Presents Webinar onAccessing Shelved Compounds Through the

CTSA Pharmaceutical Assets Portal

April 12, 2010www.fastercures.org/train

•Kate Marusina, Ph.D., MBA, Manager, Research Facilitation and Industry Alliance, Clinical and Translational Science Center, University of California Davis School of Medicine

•Dean J. Welsch, Ph.D., Research Fellow, Pfizer Global Research & Development, Indications Discovery Research Unit

•Moderator: Margaret Anderson, Executive Director, FasterCures

CTSA PHARMACEUTICAL CTSA PHARMACEUTICAL ASSETS PORTALASSETS PORTALwww.ctsapharmaportal.orgwww.ctsapharmaportal.orgKate Marusina, Ph.D., MBA December 2009

GoalsGoals

To improve information exchange between pharmaceutical companies and the CTSA Consortium/NIH regarding drugs available for repositioning

Specific emphasis in on drugs discontinued at clinical stage

Via the Portal, these unique and previously inaccessible assets will be made available to the entire CTSA academic community and the NIH intramural researchers, enabling new translational research and a considerably accelerated path to the bedside

Achievements to Date

Dr. Francis Collins expressed his support at the CTSA Industry Forum (Feb 2010)

Pfizer financially supports development of the Foci-of-Expertise, for hypothesis driven identification of the repositioning opportunities (Dec 2009).

The Portal project was presented at the dedicated forum at the NIH: “Clinical and Translational Science Awards (CTSA) Pharmaceutical Assets Portal: Matching Academia and Industry for Drug Repositioning” (Dec 2009).

The Portal Project was listed in the NIH report to the Secretary of Health and Human Services

The Portal received press coverage in the Nature Medicine, Proto Magazine, Sacramento Bee Newspaper, Drug Repositioning Summit in Boston (October 2009).

The Portal begins collaboration with AUTM and The National Academies to work out the material transfer and licensing provisions for the drugs originated from the Portal.

What is CTSA?

Clinical and Translational Science Award

The goal is to transform the local, regional and national environment for clinical and translational science, thereby increasing the efficiency, quality and speed of clinical and translational research

The largest academic integration effort to date

Required functions: Biomedical Informatics Regulatory Knowledge and Support Training and Education Community Outreach Translational Pilot studies

Power of the network (45 - 60 universities)

CTSA Pharmaceutical Assets “Database”

Inspiration: Daniel Rader and BMS-201038 (AEGR-733 ), targeted inhibition of the microsomal triglyceride transfer protein (MTP)

Project sponsored by NCRR in Sept 2008 as “Pharmaceutical Assets Database”

JANUARY 10, 2007 Penn Researchers Demonstrate Ability of New Therapy to Treat Patients With Severely Elevated Cholesterol Levels New England Journal of Medicine Publishes Report of New Therapeutic Approach That Has Implications for People With High Cholesterol

(PHILADELPHIA) - Researchers at the University of Pennsylvania School of Medicine have demonstrated the potential of a new type of therapy for patients who suffer from high cholesterol levels. In this study, patients with homozygous familial hypercholesterolemia (FH), a high-risk condition refractory to conventional therapy, had a remarkable 51% reduction in low-density lipoprotein (LDL) or “bad cholesterol” levels.

Challenges of the “database” approach

Closely guarded assets Pharma just gearing up for repositioning Lack of a systematic databasing in the

companies Data has not been published External databases only capture about 50%

of the assets

Needed to find an indirect way of accessing the information – via pharma champions

INDICATIONSDISCOVERY

Research Unit

0

10

20

30

40

501

99

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19

91

19

92

19

93

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94

19

95

19

96

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20

02

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04

20

05

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06

20

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0

10

20

30

40

50

60

PhRMA R&D Productivity(Avg Annual R&D Spend Increase = 10.3%; ’90-’07)

Source: Pharmaceutical Research and Manufacturers of America, PhRMA Annual Membership Survey, 2008; CDER

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NMEs Approved

Recent Number of NMEs Approved by FDA is Disappointing

INDICATIONSDISCOVERY

Research Unit

Research & Development Productivity Needs Attention The Challenge – 1 of 10 is Aspirational!

INDICATIONSDISCOVERY

Research Unit……..but Opportunities to Improve Abound

PreclinicalPhase 1Phase 2/

PoCPhase 3 Approval

65 55 25 65 85 Cumulative = 5%

“In times of profound change, the learners inherit the earth, while the learned find themselves beautifully equipped to deal with a world that no longer exists.”

