the pulmonarysymptoms observed, Ariad said the 180 mg dose is now preceded bydosing at 90 mg once daily for 1 week. Of 34 evaluable patients withALK-positive NSCLC, AP26113 led to 1 complete response and 21partial responses. Additionally, 80% of ALK-positive NSCLC patientswith pre-existing brain metastases (n=10) had evidence of radiographicimprovement in their metastases. Of 12 evaluable patients with EGFR-positive NSCLC with documented T790M mutation, AP26113 led to 5cases of stable disease. The Phase II portion of the trial is enrollingpatients into 5 cohorts: ALK-positive patients who are treatment-naïve; ALK-positive patients who are resistant to crizotinib; EGFR-positive patients who were resistant to a prior EGFR tyrosine kinaseinhibitor (TKI) with documented T790M mutation; c-ros proto-oncogene 1 receptor tyrosine kinase (ROS-1)-positive patients andother targets; and ALK-positive patients either naïve or resistant tocrizotinib with active brain metastases. Data were presented at theEuropean Cancer Congress in Amsterdam.

Ariad previously reported data from 55 patients in the Phase Iportion of the trial (see BioCentury, Oct. 8, 2012 & June 10, 2013). On aconference call to discuss its 2Q13 earnings, Ariad disclosed that FDAdenied breakthrough therapy designation for AP26113 for ALK-posi-tive NSCLC (see BioCentury, Aug. 12). Ariad said it “shortly” plans to begina pivotal trial with AP26113 in ALK-positive NSCLC patients who areresistant to crizotinib. Pfizer Inc. (NYSE:PFE, New York, N.Y.) marketsXalkori crizotinib.

AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.Product: AZD9291Business: CancerMolecular target: Epidermal growth factor receptor (EGFR)Description: Oral irreversible inhibitor of EGFR-activating and resis-tance mutationsIndication: Treat non-small cell lung cancer (NSCLC)Endpoint: Safety; maximum tolerated dose (MTD), pharmacokineticsand tumor response as assessed by RECIST criteriaStatus: Preliminary Phase I dataMilestone: NA

Preliminary data from an open-label, dose-escalation, internationalPhase I trial in 27 patients with advanced EGFR mutation-positiveNSCLC that progressed following treatment with an EGFR tyrosinekinase inhibitor (TKI) showed that once-daily 20, 40 and 80 mg dosesof oral AZD9291 as monotherapy were tolerated with no dose-limitingtoxicities (DLTs) reported. The 20 mg dose of AZD9291 led to 2confirmed partial responses in 6 evaluable NSCLC patients with aT790M mutation. Dose escalation and recruitment in the T790Mmutation expansion cohorts are ongoing. Data were presented at theEuropean Cancer Congress in Amsterdam.

Product: Recentin cediranib (AZD2171)Business: CancerMolecular target: Vascular endothelial growth factor (VEGF) receptor

1 (FLT1) (VEGFR-1); Vascular endothelial growth factor (VEGF) recep-tor 2 (KDR/Flk-1) (VEGFR-2)Description: Tyrosine kinase inhibitor (TKI) of VEGF receptors 1, 2 and3Indication: Treat platinum-sensitive relapsed ovarian cancerEndpoint: Progression-free survival (PFS); overall survival (OS), timeto progression (TTP), safety and quality of lifeStatus: Phase III dataMilestone: NA

The double-blind, international Phase III ICON6 trial in 456 patientswith platinum-sensitive relapsed ovarian cancer showed that once-daily20 mg cediranib plus platinum-based chemotherapy followed by eitherplacebo or cediranib maintenance for up to 18 months significantlyimproved PFS, the primary endpoint, vs. placebo plus platinum-basedchemotherapy (11.4 vs. 9.4 months, p=0.0022). On secondary endpoints,the cediranib arm improved OS (20.3 vs. 17.6 months, p=0.0419) and TTP(12.6 vs. 9.4 months) vs. placebo. The trial was conducted by the U.K.Medical Research Council. Data were presented at the European CancerCongress in Amsterdam. AstraZeneca said it has not yet reviewed the fulldata from the trial and has therefore not yet determined next steps.

Product: MEDI4736Business: CancerMolecular target: Programmed cell death 1 ligand 1 (CD274 molecule)(PD-L1) (B7-H1)Description: Human IgG1 mAb targeting programmed cell death 1 ligand1 (CD274 molecule; PD-L1; B7-H1)Indication: Treat advanced solid tumorsEndpoint: Safety; pharmacokinetics, objective response rate (ORR),disease control rate (DCR), duration of response, progression-freesurvival and overall survival (OS)Status: Preliminary Phase I dataMilestone: NA

AstraZeneca’s MedImmune LLC unit reported preliminary datafrom an open-label, dose-escalation, U.S. Phase I trial in 8 patients withadvanced solid tumors showing that IV MEDI4736 given every 14 or 21days led to no dose-limiting toxicities (DLTs) or treatment-relatedgrade ≥3 adverse events. Additionally, tumor shrinkage was observedin as early as 7 weeks. Data were presented at the European CancerCongress in Amsterdam.

BHV Pharma Inc., Research Triangle Park, N.C.Kissei Pharmaceutical Co. Ltd. (Tokyo:4547), Nagano, JapanProduct: Remogliflozin etabonate (GSK189075)Business: Endocrine/MetabolicMolecular target: Sodium-glucose cotransporter 2 (SGLT2)Description: Small molecule sodium-glucose cotransporter 2 (SGLT2)inhibitorIndication: Treat Type II diabetesEndpoint: Safety, pharmacokinetics and pharmacodynamicsStatus: Phase I dataMilestone: Additional Phase I data (2014)

An open-label, U.S. Phase I trial showed that there was no significantincrease in area under the curve (AUC) or half-life of remogliflozin in17 subjects with mild or moderate renal impairment following treat-ment with a single 250 mg dose of the compound compared to 17matched healthy controls with normal renal function. Additionally,pharmacodynamic measurements of urinary glucose excretion showedno changes in the ability of remogliflozin to inhibit SGLT2 in patientswith mild or moderate renal impairment. BHV said the results are“notable because other SGLT2 inhibitors appear to accumulate and loseefficacy” in subjects with renal impairment. The company said the Phase


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I data indicate that no dose adjustment of remogliflozin would benecessary in patients with mild or moderate renal impairment.

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK, London, U.K.), whichpreviously had rights to remogliflozin from Kissei under a deal that wasterminated in 2009, has completed 2 Phase IIb trials with remogliflozin inType II diabetics with normal renal function. BHV said it is planning a thirdPhase IIb trial in Type II diabetics and is considering enrolling a cohort ofpatients with mild or moderate renal impairment. The company did notdisclose a time frame for when the Phase IIb trial is expected to start. BHVhas exclusive rights outside of Japan, Korea and Taiwan to develop andcommercialize remogliflozin from Kissei (see BioCentury, Jan. 10, 2011).

Circassia Ltd., Oxford, U.K.Product: ToleroMune Grass, Grass-SPIREBusiness: InflammationMolecular target: NADescription: Synthetic allergen-derived peptide desensitizing vaccineagainst grass that uses ToleroMune T cell epitope desensitizationtechnologyIndication: Treat grass allergyEndpoint: Change from baseline in Total Rhinoconjunctivitis SymptomScore at up to week 25; symptom scores for nasal and non-nasalsymptoms, skin prick testing, peak nasal inspiratory flow, grass-specificIgA, IgE and IgG4 antibody levels and safetyStatus: Phase II dataMilestone: NA

A double-blind, Canadian Phase II trial in 280 patients with grassallergies showed that 8 intradermal injections of Grass-SPIRE given 2weeks apart prior to the beginning of the pollen season significantlyimproved allergy symptoms at the end of the pollen season vs. placebo(p<0.05). Grass-SPIRE was well tolerated. Circassia could not bereached for details or next steps.

Coronado Biosciences Inc. (NASDAQ:CNDO), Burlington, Mass.Dr. Falk Pharma GmbH, Freiburg, GermanyProduct: Trichuris suis ova (TSO) (CNDO-201)Business: AutoimmuneMolecular target: NADescription: Ova from the porcine helminth Trichuris suis that acts as anatural immunomodulator to regulate T cells and inflammatory cytokinesfollowing colonization of the host intestinal tractIndication: Treat Crohn’s disease (CD)Endpoint: Induction of response at week 12 as measured by the Crohn’sDisease Activity Index (CDAI); induction of remissionStatus: Phase II dataMilestone: Phase II data (4Q13)

Top-line data from the double-blind, U.S. Phase II TRUST-I trial in250 patients with moderate to severe CD showed that 7,500 Trichurissuis ova every 2 weeks missed the primary endpoint of induction ofresponse defined as a >100-point reduction in CDAI score frombaseline to week 12 vs. placebo. TSO also missed the secondaryendpoint of induction of remission defined as achieving a CDAI scoreof <150 points vs. placebo. Coronado said the lack of overall responsewas driven by a “higher-than-expected” placebo response rate inpatients with a baseline CDAI score of <290 points. TSO was welltolerated with abdominal pain reported as the most common adverseevent. Patients who completed TRUST-I had the option of enrolling ina 12-week open-label extension.

Partner Dr. Falk Pharma is evaluating TSO for CD in the double-blind, placebo-controlled, European Phase II TRUST-II trial in 240

patients, with data from a second interim analysis expected this quarter.Coronado said it will analyze the TRUST-I and TRUST-II data to identifynext steps for TSO. In April 2012, an independent DMC said the firstinterim analysis of 120 patients in TRUST-II showed no safety concernsand a positive efficacy trend with TSO. Last year, Coronado and Dr. Falkfinalized a deal to co-develop and commercialize TSO to treat CD (seeBioCentury, March 26, 2012). The product is also in investigator-initiatedPhase II trials to treat ulcerative colitis (UC), multiple sclerosis (MS),autism and psoriasis, for which data are expected this quarter.

Cosmo Pharmaceuticals S.p.A. (SIX:COPN), Lainate, ItalySantarus Inc. (NASDAQ:SNTS), San Diego, Calif.Dr. Falk Pharma GmbH, Freiburg, GermanyProduct: Rifamycin SV MMX (CB-01-11)Business: GastrointestinalMolecular target: NADescription: Broad-spectrum, semisynthetic, oral non-absorbableantibiotic formulated with MMX multi-matrix system technologyIndication: Treat travelers’ diarrheaEndpoint: Time to last unformed stool defined as the time between thefirst dose of study drug and the time that the last unformed stool waspassed before the start of clinical cure; clinical cure defined as no feverand no signs or symptoms of enteric infection and either the passageof ≤2 soft stools and no watery stools, or the passage of no stools oronly formed stoolsStatus: Additional Phase III dataMilestone: NA

Additional data from 264 patients with travelers’ diarrhea in the intent-to-treat (ITT) population of a double-blind, Mexican and Guatemalan PhaseIII trial showed that a lower proportion of patients receiving twice-daily400 mg oral rifamycin SV MMX for 3 days experienced treatment failure,a secondary endpoint, vs. placebo (18.6% vs. 43.1%). Additionally, rifamy-cin SV MMX significantly reduced the proportion of patients requiringrescue therapy vs. placebo (11.6% vs. 24.6%, p=0.01). In patients withdiarrheagenic Escherichia coli infection (n=149), rifamycin SV MMX led toa greater clinical cure rate vs. placebo (80.4% vs. 54.1%, p=0.0035) andreduced median time to last unformed stool vs. placebo (49.3 vs. 68.3hours). Data were presented at the IDWeek meeting in San Francisco.Santarus previously reported that rifamycin SV MMX met the primaryendpoint of reducing median time to last unformed stool vs. placebo (46vs. 68 hours, p=0.0008) (see BioCentury, Sept. 17, 2012).

