Inventiva Sa’s Contradictory Trial Timelines and Shifting Partnership Strategy Raise Red Flags

Date of Call: Mar 31, 2026

Guidance:

• Anticipate sharing top-line results of pivotal phase III trial (NATiV3) in Q4 2026.
• Cash runway extends to middle of Q1 2027 (or middle of Q3 2027 if tranche three warrants are fully exercised).
• Expect positive data from NATiV3 to support marketing authorization in the U.S. and Europe.

Business Commentary:

Pipeline and Resource Allocation:

• Inventiva completed enrollment for its global phase III clinical trial, NATiV3, in April 2025, marking a significant operational milestone.
• The company sold its global rights to odiparcil to Biosil, expecting up to $90 million in potential regulatory and commercial milestone payments, redirecting resources to focus entirely on lanifibranor and MASH.

Financial Position and Cash Runway:

• As of December 31, 2025, Inventiva held approximately EUR 231 million in combined cash equivalents and short-term deposits.
• The financial position was strengthened by two significant financing events: a tranche of structured financing in May generating EUR 108 million and a public offering in November generating EUR 139.4 million.

Regulatory and Commercial Preparedness:

• The company is advancing its regulatory and commercial readiness in anticipation of potential approval for lanifibranor, with a focus on strategic commercial execution and market research.
• Inventiva strengthened its leadership team with appointments in R&D, quality, and regulatory affairs to align with the opportunity's demands.

Clinical Trial Design and Endpoints:

• The pivotal phase III trial, NATiV3, is designed to confirm findings from the positive phase IIb trial, targeting a primary endpoint of fibrosis improvement and MASH resolution.
• The trial includes a diverse patient population with significant fibrosis and metabolic comorbidities, mirroring real-world patient scenarios to ensure clinically meaningful data.

Sentiment Analysis:

Overall Tone: Positive

• Andrew Obenshain stated: 'Inventiva enters 2026 well-funded, operationally focused, and ready for a consequential chapter in this company’s history.' and 'Our anticipated top-line readout in the fourth quarter of this year represents a genuine inflection point, not just for Inventiva, but for the millions of patients living with MASH.'

Q&A:

• Question from Seamus Fernandez (Guggenheim): Can you update us on how the performance of the trial has been in terms of dropouts? Can you help us understand how you’re thinking about the performance of the 800 versus the 1200 milligram dose? What you’re seeing in terms of the overall market interest and competition with Madrigal?
  Response: Dropout rate is well below the 30% threshold required for trial powering. The 800 mg dose may catch up to the 1200 mg dose over the longer 18-month trial, with potentially better tolerability. An 18% fibrosis improvement effect size is seen as the threshold for a competitive drug in the MASH market.

• Question from Dominic (Piper Sandler, on for Yasmeen Rahimi): What are the quality control protocols for analyzing biopsy samples? Any recent safety monitoring committee findings?
  Response: Quality control includes ensuring patient safety during biopsy, proper sample handling, and blinded review processes. No unusual safety findings to report; periodic safety monitoring committee meetings are held as required.

• Question from Ritu Baral (TD Cowen): What’s the effect size that the trial is powered for on the primary endpoint? How is the F3 diabetic population diagnosed and growing?
  Response: The trial is powered to over 90% for the composite endpoint of fibrosis improvement and MASH resolution, with a smaller expected effect size than the 18% seen in phase II. The F3 diabetic population is large and growing, representing about 55%-65% of patients in treatment.

• Question from Thomas Smith (Leerink Partners): What do you hope to learn from the F4 exploratory cohort in NATiV3 and how does it relate to planning for an outcome study?
  Response: The exploratory cohort will provide safety data, pharmacological activity in cirrhotic patients, and insight into disease progression, all of which will be valuable for designing a future outcome-driven trial.

• Question from Michael Yee (UBS): Does weight gain plateau in phase III, and could it decrease over time? How are regulators viewed on the fluid retention effect?
  Response: Weight gain from fluid retention appears to plateau, and could be blunted by concomitant medications like SGLT2 inhibitors. The FDA is aware of and comfortable with fluid retention as an on-target effect of PPAR gamma agonism, and no significant cardiac imbalances have been observed.

• Question from Jasmine (Barclays, on for Ellie Merle): What competitive data would be attractive in the diabetes overlap population, and how many type 2 diabetes patients have undiagnosed MASH?
  Response: An attractive profile would include an 18% fibrosis effect, HbA1c lowering, and metabolic benefits. Over half of the estimated 18 million undiagnosed MASH patients in the U.S. have diabetes.

• Question from Lucy Codrington (Jefferies): What does 'unstarted' mean for FDA accelerated approval, and is starting the confirmatory trial included in the cash runway?
  Response: Starting the confirmatory trial is included in the cash runway. 'Unstarted' means having the trial structurally in place and moving forward at the time of filing, with continued progress required during mid-cycle review.

