Inventiva Sa · EURONEXT:IVA
Inventiva Sa — Investor Presentation (May 2021)
64 slides from Inventiva Sa's investor presentation, May 2021
Slide 1: Developing innovative therapies in NASH and MPS
Developing innovative therapies in NASH and MPS Corporate Presentation May 2021
Slide 2: Disclaimer
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 s
Slide 3: Inventiva in a nutshell
Inventiva in a nutshell Clinical stage biotech with focus on oral small molecules for the treatment of NASH, MPS, and other diseases with high unmet medical needs Two unencumbered late stage assets – Lanifibranor: only pan-PPAR agonist in clinical development for NASH; positive Phase IIb topline dat
Slide 4: Management team with extensive global experience in drug development
Management team with extensive global experience across all stages of drug development and commercialization Frédéric Cren, MA/MBA, CEO and Co-Founder Wide expertise within the areas of R&D, marketing, strategy and commercial operations Held senior positions at Abbott, Fournier, Solvay Pharma an
Slide 5: Oral small molecule-focused discovery engine
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
Slide 6: Deep pipeline
Deep pipeline Candidate / IND Commercial Next Indication Discovery Phase I Phase II Phase III Program* Enabling Rights Milestone Phase III First Patient Lanifibranor NASH pan-PPAR First Visit in Q3 2021 Strategy Odiparcil MPS VI GAG clearance update in 2021 Moderate to Phase IIB Cedirogant
Slide 7: Key financials and shareholder base
Key financials and shareholder base Key financials Shareholder base(1) Founders 25% Free Float 31% Employees ISIN code FR0013233012 / US46124U1079 & Others 2% Market Euronext Paris / Nasdaq GM Sofinnova 38,630,261 (incl. 7,478,261 shares of 8% Shares outstanding the July 9 Nasdaq IPO) BVF Euronext P
Slide 8: Lanifibranor in Nonalcoholic Steatohepatitis (NASH)
Lanifibranor in Nonalcoholic Steatohepatitis (NASH)
Slide 9: Lanifibranor: the only pan-PPAR agonist in clinical development for 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, b
Slide 10: Lanifibranor is a differentiated pan-PPAR agonist
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 R
Slide 11: Activation of three PPAR isoforms addresses key features of NASH
Lanifibranor’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 ge
Slide 12: Adverse events of other PPAR agonists not observed in lanifibranor
Adverse 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
Slide 13: Phase I and IIa trials: beneficial changes in metabolic markers
Phase 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=0.0
Slide 14: Improvements demonstrated in animal models
Improvements 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 /
Slide 15: NASH is a chronic progressive disease with no approved treatment
NASH 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 TRANSPL
Slide 16: Phase IIb NATIVE trial design
The 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 dai
Slide 17: Patients randomised across sites worldwide
247 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 Mauritiu
Slide 18: Majority of patients completed 24-week treatment
The 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
Slide 19: Baseline patient population
Patient population included 58% of female and 42% of patients with T2DM 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%
Slide 20: Baseline liver enzyme, lipid and glucose parameters
A 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.
Slide 21: First candidate to achieve significance on both Phase III primary endpoints
Lanifibranor 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 popul
Slide 22: F2-F3 patients: significance on key secondary endpoints
In 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 8
Slide 23: Significant decrease in liver enzymes
A 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 ** * ** ** *
Slide 24: Changes in HDL-cholesterol and triglycerides
A 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) * p<0.01 **p<0.001 Absolute change from baseline in HDL-C Absolute change from baseline in triglycerides SECONDARY
Slide 25: Reductions in glucose, insulin and HbA1c in T2DM patients
In patients with NASH and T2DM, statistically significant reductions of fasting glucose and insulin, HbA1c were observed PHASE IIb EFFICACY OTHER Secondary endpoints in patients with NASH and T2DM (N = 103) Absolute change from baseline in HbA1c Absolute change from baseline in fasting glucose 0,5 M
Slide 26: Decrease in circulating biomarkers
A 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
Slide 27: Favourable safety profile
Lanifibranor 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%)
Slide 28: Limited number of serious TEAEs
A 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
Slide 29: Modest weight increase with no impact on efficacy
Phase 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 obser
Slide 30: Peripheral edemas not flagged as a concern
Peripheral 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
Slide 31: Physicians perceive weight gain as manageable