Dr. Falk Pharma is conducting a second Phase III trial comparingrifamycin SV MMX to ciprofloxacin in about 1,000 patients with travel-ers’ diarrhea. Santarus said the company and Dr. Falk Pharma will submitregulatory applications for rifamycin SV MMX in their respectiveterritories if data from the second trial are positive. Under separate2008 agreements, Cosmo granted U.S. rights for the product toSantarus and Australian and European rights, outside of Italy, to Dr. FalkPharma (see BioCentury, Dec. 22, 2008).

Enanta Pharmaceuticals Inc. (NASDAQ:ENTA), Watertown, Mass.AbbVie Inc. (NYSE:ABBV), Chicago, Ill.Product: ABT-267Business: InfectiousMolecular target: HCV NS5A proteinDescription: HCV NS5A protein inhibitorIndication: Treat HCV infectionEndpoint: Proportion of patients with a sustained virologic response(SVR) 12 weeks after the end of treatment and safety; SVR 24 weeks afterthe end of treatment and proportion of patients with post-treatmentrelapseStatus: Phase II data


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Milestone: Additional Phase II data (11/2013)The open-label, international Phase II PEARL-I (M13-393) trial in 82

patients with HCV genotype 1b infection showed that 100% of 39evaluable treatment-naïve patients and 87.9% of 33 evaluable null re-sponders who received ABT-450 plus ritonavir and ABT-267 for 12 weeksachieved an SVR, defined as HCV RNA levels <25 IU/mL, 4 weeks after theend of treatment. The combination was generally well tolerated withheadache, nausea, dry skin, fatigue, pruritus and diarrhea reported as themost common adverse events. One patient had grade 3 elevated alanineaminotransferase (ALT) levels and 2 patients had grade 3 elevated aspar-tate aminotransferase (AST) levels. The trial is enrolling 320 patients withHCV genotypes 1b or 4 infection. Patients received a once-daily regimenof 150 mg ABT-450 plus 100 mg ritonavir and 25 mg ABT-267. SVR12 datawill be presented at the American Association for the Study of LiverDiseases meeting in Washington D.C. in November.

In May, FDA granted breakthrough therapy designation for AbbVie’sABT-450 plus ritonavir, ABT-267 and ABT-333 triple combinationtherapy with and without ribavirin to treat HCV genotype 1 infection. Theregimen is in Phase III testing (see BioCentury, May 13). ABT-450, an oralHCV NS3/4A protease inhibitor, was discovered under a 2006 dealbetween Abbott Laboratories (NYSE:ABT, Abbott Park, Ill.) and Enantato discover, develop and commercialize HCV protease inhibitors (seeBioCentury, Dec. 18, 2006). Under the deal, AbbVie, the pharmaceuticalbusiness spinout of Abbott, is responsible for all development andcommercialization activities for ABT-450. ABT-333 is a non-nucleosideHCV NS5B polymerase inhibitor. AbbVie markets Norvir ritonavir. Roche(SIX:ROG; OTCQX:RHHBY, Basel, Switzerland) markets Copegus rib-avirin.

Product: ABT-450Business: InfectiousMolecular target: HCV NS3/4A protease complexDescription: Oral HCV NS3/4A protease inhibitorIndication: Treat HCV infectionEndpoint: Proportion of patients with a sustained virologic response(SVR) 12 weeks after the end of treatment and safety; SVR 24 weeks afterthe end of treatment and proportion of patients with post-treatmentrelapseStatus: Phase II dataMilestone: Additional Phase II data (11/2013)

The open-label, international Phase II PEARL-I (M13-393) trial in 82patients with HCV genotype 1b infection showed that 100% of 39evaluable treatment-naïve patients and 87.9% of 33 evaluable nullresponders who received ABT-450 plus ritonavir and ABT-267 for 12weeks achieved an SVR, defined as HCV RNA levels <25 IU/mL, 4 weeksafter the end of treatment. The combination was generally well toler-ated with headache, nausea, dry skin, fatigue, pruritus and diarrheareported as the most common adverse events. One patient had grade3 elevated alanine aminotransferase (ALT) levels and 2 patients hadgrade 3 elevated aspartate aminotransferase (AST) levels. The trial isenrolling 320 patients with HCV genotypes 1b or 4 infection. Patientsreceived a once-daily regimen of 150 mg ABT-450 plus 100 mg ritonavirand 25 mg ABT-267. SVR12 data will be presented at the AmericanAssociation for the Study of Liver Diseases meeting in Washington D.C.in November.

In May, FDA granted breakthrough therapy designation for AbbVie’sABT-450 plus ritonavir, ABT-267 and ABT-333 triple combinationtherapy with and without ribavirin to treat HCV genotype 1 infection.The regimen is in Phase III testing (see BioCentury, May 13). ABT-450 wasdiscovered under a 2006 deal between Abbott Laboratories (NYSE:ABT,

Abbott Park, Ill.) and Enanta to discover, develop and commercializeHCV protease inhibitors (see BioCentury, Dec. 18, 2006). Under the deal,AbbVie, the pharmaceutical business spinout of Abbott, is responsiblefor all development and commercialization activities for ABT-450.ABT-267 is an HCV NS5A protein inhibitor, and ABT-333 is a non-nucleoside HCV NS5B polymerase inhibitor. AbbVie markets Norvirritonavir. Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland)markets Copegus ribavirin.

Esteve S.A., Barcelona, SpainProduct: E-58425Business: NeurologyMolecular target: NADescription: Oral co-crystal formulation of tramadol and celecoxibIndication: Treat moderate to severe acute painEndpoint: Summed pain intensity difference (SPID) at 8 hours; SPID at12 hours and Total Pain Relief (TOTPAR) score at 8 and 12 hoursStatus: Phase II dataMilestone: NA

Top-line data from a double-blind Phase II trial in 420 patients withmoderate to severe acute pain following extraction of ≥2 impacted thirdmolars showed that the 100, 150 and 200 mg doses of E-58425 met theprimary endpoint of improving SPID scores from baseline at 8 hours vs.both placebo (p<0.0002 for all) and 100 mg tramadol (p<0.02 for all). The50 mg dose of E-58425 missed the endpoint vs. both placebo and tramadol.The 3 highest doses of E-58425 also met the secondary endpoints ofimproving SPID scores from baseline at 12 hours and TOTPAR scores frombaseline at 8 and 12 hours vs. both placebo (p<0.0002 for all) and tramadol(p<0.02 for all). Additionally, Esteve said there was a faster onset of action,longer duration of analgesia and less need for rescue medication with E-58425 compared to both placebo and tramadol. Esteve said it is seekingpartners to support Phase III testing with E-58425 in both acute and chronicmoderate to severe pain, but declined to disclose a time frame for whenPhase III testing is slated to begin.

Pfizer Inc. (NYSE:PFE, New York, N.Y.) markets celecoxib, acyclooxygenase-2 (COX-2) inhibitor, for osteoarthritis (OA) andrheumatoid arthritis (RA) in the EU as Onsenal and in the U.S. asCelebrex. The product is also approved in the U.S. to treat ankylosingspondylitis. Astellas Pharma Inc. (Tokyo:4503, Tokyo, Japan) has rightsto the compound in Japan, where it is known as Celecox.

Genentech Inc., South San Francisco, Calif.Roche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandProduct: Parsatuzumab (RG7414, RO5490248)Business: CancerMolecular target: EGF-like-domain multiple 7 (EGFL7)Description: Humanized mAb against EGF-like-domain multiple 7(EGFL7)Indication: Treat solid tumorsEndpoint: Progression-free survival (PFS)Status: Development discontinuedMilestone: NA

Roche disclosed in its 3Q13 update that it discontinued develop-ment of parsatuzumab after the compound as first-line treatment ofmetastatic non-small cell lung cancer (NSCLC) missed the primaryendpoint of improving PFS in the Phase II NILE trial. The pharma alsosaid interim data from the Phase II CONGO trial suggested thatparsatuzumab as first-line treatment of metastatic colorectal cancer(mCRC) would miss the primary endpoint of improving PFS.

Product: RG7446, MPDL3280ABusiness: Cancer


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Molecular target: Programmed cell death 1 ligand 1 (CD274 molecule)(PD-L1) (B7-H1)Description: Human mAb against programmed cell death 1 ligand 1(CD274 molecule; PD-L1; B7-H1)Indication: Treat advanced solid tumorsEndpoint: Objective response rate (ORR); duration of response,progression-free survival (PFS), pharmacokinetics and safetyStatus: Additional Phase I dataMilestone: NA

A subgroup analysis of 53 evaluable patients with locally advancedor metastatic non-small cell lung cancer (NSCLC) whose disease hadprogressed despite prior therapy in an open-label, dose-escalation,international Phase I trial showed that IV MPDL3280A once every 3weeks led to an ORR of 23% and a 24-week PFS rate of 44.7%.MPDL3280A led to an ORR of 83% in patients with tumors containing10% PD-L1-positive immune cells as measured by immunohistochem-istry (IHC), 46% in patients with tumors containing 5% PD-L1-positiveimmune cells and 31% in patients with tumors containing 1% PD-L1-positive immune cells. Data were presented at the European CancerCongress in Amsterdam. Roche’s Genentech Inc. unit previously re-ported data from 140 patients with locally advanced or metastatic solidtumors in the trial showing that MPDL3280A led to an ORR of 21% (seeBioCentury, April 15 & May 20). MPDL3280A is in Phase II testing forlocally advanced or metastatic PD-L1-positive NSCLC.

