Transcript Diapositive 1

Malam Aboubakar
Alexia Dumoulin
Hortense Masias
Diane-Laurène Smal
Faculty of Pharmacy, Lille 2 _ March 2009
Safe harbor
This is an independent study performed by
students from the Faculté des Sciences
Pharmaceutiques de Lille
The opinions expressed are our own and
not necessarily those of Genfit
Genfit presentation
Creation in 1999
A team consists of 130 people driven by :

Jean-Charles Fruchart : Executive Scientific Advisor,

Bart Staels : president of the Scientific Advisory Board,

Jean-François Mouney : chairman and chief executive officier
SCIENTIFIC & FINANCIAL EXPERTISE
Location and subsidiaries
Parc Eurasanté
Lille Metropole
885, av. Eugène Avinée
59 120 LOOS – France
245, First Street
18th floor, office 1806
Cambridge MA 02142
USA
A unique business modele
VISION: DEVELOP TOMORROW’S MEDICINES
Valuing partnerships
 A thorough clinical knowledge of the disease
 Staying at the edge of innovation
 Focusing on patients needs

Focuses on Cardiometabolic disease
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Scientific background from Pasteur Institute : PPAR
knowledge
Cardiometabolic diseases leaded to 17,5 million
deaths or 30% of global mortality in 2005
In 2007, the cardiovascular disorders market was
estimated at $143.940m (growth rate of 3.9% in
2006-07)
Limitation of current therapies
Activity field : a pluripotent market
GENFIT’S PURPOSE :
discovery and
development of
drugs
for prevention and
treatment of
common risk factors
associated with
cardiovascular and
metabolic disorders
Strong emphasis on partnerships

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Since its inception, Genfit has strongly valued the
importance of partnerships with pharmaceutical
and biotechnology companies for collaborative
research agreements.
Genfit's balanced business model of internally
funded programs and partner supported programs
allows the company to manage the risks associated
with such programs
OPTIMIZATION OF RESOURCES
creation of
GENFIT
History
4 first
alliances
And then 2
new
Alliances renewal
Increase of screening
and proteomic
capacities
Headquarters
and
laboratories
in Lille
1999
Phase II clinical trials
for GFT 505
New or renewal of
alliances
2002
2005
2006
2 new alliances
First GENFIT drug
enters preclinical
studies
Creation of GENFIT
corp
GENFIT listed on
Euronext
Alliances renewal
Phase I clinical tests for
GFT505/ launch of
phase IIa
2009
Technological Platform
Scientific expertise
A long-standing knowledge of gene regulation
Solid experience in the family of 'Nuclear Receptors‘
Nuclear receptors
form a specific family of
transcription factors
involved in the regulation
of many physiological
processes.
Over 10% of the world's 100 best selling drugs are targeting nuclear receptors.
Genfit’s therapeutic approach
Year 1990’s
1 pill, 1 risk factor
1 active substance per
pill
•Reduced treatment
efficacy and
compliance
•Durg interactions
generated by
combination therapies
possibly leading to
complication
Year 2000’s
1 pill, several risk
factors several active
substances per pill
•Complex
Pharmaceutical
development and
registratione
•Durg interactions
possibly leading to
complications
Tomorrow
1 pill, several risk
factors
1 active substances
per pill
•Maximised compliance
and efficacy of
treatments
•No drug interactions
•Patentable
•Attractive therapeutic
solution for
multifactorial deseases
Illustration in the case of cardiometabolic disease
TTomorow
Tomorow
The beginning…
LXR
PPAR
FXR
An exemple… PPAR
PPAR : Peroxisome Proliferator-Activated Receptors
A nuclear receptor activated by endogenous molecules : fatty acids, insulin…
PPARα : regulates the expression of
genes involved in lipid metabolism .
PPARγ : regulates the expression of
Genes involved in glucid metabolism
Efficience of this activation pathway
Glc
PPAR
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HDL
Chol
LDL
How to act on the transcription ?
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LDL
SNuRMs : Selective Nuclear Receptor Modulators
A new generation of safer medicines targeting nuclear receptors :
 nuclear receptor ligands having cell or tissue specific activities
 selected as compounds with an optimum efficacy/safety ratio.
Which interest ?
Ligand’s chemistry
Receptor conformation
Coactivator recruitment
Pharmacological effect
SPPARM : the selective PPAR modulator
SNuRM concept adapted to PPARs
used to select and to develop new PPAR- activators
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The technologic SPPARM platform :
in vitro pharmacologic assays (cofactor recruitment properties
such as GST pull-down,fluorescence resonance energy transfer assays),
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activation of the transcription of genes in target
cells and tissues (gene profiling and microarray)
in vivo assays (lipid and glucose metabolism, anti-inflammatory,
vascular effects, and side effects).
An added value for drug discovery
SNuRM
&
Analysis of differential
co-factor recruitment
to develop selective compounds for nuclear
receptors which optimised pharmacological effects
and less side-effects
The technological platform
How to apply the knowledge ?
Glc
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Technologic platform
Discover and select the best drug
candidate
Technological platform vs Cardiometabolic
disease
Concentrate development efforts on 3 main programs: G800,
TGFTX1 and TGFTX2:
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G800: evalues SPPARMs, property of Genfit, on
cardiometabolic disease
TGFTX1: evalues orphan nuclear receptors on atherosclerosis,
inflammation and other neurodegenerative disorders
TGFTX2 is about an enzyme from lipid metabolism in tratment
of obesity and insulino resistance
Develop tomorrow’s medicines

