annual report

INNOVATIVE
MEDICINE
FOR
EVERYONE,
EVERY WHERE
2014
annual
report
2014 \\\\\ ADOCIA ANNUAL REPORT
TABLE OF
CONTENTS
02 LETTER FROM THE CEO
04 RESEARCH & DEVELOPMENT
06 DIABETES TREATMENT
A CORE FOCUS FOR ADOCIA
KEY FIGURES
2
3
TECHNOLOGICAL PLATFORMS:
BioChaperone®
and DriveIn®
MARKETS TARGETED:
DIABETES, CHRONIC WOUND
HEALING, ONCOLOGY
4
1
PRODUCTS UNDER CLINICAL
DEVELOPMENT
PARTNERED
PROGRAM
08 PRODUCTS AND MARKETS
08 10 12 14 16 17
BioChaperone® Lispro
HinsBet®
BioChaperone® Combo
BioChaperone® PDGF
Monoclonal Antibodies
DriveIn®
18 HUMAN RESOURCES
20 FINANCIAL REPORT
23 GOVERNANCE
24 EVENTS 2015
50 ME
AVAILABLE CASH
END OF DECEMBER 2014
80
EMPLOYEES
KEY EVENTS 2014
INNOVATIVE MEDICINE
FOR EVERYONE,
EVERYWHERE
December
ADOCIA is a biotechnology company specialized
in the development of best-in-class medicines
using already approved therapeutic molecules.
Alliance with Eli Lilly & Company to co-develop
ultra-rapid insulin based on BioChaperone® technology,
after successfully completing two clinical studies in 2014.
September
Winner of the Frost & Sullivan 2014 Technology
Innovation Leadership Award in the therapeutic proteins
industry.
August
Launch of a Phase III clinical study in India for
the treatment of Diabetic Foot Ulcer.
June
Presentation of 2 posters at the 74th Annual ADA Scientific
Sessions (American Diabetes Association, in San Francisco)
on BioChaperone® Lispro and BioChaperone® Combo.
Today ADOCIA is focusing its activity on the treatment
of diabetes and one of its leading consequences,
Diabetic Foot Ulcer.
Diabetes has reached pandemic proportions,
currently affecting more than 387 million people*
worldwide, in developed countries as well as in
emerging countries.
Since 2006, our team of researchers has been
developing innovative solutions so that existing
treatments can be made more effective and widely
accessible to everyone.
Launch of ADR Program (American Deposit Receipt)
in the United States.
March
Confirmation of positive clinical results for BioChaperone®
Combo, a combination based on long-acting insulin glargine
and a fast-acting insulin analog.
January
Strengthening of the diabetic foot ulcer patent portfolio:
delivery of two of major patents, one in Japan (BC PDGF
Composition) and the other in the United States (Polymer
BioChaperone®).
* Diabetes Atlas 6th edition - International Diabetes Federation - 2014
A D O C I A A N N U A L R E P O R T PA G E 1
2014 \\\\\ ADOCIA ANNUAL REPORT
GÉRARD SOULA
CHAIRMAN AND CEO
LETTER FROM THE CEO
2014, A RENAISSANCE
FROM RECOGNITION
In 2014 we built solid evidence of the value of our
ultra rapid insulin program, evidence that convinced
Eli Lilly to enter into a new licensing agreement.
This new collaboration with our former partner is the
best recognition that ADOCIA could have aspired to.
It endorses our strategic development plan for this
project as the financial provisions we received are
significantly higher than the ones negotiated in 2011.
This new collaboration with our former
partner is the best recognition that ADOCIA
could have aspired to.
The upfront payment of USD 50 million allowed
ADOCIA to close the year with a cash position of
nearly EUR 50 million. We consequently decided
to further strengthen our financial position by executing, during the first quarter of this year, a capital
increase of EUR 32 million, representing 10% of the
capital at the time of the operation.
At the end of the first quarter 2015, the company’s cash
position amounted to approximately EUR 77 million.
This cash position allows us to look to the future with
serenity and to independently advance, the development of our products: BioChaperone® Combo,
HinsBet®, and also BioChaperone® PDGF for diabetic
foot ulcer.
The positive clinical results of our BioChaperone®
Combo in a first clinical trial in type 1 diabetic patients
strengthen our decision to initiate additional clinical
studies. Hence, BioChaperone® Combo will be at the
core of our clinical plan this year. Similarly, positive
results for HinsBet® in clinical trials are propelling that
important project forward.
For our diabetic foot ulcer treatment, we finally
received the authorization to initiate the phase III
study of BioChaperone® PDGF in India, a study that
should be completed in the first half of 2016.
The other programs, although at early stages,
are advancing in development. In particular, new
monoclonal antibodies (mAb) formulations are in
feasibility phase in collaboration with two major
pharmaceutical companies. The DriveIn® project,
which is focused on the treatment of solid tumors,
is also part of active research that might lead to
clinical trials in 2016.
ADOCIA is positioned to strengthen in the coming
years its expertise in the field of insulin formulations.
Our objective is to develop new innovations addressing unmet patient needs worlwide.
ADOCIA is positioned to strengthen in
the coming years its expertise in the field
of insulin formulations.
Our subsidiary in the US, created in March 2015, will
reinforce our presence with the medical community, will aid in identifying and advancing business
development opportunities, and will also bolster our
dialog with the financial community.