Keryx Biopharmaceuticals Inc. (NASDAQ:KERX), New York, N.Y.Panion & BF Biotech Inc., Taipei, TaiwanJapan Tobacco Inc. (Tokyo:2914; Osaka:2914), Tokyo, JapanTorii Pharmaceutical Co. Ltd. (Tokyo:4551), Tokyo, JapanProduct: Zerenex ferric citrate (JTT-751)Business: Endocrine/MetabolicMolecular target: NADescription: Oral ferric iron-based phosphate binderIndication: Treat hyperphosphatemia in non-dialysis dependent pa-tients with chronic kidney disease (CKD)Endpoint: Mean change in serum phosphorus levels from baseline toweek 12; proportion of patients achieving target serum phosphorouslevels of 2.5-4.5 mg/dL and change from baseline in fibroblast growthfactor 23 (FGF23) levelsStatus: Phase III dataMilestone: Phase II data (11/2013); submit MAA (year end 2013)

A double-blind, Japanese Phase III trial in 90 non-dialysis dependentCKD patients with baseline serum phosphorus levels of ≥5 mg/dLshowed that 1.5-6 g/day Zerenex met the primary endpoint of reducingmean serum phosphorus levels from baseline to week 12 vs. placebo(1.29 mg/dL vs. an increase of 0.06 mg/dL, p<0.0001). Zerenex also metthe secondary endpoints of a greater proportion of patients achievingtarget serum phosphorous levels of 2.5-4.5 mg/dL at week 12 vs.placebo (64.9% vs. 6.9%, p<0.0001) and of reducing median FGF23 levelsfrom baseline to week 12 vs. placebo (244 pg/mL vs. an increase of 120pg/mL, p<0.0001). Additionally, Zerenex significantly increased ironparameters (p<0.001) and hemoglobin levels (p=0.04) vs. placebo. Thetrial was funded by Japan Tobacco. Data will be presented at theAmerican Society of Nephrology meeting in Atlanta in November.

Earlier this month, FDA accepted for review an NDA for Zerenex totreat hyperphosphatemia in CKD patients on dialysis. Keryx said it expectsto receive the PDUFA data in the next few weeks. The biotech expectsa standard review, which would place the PDUFA data in the summer of2014. The product is also under review in Japan to treat hyperphosphatemiain both dialysis dependent and non-dialysis dependent CKD patients, with

a decision expected in 1Q14. Keryx plans to submit an MAA to EMA forZerenex by year end. Keryx is also conducting a Phase II trial evaluatingZerenex in anemic patients with stage III-V non-dialysis dependent CKD,with top-line data expected in early- to mid- November. Keryx hasworldwide rights to Zerenex, including Japan but excluding the rest of theAsia Pacific region, from Panion & BF. Japan Tobacco and its Torii subsidiaryhave exclusive rights to Zerenex in Japan from Keryx under a 2007 deal(see BioCentury, Oct. 7, 2007).

Medivir AB (SSE:MVIR B), Huddinge, SwedenProduct: MIV-711Business: MusculoskeletalMolecular target: Cathepsin KDescription: Reversible small molecule inhibitor of cathepsin KIndication: Treat osteoporosis and osteoarthritis (OA)Endpoint: Safety and pharmacokineticsStatus: Phase I dataMilestone: NA

A double-blind, placebo-controlled Phase I trial in 27 healthyvolunteers showed that once-daily oral MIV-711 reduced serum levelsof the bone resorption biomarker c-terminal telopeptide of type Icollage (CTX-I) from baseline to day 7 by 40% at the 50 mg dose, 54%at the 100 mg dose and 55% at the 200 mg dose. MIV-711 also reducedurinary excretion of the cartilage degradation biomarker CTX-II frombaseline to day 7 by 31% at the 50 mg dose, 58% at the 100 mg dose and72% at the 200 mg dose. In a separate cohort of 12 postmenopausalwomen, once-daily 100 mg oral MIV-711 for 28 days reduced serumCTX-I levels by 67% and urinary excretion of CTX-II by 55% frombaseline to day 28. All doses of MIV-711 were generally well toleratedwith an incidence of adverse events that was comparable to that ofplacebo. Data were presented at the American Society for Bone andMineral Research meeting in Baltimore. Medivir previously reporteddata from a Phase Ia trial evaluating single doses of MIV-711 (seeBioCentury, June 17). The company could not be reached for next steps.

Medivir AB (SSE:MVIR B), Huddinge, SwedenJohnson & Johnson (NYSE:JNJ), New Brunswick, N.J.Product: Simeprevir (Sovriad) (TMC435) (formerly TMC435350)Business: InfectiousMolecular target: HCV NS3/4A protease complexDescription: HCV NS3/4A protease inhibitorIndication: Treat HCV genotype 1 infection in patients co-infected withHIV-1Endpoint: Proportion of patients with a sustained virologic response(SVR) 12 weeks after end of treatmentStatus: Preliminary Phase III dataMilestone: NA

Preliminary data from an open-label Phase III trial in 106 patients co-infected with HCV genotype 1 and HIV-1 showed that once-daily 150 mgoral simeprevir plus peginterferon and ribavirin for 12 weeks led to an SVR12 weeks after the end of treatment, the primary endpoint, in 74% ofpatients. Additionally, SVR12 rates were 79% for treatment-naïve patients(n=53), 87% for prior relapsers (n=15), 70% for prior partial responders(n=10) and 57% for prior null responders (n=28). According to Medivir,the treatment-naïve and prior null responder cohorts had significantlyimproved SVR12 rates vs. historical controls receiving peginterferon andribavirin alone (historical control rates of 29% and 5%, respectively,p<0.001 for both). The SVR12 rate was 89% in HCV genotype 1b patients(n=18) and 70% in HCV genotype 1a patients (n=88).

Additionally, 67% of HCV genotype 1a patients with a Q80K polymor-phism at baseline achieved an SVR12 (n=30). Furthermore, SVR12 rateswere 80% for patients with mild to moderate liver fibrosis (METAVIR


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BioCentury Week in ReviewBioCentury Week in Review is published byBIOCENTURY PUBLICATIONS INC.,PO Box 1246 San Carlos CA 94070-1246. Phone 650-595-5333.Fax 650-595-5589. David Flores, President & CEO;Karen Bernstein, Ph.D., Chairman & Editor-in-Chief

BioCentury®; The Bernstein Report on BioBusiness™ ; TheBioCentury 100™ ; and The Clear Route to ROI™ are trademarksof BIOCENTURY PUBLICATIONS INC.All contents © Copyright 2013, BIOCENTURY PUBLICATIONS INC.ALL RIGHTS RESERVED. No part of this publication may bephotocopied or reproduced in any form, retransmitted, or stored in aretrieval system without prior written consent of the publisher.

scores of F0-F2) and 64% for patients with advanced liver fibrosis(METAVIR scores of F3-F4). Simeprevir was well tolerated. Treatment-naïve patients and prior relapsers without cirrhosis received response-guided therapy with peginterferon and ribavirin for up to 24 or 48 weeks.All other patients received peginterferon and ribavirin for up to 48 weeks.Data were presented at the European AIDS meeting in Brussels.

Last month, Japan’s Ministry of Health, Labor and Welfare (MHLW)approved simeprevir as Sovriad to treat HCV genotype 1 infection (seeBioCentury, Sept. 30). FDA’s Antiviral Drugs Advisory Committee will meeton Oct. 24 to discuss an NDA from J&J’s Janssen Research & DevelopmentLLC unit for simeprevir to treat HCV genotype 1 infection in adult patientswith compensated liver disease. In May, FDA accepted and granted PriorityReview to the application. A 6-month Priority Review would place thePDUFA date in November; the specific date is not disclosed (see BioCentury,May 20). Simeprevir, which has Fast Track designation in the U.S., is alsounder review in the EU. J&J’s Janssen R&D Ireland has ex-Nordic rights todevelop and commercialize simeprevir from Medivir. Roche (SIX:ROG;OTCQX:RHHBY, Basel, Switzerland) markets Pegasys peginterferon alfa-2a and Copegus ribavirin.

Merck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.Product: MK-3475 (formerly lambrolizumab)Business: CancerMolecular target: PD-1 receptor (PDCD1) (PD-1) (CD279)Description: Humanized IgG4 mAb against PD-1 receptor (PDCD1; PD-1; CD279)Indication: Treat progressive locally advanced or metastatic carcinoma,melanoma or non-small cell lung cancer (NSCLC)Endpoint: Safety and objective response rate (ORR); progression-freesurvival (PFS), overall survival (OS), duration of response and pharma-cokineticsStatus: Additional Phase Ib dataMilestone: NA

Interim data from a cohort of 38 evaluable patients with refractoryNSCLC in an open-label, U.S. Phase Ib trial showed that 10 mg/kg MK-3475 every 3 weeks led to an ORR of 24% as measured by investigator-assessed response criteria and of 21% as assessed by RECIST criteria.Data will be presented at the International Association for the Studyof Lung Cancer meeting in Sydney in October. Merck previouslyreported that MK-3475 led to an ORR of 38% as assessed by anindependent review in a cohort of 117 evaluable patients with advancedmelanoma in the trial (see BioCentury, Nov. 19, 2012 & June 10, 2013). MK-3475 is in Phase II/III testing to treat NSCLC and Phase III testing to treatmelanoma. The product has breakthrough therapy designation fromFDA to treat advanced melanoma.

Merck KGaA (Xetra:MRK), Darmstadt, GermanyBristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.Product: Erbitux cetuximabBusiness: CancerMolecular target: Epidermal growth factor receptor (EGFR)Description: Chimeric IgG1 mAb targeting EGFRIndication: First-line treatment of metastatic colorectal cancer (mCRC)Endpoint: Objective response rate (ORR); progression-free survival(PFS), overall survival (OS), resection rate and safetyStatus: Additional Phase III dataMilestone: NA

Data from 342 mCRC patients with wild-type K-Ras and neuroblas-toma Ras viral (v-Ras) oncogene (NRAS) exons 2, 3 and 4 in the open-label, German Phase III FIRE-3 trial showed that first-line treatmentwith Erbitux plus FOLFIRI chemotherapy significantly improved medianOS vs. Avastin bevacizumab plus FOLFIRI chemotherapy (33.1 vs. 25.6months, p=0.011). Erbitux plus FOLFIRI led to an ORR of 65.5% vs.59.6% for Avastin plus FOLFIRI (p=0.157), while median PFS in thesubgroup was 10.4 months in the Erbitux arm vs. 10.2 months in theAvastin arm (p=0.54). A post hoc analysis of mCRC patients with any Rasmutation (n=178) showed that Erbitux plus FOLFIRI led to a median OSof 20.3 months vs. 20.6 months for Avastin plus FOLFIRI (p=0.6).Erbitux plus FOLFIRI led to an ORR of 38% vs. 51.2% for Avastin plusFOLFIRI (p=0.097), while median PFS in the subgroup was 7.5 monthsin the Erbitux arm vs. 10.1 months in the Avastin arm (p=0.085). Thetrial was sponsored by the University of Munich. Data were presentedat the European Cancer Congress in Amsterdam.

Merck previously reported data from the intent-to-treat (ITT)population consisting of 592 mCRC patients with wild-type K-Ras exon2 in FIRE-3 showing that first-line treatment with Erbitux plus FOLFIRImissed the primary endpoint of improving ORR vs. Avastin plus FOLFIRI(62% vs. 58%, p=0.183). On secondary endpoints, median PFS wassimilar between the Erbitux and Avastin arms (10 vs. 10.3 months), butmedian OS was significantly improved in the Erbitux arm vs. Avastin arm(28.7 vs. 25 months, p=0.017) (see BioCentury, June 10). Erbitux ismarketed in the U.S. and EU for mCRC and squamous cell carcinoma ofthe head and neck (SCCHN). ImClone Systems Inc., a subsidiary of EliLilly, and Bristol-Myers market Erbitux in North America. Merckmarkets Erbitux elsewhere, except in Japan where the 3 companiesmarket the drug. Genentech Inc., a unit of Roche (SIX:ROG;OTCQX:RHHBY, Basel, Switzerland), markets Avastin in the U.S.,while Roche markets it elsewhere.