“It still holds true that man is most uniquely human when he turns obstacles into opportunities.”

- Eric Hoffer

Stage

% Survival

versus

INDICATIONSDISCOVERY

Research Unit

Initiated in ’07 as a dedicated group of scientists focused on discovering, evaluating, and pre-clinically validating additional opportunities for active and failed Pfizer Development candidates

Early portfolio progress warranted build to include ability to conduct clinical studies

Diversity of skills Broad Disease Area focus (“indication agnostic”) Leverages group, Pfizer Research Unit and external expertise Provides a systematic approach to expanding the indication options

for Pfizer compounds Goal is to deliver > 1 PoC per year

at steady state To date, have delivered

initiation of 5 new clinical studiesProducts

ProcessEvolution

Pfizer Indications Discovery

INDICATIONSDISCOVERY

Research Unit

Indications Discovery Business Plan – An Ever-Evolving Model

DISEASE RELEVANT

SCREENINGHYPOTHESISGENERATION

Reg Tox through Phase 2

Pre-ClinicalVALIDATION

Endorsement to Initiate Clinical PoC StudyInternal, Partner, Out-license

MINE EXISTINGKNOWLEDGE

• Project Teams• Clinical Data Mining• External Knowledge

• Text • Genetics• Pathways

Phase 3/MarketedCANsLDs

Active Clinical Candidates Failed compounds – “RIPs”

Those losing CoM patents

Internal, Partner

Clinical Proof of ConceptInternal, Partner, Out-license

In vivomodels

In vitro assays

INDICATIONSDISCOVERY

Research UnitPfizer Indications Discovery – Learnings

Pfizer Compounds & Drug Development expertise present significant opportunity Goals change – be quick to adapt Focus on Unmet Medical Need

Therapeutic Area agnostic Expect challenges……….create opportunities

“we don’t know how to do IPF” – collaborate with experts (IPFnet) “there’s no market opportunity” – consider Orphan drug status, Patient

Advocacy Groups, Foundations Change (Ind Disc Group) was readily embraced by broader Pfizer organization

Idea generation, scientific and technical support Early progress critical

Required building supporting infrastructure Stage Gates - unique Idea Tracker (Cmpds/MoA/Disease) Compound Book (Cmpd Data)

Understanding MoA-Disease associations is critical The Lion King – Circle of Life “There's more to see than can ever be seen, More to do than can ever be done.”It’s time to focus!

INDICATIONSDISCOVERY

Research Unit

Pfizer Indications Discovery –Key Focus Area: MoA-Disease Association

Idea Generation MoA Compound File for Screening

Internal Research Units & External Partnerships Mining Existing Knowledge

Internal Research & Development-wide IdeaFarms CTSA Portal - Research Compounds, Clinical Compounds, Other

Idea Validation Foci of Expertise (FoX) Tool Internal Research Units & Academic Medical Centers

Clinical Confirmation Expand Indications Discovery expertise/capacity Need to leverage external expertise (e.g., IPFnet) Biomarkers of Target MoA & Disease Efficacy Patient Selection (e.g., Novartis’ ILARIS for Cryoptyrin-Associated

Periodic Syndromes; CAPS) Multi-site Protocols

“Generic Agreements”

Collaboration

INDICATIONSDISCOVERY

Research UnitAn Invitation to Collaboration

Improving health through scientific discovery is a lofty goal, in today’s economic and organizational environment there are many challenges, and many exciting opportunities.

Pfizer’s Indications Discovery group seeks novel cross-functional partnerships that bring new medicines to patients.

Discussions like these, and those we’ve had with NIH Chemical Genomics Center (NCGC), Foundation for NIH (FNIH), NIH Office of Technology Transfer, and CTSA, are expected to advance our common interests.

The CTSA Pharmaceutical Assets portal and Foci-of-Expertise tool are but two examples of Pfizer’s Indications Discovery efforts to expand possibilities via collaboration.

Coming together is a beginning; keeping together is progress; working together is success.

- Henry Ford

Two ways to create a match Two ways to create a match between Academia and Pharmabetween Academia and Pharma

From Academia to PharmaFrom Academia to Pharma

1. Known compound for PRE-clinical studies: http://www.pfizer.com/research/licensing/compound_gift.jsp

Please fill out this form http://www.ctsapharmaportal.org/files/Pfizer_Write_in_Request_Form.doc

2. Known compound for CLINICAL studies: http://www.pfizer.com/research/investigator/investigator_initiative.jsp Submit the request directly via the website.

