Developing innovative therapies in - NASH Corporate Presentation June 2022 - Inventiva Pharma
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Developing innovative therapies in NASH Corporate Presentation June 2022
DISCLAIMER This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential" "predict," "project," "should," "target," or "will" or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the success, cost and timing of our product development activities and clinical trials; our expectations about the timing of achieving regulatory approval and the cost of our development programs; our ability to obtain funding for our operations, including funding necessary to complete further development of our product candidates; the commercialization of our product candidates, if approved; our plans to research, develop and commercialize our product candidates; our ability to attract collaborators with development, regulatory and commercialization expertise; our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates; future agreements with third parties in connection with the commercialization of our product candidates; our ability to maintain, expand, protect and enforce our intellectual property portfolio; our ability to operate our business without infringing, misappropriating or otherwise violating the intellectual property rights of third parties; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; the rate and degree of market acceptance of our product candidates; regulatory developments in the United States, Europe and other jurisdictions; our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately; the success of competing therapies that are or may become available; and our ability to attract and retain key scientific or management personnel. For additional information in relation to such factors, risks and uncertainties, please refer to the Universal Registration Document for the year ended December 31, 2020 filed with the Autorité des Marchés Financiers on March 15, 2021, the Annual Report on Form 20-F for the year ended December 31, 2020 filed with the Securities and Exchange Commission on March 15, 2021, Amendment No. 1 to the Annual Report on Form 20-F for the year ended December 31, 2020 filed with the Securities and Exchange Commission on March 24, 2021, as well as the half-year financial report for the six months ended June 30, 2021 as well as our other documents or reports that we may file with or furnish to the SEC from time to time, available at www.sec.gov. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 2
Key take-aways
A Phase III First-in Class & Best- A Phase IIb Clinical Stage Strong R&D Capabilities and
in-Class NASH Drug Collaboration with AbbVie Cash Position
Lanifibranor: only pan-PPAR agonist Cedirogant/ABBV-157 Small R&D capabilities including wholly-
in clinical development for NASH molecule RORT Inverse Agonist owned ‘pharma scale’ discovery
facilities with a discovery engine
Positive Phase IIb topline data with Potential to more effectively inhibit IL- focused on nuclear receptors,
statistical significance on NASH 17 production than antagonist transcription factors and epigenetic
resolution and one stage fibrosis approaches targets
reduction
Promising activity in Phase I study in Clinical Ops team in place in Europe
Mechanism of action addressing all key psoriasis patients and the United States
features of NASH
Phase IIb dose-ranging study initiated Strong U.S. and European
Breakthrough Therapy Designation Q4 2021 and expected to end Q1 2023 shareholder base and experienced
granted by FDA senior management team
Inventiva eligible to receive milestone
Pivotal Phase III initiated in Q3 2021 payments and sales royalties Cash position allowing a runway
with topline results expected H2 2024 through the end of Q1 2023, excluding
the €50m bullet loan facility secured
Two Phase 2 trials ongoing with results with the European Investment Bank
expected in H2 2022 and H2 2023
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 3
Management team with extensive global experience across all stages
of drug development and commercialization
Frédéric Cren, MA/MBA, CEO and Co- Pierre Broqua, Ph.D., CSO and Co-Founder
Founder Successfully managed numerous research
Wide expertise within the areas of R&D, programs leading to the discovery, development
marketing, strategy and commercial operations and commercialization of innovative compounds,
including lanifibranor and Degarelix/ Firmagon®
Held senior positions at Abbott, Fournier, Solvay
Pharma and The Boston Consulting Group Held several senior research positions at
Fournier, Solvay Pharma and Abbott
Former member of both Fournier and Solvay
Pharma Executive Committees
Jean Volatier, MA, CFO Michael Cooreman, MD, CMO
Former Head of controlling at URGO & Gastroenterologist-hepatologis
Financial Director International Operations of Held global roles in several companies including
Fournier Takeda Pharmaceuticals, Merck, Mitsubishi
Held various positions as CFO and started his Tanabe, ImmusanT and Novartis
career with PwC in Paris and Philadelphia U.S. based
Alice Roudot-Ketelers, PharmD, VP David Nikodem, Ph.D., VP U.S. Operations
Clinical Operations and Pharmaceutical Former buyside portfolio manager and analyst for
Development +15 years in public equities and VC
U.S. based
Previously in charge of all drug development
programs and cross-functional teams in
Chemistry, CMC, non-clinical and clinical
development up to Phase III at one of the major
biotech companies in the NASH field
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 4
Oral small molecule-focused discovery engine targeting nuclear
receptors, transcription factors and epigenetic modulation
Expertise: nuclear
receptors,
transcription
factors, epigenetic
Library of ~240,000 Wholly-owned targets
compounds of which 129,000 square
60% proprietary foot pharma-like
R&D facilities Clinical and
Medical team
based in Europe
Highly and in the US
experienced
R&D team of
~80 people
Power of discovery engine underpins deep pipeline of clinical and discovery stage assets