Novartis AG (NYSE:NVS; SIX:NOVN), Basel, SwitzerlandProduct: Secukinumab (AIN457)Business: AutoimmuneMolecular target: Interleukin-17A (IL-17A)Description: Human IgG1 mAb targeting IL-17AIndication: Treat moderate to severe chronic plaque psoriasisEndpoint: Efficacy vs. placebo at 12 weeks as measured by Psoriasis Areaand Severity Index (PASI) 75 and Investigator’s Global Assessment(IGA); efficacy vs. Enbrel at 12 weeks as measured by PASI 75, PASI 90,PASI 100 and IGA, patient-reported quality of life and safetyStatus: Additional Phase III dataMilestone: Submit regulatory application (4Q13); Phase III data (2014)

Additional data from the double-blind, international Phase III FIX-TURE trial in 1,306 patients with moderate to severe chronic plaquepsoriasis showed that subcutaneous secukinumab led to a PASI 75response rate at week 12, a co-primary endpoint, of 67% at the 150 mgdose and 77% at the 300 mg dose vs. 5% for placebo (p<0.0001 for both)and 44% for Enbrel etanercept (p=0.025 for both). On the other co-


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primary endpoint, secukinumab led to IGA response rates, defined asachieving an IGA score of “clear” or “almost clear,” at week 12 of 51%in the low-dose secukinumab arm and 63% in the high-dose secukinumabarm vs. 3% for placebo (p<0.0001 for both) and 27% for Enbrel (p=0.025for both). Additionally, PASI 90 response rates at week 12 were 42%in the low-dose secukinumab arm and 54% in the high-dose secukinumabarm vs. 2% for placebo and 21% for Enbrel. PASI 100 response rates atweek 12 were 14% in the low-dose secukinumab arm and 24% in thehigh-dose secukinumab arm vs. 0% for placebo and 4% for Enbrel.Furthermore, PASI 90 response rates for high-dose secukinumab were72% at week 16 and 65% at week 52 vs. 30% and 33%, respectively, forEnbrel. Patients received 150 or 300 mg secukinumab, 50 mg Enbrel orplacebo for 12 weeks. Data were presented at the European Associa-tion of Dermatology and Venereology meeting in Istanbul.

Novartis previously reported that secukinumab met the co-primaryendpoints of improving PASI 75 and IGA response rates at week 12 vs.placebo and met the secondary endpoints of improving PASI 75 and IGAresponse rates at week 12 vs. Enbrel (see BioCentury, July 15). This quarter,the pharma plans to submit regulatory applications for secukinumab totreat moderate to severe plaque psoriasis in the U.S. and EU. Data from2 additional Phase III trials of secukinumab in moderate to severe plaquepsoriasis are expected next year. Secukinumab is also in Phase III testingto treat rheumatoid arthritis (RA), ankylosing spondylitis and psoriaticarthritis, and in Phase II testing to treat multiple sclerosis (MS). Data fromPhase III trials of secukinumab in arthritic indications are also expected in2014. Pfizer Inc. (NYSE:PFE, New York, N.Y.) and Amgen Inc.(NASDAQ:AMGN, Thousand Oaks, Calif.) market Enbrel.

Regeneron Pharmaceuticals Inc. (NASDAQ:REGN), Tarrytown,N.Y.Sanofi (Euronext:SAN; NYSE:SNY), Paris, FranceProduct: Alirocumab (SAR236553, REGN727)Business: Endocrine/MetabolicMolecular target: Proprotein convertase subtilisin/kexin type 9 (PCSK9)Description: Human mAb targeting proprotein convertase subtilisin/kexin type 9 (PCSK9)Indication: Treat primary hypercholesterolemiaEndpoint: Mean percent change from baseline in LDL-C at week 24;percent change from baseline in LDL-C at week 12 and other lipidparametersStatus: Phase III dataMilestone: Additional Phase III data (2014)

Top-line data from the double-blind, international Phase III ODYS-SEY MONO trial in 103 patients with primary hypercholesterolemia andmoderate cardiovascular risk showed that subcutaneous alirocumabevery 2 weeks met the primary endpoint of reducing mean LDL-C frombaseline to week 24 vs. 10 mg ezetimibe (47.2% vs. 15.6%, p<0.0001).The most common class of adverse events was infections, whichincluded nasopharyngitis, influenza and upper respiratory tract infec-tions. Patients received alirocumab at an initial dose of 75 mg, which wasincreased to 150 mg at week 12 in patients whose LDL-C level was >70mg/dL at week 8. Sanofi and Regeneron said the majority of patientsremained on the initial dose.

The ODYSSEY MONO data are the first data from the 12-trial PhaseIII ODYSSEY program evaluating alirocumab as monotherapy and incombination with other lipid-lowering agents in over 23,000 patients.Data from additional ODYSSEY trials are expected next year. Sanofi andRegeneron are co-developing alirocumab under a 2007 deal (seeBioCentury, Dec. 3, 2007 & Nov. 16, 2009). Merck & Co. Inc. (NYSE:MRK,Whitehouse Station, N.J.) markets Zetia ezetimibe.

Sanofi (Euronext:SAN; NYSE:SNY), Paris, FranceProduct: Aubagio teriflunomideBusiness: AutoimmuneMolecular target: Dihydroorotate dehydrogenase (DHODH)Description: Dihydroorotate dehydrogenase (DHODH) inhibitorIndication: Prevent or delay conversion of clinically isolated syndrome(CIS) to clinically definite multiple sclerosis (MS)Endpoint: Reduce the risk of conversion to clinically definite MS over2 years; annualized relapse rate (ARR), disability progression as mea-sured by the Kurtzke Expanded Disability Status Scale (EDSS) andpatient-reported fatigue as assessed by the Fatigue Impact Scale (FIS)Status: Additional Phase III dataMilestone: NA

Additional data from the double-blind, international Phase III TOPICtrial in 618 patients who had experienced their first neurologicalsymptoms consistent with CIS showed that once-daily 7 and 14 mgdoses of oral Aubagio each significantly reduced the risk of occurrenceof a new clinical relapse or MRI lesion over 2 years vs. placebo.Specifically, Aubagio reduced the risk of occurrence of a new clinicalrelapse or MRI lesion by 31.4% in the low-dose group (p=0.002) and by34.9% in the high-dose group (p=0.0003) compared to placebo. Addi-tionally, there was a 5% increase in total lesion volume in patientsreceiving high-dose Aubagio as measure by MRI over 2 years vs. a 28%increase for placebo (p=0.0374). Furthermore, high-dose Aubagio ledto a 59% reduction in gadolinium-enhancing T1 lesions compared toplacebo (p=0.0008). The trial enrolled patients who had experienceda first acute or sub-acute, well-defined neurological event consistentwith demyelination, as well as onset of MS symptoms within 90 days ofrandomization and MRI scan showing ≥2 T2 lesions characteristic of MS.Data were presented at the European Committee for Treatment andResearch in Multiple Sclerosis meeting in Copenhagen.

Sanofi and its Genzyme Corp. unit previously reported that once-daily 7 and 14 mg doses of oral Aubagio each met the primary endpointof reducing the risk of conversion to clinically definite MS over 2 yearsvs. placebo. Specifically, Aubagio led to placebo-adjusted reductions inthe risk of conversion to clinically definite MS of 37% in the low-dosegroup (p=0.0271) and 43% in the high-dose group (p=0.0087) (seeBioCentury, April 29). Aubagio is approved in the U.S., EU, Australia,Argentina, Chile, South Korea and Mexico to treat relapsing forms ofMS.

Synta Pharmaceuticals Corp. (NASDAQ:SNTA), Lexington, Mass.Product: Ganetespib (formerly STA-9090)Business: CancerMolecular target: Heat shock protein 90 (Hsp90)Description: Small molecule heat shock protein 90 (Hsp90) inhibitorIndication: Treat advanced, metastatic non-small cell lung cancer (NSCLC)Endpoint: Progression-free survival (PFS) in patients with elevatedbaseline lactate dehydrogenase (LDH) levels and in patients withmutant K-Ras NSCLC (Phase IIb); PFS in the overall population, overallsurvival (OS), overall response rate (ORR), mean tumor size change,disease control rate (DCR), pharmacokinetics, quality of life and safetyStatus: Additional Phase IIb dataMilestone: Final Phase IIb/III data (4Q13); Phase III data (2014)

Data from 76 stage IIIB/IV NSCLC adenocarcinoma patients withelevated baseline LDH levels in the open-label Phase IIb portion of theinternational Phase IIb/III GALAXY-1 trial showed that ganetespib plusdocetaxel as second-line treatment led to a median PFS of 3.4 monthsvs. 1.9 months for docetaxel alone (unadjusted HR=0.88, p=0.309).Ganetespib plus docetaxel led to a median OS of 6.1 months in thesubgroup vs. 4.3 months for docetaxel alone (unadjusted HR=0.63,p=0.046). In 63 patients with mutant K-Ras stage IIIB/IV NSCLC adeno-



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carcinoma, ganetespib plus docetaxel led to a median PFS of 4.1 monthsvs. 3 months for docetaxel alone (unadjusted HR=0.83, p=0.271).Ganetespib plus docetaxel led to a median OS of 9.8 months in thesubgroup vs. 6.3 months for docetaxel alone (unadjusted HR=0.85,p=0.313). Patients received 150 mg/m2 ganetespib on days 1 and 15 plus75 mg/m2 docetaxel on day 1 of a 21-day cycle. Data were presented atthe European Cancer Congress in Amsterdam.

Synta previously reported data from all 252 patients in the Phase IIbportion of the trial as well as from patients who were enrolled in thetrial >6 months after diagnosis (see BioCentury, July 2, 2012; Oct. 8, 2012;& June 10, 2013). Data from the Phase III GALAXY-2 trial evaluatingganetespib plus docetaxel compared to docetaxel alone are expectedin 2014. The primary endpoint of GALAXY-2 is OS and the trial isenrolling patients with stage IIIB/IV NSCLC who have received 1 priorchemotherapy-based regimen and were diagnosed with advanced NSCLC>6 months prior to enrollment. Ganetespib is also in the Phase IIENCHANT-1 trial as first-line treatment of metastatic HER2-positiveor triple-negative breast cancer (TNBC) (see BioCentury, Aug. 5).Ganetespib has Fast Track designation in the U.S. to treat metastaticNSCLC. Sanofi (Euronext:SAN; NYSE:SNY, Paris, France) marketsTaxotere docetaxel.

