Lanifibranor in Nonalcoholic Steatohepatitis (NASH) NATIVE Phase IIb Topline Results June 16, 2020
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 marchés financiers ), available on the Company’s website (www.inventivapharma.com) and on the website of the AMF. The Company may not actually achieve the plans, in tents 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 a ctual 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 ex pectations 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. NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 2
Today’s speakers Frédéric Cren, MA/MBA, Chairman, CEO and cofounder Pierre Broqua, Ph.D., CSO and cofounder Marie-Paule Richard, MD, CMO Prof. Sven Francque, MD University Hospital Antwerp, Principal Investigator of NATIVE trial Prof. Manal Abdelmalek, MD Division of Gastroenterology and Hepatology at Duke University, Principal Investigator of NATIVE trial NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 3
Highlights of topline results ► Lanifibranor met the primary endpoint with a statistically significant reduction after 6 months of treatment of the Steatosis Activity Fibrosis score (SAF), which combines assessments of hepatocellular inflammation and ballooning, with no worsening of fibrosis in the Intention To Treat (ITT) 1 and Per Protocol (PP) 2 populations ► Lanifibranor also met key secondary endpoints including NASH resolution with no worsening of fibrosis and improvement of liver fibrosis with no worsening of NASH in both ITT and PP populations ► Lanifibranor is the first drug candidate to achieve statistically significant effects on the FDA and EMA primary endpoints relevant for seeking accelerated approval: ► NASH resolution with no worsening of fibrosis ► Improvement of fibrosis with no worsening of NASH ► Lanifibranor continued to show a favorable tolerability profile ► Positive topline results support Inventiva’s decision to move forward with the clinical development of lanifibranor and enter into pivotal Phase III development 1 ITT: includes all patients randomized in the trial. 2 PP: includes all patients with paired biopsies and without deviation impacting efficacy assessment. NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 4
Lanifibranor: the only pan-PPAR agonist in clinical development for the treatment of NASH Moderate and balanced pan-PPAR agonist activity PPAR a PPAR d PPAR g Compound Differentiated EC50 (nM) EC50 (nM) EC50 (nM) chemical structure Lanifibranor (1) 1630 850 230 Once daily oral administration Fenofibrate 2400 - - Pioglitazone - - 263 Composition of matter patent granted in 55 Rosiglitazone countries and method of use patent granted in - - 13 the US, China and in the EU: limit of Elafibranor (2) 10 100 - exclusivity in the US is 2035 Seladelpar (3) FAST Track designation granted by FDA - 2 - Results justifying a NASH development Favorable tolerability profile Effects observed on insulin-sensitivity, 24-months rodent and 12-month monkey studies leading to PPAR dyslipidemia, steatosis, ballooning, class clinical hold lifted by FDA inflammation, hepatic fibrosis and cirrhosis in Phase I trials with more than 200 healthy volunteers (2) and Phase IIa preclinical models trial with 47 TD2M patients Phase IIa (1) trial demonstrated pan-PPAR Approximately 250 patients treated for 24 or 48 weeks in Inventiva’s agonist activity, supporting dose selection for completed Phase IIb clinical trials NASH clinical trial In connection with these trials, lanifibranor has undergone a total of 7 DSMB reviews without recommendations of protocol change (1) Conducted by Abbott prior to our founding; (2) Including 125 healthy volunteers in the phase I conducted by Abbott prior to our founding. NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 5
Trial design Clinicaltrials.gov identifier: NCT03008070 24-week treatment + 4-week follow-up Screening End of treatment Double blind, randomized, placebo-controlled Liver biopsy Liver biopsy Placebo Lanifibranor, 800 mg once daily • Randomisation 1/1/1 • Stratification on Lanifibranor, 1200 mg once daily type 2 diabetes mellitus (T2DM) 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, and <4 for fibrosis More information on : http://www.native-trial.com/ NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 6
247 patients randomized in 71 sites worldwide 49 sites in 4 sites in Europe Canada Patients Country randomized Europe 183 (74%) US 36 (15%) Australia 13 (5%) 12 sites in the Canada 8 (3%) United States Mauritius 7 (3%) Total 247 (100%) 1 site in 5 sites in Mauritius Australia 17 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) NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 7
Efficacy endpoints Primary endpoint Decrease from baseline to week 24 of at least 2 points of inflammation and ballooning and no worsening of fibrosis (as measured by SAF activity score) Secondary endpoints Resolution of NASH and no worsening of fibrosis Improvement of fibrosis by at least 1 stage and no worsening of NASH Decrease from baseline to week 24 of at least 2 points of the NAS CRN score and no worsening of fibrosis Resolution of NASH and improvement of fibrosis by at least 1 stage Change in glucose metabolism parameters (fasting glucose, insulin, HOMA index, HbA1c, …) Change in liver enzymes tests (ALT, AST, GGT, Alkaline Phosphatase, Total Bilirubin) Change in main plasma lipid parameters (TC, HDL-C, calculated LDL- C, TG,…) Other outcome measures Change in inflammatory markers (fibrinogen, hs- CRP, alpha2 macroglobulin, haptoglobin,…) Change in fibrosis markers (TIMP-1, TIMP-2, Hyaluronic acid, P3NP, NFS, FIB-4 score, ELF score, Pro- C3,…) NATIVE Phase IIb Webcast | June 2020 Property of Inventiva │ 8
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