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 5
Deep pipeline
Candidate / IND Commercial Next
Indication Discovery Phase I Phase II Phase III
Program* Enabling Rights Milestone
Phase III Last
Patient First
Lanifibranor NASH pan-PPAR
Visit in H1
2023
Phase IIB
Cedirogant Moderate to ROR study
severe psoriasis completion Q1
2023
GAG clearance Strategy
Odiparcil MPS VI update in 2022
Non-small cell Candidate
Yap-Tead Selection
lung cancer and
mesothelioma
Idiopathic Lead
TGF-β Generation*
pulmonary
fibrosis (IPF)
* Lead generation means identifying molecules in anticipation of selecting candidates
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 6
Key financials and shareholder base
Key financials Shareholder base
Sofinnova Employees &
8,0% Others
2,4%
NEA
13,2% Free Float
ISIN code FR0013233012 / US46124U1079 32,6%
Market Euronext Paris / Nasdaq GM
BVF
20,6%
Shares outstanding 40 873 551 Founders
23,2%
Market cap Euronext Paris: €353m / Nasdaq
(June 1, 2022) Global Market: $368m Analyst coverage
€80.5m (vs €95.4m as of December
Jefferies L. Codrington / M. J. Yee
Cash position 31, 2021)
(as of March 31,2022) Current expected cash runway Guggenheim S. Fernandez
through the end of Q1 2023 HC Wainwright E. Arce
Roth Capital Z. Jallah
2021 revenues €4.2m compared to €0.4m in 2020 KBC J. Van den Bossche
Société Générale D. Le Louët
Bryan Garnier JJ. Lefur
R&D expenditures Portzamparc M. Kaabouni
€48.4m compared to €23.7m in 2020
in 2021
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 7
Lanifibranor in Nonalcoholic Steatohepatitis (NASH)
Lanifibranor: the only pan-PPAR agonist in clinical development for
the treatment of NASH
Moderate and balanced pan-PPAR agonist activity (PPAR, PPAR and PPAR) with differentiated
chemical structure
Once daily oral administration
Effects observed on insulin-sensitivity, dyslipidemia, steatosis, ballooning, inflammation, hepatic fibrosis
and cirrhosis in pre-clinical models
Phase IIa(1) trial demonstrated pan-PPAR agonist activity, supporting dose selection for NASH Phase IIb
clinical trial
Positive Phase IIb trial topline results announced in June 2020 and published by the New England
Journal of Medicine
Favorable tolerability profile observed in:
24-months rodent and 12-month monkey studies leading to PPAR class clinical hold lifted by FDA
Non-clinical toxicology package considered by FDA as complete and acceptable to support NDA
filing for the treatment of NASH and improvement of liver fibrosis
Phase I trials with more than 200 healthy volunteers(2) and Phase IIa trial with 47 T2D patients
Over 250 patients treated for 24 or 48 weeks in Phase IIb clinical trials in NASH and other indications
In connection with these trials, lanifibranor underwent a total of 7 DSMB reviews without changes
recommended to the different trial protocols
Thorough QT/QTc study completed demonstrating no impact on QT intervals
Composition of matter patent delivered in 55 countries and method of use patent granted in the U.S., China
and in the EU: limit of exclusivity in the U.S. is 2035
FAST Track (including in NASH patients with compensated cirrhosis) and Breakthrough Therapy
designations granted by FDA
(1) Conducted by Abbott prior to our founding; (2) Including 125 healthy volunteers in the Phase I conducted by Abbott prior to our founding
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 9
Lanifibranor is a differentiated pan-PPAR agonist with moderate and
well balanced activity on the three PPAR isoforms
LANIFIBRANOR
Differentiated oral small molecule … … that binds differently than glitazone to PPARγ
Small molecule that
activates all three PPAR
isoforms
Differentiated chemical ROSI
structure with once daily
oral administration LANI
Offered in two dosage Induces different coactivator recruitment^^
forms (800 mg, 1200 mg)
Moderate and balanced pan-PPAR agonist activity
150 PPAR PPAR PPAR
Compound
EC50 (nM) EC50 (nM) EC50 (nM)
125
%Activation
hPPAR
100 hPPAR Lanifibranor* 1630 850 230
hPPAR
75 Fenofibrate 2400 - -
50 Pioglitazone - - 263
25 Rosiglitazone - - 13
0 Elafibranor** 10 100 -
-10 -8 -6 -4
Seladelpar^ - 2 -
lanifibranor (M)
Source: * Company data ** Hanf R et al, Diabetes & Vascular Dis Res 2014 ^ Cymabay company presentation ^^ J Med Chem. 2018 Feb 15. doi: 10.1021/acs.jmedchem.7b01285
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 10Lanifibranor’s activation of the three PPAR isoforms addresses the
key features of NASH
LANIFIBRANOR
Pan-PPAR activity expected to ensure improved efficacy
INFLAMMATION AND
METABOLISM STEATOSIS
BALLOONING
PPARα PPARδ PPARγ PPARγ PPARα PPARδ PPARγ
Insulin sensitivity FA uptake NFkB-dependent
PPARα gene activation
HDLc FA catabolism
Inflammasome
Triglycerides Lipogenesis
Ballooning
FIBROSIS VASCULAR
PPARβ/δ PPARγ
PPARδ PPARγ PPARα PPARγ
LANIFIBRANOR Stellate cell Portal pressure
proliferation and
activation LSEC capillarization
Collagen and Intrahepatic vascular
fibronectin production resistance
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 11Adverse events and toxicity previously seen in other single and dual
PPAR agonists are not observed in lanifibranor
SAFETY
Organ Isoforms activated Reported PPAR side effects lanifibranor effects
Fluid retention
HEART PPARγ Cardiac hypertrophy
SKELETAL
PPARα Myofiber degeneration
MUSCLE NOT
> 50% increases in creatinine, degenerative OBSERVED
KIDNEY PPARα changes in renal tubules
URINARY
BLADDER
PPARγ Proliferative changes in bladder epithelium
Adverse events and toxicity of single / dual PPAR agonists not observed in primate and rodent studies
No adverse clinical signs observed at any dose-level tested
FAVOURABLE
No effects on body and heart weight, no haemodilution or creatinine increase
TOLERABILITY PROFILE in
a 12-month monkey study … Electrocardiography and clinical pathology investigations did not reveal any
undesirable effects
Rat: no observed neoplastic change or increase in tumor types commonly associated
… and in two-year with single PPAR and dual PPARagonists (liver, adipose, bladder, renal and
CARCINOGENITY STUDIES skin)
performed in rat and mice