Taisho Pharmaceutical Holdings Co. Ltd. (Tokyo:4581), Tokyo,JapanProduct: Luseogliflozin (TS-071)Business: Endocrine/MetabolicMolecular target: Sodium-glucose cotransporter 2 (SGLT2)Description: Oral sodium-glucose cotransporter 2 (SGLT2) inhibitorIndication: Treat Type II diabetesEndpoint: Change from baseline in HbA1c at week 52; postprandialblood glucose levels 2 hours after meals, fasting plasma glucose (FPG),body weight and abdominal circumferenceStatus: Phase III dataMilestone: NA

The open-label, Japanese Phase III Study-2 in 299 Type II diabeticsshowed that once-daily oral luseogliflozin met the primary endpoint ofreducing HbA1c at week 52 compared to baseline (0.5% reduction frombaseline, p<0.05). On secondary endpoints, luseogliflozin significantlyimproved postprandial blood glucose levels 2 hours after meals, FPG,body weight and abdominal circumference. Patients receivedluseogliflozin at 2.5 mg with the dose increased to 5 mg if glycemiccontrol was insufficient. Data were presented at the European Asso-ciation for the Study of Diabetes meeting in Barcelona. In April, Taisho’sTaisho Pharmaceutical Co. Ltd. subsidiary submitted a regulatoryapplication to Japan’s Ministry of Health, Labor and Welfare (MHLW)for luseogliflozin to treat Type II diabetes.

Indication: Treat Type II diabetesEndpoint: Change from baseline in HbA1c at week 24; postprandialblood glucose levels 2 hours after meals, fasting plasma glucose (FPG),body weight and abdominal circumferenceStatus: Phase III dataMilestone: NA

The double-blind, Japanese Phase III Study-1 in 158 Type II diabeticsshowed that once-daily 2.5 mg oral luseogliflozin met the primaryendpoint of reducing HabA1c from baseline to week 24 vs. placebo(placebo-adjusted reduction of 0.75%, p<0.001). On secondary end-points, luseogliflozin significantly improved postprandial blood glucoselevels 2 hours after meals, FPG, body weight and abdominal circumfer-ence. Data were presented at the European Association for the Study

of Diabetes meeting in Barcelona. In April, Taisho’s Taisho Pharmaceu-tical Co. Ltd. subsidiary submitted a regulatory application to Japan’sMinistry of Health, Labor and Welfare (MHLW) for luseogliflozin totreat Type II diabetes.

Takeda Pharmaceutical Co. Ltd. (Tokyo:4502), Osaka, JapanGlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.Product: Norovirus VLP intramuscular vaccineBusiness: InfectiousMolecular target: Not applicableDescription: Liquid formulation of a bivalent virus-like particle (VLP)vaccine adjuvanted with monophosphoryl lipid A (MPL) and aluminumhydroxideIndication: Prevent acute gastroenteritis due to norovirus infectionEndpoint: Illness rate of viral acute gastroenteritis due to norovirusinfection and safetyStatus: Phase I/II dataMilestone: NA

A double-blind Phase I/II trial in 98 healthy volunteers aged 18-50years showed that Norovirus VLP intramuscular vaccine missed thecomposite primary endpoint of reducing the incidence of acute gastro-enteritis of any severity and norovirus as ascertained by laboratoryassay vs. placebo. Specifically, the vaccine led to a 22% reduction on theendpoint compared to placebo (p=0.509). Takeda said that the illnessdefinitions and measures used to confirm illness on the primaryendpoint — a 4-fold increase in antibody titer and the presence of DNAin stool as measured by PCR — were unable to differentiate betweeninfection and disease. Following challenge, 52% of subjects who re-ceived the vaccine were infected with the virus vs. 60.4% for placebo.

There were no cases of severe vomiting and/or diarrhea in thevaccine group vs. 4 in the placebo group following challenge (0% vs.8.3%, p=0.054). Furthermore, 6% of subjects receiving the vaccinereported moderate or severe vomiting or diarrhea vs. 18.8% forplacebo (p=0.068). The vaccine did meet the secondary endpoint ofreducing vomiting and/or diarrhea of any severity vs. placebo (20% vs.41.7%, p=0.028). The vaccine was well tolerated with headache re-ported as the most common systemic reaction. Subjects received 2vaccinations with placebo or Norovirus VLP intramuscular vaccine 28days apart and were challenged with the norovirus genotype GII.4 strainat least 28 days after the second vaccination. Data were presented atthe IDWeek meeting in San Francisco. The vaccine uses an MPL adjuvantfrom GlaxoSmithKline. Takeda said the trial demonstrates proof ofconcept (POC) and qualifies the vaccine for continued development, butdeclined to disclose details.

Tekmira Pharmaceuticals Corp. (TSX:TKM; NASDAQ:TKMR),Burnaby, B.C.Product: TKM-PLK1 (PLK1424) (TKM-080301) (formerly PLK1 SNALP)Business: CancerMolecular target: Polo-like kinase 1 (PLK1) (STPK13)Description: Short interfering RNA (siRNA) targeting polo-like kinase1 (PLK1; STPK13) formulated in stable nucleic acid lipid particles(SNALP)Indication: Treat advanced solid tumorsEndpoint: Safety, maximum tolerated dose (MTD) and dose-limitingtoxicities (DLTs); pharmacokinetics and antitumor activityStatus: Additional Phase I dataMilestone: Phase I/II data (mid-2014); start pivotal trial (2014)

Additional data from an open-label, dose-escalation, U.S. Phase Itrial showed that 6 of 15 evaluable patients receiving IV TKM-PLK1 atdoses of ≥0.6 mg/kg showed a clinical benefit. There were 3 cases ofstable disease in 4 evaluable patients with adrenocortical carcinoma,


including 1 patient who achieved a 19.3% reduction in tumor size. Of2 patients with advanced gastrointestinal neuroendocrine tumors (GI-NETs), 1 patient had a partial response and 1 patient had stable diseasewith a >50% reduction in chromogranin A levels. Tekmira said loweredlevels of chromogranin A are linked to improved survival and favorableresponse to treatment in patients with neuroendocrine tumors. Thetrial enrolled 36 patients with advanced solid tumors to receive once-weekly 0.15 to 0.9 mg/kg IV TKM-PLK1, including a 10-patient expansioncohort receiving the MTD of 0.75 mg/kg TKM-PLK1. Data were pre-sented at the North American Neuroendocrine Tumor Society meetingin Charleston.

Tekmira previously reported data from 9 evaluable patients in thetrial. By mid-2014, the company plans to report data from an open-labelPhase I/II trial with TKM-PLK1 in about 20 patients with either adreno-cortical carcinoma or GI-NETs. Tekmira hopes to start a pivotal trialwithTKM-PK1 to treat GI-NETs in 2014.

CLINICAL STATUS

Alkermes plc (NASDAQ:ALKS), Dublin, IrelandProduct: Aripiprazole lauroxil (ALKS 9070, ALKS 9072)Business: NeurologyMolecular target: Dopamine D2 receptor; Serotonin (5-HT) receptorDescription: Injectable, extended-release formulation of aripiprazoleusing LinkeRx technologyIndication: Treat schizophreniaEndpoint: Change in Positive and Negative Syndrome Scale (PANSS)total score from baseline; safety and tolerabilityStatus: Completed Phase III enrollmentMilestone: Phase III data (1H14)

Alkermes completed enrollment of more than 600 patients expe-riencing an acute exacerbation of schizophrenia in a double-blind,placebo-controlled, international Phase III trial evaluating once-monthly300 and 600 mg intramuscular aripiprazole lauroxil for 12 weeks. Aninterim analysis of sample size indicated that a sample size of ≥540patients would have sufficient statistical power to evaluate the primaryendpoint. The trial includes a 12-month, open-label extension.

Ariad Pharmaceuticals Inc. (NASDAQ:ARIA), Cambridge, Mass.Product: Iclusig ponatinib (formerly AP24534)Business: CancerMolecular target: BCR-ABL tyrosine kinase; FMS-like tyrosine kinase3 (FLT3) (CD135)Description: Pan-BCR-ABL tyrosine kinase inhibitor (TKI)Indication: Treat chronic resistant or intolerant chronic myelogenousleukemia (CML) and Philadelphia chromosome-positive (Ph+) acutelymphoblastic leukemia (ALL)Endpoint: Major cytogenetic response (MCyR) rate (chronic phasepatients) and major hematologic response rate (accelerated or blastphase CML and Ph+ ALL patients); major molecular response, durationof response, progression-free survival (PFS) and overall survival (OS)Status: Phase III discontinuedMilestone: NA

Ariad discontinued the confirmatory Phase III EPIC trial evaluatingIclusig ponatinib in newly diagnosed leukemia patients due to arterialthrombotic events observed in patients treated with the drug. Ariadsaid the decision was based on an analysis of safety data from the trialthat was conducted after FDA placed a partial clinical hold on all trialsof Iclusig. EPIC had enrolled 307 patients of a planned 500.

FDA placed the hold earlier this month after 2-year follow-up data

from the pivotal Phase II PACE trial showed longer use of Iclusig wasassociated with an increase in treatment-emergent serious arterialthrombotic events. PACE evaluated Iclusig in heavily pretreated pa-tients. Data from the trial were the basis for accelerated approval forIclusig; the 2-year follow-up data are required to secure full approval(see BioCentury, Oct. 14).

Last December, FDA granted accelerated approval to Iclusig forCML and Ph+ ALL that is resistant or intolerant to prior treatment withTKIs. On a conference call to discuss EPIC’s termination, Ariad said itexpects FDA to narrow the label for Iclusig to patients who have failedother therapies. The European Commission approved Iclusig for CMLand Ph+ ALL in July with a label limited to patients who are resistantto or intolerant of or unsuited for dasatinib and imatinib treatment, orpatients who have the T315I variant of BCR-ABL tyrosine kinase (seeBioCentury, Dec. 17, 2012; June 10, 2013 & July 15, 2013). Iclusig is underreview in Canada and Australia and has Orphan Drug status to treat CMLand Ph+ ALL in the U.S. and EU.

Novartis AG (NYSE:NVS; SIX:NOVN, Basel, Switzerland) marketsTasigna nilotinib and Glivec imatinib. Bristol-Myers Squibb Co.(NYSE:BMY, New York, N.Y.) and Otsuka Pharmaceutical Co. Ltd.(Tokyo, Japan) market Sprycel dasatinib.

Arrowhead Research Corp. (NASDAQ:ARWR), Pasadena, Calif.Product: ARC-520Business: InfectiousMolecular target: NADescription: siRNAs targeting 2 regions of the HBV genome conjugatedto N-acetylgalactosamine-polymer and cholesterol ligands usingArrowhead’s Dynamic Polyconjugate delivery systemIndication: Treat HBV infectionEndpoint: Safety; maximum tolerated dose (MTD) and pharmacokineticsStatus: Completed Phase I enrollmentMilestone: Start Phase IIa (2014)

Arrowhead completed enrollment of 36 healthy volunteers in adouble-blind, placebo-controlled, Australian Phase I trial evaluatingsingle ascending-doses of 0.01-2 mg/kg IV ARC-520.