Physicians 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 ACCEPTAB
Slide 32: Tolerability versus other oral NASH candidates
Lanifibranor tolerability profile characteristics and other oral NASH drug candidates SAFETY NATIVE FLINT Phase REGENERATE ARREST BALANCED Phase IIb Phase IIb Phase IIb IIb Ph. III Phase IIb Phase IIa DEATHS None 2 3 None None None 1 9% placebo 7% placebo 11% placebo 12.5% placebo 4.8% placebo TRIAL
Slide 33: Differentiated potential to address all features of NASH
Lanifibranor has a differentiated potential to address all features of NASH in a safe and efficacious manner EFFICACY AND SAFETY Targeting all features of NASH… … ensures favourable comparison against competitors NASH resolution with no worsening of fibrosis METABOLISM STEATOSIS VASCULAR Fibrosis im
Slide 34: NATIVE results versus other oral NASH candidates
Lanifibranor NATIVE results and other oral NASH drug candidates DIFFERENTIATION NASH resolution with no worsening of fibrosis <0.001 xx Statistically significant in accordance to the statistical analysis plan (SAP) Placebo Active xx Non- statistically significant 0.03 0.045 0.0659 45% 0.051 0.1268 1
Slide 35: F2-F3 Phase III design
The F2-F3 Phase III consists of two parts, with inclusion criteria and patient profile in line with the NATIVE Phase IIb trial PHASE III F2 F3 Patients A randomized, double-blind, placebo-controlled, multicenter, Phase III study evaluating long-term efficacy and safety of lanifibranor in adult patie
Slide 36: Primary endpoint will help differentiate from competitors
The primary 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 r
Slide 37: Phase III sites worldwide
The Phase III patients will be randomised across approximately 300 sites worldwide PHASE III DESIGN SITE SELECTION Nativ3 countries 25 countries worldwide for close to 300 sites expected to participate Corporate Presentation | 2021 Non-confidential – Property of Inventiva │ 37
Slide 38: Key milestones of the Phase III study in NASH (Part 1)
Key milestones of the Phase III study in NASH (Part 1) PHASE III MILESTONES 2021 2022 2023 2024 F2-F3 Phase III Q3 2021 H2 2022 H1 2024 First Patient Part 1: Last Patient Part 1: Last First Visit First Visit Patient Last Visit (c.900 patients) (c.900 patients) Q2 2021 First Site Active H2 2024 Part
Slide 39: Ongoing Phase II trial in NAFLD and T2DM
The ongoing Phase II trial in patients with NAFLD and T2DM could provide additional supporting clinical data for lanifibranor in NASH PHASE II NAFLD T2DM TRIAL Trial design Principal investigator Primary endpoint Prof. Kenneth Cusi (University of Florida) Change from baseline to week 24 in IHTG
Slide 40: Odiparcil – MPS
Odiparcil – MPS
Slide 41: MPS are devastating diseases with high unmet medical needs
Mucopolysaccharidoses (MPS) are devastating diseases with high unmet medical needs MPS is a group of inherited lysosomal storage disorders Lysosomes function as the primary digestive units within cells: enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrat
Slide 42: ERT commercially successful but unmet needs remain
Despite enzyme replacement therapies (ERT) being commercially successful, many unmet medical needs remain Enzyme replacement therapies are standard of care in MPS Recombinant human enzymes, requiring a once a week intravenous infusion over 4 hours Limited penetration into protected or poorly vas
Slide 43: Odiparcil: oral small molecule GAG reduction therapy
Odiparcil: an orally available small molecule GAG reduction therapy designed to treat several forms of MPS Acts to decrease lysosomal accumulation of GAGs by promoting formation of soluble DS / CS which can be excreted in the urine Oral administration and distribution in tissues that are poorly pene
Slide 44: Differentiated mechanism of action potentially synergistic with ERT
Differentiated mechanism of action potentially synergistic with ERT Odiparcil acts to divert endogenous protein-bound GAG synthesis to soluble odiparcil- bound chondroitin sulfate (CS) and dermatan sulfate (DS) synthesis Galactosyl transferase I (GTI) Galactosyl transferase I (GTI) Synthesis of prot
Slide 45: Mechanism relevant to MPS subtypes with excess DS and CS
Odiparcil mechanism of action potentially relevant to MPS subtypes with excess DS and CS MPS Type Frequency DS CS HS(1) KS(2) MPS I-H MPS I-S 1/100,000 MPS I-H/S MPS II Types A & B 1/100,000 1/40,000 to MPS IV Type A 1/200,000 1/240,000 to MPS VI 1/400,000 MPS VII Very rare
Slide 46: GAG clearance mechanism observed in MPS VI mice
Odiparcil GAG clearance mechanism of action observed in MPS VI mice Odiparcil and GAG accumulation in livers tissues 40 GAG in liver [Area * Index] p<0.001 p<0.001 Soluble GAGs produced from 30 odiparcil are excreted in urine 20 Sulfated GAG (µg/mg of creatinine) 6000 p<0.0001 10 0 4000 WT MPS VI MP
Slide 47: Odiparcil penetrates tissues where ERT has limited efficacy
Odiparcil penetrates tissues where ERT has limited efficacy Odiparcil observed to be well distributed in tissues and organs poorly penetrated by recombinant enzymes Heart Bone Cornea Cartilage Odiparcil(1) rhASB(2) Not tested Not detected Not detected Meaningful concentrations of odiparcil observed
