Good day and thank you for standing by. Welcome to Inventiva’s 2021 Full Year Results Presentation. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions] Right now, I turn the conference over to your first speaker today, Frédéric Cren. Please go ahead. Frédéric Cren: Thank you and welcome everybody to the full year financial results presentation. As traditionally, we’d say I will share the floor with Pierre, our CSO will go over lanifibranor; Michael, our CMO also will present the clinical studies of Phase II done by Professor Cusi and the LEGEND study, while Pierre will cover an update on the Phase III. And then we’ll end up with Jean, our CFO, who will give more granularity on the seeker [phonetic]. So before we go into the details of the clinical update, I just would like to provide some of the key highlights of 2021 which I think has been, when you look at everything that has been achieved, quite successful. So if we start with lani, so we had committed to start the NATiV3 Phase III pivotal study, which we did and on top of that, we also announced the design of the LEGEND study, our combination study between lani and SGLT2 inhibitor empagliflozin. And this morning, you’ve seen that we’ve received positive feedback from FDA and the IND application has been accepted by the diabetes division. The interaction with FDA, I would say, overall, during the year has been very positive. So my lights are certainly the fact that the past drug which we had secured for patients with F2-F3 has been extended by FDA to cover patient with compensated cirrhosis. We’re also extremely pleased by confirmation, the feedback, we got from FDA concerning the…

Okay, thank you, Frédéric. So we’re now moving on Page 10. So as you know, lanifibranor is a pan-PPAR agonist in clinical development Phase III for the indication, treatment of NASH and improvement in liver fibrosis. It has unprecedented structure and pharmacological profile. It’s a pan-PPAR agonist with moderate and well-balanced activity across the three PPAR isoforms. It’s not a thiazolidinedione and it’s not a fibrate. You’re very much aware about the number of pre-clinical investigations that we have performed and showing that most, if not all, of the pathological features of NASH can be addressed by lanifibranor through the activation of several PPAR isoforms, for example, the delta and the gamma activation, we think is really important and leads to the strong anti-fibrosis activity of the compound, whereas the three isoforms are involved in the inhibition of inflammation and ballooning. And the potential of lanifibranor to address most, if not all, pathological features in NASH has been, as you know, validated in the NATiV3 Phase IIb trial in non-psoriatic NASH patients and the results of this study actually supported breakthrough therapy designation by FDA, which came on top of the Fast Track designation that was already granted for lanifibranor. From a safety point of view, as you know, the non-clinical tox package, which actually included long-term studies, up to two years, showed that lanifibranor had a good safety profile and FDA confirmed that this tox package is complete and acceptable to support the filing of a New Drug Application, NDA. Lanifibranor in the clinic has also favorable to the reliability profile, evidence as of today now in close to 500 patients or healthy volunteers. So importantly, this year we have completed a thorough QT/QTc study, which is a standard component of all clinical development programs for any new therapeutic…

Thank you, Pierre. So I will cover two studies, which further support and profile lanifibranor with regard to its efficacy in patients with NASH and also patients with type 2 diabetes. First study on slide number 19 is a study in patients who have NASH and NAFLD and type 2 diabetes and this is really a study to further understand the mechanisms how lanifibranor works at a pan-PPAR agonist on several aspects of these metabolic diseases. So, the primary efficacy endpoint is a reduction in intrahepatic triglyceride accumulation. So, I think that but also we look quite in depth in how this is associated with changes in adipose tissue and insulin resistance in the main organs, fat tissue, liver, and muscle, which are all affected by metabolic diseases and also to look at a broader picture of how the cardiometabolic risk profile, so the marks of cardio metabolic health in patients with NAFLD and type 2 diabetes are beneficially affected by lanifibranor. As a background, non-alcoholic fatty liver disease on NASH and type 2 diabetes have a common underlying disease biology and so, in many, in high percentage these diseases overlap, 70% is actually on the low estimate. The more progress these diseases become, the more frequently you find that they coincide. They occur together and it has to do with the fact that diabetes -- patients have diabetes, NASH is more severe and vice versa, there is an interaction between the two conditions. So in diabetes itself, it becomes more difficult to control and patients with NASH need more medication, substantial proportion of these patients will have a more severe form of NAFLD with death of hepatocyte, which is described as ballooning, inflammation of the liver, and the progression of fibrosis towards cirrhosis, so more severe and progresses more…