Mice: no observed neoplastic changes of human relevance
Confirmation by FDA that the non-clinical toxicology package is complete and acceptable
to support NDA filing in NASH
Source: Company data
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 12Phase I and Phase IIa clinical trials* in type 2 diabetes patients:
beneficial changes in key metabolic markers
PHASE I AND IIa
Lanifibranor metabolic markers in type II diabetic patients
Adiponectin (PPAR)** HDL Cholesterol (PPAR)^ Triglycerides (PPAR) ^^
baseline
baseline
baseline
300 p=0.05 40 0
baseline
baseline
baseline
p=0.05 pImprovements in metabolic parameters and liver histology with anti-
fibrotic activity have been demonstrated in animal models
LANIFIBRANOR
ANIMAL MODELS, BY MODEL TYPE
METABOLIC NASH & NAFLD FIBROSIS CIRRHOSIS
Diet induced obesity high Methionine Choline Carbon tetrachloride
Thiocetamide (TAA)
fat / high sucrose Deficient diet (MCD) (CCL4)
Foz / Foz model
Choline-deficient amino-acid and
In vivo models high fat diet
Hepatoma and muscle
Macrophages biology Hepatic Stellate Cells (HSC) biology
cells biology
Endothelial biology
In vitro models
OBSERVED EFFECTS, BY MODEL TYPE
Improvements in Improvements in Improvement of Reductions in
– Insulin – Steatosis fibrosis – Portal pressure
resistance – Inflammation Inhibition of stellate – Established
– Non fasting – Ballooning cell activation fibrosis
glucose Improvements in
– Homa-IR NAS score
– Lipid profile
Maintenance of
body weight
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 14NASH is a chronic progressive disease with no currently approved
treatment options
NASH OVERVIEW
Chronic disease that may progress to cirrhosis
Reversible Severe liver damage
HEALTHY HEPATO-
CIRRHOSIS* CARCINOMA
DEATH**
LIVER
NAFLD NASH NASH with fibrosis
LIVER
c.25% of global c.25% of NAFLD TRANSPLANT
population
NASH …
… can be classified based … is associated with … is currently mainly … is characterised by
on histologic features type 2 diabetes (T2D) diagnosed through liver high unmet needs
biopsy
FIBROSIS STAGE F2
T2D KEY UNMET NEED
F0 F1 F2 F3 F4 F3
NAS SCORE NASH Treatment targeting both
Reflects disease activity; Liver biopsy is currently the NASH resolution and fibrosis
T2D patients tend to
composite of three features present with more gold standard; broader
(steatosis, inflammation, severe and faster adoption of non-invasive KEY UNMET NEED F4
ballooning) progressing NASH tests and launch of disease-
modifying therapies may Treatment of cirrhosis
SAF SCORE
make diagnosis easier
Semi-quantitative score of
steatosis, activity, fibrosis
Note: * More than 20% of patients with NASH progress to cirrhosis within a decade of diagnosis; ** Compared to the general population patients with NASH have a ten-fold greater risk of liver-related mortality
Source: PanNASH; NASH Market, Allied Market Research 2016 ; Deutsche Bank Markets Research; HCV Trials; Duseja (2019) L.E.K. interviews, research, and analysis
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 15Lanifibranor overall development plan in NASH
CLINICAL DEVELOPMENT
Phase III in patients with NASH
Registration
and F2-F3 fibrosis
Phase I Phase IIa Phase IIb (NATIVE) III OVERVIEW
• 72 week Part 1 + Part 2 extension
IIb DESIGN
period
• 24 weeks • Inclusion criteria and patient profile in
• 800 mg and 1200 mg line with NATIVE Phase IIb
once-daily lanifibranor
• Primary composite endpoint
combining NASH resolution and
IIb EFFICACY fibrosis improvement
• First candidate to
achieve statistically
significant results on the Phase II in NAFLD patients
two Phase III FDA and with T2D
EMA primary endpoints
Lanifibranor + empagliflozine
IIb SAFETY Phase II in NASH patients
• Favourable profile with T2D
Completed clinical trials
Ongoing clinical trials
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 16The Phase IIb NATIVE trial studied 800 mg and 1200 mg once-daily
lanifibranor across 247 patients
PHASE IIb DESIGN OVERVIEW
24-week treatment + 4-week follow-up
Screening Double blind, randomized, placebo-controlled End of treatment
Liver biopsy Liver biopsy
Placebo
lanifibranor, 800 mg once daily
• Randomisation 1/1/1
• Stratification on
type 2 diabetes
lanifibranor, 1200 mg once daily
mellitus (T2D)
Patient population # patients Definition
Patients randomized having received at least one dose of
Safety / Intention-to-Treat (ITT) 247
lanifibranor/placebo
Patients with paired biopsies and without deviation impacting efficacy
Per Protocol (PP) 194
results
Main inclusion criteria: patients with biopsy-proven NASH confirmed by central reader having Steatosis-Activity-Fibrosis
(SAF) scores of 1-3 for steatosis, 3-4 for activity, and247 patients were randomised across 71 sites worldwide, with the
majority of patients based in Europe
PHASE IIb DESIGN SITE SELECTION
4 sites in 49 sites in
Canada Europe
Patients
Country
randomized
Europe 183 (74%)
U.S. 36 (15%)
Australia 13 (5%)
12 sites in the Canada 8 (3%)
United States
Mauritius 7 (3%)
1 site in 5 sites in Total 247 (100%)
Mauritius Australia
16 countries worldwide (number of sites having randomized at least 1 patient)
► Europe: Austria (1), Belgium (5), Bulgaria (5), Czech Republic (3), France (13), Germany (5), Italy (4), Poland (3),
Slovenia (1), Spain (4), Switzerland (2), United Kingdom (3)
► North America: United States (12), Canada (4)
► Australia (5)
► Mauritius (1)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 18The majority of patients successfully completed the 24-week
treatment
PHASE IIb DESIGN TREATMENT ARMS
247 patients randomised and treated
Placebo lanifibranor 800 mg/day lanifibranor 1200 mg/day
N = 81 N = 83 N = 83
74 (91%) patients completed 77 (93%) patients completed 77 ( 93%) patients completed
the 24-week treatment the 24-week treatment the 24-week treatment
7 (9%) patients prematurely 6 (7%) patients prematurely 6 (7%) patients prematurely
withdrawn: withdrawn: withdrawn:
- Adverse events (n=3) - Adverse events (n=3) - Adverse events (n=3)
- Withdrawal by patient (n=2) - Lost to follow-up (n=1) - Lost to follow-up (n=1)