I would like to thank ADOCIA’s staff whose talent and
motivation are the keys to our success and to our
future.
All my thanks go to our shareholders who support us
in our daily efforts to provide patients with innovative
and efficient medicine.
A D O C I A A N N U A L R E P O R T PA G E 3
2014 \\\\\ ADOCIA ANNUAL REPORT
RESEARCH & DEVELOPMENT
I N N O VAT I O N F I R S T !
ADOCIA’s mission is to develop “best-in-class”
medicines for mass pathologies by developing
innovative formulations of already approved therapeutic proteins. This approach of innovation,
called re-formulation, takes advantage of the track
record, in terms of safety and efficacy, of these
proteins. But the goal is to overcome the limits that
the current formulations of these proteins have.
In addition, ADOCIA’s ambition is to make its products
accessible to the greatest number of people by
enabling a cost-effective approach to innovation.
ADOCIA has invented a technological platform of
innovative molecules - considered to be excipients* called BioChaperone®. BioChaperone® enhances the
medical benefits of therapeutic proteins without
adding significant cost to their manufacture - for
innovation without a premium.
This product development pathway reduces the risk of
failure and the total cost of development. In addition,
a re-formulation of an approved active substance is
eligible for a shorter clinical development plan.
ADOCIA’S BUSINESS MODEL
ADOCIA’s business model is based on partnerships
with pharmaceutical companies, biotech companies,
or medical device companies. The strategy is to
license our proprietary innovations based on the
proof of concept in humans transferring production
or commercialization responsibilities to the partner.
This business model is less capital-intensive than full
development (up to commercialization) and allows a
more rapid return on investment. In addition, the early
development phase, up to the proof of concept, is the
least costly.
ADOCIA’s strategy takes into account three key
parameters of its environment.
NEED FOR NEW PRODUCTS FROM LARGE
PHARMACEUTICAL GROUPS
Pharmaceutical companies face the expiration of
patents protecting their leading products from generics and biosimilars. ADOCIA enables to regenerate
intellectual property on the proteins that felt in the
public domain with more efficient next-generation
formulations.
THE GLOBAL PHARMACO-ECONOMIC CONTEXT
Population growth and aging, as well as a political
context of control over public health expenses, reinforce the pressure on treatment pricing. The BioChaperone® technology is designed to help address
these economic issues. The BioChaperone® platform
offers an array of important and clinically meaningful
changes to the action of proteins, sometimes allowing
a dosage reduction, or changing the number of
applications, or impacting the duration of treatment.
In addition, BioChaperone® is compatible with current
manufacturing processes and does not require any
large investment in the overhaul of manufacturing
plants. BioChaperone® essentially takes advantage
of the maturity of the proteins it is combined with.
THE DEMAND OF EMERGING COUNTRIES
With the rapidly increasing demand for pharmaceutical products in emerging countries, access to healthcare and to drugs remains very problematic and even
critical in some areas. The World Health Organization
notes that more than 80% of deaths resulting from
chronic pathologies occur in countries with low
and middle incomes. With potential “Best-in-Class
Products” using mature proteins, our strategy is
particularly adapted to meet the mass demand of
these emerging countries.
* An excipient refers to any substance other than the active principle
contained in a drug, cosmetic or food
A D O C I A A N N U A L R E P O R T PA G E 4
R&D AND INTELLECTUAL PROPERTY
Since its inception, ADOCIA has innovated in
several major therapeutic areas such as the
healing of chronic wounds and insulin therapy
for diabetes.
With the new technology of DriveIn® nanoparticles, ADOCIA has expanded its areas of
activity to include oncology.
The company’s success depends, at least in
part, on the ability to protect its inventions.
This is globally accomplished by filing and
following the grant procedure, in particular by
defending the patentability of our inventions,
before the different patent offices.
We actively pursue this patent strategy for
products currently in clinical development
as well as for our array of backup, secondary
products.
10
25
100
43
INVENTORS
AT ADOCIA
PATENT
FAMILIES
PATENT
APPLICATIONS
PATENTS
GRANTED
ADOCIA: A SOLID AND DIVERSIFIED PORTFOLIO OF PRODUCTS
In Vitro
Preclinical
Phase I / II
Phase III
Partner
Combo Rapid Ultra Rapid
BioChaperone® Insulins - Diabetes
Completed
Ongoing
BC Lispro U100
BC Lispro U200
HinsBet® U100
HinsBet® U500
BC Combo
BioChaperone® PDGF - Diabetic Foot Ulcer
DriveIn® - Targeted Nanodelivery for Oncology
Collaborative Developments - BioChaperone® Monoclonal Antibodies
Two partnerships
Confidential
A D O C I A A N N U A L R E P O R T PA G E 5
2014 \\\\\ ADOCIA ANNUAL REPORT
FOCUS
D I A B E T E S T R E AT M E N T
A CORE FOCUS FOR ADOCIA
WHAT IS DIABETES ?
DIABETES IS A WORLDWIDE PANDEMIC
Diabetes is characterized by chronically high
levels of blood glucose.
Type 2 diabetes incidence increases with urbanization
and population aging, and is especially on the rise in
emerging countries.
It is a chronic disease stemming from an absence of
insulin production in people with type 1 diabetes and
a relentless decline in insulin production - coupled
with growing resistance to its action - in people with
type 2 diabetes.