Thank you, Michael. So let’s indeed switch gear for cedirogant. So can we be on page 29, please. So, as you probably know, cedirogant is an oral, once daily administered ROR gamma inverse agonist which is currently investigated in the Phase IIb clinical trial for the treatment of moderate to severe psoriasis. And this decision came out from, say, a successful Phase Ib study in patients with moderate to severe psoriasis. Cedirogant was discovered jointly by Inventiva and AbbVie and cedirogant royalties really have the potential to be an important source of revenues for Inventiva. Indeed, if you consider the success of anti-IL17 or anti-IL23 biologics in the treatment of psoriasis, which is validating actually this IL23-IL17 pathway as an important target for therapy, then you may see that there is quite a significant market opportunity for an overall an efficacious treatment acting on ROR gamma in psoriasis, but there is also a potential market opportunity for this approach in other immunology indications where IL-17 is relevant. Next slide please. So why is the IL23-IL17 pathways so relevant in psoriasis. Actually one of the primary drivers of the inflammatory response in psoriasis is IL-17, which is secreted from Th17 cells. IL-17 regulates the proliferation of keratinocytes and down regulates their differentiation. It also induces keratinocytes to secrete chemokine that drive the influx of immune cells including neutrophils and dendritic cells. ROR gamma is a nuclear receptor, which controls Th17 cell differentiation and effector function, regulating the transcription of IL-17A and IL-17F and blocking ROR gamma actually prevents Th17 differentiation and in a bit IL-17 production. Next slide please. And this is actually illustrated in one of our publication exemplified here; so, for example, if we consider A-9758, which is one of the early POR gamma inverse agonist that we discovered…

Good afternoon and good morning. So we will review the financial performance in two slides. First of all, the big picture of the shareholder base, which is stable, and has even been consolidated, thanks to the ATM of 32 million US dollars, so embarking existing shareholders plus opening to new comer in the shoulder base. So the market cap is at $450 million. The performance on the market was quite positive in 2021, although, as all the business sectors, and biotechs in particular, we are suffering from the Ukrainian crisis. In terms of cash, it’s quite easy to remember the figures, we are close to 100 million, if we take into consideration the 4 million Euros milestones received in January from AbbVie. And our estimate for the cash runway is one year from now. And next slide, perfect thanks. So the figures are quite easy to read. They are in continuity of what were discussed for the H1 financial performance. The revenues are made up of the milestone from AbbVie, it is 4.2 million. The key information for us is the R&D expense, which has doubled in ‘21 compared to 2020 with 48.4 – 48.5 million. The G&A -- of course, it’s technically related to what has been explained in the activity of clinical development and on our assets, in particular on lanifibranor. The G&A, as expected, increased by 31%. It was fully expected. It is the first year for Inventiva, complete year with the dual listing status. So no surprise on this line, it is under control. And cash wise, as I said, we’re close to 100, exactly 95.4 million and top of which we can consider the 4 million received in January, so it gives us, as I said, one year of cash to operate. And the way…

[Operator Instructions] Your first question is from the line of Lucy Codrington from Jefferies. Please go ahead.

Hi, there. Thanks for taking my questions. Just a few please. Firstly, on the cash runway, Jean, can I confirm, does that include the costs for the LEGEND trial? And I’m assuming, it doesn’t include any other potential milestones from AbbVie or other things from other parcel. And secondly, and apologies if I’ve missed it, regarding the Phase III recruitment, is that progressing as planned? I noticed on the slides that it looked like Russia and Ukraine account for about 22 sites, which is about half of the EU sites currently active, how many of those 22 sites were active and what drives confidence that there is -- this won’t lead to a delay in the data? And then just finally, on the milestones remaining from AbbVie, I believe it was 35 million and we’ve had two, so am I right in thinking there’s 27.5 million Euro is left for those milestones? Thank you. Frédéric Cren: Thank you, Lucia. For the cash runway, maybe Jean you want address.

To your question about LEGEND, the budget is definitely taking into consideration this additional study. It’s clear. Considering the milestones from AbbVie, there are no milestones planned in ‘22, according to the development plan. We may hope that in ‘23, if they are good news, we could have an additional milestone, as per the contract. The second question – Frédéric Cren: It was on the remaining milestones from AbbVie. I don’t have that one hand, we can get back to you on that.

