Inventiva SA · EURONEXT:IVA
Inventiva SA — Investor Presentation (November 2020)
58 slides from Inventiva SA's investor presentation, November 2020
Slide 1: Developing innovative therapies in NASH and MPS
Developing innovative therapies in NASH and MPS Corporate Presentation November 2020
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 da
Slide 4: Management team with extensive experience across all stages of drug development
Management team with extensive 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 and The B
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 End of Phase IIb Lanifibranor NASH pan-PPAR meetings in Q4 2020 Initiation of Phase Ib/II in Odiparcil MPS VI GAG clearance children in H1 2021 Moderate to Clini
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 1% Market Euronext Paris / Nasdaq GM Sofinnova 38,393,011 (incl. 7,478,261 shares 8% Shares outstanding of the July 9 Nasdaq IPO) NEA BVF Market
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 with balanced activity
Lanifibranor is a differentiated pan-PPAR agonist with moderate and well balanced activity on the 3 PPAR isoforms Lanifibranor human dose response curves and EC50s for various PPAR agonists PPAR PPAR PPAR Compound EC50 (nM) EC50 (nM) EC50 (nM) 150 hPPAR Lanifibranor(1) 1630 850 230 125 hPPAR
Slide 11: Favorable tolerability profile differing from previously developed PPARs
Favorable tolerability profile differing from previously developed PPARs PPAR isoforms Reported Lanifibranor Organ activated PPAR liabilities effects Fluid retention Heart PPAR Cardiac hypertrophy Not observed Skeletal muscle PPAR Myofiber degeneration Not observed > 50% increases in c
Slide 12: Phase I and IIa trials in type 2 diabetes patients: metabolic markers
Phase I and Phase IIa clinical trials(1) in type 2 diabetes patients: beneficial changes in key metabolic markers Lanifibranor metabolic markers in type II diabetic patients Adiponectin (PPAR)(2) HDL Cholesterol (PPAR)(3) Triglycerides (PPAR) (4) baseline baseline baseline 300 p=0.05 40 0 bas
Slide 13: NASH overview
NASH overview A progressive chronic disease with no currently approved treatment Healthy Liver Cirrhosis* NASH Hepato- NAFLD NASH with Death** carcinoma fibrosis Severe liver Reversible damage Liver transplant * More than 20% of patients with NASH progress to cirrhosis within a decade of diagnosis *
Slide 14: Lanifibranor observation in animal models
Lanifibranor observation in animal models: improvements in metabolic parameters and liver histology with anti-fibrotic activity NASH & NAFLD Metabolic models models Fibrosis models Cirrhosis models Diet induced obesity Methionine Choline Carbon tetrachloride Thiocetamide (TAA) high fat / high sucros
Slide 15: Lanifibranor's pan-PPAR mechanism of action
Lanifibranor’s pan-PPAR mechanism of action designed to address all the key features of NASH Metabolism Steatosis Insulin sensitivity FA uptake PPAR HDLc PPAR FA catabolism TG Lipogenesis Inflammation and Ballooning Fibrosis NFkB-dependent gene Stellate cell proliferation PPAR activation
Slide 16: NATIVE Phase III enabling trial: design
NATIVE Phase III enabling trial: design Clinicaltrials.gov identifier: NCT03008070 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
Slide 17: 247 patients randomized in 71 sites worldwide
247 patients randomized in 71 sites worldwide 4 sites in 49 sites in Canada Europe Patients Country randomized Europe 183 (74%) US 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
Slide 18: Patient disposition (N = 247)
Patient disposition (N = 247) 247 patients randomized 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%
Slide 19: Patient Baseline Demographics and Characteristics (I/II)
Patient Baseline Demographics and Characteristics (I/II) ITT (N = 247) 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 5
Slide 20: Patient Baseline Demographics and Characteristics (II/II)
Patient Baseline Demographics and Characteristics (II/II) ITT (N = 247) 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 (
Slide 21: First drug candidate to achieve significance on the two Phase III primary endpoints
Lanifibranor is the first drug candidate to achieve statistically significant results on the two Phase III FDA and EMA primary endpoints Intention to Treat Population Per Protocol Population Statistically significant in accordance to the xx statistical analysis plan (SAP) Lanifibranor Lanifibranor x
Slide 22: Statistically significant decrease in liver enzymes
Statistically significant decrease in liver enzymes 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 ** * ** ** * ** ‐30 ** * ** ** ‐20 * ** 00 4 W4 8 12
Slide 23: Circulating biomarkers in NATIVE
Circulating biomarkers in NATIVE: significant decrease under lanifibranor treatment after 24-weeks Median relative change (%) lanifibranor placebo Pvalue Pro-C3 -13.9% -4.1% p= 0.005* Fibrosis Pro-C3 >14 at baseline -20.5% -12.8% p= 0.017* Ratio TIMP-1/MMP-2 -22.5% -4.6% p < 0.001* Apoptosis CK18-M3
Slide 24: Significant change in HDL-cholesterol and triglycerides
Statistically significant change in HDL-cholesterol and triglycerides Other secondary endpoints in ITT (N = 247) Absolute change from baseline in HDL-C Absolute change from baseline in triglycerides 0,25 0,2 Mean absolute change (mmol/L) Mean absolute change (mmol/L) ** ** 0 0,15 ** ** * ‐0,2 ** 0,0