3. Request a compound based on the mechanism of action. Fill out Indications Discovery Form (“Dream List”). Requests are forwarded to the Indications Discovery Unit at Pfizer for review.

How to join the Portal (www.ctsapharmaportal.org)

Members of the Portal (as of June 09)

Institution Frequency Percent Vanderbilt Univ. 102 28.7 Univ. of Penn 33 9.3 Tufts University 29 8.1 Other (e.g., NIH, Industry) 27 7.6 Univ. of Washington 18 5.1 Northwestern 17 4.8 Mayo Clinic College of Medicine 16 4.5 Univ. of Colorado, Denver 16 4.5 Stanford University 14 3.9 UNC Chapel Hill 14 3.9 Univ. of Alabama at Birmingham 12 3.4 UC Davis 11 3.1 Univ. of Texas Health Sci. Ctr. at San Antonio

10 2.8

Washington Univ. 9 2.5 Emory University 9 2.5 Albert Einstein 7 2.0 Rockefeller University 7 2.0 Univ. of Iowa 3 0.8 Boston University 1 0.3 Johns Hopkins 1 0.3

The Portal at a glanceThe Portal at a glance

348 researchers nation-wide, including NIH

Main interest areas of Portal participants:

The Portal at a glanceThe Portal at a glance

80% of participants desire a compound at clinical stage

>80% desire to run a clinical trials after proof of concept is established

50% had prior experience in obtaining investigational drugs Learned about a drug from public sources Only ½ of these attempts succeeded Failed largely because of contractual issues

(40%)

Specific target/disease interests (~150)

Two ways to create a match Two ways to create a match between Academia and Pharmabetween Academia and Pharma

From Pharma to CTSA via From Pharma to CTSA via FoXFoX

targettarget

Disease ADisease A

Disease ADisease A

Disease CDisease C

Disease BDisease B

Disease DDisease D

Disease BDisease B

FoX Pilot for 5 universities

Obtained data from Biovista (www.biovista.com) Researcher-target Researcher-disease

By mining OMIM, KEGG etc: target-target target-disease

Large scale network visualization based on biological interaction between proteins using OCTRI Synergy Tool, developed by OHSU

Currently building for 45 universities

Data cloud for a target X Data cloud for a target X

Examples of Filters

Who published the most By university By disease Who published within last X years Time slider – visualize new disease

appearance

Example of a FilterExample of a Filter

Pharma Concerns re: research with their compounds

Different Timing: Execution of the study Contract negotiation

Dialog Appreciation and learning of what it takes to

develop a drug Unreasonable valuation of academic contribution Early publication may affect competitive

standing Releasing “real” compounds vs “tool”

compounds

Next steps – Contractual Issues Workgroup

Guiding Principles for the MTAs for the compounds originating from the Portal (draft accessible on the website: www.ctsapharmaportal.org)

Guiding Principles for licensing for the method of use patents on the compounds originated from the Portal

Recognize that we are a small part of the drug development process

Be sensitive to “shelved” compound issues

Call for Action to the Foundations Spread the word about the Portal among

your constituency Work with the scientists to prepare

“Dream Lists” and “Dream Proposals” Consider broad-scope translational

assessments No indication is too small! Make a “match” via the Portal

Summary - Future PlansSummary - Future Plans

Proactively engage the pharmaceutical industry in providing information about the compounds that may be available to the research community.

Actively increase awareness of availability of the Portal among CTSA Researchers and promote availability of compounds to the research community

Define the mutually agreeable “principles or points to consider” for materials transfer as related to drugs originated from the Portal.

Team :Team :

UC Davis – Project Management, Company Contacts Kate Marusina

OHSU – Foci of Expertise Aaron Cohen, Nathan Bahr

UW – researchers outreach and survey Doug Brock, Pamela Nagasawa, Lynn Rose

U Penn – Analysis of key MTA provisions Terry Fadem

U of Chicago – Advisory Eric Ginsburg

Special Thanks to Pfizer Indications Discovery Unit Dean Welsch Don Frail

QUESTIONS AND ANSWERS

WEBINARAccessing Shelved Compounds Through the

CTSA Pharmaceutical Assets Portal

•Kate Marusina, Ph.D., MBA, Manager, Research Facilitation and Industry Alliance, Clinical and Translational Science Center, University of California Davis School of Medicine

•Dean J. Welsch, Ph.D., Research Fellow, Pfizer Global Research & Development, Indications Discovery Research Unit

•Moderator: Margaret Anderson, Executive Director, FasterCures