developing breakthrough therapies in nash and ... · non-confidential – property of inventiva │...
TRANSCRIPT
Developing breakthrough therapies inNASH and mucopolysaccharidosis
Corporate PresentationJune 2019
Non-confidential – Property of Inventiva │ 2
DISCLAIMER
This document has been prepared by Inventiva (the "Company") solely for the purpose of this presentation. This presentation includes only summary information and does not purport to be comprehensive. Any information in this presentation, whether from internal or from external sources, is purely indicative and has no contractual value. The information contained in this presentation are provided as at the date of this presentation. Certain information included in this presentation and other statements or materials published or to be published by the Company are not historical facts but are forward-looking statements. The forward-looking statements are based on current beliefs, expectations and assumptions, including, without limitation, assumptions regarding present and future business strategies and market in which the Company operates, and involve known and unknown risk, uncertainties and other factors, which may cause actual results, performance or achievements, or industry results or other events, to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include those discussed or identified under Chapter “Risk factors” in the Company’s registration document (document de reference) filed with the French Financial markets authority (AMF – Autorité des marchésfinanciers), available on the Company’s website (www.inventivapharma.com) and on the website of the AMF. The Company may not actually achieve the plans, intents or expectations disclosed in its forward-looking statements and you should not place undue reliance on the forward-looking statements contained herein. There can be no assurance that the actual results of the Company’s development activities and results of operations will not differ materially from the Company’s expectations. Factors that could cause actual results to differ from expectations include, among others, the Company’s ability to develop safe and effective products, to achieve positive results in clinical trials, to obtain marketing approval and market acceptance for its products, and to enter into and maintain collaborations; as well as the impact of competition and technological change; existing and future regulations affecting the Company’s business; and the future scope of the Company’s patent coverage or that of third parties.
The information contained in this presentation has not been subject to independent verification. No representation or warranty, express or implied, is made by the Company or any of its affiliates, advisors, representatives, agents or employees as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the information, or opinions contained herein. Neither the Company, nor any of its respective affiliates, advisors, representatives, agents or employees, shall bear any responsibility or liability whatsoever (for negligence or otherwise) for any loss howsoever arising from any use of this presentation or its contents or otherwise arising in connection with this presentation. Such information is subject to modification at any time, including without limitation as a result of regulatory changes or changes with respect to market conditions, and neither the Company, nor any of its affiliates, advisors, representatives, agents or employees, shall, nor has any duty to, update you.
Corporate Presentation | 2019
Non-confidential – Property of Inventiva │ 3Corporate Presentation | 2019
Inventiva investment highlights
Clinical stage biotech with focus on oral small molecules for high unmet need in fibrosis, lysosomal storage disorders and oncology
Two unencumbered late stage assets in two high value indications– Lanifibranor – only pan-PPAR agonist in clinical development for NASH, Phase IIb data
due H1 2020– Odiparcil – first orally available therapy for MPS, Phase IIa data due H2 2019
State of the art R&D capabilities including wholly owned ‘pharma scale’ discovery facilities