• Question from Jayed (Stifel, on for Annabel Samimy): What is the impact of background GLP-1 use on lanifibranor effect size, and are you planning to use the newly FDA-qualified AIM-MASH tool?
  Response: Background GLP-1 use is expected to have minimal impact on treatment response. The PathAI tool is being evaluated for use in future trials but not in the current NATiV3.

• Question from Rami Katkhuda (LifeSci Capital): Can you remind us of lanifibranor’s effect in F2 vs. F3 patients from phase II and how that impacts NATiV3 expectations given the higher proportion of F3 patients?
  Response: The drug works equally well in F2 and F3 patients, with effect sizes remaining consistent. The higher proportion of F3 patients in NATiV3 aligns with the real-world patient population.

• Question from Anna Andre Kripa (Truist Securities): Do you expect an update to MASH guidelines this year, and what triggers access to the third tranche of warrants?
  Response: Guideline updates will come after data is available. Access to the third tranche requires a positive trial result, allowing warrant holders to purchase shares at €50.

• Question from Sheila Hernandez (Van Lanschot Kempen): Could you elaborate on your regulatory and commercial infrastructure and steps to act with speed post-data?
  Response: Regulatory and quality teams are fully staffed to prepare a strong filing. Commercial team is focused on strategic execution, with plans to staff up aggressively only after positive data.

Contradiction Point 1

Trial Powering Assumptions

Conflicting statements on the trial's power and effect size expectations.

What are your key priorities for the upcoming quarter? - Ritu Baral (TD Cowen)

2025Q4: The trial is powered to over 90% for the composite endpoint... with a smaller treatment effect than phase II but accounting for a higher placebo response. - Dr. Jason Campagna(CMO)

What is the effect size the trial is powered for on the primary endpoint and the expected placebo response? - Rami Katkhuda (LifeSci Capital)

2024Q4: The trial is powered at 90%. A cautious approach was used... but reducing the effect size by a few percentages. - Frédéric Cren(CFO)

Contradiction Point 2

Enrollment/Financing Confidence

Contradiction on the confidence level and timeline for completing patient enrollment and securing financing.

Lucy Codrington (Jefferies) - Lucy Codrington (Jefferies)

2025Q4: Confirmed starting the confirmatory trial is included in the cash runway (mid-Q3 2027). The key is obtaining... approval... requiring the confirmatory trial to be structurally in place... at the time of filing. - Dr. Jason Campagna(CMO)

How does "trial meaningfully underway" impact FDA accelerated approval and its inclusion in the cash runway? - Unidentified Analyst (Jefferies & Co.)

2024Q4: High confidence... reaching the target... is expected by the end of April. - Frédéric Cren(CFO)

Contradiction Point 3

Status and Timeline for Confirmatory Phase 3 Trial

Inconsistent statements about the trial's status and readiness for regulatory submission.

Lucy Codrington (Jefferies) - Lucy Codrington (Jefferies)

2025Q4: Confirmed starting the confirmatory trial is included in the cash runway (mid-Q3 2027). Accelerated approval is a review timing issue. The key is obtaining conditional approval under Subpart H, requiring the confirmatory trial to be structurally in place (protocol approved, CRO selected, sites open) at the time of filing... - Dr. Jason Campagna(CMO)

What does "trial meaningfully underway" mean for FDA accelerated approval, and is it included in the cash runway? - Seamus Fernandez (Guggenheim Securities)

2023Q4: The confirmatory Phase 3 trial (for full approval) is planned in patients with compensated cirrhosis. - Frederic Cren(CEO)

Contradiction Point 4

Strategy Regarding Partnerships and Commercialization

Shift from an open partnership strategy to a closed, self-commercialization focus.

Rami Katkhuda (LifeSci Capital) - Rami Katkhuda (LifeSci Capital)

2025Q4: Currently focused on self-commercialization; partnerships are not necessary given strong cash position and access to capital markets. - Andrew Obenshain(CEO)

"When will the MASH guidelines be updated and how will lanifibranor be included, and what triggers access to the third tranche of warrants and are you pursuing non-dilutive funding or partnerships?" - Rami Katkhuda (LifeSci Capital) - Follow-up

2023Q4: The strategy is to partner the U.S. and Europe together as a bundle, not separately. The preferred timing is post-Phase 3, once the company is confident in the data and ability to gain approval based on the NATiV3 results. - Frederic Cren(CEO)

Contradiction Point 5

Characterization of Phase 3 Trial's Patient Population

Contradiction over whether the Phase 3 trial includes patients with compensated cirrhosis (F4).

Thomas Smith (Leerink Partners) - Thomas Smith (Leerink Partners)

2025Q4: The exploratory cohort (approx. 75 patients) will provide safety data for lanifibranor in a sicker population... - Dr. Jason Campagna(CMO)

What insights do you expect from the exploratory F4 cohort in NATiV3 and how will they inform future outcome studies? - Seamus Fernandez (Guggenheim Securities)

2023Q4: The confirmatory Phase 3 trial (for full approval) is planned in patients with compensated cirrhosis. - Frederic Cren(CEO)