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Transcript of RA 2013 BioAlliancePharma Report
INNOVATION& PERFORMANCE
2013 ANNUAL REPORT
CO
NT
EN
TS OVERVIEW OF BIOALLIANCE PHARMA
MESSAGE FROM CHAIRMAN OF THE BOARD OF DIRECTOR
MESSAGE FROM CHIEF EXECUTIVE OFFICER
KEY FIGURES
2013 HIGHLIGHTS
MAJOR ADVANCES WITH ORPHAN PRODUCTS IN ONCOLOGY
LIVATAG®
VALIDIVE®
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
R&D
STRATEGY AND MEDICAL AFFAIRS
BUSINESS DEVELOPMENT
QUALITY
PRODUCTION
FINANCE AND HUMAN RESOURCES
GOVERNANCE
STOCK MARKET AND SHAREHOLDERS
SIMPLIFIED FINANCIAL REPORT
CONSOLIDATED BALANCE SHEET
CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME
STATEMENT OF CONSOLIDATED CASH FLOW
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3BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
CANCER AND ASSOCIATED PATHOLOGIES
BioAlliance Pharma conceives and develops innovative drugs used in the treatment of cancer with a particular approach based on rare and orphan diseases.
THERAPEUTIC APPROACHES DESIGNED TO TACKLE FUTURE CHALLENGES
Targeting (mucosal, cellular and molecular) and the control of resistance - for which targeting can be a key efficacy factor - are at the core of BioAlliance Pharma’s therapeutic approaches.
The Company develops breakthrough technologies, whether for nanoparticulate formulation, mucosal deli-very or targeted therapies, that make it possible to act precisely on a therapeutic target and to reduce drug resistance and/or intolerance.
A STRATEGY FOR GROWTH
The Company’s growth strategy is driven by the deve-lopment of its advanced products for orphan diseases in oncology. These are products with very high sales potential which benefit from more favorable price and reimbursement policies, and meet an established and unaddressed therapeutic need for a relatively limited segment of patients.
In the medium and long term, the Company could mar-ket these high added value products in Europe directly, in order to benefit from the full margin generated, and enter into partnership agreements for other regions in the world.
In addition to this strategic portfolio, BioAlliance Pharma has successfully developed and registered two initial drugs in Europe and the United States, thereby demons-trating the ability of its teams, and already enabling it to register income through international partnerships.
STRENGTHSUNDERPINNING GROWTH
Advanced strategic programs in severe orphan
diseases in oncology, the basis of its growth
strategy;
Two technological platforms targeting and figh-
ting drug resistance:
The Lauriad® mucoadhesive platform with two
products developed and registered and one pro-
duct currently undergoing its Phase II clinical
trial;
The nanoparticulate platform Transdrug™, with
one product undergoing Phase III clinical deve-
lopment;
Drug development and registration expertise in
Europe and the United States;
Scientific expertise in Oncology, Hepatology and
the field of Nanomedicines;
Strong Business Development skills with esta-
blished international commercial partnerships,
which have already earned the Company more
than fifty-five million euros since 2007;
A strong portfolio of patent and trademark sub-
missions and registrations, offering long-term
protection for all the products developed by the
Company.
OVERVIEW OF BIOALLIANCE PHARMA
4BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
“BIOALLIANCE, A FRENCH SME IN THE BIOTECH WORLD”
5BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
The main challenge for an SME in the field of new
drug research is to reconcile conflicting influences.
While defining a long-term strategy in order to
actually finish up with a drug for the patient, an
SME must constantly adapt to the risks of the pro-
ducts and to developments in the world of science,
developing a position of expertise and leadership in
its selected therapeutic fields, and finally securing
the necessary financial resources. It is important to
understand our own strengths and limitations, but
we must also be bold.
BioAlliance faces up to these challenges through
the commitment of its teams and the support of its
Board of Directors. I would like to stress the quality
of our Board of Directors of international renown,
which boasts the highest level of expertise in a
variety of fields, and to congratulate each member
for the energy and commitment they bring to
their role. The entire Board of Directors is actively
involved alongside the company employees, conti-
nuously providing them with the benefit of our
expertise and experience.
BioAlliance Pharma is driven forward by motivated,
competent and ambitious teams facing up to the
daily challenges with enthusiasm, and I salute their
commitment.
2013 and early 2014 were marked by decisive
advances in terms of the growth of BioAlliance
Pharma and the value of its assets. These events
reinforced the confidence and support of the
shareholders who have been fully behind the Com-
pany’s strategic decisions.
This dynamic will continue in 2014 with the advan-
cement, deployment and conclusion of key stages
in the research program cycle. In order to tackle
these challenges and to reinforce its financial flexi-
bility, BioAlliance Pharma is pursuing its efforts to
diversify its sources of funding and to widen its
shareholder base.
We are confident in the future of BioAlliance
Pharma and in its ability to pursue and exceed its
objectives of creating value and new perspectives.
PATRICK LANGLOISCHAIRMAN OF THE BOARD OF DIRECTORS
MESSAGE FROM CHAIRMANOF THE BOARD OF DIRECTORS
6BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
JUDITH GRECIETCHIEF EXECUTIVE OFFICER
COMMENTS ON THE 2013 PERFORMANCE AND SETS OUT THE STRATEGY FOR 2014
“
”
2013 for BioAlliance Pharma was a year full of progress and events in the development of its orphan drugs in oncology. It was also marked by the deployment of Sita-vig® with its marketing authorization in the United States for the prevention of labial herpes in early 2014, along-side the licensing agreement for marketing the drug in the USA. What are your main highlights from 2013?
It has been a very busy year, just as in 2012, a year of major advances and key progress with our development pro-grams.