Portfolio underpinned by discovery engine focused on nuclear receptors, transcription factors and epigenetic targets with a 240,000 compound library, 60% of which are proprietary
Compelling early stage pipeline leveraging power of discovery engine in fibrotic disease and oncology, supported by validating partnerships with AbbVie and Boehringer Ingelheim
– ABBV-157 RORγ program: first phase I completed and second one in 60 healthy volunteers and patients with chronic plaque psoriasis due to start in May 2019
– YAP-TEAD program in late pre-clinical stage, clinical candidate selection expected in 2019
Strong US and European shareholder base and experienced senior management team with a track record of operational and scientific excellence
Non-confidential – Property of Inventiva │ 4
Validated oral small molecule-focused discovery engine targeting nuclear receptors, transcription factors and epigenetic modulation
Corporate Presentation | 2019
Power of discovery engine underpins deep pipelineof clinical and discovery stage assets
Library of ~240,000 compounds of which 60% proprietary
Wholly-owned 129,000 square foot pharma-like R&D facilities
Expertise: nuclear receptors, transcription factors, epigenetic targets
Strong scientific team of ~90 people
Non-confidential – Property of Inventiva │ 5
Deep pipeline approaching major near term value inflection points
Corporate Presentation | 2019
Candidate / Program Indication Discovery IND
Enabling Phase I Phase II Phase III Commercial Rights
Lanifibranor NASHPhase IIb
results: H1 2020
Odiparcil MPS VIPhase IIa
results: H2 2019
ABBV-157 Moderate to severepsoriasis
SAD phase I completed(1)
HippoNon-small cell
lung cancer and mesothelioma
Candidate Selection: 2019
TGF-β Idiopathic pulmonary fibrosis (IPF)
Lead Op(2)
GAG clearance
ROR𝛾𝛾
pan-PPAR
YAP/TEAD
(1) SAD: Single Ascending Dose; (2) Lead optimization means refining molecules in advance of selecting candidates
Non-confidential – Property of Inventiva │ 6
Key financials and shareholder base
ISIN code FR0013233012
Market Euronext Paris
Shares outstanding 22.294.677Market cap(May 24 2019)
€54m
Cash position(March 31 2019)
€47,3m compared to €56,7m as of December 2018.Successful €48.5m Euronext IPO (February 2017) and €35.5m private placement (April 2018)
Revenues(December 31 2018)
€3.2m compared to €4.8m in 2017
R&D expenditures(December 31 2018)
€31,6m compared to €26,7m in 2017
Key financials Shareholder base
Analyst coverage
HC WainwrightLifeSci CapitalJefferiesKBCSociété GénéraleGilbert DupontKepler Chevreux
Ed ArcePatrick DolezalPeter WelfordLenny Van SteenhuyseDelphine Le LouëtJamila El BougriniArsene Guekam
Corporate Presentation | 2019
Free float*22.1%
BVF15.0%
Novo 8.8%
Sofinnova 7.1%Employees & Others
3.1%
Founders43.9%
*Including Perceptive Advisors
Lanifibranor in NonalcoholicSteatohepatitis (NASH)
Non-confidential – Property of Inventiva │ 8
Lanifibranor is a differentiated pan-PPAR agonist with moderate and well balanced activity on the 3 PPAR isoforms
Corporate Presentation | 2019
Compound PPARαEC50 (nM)
PPARδEC50 (nM)
PPARγEC50 (nM)
Lanifibranor(1) 1630 850 230 Fenofibrate 2400 - -
Pioglitazone - - 263
Rosiglitazone - - 13
Elafibranor(2) 10 100 -
Seladelpar(3) - 2 -
Lanifibranor human dose response curves and EC50s for various PPAR agonists
-10 -8 -6 -40
25
50
75
100
125
150
%A
ctiv
atio
n
hPPARα
hPPARδhPPARγ
Lanifibranor (M)
Potency scale: red 10 nM; grey: 500 nM; green 5 000 nM
Lanifibranor binds differently than rosiglitazone to PPARγ inducing different coactivator recruitment(4)
Source: (1) Company data (2) Hanf R et al, Diabetes & Vascular Dis Res 2014 (3) Cymabay company presentation (4) J Med Chem. 2018 Feb 15. doi: 10.1021/acs.jmedchem.7b01285
Non-confidential – Property of Inventiva │ 9
Favorable safety profile differing from previously developed PPARs
Corporate Presentation | 2019
Organ PPAR isoforms activated
ReportedPPAR liabilities
Lanifibranoreffects
Heart PPARγ Fluid retention Cardiac hypertrophy Not observed
Skeletalmuscle PPARα Myofiber degeneration Not observed
Kidney PPARα
> 50% increases in creatinine,degenerative changes in renal tubules
Not observed
Urinarybladder PPARγ Proliferative changes
in bladder epithelium Not observed