We can come back to you. It will be specified in the filing, in the URD and the 20-F that will be filed the tentatively next Friday. But if it’s not written down in this document, but I think is it is documented, we you can call back to us. Frédéric Cren: Yeah. But once again, what is important, of course, it is nice and always nice to receive but what really makes the value of this contract are the royalties, which are we view them as very meaningful. And the double digit level is triggered at the sales level where I am personally very confident this program will reach. Then to your question about the Ukrainian and Russian site, so we have -- we were planning to open 10 sites in Ukraine. So Ukraine is one of – it is part of one of the 11 countries that are currently open. And we had three sites that had started screening patient, the other seven were not open. And as you can imagine, these 10 sites all activities have been paused. Given the situation, I would say that we have very limited hope that activity will we resume there. The other 12 sites are in Russia, Russia is not a country that is open yet. So we -- regulatory filing are still going, so no impact I would say on the current screening activity for Russia. And overall, so we have 22 sites that we need to recover, so if you look at our various presentation, you will know that we have increased the number of target sites. We are now targeting 350 or above. We were -- I think when we started this trial looking at 250 and we have increased that. For example, as Pierre mentioned, we recently contracted with Summit [phonetic], which is specialized in recruitment in NASH, very efficient organization, which sites mostly in US but also in Europe and so that also will contribute to reduce the impact of the situation. Of course, in addition to that, we are working with ICON to see if we can find the additional sites.

Thank you very much.

Thank you. The next question is from the line of Jeroen Van den Bossche from KBC Securities. Please go ahead.

Yeah, thank you, and congratulations on yet another great year, definitely with lanifibranor. Building on maybe the question from my company, really quick a first question. Looking at empagliflozin, the data today, as it stands, is that based only on existing data or is there currently also other information that you’ve been used preclinical data to build the LEGEND trial? And then maybe going further, how are you looking at the future of lani and cedirogant and Odiparcil? Are you still open to potential other collaboration building the market together with other organizations or are you really focusing on bringing it to market yourself? Frédéric Cren: Okay, thank you, Jeroen. So, maybe for the empa rationale and data available in odi, Pierre or Michael, you want to take this question?

Yeah, I can -- I think we can refer to Michael because the rationale is very much coming out of a number of clinical trials, where empa or other SGLT2 inhibitor were given on top of patients being treated by pioglitazone, for example, and where you would see there a decrease in body weight. So I know, Michael, if you want to elaborate on that.

Well, just you know, that this summarizes itself, yeah, but the mechanism of action of these compounds is well known. And that’s true for lanifibranor, it is pan-PPAR agonist and it’s true for empagliflozin as an NASH SGLT2 inhibitor and the efficacy in humans is also well known. Empagliflozin has been approved for a while and there are many data on patient in diabetes and in cardiology. So, that provides a strong rationale for the combination right, so we do not need for this purposed, non-clinical data.

So if I understand this correctly, there is, in your view, enough, let’s say, circumstantial data through which you don’t expect any combinational use of the drug.

Correct. Well, empagliflozin is approved anyway and so, in patients with metabolic immune diseases, which includes atherosclerosis in diabetes and so on, these patients have multiple drugs and combinations automatically the case. Many patients have statins for example. So, this is not an unusual combination. We are actually studying it in for the purposes that explained to show that such a combination can have additional benefits on the efficacy readouts in NASH and type 2 diabetes and as a weight management plan for those patients who may need it. But there is no need to look at the support, if you wish, not in clinical data in order to have a strong rationale. And specifically for pioglitazone, there have been four large studies published that were conducted in basically every -- globally combining pioglitazone with all four major SGLT2 inhibitors on the markets and the findings are very consistent.

Sorry. So in these indications, would it be open to the idea to market them by yourself or in combination with other partners or how do you see that going forward?

Right now we are moving – Frédéric, you want to continue or -- Frédéric Cren: Yeah, yeah, on the [indiscernible] to answer the second part of your question, so, for lani, we view it as a tremendous opportunity for big pharma and NASH is certainly a very large market, but you need the muscle, the experience, the commercial capabilities of big pharma. So, our objective is to find a partner, we believe that the asset has great value, great chance to make it to the finish line. And we are open to find a partner, so most likely, we’ll be in a better position once we have the Phase III data but of course, if somebody knocks on the door before, we are certainly open to discuss. For the other product, the easy one is the cedirogant, so everything is in the end of AbbVie, they decided to start developing in psoriasis, they can decide to look at the other indication, but that’s clearly on their end and they are in charge of fully funding the development as well as the commercialization cost. And then the last one is odiparcil, there we have not changed our strategy. We were not -- we do not have the capabilities to develop NASH lani in NASH, and Odiparcil in MPS VI in parallel. So, we remain committed to find an opportunity or new home because we believe the patient with MPS VI deserve to have a new treatment and Odiparcil could be this new form treatment that they are looking.