Advances were first of all made with the portfolio driving the growth of the Company, namely orphan drugs in onco-logy, with Livatag® in primary liver cancer and Validive® in severe oral mucositis induced by radiotherapy and chemo-therapy in patients suffering from head and neck cancer. It is important to remember that these drugs are now in a very strong position and that we are approaching the years of fruition for all the efforts made and the key deve-lopment stages successfully completed.
The Livatag® trial is in its final phase of development, Phase III. The study is being extended geographically in both Europe and the United States following FDA authorization obtained in late 2013 to carry out the trial in the USA.
It should also be noted at this stage that the good tole-rance profile of the product has been confirmed by the independent expert committee assigned the task of ensu-ring patient safety, a decisive factor in the trial. As set out in the study protocol, the committee meets every 6 months to review the Livatag® tolerance data and on three occasions to date has issued a recommendation for the trial to continue without modification.
The Validive® Phase II trial for its part is about to complete the patient recruitment phase, and initial results are expec-ted during the fourth quarter of this year. Furthermore, the fast-track status granted by the FDA in early 2014 confirms the severity of the pathology being treated, severe oral mucositis, and the medical need which currently remains unaddressed. This status will provide closer contacts with the American agency, an accelerated review process and optimized development times. All these elements precede and prepare for the subsequent development phases: pro-duct phase III followed by registration.
Activities over recent months have also been focused on Sitavig®, our treatment for the prevention of labial herpes. For the second time in its history, BioAlliance Pharma has successfully undergone the product development phases to achieve registration in both Europe and the United States. We are the only French biotechnology company to have successfully completed this journey through the American agency, an achievement that is the result of not only our know-how and expertise but also the com-mitment and determination of our teams, of which I am particularly proud. And we are presently at the product’s commercialization stage with the signing in early March of a partnership agreement with a US company, Innocu-tis, which plans to launch the product in the United States during the third quarter of this year.
7BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
The strategy of BioAlliance Pharma appears to be turning towards the development of drugs for the treatment of orphan diseases in oncology: is this your main strategic focus?
BioAlliance Pharma aims to become a major player in the field of orphan drugs in oncology. It is in this area that we wish to develop the position of the laboratory and from which we will enjoy growth in the future. Our portfolio is already very rich and highly advanced with Livatag® and Validive®. It currently demonstrates our clear priorities in terms of human and financial investment. The field of orphan drugs in oncology represents a strategic area of significant value creation, both for patients by providing innovative therapeutic solutions and for the company and its shareholders.
In this strategic sector we are targeting pathologies with a significant degree of unaddressed medical need which represent massive market potential. The two drugs developed, Livatag® and Validive®, are innovative drugs designed to provide a strong therapeutic response in diseases for which there currently exists no or very few effective treatments. Furthermore, for these orphan diseases the development programs can be optimized in terms of time and cost and are therefore of major strategic interest to companies such as BioAlliance Pharma.
You currently have two drugs on the market emanating from your own research, where are they positioned in your product «landscape»?
The drugs we have brought to the market, Loramyc® and Sitavig®, are indeed the result of our own research and are proof of our expertise. Twice now we have been able to bring a development right through to registration, with authorities in both Europe and the United States. These drugs are planned to be marketed via partnership agree-ments and to generate recurrent income for the Company. However, the field of so-called «specialty» drugs, bringing an improvement to the drugs already being marketed through galenic formulation, is not the thrust of our strate-gic development. These drugs have provided and will continue to provide the Company with income, as has been the case with Loramyc® since 2007 (over €55m through licensing agreements) but will not drive the future growth of the Company.
Do you also plan to establish partnerships to develop sales of Livatag® and Validive® in certain countries?
A strategy of partnerships with these products is clearly an option we are already considering. It is possible to ima-gine that we will retain the product in-house for direct marketing activities in certain areas such as Europe, and entrust it to partners under license in other regions of the world.
With the roll-out and culmination of your research pro-grams, which should also be accompanied by a change of financial scale, what is your financing strategy to support the growth?
Our financing strategy is clearly one of the current ques-tions under review in light of the anticipated revenues, their timing and the needs of the Company.
Beyond the development expertise and right up to pro-duct registration, our products on the market are certainly important due to the substantial income they bring in, but they are in no way intended to provide the full amount of investment required for the development of our orphan drugs in oncology. Apart from certain agreements due to be concluded over the coming months, the Company is analyzing the most appropriate financing solutions in order to actively pursue the deployment of its programs.
You have confidence in the future of BioAlliance Pharma?
Yes, absolute confidence! We have major challenges ahead of us, but also the means, expertise and courage to meet them with success. We are duty-bound to complete our mission of understanding and meeting patient needs with innovative products.
And finally, I would like to thank all BioAlliance employees for their unfailing commitment, day in and day out, and also the Board of Directors under the leadership of Patrick Langlois, for its effectiveness and constant support. And our shareholders, for the faith they have placed in us, now more than ever.
MESSAGE FROM CHIEF EXECUTIVE OFFICER
8BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
€55malready receivedfrom partnerships
Over
€1,5min consolidated salesin 2013
€11,3mcash positionas of 31 December 2013
€10min R&D investment
251 patentsand published patent applicationsat 31 December 2013
1in Europe and the United States
drug registered and marketed
21 Phase III started in 20121 Phase II with recruitment undergoing completion (inclusion of last patient anticipated in H1 2014)
internationalclinical trials
SUBSTANTIAL ASSETS
52all experts in their field
employees 81 international and balancedBoard of Directors
directors
KEY FIGURES
9including United States and 8 countries in Europe for Livatag®United States and 5 countries in Europe for Validive®
countriesIn
70including 40 centers in Europe for Livatag®33 centers in the United States and Europe for Validive®
active clinical centers
Over
1in Europe and the United States
drug registered
9BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
JANUARYThe FDA authorizes the start of the Phase II clinical trial for Validive® (clonidine Lauriad®) in the United States for the prevention of severe oral mucositis induced by radiotherapy or chemotherapy in the treatment of head and neck cancer.