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Leading technologies for innovative therapeutic
solutions
Genfit’s drug development strategy is based on the proven
combination of leading edge in-house science complimented by
Naturalpha’s optimized clinical research expertise.
Glc
PPAR
TG
HDL
Chol
LDL
1. Research for partners
Genfit rents its technological platform to international pharmaceutical groups
thanks to :
• High scientific value-added
• Constant innovation
• Mainly with valided targets or with products which had in vivo approval
Genfit income = a stable financial situation
Glc
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PPAR
€
HDL
LDL
2. Research for themselves
GFT 505
A Pluripotent Drug Candidate for Treatment of Global Cardiometabolic Risk

Oral treatment acting on the 2 sub-types of PPAR receptors :
- PPARα (preferential action)
Atherogenic dyslipidemia
↓TG, ↓LDL-C, ↑HDL-C
- PPARγ

Insulin resistance
Indications : Treatment of micro and
macro-vascular events on overweight
patients with or without diabetes
GFT 505 : Preclinical Trials

Doses study : in dyslipidemic mice during 8 days
GFT505 potently reduces plasma triglycerides and LDL-C
GFT 505 : Preclinical Trials

Doses study : in transgenic mice for human ApoA-I (HDL) during 7
days
GFT505 increases
plasma hApoA-I concentration
A milestone in 2005…
Own drug
candidates
Clinical
Trials
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10,000,000
€
… and an IPO in 2006
A raise fund ….
Shareholder structure
Weighted average number of share
Year 2007
Year 2006
11 270 626
9 743 918
GFT 505 : Clinical Trials
Phase I : 14 days at 30mg/day (July 2006 to March 2007)
- excellent tolerance on 48 healthy volunteers
Phase IIa : GFT505 vs placebo during 28 days with 30mg/day
37 patients : limits the statistical power with type IIb dyslipidemia;
completed in March 2008
- broad profile of activity :
↓TG; LDL-C and the levels of ApoC3, ApoB and ApoE (VLDL & LDL)
↑ the levels of ApoA1 and ApoA2 (HDL)
Encouraging preliminary efficacy results
+ absence of any adverse effects
GFT 505 : Clinical Trials
Additional Phase I and Phase IIa studies in order to
measure the product efficacy at up to 100mg/day
Phase I : 14 days at 100mg/day (2008)
Excellent tolerance : no side effects on healthy voulunteers
Phase IIa : GFT505 vs placebo during 28 days
Efficacy ‘s endpoints evaluated with : plasma lipids, glucose
metabolism and on markers combined with a microcirculatory
malfunction
Results are expected before the end of 2009
But since the ENHANCE study…
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Ezetimibe shows a reduction of LDL-C
But the effect of Ezetimibe on the progression of atherosclerosis remains
unknown
And the only criteria to remember is a morbi-mortality study
GFT 14…A drug candidate to target mixed type IIb dyslipidemia
Structurally very close to natural triglycerides

Phase I trial: single dose (50 – 500mg) or repeated dose over 14 days (50300 mg/day): (initiated in March 2005)
over 100 healthy volunteers
Very good tolerance + Excellent security profile + No risk of drug-drug interaction