387 M
Diabetics
207M
SOONER OR LATER,
INSULIN IS NECESSARY
Diagnosed
103M
Insulin is the fundamental treatment for type 1
diabetic patients and becomes inevitable for type 2
patients when glycemia is no longer controlled by
oral antidiabetics and non-insulin injectables.
Treated
IDF Diabetes Atlas, International Diabetes Federation 2014.
GOAL OF
INSULIN THERAPY
The target of insulin therapy is
mimicry of the normal-healthy
insulin action profile.
Three classes of insulin products
are currently available:
Prandial, for mealtime glucose
control
Basal, for fasting glucose control
Premix, for fasting and prandial
glucose control
ADOCIA’s estimates, based on 2014 data from Novo Nordisk, Eli Lilly and Sanofi
These insulin options only approximate physiologic insulin, often resulting in
persistent and damaging hyperglycemia and the tangible risk of hypoglycemia.
In fact, 80% of insulin-treated patients in the US are not at their glycemic goals.
Chen Y et al, Poster presented at the 2012 ACCP Annual Meeting, October 21 – 24, 2012, Hollywood, Florida, USA
A D O C I A A N N U A L R E P O R T PA G E 6
25M
Insulin
users
BIOCHAPERONE® TECHNOLOGY
IMPROVES INSULIN MEDICAL BENEFITS
ADOCIA’s insulin products have the potential to
become best-in-class based on significant advantages of the reformulation strategy.
Current standard
1st Generation
+
gEstablished safety and efficacy
gOff-patent
gPart of patients’ everyday life
BioChaperone®
Best-in-class
2nd Generation
2 Simple to add
2 Short clinical development
2 Safe and well tolerated
2 Compatible with every device
22
Better glycemic
control with less risk
of hypoglycemia
ADOCIA’S INSULIN PROGRAMS ADDRESS
A DIVERSITY OF UNMET NEEDS
Each insulin program addresses specific needs for
better treatments of various patient groups for costeffective way.
From diabetic patients living in low-income countries
to severely insulin-resistant patients living in highincome countries, the medical needs are diverse.
PERFORMANCE
FOCUS
U100
BioChaperone Lispro*
U200
U100
HinsBet
U500
BioChaperone Combo
COST
FOCUS
SIMPLICITY
FOCUS
A D O C I A A N N U A L R E P O R T PA G E 7
*Collaborative Research & License
Agreement with Eli Lilly
2014 \\\\\ ADOCIA ANNUAL REPORT
B I O C H A PE RO N E ® L I S P R O
A MORE PHYSIOLOGIC ULTRA RAPID INSULIN
Prandial insulins are used to regulate glycemia after
a meal. In a healthy individual, meal consumption
immediately triggers insulin secretion to metabolize
carbohydrates.
This secretion decreases when the blood glucose
level goes down again. Consequently, in order to
match this action profile, injected prandial insulins
must act very rapidly and for only a few hours.
This need has led to prandial insulin treatment
evolving towards faster-acting insulins.
Currently marketed insulin analogs need to be injected
5 to 15 minutes before a meal (vs. 30 minutes for older
treatments such as recombinant human insulin).
Potential medical benefits of ultra rapid insulin
less hyperglycemia
and less hypoglycemia
AN ULTRA RAPID INSULIN IS ESSENTIAL FOR THREE MAIN DIABETIC PATIENT CATEGORIES
CHILDREN
PUMP USERS
>15 000
Diagnosed each year in America
HIGH DOSE T2 PATIENTS
46%
American T1D use pumps1
«Standard» U100
«Concentrated» U200
Sources:
1
Halozyme 2011
2
Daousi et al (2006) Postgrad Med J 2006;82: 280-284
A D O C I A A N N U A L R E P O R T PA G E 8
86%
Overweight T2D2
BIOCHAPERONE® LISPRO HAS BEEN SUCCESSFULLY TESTED IN 3 CLINICAL STUDIES
ADOCIA has applied its BioChaperone® technology
to accelerate the action of insulin Lispro (Humalog®,
Eli Lilly). An illustrative result from these studies is
the pharmacokinetic profile of BioChaperone® Lispro
versus Humalog®. The chart demonstrates that
BioChaperone® Lispro is significantly faster than
Humalog® with both a faster-in and faster-out profile.
Insulin [μU/ml]
110
42 min
100
p<10-4
BioChaperone® Lispro
90
Humalog®
80
70
Tmax
-35% (p<10-4)
AUClispro — 0-30 min +170% (p<10-4)
60
50
40
30
20
10
0
0
1
2
3
4
Cf. Press release ADOCIA France, April 9, 2014 - Extract from the clinical trial report, Aug 4, 2014– PROFIL GmbH
These clinical results were presented
at the two major diabetes congresses in 2014.
The results from the dose response study
have been presented at the scientific session
of ADA 2015.
5
6
Time [h]
A U200 formulation of BioChaperone® Lispro
is also under development and should be tested
in a clinical study in Q3 2015.
In December 2014, ADOCIA and Lilly
entered into a license agreement
for the BioChaperone® Lispro programs.
The first clinical study of the partnership,
consisting of a meal tolerance test, was
successfully completed in June 2015.