FEBRUARYCollaboration agreement with one of the world’s leading vaccine companies for the development of vaccinal application of the patented Lauriad® mucoadhesive technology.
MARCHContinuation of the Loramyc® development plan in Japan by its partner Sosei with the initiation of the pivotal Phase III registration phase.
APRILMarketing Authorization from the U.S. Food and Drug Administration (FDA) for Sitavig® in the treatment of recurrent labial herpes.
MAYFollowing the review of tolerance data, second positive recommendation from the independent European expert committee (Data Safety and Monitoring Board) to continue with the ReLive trial without modification (Phase III Livatag® trial in primary liver cancer).
JUNEInitiation in the United States of the Phase II clinical trial for Validive® (clonidine Lauriad®) for the prevention of severe oral mucositis induced by radiotherapy or chemotherapy in the treatment of head and neck cancer.
BioAlliance Pharma Combined General Meeting: Appointment of Russell Greig and Danièle Guyot-Caparros, Independent Directors.
JULYBioAlliance Pharma obtains funding of €4.3m from bpifrance (formerly OSEO)to accelerate the industrial development of Livatag® - Creation of the NICE consortium: first nanomedicine sector in France, BioAlliance Pharma lead member of the consortium.
Issue of two patents by the American and Japanese authorities for its drugs Oravig® (miconazole in the treatment of oropharyngeal candidiasis) and Sitavig® (acyclovir in the treatment of labial herpes).
Successful raising of capital: Gross amount raised: 8.7 million euros; Operation oversubscribed at 155%; Exercise of extension clause.
SEPTEMBERFirst meeting of the international expert committee into oral mucositis and its associated clinical development program conducted with Validive® (clonidine Lauriad®).
OCTOBERThird positive recommendation from the independent European expert committee (Data Safety and Monitoring Board) to continue with the ReLive trial without modification (Phase III Livatag® trial in primary liver cancer).
NOVEMBERCommercial exclusivity of Sitavig® strengthened by the issue of 2 new patents: industrial protection extended in the United States until 2029.
DECEMBERAuthorization received for the Phase III ReLive (Livatag®) trial in primary liver cancer in the United States and Germany.
2013 HIGHLIGHTS
10BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
MAJOR ADVANCES WITH ORPHAN PRODUCTSIN ONCOLOGY
LIVATAG®(DOXORUBICIN TRANSDRUG™), MAJOR PROGRESS WITH THE PHASE III CLINICAL TRIAL INTO PRIMARY LIVER CANCER
LIVATAG®, IN BRIEF
Primary liver cancer, also called hepatocellular car-
cinoma (HCC), is an aggressive cancer which is resistant
to treatment by chemotherapy and is the second highest
cause of death through cancer worldwide. It is commonly
diagnosed at an advanced stage at which time few thera-
peutic alternatives exist, presenting a strong therapeutic
need. Hepatocellular carcinoma (HCC) develops from
liver cells (hepatocytes) and represents 85% of primary
liver cancers. In the great majority of cases (>90%), it
occurs when the liver is already abnormal (cirrhosis). The
risk factors are well known: infection by hepatitis viruses
(B and C), overconsumption of alcohol (another major
cause of cirrhosis) and metabolic disease, especially obe-
sity, are growing causes of cirrhosis and HCC.
Livatag® is an innovative treatment designed to over-
come the mechanisms of resistance by using nanoparticles
to deliver doxorubicin into chemotherapy-resistant cells.
Livatag® enjoys orphan drug status in Europe and the
United States, enabling optimization of the product’s
development plan in terms of cost and duration, as well
as strengthening its protection (market exclusivity). The
product’s sales potential is estimated at 800 million euros
worldwide.
Livatag® is protected by two families of patents
protecting its composition (doxorubicin contained in
nanoparticles) and its specific administration regimen
until 2031, until which time no generic product may be
marketed.
LIVATAG®, THE ACHIEVEMENTS
The international randomized Phase III trial, started in
June 2012, aims at demonstrating the efficacy of Livatag®
on survival in nearly 400 patients with hepatocellular
carcinoma after failure or intolerance to Sorafenib. Some
twenty centers have been opened in France. During
2013, the trial was rolled out across Europe to 7 other
countries (Germany, Spain, Italy, Russia, Hungary, Austria
and Belgium). After reviewing the development plan for
Livatag®, in December 2013 the FDA (Food and Drug
Administration) gave its authorization for the trial to be
conducted in the United States.
As of the date of this report, over 100 patients have been
recruited. The extension of the trial to the United States
and in Europe should enable recruitment to be accelerated
from 2014. Recruitment is due to be completed in 2015
with preliminary results anticipated in 2016.
A committee of independent European experts (Data
Safety and Monitoring Board, DSMB) chaired by Professor
Michel Beaugrand continuously monitors the trial. This
type of committee is usually set up in pivotal Phase III
clinical trials to ensure patient safety and the integrity
of the study’s process, and to recommend possible
amendments to the protocol. Since the start of the trial,
the independent expert committee has met three times
and unanimously recommended continuing the study
without modification.
11BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
LIVATAG®REPRESENTSA NEW THERAPEUTIC OPTION COMPARED TO EXISTING TREATMENTS
“
”
MAJOR ADVANCES WITH ORPHAN PRODUCTS IN ONCOLOGY
«Liver cancer is a particularly severe and common
form of cancer. Today it is the second most
frequent cause of death from cancer and its
incidence is set to triple by 2020/2025. There
is a major need for effective treatments for
the most advanced forms in order to improve
patient survival rates. Livatag® represents a
new therapeutic option compared to existing
treatments due to its nanoparticulate formulation
which enables tumor resistance mechanisms to
be overcome and should provide it with very
interesting active properties. We hope that the
ReLive trial will enable us to confirm the patient
benefit, a decisive criterion for the registration of
the product and its accessibility by patients and
doctors.»