Slide 25: Reductions of fasting glucose, insulin, HbA1c in T2DM patients
Statistically significant reductions of fasting glucose and insulin, HbA1c in type 2 diabetes (T2DM) patients with NASH Secondary endpoints in T2DM patients with NASH (N = 103) Absolute change from baseline in fasting Absolute change from baseline in HbA1c glucose 0,5 Mean absolute change (%) 0,5 Me
Slide 26: Lanifibranor: a continued favorable tolerability profile (I/II)
Lanifibranor: a continued favorable tolerability profile (I/II) Safety population N = 247 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 27: Lanifibranor: a continued favorable tolerability profile (II/II)
Lanifibranor: a continued favorable tolerability profile (II/II) Safety population N = 247 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-
Slide 28: Lanifibranor: modest weight increase with no impact on efficacy
Lanifibranor: modest weight increase with no impact on efficacy 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 pioglita
Slide 29: TEAEs oedema peripheral reported in NATIVE trial
Lanifibranor: TEAEs oedema peripheral reported in NATIVE trial Treatment Verbatim of AE Action taken or Corrective Relationship # Intensity group Oedema peripheral treatment to treatment 1 oedema in the lower leg and knees Moderate IMP interrupted + Meloxicam Unlikely Placebo 2 bilateral lower extre
Slide 30: Lanifibranor results viewed very positively by physicians
Lanifibranor results viewed very positively by physicians, especially its ability to target both fibrosis improvement and NASH resolution Physicians valued lanifibranor's efficacy on fibrosis and NASH resolution The benefits of a pan-PPAR compound targeting multiple isoforms are clear to most phys
Slide 31: Tolerability profile versus other oral NASH drug candidates
Lanifibranor tolerability profile characteristics and other oral NASH drug candidates NATIVE FLINT REGENERATE ARREST Phase IIb trial Phase IIb trial Phase IIb trial Phase III trial Phase II trial Deaths None 2 3 None None 9% placebo 11% placebo 12.5% placebo Trial 7% placebo 5% placebo 7% 800mg 11%
Slide 32: NATIVE results and other oral NASH drug candidates
Lanifibranor NATIVE results and other oral NASH drug candidates 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 25% 19% 17% 19% 1
Slide 33: Ongoing Phase II trial in type 2 diabetes patients with NAFLD
Ongoing Phase II trial in type 2 diabetes patients with NAFLD evaluating the effect of lanifibranor on liver triglycerides Trial design Principal investigator Primary endpoint Prof. Kenneth Cusi (University of Florida) Change from baseline to week 24 in IHTG Randomisation Key secondary endpoints
Slide 34: Lanifibranor: next key milestones in NASH
Lanifibranor: next key milestones in NASH Finalization of Phase III synopsis and protocol: ongoing End of Phase IIb meeting with FDA: scheduled in Q4 2020 Scientific advice meeting with EMA: scheduled in Q4 2020 Finalization of Phase II trial in NAFLD patients with TD2M conducted by Pr. Cusi
Slide 35: Odiparcil – MPS
Odiparcil – MPS
Slide 36: 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 37: Despite ERT being commercially successful, 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 38: Odiparcil: an orally available 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 39: 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 40: 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 41: Odiparcil 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 42: 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 43: 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 44: 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 45: 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 46: Odiparcil pharmacodynamics: total GAG levels in urine
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 47: 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 48: Efficacy data: 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 49: Patients treated by 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 50: 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 51: Odiparcil: 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 52: ABBV-157
ABBV-157
Slide 53: ABBV-157, a clinical compound co-discovered by Inventiva
ABBV-157, a clinical compound co-discovered by Inventiva, with potential in several auto-immune diseases ROR believed to be a master regulator of IL-17 / 23 approach has been validated by Th17 differentiation and IL-17 expression several successful biologics RORt = Retinoic acid-related Orphan Rec
Slide 54: YAP-TEAD and TGF-β programs
YAP-TEAD and TGF- programs
Slide 55: 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 56: Recent and upcoming catalysts
Recent and upcoming catalysts
Slide 57: Recent and anticipated upcoming key milestones
Recent and anticipated upcoming key milestones Lanifibranor Positive topline results of NATIVE Phase IIb trial in NASH – June 2020 Breakthrough Designation Therapy granted by FDA NATIVE Phase IIb meeting with FDA and Scientific Advice meeting with EMA – Q4 2020 Odiparcil Positive results of
Slide 58: 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 [email protected] [email protected] [email protected] +33 (0)3 80 44 75 00 + 33 1 53 96 83 8