Source: Company data
Lanifibranor not associated with typical single or dual PPAR liabilities
Non-confidential – Property of Inventiva │ 10
In long-term toxicological studies lanifibranor presents a safe and differentiating profile
After review of carcinogenicity studies, FDA has lifted PPAR class clinical hold and allowed long-term clinical studies in NASH with lanifibranor
Corporate Presentation | 2019
Lanifibranor shows a very favorable profile in 12 month monkey study …
− No adverse clinical signs were observed at any dose-level tested
− No effects on body weight and heart weight, no haemodilution or creatinine increase
− Electrocardiography and clinical pathology investigations did not reveal any undesirable effects
… and in two-year carcinogenicity studies performed in rat and mice
− Rat: no neoplastic changes and increase in tumor types commonly associated with single PPARγ and dual PPARα/γ agonists: liver, adipose, bladder, renal and skin
− Mice: no neoplastic changes and increase in tumor types of human relevance
No carcinogenic effect relevant to humans, contrasting with some other PPARγ and PPARα/γ agonists
Non-confidential – Property of Inventiva │ 11
Phase I and Phase IIa clinical studies(1) demonstrated lanifibranorbeneficial effects on key metabolic markers
Corporate Presentation | 2019
Lanifibranor has beneficial effects on key metabolic markers in type II diabetic patients
Source: Company data ; (1) Conducted by Abbott
(2) A placebo controlled trail of Pioglitazone in subjects with nonalcoholic steatohepatitis Belfort et Al; N Engl J Med 355;22 November 30, 2006; 6 month treatment
(3) Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism ; Diabetes Care. 2011 Sep;34(9):2008-14. doi: 10.2337/dc11-0093. Epub 2011 Aug 4. 4 week treatment study 1
(4) A Novel Peroxisome Proliferator Receptor-δ Agonist: Lipid and Other Metabolic Effects in Dyslipidemic Overweight Patients Treated with and without Atorvastatin The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 9, 1 September 2011, Pages 2889–2897, https://doi.org/10.1210/jc.2011-1061; 8 week treament
Placebo 400 mg 800 mg 1400 mg 0
100
200
300
IVA337 IVA337IVA337
p=0.08
p=0.05
p=0.05
Perc
ent c
hang
e of
bas
elin
e
Adiponectin (PPARγ)
Perc
ent c
hang
e fr
om b
asel
ine
lanifibranor lanifibranor lanifibranorPlacebo 400 mg 800 mg 1400 mg
0
10
20
30
40
IVA337 IVA337IVA337
p=0.13
p<0.05
p<0.05
Perc
ent c
hang
e of
bas
elin
e
HDL Cholesterol (PPARα/δ)
Perc
ent c
hang
e fr
om b
asel
ine
lanifibranor lanifibranor lanifibranorPlacebo 400 mg 800 mg 1400 mg
-50
-40
-30
-20
-10
0
IVA337 IVA337IVA337
p=0.08
p<0.05p<0.05
Perc
ent c
hang
e of
bas
elin
e
Triglycerides (PPARα/δ)
Perc
ent c
hang
e fr
om b
asel
ine
lanifibranor lanifibranor lanifibranor
HDL increase:Lanifibranor (800/1400mg): +18%/28%Elafibranor(3) (80mg): +7,8%Seladelpar(4) (50mg): +9,9%
TG decrease:Lanifibranor (800/1400mg): -24%/28%Elafibranor (80mg)(3): -16,7%Seladelpar(4) (50mg): -32,4%
Adiponectin fold: Lanifibranor (800/1400mg): +2.8/+3.2 Pioglitazone(2) (45mg): +2.3Homa-IR: Lanifibranor (800/1400mg): -20%/-44%
Non-confidential – Property of Inventiva │ 12
Phase I and Phase IIa clinical studies(1) confirmed lanifibranor safety
Corporate Presentation | 2019
Good overall tolerance and no major safety findings
– No increases of creatinine, liver function test (LFT) or creatine phosphokinase (CPK)
– No changes in blood pressure
– No signal of fluid overload or hemodilution
– No clinically relevant weight gain
No significant differences in SAE and AE between placebo and lanifibranor in the phase IIa
Clinical findings underline the favorable tolerability of lanifibranor
Source: Company data and * Ohashi, Endocr Metab Immune Disord Drug Targets. 2015. Note: (1) Conducted by Abbott ; (2) Pioglitazone data obtained after 6 month treatment (Belfort 2006); elafibranor after 4 week and seladelpar after 8 week
Non-confidential – Property of Inventiva │ 13
NASH overview
Source: NASH Market, Allied Market Research 2016 ; Deutsche Bank Markets Research; Intercept website.; Epidemiology and natural history of non-alcoholic steatohepatitis.Clinical Liver Disease.2009 Nov;13(4):511-31.