FOCUS LIVATAG®AN EXPERT’S POINT OF VIEW
PROFESSOR PHILIPPE MERLEHEPATOLOGY DEPARTMENT, CROIX ROUSSE HOSPITAL IN LYON,AND CENTRE DE RECHERCHE EN CANCÉROLOGIE (ONCOLOGY RESEARCH CENTRE) IN LYON, INSERM U871, INTERNATIONAL COORDINATOR OF THE RELIVE TRIAL
12BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
VALIDIVE® (CLONIDINE LAURIAD®), ACTIVE PURSUIT OF THE INTERNATIONAL PHASE II TRIAL WITH RECRUITMENT SCHEDULED TO BE CONCLUDED IN EARLY 2014 AND INITIAL RESULTS DURING THE SECOND HALF OF 2014
VALIDIVE®, IN BRIEF
Oral mucositis consists of erythematous and ulcerative
lesions of the oral mucous membrane. It is one of the
most common complications of radiotherapy and
chemotherapy.
This severe pathology affects nearly 80% of patients
suffering from a head and neck cancer treated by
radiotherapy or chemotherapy (120,000 new patients
per year estimated in Europe and the United States). Oral
mucositis currently has no proven cure. The consequences
of mucositis are significant pain, difficulty ingesting solid
and even liquid food which may require parenteral or
enteral feeding, hospitalization in 30% of cases, degraded
general condition and sometimes the cessation for a
longer or shorter period of the cancer treatment protocol
which may reduce its efficacy.
BioAlliance is developing Validive® (clonidine Lauriad®)
for the treatment or oral mucositis induced by radiotherapy
or chemotherapy in patients suffering from a head and
neck cancer. It consists of a novel therapeutic application
of clonidine (an agonist of the alpha-2 adrenergic
receptors traditionally used to counter hypertension)
based on Lauriad® mucoadhesive technology. Clonidine
acts as an agonist of the alpha-2 adrenergic receptors
on leucocytes and macrophages, thereby decreasing the
expression of the pro-inflammatory genes and the release
of cytokines IL6, IL1β and TNFα. The liberation of these
pro-inflammatory cytokines causes mucositis and the
effect of clonidine is to suppress the pro-inflammatory
mechanisms. Validive® also acts on the anti-inflammatory
mechanisms by increasing the release of TGF β. Clonidine
therefore has painkilling and anti-inflammatory properties.
Validive® enjoys orphan drug status in Europe and
the United States, enabling optimization of the product’s
development plan in terms of cost and duration, as well
as strengthening its protection (market exclusivity). The
product’s sales potential is estimated at between 200 and
400 million euros worldwide.
Validive® is protected by a family of patents covering
the treatment and prevention of inflammation, and
especially mucositis, through clonidine. Protection is
provided until 2029.
VALIDIVE®, THE ACHIEVEMENTS
The international double-blind, placebo-controlled Phase
II trial is underway in Europe and the United States. As of
the date of this report, 95% of the patients planned for
the trial have been recruited. Recruitment is due to be
concluded during the first half of 2014 with initial results
anticipated during the second half of the year.
In January 2014, Validive® received fast-track status from
the Food and Drug Administration (FDA), providing it
with accelerated and continuous review by the American
agency in recognition of the severity of the pathology
being treated and the urgent need for suitable treatment.
A new step in the industrialization of Validive® was taken
with the signing of an agreement with Penn Pharma for
the pharmaceutical development of Validive®, including
the production of Phase III clinical batches and commer-
cial production.
In September 2013, a European and American expert
committee of international renown in the fields of oral
mucositis, oral medicine, oncology and radiotherapy was
created around oral mucositis and Validive® and its asso-
ciated clinical development program. Its role is to bring
its expertise and recommendations to bear on the deve-
lopment strategy for Validive® and its medical positioning
within oral mucositis.
MAJOR ADVANCES WITH ORPHAN PRODUCTS IN ONCOLOGY
13BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
«We are permanently confronted with the
sequelae of radiation’s side effects: Patients
that are irradiated in the head and neck area are
particularly suffering from inflammation of the
oral mucosa. Pain and hindered ingestion of food
and liquids are the consequences and finally
may lead to a general deterioration requiring
hospitalization and intensive medical attention.
Although modern techniques may help to
protect normal tissue from radiation exposure,
pharmacological methods to prevent or
treat radiation-induced mucositis are so far
- unfortunately - limited. Extensive research,
therefore, is underway to better understand the
pathophysiology of mucositis and to design new
treatment options. Recently the inflammatory
component of the process moved into focus and
very promising first signs of anti-inflammation
directed interventions seem to be ready to hand.
Given that we are lucky to participate in first
line in the Clonidine-Lauriad-Trial, a study using
a „topical“ formulation of an anti-inflammatory
agent with virtually no side effects on the general
condition of these heavily stressed patients.
We are looking forward to see first results of this
trial in 2014 and hopefully will dispose thereafter
of means to better control devasting oral
mucositis in our patients being irradiated in the
head and neck area.».
FOCUS ON VALIDIVE®AN EXPERT’S POINT OF VIEW
...THE FIRST VERY PROMISING METHODS OF TACKLING THE INFLAMMATION...
“
”
PROFESSOR MICKAEL HENKERADIO-ONCOLOGIST, FREIBURG UNIVERSITY HOSPITAL,TRIAL COORDINATOR FOR GERMANY
MAJOR ADVANCES WITH ORPHAN PRODUCTS IN ONCOLOGY
14BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
ACTIVITIES AND ACHIEVEMENTSOF THE DEPARTMENTS
R&D
Nearly 70% of employees currently work in the R&D
Department, covering Preclinical, Clinical and Regulatory
activities.
