Inventiva S.A.

Good afternoon, ladies and gentlemen, and thank you for standing by. Welcome to today's Inventiva's full year 2020 results presentation. At this time, all participants are in listen-only mode. Presentation will be followed by a question and answer session, at which time, if you'd like to ask your questions on the phone, please press star and one and wait for your name to be introduced. I must also advise you, meeting is being recorded today, on Friday, the 5th of March 2021. And may I hand the meeting over to your host today, Frederick Crenn, Chairman, CEO and co-founder of Inventiva. Please, go ahead, sir.

Thank you, operator, and welcome everybody. Good morning and good afternoon. And I'm very pleased to launch this 2020 financial webcast. As you know, 2020 has been a fantastic year for inventiva. I'll be doing some, with my colleagues, some forward-looking statements, so please look at the regulatory documentation that is available on our website. I'll be sharing the floor today with Pierre, our CFO and co-founder with me, with Michael Korman, our new CMO, he's been dialing from the U.S., and with Jean that will give us an overview of the figures. So let me go immediately in the core of the presentation and just give you some highlights of this fantastic 2020. So if we start with Lani, our lead program in NASH, I don't want to spend too much time detailing the fantastic achievements that have been done in 2020. Here we go through the results of native that led us to obtain breakthrough designation. and two very positive meetings with both FDA and MEA. And Michael will run you through the Native 3 trial that is starting in a few weeks. I would nevertheless like to point out a very important view that we got from the FDA very recently. It's a couple of days old. And that concerns the fact that the FDA has confirmed that the toxicology package is complete and acceptable to support NDA filing. This is another step in de-arresting the lanifibrinor and another step towards the potential commercialization of the product in NASH. If we turn to the parcel in MPS, as you know, we are truly fond of this program, of the clinical data we published late 2019. We also obtained in 2020 fast-track designation from FDA. But you've been following us and you know that we have decided to focus our resources, both financially and human, in NASH and decided to look for a new home for the parcel to continue the program. This evaluation of the strategic option is currently ongoing, and we are confident we'll be able to update all of you in 2021 about the future of this compound. Looking to ABVV 157, actually I should say it's a derogant. This is a new name that has been awarded by the We are extremely excited by this program. We have seen regularly AbbVie giving updates at JPM or during their and it's great to see that when they speak about early promising compounds, they often mention sedirogan. So that's great and we're looking to obtain the result, the clinical proof of concept in Q2 2021, a slight delay compared to Q1 as previously announced due to COVID situation. On the news, of course, you know that we are actively preparing the launch of the phase three of Lani in Nash. And to do that, we have opened the U.S. subsidiary of Inventiva. It's open and live, and we're building our team there. This is one of the first tasks of Michael, who has joined us since a couple of months ago, and he's actively building the team. We've also reinforced our KOL network and we're extremely pleased of the collaboration we've established with Dr. Sagnal who has been instrumental in our discussion with the FDA. Of course, financials also, we've been extremely busy with Jean and the rest of the team to reinforce our position. Several capital increases, also one agreement with the French government for 10 million, and especially the IPO in July on the back of the positive data. Now we have a comfortable and strong cash position, ensuring a cash runway through Q4 2022. Let me now turn to Lani and to Pierre, who will go through the product, and Michael will then present you the native phase 3.