First Phase IIa pilot (initiated in May 2006)
128 patients
Excellent safety profile
BUT
Compared to fenofibrate: not competitive in terms of lowering
triglycerides (250 mg/day)
They gave up their product !
Genfit Operational and Net result
3000
2000
1000
0
-1000
2003
2004
2005
2006
-2000
-3000
-4000
-5000
-6000
10
-Sub contracting fees
- Status changement
2007
Operational Result
Net Result
Genfit operational results…
(in 000’s of euros)
Year 2007
Year 2006
Net turnover
9 477,3
10 051,3
0ther income
180,6
1 369,6
9 657,9
11 421,5
Purchases consumed
Operational subcontracting
Personnel expenses
Other operational expenses
Net expenses for depreciation, provisions , losses in value
Results on disposals of non current assets
-2 005,2
-3 697,4
-6 201,5
-2 898,5
-850,8
5,0
-1 685,6
-2 505,4
-4 805,9
-2 440,2
-537,7
0,0
Operational result
-5 990,6
-553,3
611,0
223,6
Tax burden
2 578,8
665,4
Net result
-2 800,8
335,7
Total revenues
Financial result
Genfit net turnover evolution
In million euros
12410
(in 000 euros)
12770
10810
10510
9260
9477
6600
2560
2000
2001
2002
2003
Year
2004
2005
2006
2007
Genfit Net turnover
(in 000’s of euros)
Year 2007 Year 2006
Net turnover
9 477,3
10 051,3
0ther income
180,6
1 369,6
9 657,9
11 421,5
Purchases consumed
Operational subcontracting
Personnel expenses
Other operational expenses
Net expenses for depreciation, provisions , losses in value
Results on disposals of non current assets
-2 005,2
-3 697,4
-6 201,5
-2 898,5
-850,8
5,0
-1 685,6
-2 505,4
-4 805,9
-2 440,2
-537,7
0,0
Operational result
-5 990,6
-553,3
611,0
223,6
Tax burden
2 578,8
665,4
Net result
-2 800,8
335,7
Total revenues
Financial result
Genfit analysis
SWOT analysis
STRENGTH
• Strategic alliance
• Genomic & proteomic expertise
• Innovant technological platform
• Patents
SWOT analysis
STRENGTH
WEAKNESSES
• Strategic alliance
• Financially dependant on its partnerships
• Genomic & proteomic expertise
• R&D budget too high
• Innovant technological platform
• Early stage of development
• Patents
• No product on the market
SWOT analysis
STRENGTH
WEAKNESSES
• Strategic alliance
• Financially dependant on its partnerships
• Genomic & proteomic expertise
• R&D budget too high
• Innovant technological platform
• Early stage of development
• Patents
• No product on the market
OPPORTUNITIES
• To strengthen the partners network
• An expanding market
• Neurodegenerative disease
• Design of clinical trial program
SWOT analysis
STRENGTH
WEAKNESSES
• Strategic alliance
• Financially dependant on its partnerships
• Genomic & proteomic expertise
• R&D budget too high
• Innovant technological platform
• Early stage of development
• Patents
• No product on the market
OPPORTUNITIES
THREATS
• To strengthen the partners network
• Failure of pipeline development
• An expanding market
• Competitors
• Neurodegenerative disease
• Regulations
• Design of clinical trial program
• Development process longer and more
expensive
To conclude
Strategy for future
Advance the clinical development of GFT505
& New drugs discovery
Out-license our lead clinical compound to a pharmaceutical
partner after completion of Phase II clinical trials.
Maintain, renew, strenghten partnerships
Diversify therapeutic interest by exploring neurodegenerative
indications
Proactively and selectively explore in-licensing. opportunities
Last news from Genfit…

Alliance with Servier extended through 2010

Alliance with Sanofi-Aventis extended through 2010
SAVX1 program turns towards neurodegenerative diseases after diabetes and vascular
inflammation

Genfit unveils its Theranostic Strategy
Biomarker programs developed in the field of cardiometabolic and neurodegenerative
diseases

BMGFT01 is dedicated to early detection of artherosclerosis

BMGFT03 focuses on neurodegenerative diseases
Which future ?
Own drug
candidates
Genfit Pharmaceuticals
Clinical
Trials
Glc
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PPAR
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LDL
Genfit Technology
THANK YOU FOR YOUR
ATTENTION
Questions?