Corporate Presentation | 2019
The overall NASH prevalence in the adult population of the United States is believed to be approximately 12%
A severe disease with no currently approved treatment
Hepato-carcinoma Death
Liver transplant
Reversible40-50%
15-20%
Severe liverdamage
HealthyLiver
NASHNAFLD
Cirrhosis
NASHwith
fibrosis 2-3% per year 30-40%
Non-confidential – Property of Inventiva │ 14
Lanifibranor’s mechanism of action addresses all the key features of NASH
Corporate Presentation | 2019
Insulin sensitivity
HDLc
TG
PPARα,δ,γ
Metabolism
FA uptake
FA catabolism
Lipogenesis
PPARα,γ
Steatosis
Inflammation and Ballooning
NFkB-dependent gene activation
Inflammasome
Ballooning
PPARα,δ,γ
Stellate cell proliferation and activation
Collagen and fibronectin production
PPARγ
Fibrosis
Non-confidential – Property of Inventiva │ 15
Pioglitazone PPARγ NASH resolution efficacy results are still unmatched
Corporate Presentation | 2019
Pioglitazone Cusi study (45 mg, 18 month), Annals of Internal Medicine, 2016 ; Ocaliva Regenerate Phase III study (25 mg, 18 months), press release Feb. 19, 2019
CVC Centaur Phase II study (150 mg, 12 months), Hepatology 2017 ; Elafibranor Golden 505 Phase II study (120 mg, 12 months), Gastroenterology. 2016
MGL-3196 Phase II study (100mg, 8 months), press release May 31, 2018 ; Aramchol Arrest Phase II study (600 mg, 12 months) – press release June 12, 2018
pbo19%
pbo8%
pbo12% pbo
6%pbo6%
pbo7%
51%
12%19%
8%
27%
19%
0%
10%
20%
30%
40%
50%
60%
Pioglitazone Ocaliva Elafibranor CVC MGL-3196 Aramchol
Patie
nts
with
impr
ovem
ent,
%
Resolution of NASH without worsening of fibrosis
Non-confidential – Property of Inventiva │ 16
Overview of NATIVE trial design (I/II)
Corporate Presentation | 2019
More information on: http://www.native-trial.com/
Trial design
225 patients24 week treatment
Double blind randomized placebo controlled
End of treatment Liver biopsy
Placebo, 75 patientsLanifibranor, 800 mg once daily, 75 patientsLanifibranor, 1200 mg once daily, 75 patients
Principal investigator Prof. Francque (Universitair Ziekenhuis,
Antwerpen, Belgium) Prof. Manal Abdelmalek (Duke University,
USA)Status Trial enrolling Results expected first-half 2020
Clinicaltrials.gov identifier: NCT03008070
Inclusion criteria Severe patients with an inflammation and
ballooning score of 3 or 4 Steatosis score ≥ 1 and fibrosis score < 4 (no
cirrhosis)Primary endpoint Decrease from baseline ≥ 2 points of the
inflammation and ballooning score without worsening of fibrosis
Screening Liver biopsy
Non-confidential – Property of Inventiva │ 17
Overview of NATIVE trial design (II/II)
Corporate Presentation | 2019
17 countries worldwide
► 13 in EU► United States► Canada► Australia► Mauritius
92 sites involved91 sites activated82 sites screening
14 sites selected in the United-States
Status
756 patients screened and 192 patients randomized (85%) at end of May 2019 3 positive DSMB reviews recommending to continue the study without any changes Limited number of edema (blinded data): 7 patients treated with placebo or lanifibranor reported
mild or moderate edemas of short duration and which did not require treatment discontinuation Results expected first-half 2020
Non-confidential – Property of Inventiva │ 18
NATIVE study results will also be backed by the Phase II trial in T2DM patients with NAFLD
(1) Intrahepatic triglycerides (2) Magnetic resonance elastography (3) De-novo lipogenesis
A positive study result would further reinforce lanifibranor’s profile in NAFLD and NASH patients with type 2 diabetes
Corporate Presentation | 2019
64 patients24 week treatment
Double blind randomized placebo controlled