- Forbidden concomitant - Withdrawal by patient* (n=1) - Withdrawal by patient (n=2)
medication (n=2)
- Non-compliance (n=1)
Note: * And adverse event as secondary reason
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 19Patient population included 58% of female and 42% of patients with
T2D at baseline
PHASE IIb DESIGN BASELINE
Placebo lanifibranor lanifibranor Overall
Parameters (unit)
- 800 mg/day 1200 mg/day -
n (%) or mean ± SD
N = 81 N = 83 N = 83 N = 247
Demographics
Female 41 (51%) 54 (65%) 49 (59%) 144 (58%)
Age (years) 53.4 ± 13.1 55.0 ± 10.4 52.2 ± 13.8 53.6 ± 12.5
White 74 (91%) 80 (96%) 78 (94%) 232 (94%)
Weight (kg) 95.1 ± 17.3 91.6 ± 19.3 93.0 ± 19.9 93.2 ± 18.9
Body Mass Index (kg/m²) 32.8 ± 5.1 32.5 ± 5.5 33.3 ± 5.5 32.9 ± 5.4
Type 2 diabetes 35 (43%) 33 (40%) 35 (42%) 103 (42%)
Liver biopsy characteristics
SAF Activity score
3.3 ± 0.5 3.2 ± 0.5 3.3 ± 0.5 3.3 ± 0.5
(inflammation + ballooning)
NAFLD Activity Score (NAS) ≥6 56 (69.1%) 63 (75.9%) 61 (73.5%) 180 (72.9%)
Fibrosis stage F2/F3 57 (70.4%) 68 (81.9%) 63 (75.9%) 188 (76.1%)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 20A number of liver enzyme, plasma lipid level and glucose metabolism
parameters were recorded at baseline
PHASE IIb DESIGN BASELINE
Placebo lanifibranor lanifibranor
Parameters (unit)
- 800 mg/day 1200 mg/day
mean ± SD
N = 81 N = 83 N = 83
Liver enzymes
Alanine aminotransferase, ALT (UI/L) 56.9 ± 31.6 64.1 ± 41.4 63.6 ± 43.4
Aspartate aminotransferase, AST (UI/L) 43.3 ± 24.1 53.9 ± 43.4 43.9 ± 24.8
Gamma glutamyl transferase, GGT (UI/L) 67.9 ± 80.4 101.6 ± 146.1 67.1 ± 93.1
Plasma lipid levels
HDL-Cholesterol (mmol/L) 1.2 ± 0.3 1.3 ± 0.3 1.2 ± 0.3
Triglycerides (mmol/L) 2.0 ± 0.8 1.9 ± 0.9 2.0 ± 0.9
Glucose metabolism for diabetic patients
(n= 103)
Fasting Glucose (mmol/L) 6.9 ± 2.0 7.3 ± 2.2 6.6 ±1.2
HbA1c (%) 6.5 ± 0.7 6.7 ± 0.8 6.6 ± 0.7
Insulin (pmol/L) 222.7 ± 186.5 246.3 ± 213.4 278.5 ± 233.5
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 21Lanifibranor is the first candidate to achieve statistically significant
results on the two Phase III FDA and EMA primary endpoints
PHASE IIb EFFICACY KEY ENDPOINTS
xx Statistically significant xx Non-statistically significant
Key Phase IIb results by endpoint
N = 247 ITT population N = 197 PP population
Placebo 800 mg 1200 mg Placebo
Placebo
800 mg
800 mg
1200 mg
1200 mg
(N = 81) (N = 83) (N = 83) (N = 62) (N = 63) (N = 69)
ENDPOINT
PRIMARY
Decrease of ≥2 points of SAF 27% 41% 49% 34%
51% 55%
activity score* and no worsening
0.061 0.004 0.058 0.015
of fibrosis
Resolution of NASH and no 45% 40% 49%
19% 33% 23%
worsening of fibrosis** 0.043In F2-F3 patients, statistical significance was demonstrated for the
main key histological secondary endpoints
PHASE IIb EFFICACY F2-F3 POPULATION
xx Statistically significant xx Non-statistically significant
Key secondary endpoints in FAS F2 F3 patients (N=188)
lanifibranor
Placebo
Placebo 800 mg
800 mg 1200 mg
1200 mg
(N = 57) (N = 68) (N = 63)
Resolution of NASH and no 44%
34%
worsening of fibrosis* 9%
SECONDARY ENDPOINTS
0.001Effect of lanifibranor therapy on histological endpoints,
in the overall population and the subgroup of F2-F3
Reduction of 2 points of SAF Activity Score and Fibrosis improvement w/o worsening of NASH
no worsening of fibrosis
All F2‐F3
48%
49% 51% N=247 N=188 42%
41% 43%
30% 32%
28%
27% 24%
21%
p=0.061 p=0.004 p=0.53 p=0.011
p=0.01 PA statistically significant decrease in liver enzymes was observed
PHASE IIb EFFICACY OTHER
Other secondary endpoints in ITT (N = 247)
Absolute change from baseline in ALT Absolute change from baseline in AST
10 10
Mean absolute change (UI/L)
Mean absolute change (UI/L)
0
0
‐10
‐10
‐20 ** *
** ** * **
** *
SECONDARY ENDPOINTS
‐30 ** ‐20
** * **
00 4
W4 8 12 W14 16 20 24
W24 00 W4
4 8 12 W14 16 20 W24
24
Placebo Lanifibranor 800mg Lanifibranor 1200mg Placebo Lanifibranor 800mg Lanifibranor 1200mg
* pEffect of lanifibranor therapy on liver enzymes
Percentage of patients with normal ALT values Percentage of patients with normal AST values
73% 76%
71% 69%
54%
50%
43% 46%
38%
33% End of
Baseline treatment
25% 25% (Week 24)
Placebo Lanifibranor 800mg Lanifibranor 1200mg Placebo Lanifibranor 800mg Lanifibranor 1200mg
Lower Limit of Normal (LLN)= 0 U/L, Upper Limit of Normal (ULN)= 41 U/L for males, 33 U/L for LLN= 0 U/L, ULN= 40 U/L for males, 32 U/L for females
females
Percentage of patients with normal GGT values
85%
74%
63%
53% 53%
Significant higher percentage of patients under
40% lanifibranor treatment
reach normal liver enzymes at end of treatment
Placebo Lanifibranor 800mg Lanifibranor 1200mg
LLN= 8 U/L for males, 5 U/L for females; ULN= 61 U/L for males, 36 U/L for females
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 26A statistically significant change in HDL-cholesterol and triglycerides
was seen, without a change in LDL-cholesterol
PHASE IIb EFFICACY OTHER
Other secondary endpoints in ITT (N = 247) * pIn patients with NASH and T2D, statistically significant reductions of
fasting glucose and insulin, HbA1c were observed
PHASE IIb EFFICACY OTHER
Secondary endpoints in patients with NASH and T2D (N = 103)
Absolute change from baseline in HbA1c Absolute change from baseline in fasting glucose
0,5
Mean absolute change (%)
0,5
Mean absolute change (mmol/L)
0 0
‐0,5
‐0,5 ** ‐1 **
** ** **
** ‐1,5 **
SECONDARY ENDPOINTS
‐1 **
‐2 ** **
00 W44 8 12W14 16 20 W2424
00 W44 8 12 W14 16 20 W2424
Placebo (N = 35) Lanifibranor 800mg (N = 33)
Placebo (N= 35) Lanifibranor 800mg (N= 33)
Lanifibranor 1200mg (N = 35) Lanifibranor 1200mg (N= 35)
**pA significant decrease in circulating biomarkers was observed under
lanifibranor treatment after 24-weeks
PHASE IIb EFFICACY OTHER
lanifibranor
Median relative change (%) Placebo Pvalue
(Two doses pooled)
Pro-C3 (4.1%) (13.9%) p= 0.005*
OTHER OUTCOME MEASURES
Pro-C3 >14 at
Fibrosis (12.8%) (20.5%) p= 0.017*
baseline(1)
Ratio TIMP-1/MMP-2 (4.6%) (22.5%) p < 0.001*
Apoptosis CK18-M30 0.5% (41.1%) p < 0.001*
Ferritin (9.1%) (29.4%) p < 0.001*
Inflammation
hs-CRP 13.0% (35.5%) p < 0.001*
(1) Level where it is estimated that fibrogenesis is active and corresponding to F2/F3 patients