Okay. Clear. Thank you.

Thank you. The next question is from the line of Jean-Jacques Le Fur from Bryan, Garnier. Please go ahead

Yeah, good afternoon and congrats again for this good year -- very strong year. Three question if I may. The first one is on -- hello, can you hear me? Frédéric Cren: Yes, yes, perfectly. Go ahead.

Hello. Frédéric Cren: Yes, we can hear you.

Can you hear me?

Yes.

Okay, so sorry. So, okay, great. First on the LEGEND trial, could you remind us why you have chosen the lani 800 milligram and not the 1200, I think the 800 milligram was not the best during NATiV3 trial, especially regarding efficacy. The second question is, you well highlighted that you are quite busy with lani but could we -- can we have an update on the -- any update, for example, program or do you have other products in the pipeline which may move forward in the next few months, for example, or this year, for which we may have some news, even if they are preclinical or very early stage. And the last one is back to the envelope calculation, is that -- since you have cash runway until -- for one year, that means you are expected to spend about 100 million this year. So what are the main drivers for the significant increase compared to last year? Is it mainly the Phase III for lani, the addition of LEGEND, what are the key drivers there? Thank you. Frédéric Cren: Okay. Thank you. Maybe Michael you can take the LEGEND. Pierre can go over emp and Jean will talk about the cash.

We’ve just lost Michael’s line from the call. We are just going to try and reconnect him. Frédéric Cren: Okay, very good. So, maybe Pierre, can you cover emp.

Yeah, sure. I think I can cover partly lani 800 milligram and also the choice was basically made on the fact that the -- as you seen, heard Michael, the primary endpoint is HbA1c 800 milligram is actually a dose that is producing already a maximum efficacy. On HbA1c, there is no difference between 800, 1200 milligram and then this is I think the major reason why this dose was chosen in this study, but Michael can elaborate maybe more once he’s reconnected.

I have reconnected.

Okay. Do you want to commend, Michael?

Sorry, I was reconnected briefly but it’s true that if you look at histology and the fibrosis qualification of histology or staging or specifically 1200 milligram is better than 800 milligram after six months, which is actually a very short time frame to evaluate fibrosis. But on many other markets, there was two doses, the two doses were actually pretty equally potent with regard to efficacy, specifically on metabolic markers. And since fibrosis is driven by metabolic abnormalities and inflammation, it is actually an expectation and if you treat longer, both doses maybe compatible. We don’t know that, of course, NATiV3 will tell us that but that’s also a main reason why we kept two doses in NATiV3, and why we chose 800 milligram in LEGEND because in that study, we don’t look at fibrosis histologically, we look manly at metabolic immune markers, and we expect an additive effect from the combination therapy. So, these are the main reasons why we chose the 800 milligrams for LEGEND.

And for emp, so we have identified lead compounds, couple of lead compounds that we are now progressing in vivo in models of a hepatic cancer and renal cancer, why because we have seen quite interesting and potent [indiscernible] effects in vitro in a number of renal cancer cell lines, and a couple of HCC or liver cancer cell lines, plus these are products that are quite well distributed to the liver and the kidney. So we are now starting to profile those compounds in animal models of hepatic cancer, HCC, and renal cancer and we’ll keep you posted on that. Frédéric Cren: The last question of the cash, yeah, I mean, I think everything is mostly driven by NATiV3.

Yes definitely. We finished 2020 with a slow H2 after the result of the Phase II. So, in ‘21 the increases 80%, 90% due to NATiV3 to the preparation and launch of the studies and we have also -- tripled the cost of CROs and CDMOs in ‘21 and we also consolidated the development and pharma team, pharmacovigilance regulatory team, to phase the phase three and the trend for ‘22 will be in this direction to get the fittest quasi for the phase three expense this year. Yes, so driven essentially by NATiV3.