Healthy non-obese control group, 10 subjectsPlacebo, 32 patientsLanifibranor, 800 mg once daily, 32 patients
Principal investigator Prof. Kenneth Cusi (University of Florida)Randomisation N=64 assuming a 35% reduction of IHGT(1)
StatusIND approved First Patient First Visit: August 2018
Results expected first-half of 2020
Primary endpoint Change from baseline to week 24 in IHTGKey secondary endpoints Proportion of responders; change in hepatic
fibrosis (MRE(2), biomarkers); change in metabolic outcomes
SafetyClinicaltrials.gov identifier: NCT03459079
Trial design
Odiparcil – MPS
Non-confidential – Property of Inventiva │ 20
Mucopolysaccharidoses (MPS) are devastating diseases with high unmet medical need
Corporate Presentation | 2019
Source: (1) Source: Rheumatology 2011 Therapy for mucopolysaccharodises; Vassili Valayannopoulos and Frits A. Wijburg
Autosomal recessive disorders characterized by accumulation of glycosaminoglycan(s) (GAGs) due to deficient lysosomal enzymes
Seven distinct clinical types based on the enzyme affected: odiparcil could be the first substrate reduction therapy for five forms of MPS with the following incidences: Kathleen (MPS I)
Scotty (MPS II)
Karima (MPS VI)
MPS is a group of inherited lysosomal storage disorders
MPS has devastating clinical consequences: example MPS I, II and VI
MPS I
Mental retardation Coarse facies, short stature Dysostosis multiplex Joint stiffness Spinal cord compression Organomegaly Poor vision (corneal clouding) Hearing loss Cardiac/respiratory disease
MPS II MPS VIConsequences
(1) Retinal degeneration with no corneal clouding Odontoid hypoplasia Kyphoscoliosis, genu valgum
Pebbled skin Diarrhoea
(1)
Non-confidential – Property of Inventiva │ 21
Enzyme replacement therapy (ERT) is commercially successful, but with limited therapeutic efficacy
Source: (1) H. Noh, J. I. Lee; Current and potential therapeutic strategies for mucopolysaccharidoses; Journal of Clinical Pharmacy
Corporate Presentation | 2019
Recombinant human enzymes, weekly intravenous infusion over 4 hours Approx. 50% of patients experience infusion reactions initially, some can be life threatening Limited penetration into protected or poorly vascularized tissues such as cornea or cartilage
Product Company MPS Est. yearly cost 2018 sales
MPS I $ 217K $ 206M
MPS II $ 522K $ 616M(1)
MPS IVA $ 578K $ 482M
MPS VI $ 476K $ 345M
MPS VII $ 550K $ 8M
ERT is expensive and usually requires outpatient administration. Significant unmet need remains in addressing symptoms in organs where ERT fails to penetrate
Enzyme replacement therapies are standard of care in MPS
Source: Sales - Company annual reports 2017; WAC without discounts for a 25-kg patient - BioCentury “Making of MEPSEVII” Dec 11, 2017 ; (1) 2017 sales
Non-confidential – Property of Inventiva │ 22
Unique mechanism of action potentially synergistic with ERT
Corporate Presentation | 2019
Source: H. Noh, J. I. Lee; Current and potential therapeutic strategies for mucopolysaccharidoses; Journal of Clinical Pharmacy, company data
Odiparcil diverts endogenous protein-bound GAG synthesis to soluble odiparcil-bound chondroitin sulfate (CS) and dermatan sulfate (DS) synthesis
Odiparcil decreases intracellular GAG accumulation in vitro in MPS VI patient cells
Galactosyl transferase I (GTI)
Synthesis of proteoglycans (HS, CS, DS)
Synthesis of soluble DS and CS
Odiparcil
Odiparcil
Galactosyl transferase I (GTI)
MPS VI fibroblastsGAG overloaded
cells
Intracellular CS storage Extracellular GAG
0
5
10
15
20
25
10- 8 10- 7 10- 6 10- 5
MPS VI (IC50=3 µM)
Veh.Odiparcil concentration (M)
Tota
l sul
fate
d G
AGS
(µg/
mL)
0
100000
200000
300000
10- 8 10- 7 10- 6 10- 5