FAS (Full Analysis Set) population with available data at baseline and at week 24
* Statistically significant
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 29Addtional analysis on NATIVE phase 2b results have enlarged
lanifibranor spectrum of efficacy
EFICACY: Sub-analysis
Presentation during the plenary session of NATIVE phase 2b trial
Lanifibranor effect on histology endpoints is higher in the F2-F3 patients
Lanifibranor has beneficial effects on cardiovascular risk biomarkers
Preclinical data showing the combination of lanifibranor and firsocostat, an ACC
inhibitor from Gilead, reached greater efficacy than monotherapy
Lanifibranor improves markers of glucose metabolism in prediabetic patients
Analysis showing a decrease in lanifibranor treated patients of steatosis
measured by CAP/Fibroscan(1)
Following treatment with lanifibranor NASH resolution responders were
significantly more likely to also be fibrosis improvers
Lanifibranor showed reduction in LSEC(2) capillarization
Lanifibranor improves NASH, fibrosis and diastolic dysfunction in a hamster
model of diet-induced NASH and diastolic dysfunction
(1) CAP: Controlled Attenuation Parameter (2) Liver Sinusoidal Endothelial Cell
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 30Lanifibranor has continued to show a favourable safety profile
PHASE IIb SAFETY OVERALL
Placebo 800 mg 1200 mg
N (%) patients reporting Adverse Event (AE)
(N = 81) (N = 83) (N = 83)
Any Treatment-Emergent AE (TEAE) 50 (61.7%) 59 (71.1%) 62 (74.7%)
Drug-related TEAE 19 (23.5%) 25 (30.1%) 23 (27.7%)
Any TEAE leading to drug withdrawal 3 (3.7%) 4 (4.8%) 3 (3.6%)
Drug-related TEAE leading to drug withdrawal 2 (2.5%) 1 (1.2%)(1) 2 (2.4%)(2)
Any Serious TEAE 3 (3.7%) 3 (3.6%) 7 (8.4%)
Drug-related Serious TEAE 2 (2.5%)(3) - -
(1) One patient with moderate diarrhea Focus of next slide
(2) One patient with mild cardiac failure; one patient with mild diarrhea, abdominal pain, dizziness
(3) 2 SUSARs: one patient with mild cardiac failure; one patient with moderate urticaria
Consistent with known insulin sensitizing pharmacology, a mean weight increase from baseline of 2.4 kg (2.6%) at the
800 mg/day dose and 2.7 kg (3.1%) at the 1200 mg/day dose was observed.
Placebo 800 mg 1200 mg
(N = 81) (N = 83) (N = 81)
Peripheral edema 2 (2.5%) 5 (6.0%) 7* (8.4%)
Drug-related peripheral edema - 2 (2.4%) 2 (2.4%)
* One AE of severe intensity
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 31A limited number of serious TEAEs occurred
PHASE IIb SAFETY SERIOUS TEAE
Patients reporting treatment-emergent Placebo 800 mg 1200 mg
Serious AE (SAE); N (%) (N = 81) (N = 83) (N = 83)
Total 3 (3.7%) 3 (3.6%) 7 (8.4%)
Treatment-Emergent Serious AE linked to biopsy procedure
Post-procedural haematoma/haemorrhage - 1 (1.2%) 1 (1.2%)
Post-procedural pain - - 1 (1.2%)
Pneumobilia (post-procedural) - - 1 (1.2%)
Other Treatment-Emergent Serious AE
Wrist fracture 1 (1.2%) - -
Angina unstable - - 1 (1.2%)
Cardiac failure 1 (1.2%) - -
Gastroenteritis - - 1 (1.2%)
Pyelonephritis - - 1 (1.2%)
Pancreatitis - 1 (1.2%) -
Undifferentiated connective tissue disease - 1 (1.2%) -
Urticaria 1 (1.2%) - -
Foot operation - - 1 (1.2%)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 32Phase II results have demonstrated modest weight increase with no
impact on efficacy
PHASE IIb SAFETY WEIGHT GAIN
CONSISTENT WITH KNOWN INSULIN-SENSITIZING PHARMACOLOGY, a mean weight increase from baseline of
2.4 kg (2.6%) at the 800 mg/day dose and 2.7 kg (3.1%) at the 1200 mg/day dose was observed
According to a six month study with pioglitazone in patients * with NASH body weight gain is likely attributed to an
INCREASE IN ADIPOSE TISSUE and NOT WATER RETENTION
Based on a 52-week lanifibranor trial in systemic sclerosis (SSc) patient weight gain is expected TO REACH A
MAXIMUM BY WEEK 24
SSc lanifibranor study: weight (kg) relative change from baseline over 52 weeks
(Observed cases under treatment – FAS population)
Except for two patients (one placebo, one 600mg BID),
Kg TEAE time of onset related to weight increase happened in
6 the first 24 weeks of treatment
4
2
0 Weeks
0 2 4 8 12 16 20 24 28 32 36 40 44 48 52
Lanifibranor 600 mg BID Placebo
Note: * Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholiv steatohepatitis ; Balas, Belfort, Harrison et al. ; Journal of Hepatology 47 (2007) 565-570
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 33Peripheral edemas were not flagged as a concern by study
investigators
PHASE IIb SAFETY PERIPHERAL OEDEMA
Treatment Verbatim of AE Action taken or Corrective Relationship
# Intensity
group edema peripheral treatment to treatment
1 edema in the lower leg and knees Moderate IMP interrupted + Meloxicam Unlikely
Placebo
2 bilateral lower extremity edema Mild No actions taken Unlikely
3 bilateral lower extremity edema Unrelated
4 edema in bilateral feet Unlikely
Mild No actions taken
5 800 mg peripheral edema bilateral Possible
6 right and left ankle swelling Possible
7 foot edema bilateral Moderate Bioflavonoids Unrelated
8 leg edema - both legs Torasemid Unrelated
9 edema in the 2 ankles Unrelated
10 edema lower leg, both sides Mild Unrelated
No actions taken
11 1200 mg peripheral edema , both ankles Unrelated
12 bilateral edema leg Probable
13 bilateral postural extremities edema Moderate IMP stopped Unrelated
14 legs edema Severe IMP interrupted Possible
Peripheral edemas were not flagged as a concern by study investigators and were:
Limited
Transient
Mostly mild
Majority unrelated and not requiring treatment
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 34Compared to key competitors, lanifibranor is the only asset that
addresses all key features of NASH
EFFICACY
Lanifibranor Ocaliva Resmetirom Aramchol Efruxifermin Semaglutide
(PPAR) (FXR) (THR-β) (Other) (FGF) (GLP-1)
STATUS Phase III CRL Phase III Phase III Phase II Phase III
ROUTE OF
Oral Oral Oral Oral Injectable Injectable
ADMINISTRATION
INSULIN-
RESISTANCE
STEATOSIS
NECRO-
Unclear
INFLAMMATION
FIBROSIS Unclear
Source: Newsome et al., 2020; Company websites