A D O C I A A N N U A L R E P O R T PA G E 9
2014 \\\\\ ADOCIA ANNUAL REPORT
H i n s Bet ® U 1 0 0
A COST-EFFECTIVE RAPID INSULIN
FOR PEOPLE WITH TYPE 1 AND TYPE 2 DIABETES IN PATIENTS IN LOW AND MIDDLE INCOME COUNTRIES
77% of diabetic patients live in low- to middle-income
countries where human insulin is the main type of
insulin used.
For these diabetic patients, there is a real need for a
low cost, prandial human insulin that acts as fast as
insulin analogs.
ADOCIA has successfully tested HinsBet® U100 in a
clinical study on 36 people with type 1 diabetic patients.
In this study, HinsBet® was compared to Humalog®
(insulin lispro, Eli Lilly) and Humulin® (human insulin,
Eli Lilly).
HinsBet® U100 was comparable to Humalog® on the
early glucose infusion rate (GIR), a critical parameter for
prandial insulins. HinsBet® is significantly faster than
Humulin® with a 70% earlier onset and a doubling
of the early metabolic effect.
HinsBet® U100 is a standard-concentration formulation
of human insulin with BioChaperone® added in order
to accelerate human insulin onset of action.
GIR (mg/kg/min)
Early Glucose Infusion Rate
2.5
2
HinsBet® U100
Humalog®
Humulin®
1.5
1
0.5
0
0
5
10
15
20
25
30
Time (min)
Cf. Press release Adocia February 05, 2015 - Extract from the clinical trial report, Feb 18, 2015– PROFIL GmbH
We plan to test HinsBet® U100
in a meal tolerance test study in Q4 2015.
A D O C I A A N N U A L R E P O R T PA G E 1 0
H i ns B et ® U 5 0 0
A CONCENTRATED RAPID INSULIN
FOR SEVERELY INSULIN RESISTANT PEOPLE WITH DIABETES IN HIGH INCOME COUNTRIES
Some people with type 2 diabetes are severely
insulin-resistant and their treatment can require
insulin daily doses that are more than two to three
times higher than standard doses for people with
type 2 diabetes, above 200 units per day.
The main insulin treatment option for highly insulin
resistant patients in the United States is Humulin®
U500 (Eli Lilly), a human insulin formulation at
500 UI/ml, i.e. five times more concentrated than
standard commercial products.
It is difficult for these patients to use popular
formulations of insulin analogs at 100 IU/ml, like
Humalog®, since the volumes required for daily
administration are simply too large.
This product has rapidly growing U.S. revenues
that, in 2014, were expected to total more than
USD 300 million*.
HinsBet® U500 is a high concentration
formulation of human insulin with
BioChaperone® in order to deliver an early
onset of action at this high concentration.
We plan to test HinsBet® U500
in type 1 diabetic patients
in a PK/PD study in Q4 2015.
* RED BOOK 2013 - Truven Health Analytics - Thomson Reuters
A D O C I A A N N U A L R E P O R T PA G E 1 1
2014 \\\\\ ADOCIA ANNUAL REPORT
BIOCHAPE RONE ® C O M B O
A MORE EFFECTIVE TWO-IN-ONE INSULIN PRODUCT
Insulin treatment intensification for type 2 diabetic
patients usually requires the addition of prandial insulin
to an existing basal regimen when patients are not
reaching treatment goals on basal insulin alone. The
combined use of a prandial and a basal is also called
the basal/bolus regimen.
This regimen complicates treatment as it entails two
different insulin products, and requires close patient
attention to injection timing and the injected dose.
Importantly, it dramatically raises the shot burden
for patients, increasing number of daily injections,
from 1 to 4 (or more).
A basal/bolus regimen is not always a
realistic option for a large number of patients.
Elderly patients can really have important difficulties
with the basal/bolus regimen. Such patients are
eligible for insulin premix. Premixes are a fixed
combination of a soluble insulin and a precipitated
fast-acting insulin analog, usually injected 2 times
per day. Premix insulins do not offer ideal medical
performance because of delayed and prolonged
prandial action, a basal action profile shorter than
24 hours, and an elevated risk of hypo-glycemia.
The aim of BioChaperone® Combo is to improve
patient options and outcomes by developing an
insulin product combining the relative ease-of-use
and simplicity of a premix regimen with the tighter,
more physiologic control of a basal/bolus regimen.
GLYCEMIC CONTROL
BioChaperone® Combo
BioChaperone® Combo
Single product with
prandial control
Basal/Bolus
Single product with
reduced hypoglycemia risk
Two products
with High Shot Burden
Premix
Single product with
hypoglycemia risk
Basal
Single product without
a prandial control
One shot a day
Two shots a day
Four shots a day
INSULIN TREATMENT INTENSIFICATION
A D O C I A A N N U A L R E P O R T PA G E 1 2
A UNIQUE COMBINATION BASED ON INSULIN GLARGINE
BioChaperone® Combo is an innovative formulation
which combines insulin glargine (Lantus®, Sanofi),
the gold standard basal insulin, with a rapid insulin
analog, lispro (Humalog®, Eli Lilly) using BioChaperone® technology.
Insulin Glargine
N°1 basal insulin
BioChaperone® Combo significantly simplifies insulin
treatment by providing prandial and basal insulins
in a single injection in a single product.
Insulin Lispro
N° 2 prandial insulin
BioChaperone® Combo
glargine lispro
BioChaperone® Combo has been successfully tested
in a clinical trial.
BioChaperone® Combo demonstrated significantly
faster prandial action compared to Humalog® Mix in
type 1 diabetic patients.