Control (IC50=2.8 µM)MPS VI (IC50=2.7 µM)
Veh.Odiparcil concentration (M)
Fluo
resc
ence
inte
nsity
Odiparcil observed to reduce GAG accumulation in MPS VI patient cells
Odiparcil
Non-confidential – Property of Inventiva │ 23
By producing soluble dermatan and chondroitin sulfates, odiparcilcan address several types of MPS
Source: Rheumatology 2011 Therapy for mucopolysaccharodises; Vassili Valayannopoulos and Frits A. Wijburg
Type Name DS CS HS KS
MPS I-H Hurler syndrome
MPS I-S Scheie syndrome
MPS I-H/S Hurler-Scheie syndrome
MPS II Types A & B Hunter syndrome
MPS IV Type A Morquio syndrome
MPS VI Maroteaux-Lamysyndrome
MPS VII Sly syndrome
Corporate Presentation | 2019
Non-confidential – Property of Inventiva │ 24
Odiparcil decreases GAG content in vivo and improves mobility in a MPS VI model
Corporate Presentation | 2019
Source: Company data
0
10
20
30
40 p<0.001
WT MPS VI MPS VI + Odi
p<0.05
time
on p
ole
[sec
]
0
10
20
30
40p<0.001
WT MPS VI MPS VI + Odi
p<0.001
GAG
in li
ver
[Are
a *
Inde
x]
± Odiparcil*Given in food
6 monthsWild-type and MPS VI miceTreatment starts when animals are one month old
►Sulfated GAGs in organs/tissues and urine►Mobility test►Corneal structure/clouding
* The doses administered provide exposure levels similar to that to be used in clinic
Liver
Odiparcil decreases GAG accumulation in tissues
Odiparcil improves animal mobility
Chow dietOdiparcil : 4.5 g/kg in food
Odiparcil decreases intra-cellular GAG
0
20
40
60
80%
cells
with
> 1
0 G
AG g
ranu
les
p<0.001p<0.001
MPS VI MPS VI+OdiWT
Leukocytes Pole Test
Non-confidential – Property of Inventiva │ 25
Odiparcil penetrates tissues that ERT cannot reach
Meaningful concentrations of odiparcil observed also in tissues that are poorly vascularized or protected by a barrier: bone, corneal tissue and cartilage
Corporate Presentation | 2019
Odiparcil is well distributed in tissues and organs poorly penetrated by recombinant enzymes
Heart CorneaBone Cartilage
Odiparcil(1)
rhASB(2) Not detectedNot tested Not detected
Non-confidential – Property of Inventiva │ 26
Odiparcil shows promising results in poorly vascularized tissues not treated by ERT
Corporate Presentation | 2019
Source: Company data
Decreases in GAG accumulation and improvements in corneal structure expected to improve corneal function and ocular impairment
WT control MPSVI
epithelium stroma
MPS VI + Odi0
10
20
30
40p<0.001
WT MPS VI
p<0.0001
MPS VI + Odi
thic
knes
s (µ
m)
Odiparcil effect on corneal structure and epithelium thickness
Chow dietOdiparcil : 4.5 g/kg in food
Odiparcil decreases trachea and knee cartilage thickness
0
20
40
60
80
100p<0.0001
-31%
Trac
hea
carti
llage
thic
knes
s in
µm
MPS VI MPS VI + OdiWT
Chow dietOdiparcil : 4.5 g/kg in food
0
100
200
300p<0.0001
-26%
WT MPS VI
p<0.0001
MPS VI + Odi
Dis
tal f
emor
al g
row
th p
late
thic
knes
s[µ
m]
Chow dietOdiparcil : 4.5 g/kg in food
By decreasing GAG storage in cartilage, odiparcil improves cartilage-linked disease manifestations
Non-confidential – Property of Inventiva │ 27
Odiparcil has the potential to positively differentiate versus current MPS treatment options
Corporate Presentation | 2019
Source: Company evaluation
Effect on mobility
Effect on eye, cartilage, bones, heart valves, spinal cord compression
Distribution type Oral Intravenous Infusion Transplantation
OdiparcilAldurazyme, Elaprase,
Naglazyme, Vimizim, Mepsevii HSCT(Hematopoietic stem cell transplantation)
Non-confidential – Property of Inventiva │ 28
Odiparcil overall development plan in MPS VI
Corporate Presentation | 2019
(1) leukoGAG: GAG levels in circulating leukocytes; UGAG: urinary GAG)
Biomarker Study12 MPS VI patients