These 3 activities are at the heart of the development of
a drug, which demands interaction and teamwork as each
activity relies heavily on the work of the other two.
BioAlliance Pharma employees, specializing in Preclinical
and Clinical, pharmacology, biochemistry and molecular
biology, exploit their expertise in support of preclinical
product development, notably by providing proof of
concepts and the toxicological and pharmacokinetic
prerequisites required for the product to enter the clinical
phase and by developing in vitro or animal models in
response to the requirements of product development
strategy. Our experts in galenic pharmacy carry out
pharmaceutical development, notably with innovative
forms such as nanoparticulate and mucoadhesive
formulations. The experience acquired through the
international registration of 2 products, Loramyc®
and Sitavig®, supports the optimization process of
developments with a view to gaining MAs for our future
drugs
The Preclinical and Clinical team actively contributes
to the dynamism of partnerships with academic
departments, as demonstrated once again with the teams
from Paris Sud University in the field of nanotechnology
with the creation of the NICE consortium, a reflection
of the success of BioAlliance in the management of its
academic alliances.
The BioAlliance Clinical team is responsible for carrying
out clinical trials from Phase I (which tests for tolerance
and detects the first signs of efficacy), Phase II (which
researches the optimum dose in terms of efficacy and
tolerance) and Phase III (which confirms the large-scale
efficacy of the drug on a defined patient population).
The application of clinical trial protocols and the
performance of a clinical trial must comply with extremely
strict regulations and requirements, designed to ensure
patient safety and respect and to guarantee the quality,
veracity and integrity of the results obtained.
The Clinical team, consisting of experienced Project
Managers and Clinical Coordinators, implements the
trials, monitors investigation centers and is in permanent
contact with the investigation centers, authorities and
experts, while coordinating activities with the CROs
(Clinical Research Organizations) which are responsible
for the day-to-day management of all the investigation
centers worldwide.
In 2013, the team obtained authorization from the FDA for two Phase II and Phase III clinical trials, of Validive® in the USA in early 2013 and of Relive (Livatag®) at year end. Thanks to its ability to set up numerous investigation centers in the United States and Europe, recruitment for the Validive® trial has been significantly accelerated and should be completed over the coming weeks, with preliminary results anticipated during the fourth quarter of 2014.
DA key support department for the Preclinical and Clinical teams, the Regulatory Affairs Department is largely responsible for development and registration strategy. It analyzes guidelines and requirements in order to give advice to the other teams regarding the choices to be made throughout the development of the drug, with the objective of creating maximum opportunity for success while ensuring compliance with regulatory requirements issued by the authorities.
Three regulatory affairs specialists are responsible at BioAlliance for providing day-to-day regulatory analysis of project activities, combining regulatory watch with critical evaluation in the light of the demands of the various health authorities.
This expertise was once again demonstrated in 2013, crowned by the successful FDA registration of Sitavig® in the USA. In Europe, Sitavig® had already been approved in 8 countries and the latest registrations, in France and Germany, were achieved in March 2014.
15BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
STRATEGY AND MEDICAL AFFAIRS
The Strategy and Medical Affairs team works on the
medical positioning and market access of products
under development and those already on the market.
This department’s work is based on a variety of activities,
notably scientific and medical watch and competitor
assessment. The monitoring of the good safety profile
of existing and development products is also one of the
team’s responsibilities.
In 2013, analysis of the possibility of extending the
development programs was carried out to accelerate
and widen the commercialization of our products to the
emerging BRIC markets of Brazil, Russia, India and China.
The creation of international expert committees for two
of our products undergoing clinical development was a
highlight of 2013. The objective of these committees is
to optimize the development plans, to smooth the way
for registration and enable market access under optimal
conditions, in order to ensure an appropriate response to
the needs of both patients and the medical profession.
The granting to Validive® of Fast Track Designation by
the FDA is one of the most significant outcomes of the
strategies that we have implemented.
Granting of Fast Track status to Validive® by the Food
and Drug Administration (FDA) in the prevention and
treatment of oral mucositis induced by radiotherapy and/
or chemotherapy in patients being treated for cancer. This
status recognizes that Validive® is a drug being developed
for a severe or life-threatening pathology with a significant
medical need. It will allow enhanced interaction with the
FDA and optimize the evaluation schedule of the product
during development and right up to registration.
PIERRE ATTALICHIEF OPERATING OFFICER,STRATEGY & MEDICAL AFFAIRS
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
16BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
BUSINESS DEVELOPMENT
Business Development is a key and strategic activity
for BioAlliance Pharma. Partnership agreements for
registered products are a significant source of income for
the Company and also a means of accelerating product
development, notably by opening up potential markets
which BioAlliance does not have the resources to develop
directly. In the early stages of such projects, business
development also consists of seeking grants and putting
together consortia with academic and industrial partners
around shared themes in order to obtain non-dilutive
financing for conducting the projects.
The main objectives of Business Development in 2014 and
the years ahead are to actively pursue agreements in key
territories for Sitavig®, notably in Europe, and to identify
partners for Validive® and Livatag®. To this end, BioAlliance
is actively seeking partners and is notably taking part
in BioPartnering, a unique opportunity to participate in
numerous events and to present our products to potential
partners.
Granting of a European patent strengthening and
extending the protection of Livatag® by an additional 12
years until 2031, representing a very significant level of
additional earnings for the drug.
Signing of two licensing agreements: the first with
the American company Innocutis for the marketing of
Sitavig® in the United States, and the second with the
Korean company Daewoong Pharmaceutical Co. Ltd for
marketing in South Korea.