In addition, BioChaperone® Combo also proved to
offer a full-day of fasting glucose coverage equivalent
to Lantus.
Cf. Press release ADOCIA Feb 2014 - Extract from the clinical trial report, Aug 6, 2014– PROFIL GmbH
These clinical results were presented
at two significant diabetes congresses in 2014.
Two clinical studies have been initiated in Q3 2015,
a meal tolerance test against an insulin analog premix
in type 1 diabetic patients and an euglycemic clamp
study against basal bolus and an insulin analog premix
in type 2 diabetic patients.
A D O C I A A N N U A L R E P O R T PA G E 1 3
2014 \\\\\ ADOCIA ANNUAL REPORT
BIOCHAPERONE ® P D G F
A SIMPLIFIED TREATMENT FOR DIABETIC FOOT ULCER
When diabetes is not well controlled, patients experience chronic hyperglycemia leading to a number
of complications over the long term.
The loss of sensitivity in the feet, often associated
with poor circulation, commonly leads to the development of a Diabetic Foot Ulcer (DFU) .
These include peripheral neuropathy – damage
to nerves in the hands and feet – and ischemia
restriction in blood supply – particularly in the limbs.
DFUs are chronic wounds that fail to heal and are a
major cause of amputations due to infection.
THE DIABETIC FOOT ULCER, A REAL BUT UNDERSERVED MEDICAL NEED
Chronic Hyperglycemia
15%
Neuropathy
of diabetic patients
will develop a DFU
Neuroischemia
annual growth of DFU prevalence
in western countries
Ischemia
5%
Diabetic foot ulcer
15M patients worldwide
50%
or more neuroischemic patients
in western countries
Wounds International 2013 - Singh N, et al. The Journal of American Medical Association, 2005 - Global Data 2014, DFU Opportunity analysis & Forecast to 2017.
REGRANEX® IS THE ONLY FDA APPROVED BIOLOGIC FOR DFU
The standard of Care (SoC) for DFU consists of debridement of the wound, management of any infection
and off-loading.
Fewer
Amputations
Faster Healing
Annual
Cost Savings
Minus
30%
6 weeks
less
USD 2,270
Only one biologic has been approved by FDA and EMA
as an adjunct to SoC: PDGF-BB, brand name Regranex®
from Smith & Nephew.
The medical benefit and cost-effectiveness of
Regranex® has been clinically proven (versus SoC).
Cf. Gilligan AM. et al. Wound Repair Regen. 2015
A D O C I A A N N U A L R E P O R T PA G E 1 4
A REFORMULATION THAT MAKES PDGF USE EASIER
BioChaperone® PDGF is a second generation
formulation of PDGF-BB, offering important improvements compared to Regranex®:
2 Reduced frequency of application
and wound handling - once every two days
2 Sterile spray
2 Reduction of PDGF dose
2 Reduction in dressings used
2 Stability at room temperature
REGRANEX®
BioChaperone® PDGF-BB
Gel Tube
Spray
CALENDAR
CALENDAR
Applied every day
(
)
1 Dose
(
)
Applied once
every two days
Dressings
(
CLINICAL PROOF OF CONCEPT
BioChaperone® PDGF spray was compared to
Regranex® in a phase I/II clinical study conducted
in 200 diabetic patients in India in 2013 and was
non-inferior to Regranex® on the primary clinical
endpoint, incidence of complete wound closure after
20 weeks of treatment.
In addition, a trend for a lower wound reopening was
also observed for BioChaperone® PDGF compared to
Regranex®.
3 times lower dose
)
2 times less dressings
Complete wound closure after 20 weeks
80%
79%
70%
38/48
66%
60%
31/47
50%
20w
Regranex®
Based on these positive clinical results, a phase III
study was launched in 2014 in India to compare
BioChaperone® PDGF to placebo in double blind
setting.
20w
BC PDGF-BB
Cf. Press release ADOCIA April 23, 2012
In parallel, ADOCIA is preparing
phase III studies in Europe and in the US,
scheduled for the second half of 2016.
A D O C I A A N N U A L R E P O R T PA G E 1 5
2014 \\\\\ ADOCIA ANNUAL REPORT
MONOCLONAL ANTIBODIES
IMPROVED FORMULATIONS OF MABS
7 OF THE TOP 10 BIOLOGICS
ARE MONOCLONAL ANTIBODIES
mAbs have become reference treatments for many
severe pathologies such as chronic inflammatory
disease or oncology.
The mAbs market was valued at USD 63 billion in
2013, and expected to grow by more than 10% in
the coming years*.
Treatments by subcutaneous administration require
a high concentration of mAbs, which generates
issues regarding the viscosity of the solution and
stability of the mAbs.
ADOCIA has developed innovative formulation technologies to address these issues. Two feasibility studies
are ongoing with large pharmaceutical companies.
ADDRESSING TWO IMPORTANT
FORMULATION CHALLENGES
- Reducing aggregates formation to avoid immune
response.
- Reducing viscosity of highly concentrated mAbs
solutions to enable subcutaneous injection.
* mAb market 2009-2015 report - DataMonitor
Two feasibility studies of
monoclonal antibody formulations
are ongoing.