Atterocor Inc., Ann Arbor, Mich.Product: ATR-101Business: CancerMolecular target: Sterol O-acyltransferase 1 (SOAT1) (ACAT1)Description: Selective inhibitor of sterol O-acyltransferase 1 (SOAT1;ACAT1)Indication: Treat adrenocortical carcinomaEndpoint: Safety; pharmacokinetics, change in plasma cortisol levels andchange in tumor sizeStatus: Phase I startedMilestone: NA

Atterocor began an open-label, U.S. Phase I trial to evaluateascending doses of oral ATR-101 in about 21 patients. Atterocor alsosaid ATR-101 received Orphan Drug designation in the U.S. and EU.

BioMarin Pharmaceutical Inc. (NASDAQ:BMRN), Novato, Calif.Catalyst Pharmaceutical Partners Inc. (NASDAQ:CPRX), CoralGables, Fla.Jazz Pharmaceuticals plc (NASDAQ:JAZZ), Dublin, IrelandProduct: Firdapse amifampridineBusiness: AutoimmuneMolecular target: Potassium channelDescription: Potassium channel blockerIndication: Treat Lambert-Eaton myasthenic syndrome (LEMS)Endpoint: Quantitative myasthenia gravis score; timed 25-foot walk

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Clinical Status,from previous page


testStatus: Phase III ongoingMilestone: Complete Phase III enrollment (4Q13); Phase III data (2Q14)

Catalyst said an IDMC recommended continuation of a double-blind, placebo-controlled, international Phase III trial of Firdapse basedon a review of safety and clinical data. The trial is evaluating Firdapsegiven 3-4 times daily in about 36 patients, who will receive a total dailydose of 30-80 mg, except in patients with moderate renal impairment,who will receive a starting dose of 10 mg.

Last year, BioMarin granted Catalyst exclusive, North Americanrights to Firdapse (see BioCentury, Nov. 5, 2012). The product is approvedfor LEMS in the EU, has breakthrough therapy designation in the U.S. andhas Orphan Drug designation in the U.S., EU and Switzerland. BioMaringained the compound through its 2009 acquisition of Huxley Pharma-ceuticals Inc. which licensed it from EUSA Pharma Inc. Jazz acquiredEUSA last year (see BioCentury, Nov. 2, 2009 & June 18, 2012). LEMS is arare disorder of neuromuscular transmission caused by impairedpresynaptic release of acetylcholine.

Celtaxsys Inc., Atlanta, Ga.Product: CTX-4430 (formerly EP-501)Business: PulmonaryMolecular target: Leukotriene A4 hydrolase (LTA4H)Description: Leukotriene A4 hydrolase (LTA4H) inhibitorIndication: Treat cystic fibrosis (CF)Endpoint: Safety and pharmacokineticsStatus: Phase I startedMilestone: NA

Celtaxsys began a double-blind, placebo-controlled, U.K. Phase Itrial to evaluate 4 dose levels of oral CTX-4430 once daily for 15 daysin about 36 patients. Celtaxsys acquired the compound from EstrellitaPharmaceuticals Inc. (Belmont, Calif.) last year (see BioCentury, Jan. 16,2012).

Chugai Pharmaceutical Co. Ltd. (Tokyo:4519), Tokyo, JapanDaiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, JapanRoche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandProduct: Zelboraf vemurafenib (PLX4032, R7204, RG7204, RO5185426)Business: CancerMolecular target: BRAFDescription: Oral small molecule inhibitor of the oncogenic BRAFV600EIndication: Treat BRAF mutation-positive melanomaEndpoint: Progression-free survival (PFS); overall survival (OS), re-sponse rate and duration, safety, tumor perfusion and correlation ofblood marker mutation with efficacyStatus: Phase II startedMilestone: NA

The Melanoma Research Foundation (MRF) Breakthrough Consor-tium began an open-label, U.S. Phase II trial to evaluate 15 mg/kg IVAvastin bevacizumab every 3 weeks plus 960 mg oral Zelboraf twicedaily vs. Zelboraf alone in about 180 patients with BRAF V600 mutation-positive metastatic melanoma. Genentech Inc., a unit of Roche, marketsAvastin in the U.S., while Roche markets it elsewhere. Avastin is ahumanized mAb against VEGF. Roche, which markets Zelboraf, hasrights from Plexxikon Inc., which Daiichi acquired in 2011. Chugai,which is majority owned by Roche, has rights to Zelboraf in Japan.

D-Pharm Ltd. (Tel Aviv:DPRM), Rehovot, IsraelProduct: DP-b99

Business: GastrointestinalMolecular target: NADescription: Membrane-activated lipophilic chelator of zinc, copperand calcium ionsIndication: Treat acute pancreatitisEndpoint: Clinical assessment scales, inflammatory biomarkers andabdominal imagingStatus: Phase II startMilestone: Start Phase II (4Q13)

This quarter, D-Pharm will begin a double-blind, placebo-con-trolled Phase II trial to evaluate DP-b99 in patients with acute pancre-atitis. Last year, the company discontinued development of the com-pound to treat ischemic stroke due to lack of efficacy in a Phase III trial(see BioCentury, March 5, 2012).

Product: THR-18Business: NeurologyMolecular target: NADescription: Short peptide plasminogen activator inhibitor-1 (PAI-1)Indication: Treat ischemic strokeEndpoint: Safety and pharmacokineticsStatus: Phase IIa startMilestone: Start Phase IIa (10/22/2013)

On Oct. 22, D-Pharm said it will begin a double-blind, placebo-controlled, Ukrainian Phase IIa trial to evaluate 3 single ascending-doses of THR-18 in combination with tissue plasminogen activator(tPA) in about 30 patients with acute ischemic stroke. D-Pharm gainedTHR-18 through its merger with Thrombotech Ltd. in 2012 (seeBioCentury, May 28, 2012).

Dynavax Technologies Corp. (NASDAQ:DVAX), Berkeley, Calif.AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.Product: Inhaled ISIS (AZD1419)Business: InflammationMolecular target: Toll-like receptor 9 (TLR9)Description: Toll-like receptor 9 (TLR9) agonistIndication: Treat asthmaEndpoint: SafetyStatus: Phase I startedMilestone: Phase I data (mid-2014)

Dynavax began a double-blind, placebo-controlled, European PhaseI trial to evaluate single and multiple ascending-doses of AZD1419 inup to 45 healthy volunteers in the first part of the study and about 24patients with mild asthma in the second part. Dynavax and AstraZenecapartnered in 2006 to discover, develop and commercialize TLR9agonists based on Dynavax’s second-generation immunostimulatorysequences to treat asthma and chronic obstructive pulmonary disease(COPD). In 2011, the partners amended the deal to accelerate clinicaldevelopment of AZD1419 to treat asthma. The pharma has an optionto develop and commercialize the compound following Phase IIa testing(see BioCentury, Oct. 11, 2011).

Genentech Inc., South San Francisco, Calif.Chugai Pharmaceutical Co. Ltd. (Tokyo:4519), Tokyo, JapanRoche (SIX:ROG; OTCQX:RHHBY), Basel, SwitzerlandProduct: Avastin bevacizumab (RG435)Business: CancerMolecular target: Vascular endothelial growth factor (VEGF)Description: Humanized mAb against VEGFIndication: Treat BRAF mutation-positive melanomaEndpoint: Progression-free survival (PFS); overall survival (OS), re-sponse rate and duration, safety, tumor perfusion and correlation of

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blood marker mutation with efficacyStatus: Phase II startedMilestone: NA

The Melanoma Research Foundation (MRF) Breakthrough Consor-tium began an open-label, U.S. Phase II trial to evaluate 15 mg/kg IVAvastin every 3 weeks plus 960 mg oral Zelboraf vemurafenib twicedaily vs. Zelboraf alone in about 180 patients with BRAF V600 mutation-positive metastatic melanoma. Roche’s Genentech Inc. unit marketsAvastin in the U.S., while Roche markets it elsewhere. Chugai, whichis majority owned by Roche, markets Avastin in Japan. Roche, whichmarkets Zelboraf, has rights from Plexxikon Inc., which Daiichi SankyoCo. Ltd. (Tokyo:4568; Osaka:4568, Tokyo, Japan) acquired in 2011.Zelboraf is an oral small molecule inhibitor of the oncogenic BRAFV600E.

H. Lundbeck A/S (CSE:LUN), Copenhagen, DenmarkOtsuka Pharmaceutical Co. Ltd., Tokyo, JapanProduct: Lu AE58054Business: NeurologyMolecular target: Serotonin (5-HT6) receptorDescription: Selective serotonin (5-HT6) receptor antagonistIndication: Treat Alzheimer’s disease (AD)Endpoint: Change in Alzheimer’s Disease Assessment Scale-cognitive(ADAS-cog) subscale total score; Alzheimer’s Disease CooperativeStudy-Clinical Global Impression of Change (ADCS-CGIC) score,Alzheimer’s Disease Cooperative Study-Activities of Daily Living In-ventory (ADCS-ADL23) total score, Neuropsychiatric Inventory (NPI)total score and safetyStatus: Phase III startedMilestone: NA

Lundbeck and Otsuka began a double-blind, placebo-controlled,international Phase III trial to evaluate 30 and 60 mg oral Lu AE58054once daily as an adjunct to 10 mg Aricept donepezil in about 930 patients.The trial is the first of 4 planned Phase III trials in about 3,000 patients.In March, Lundbeck granted Otsuka co-development and co-commer-cialization rights to Lu AE58054 in the U.S., Canada, East Asia, majorEuropean countries and Nordic countries as part of a 2011 deal (seeBioCentury, April 1). Pfizer Inc. (NYSE:PFE, New York, N.Y.) and Eisai Co.Ltd. (Tokyo:4523; Osaka:4523, Tokyo, Japan) market Aricept.

Hanmi Pharmaceutical Co. Ltd. (KOSDAQ:128940), Seoul, SouthKoreaProduct: LAPS-Exendin4 (HM11260C)Business: Endocrine/MetabolicMolecular target: Glucagon-like peptide-1 receptor (GLP-1R) (GLP1R)Description: Long-acting exendin-4 analogIndication: Treat Type II diabetesEndpoint: SafetyStatus: Phase IIb startedMilestone: NA

Hanmi began an international Phase IIb trial to evaluate LAPS-Exendin4 given once weekly or monthly in about 700 patients with TypeII diabetes or obesity.

Insmed Inc. (NASDAQ:INSM), Monmouth Junction, N.J.Product: Arikace amikacin (formerly SLIT amikacin)Business: InfectiousMolecular target: Ribosomal 30S subunitDescription: Inhaled liposomal amikacinIndication: Treat non-tuberculosis mycobacterial (NTM) lung infection

Endpoint: Change in mycobacterial density from baseline to 84 days;proportion of patients with culture conversion to negative, time to“rescue” anti-mycobacterial drugs, change in 6-minute walk distance(6MWD), oxygen saturation, Patient-Reported Outcomes and safetyStatus: Completed Phase II enrollmentMilestone: Phase II data (1Q14)

Insmed completed enrollment of 90 patients in the double-blind,placebo-controlled, North American Phase II TARGET-NTM trial evalu-ating once-daily 560 mg Arikace administered with the eFlow NebulizerSystem from Pari GmbH (Starnberg, Germany) for 84 days. Followingthe double-blind portion, patients may enroll in an 84-day, open-labelportion.