Signing of a contract between Japanese partner
Sosei and Fujifilm Pharma, with a view to the future
marketing of Loramyc® in Japan after receipt of marketing
authorization for the country.
Advances in clinical development programs carried
out by its partners with a view to registering Loramyc® in
Japan (Sosei) and in Chine (SciClone Pharmaceuticals).
Retrieval of commercialization and Marketing
Authorization rights for Oravig® in the United States
and advanced discussions with potential partners for
marketing acquisition or license.
Receipt of funding from bpifrance of nearly €9m, of
which €4.3m awarded directly to BioAlliance Pharma via
a Strategic Industrial Innovation (ISI) program enabling
acceleration of the industrial development of Livatag®
and supporting the establishment of the NICE (Nano
Innovation for Cancer) consortium.
17BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
AUDE MICHELHEAD OF CORPORATE BUSINESS DEVELOPMENT
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
18BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
QUALITY
The Quality Policy within BioAlliance Pharma is mainly
designed to ensure that all of our activities, from Clini-
cal and Pharmaceutical Development and Production to
Pharmacovigilance, are carried out in accordance with
regulations and international Good Practices.
Through regular inspections by the health authorities,
the ultimate representatives of patients, the day-to-day
implementation of the Quality Policy is verified. It is
also an essential prerequisite for approval of our Marke-
ting Authorization applications, such as in 2013 with the
various inspections carried out by the Food and Drug
Administration prior to the granting of the NDA for Sita-
vig® in the United States (production unit and several
clinical centers that took part in the clinical trials for Sita-
vig®).
In 2014, quality activities will mainly be associated with
the deployment of Quality Plans for Livatag® and Vali-
dive®.
PRODUCTION
Providing our partners with the products they market in
the various territories, and complying with quality, quan-
tity and cost criteria, are the day-to-day responsibilities
of the team.
They must also prepare for the future, in particular by
selecting the right industrial partner at the right time
for the production of batches intended for the market.
The selection process, carried out during product deve-
lopment upstream of commercialization, is based on a
number of criteria such as expertise, production capacity,
quality level and international recognition.
In 2013 this work, carried out in collaboration with various
departments throughout BioAlliance, led to the selection
of Penn Pharma for the development, industrialization
and future production of Validive®.
Optimization of the development and commerciali-
zation program: commencement of industrialization via
an agreement with Penn Pharma for the pharmaceutical
development of Validive®, including the production of
Phase III clinical batches and commercial production.
MICHEL FORESTCHIEF PHARMACIST & QUALITY ASSURANCE DIRECTOR
19BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
NICOLAS FELLMANNCHIEF FINANCIALAND HUMAN RESOURCES OFFICER
ACTIVITIES AND ACHIEVEMENTS OF THE DEPARTMENTS
FINANCEAND HUMAN RESOURCES
The Finance and Human Resources Department covers all
financial, human resources management, corporate legal
and other support services.
It supports the Company’s strategy by managing the
budget, finance & cash flow and relationships with the
financial community, also performing financial risk control
and financial & fiscal optimization activities. Finance
Department teams (accounts and management control)
stay close to operational employees on a day-to-day basis,
thereby ensuring constant and rigorous management
of expenditure and investment commitments within a
culture deliberately focused on cash flow optimization.
The management of obligations in terms of company
and stock market law, including compliance with the
disclosure obligations of listed companies and executive
management, in support of Director and Shareholder
meetings, is another important dimension of the team’s
work.
Finally, the department provides the men and women
who give BioAlliance Pharma its distinctive value all the
support they may require in the field of human resources.
The culture of the Company is based on strong values
of innovation and excellence, but also of teamwork and
solidarity, values which are continually reiterated through
a very high level of interaction between the Human
Resources Department, management and employees.
In 2013, successful capital increase of 8.7 million euros,
155% subscribed, notably intended for the acceleration
and completion of the Validive® Phase II trial.
20BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
GOVERNANCE
Rémi Drol ler, Russel l Greig, Thomas Hofstaetter, David Solomon, Judith Grec iet , Nicolas Trebouta, Patr ick Langlois , Danièle Guyot-Caparros
«We became a shareholder of BioAlliance five years ago with a long-term vision. We are today very happy with our decision on account of this independent company having two products registered in the USA, two others with very strong potential which have commenced their final clinical trial phases, a Board of Directors composed of pragmatic professionals and a management team led by Judith Greciet with all the expertise and determination required to successfully see its development through. These are just some of the reasons behind our continued faith and support over the years ahead»NICOLAS TREBOUTAREPRESENTING FINANCIÈRE DE LA MONTAGNE
«For me it is a privilege to sit on the Board of Directors of BioAlliance Pharma, a French biotechnology company engaged in the development of innovative drugs to treat rare cancers, and which has already been able to successfully develop and register two drugs exploiting leading-edge technology. It is with conviction and enthusiasm that I commit myself to my role as Board member - a rewarding and gratifying experience »THOMAS HOFSTAETTER
21BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
The Board of Directors determines the Company’s business policies, approves the strategy and oversees its implementation.
The composition of the Board of Directors of BioAlliance Pharma changed during 2013. Following the expiry and non-renewal of the terms of office of Catherine Dunand and Michel Arié following the General Shareholders’ Meeting of 26 June 2013, the same meeting approved the appointment of Danièle Guyot-Caparros, Independent Director, and Russell Greig, previously and since 17 July 2012 a permanent guest member of the Board and also an Independent Director.
The Board of Directors consists of eight high-level professionals in the pharmaceutical and finance industries, including five independent directors and two representatives of the Company’s main shareholders:
Chairman: Patrick Langlois, PhD in Economics and Finance, General Partner of PJL Conseil and member of the boards and non-executive director of biotech organizations in Europe and the U.S.