A D O C I A A N N U A L R E P O R T PA G E 1 6
DriveIn ®
TARGETED DELIVERY OF CHEMOTHERAPEUTIC AGENTS
CHEMOTHERAPEUTIC ACTION
NEEDS SELECTIVITY
Chemotherapeutic agents are often used as firstline therapies for cancer in millions of patients.
These drugs are particularly active against tumors
but their cytotoxicity also affects healthy cells
causing severe side effects.
A drug delivery system that would allow these
potent drugs to selectively attack the tumor while
limiting systemic distribution throughout the patient’s
body would fit a tremendous marketplace need.
DriveIn® is a biomimetic drug delivery system for
chemotherapeutic agents targeting tumor cells.
DriveIn® nanoparticles are coated with hyaluronan,
a natural polysaccharide, which is also the natural
ligand of cellular receptors CD44. These receptors
are known to promote cellular internalization and to
be particularly abundant on certain types of tumors.
This technology was developed by Professor
Sébastien Lecommandoux and his team at the
Laboratoire de Chimie des Polymères Organiques
(LCPO, UMR5629 CNRS - Université de Bordeaux I Institut polytechnique de Bordeaux). It is efficient in
carrying active molecules and delivering them within
solid tumors.
This work has been published in multiple peerreviewed journals.
ADOCIA will adopt a dual strategy for the development of this technology:
- Develop proprietary products based on generic
doxorubicin and docetaxel.
- Partner the technology with leading oncology
players for their proprietary drugs in development.
ADOCIA is currently testing DriveIn®
in the preclinical setting .
A D O C I A A N N U A L R E P O R T PA G E 1 7
2014 \\\\\ ADOCIA ANNUAL REPORT
HUMAN RESOURCES
AN INTERNATIONAL TEAM TO SERVE INNOVATION
80
COLLABORATORS
43
EXECUTIVES
37
TECHNICIANS
A D O C I A A N N U A L R E P O R T PA G E 1 8
34
YEARS
18
NEW
AVERAGE AGE
COLLABORATORS
A HIGHLY QUALIFIED TEAM
CAREER DEVELOPMENT THROUGH
TRAINING AND INTERNAL MOBILITY
As a public company focused on innovation in
the healthcare sector, ADOCIA aims not only for
scientific and technical excellence, but also for
social innovation, contributing to the development
of each employee.
ADOCIA’s sustainability is related to its ability to
attract, motivate and retain talent. This is particularly
important to ADOCIA given the competitive environment in which it operates.
80%
ADOCIA offers each employee the opportunity to
expand their skills and expertise through professional
training and participation in scientific conferences.
of employees
dedicated to R&D
In 9 years, ADOCIA has assembled a team of highly
qualified scientists and researchers. 80% of ADOCIA’s
employees are dedicated to R&D. The R&D team
is constituted of lab technicians, engineers and PhDs
in various disciplines: chemistry, biology, biochemistry,
physico-chemistry, analytical chemistry, patent engineering.
29
PHDs
150
training programs
in 2014
20
scientific congresses
attended
The company is managed by a team with extensive
experience in the management of technological
innovation and partnerships with large corporations,
both in pharmaceuticals and biotechnology.
A D O C I A A N N U A L R E P O R T PA G E 1 9
2014 \\\\\ ADOCIA ANNUAL REPORT
FINANCIAL REPORT
A SOLID AND STRENGTHENED
FINANCIAL POSITION
OPERATING INCOME
OPERATING EXPENSES
Revenues for 2014 are due, primarily, to the agreement
signed with Eli Lilly on December 18, 2014 for the development of an ultra-rapid insulin, based on BioChaperone®
technology, BioChaperone® Lispro. Pursuant to this
agreement, at the end of December 2014, ADOCIA
received a non-refundable and non-reimbursable initial
payment of USD 50 million (EUR 41 million).
Under IFRS rules, this revenue is recognized linearly
over the duration of the development plan, as anticipated at the time of the signature of the agreement.
Therefore, an amount of EUR 0.4 million has been recognized for the 2014 fiscal year. Under French rules, this
initial payment is recognized entirely in the 2014 fiscal year.
Research and Development expenses include personnel costs
assigned to research and development, subcontracting
costs related to non-clinical and clinical studies, intellectual
property costs and the costs of reagents, other consumables
and pharmaceutical products.
For the fiscal year ended on December 31, 2014, these
expenditures amount to EUR 18.7 million, representing 87%
of operating expenses for the same periods.
Revenues from research and collaborative development
contracts add EUR 0.4 million to total revenue.
In the 2014 fiscal year, contracts for innovative formulations of monoclonal antibodies, primarily feasibility studies,
represent the majority of this revenue at EUR 0.3 million.
For 2014, SG&A expenses total EUR 2.7 million.
After taking into account the financial results, taxes (resulting from the fiscal profit recorded under French rules) and
profit sharing, the net loss for 2014 period under IFRS rules
amounts to EUR 20.7 million in 2014.
3%
4%
For 2014, other operating income is mainly constituted by
the research tax credit, which amounts to EUR 3.2 million.