Arikace has Orphan Drug designation in the U.S. and Europe to treatPseudomonas aeruginosa infection in patients with cystic fibrosis (CF),Orphan Drug designation in the U.S. to treat bronchiectasis in patientswith P. aeruginosa infection, and Qualified Infectious Disease Product(QIDP), Orphan Drug and Fast Track designations in the U.S. to treatNTM lung infection. Insmed gained Arikace through its 2010 acquisitionof Transave Inc. (see BioCentury, Dec. 6, 2010).

PledPharma AB (SSE:PLED), Stockholm, SwedenProduct: PledOx calmangafodipirBusiness: HematologyMolecular target: Superoxide dismutase 2 mitochondrial (SOD2)(MNSOD)Description: Pyridoxyl ethyldiamine (PLED) analog in which 80% of themanganese in the MRI contrast agent mangafodipir has been replaced bycalciumIndication: Treat side effects of FOLFOX chemotherapy in patients withadvanced metastatic colorectal cancer (mCRC)Endpoint: Change from baseline in absolute neutrophil count; febrileneutropenia, neuropathy, response rate, progression-free survival(PFS), oral mucositis, pharmacokinetics and overall survival (OS)Status: Phase IIb ongoingMilestone: Phase IIb data (1Q14)

PledPharma said a DSMB recommended continued dosing in thedouble-blind, placebo-controlled, international Phase IIb PLIANT trialevaluating 2 and 10 µmol/kg IV PledOx given 30 minutes prior toFOLFOX6 (5-FU, leucovorin, and oxaliplatin) chemotherapy afteranalyzing data from the sixth patient in the dose-escalation portion.PledPharma said the patient can continue to receive the second cycleof the higher PledOx dose. PLIANT is enrolling about 138 mCRCpatients. The company expects to report data from the dose-escalationportion in 1Q14. PledPharma also expects a DSMB decision during theweek of Nov. 11 on whether to begin the randomized portion of thetrial in 126 patients in Europe and the U.S.

Portola Pharmaceuticals Inc. (NASDAQ:PTLA), South San Fran-cisco, Calif.Product: PRT062070, PRT2070Business: CancerMolecular target: Spleen tyrosine kinase (SYK); JAK kinase (JAK)Description: Dual inhibitor of spleen tyrosine kinase (SYK) and JAKkinase (JAK)Indication: Treat hematologic malignanciesEndpoint: Safety, pharmacokinetics and clinical activityStatus: Phase I/II startedMilestone: Phase I/II data (2014)

Portola began an open-label Phase I/II trial of PRT2070. The PhaseI portion will evaluate escalating doses of PTR2070 in patients withrelapsed or refractory chronic lymphocytic leukemia (CLL)/small lym-phocytic lymphoma (SLL) and non-Hodgkin lymphoma (NHL) until the

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OFFERINGS & SECURITIES TRANSACTIONS

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Week ended 10/18/13. Shares af-ter offering refers to shares out-standing. Proceeds are gross, notnet. Shares offered don’t includeoverallotments. Currency rates usedin the week: C$=$0.965; €=$1.3563;£=$1.5976

Completed Offerings

ADMA Biologics Inc. (OTCQB:ADMA), Hackensack, N.J.Business: Hematology, InfectiousDate completed: 10/17/13Type: IPORaised: $28.5 millionShares: 3.4 millionPrice: $8.50Shares after offering: 9.2 millionUnderwriters: Oppenheimer;Ladenburg Thalmann; MaximGroup; LaidlawOverallotment: 502,941

Advaxis Inc. (NASDAQ:ADXS),North Brunswick, N.J.Business: Cancer, InfectiousDate completed: 10/17/13Type: Follow-onRaised: $26.5 millionShares: 6.6 millionPrice: $4Shares after offering: 12.6 millionUnderwriter: Aegis CapitalOverallotment: 862,500Note: The follow-on includes the

sale of five-year warrants to pur-chase 2.9 million shares at $0.001per warrant. The warrants areexercisable at $5. Advaxis alsobegan trading on NASDAQ andceased trading on OTCQB. Theamount raised and share figuresinclude the overallotment sale onAug. 18 of 862,500 shares andwarrants to purchase up to431,250 shares.

Alliance Pharma plc (LSE:APH),Chippenham, U.K.Business: Neurology, Cardiovas-cular, DermatologyDate completed: 10/11/13Type: Debt financingRaised: £25 million ($39.9 mil-lion)Investors: Lloyds Bank; Royal Bankof ScotlandNote: The company also receiveda £25 million ($39.9 million) re-volving credit facility and a £5 mil-lion ($8 million) working capitalfacility. The loan and facilities bearabout 3.25% interest and matureJune 30, 2018.

Biodesy Inc., Burlingame, Calif.Business: Supply/Service, Compu-tational chemistry/biology, Pro-teomicsDate completed: 10/17/13Type: Venture financingRaised: $15 million

Investors: 5AM Ventures; PfizerVenture Investments; Roche Ven-ture Fund

Galectin Therapeutics Inc.(NASDAQ:GALT), Norcross, Ga.Business: Cancer, HepaticDate completed: 10/17/13Type: Warrant exerciseRaised: $900,000Shares: 300,000Price: $3Shares after offering: 18 millionInvestor: 10X Fund

G1 Therapeutics Inc., ChapelHill, N.C.Business: HematologyDate completed: 10/16/13Type: Venture financingRaised: $12.5 millionInvestors: MedImmune Ventures;Hatteras Venture Partners; Moun-tain Group Capital

Hybrigenics S.A. (Euronext:ALHYG), Paris, FranceBusiness: Cancer, Proteomics,Supply/ServiceDate completed: 10/11/13Type: Private placementRaised: €1.3 million ($1.8 million)Shares: 2.5 millionPrice: €0.52Shares after offering: 21.9 millionInvestor: Pradeyrol Developpe-ment

immatics biotechnologiesGmbH, Tuebingen, GermanyBusiness: CancerDate completed: 10/15/13Type: Venture financingRaised: €12 million ($16.3 mil-lion)Investors: dievini Hopp BioTech;Wellington Partners; MIG Funds;AT Impf; existing investorsNote: The company raised €12million ($16.3 million) in the firsttranche of a €34 million ($46.1million) series D round.

Portola Pharmaceuticals Inc.(NASDAQ:PTLA), South San Fran-cisco, Calif.Business: Cardiovascular, Au-toimmune, CancerDate completed: 10/16/13Type: Follow-onRaised: $105.9 millionShares: 4.5 millionPrice: $23.75Shares after offering: 39.6 millionUnderwriters: Morgan Stanley;Credit Suisse; Cowen; WilliamBlair; Sanford C. BernsteinOverallotment: 954,976Note: Portola shareholders alsosold 1.9 million shares at $23.75in a concurrent secondary offer-ing.

Rexahn Pharmaceuticals Inc.(NYSE-M:RNN), Rockville, Md.


maximum tolerated dose (MTD) is reached. The Phase II portion of thetrial will evaluate PRT2070 in an expansion cohort in cancer typesidentified based on the responses seen in the previous portion. InFebruary, Portola granted Aciex Therapeutics Inc. (Westborough,Mass.) an exclusive license to co-develop and co-commercialize PRT2070for non-systemic indications, such as ophthalmic indications and aller-gic rhinitis.

Promedior Inc., Lexington, Mass.Product: PRM-151Business: HematologyMolecular target: Serum amyloid P component (SAP) (APCS)Description: Recombinant version of pentraxin-2 (PTX-2), a humanserum amyloid P component (SAP; APCS) protein

Indication: Treat myelofibrosis (MF)Endpoint: Response rate according to International Working Groupfor Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteriaStatus: Phase II startedMilestone: Complete Phase II (2014)

Promedior began a 2-stage, open-label, North American Phase IItrial to evaluate PRM-151 alone and in combination with ruxolitinib inup to about 104 patients with primary myelofibrosis and post poly-cythemia vera/essential thrombocythemia myelofibrosis (PPV-MF/PET-MF). In the first stage, about 24 patients will receive weekly or monthlyPRM-151 with or without ruxolitinib. Up to an additional 80 patientswill be enrolled in the second stage.

Ruxolitinib from Incyte Corp. (NASDAQ:INCY, Wilmington, Del.)is approved in the U.S. as Jakafi to treat intermediate or high-risk MF,including primary MF and PPV-MF/PET-MF. In the EU, the drug isapproved as Jakavi to treat disease-related splenomegaly or symptomsin adults with chronic idiopathic MF, PPV-MF or PET-MF. Novartis AG(NYSE:NVS; SIX:NOVN, Basel, Switzerland) has exclusive ex-U.S. rightsto ruxolitinib from Incyte.



raise up to $50 million. The com-pany also added Feltl; CantorFitzgerald; and Dougherty as un-derwriters. Earlier this month,Cancer Genetics filed to raise upto $46 million.

Mirati Therapeutics Inc.(NASDAQ:MRTX), San Diego,Calif.Business: Cancer, InfectiousDate announced: 10/16/13Type: Follow-onTo be raised: Up to $57.5 millionShares: 3 millionPrice prior: $16.42Underwriters: Jefferies; Leerink;Piper JaffrayOverallotment: 450,000Note: The company amended itsfollow-on and plans to sell 3 mil-lion shares. Mirati proposed toraise up to $57.5 million in theoffering earlier this month.

Relypsa Inc., Redwood City, Ca-lif.Business: Endocrine/MetabolicDate announced: 10/17/13Type: IPOTo be raised: Up to $138 millionShares: TBDPrice: TBDUnderwriters: Morgan Stanley;BofA Merrill Lynch; Cowen; Stifel,Nicolaus; WedbushNote: Relypsa amended its IPOand now plans to raise up to $138million. The company filed to raiseup to $126.5 million in the IPO lastmonth.

Ruthigen Inc., Petaluma, Calif.Business: InfectiousDate announced: 10/16/13Type: IPOTo be raised: Up to $21 millionShares: 1.5 millionPrice: $12-$14Underwriters: Aegis Capital;Dawson James Securities; ChardanCapital Markets LLCOverallotment: 225,000Note: Ruthigen, a subsidiary ofOculus Innovative Sciences Inc.(NASDAQ:OCLS, Petaluma, Ca-lif.), amended its IPO and nowplans to sell 1.5 million shares at$12-$14. According to a publicS-1 registration statement onAug . 8 , the subs id iary hadplanned to raise up to $25.3

Completed Offerings,from previous page

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Business: Cancer, Neurology,GenitourinaryDate completed: 10/11/13Type: Direct public offeringRaised: $5.3 millionUnits: 10.2 millionPrice: $0.52 (unit)Shares after offering: 146.7 millionPlacement agent: H.C. Wain-wrightInvestors: Institutional investorsNote: Each unit comprises a shareand a five-year warrant to pur-chase 0.35 shares, with each wholewarrant exercisable at $0.58.