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 35Lanifibranor compares favourably in its ability to target both fibrosis
improvement and NASH resolution
EFFICACY Active Placebo xx Statistically significant xx Non-statistically significant
Only drug achieving statistical
Injectables
significance on both endpoints
Lanifibranor Ocaliva Resmetirom Aramchol Efruxifermin* Semaglutide
Time point of Phase IIb Phase III Phase IIb Phase IIb Phase IIa Phase IIb
data collection 6 months 18 months 9 months 12 months 4 months 18 months
# of patients 247 931 125 247 80 320
NASH resolution with no worsening of fibrosis
59%
45% 50%
43%
19% 24%
12% 17% 17%
8% 7% 5%Physicians are positive about anifibranor's value proposition, noting
its ability to target both fibrosis and NASH resolution
EFFICACY
The benefits of a pan-PPAR targeting multiple isoforms are clear to most physicians, who
comment positively on lanifibranor's efficacy on fibrosis and NASH resolution whilst also improving
glycaemic control and insulin sensitivity
“… This product is a dream come true, it targets all the things I would want it to; it resolves the
NASH, the fibrosis and you get improvement of glycaemic control and insulin resistance …”
Physician #1, US
Physicians valued “… You have to attack both NASH and fibrosis because if you reverse fibrosis and still have NASH,
Lanifibranor's that’s going to lead to more fibrosis …” Physician #2, US
efficacy on multiple
endpoints “… It is attractive, I do like that it has an effect on HbAC1 as the most common co-morbidity is T2D …”
Physician #3, US
Physicians confirm F2-F3 is a correct patient population to target, noting lanifibranor's MoA
(targeting multiple metabolic pathways) makes it highly suited to the F2-F3 population
– clinicians also want to treat the disease at its asymptomatic stage prior to complications
occurring; some prefer this population over F4, as the latter is considered irreversible
– some also suggested they would like to use it in F0-1 if possible, in order to slow or prevent
progression to F2-F3
Lanifibranor's oral administration is considered attractive, highlighting a once-daily oral pill
will increase ease of use to the patient
A once a day oral is “… It is a once a day oral drug so compliance will be as good as you can get. At this point it
considered optimal would all be about education – it is important to educate the patient that they need to take this
product, even if they are asymptomatic …” Physician #5, US
Source: L.E.K. Interviews, research and analysis (dated August 2020)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 37Physicians perceive weight gain due to lanifibranor as manageable,
with the risk profile viewed positively
SAFETY
Physician express differing views on the importance of weight gain
– the majority of physicians believed that given lanifibranor's efficacy profile the risk-benefit
ratio was acceptable, and with proper patient counselling around weight loss some of the
weight gain could be offset
– some suggested combination therapy could be used to manage or reduce weight gain
Weight gain (e.g., GLP-1, SGLT2)
appears acceptable
and manageable, “…Weight increase can be limiting, but I don’t think it be a problem if we can find something
with limited to use in combination to offset potential increase in fat tissue …” – Physician, U.S., August
concerns 2020
expressed around
"… I am surprised by the weight gain but I do not see it as a big concern. It would only
edemas become an issue if the weight gains happens continuously, for example if you increase 2-
3kgs every 2 months… Physician, DE, August 2020
Physicians express less concerned about oedema noting the majority are mild
“… The mechanism of edema determines how bad it is, it is not alarming…” – Physician,
FR, August 2020
“… edema is not relevant …” Physician, DE, August 2020
Source: L.E.K. Interviews, research and analysis (dated August 2020)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 38FDA’s current thinking on NASH (May 2021)
“The “Division of Hepatology and Nutrition (DHN) at the FDA views NASH
with liver fibrosis as a serious and life-threatening condition”
“Patients with NASH are also vulnerable to other diseases, and the
investigational drugs should not worsen other comorbidities, including
cardiovascular disease, hyperlipidemia, metabolic disease and diabetes”
“The accelerated approval pathway for drugs intended to treat NASH with
liver fibrosis is appropriate because of the seriousness of the condition”
“Phase 3 studies demonstrating a successful treatment difference on liver
histology surrogate end-point(s) and an adequate safety profile can receive
an accelerated approval with a requirement to verify and confirm clinical
benefit after approval”
“We encourage use and evaluation of noninvasive biomarkers … to be
considered for use as a surrogate efficacy endpoint reasonably likely to
predict clinical benefit”
Source: Anania FA, Dimick-Santos L, Mehta R, Toerner J, Beitz J. Nonalcoholic Steatohepatitis: Current Thinking From the Division of Hepatology and Nutrition at the Food and Drug Administration. Hepatology. 2021
May;73(5):2023-2027. doi: 10.1002/hep.31687. PMID: 33340111.
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 39Phase III NATiV3 clinical trial: design overview
PHASE III OVERVIEW
A randomized, double-blind, placebo-controlled, multicenter, Phase III study evaluating long-term
efficacy and safety of lanifibranor in adult patients with NASH with liver fibrosis
Part 1: 72 week treatment Part 2: Extension period
Screening Placebo Biopsy Placebo Biopsy
Biopsy Part I Part II
lanifibranor, 800 mg once daily lanifibranor, 800 mg once daily
lanifibranor, 1200 mg once daily lanifibranor, 1200 mg once daily
PRINCIPAL INVESTIGATORS: Pr. Sven Francque and Pr. Arun Sanyal
MAIN INCLUSION CRITERIA aligned to Phase IIb trial:
Adults 18 years of age diagnosed with NASH using SAF scoring (steatosis ≥1, activity ≥3 and fibrosis score
of F2-F3)
RANDOMISATION AND STRATIFICATION
Randomisation 1:1:1
Stratification on T2DM and F2/F3 patients
At least 30% of patients from the U.S.