2%
39%
Income Statement 2014
2013
52%
2012
(in thousand euros)
Revenue
704
5 588
3 995
Other operating income
3 459
3 233
3 241
Total operating income
4 163
8 822
7 236
R&D expenses
SG&A
Total operating expenses
-18 656
-11 475
-11 784
-2 668
-1 649
-1 522
-21 324
-13 124
-13 306
(in thousand euros)
622
961
Taxes
and fees
Purchase
397
11025
Amortization Personnel
expenses
8319
External
expenses
Operating income (Loss)
-17 161
-4 302
-6 070
Financial result
524
9
75
Pre-tax income
-16 637
-4 293
-5 995
Tax expenses
Net income (Loss)
-4 078
-20 715
-4 293
-5 995
87%
OF THE OPERATING
EXPENSES ARE
DEDICATED TO R&D
A D O C I A A N N U A L R E P O R T PA G E 2 0
0.7MD
LONG-TERM DEBT
Balance sheet
2014
2013
Total Asset
52 544
24 729
36 627
Cash and cash equivalents
49 800
19 415
30 462
Equity
2 505
19 130
23 028
Debts
2 301
2 234
2 234
44 672
1 245
7 111
Capital assets
2012
(in thousand euros)
Financial liabilities
Equity
Debts
Other debts
Cash-flow
Financial
liabilities
49.8Me
44.6Me
Focus on 2014
TREASURY
Excluding the payment received from Eli Lilly, ADOCIA’s 2014
burn-rate amounts to EUR 10.4 million and remains stable
compared to 2013 fiscal year (EUR 11 million). The receipt of
Eli Lilly’s initial payment at the end of 2014 enables ADOCIA
to report a positive cash position of EUR 49.8 million (versus
EUR 19.4 million at the end of December 2013).
Cash-flow statement
At the end of 2014, the company’s amount of cash and cash
equivalents totals EUR 49.8 million.
As of March 2015, after a private placement of approximately
EUR 32 million from healthcare specialist investors, the company’s cash position is EUR 76.8 million.
2014
2013
2012
30 561
-10 796
919
Cash-flow related to investing activities
-174
57
-1 774
Cash-flow related to financing activities
0
-309
25 413
Change in the net cash
30 387
-11 048
24 558
Opening cash
19 415
30 462
5 905
Closing cash
49 800
19 415
30 462
Cash and cash equivalents
(in thousand euros)
Cash-flow generated by operating activities
10.4MD
BURN RATE IN 2014
(EXCLUDING LILLY’S
INITIAL PAYMENT)
76.8Me
49.8Me
19.4Me
49.8MD
CASH
DECEMBER 2014
Cash-flow
1/1/2014
A D O C I A A N N U A L R E P O R T PA G E 2 1
Cash-flow
31/12/2014
Cash-flow
31/3/2015
2014 \\\\\ ADOCIA ANNUAL REPORT
Self control
0%
Shareholding
at March 31, 2015
Soula family
1 525 933
Bpi
981 648
Sham
320 000
Viveris
95 712
Oréo Finance
81 561
Deleage
17 090
Key managers
41 890
Float (*)
3 775 552
Self control
1 377
6 840 763
Float*
55,2%
22,3%
14,3%
4,7%
1,4%
1,2%
0,2%
0,6%
55,2%
0,0%
Soula Family
22,3%
Bpi
14,3%
Sham
14,3%
100,0%
(*) Including the shares, when appropriate, held by the founding financial investors of the company
and newcomers (US investors such as KKR, Alken and BVF) from the private placement realized in March 2015.
Oréo Finance Deleage Managers Viveris
1,2%
0,2%
0,6%
1,4%
2014 STOCK PERFORMANCE
During 2014, regular news flow of positive clinical
study results and the signature of a major licensing
contract mid-December propelled the stock from
EUR 5.97 at the beginning of 2014 to EUR 48.25
at year end, the company’s market capitalization
increased correspondingly from EUR 37 million to
EUR 300 million.
During the first months of 2015, the stock price per
share has steadily increased, along with a rise in daily
traded volume.
ADOCIA SHARE VALUE OVER THE PAST YEAR
EUR 62.3
ADOCIA
Share price as
of April 7, 2015
EUR 15.88
Next Biotech ADOCIA IPO Share price
CAC40
(Feb. 20, 2012)
EUR 5.97
Share price as of
January 1, 2014
Mar 2014
May 2014
Jul 2014
ADR Program (American Deposit Receipt)
Type of ADR Program: Sponsored Level 1
Exchange: OTC (Over the Counter)
Symbol: ADOCY
CUSIP: 00725j102
Ratio: 1:1
Market Analysts US
Life Sci Advisors: Andrew Mc Donald
Leerink: Seamus Fernandez
Sept 2014
Nov 2014
2015
Mar 2015
Stock market: Euronext Paris - Compartiment B
First trading day of the company’s shares:
February 20, 2012
ISIN Code: FR0011184241
Mnemonique/Reuters/Bloomberg:
ADOC/ADOC.PA/ADOC.FP
Total number of shares in circulation (March 2015):
6 840 673
Sector: Pharmacy and biotechnology
Index: Next Biotech - CAC PME
OSEO Label: Eligible to investment in FCPI
Market Analysts France
Kepler Cheuvreux: Lionel Labourdette
Invest Securities: Martial Descoutures
Bryan, Garnier & Co: Eric le Berrigaud
A D O C I A A N N U A L R E P O R T PA G E 2 2
A N O P E N A N D C O L L A B O R AT I V E G O V E R N A N C E
THE MANAGEMENT COMMITTEE
SPECIALIZED COMMITTEES
Rémi Soula
Director of Business Development and Intellectual
Property.
