- The phase II study led by Dr. Kenneth Cusi evaluating lanifibranor in patients with T2D and MASLD was selected as late breaker.
- Two additional scientific abstracts from the NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH have been selected for presentation. The two abstracts show:
- the correlation between the increase of adiponectin under lanifibranor and the improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis.
- the improvement of liver histology and markers of cardiometabolic health in patients with NASH treated with lanifibranor, independent of PNPLA3 genotype.
Daix (France), Long Island City (New York, United States), November 6, 2023 – Inventiva (Euronext Paris and Nasdaq: IVA) (the “Company”), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of nonalcoholic steatohepatitis (NASH) and other diseases with significant unmet medical needs, today announced that the phase II trial led by Dr. Cusi in patients with type two diabetes (T2D) has been accepted as late breaker, at the upcoming The Liver Meeting® 2023 hosted by the American Association for the Study of Liver Diseases on November 10-14, 2023 in Boston. In addition two other scientific abstracts have been selected for poster presentation.
The late breaker abstract “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” presents results from a study sponsored by Dr. Cusi at the University of Florida, that evaluates the effect of lanifibranor on insulin resistance in the liver, muscle and adipose tissue, as well as its effect on intrahepatic triglyceride (IHTG) content in patients with T2D and Metabolic dysfunction associated steatotic liver disease (MASLD)1.
The second abstract evaluates the correlation between adiponectin response with lanifibranor and the improvement of histological and serum markers of NASH severity, both in terms of disease activity and fibrosis. The change in adiponectin levels at end of treatment (categorized as unchanged, moderate or high increase) correlated positively to histological endpoints of NASH resolution and no worsening of fibrosis, improvement of fibrosis and no worsening of NASH, and NASH resolution and fibrosis improvement. The degree of adiponectin level increase correlated also with improvement of the NASH-CRN and SAF-Activity scores as well as with improvement of the individual components: steatosis, inflammation and ballooning. Lanifibranor-associated adiponectin increase also correlated with the improvement in histological fibrosis stage, pro-C3 levels and MACK-3 score. These data further support that adiponectin is a biomarker for the efficacy of lanifibranor treatment across the disease spectrum of NASH, from cardiometabolic health – as previously shown – to hepatic health. As a reminder, a 3.82 and 4.50 fold increase in adiponectin level were respectively reported in the 800mg arm and 1200mg arm during Inventiva’s NATIVE Phase IIb clinical trial.
The third abstract evaluates the impact of the PNPLA3 variant I148M, which is strongly associated with risk for and the progression of NASH, on the histological and cardiometabolic response to lanifibranor. In a retrospective analysis of Inventiva’s NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH, histological and circulating marker responses were evaluated by PNPLA3 genotype subgroup. The response to lanifibranor treatment on the histological endpoints was similar across the three PNPLA3 genotype (II/IM/MM) despite a higher activity score measured at baseline in patients with MM genotype.
In addition, the improvement of cardiometabolic health markers (glycemic control, insulin, HOMA-IR, HsCRP, CAP and adiponectin) following treatment with lanifibranor was similar in the three PNPLA3 genotypes. These results demonstrate that the efficacy of lanifibranor on both liver histology and markers of cardiometabolic health appears to be independent of PNPLA3 status.
The details of the presentation are as follows:
Abstracts:
| Abstract title: | “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” |
| Poster number: | 5035-C |
| Presentation type: | Late breaker poster presentation |
| Authors: | Diana Barb, Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Fernando Bril, Philippe Huot-Marchand, Lucile Dzen, Jean-Louis Junien, Pierre Broqua, Andrea Ortiz Rocha, Romina Lomonaco, Michael P Cooreman, Ken Cusi |
| Date: | November 12, 2023 – 1:00pm - 2:00pm (EST) |
| Abstract title: | “Lanifibranor-associated adiponectin increase correlates with improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis” |
| Poster number: | 2458-C |
| Presentation type: | Poster presentation |
| Authors: | Michael P. Cooreman, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Sven Francque |
| Date: | November 11, 2023 – 8:30am - 5:00pm (EST) |
| Abstract title: | “Lanifibranor improves liver histology and markers of cardiometabolic health in patients with NASH independent of PNPLA3 genotype: a retrospective analysis of the native study” |
| Poster number: | 2457-C |
| Presentation type: | Poster presentation |
| Authors: | Louis Griffel, Sven Francque, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Michael P. Cooreman |
| Date: | November 11, 2023 – 8:30am - 5:00pm (EST) |
Inventiva will also be present with a booth: we are inviting you to visit us from Saturday November 11 through Monday November 13, 2023, during exhibition hall opening hours at booth #D3027 located in the exhibition hall of the conference center.
