Inventiva H1 2026 Earnings Call: Complete Transcript

On Monday, Inventiva (NASDAQ: IVA ) discussed quarterly financial results during its earnings call. The full transcript is provided below. This content is powered APIs. 9 million in cash and equivalents as of June 30, 2026, and completed significant capital structure optimization.

The company is advancing its lead drug, lanafibranor, towards Phase 3 top-line results expected in Q4 2026 for NASH, with potential regulatory filings in 2027. Lanafibranor is designed to address both metabolic and hepatic drivers of MASH, with promising Phase 2b data showing significant improvements in fibrosis and MASH resolution. S. launch in 2028, with ongoing preparations for regulatory submissions.

The NATIVE3 trial is fully recruited, and the company is confident in the trial design, which includes sensitivity analyses for potential therapeutic drop-ins like GLP-1s and SGLT2 inhibitors. Full Transcript OPERATOR (Operator) Good day and thank you for standing by. Welcome to Inventiva's first half of 2026 financial results conference call. At this time all participants are in listen-only mode.

After the speaker's presentation, there will be a question-and-answer session. As a reminder, today's conference call is being recorded. I would now like to hand the call over to David Nikodem, Head of Investor Relations for Inventiva. Please go ahead.

D. — Head of Investor Relations & Special Projects Thank you. Good morning, good afternoon. Thank you for joining Inventiva's first half 2026 financial results and business update.

This morning we issued our press release reporting our full financial results for the first half of 2026. A replay of this webcast will be available in the Investor section of our website following the call. Before we begin, a quick reminder that the statements we make today, including during the Q&A, may include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements reflect our views only as of today and should not be relied upon at any later date.

Please refer to Slide 2 and to our filings with the SEC and the AMF for a discussion of the associated risks. Joining me today are Andrew Obenshain, our Chief Executive Officer, Dr. Jason Campagna, our Chief Medical Officer and President of R&D, and Axel Sven Malcomes, our Chief Financial Officer. Chris Benecki, our recently appointed Chief Operating Officer, will be joining us for the Q&A portion of the call.

With that, I'll turn the call over to Andrew. Andrew Obenshain, Chief Executive Officer Thank you, David, and welcome everyone. Today I'll start by providing an update on the company and our priorities. Jason will overview our lanafibranor development program.

Axel will walk through our first half of 2026 financial highlights and then we will open the call for Q&A. The first half of 2026 has been a defining period for Inventiva. We have stayed focused on our near-term objectives, advancing lanafibranor toward the Phase 3 top-line results readout in NASH expected in Q4 2026, preparing for regulatory filing, while building the organization to support a potential commercial launch. Let me start with why we believe in the potential of lanafibranor and why a potential new therapy for MASH is so important.

It comes down to three key elements: differentiation, late-stage validation, and market opportunity. Let's begin with differentiation. MASH is driven by both intrahepatic and extrahepatic processes and lanafibranor is designed to address both through a single once-daily oral therapy. In our NATIVE Phase 2b study, lanafibranor showed improvement across all key histological endpoints.

Next is validation. We designed the NATIVE3 Phase 3 trial to build on the foundation established in our positive Phase 2b study. We look forward to reporting top-line data in the fourth quarter of this year. And finally, market opportunity.

The market is being built in front of us. If lanafibranor is approved, we will enter an established therapeutic area with a market potential expected to exceed $15 billion by 2035. However, significant unmet need remains and this represents a meaningful opportunity for Inventiva to bring a potentially differentiated treatment option with lanafibranor to people diagnosed with MASH, if approved. Let me take each in turn and then lay out our priorities for the year ahead.

Let's start with differentiation, and it begins with understanding the biology of the disease. MASH is not simply a liver problem. It is the hepatic expression of a broader systemic metabolic dysfunction. As Slide 6 shows, the disease is driven by multiple interconnected pathways both outside and inside the liver.

These include insulin resistance, adipose dysfunction, and dyslipidemia on the extrahepatic side, and steatosis, inflammation, and fibrosis within the liver itself. That has clear implications for treatment. If the disease is driven by several processes at once, there is an opportunity for next-generation treatment to target more than just one driver. That is the unmet need we believe lanafibranor could address if approved.

Our aim is not only to target the liver; it is to modulate pathways across both the metabolic and hepatic components of the disease and bring a differentiated treatment option to patients with NASH. The differentiated mechanism of lanafibranor, modulating both pathways, is reflected in compelling clinical data in our Phase 2b study. After six months, lanafibranor delivered an 18% placebo-adjusted improvement in fibrosis, 26% MASH resolution, and 24% on the composite endpoint. Those results are the foundation for NATIVE3.

We are now testing the same approach in a larger, controlled Phase 3 population of patients with F2 and F3. That is what makes NATIVE3 so impactful. It was designed to confirm, at pivotal scale, the biology and activity we observed in our Phase 2b study, and we are pursuing this in a market with substantial and growing unmet need. Slide 8 shows there are an estimated 18 million Americans living with MASH, yet only 10% are diagnosed.