Sage Therapeutics Inc., Cam-bridge, Mass.Business: NeurologyDate completed: 10/16/13Type: Venture financingRaised: $20 millionInvestors: Arch Venture Partners;Third Rock Ventures

Seragon Pharmaceuticals Inc.,San Diego, Calif.Business: CancerDate completed: 9/27/13Type: Venture financingRaised: $30 millionInvestors: venBio; Topspin Fund;Aisling Capital; OrbiMed Advisors;The Column GroupNote: Aragon Pharmaceuticals Inc.spun out Seragon in August, whenJohnson & Johnson (NYSE:JNJ,New Brunswick, N.J.) acquiredAragon.

Sofie Biosciences Inc., CulverCity, Calif.Business: DiagnosticDate completed: 10/15/13Type: Venture financingRaised: $5 millionInvestors: Tata Industries; CycadGroup; MRM Capital

Tekmira PharmaceuticalsCorp. (TSX:TKM; NASDAQ:TKMR), Burnaby, B.C.Business: Cancer, Drug deliveryDate completed: 10/17/13Type: Follow-onRaised: $30 millionShares: 3.8 millionPrice: $8Shares after offering: 18.4 millionUnderwriters: Stifel, Nicolaus;

Maxim GroupOverallotment: 562,500

Theravectys S.A., Paris, FranceBusiness: InfectiousDate completed: 10/16/13Type: Venture financingRaised: €14.7 million ($19.9 mil-lion)Investors: Tethys; FGP Capital;Financiere IDAT; existing inves-tors; private investors

Proposed Offerings

Egalet Ltd., Vaerlose, DenmarkBusiness: Neurology, Cardiovas-cular, Drug deliveryDate announced: 10/16/13Type: IPOTo be raised: Up to $69 millionShares: TBDPrice: TBDUnderwriters: Stifel, Nicolaus;JMP Securities; Canaccord; JanneyMontgomery Scott

Oxford Immunotec Globalplc, Abin, U.K.Business: DiagnosticDate announced: 10/15/13Type: IPOTo be raised: Up to $86.3 millionShares: TBDPrice: TBDUnderwriters: JPMorgan; PiperJaffray; Cowen; Baird

Plethora Solutions Holdingsplc (LSE:PLE), London, U.K.Business: GenitourinaryDate announced: 10/15/13Type: PlacingTo be raised: Up to £4.4 million($7 million)Shares: 49 millionPrice: 9pPlacement agents: Hybridan;Daniel StewartShares outstanding prior: 346.4millionInvestors: Company directors;institutional investors

Stemline Therapeutics Inc.(NASDAQ:STML), New York,N.Y.Business: CancerDate announced: 10/17/13Type: Follow-onTo be raised: Up to $90 millionShares: TBD

Price prior: $37.99Underwriters: JPMorgan; Jeffer-ies; Aegis Capital; Ladenburg Thal-mann; Roth Capital Partners; H.C.Wainwright

TetraLogic Pharmaceuticals,Malvern, Pa.Business: CancerDate announced: 10/18/13Type: IPOTo be raised: Up to $103.5 millionShares: TBDPrice: TBD

Verona Pharma plc (LSE:VRP),London, U.K.Business: Inflammation, Pulmo-naryDate announced: 10/4/13Type: PlacingTo be raised: About £801,300($1.3 million)Shares: 36.4 millionPrice: 2.2pShares outstanding prior: 336.2million

Amended Offerings

Aerie Pharmaceuticals Inc.,Bedminster, N.J.Business: OphthalmicDate announced: 10/15/13Type: IPOTo be raised: Up to $73.5 millionShares: 5.3 millionPrice: $12-$14Underwriters: RBC Capital Mar-kets; Stifel Nicolaus; Lazard;CanaccordOverallotment: 787,500Note: Aerie amended its IPO andsaid it hopes to sell 5.3 millionshares at $12-$14. Aerie filed toraise up to $57.5 million in theIPO in September.

Cancer Genetics Inc.(NASDAQ:CGIX), Rutherford,N.J.Business: Diagnostic, Cancer,Supply/ServiceDate announced: 10/17/13Type: Follow-onTo be raised: Up to $50 millionShares: TBDPrice prior: $18.75Underwriters: Aegis Capital; Feltl;Cantor Fitzgerald; DoughertyNote: Cancer Genetics amendedits follow-on and now plans to


million in an IPO. Ruthigen hadsubmitted a confidential draftregistration statement to theSEC in May. Companies can con-fidentially file a registration state-ment under the Jumpstart OurBusiness Startups (JOBS) Act, butare still required to file publicly atleast 21 days prior to starting aroad show.

Veracyte Inc., South San Fran-cisco, Calif.Business: DiagnosticDate announced: 10/17/13Type: IPOTo be raised: Up to $70.5 millionShares: 4.7 millionPrice: $13-$15Underwriters: Morgan Stanley;Leerink; William Blair; CowenOverallotment: 705,000Note: The company amended itsIPO and plans to sell 4.7 millionshares at $13-$15. Veracyte filedto raise up to $74.8 million inSeptember.

Other Financial News

Aastrom Biosciences Inc.(NASDAQ:ASTM), Ann Arbor,Mich.Business: Gene/Cell therapyDate announced: 10/16/13

Aastrom implemented a 1-for-20 reverse stock split. Aastromimplemented the split to regaincompliance with NASDAQ’s $1minimum bid price requirementfor continued listing. Followingthe split, the company has about4.4 million shares outstanding.

Amgen Inc. (NASDAQ:AMGN),Thousand Oaks, Calif.Business: BiopharmaceuticalsDate announced: 10/16/13

Amgen said its board declareda 4Q13 dividend of $0.47 per shareto be paid on Dec. 6 to sharehold-ers of record as of Nov. 14. Thecompany, which closed Friday at$114.92, has about 753.4 millionshares outstanding.

Cambridge Innovation Capitalplc, Cambridge, U.K.Business: Finance

Date announced: 10/10/13IP commercialization company

IP Group plc (LSE:IPO, London,U.K.), along with the University ofCambridge Endowment Fund,ARM Holdings, Invesco Perpetualand Lansdowne Partners, haveinvested £5 million ($8 million) inCambridge Innovation Capital.The IP Group also signed amemorandum of understandingwith Cambridge Innovation toshare information on investmentopportunities in the CambridgeCluster. IP Group holds an 8%stake in Cambridge Innovation,which has raised £50 million($79.9 million).

Chimerix Inc. (NASDAQ:CMRX), Durham, N.C.Business: InfectiousDate announced: 10/18/13

Chimerix said shareholderssold 2.5 million shares at $16.50in a secondary offering underwrit-ten by Morgan Stanley and Cowen.Participating shareholders includeSanderling Venture Partners; NewLeaf Ventures; Canaan Partners;and Alta Biopharma Partners. Ear-lier this month, the shareholdersproposed to sell up to $50 millionin the offering.

5AM Ventures, Menlo Park,Calif.Business: FinanceDate announced: 10/16/13

5AM Ventures plans to raise$240 million for its fourth fund,according to an SEC filing. 5AM,which closed its previous fund at$200 million in 2009, focuses onearly stage investments in life sci-ences companies. 5AM has about$435 million under management.

Guided Therapeutics Inc.(OTCBB:GTHP), Norcross, Ga.Business: DiagnosticDate announced: 10/15/13

Guided Therapeutics began anoffer to exchange 22 warrants topurchase up to 3.6 million sharesfor new warrants with a lowerexercise price and a shortenedexpiration period. The existingwarrants are exercisable at $0.65and expire March 1, 2014, whilethe new warrants will be exercis-able at $0.40 and expire Nov. 27.The offer ends on Nov. 13.

iBio Inc. (NYSE-M:IBIO), New-ark, Del.Business: InfectiousDate announced: 10/15/13

iBio amended its warrants is-sued in a January 2012 offering tolower the exercise price to $0.40from $0.88 until Nov. 12. Theother terms of the warrants re-main unchanged. The warrantsexpire Jan. 14, 2014.

MacroGenics Inc. (NASDAQ:MGNX), Rockville, Md.Business: Cancer, Autoimmune,InfectiousDate announced: 10/16/13

MacroGenics raised $12 mil-lion through the sale of 750,000shares at $16 to cover theoverallotment from its Oct. 9 IPO,bringing the total raised to $92million. The company, whichclosed Friday at $25.41, has 24.8million shares outstanding.

Mithril Capital Management,San Francisco, Calif.Business: FinanceDate announced: 10/18/13

Mithril Capital Managementclosed its first fund in March at$537.7 million. LPs include fam-ilies and sovereign wealth funds.Mithril invests in technology-based companies and is agnosticabout sector and geography. Thefund has made five investments,none of which are in the biotechspace, but Mithril said it is opento the sector. Co-founder PeterThiel chairs Mithril’s investmentcommittee. He is a director atFacebook Inc. (NASDAQ:FB,Menlo Park, Calif.) and co-founder of PayPal, which is partof eBay Inc. (NASDAQ:EBAY,San Jose, Calif.). The Thiel Foun-dation launched its BreakoutLabs program in 2011 to investin life science startups.

Neptune Technologies & Bior-essources Inc. (NASDAQ:NEPT;TSX:NTB), Laval, QuebecBusiness: Nutraceuticals, Cardio-vascular, NeurologyDate announced: 10/11/13

Neptune secured a C$12.5 mil-lion ($12.1 million) loan from theQuebec provincial government.The loan bears interest at 7% andis due in four years.

Sage Therapeutics Inc., Cam-bridge, Mass.Business: NeurologyDate announced: 10/16/13

Sage raised an additional $2.8million in September in an expan-sion of a series A round, bringingthe total raised in the round to$37.8 million. Third Rock led theround, and new investor ArchVentures participated. The com-pany raised $35 million in theround in October 2011.

SQI Diagnostics Inc. (TSX-V:SQD), Toronto, OntarioBusiness: DiagnosticDate announced: 10/15/13

SQI Diagnostics extended theexpiry date to Oct. 25, 2016, of 2.3million warrants to purchaseshares at C$2.50. The two-yearwarrants were issued in a C$4.6million ($4.4 million) unit offeringin October 2011.

Vaccinogen Inc. (OTCQB:VGEN), Frederick, Md.Business: CancerDate announced: 10/17/13

Vaccinogen transferred its list-ing to OTCQB under the ticker“VGEN” from OTC Link via theForm 10 pathway. Vaccinogen filedfor a public listing in July.

Versant Ventures, Menlo Park,Calif.Business: FinanceDate announced: 10/18/13

Versant Ventures is aiming toraise up to $250 million for itsfifth fund, according to an SECfiling. Versant, which invests inbiotech and medical device com-panies, raised $500 million in itsfourth fund in 2008. About half ofthat fund was invested in thera-peutics companies, with the otherhalf in medical device companies.Versant has about $1.6 billionunder management.

Zalicus Inc. (NASDAQ:ZLCS),Cambridge, Mass.Business: Autoimmune, Neurol-ogy, InflammationDate announced: 10/15/13

Zalicus received notice fromNASDAQ that it regained compli-ance with the $1 minimum bidrequirement for continued list-ing.

Amended Offerings,from previous page

October 21, 2013 - TransCelerate - Pharmaceutical … Portola; Receptos; Tekmira; XenoPort, et...

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