Doctor in Chemistry of Polymers, graduate of CPE
Lyon, holder of a MBA from HEC Paris, he is co-author
of 30 patents and of 6 scientific publications.
The audit committee
Its mission, independent of the company’s management, is to assist the board of directors and ensure
the integrity of the financial statements, quality of
internal control, adequacy of the information provided
as well as the statutory auditors’ effective exercise
for their mission.
In 2014, members of the audit committee are
Ms. Dominique Takizawa and Mr. Olivier Martinez.
Gérard Soula
Chairman of the Board of Directors and Chief Executive Officer.
Doctor in Organic Chemistry from Ecole Centrale
of Marseille, holder of a MBA from IAE of Marseille.
He is co-author of more than 120 patents.
He founded Flamel Technologies in 1990.
Valérie Danaguezian
Administrative and Financial Director.
Graduate of ISC, she has gained significant experience
in terms of controlling, international standards rules
and internal control.
Olivier Soula
Deputy General Manager, R&D Director.
Doctor in Physical chemistry of Polymers, graduate
of ENSIC Mulhouse and holder of a MBA from IAE
(Lyon), he is co-author of 40 patents.
THE BOARD OF DIRECTORS
The company’s board of directors is composed of
6 members: Gérard Soula, Olivier Soula, Olivier
Martinez (BPI France), Laurent Arthaud (BPI France),
Dominique Takizawa (independent director) and
Dr. Ekaterina Smirnyagina (independent director).
The compensation committee
The compensation committee is composed of
Mr. Laurent Arthaud and Dr. Ekaterina Smirnyagina.
The scientific committee
This committee, directed by Olivier Soula, has the
responsibility to provide ADOCIA with sound scientific advice about its scientific orientations and to draw
its attention to new and emerging technologies.
The external members of the scientific committee are
Pr. Jean-Marie Lehn, Nobel Prize in Chemistry (1987),
Director of the Molecular Interaction Chemistry Lab
at the Collège de France. In addition, he is Director
of the Supramolecular Chemistry Lab at University
Louis Pasteur in Strasbourg. As far as Dr. Bernard
Cabane is concerned, he is Physicist and Chemist,
Director of Research at CNRS and at the ESPCI Paris
Tech.
A D O C I A A N N U A L R E P O R T PA G E 2 3
2014 \\\\\ ADOCIA ANNUAL REPORT
Disclaimer
This document contains certain forward-looking statements concerning ADOCIA and its business. Such forward-looking
statements are based on assumptions that ADOCIA considers to be reasonable. However, there can be no assurance that the
anticipated events in such forward-looking statements will occur. Forward-looking statements are subject to numerous risks
and uncertainties including the risks set forth in the “Risk Factors” section of the reference document of the company registered by the Autorité des marchés financiers (French Financial Markets Authority) on April 30, 2015 under number R.15-032
(a copy of which is available on www.adocia.com) and, in particular to the uncertainties linked to research and development,
future clinical data and analysis, and to the development of economic conditions, financial markets and the markets in which
ADOCIA operates. The forward-looking statements contained in this document are also subject to risks not yet known to
ADOCIA or not currently considered material by ADOCIA. The occurrence of all or part of such risks could cause actual results,
financial conditions, performance or achievements of ADOCIA to be materially different from such forward-looking statements.
This document and the information it contains does not constitute neither an offer to sell, nor the solicitation of an offer to
purchase or subscribe for ADOCIA shares in any country.
A D O C I A A N N U A L R E P O R T PA G E 2 4
EVENTS 2015
January 20th
First study of the partnership with Eli Lilly
and Company
September 15th-18th
EASD
Stockholm – Sweden
February 5th
Positive results from Phase IIa clinical study
of fast-acting human insulin, HinsBet®
September 16th-18th
Kepler Cheuvreux Conference
Paris – France
March 5th
A subsidiary in the US opened:
ADOCIA Incorporated
October 7th-8th
European Large and Midcap Event
Paris – France
March 27th
EUR 32 million raised from healthcare
specialist investors
November 2nd-4th
BIO Europe
Munich – Germany
April 2nd
Eligibility for PEA-PME and integration
of ADOCIA in the CAC PME index
November 5th
Société Générale Biotechnology
and Healthcare Conference
Paris – France
May 4th
Entry in the EnterNext Tech 40 Index
May 26th
Invitation to present at Jefferies Healthcare
Conference in New York City
May 28th
Poster presentation of positive clinical
results for BioChaperone® Lispro at
the American Diabetes Association (ADA)
June 25th
Positive Phase 1b topline results on the postmeal effect of ultra-rapid BioChaperone® Lispro
in patients with type 1 diabetes
July 10th
Initiation of two clinical studies on a combination
of long-acting insulin glargine and fast-acting
insulin lispro, BioChaperone® Combo
November 20th-21st
Actionaria
Paris – France
December 1st- 2nd
Piper Jaffray Annual Healthcare Conference
New York – USA
February 3rd-6th, 2016
ATTD 2016
Milano – Italy
ADOCIA
115 avenue Lacassagne
69003 Lyon - France
Tél. +33 4 72 610 610
Fax. +33 4 72 363 967
Edited by ADOCIA in July 2015 - Layout: Alkantara - Pictures copyrights Philippe Somnolet - All rights reserved - Printed in the Rhône-Alpes Region
www.adocia.com
Limited company with a capital of EUR 684,076.30 - RCS Lyon 487 647 737 00021