Chief Executive Officer: Judith Greciet, PhD in Pharmacy, joined BioAlliance in March 2011 after a successful managerial career with increasing operational and strategic responsibilities at Laboratoire EISAI France, Wyeth Pharmaceuticals France (now Pfizer), LFB (Laboratoire Français du fractionnement et des Biotechnologies), Zeneca and Pharmacia.
Russell Greig has over thirty years of experience in the pharmaceutical industry, with expertise in research & development and business development. Russell Greig spent a significant part of his career at GlaxoSmithKline (USA/UK) where he was Senior Vice President of Worldwide Business Development R&D.
Danièle Guyot-Caparros is a chartered accountant and a finance and accountancy graduate of the Ecole Supérieure de Commerce in Nancy. After experience with an audit firm carrying out international assignments she joined Rhône-Poulenc, later to become Aventis and then Sanofi, occupying several important posts, notably with responsibilities carried out in France at European level and then in business planning and performance monitoring on a worldwide level. Over the past 5 years, Danièle Guyot-Caparros has been a consultant specializing in the field of life sciences and health.
Thomas Hofstaetter has over thirty years of experience in the development and acquisition of biotechnology companies and technological cooperation agreements, including at Wyeth, Inc. and Aventis, VaxInnate Corporation and Geron Corporation.
David Solomon, Physician Pharmacologist, CEO of Zealand Pharma (Denmark), holding various positions with executive responsibilities in biotech companies since 2006.
Financière de la Montagne, represented by Nicolas Trebouta. Financière de la Montagne has been a director of BioAlliance Pharma since June 2011. Nicolas Trebouta has managed investments in biotechnology companies directly through his Company, Financière de la Montagne, or through funds.
Kurma Life Sciences Partners, represented by Rémi Droller. Kurma Life Sciences Partners has been a director of BioAlliance Pharma since 16 December 2010. Rémi Droller joined Kurma as Partner in September 2010 after more than 10 years of experience in the field of healthcare investment.
The board sat on 7 occasions during 2013. It is assisted in the preparation of its decisions by two specialized committees, the Audit Committee and the Appointments and Remuneration Committee.
OPERATIONALDECISION-MAKING BODIES
STRATEGY COMMITTEEThe Strategy Committee sets the strategy, major policies and growth scenarios of the Company and oversees their implementation. It ensures that the company is managed collectively and cross-functionally.
Its members are as follows:• Judith GRECIET, Chief Executive Officer• Pierre ATTALI, Chief Operating Officer, Strategy & Medical Affairs• Nicolas FELLMANN, Chief Financial and Human Resources Officer• Michel FOREST, Chief Pharmacist & Quality Assurance Manager• Aude MICHEL, Head of Corporate Business Development
OPERATIONS COMMITTEEComposed of the Executive Management, department heads
and R&D operational departments, the Operations Committee sets the operating strategy, systematically reviews and validates progress of projects, and coordinates the teams.
RISK MANAGEMENT COMMITTEEThis committee updates the Company’s risk mapping and monitors action plans with the departments concerned.
AN INTERNATIONAL BOARD OF DIRECTORSTO GUIDE THE COMPANY’S GROWTH
22BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
STOCK MARKETAND SHAREHOLDERS
FINANCIAL CALENDAR27/02/2014 Publication of the consolidated financial statements for 2013
28/02/2014 2013 accounts presentation meeting
08/04/2014 Combined Shareholders’ Meeting
15/04/2014 Publication of the revenue statement for Q1 2014
22/09/2014 Publication of the half-year financial report
23/09/2014 2014 half-year accounts presentation meeting
07/10/2014 Publication of the revenue statement for Q3 2014
ISIN DETAILS
Code ISIN/Euronext - FR0010095596
Code Mnémonique : BIO
Euronext Paris - Compartiment C
Shares outstanding at 31/12/2013 : 20 682 992
Share capital : € 5 170 748
Simple voting rights only
Liquidity contract: CM-CIC Securities
50,0%Retail
13,6%Financière
de la Montagne
5,2%IDInvest Partners
31,2%Other
institutional
SHAREHOLDINGAT 31 DECEMBER 2013
3,0
3,5
4,0
4,5
5,0
5,5
01 02 111009080706050403 12
6,0 Price at 02 January 2013:
Price at 31 December 2013:
Highest share price: at 25/01/2013
Lowest share price: 02/07/2013 :
Market capitalisation at 31/12/2013:
4,83 €
4,28 €
5,80 €
3,42 €
88,50 M€
SHARE PERFORMANCE 2013
23BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
SIMPLIFIEDFINANCIAL REPORT
CONSOLIDATED BALANCE SHEET
ASSETS (IN EURO)
NON-CURRENT ASSETS
Intangible assets
Tangible assets
Financial assets
Other non-current assets
Total non-current assets
CURRENT ASSETS
Inventories and work in-progress
Trade receivables
Other receivables
Marketable securities
Cash
Total current assets
TOTAL ASSETS
31/12/2012
32 519
1 085 533
421 565
0
1 539 616
2 739
2 088 957
3 985 696
7 892 826
6 610 308
20 580 526
22 120 142
31/12/2013
22 785
908 313
368 998
0
1 300 096
3 145
338 113
4 772 870
7 357 014
3 972 013
16 443 156
17 743 252
LIABILITIES (IN EURO)
SHAREHOLDERS’ EQUITY
Share capital
Less: treasury shares
Additional paid-in capital
Reserves
Minority interests
Net income/(loss) for the year