STATISTICAL POWERING: 90% considered for sample size calculations
CENTRAL BIOPSY review done by three pathologists
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 40Phase III NATiV3 Part 1 interim histology analysis will enable to
seek U.S. accelerated approval and E.U. conditional approval
PHASE III OVERVIEW
Part 1 F2-F3 Phase III
Part 1: 72 week treatment
Screening Placebo Biopsy
Eligible for U.S. ACCELERATED
Biopsy Part I
lanifibranor, 800 mg once daily APPROVAL and EU CONDITIONAL
APPROVAL
lanifibranor, 1200 mg once daily
PRIMARY ENDPOINT at week 72 on c.900 patients
• Composite endpoint of patients having both NASH resolution and fibrosis improvement of at least one stage
KEY SECONDARY ENDPOINTS
• NASH resolution and no worsening of fibrosis
• Improvement of fibrosis and no worsening of NASH
OTHER SECONDARY ENDPOINTS AND HIGH-LEVEL KEY EXPLORATORY ENDPOINTS (non-exhaustive)
• Glycaemic parameters at week 12 and week 24 in patients with T2DM not well controlled: proportion of patients
with HbA1c back to normal
• Composite endpoint of diabetic patients having both NASH resolution and fibrosis improvement
• Improvement in renal function
• Reduction of cardiovascular risk (including major adverse cardiovascular events ‘MACE’; non-fatal myocardial
infarction, non-fatal stroke, cardiovascular death, hospitalisation for unstable angina)
• Quality of life (NASH-CLDQ) and PRO (PROMIS)
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 41Phase III NATiV3 Part 2 extension study will allow for
a broader “full approval”
PHASE III OVERVIEW
Part 2 F2-F3 Phase III
Part 2: Extension period
Placebo Biopsy
Part II Potential for FULL
lanifibranor, 800 mg once daily
APPROVAL in U.S. and EU
lanifibranor, 1200 mg once daily
KEY ENDPOINTS IN PART 2 (non-exhaustive) TRIAL END DATE TIMING OF FINAL BIOPSY
Based on time to first clinical event on c.2,000 Defined by first On per-patient basis,
patients occurrence of following defined by:
• histological progression to cirrhosis events (whichever – Suggested progression
comes first): to cirrhosis based on
• all cause mortality
– pre-defined number non-invasive testing, or
• hepatic decompensation events of clinical events – trial has ended
− hepatic encephalopathy registered
− variceal bleeding
− new onset ascites requiring treatment
− spontaneous bacterial peritonitis
• MELD score ≥15
• liver transplant
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 42The Phase III patients will be randomised across 350 to 400 sites
worldwide
PHASE III DESIGN SITE SELECTION
24 countries included of which 23 countries with full
regulatory approval
Activities paused in Ukraine where 10 sites were
qualified including 3 sites already screening patients
Company decision to cancel the participation of
Russia (12 sites)
>380 sites qualified
Study conducted with our global partner ICON
NATiV3 country on hold Addition of two clinical research networks in the US
NATiV3 participating countries
and Europe with recruitment objectives additive to
those of ICON ones
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 43The primary composite endpoint combining NASH resolution and
fibrosis improvement will help differentiate from key competitors
PHASE III EFFICACY
The primary endpoint “resolution of NASH and improvement of fibrosis” addresses the major pathways of the disease:
achieving both of these histological outcomes reflects a stronger impact on disease modification compared with
improvement in either steatohepatitis or fibrosis alone
If met, a label for the treatment of NASH and the improvement in liver fibrosis in adult non-cirrhotic NASH patients will
be requested
lanifibranor Obeticholic acid Resmetirom Semaglutide
Phase III study (800 - 1200mg) (10 - 25mg) (80 - 100mg) -
At W72 At W72 At W52 At W72
Resolution of NASH and Secondary
Primary / Secondary
improvement of fibrosis (not met)
Fibrosis improvement and no Primary
Key secondary Primary Primary
worsening of NASH (met)
Primary
NASH resolution and no Primary Primary
Key secondary (with reduction of at
worsening of fibrosis (not met)
least 2 pts of NAS)
NASH resolution and fibrosis
improvement in patients with Secondary / /
diabetes
Note:* / : information not available
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 44Key milestones of the Phase III study in NASH (Part 1)
PHASE III MILESTONES
2023 2024 2025
F2-F3 Phase III H1 2023 H2 2024 H1 2025
Part 1: Last Patient Part 1: Last Patient Part 1: Topline
First Visit Last Visit results
(c.900 patients) (c.900 patients)
H2 2025
NDA
submission
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 45Lanifibranor clinical trial in patients with NAFLD and T2D
PHASE II NAFLD T2D TRIAL
Objective: Establish safety, efficacy and mechanism of action of lanifibranor in patients with T2D and NAFLD. Specifically
determine if lanifibranor decreases IHTG(1), improves hepatic insulin sensitivity, endogenous (hepatic) glucose production,
gluconeogenesis and DNL(2)
Principal investigator Primary endpoint
Prof. Kenneth Cusi (University of Florida) Change in IHTG quantified by H-MRS(3) from baseline to week 24
Randomisation Key secondary endpoints
Randomized (1:1), double-blind, placebo-controlled Proportion of responders (patients with a IHTG decrease ≥ 30%)
N=34 and 10 healthy non-obese as “normal” NAFLD resolution (patients with IHTG ≤ 5%)
controls for all the metabolic and imaging tests Change in hepatic fibrosis (MRE(4), fibroscan, biomarkers)
Sample calculated assuming a 35% relative Change in metabolic outcomes (insulin sensitivity, DNL(3), glycemic
reduction of IHGT control/HbA1c, lipids)
Status Safety
Results expected for H2 2022
34 patients; 24 week treatment
Double blind randomized placebo controlled
Healthy non-obese control group, 10 subjects
Placebo, 17 patients
Lanifibranor, 800 mg once daily, 17 patients
Trial could provide additional supporting clinical data regarding
lanifibranor’s potential for the treatment of NASH
(1) Intrahepatic triglycerides (2) De-novo lipogenesis (3) Proton Magnetic Resonance Spectroscopy (4) Magnetic resonance elastography
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 46Lanifibranor can be used in association with other therapies to
further strengthen its value proposition
OUTLOOK Combination therapies
Examples and potential benefits of combination therapies
GLP-1
Potential complementary effects on the multistep disease
biology of NASH (disturbances of lipid and carbohydrate
metabolism, insulin resistance, inflammation, fibrosis)
Eventually potentiate therapeutic efficacy on histological
SGLT-2 endpoints: NASH resolution and fibrosis
Ideally could manage metabolically ‘healthy’ weight increase
in association with lanifibranor
LANIFIBRANOR
ACC
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 47Combination of SGLT2 with pioglitazone has shown additional
metabolic health benefits and favorable weight management
OUTLOOK SGLT2 combination study
Lanifibranor and SGLT2 rationale
Four randomized trials
– Pioglitazone alone vs pioglitazone + sGLT2i
– N = 1411 T2D patients
• Centers were in US, Canada, South America, China, Japan,
India, Europe
• Patients were on a stable dose of pioglitazone (monotherapy
GLP-1
or with metformin)
– Duration 24-72 weeks