That is changing fast. As the treatment landscape has matured, diagnosis has increased up roughly 25% versus 2024 and that is translating into a larger population being actively identified and managed. Today approximately 374,000 patients with F2 or F3 disease are already in treatment or under the care of a physician. The picture is clear: a large prevalent patient population expanding rapidly as awareness and testing improve.

A compelling opportunity for lanafibranor, if approved. Turning to Slide 9 to see where lanafibranor may fit in the treatment paradigm, it helps to think about MASH in terms of two factors that are top of mind for physicians: the severity of fibrosis and the cardiometabolic factors that can influence the risk of disease progression. Put fibrosis on one axis and cardiometabolic risk on the other and four clinically distinct populations come into view. Start with the lower-right quadrant.

We have patients with F3 NASH and cardiometabolic risk, such as type 2 diabetes. This is a population with high unmet medical need where the mechanism of action of lanafibranor can be compelling in that it targets both the liver and the metabolic driver simultaneously. In our Phase 2b trial, lanafibranor demonstrated an 18% placebo-adjusted improvement in fibrosis at just 6 months. Similarly, in the lower left, although these patients have earlier-stage F2 fibrosis, their cardiometabolic risk factors can put them at risk for more rapid disease progression.

For these patients, physicians may also want to act urgently, and lanafibranor could potentially offer an opportunity to intervene earlier in the course of the disease, if approved. Moving to the top-right quadrant. By extension, lanafibranor could be well positioned in patients with F3 fibrosis without significant cardiometabolic risk. Here, that fibrosis itself is the primary concern and lanafibranor may have the potential to address the underlying liver disease before progressing.

Taken together, these three quadrants represent a large population with significant unmet need and, if approved, we believe lanafibranor has the potential to play an important role in addressing the needs of these patients. With that overview of why we believe in the potential of lanafibranor, let me lay out three key priorities we are focused on to unlock new opportunities for patients with MASH. First, the NATIVE3 trial. We remain on track to report top-line data in the fourth quarter of 2026.

Earlier this month the last patient completed their final 72-week visit. The main cohort enrolled 1,009 participants, all with biopsy-confirmed non-cirrhotic NASH and F2 or F3 fibrosis. Second, regulatory readiness. We are advancing our preparations now to support a potential NDA submission with the FDA in the first half of 2027, positioning us to move quickly into regulatory interactions if the top-line data readout is positive.

And third, commercial readiness. We are building a commercial organization with the depth and breadth of experience with best-in-class products to be ready for the potential launch in 2028. We believe we are moving forward with lanafibranor from a position of strength and with the potential for a differentiated profile, a late-stage validation opportunity with NATIVE3, and a significant market opportunity, if approved. I'm truly energized by the potential to make a real difference for millions of people living with this serious disease.

With that, let me hand it over to Jason to take you through the science behind lanafibranor and our clinical program. Jason Campagna (Chief Medical Officer and President of R&D) Jason, thank you Andrew, and greetings everyone. I'll spend a few minutes on four aspects of our lanifibranor development program in MASH: one, how lanifibranor is designed to address the spectrum of disease; two, what we've observed in the positive NATIVE Phase IIb clinical trial; third, how our NATIVE 3 Phase 3 trial is built to confirm that Phase 2 study; and lastly, where we're thinking of taking the program next. Let me start with the molecule.

Slide 11 shows lanifibranor as a potential novel new chemical entity, structurally and mechanistically distinct from both fibrates and thiazolidinediones, and recognized by the FDA with both Breakthrough Therapy and Fast Track designations. It was informed by decades of research on PPAR biology and the development learnings of prior compounds, and it rests on one critical concept: balance. Lanifibranor engages all three PPAR isoforms—alpha, delta, and gamma—in a low-potency, balanced manner such that no single receptor biology dominates. It was also engineered to have only partial agonism of the PPAR gamma receptor.

The combination of this balanced, low-potency pharmacology and partial PPAR gamma agonism are the keys to our differentiation. It is what lets lanifibranor modulate, in harmony, the metabolic, inflammatory, and antifibrotic pathways of MASH combined, rather than forcing one mechanism or receptor at the expense of the others. The two charts on the right illustrate this design. Pharmacology: on the first panel we see the balanced activation profile and the approximately 80% gamma activation with lanifibranor, while on the far right, the cofactor recruitment fingerprint that sets lanifibranor apart from full TZD gamma agonists.

The result is a once-daily oral therapy intended to deliver a physiologic balance between achieving pan-PPAR activation while avoiding any one receptor dominance. Moving now to our Phase 2b NATIVE clinical trial data, Andrew shared our overall histology efficacy data, but that included patients with lower-risk, earlier F1 disease. When we exclude these patients with earlier-stage disease, we continue to see robust effects across all three histologic endpoints, showing that the drug worked equally well in both early and later-stage disease—and these results were achieved after only six months of treatment.