About lanifibranor
Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (PPAR) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of NASH. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and pre-clinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of NASH.
About Inventiva
Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with NASH (also known as metabolic dysfunction-associated steatohepatitis (MASH)), mucopolysaccharidoses (“MPS”) and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline.
Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with NASH, a common and progressive chronic liver disease for which there are currently no approved therapies.
Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting an oncology development candidate for its Hippo signaling pathway program.
The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly-owned research and development facility.
Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com
Contacts
| Inventiva Pascaline Clerc EVP, Strategy and Corporate Affairs media@inventivapharma.com +1 240 620 9175 | Brunswick Group Tristan Roquet Montegon / Aude Lepreux / Matthieu Benoist Media relations inventiva@brunswickgroup.com +33 1 53 96 83 83 | Westwicke, an ICR Company Patricia L. Bank Investor relations patti.bank@westwicke.com +1 415 513-1284 |
Important Notice
This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, pre-clinical programs and clinical trials, including design, duration, timing, recruitment costs, screening and enrolment for those trials, including the ongoing NATiV3 Phase III clinical trial with lanifibranor in NASH and LEGEND Phase IIa clinial trial, clinical trial data releases and publications, the information, insights and impacts that may be gathered from clinical trials, the potential therapeutic benefits of Inventiva’s product candidates, including lanifibranor and Inventiva’s pipeline and preclinical and clinical development plans, future activities, expectations, plans, growth, potential revenues and prospects of Inventiva. 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There can be no guarantees with respect to pipeline product candidates that the clinical trial results will be available on their anticipated timeline, that future clinical trials will be initiated as anticipated, that product candidates will receive the necessary regulatory approvals on their expected timeline, or at all. Actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates, due to a number of factors, including that Inventiva is a clinical-stage company with no approved products and no historical product revenues, Inventiva has incurred significant losses since inception, Inventiva has a limited operating history and has never generated any revenue from product sales, Inventiva will require additional capital to finance its operations, in the absence of which, Inventiva may be required to significantly curtail, delay or discontinue one or more of its research or development programs or be unable to expand its operations or otherwise capitalize on its business opportunities and may be unable to continue as a going concern, Inventiva's future success is dependent on the successful clinical development, regulatory approval and subsequent commercialization of current and any future product candidates, preclinical studies or earlier clinical trials are not necessarily predictive of future results and the results of Inventiva's clinical trials may not support Inventiva's product candidate claims, Inventiva’s expectations with respect to the changes to the clinical development plan for lanifibranor for the treatment of NASH may not be realized and may not support the approval of a New Drug Application, Inventiva and its partners may encounter substantial delays in their clinical trials or fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities, the ability of Inventiva and its partners to recruit and retain patients in clinical studies, enrolment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside Inventiva's and its partners’ control, Inventiva's product candidates may cause adverse drug reactions or have other properties that could delay or prevent their regulatory approval, or limit their commercial potential, Inventiva faces substantial competition and Inventiva’s and its partners’ business, and preclinical studies and clinical development programs and timelines, its financial condition and results of operations could be materially and adversely affected by geopolitical events, such as the conflict between Russia and Ukraine and the Gaza and Israel related sanctions and related impacts and potential impacts on the initiation, enrolment and completion of Inventiva’s and its partners’ clinical trials on anticipated timelines, health epidemics, and macroeconomic conditions, including global inflation, interest rates, uncertain financial markets and disruptions in banking systems. Given these risks and uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.
Please refer to the Universal Registration Document for the year ended December 31, 2022 filed with the Autorité des Marchés Financiers on March 30, 2023, the Annual Report on Form 20-F for the year ended December 31, 2022 filed with the Securities and Exchange Commission on March 30, 2023 and the Company’s half-year report for the period ended June 30, 2023 for other risks and uncertainties affecting Inventiva, including those described from time to time under the caption “Risk Factors”. Other risks and uncertainties of which Inventiva is not currently aware may also affect its forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated.
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1 Inventiva-PR-Cusi-Lani-Topline-Results-EN-06132023.pdf (inventivapharma.com)
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