Efficts of combination vs monotherapy with pioglitazone
– Efficacy:
SGLT-2
• Larger decrease of HbA1c; more patients reaching HbA1C <
7%
LANIFIBRANOR • Larger reduction of fasting blood glucose level
• Weight reduction
ACC
• Blood pressure reduction
– Safety
• No difference in death, heart failure, hypoglycemia, urinary
tract infection
• More frequent genital infections
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 48LEGEND Study Design
PHASE II Lani + SGLT2i
Lanifibranor in Combination with the SGLT2 Inhibitor empagliflozin in patients with NASH and Type 2 Diabetes
LEGEND Study
Principal investigator Inclusion criteria
Prof. M. Lai, gastroenterologist-hepatologist, Adult patients with diabetes and NASH
associate professor of medicine; Beth Israel Primary outcome measures
Deaconess Medical Center (USA)
HbA1c change
Prof. O. Holleboom, academic medical specialist
(diabetes and metabolism) at the Amsterdam Secondary outcome measures
University Medical Center (NL) MRI-based imaging to collect non-invasive data on hepatic fat,
Status inflammation and fibrosis
Study to be conducted in 5 countries (US and Glycaemic/lipid parameters, inflammatory markers
four western European countries) in approx. 40 Changes in body fat composition
sites
Other outcome measures (safety/exploratory)
IND accepted by FDA
AEs, body weight, PK, IHTG, cT1, biomarkers
First site activated: H1 2022
Topline results: H2 2023
63 patients / 24 week treatment
Randomized, double-blind for lanifibranor and placebo, open label for
Up to 4 weeks the combination, placebo-controlled 4 weeks
Lanifibranor 800 mg + empagliflozin 10 mg, 21 patients
Screen and Lanifibranor 800mg, 21 patients Follow-up
randomization
Placebo, 21 patients
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 49Lanifibranor upcoming clinical readouts
CLINICAL READOUTS
Patients with Patients with
Patients with
NAFLD and NASH F2 F3
NASH and T2D
T2D fibrosis stage
2022 2023 2024 2025
Clinical
readouts H2 2022
Topline results of
the phase II trial of H2 2023
lanifibranor in Topline results of the
patients with phase II trial of H1 2025
NAFLD and T2D lanifibranor in Topline results of the
combination with phase III trial (part 1)
SGLT2i of lanifibranor in
empagliflozine in patients with NASH
patients with NASH
and T2D
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 50Cedirogant
ROR controls Th17 cell differentiation and effector function The success of anti-IL17 or anti-IL23 biologics in the treatment of psoriasis validates the IL23-IL17 pathway as an important target for therapy Source: Jetten et al. Nature 2010 Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 52
Cedirogant: a clinical stage ROR inverse agonist with potential in
several auto-immune diseases
ROR is believed to be a master regulator of Th17 differentiation and IL-17 expression, an approach validated by
several successful biologics
Pharmacological inhibition of ROR by small molecules has been observed to suppress Th17 production, block
cutaneous inflammation in animal models of psoriasis and inhibit TH17 signature gene expression by cells isolated
from psoriatic patient samples
Potential to more effectively inhibit IL-17 production than antagonist approaches
ROR: a validated drug target for the treatment of psoriasis and other auto-immune diseases
A-9758(1) attenuates IL-23 mediated skin inflammation A-9758(1) blocks GPI-mediated arthritis
Effect of ROR inhibition on IL-23 Effect of ROR inhibition on paw swelling both on prophylactic and late
mediated psoriasiform dermatitis prophylactic treatment
(1) A-9758 is first generation compound developed within the collaboration with AbbVie previously to identifying cedirogant
Source: Inhibition of interleukin-32 mediated inflammation with a novel small molecule inverse agonosit RORt; The Journal of Pharmacology and Experimental Therapeutics 371:208-218, October 2019
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 53Psoriasis: a $20b global market dominated by injectables
Psoriasis is a common skin condition that affects 2-4% of the population in western countries with global sales in 2020 of
approx. $20b(1)
The market is dominated by IL-12/23, IL-17 and TNF which, despite being injectables, account for more than 80% of the
market(1)
Despite an inferior efficacy and safety profile to approved injectables, Otezla (PDE4, oral) generated $2,2b(2) of sales and was
acquired by Amgen for $13,4b in 2019
There is space for more efficacious oral drugs in psoriasis
100 Injectable; 12 week data
PASI 75 efficacy (placebo corrected)(3)
Oral; 16 week data
80
Opportunity for a safe and
% of patients
60 efficacious oral treatment
40
20
0
IL-17 IL-23 IL-12/23 TNF TYK2 PDE4
• Efficacy • Efficacy • Safety • Safety • Oral • Oral
• Safety • Safety • Infrequent dosing • Efficacy vs
• Infrequent dosing PDE4
• Injectable • Injectable • Injectable • Injectable • Efficacy • Efficacy
• Frequent dosing • Frequent dosing • Potential • GI toxicity
JAK labeling
(1) Evaluate Pharma ; (2) 2021 company annual report; (3) Efficacy represents average of PASI-75 in 2 Phase III trials; IL17 trials : FIXTURE and UNDERCOVER 2; IL23 trials ULtIMMa-1 & ULtIMMa-2; TNF: REVEAL and
CHAMPION; IL-12/23 trials: PHOENIX 1 and PHOENIX 2; TYK2 trials: POETYK PSO 1 and POETYK PSO 2; PDE4 trials: ESTEEM 1 and ESTEEM 2
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 54Cedirogant (ABBV-157) is currently evaluated in a Phase IIb trial in
adults with moderate to severe psoriasis
Single ascending dose and multiple ascending dose trials in healthy volunteers completed
Phase Ib: A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety
and Tolerability of ABBV-157 in Healthy Volunteers and in Subjects With Chronic Plaque Psoriasis
‒ 4 week, 65 participants (patients and healthy volunteers)
‒ in patients with chronic plaque psoriasis, cedirogant showed promising activity as an oral psoriasis agent
Phase IIb initiated in November 2021
2020 2021 2022 2023 2024
December 2019 April 2021 November 2021 March 2023
• 3.5 M€ milestone for the • Phase Ib • Launch of phase IIb trial in • Trial completion date of
inclusion of the first trial psoriasis (2) phase IIb trial in psoriasis(2)
patient with psoriasis in completion January 2022
a Phase Ib trial date (1) • 4.0 M€ milestone payment
for first patient randomized
“In our Phase Ib study, 157 showed promising activity as an oral psoriasis agent and we plan to move the asset
forward to a larger Phase IIb dose-ranging study in the second half of this year … with respect to oral psoriasis
agents, we would want to come in from an efficacy perspective with something that clearly exceeded the threshold that
existed in the past with Otezla ... we'd be looking for that Humira-like efficacy or greater as something that we would
like to use to enter the space within oral, obviously, coupled with a strong safety profile.”
Dr. Michael Severino AbbVie Vice Chairman and President(3)
ABBV-157 is Cedirogant AbbVie code; (1) Source clinicaltrials.gov NCT03922607; (2) Source clinicaltrials.gov NCT05044234; (3) AbbVie Q1 2021 earnings call April 30 2021 9 AM ET; Transcript from FactSet
Corporate Presentation | 2022 Non-confidential – Property of Inventiva │ 55You can also read