Looking more closely at the data for the composite endpoint, you can see that treated patients were roughly eight times more likely than placebo patients to achieve dual histologic improvement in the type 2 diabetes subgroup. This tells us that spontaneous regression of the disease was uncommon and that the treatment effect of lanifibranor was strong. Together with the early- and late-stage data, these results underscore the potential of lanifibranor to perform across the disease spectrum, including in patients with the most urgent disease. Let me now turn to safety and tolerability.

On slide 13, we show the most frequently reported adverse events by investigators in our NATIVE Phase 2b clinical trial. Lanifibranor was generally well tolerated across the totality of our Phase II program, but the adverse event profile in NATIVE 2b tracked closely with the underlying scientific design of lanifibranor. Consistent with our preclinical toxicology data, we saw minimal classic alpha or delta toxicities. On gamma-related effects—weight gain, edema, and hemoglobin decline—these were present but attenuated relative to the full TZD-class gamma agonists.

The weight gain we observed in patients treated with lanifibranor is biphasic. Early on, the partial PPAR gamma activation acts on a sodium channel in the kidney, resulting in sodium and water retention, while in a later phase that same partial PPAR gamma activation drives improved insulin sensitization and adipose remodeling, reflected in the rise in adiponectin, which is itself tied to histologic efficacy. Both phases are consistent with the known pharmacology of PPAR gamma engagement. Based on our LEGEND study, these gamma-related effects were mitigated by adding an SGLT2 inhibitor, empagliflozin, while also preserving the metabolic benefit of lanifibranor.

This brings me to NATIVE 3. This is a Phase 3 global registrational trial, and it was deliberately designed to build on our Phase 2b: the same two doses, a similar patient population, and a primary composite endpoint of NASH resolution and at least one-stage fibrosis improvement in the same patient. Secondary endpoints include MASH resolution and fibrosis improvement of one stage or more. The trial enrolled approximately 1,400 patients across two cohorts: a placebo-controlled, randomized portion consisting of 1,009 patients with biopsy-confirmed F2 or F3 MASH, and an exploratory cohort of 410 patients with predominantly F1 or F4 disease.

Both cohorts were treated for 72 weeks. All patients who completed the trial are eligible for an active treatment extension to support a longer-term view of the safety and tolerability of lanifibranor. The main cohort will serve as the basis for global marketing registration, and the primary endpoint is powered at 90% on deliberately conservative assumptions, with a higher placebo response and a lower treatment effect than we observed in the Phase 2b NATIVE trial. It is stratified by fibrosis stage and diabetes status.

This main cohort also reflects the real world. The NATIVE 3 population is a contemporary MASH population with higher diabetes prevalence, more advanced fibrosis, and more use of GLP-1s and SGLT2 inhibitors compared to our Phase 2b trial. As Andrew noted, it has been fully recruited, and the last patient visit for the Week 72 portion of the trial was completed earlier this month, and as Andrew shared, we are excited for top-line data in the fourth quarter of this year. Subject to positive Phase 3 results, we intend to file for accelerated approval with the FDA and conditional approval with the EMA.

We will also be initiating a confirmatory clinical outcomes trial designed to evaluate the effects of lanifibranor in patients with more advanced disease. That's worth pause on, because everything I've described targets the core pathophysiology of MASH, but that same pathophysiology also underlies compensated advanced chronic liver disease, or cACLD, due to MASH. These are patients who have progressed to advanced fibrosis or early histologic cirrhosis, yet they remain clinically compensated but have evidence of clinically significant portal hypertension, the primary driver of adverse liver-related outcomes.

This subgroup of patients has no approved disease-modifying therapy. It is a significant area of high unmet need in the disease. We believe that lanifibranor is mechanistically compelling in cACLD because the same PPAR isoforms that drive the histologic and metabolic effect in the non-cirrhotic NASH population also act on the vascular biology that underpins portal hypertension in this more advanced group. And in cACLD, portal pressure matters because, as the disease advances, portal hypertension—and not fibrosis alone—becomes a key driver of these hard clinical outcomes, including bleeding, ascites, and liver transplant.

We recently published an analysis of our Phase 2b NATIVE trial showing a correlation in patient biopsies with vascular remodeling we've observed preclinically. These are exploratory analyses, but they add to our conviction to pursue further advanced disease states in MASH. With that, I'll hand it over to Axel. D.

— Head of Investor Relations & Special Projects And I will pick up for Axel here. Axel Sven Malcomes (Chief Financial Officer) Yeah, I'm sorry, I lost my text. Please go ahead. D.

— Head of Investor Relations & Special Projects Yep. So, this morning we issued our press release reporting our full financial results for the first half of 2026. Axel will focus on the key financial highlights and our financial position as we approach the NATIVE 3 top-line readout. Axel, are you ready to take over?

Okay.