Thank you, Frédéric. So, as you all know, Lani Fibonor is the only pantyparagonist in clinical development for the indication treatment of NASH and improvement of liver fibrosis. You know that it has an unprecedented Chemical Structure and Unprecedented Pharmacological Profile. It's pan-PPAR agonist with moderate and well-balanced activity across the three PPAR isoforms, not a TZD and not a fibrate. Recently, a few months ago, we obtained breakthrough therapy and fast track designations that was granted by FDA. Can we turn on the next slide? So preclinical investigations. have shown that most, if not all, of the pathological features of NASH can be addressed by laniflubinol through activation of several PPAR isoforms. So, for example, the PPAR delta and gamma activation leads to a strong anti-fibotic activity, The three isoforms are involved in the inhibition of inflammation and ballooning induced by lanifibrinol, while the alpha and gamma isoforms are involved in the reduction of anti-hepatic vascular resistance and portal pressure, which was observed in animal models of cirrhosis, and the data have been published recently. Next slide. So in non-clinical studies with lanifibrinol, A favorable tolerability profile was observed. This profile differentiated from what was previously reported by single or dual PPAR agonists from different chemical classes. And as mentioned by Frederic, it's important to note today that recently FDA confirmed that this non-clinical tox package is complete and many more. Next slide, please. So, following the successful outcome of the native Phase IIb trial with Lani-Fubinor in NASH, we have been this last month very busy discussing with the regulatory authorities, FD&EMA, to finalize the Phase III design. and Michael Korman, our CMO, will present the details and the key milestones of this study. To complete the clinical development plan of lanifluvonor in NASH, and besides the study in collaboration with Professor Cusi, evaluating the effect of lanifluvonor on liver insulin resistance in diabetic patients with NAFLD, we are also working on the preparation of additional profiling studies evaluating, for example, the potential of laniflubinol in NASH-compensated cirrhosis on the back of these positive clinical findings. And we also are working on investigating the potential of laniflubinol to be used in combination with other therapies to further strengthen its value proposition. Next slide. So before going into the details of the Phase III trial design, let me recap on the outcome of the Phase IIb native trial. As you all know, this study investigated the efficacy and safety of Lamifibonor 800 and 1200 milligrams once daily in non-serotic NASH patients. Next slide, please. In the ITT population, all histological endpoints were met. The high dose had a significant effect on improvement of fibrosis by at least one stage and no worsening of NASH, and both doses had a significant effect on resolution of NASH and no worsening of fibrosis, as well as on the composite endpoint of resolution of NASH and improvement in fibrosis where a responder is defined as a patient showing both NASH resolution and improvement in fibrosis. And for this composite endpoint, compared to placebo, we observed three and four times more responders in the low and high-dose group respectively. Next slide. and if we actually focus on the F2, F3 subpopulation which represented 76% of the patients in native 2 and will be the target population investigated in native 3, we can see that the overall picture is similar with a statistically significant effect of the two doses on national solution and no worsening of fibrosis as well as on the composite endpoint and the statistical significant effect of the high dose on the improvement of fibrosis with no worsening of NASH. So consistent with these histological data and the mechanism of action of planifubinor, we also observed an effect on several circulating biomarkers that are relevant of NASH pathophysiology as exemplified here. on fibrosis, apoptosis, and inflammation. The native biomarker database actually includes data on more than 80 circulating biomarkers, and this database will be further analyzed by Professor Jérôme Bourcier and his team in order to identify, one, several or a composite score of biomarkers linked to Lani-Febrano histological response, and these to be considered for use as the surrogate efficacy endpoint reasonably likely to predict histological improvement in the commercial setting. The selected biomarkers or the biomarker composite score would then be validated during the upcoming NATIVE-3 trial. Next slide, please. So additional data from a NATIVE-3 trial on metabolic parameters of patients with NASH are following. So first we see here the effect of Lelifrubinol on liver enzymes. As you recall, we had quite a quick normalization of ALTST and gamma-GT that was sustained all over the study duration. Next slide. Consistent with the PPAR alpha and delta activation We also observed a positive effect on the lipid profile with an increase in HDL cholesterol, which achieved maximal effect already at week four, as well as a sustained decrease of triglycerides. And there were no changes at all in the LDL cholesterol in those patients. Regarding glycemic control, so this is in diabetic patients. Laniflubinol further improved glycemic control with a decrease of glycated hemoglobin by minus 0.5%. That was already achieved by week 14 post-treatment initiation. And this, of course, is a consequence of improved insulin sensitivity by Laniflubinol. Next slide. So in terms of safety, Laniflubinol continues to show a favorable safety profile. with dropouts due to AE well-balanced between the three arms. There was a modest body weight increase, which is a consequence of insulin sensitization, and I'll give you more details on that in the forthcoming slides. And there were two adverse events, peripheral edema, that were considered drug-related in each Lenifribinol dose group.