Phase IIa, 6-month treatment24 MPS VI adults
Add on to ERT and Naïve
Phase Ib/II, 6-month treatment9 MPS VI children
Add on to ERT
Phase IIIMPS VI (5y-adult)
• Validate LeukoGAG(1) assay in human: potential efficacy biomarker
• Safety and tolerability• PK data with pediatric formulation• PD data, biomarkers (uGAG, leukoGAG, skin GAG)
• Identify signals of clinical efficacy
• Safety and tolerability• Identify signals of clinical efficacy and potential as stand-alone therapy
• PK/PD, biomarkers (uGAG(2), leukoGAG, skin GAG)
• Safety and Tolerability• Efficacy
R&D collaborations and Hippo pathway program update
Non-confidential – Property of Inventiva │ 30
Key validating collaborations with AbbVie and Boehringer Ingelheim
Corporate Presentation | 2019
Inventiva eligible to future milestone payments and sales royaltieson all ROR molecules identified during the collaboration
RORγ collaboration in inflammatory disease RORγ program addresses large markets currently dominated by biologics and could prove to
be superior to biologics Single ascending dose phase I completed with ABBV-157, the clinical candidate coming from
the partnership Next step: A randomized, double-blind, placebo-controlled, multiple-dose study to evaluate the
pharmacokinetics, safety and tolerability of ABBV-157 in 60 healthy volunteers and patients with chronic plaque psoriasis (clinicaltrials.gov identifier: NCT03922607)– Study start date: May 2019– Study completion: September 2020(1)
Inventiva eligible to up to ~€170m in milestones and sales royalties
Fibrosis collaboration
Multi-year R&D collaboration and licensing partnership. Joint team until pre-CC stage. BI to take full responsibility of clinical development and commercialization
Program progressing as planned with first screening performed
(1) Source: clinicaltrial.gov
Non-confidential – Property of Inventiva │ 31
YAP-TEAD program: significant progress achieved and clinical candidate selection planned in 2019
The program is expected to enter into Phase I/II enablingpreclinical development in 2019
Corporate Presentation | 2019
Novel cancer pathway involved in drug resistance, immune evasion, tumor progression and metastases
Relevant in multiple, commercially attractive cancer indications
Proprietary chemistry Lead and back-up compounds
available IP protected
Preclinical candidate screening ongoing
Clinical candidate selection in 2019
Phase I/II start planned in 2020
In vitro evidence for synergies with standard of care and suppression of tumorresistance
In vivo efficacy shown (alone and in combination with standard of care)
First in class YAP-TEAD program
Conclusions
Non-confidential – Property of Inventiva │ 33
Recent achievements and upcoming expected milestones
Corporate Presentation | 2019
2019
Lani
fibra
nor
Odi
parc
ilAB
BV-
157
Rare pediatric disease designation MPS VI Phase IIa in MPS VI: last patient recruited Phase IIa in MPS VI results - H2 2019
YAP-
TEAD
FDA decision to lift lanifibranor clinical hold Last patient Phase IIb NASH Last patient Prof. Cusi study in NAFLD
patients with TD2M
2020
Clinical candidate selection
ABBV-157 multiple-ascending dose in healthy volunteers and psoriatic patients phase I initiation
SAD(1) Phase I with ABBV-157 completed
(1) SAD: Single Ascending Dose
ABBV-157 development in psoriasis
Phase IIb NASH results – H1 2020 Phase II in NAFLD patients with TD2M
results – H1 2020
Launch of phase IB/II in MPS VI children
Launch of Phase I/II in mesotheliomapatients
Contacts
Inventiva
Frédéric Cren
CEO
+33 (0)3 80 44 75 00
Brunswick
Yannick Tetzlaff / Tristan Roquet Montégon
Media relations
+ 33 1 53 96 83 83
LifeSci Advisors
Monique Kosse
Investor relations