Total shareholders’ equity
NON-CURRENT LIABILITIES
Provisions
Other liabilities
Total non-current liabilities
CURRENT LIABILITIES
Short-term debt
Trade payables
Other liabilities
Total current liabilities
TOTAL LIABILITIES AND EQUITY
31/12/2012
4 414 929
(25 147)
118 081 366
(99 180 837)
0
(11 547 921)
11 742 389
751 910
3 479 260
4 231 170
56 931
3 791 419
2 298 232
6 146 582
22 120 142
31/12/2013
5 170 748
(58 512)
128 044 120
(110 398 366)
0
(15 320 256)
7 437 734
456 878
3 030 220
3 487 098
91 182
4 557 185
2 170 054
6 818 420
17 743 252
All regulatory information on BioAlliance Pharma can be viewed at its websitewww.bioalliancepharma.com
24BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
SIMPLIFIED FINANCIAL REPORT
CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME
€
Net sales
Other income
Purchases
Personnel costs
External expenses
Taxes other than on income
Depreciation and amortisation, net
Allowances to provisions, net
Other operating income
Other operating expenses
Operating expenses
Operating loss
Income from cash and cash equivalents
Other financial income
Financial expenses
Financial loss
Income/(loss) before taxation
Income tax expense
Net income/(loss)
Earnings per share
Diluted earnings per share
Income/(loss) for the period
Other elements of the comprehensive income for the period net of taxes
Total comprehensive income for the period
31/12/2012
4 028 124
546
(375 231)
(4 821 647)
(7 938 743)
(1 946 732)
(214 955)
(106 130)
15 364
(155 799)
(15 559 238)
(11 515 203)
249 520
21 640
(303 879)
(32 718)
(11 547 921)
0
(11 547 921)
(0,65)
(0,65)
(11 547 921)
332 490
(11 215 431)
31/12/2013
1 466 712
16
(264 271)
(5 346 986)
(10 706 716)
(297 740)
(232 994)
64 774
5 381
(125 028)
(16 908 960)
(15 436 850)
281 173
122 680
(287 260)
116 593
(15 320 256)
0
(15 320 256)
(0,74)
(0,74)
(15 320 256)
253 332
(15 066 923)
25BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
STATEMENT OF CONSOLIDATED CASH FLOW
31/12/2012
(11 547 921)
603 058
38 424
339 495
(99 730)
(75)
(10 666 749)
(5 706)
(10 672 454)
(3 409 121)
(14 081 575)
(53 813)
1 262
(10 622)
137
(63 036)
27 000
34 827
56 436
(122 606)
70 679
(71 527)
(5 191)
(12 723)
(14 162 525)
28 665 659
14 503 134
31/12/2013
(15 320 256)
3 419
(44 944)
300 075
(14 542)
(0)
(15 076 249)
(71 532)
(15 147 781)
1 055 915
(14 091 866)
(58 254)
12 540
2 973
(42 741)
10 718 574
(51 538)
83 148
75 456
71 532
14 838
10 912 010
48 490
(3 174 107)
14 503 134
11 329 027
€
CONSOLIDATED NET LOSS
+/- Depreciation, amortisation and provisions, net
(excluding provisions against working capital)
-/+ Unrealised gains and losses related to changes in fair value
+/- Non-cash income and expenses on stock options and similar items
-/+ Other non-cash income and expenses
-/+ Capital gains or losses on disposal
-/+ Capital gains or losses on dilution
+/- Share of earnings of associates
- Dividends (non-consolidated investments)
Gross operating cash flow after cost of net debt and taxes
+ Cost of net debt
+/- Tax expense (including deferred taxes)
Gross operating cash flow before cost of net debt and taxes
- Taxes paid
+/- variation of BFR linked to the activity
Change in working capital (including employee benefit liabilities)
NET CASH FLOW FROM OPERATING ACTIVITIES
- Expenditures on acquisition of tangible and intangible assets
+ Proceeds of disposal of tangible and intangible assets
- Expenditures on acquisition of financial assets (non-consolidated investments)
+ Proceeds of disposal of financial assets (non-consolidated investments)
+/- Effect of changes in scope of consolidation
+ Dividends received (equity accounted investments, non-consolidated investments)
+/- Change in loans and advances granted
+ Capital grants received
+/- Other flows relating to investment activities
NET CASH FLOWS FROM INVESTING ACTIVITIES
+ Net amounts received from shareholders on capital increases
Paid by shareholders of the parent company
Paid by minority interest in consolidated companies
Amounts received on exercise of stock options
-/+ Purchases and sales of treasury shares
- Dividends paid in the year
Dividends paid to shareholders of the parent company
Dividends paid to minority shareholders in consolidated companies
+ Amounts received on issuance of new loans
- Reimbursements of loans (including finance leases)
- Net interest received (including finance leases)
+/- Other flows related to financing activities
NET CASH FLOWS FROM FINANCING ACTIVITIES
+/- Effect of fluctuations in foreign exchange rates
CHANGE IN CASH AND CASH EQUIVALENTS
Cash and cash equivalents at start of year
CASH AND CASH EQUIVALENTS AT YEAR END
SIMPLIFIED FINANCIAL REPORT
26BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
BIOALLIANCE PHARMA49, boulevard du Général Martial Valin,75015 Paris
Tél. : + 33 (0) 1 45 58 76 [email protected]. bioalliancepharma.com
27BIOALLIANCE PHARMA | 2013 ANNUAL REPORT
Photo credits : Image BioAlliance Pharma,
Xavier Granet, Enguerran Ouvray, Tek Image
Publisher : BioAlliance Pharma
Design and production : Limbus Studio
BIOALLIANCE PHARMA49, boulevard du Général Martial Valin,75015 Paris
Tél. : + 33 (0) 1 45 58 76 [email protected]. bioalliancepharma.com
Contact : BioAlliance Pharma - Nicolas Fellmann49, boulevard du Général Martial Valin,75015 ParisTél. : + 33 (0) 1 45 58 76 [email protected]. bioalliancepharma.com