Slide 48: Odiparcil reverses corneal impairment in MPS VI mice
Odiparcil reverses corneal impairment in MPS VI mice Odiparcil administration observed to affect corneal structure and corneal GAG storage epithelium stroma WT MPSVI MPS VI + Odi Odiparcil effect on corneal Odiparcil effect on number Odiparcil effect on GAG storage in corneal stroma epithelium thick
Slide 49: iMProveS Phase IIa trial of odiparcil in MPS VI
iMProveS Phase IIa trial of odiparcil in MPS VI Phase IIa Population ► Safety and efficacy trial with evidence for dose selection and PK / PD response characterization ≥ 16yo ► Clinicaltrials.gov identifier: NCT03370653 15 patients double blind + 5 patients open label 6 weeks 4 weeks 26 week treatme
Slide 50: Safety data
Safety data The clinical trial met its safety primary endpoint with a favourable tolerability profile consistent with that observed in previous Phase I and Phase II clinical trials The majority of adverse events were mild or moderate One death occurred in the placebo group Three serious adve
Slide 51: Pharmacodynamics: total urinary GAG levels
Odiparcil pharmacodynamics: total GAG levels in urine and PK/PD correlation A dose-dependent urinary GAGs clearance, used as an activity biomarker, was observed in the odiparcil treated patient population 3000 Total urinary GAG µg/mg creatinine 2000 1000 0 Bsl V4 Bsl V4 Bsl V4 Bsl V4 V2 V7 V2 V7 V2
Slide 52: Efficacy endpoints
Efficacy endpoints Not addressed by ERT (hard-to-reach Partially addressed by ERT tissues) Endurance and mobility Cardiac and vascular system 6-minute walk test (6MWT) ECG, Echocardiogram 9 hole peg test (9HPT) Carotid intima media thickness (CIMT) Range of motion of left and right shoulde
Slide 53: Trends of improvement on 6MWT and FVC
Efficacy data: trends of improvement on 6MWT and FVC 6MWT FVC ERT-PLB ERT-PLB ERT-250 BID ERT-250 BID ERT-500 BID ERT-500 BID non-ERT-500 BID non-ERT-500 BID -150 -100 -50 0 50 -150 -100 -50 0 50 100 worsening improvement worsening improvement change from reference (m) change from reference (mL) Tre
Slide 54: Patients treated with ERT and odiparcil show improvements
Efficacy data: several patients treated by ERT and odiparcil show improvements in one or several parameters Treatment Respiratory Ophthalmology Cardiology (N=10) (FVC) (COM left eye, right eye) 1 1 (slightly improved) (slightly improved) Placebo + ERT 0 Patient A(1): +4, +11 - (N=4) - Patient B: ↓ 3
Slide 55: Signals of activity in patients treated only with odiparcil
Efficacy data: signals of activity were also detected in patients only treated with odiparcil Odiparcil Respiratory 500mg Bid Ophthalmology Cardiology Range of Motion Other (FVC) (N=3) Improved range of Improved FVC motion on both Patient H NA Stable Pain improved by +18% shoulders (+17.8%/+21.0%) I
Slide 56: Anticipated clinical development path in MPS VI
Odiparcil: anticipated clinical development path for approval in MPS VI Phase IIa (6-m treatment) MPS VI adults (16y+) Safety - Add on to ERT, n=15 PK, PD (uGAG) and BM (leukoGAG, skinGAG) - Not receiving ERT, n=5 Exploratory assessment of efficacy Open-label (iMProveS Extension) extension Com
Slide 57: Cedirogant
Cedirogant
Slide 58: Cedirogant: clinical stage ROR inverse agonist (I)
Cedirogant: a clinical stage ROR inverse agonist co-discovered by Inventiva with potential in several auto-immune diseases (I) ROR is believed to be a master regulator of Th17 differentiation and IL-17 expression, an approach validated by several successful biologics Pharmacological inhibition o
Slide 59: Cedirogant: clinical stage ROR inverse agonist (II)
Cedirogant: a clinical stage ROR inverse agonist co-discovered by Inventiva with potential in several auto-immune diseases (II) Cedirogant (ABBV-157) is an orally-available inverse agonist of the nuclear receptor ROR for the treatment of moderate to severe psoriasis and other auto-immune diseases,
Slide 60: YAP-TEAD and TGF-β programs
YAP-TEAD and TGF- programs
Slide 61: YAP-TEAD and TGF-β programs
YAP-TEAD and TGF- programs YAP-TEAD program Hippo signalling pathway is potentially implicated in the process of cell differentiation and proliferation, tissue growth and organ size Inventiva compounds observed to disrupt interaction between YAP and TEAD along the pathway Potentially relevant
Slide 62: Recent and upcoming catalysts
Recent and upcoming catalysts
Slide 63: Recent and anticipated key milestones
Recent and anticipated key milestones Lanifibranor Positive topline results of NATIVE Phase IIb trial in NASH Breakthrough Therapy Designation granted by FDA NATIVE Phase IIb meeting with FDA and EMA Scientific Advice First Patient First Visit of phase III trial in NASH – H2 2021 Results o
Slide 64: Contacts
Contacts Inventiva Brunswick Westwicke, an ICR Company Frédéric Cren Yannick Tetzlaff / Tristan Roquet Montégon Patricia L. Bank / Aude Lepreux CEO Investor relations Media relations info@inventivapharma.com inventiva@brunswickgroup.com patti.bank@westwicke.com +33 (0)3 80 44 75 00 + 33 1 53 96 83 8