Okay. If I may just a quick add on, if you need to -- you will need to have new funds or new financing during probably this year. Do you have any idea right now of what could be -- how you can deal such raise? Would it be dilutive, non-dilutive and so on? Frédéric Cren: Well, I think all the options on the table, non-dilutive with potentially business development activity on our pipeline in especially non-strategic area like Asia. We are also looking at loans for deals and of course, as mentioned, we also have an ATM in place. So we’ll see at the right moment, what is the best option for the company to move forward?

Okay. Great. Thank you.

Thank you. The next question is from the line of Seamus Fernandez from Guggenheim Securities. Please go ahead.

Hi, this is Ivan Wang on Seamus. So question on the ROR gamma program, can you talk more about the proof observed in Phase I and how that gives confidence setting into the Phase IIb, especially for a competitive program, product profile, I guess relative to other upcoming orals for psoriasis. And I know you can’t give me specifics on future indications, but what other indications may be most appropriate for this kind of target? Thanks. Frédéric Cren: Pierre, you want to try to answer that?

Well, I think the Phase Ib data are not public. So they are going to be -- well it might be that AbbVie will this year present the data of the Phase Ib in a dedicated conference but these data are not available. I think AbbVie made the decision to enter into Phase B – Phase IIb, which, as you see -- have seen is quite an important study with 200 patients, 16 weeks, based on data that were convincing. So I trust very much on the decision of AbbVie moving forward with cedirogant. And yeah, so we’ll see if the data will be published this year. And relatively to your question about additional indications where basically there are several indications where immunology indication where we know IL-17 inhibition is relevant. Maybe well, you probably know them, this is basically axial spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, idiopathic arthritis, etc, etc. Based on the data we have obtained with this early ROR gamma inverse agonist we could discovered with AbbVie on animal model for rheumatoid arthritis, where we see quite a significant reduction of toe inflammation, it could be that rheumatoid arthritis would also make sense for such a molecule. And we know also that spondylitis colitis is a potential additional indication for this type of mechanism of action.

Thank you. [Operator Instructions] And the next is from the line of Delphine Le Louët from Société Générale. Please go ahead. Delphine Le Louët: Thank you. Good afternoon and good morning, everybody. Just to be back on the run away regarding the cash position for ‘22 and ‘23 and possibly doing for ‘24. I don’t see any reason so far to have a massive cut into the R&D in ‘23, ‘24. So, meaning that more or less ‘22 number could be extrapolate for the following year. Jean, can you confirm that to me, please. And secondly, Frédéric a quick question for you, regarding the situation in eastern Europe and so when I make the calculation more or less for 46% of the patient for the NATiV3 trial will be will be impacted. So do you think yourself you are [Technical Difficulty] broadening the last patient first visit timelines? How do you see the completion of the trials so far, despite the fact you get another shareholder on board, CMO on board, how you’re optimistic or do you think we are -- unfortunately we’ll have to see some delay going forward? And how will that impact between the European population and the US, I mean, the other type of population can you make in Europe other site recruiting more patients to get the same Caucasian population?

Good afternoon, Delphine. I take the first questions you are right about the range of expense that we may incur in ‘23. According to our best estimates, the projections in ‘23 are in the same amplitude as for 2022. Delphine Le Louët: Okay, thank you. Frédéric Cren: On the question about what is the impact of Ukraine and Russia situation on the trial, so we don’t think that this jeopardizes the overall recruitment of the trial. So we stick to the guideline we provided, which is to finalize the recruitment this year. Of course, we need to find and monitor – I would say monitor the situation and also find the other option in a certain sense, we had also anticipated or we had also increased the overall number of sites. Once again, we are now 350 sites on target. This is above what we had planned at the beginning. And so we are looking with ICON at alternative. First is to find in the countries that are open sites that have the capabilities to recruit efficiently the patient for the part one. And then the second alternative is to go into new countries, but of course, if we do that this would be patient given the regulatory timelines that could come in most likely for the part two rather than the part one. Delphine Le Louët: Okay, thank you. Frédéric Cren: Otherwise we had a question on the -- via internet, I think we covered most of most of them. The only one we did not cover, well, there was a question if we believe we can do a partnership before or after the data. And, of course, I cannot give any input on that as we -- what we can say that we believe NASH is a playground for big pharma, we’re open to do a partnership. If the terms are good, we can do it in the short term, otherwise, it will have to be post Phase III.

And we don’t have any other questions over the phones at the moment. Frédéric Cren: Okay. So, then I think it’s a moment to conclude. So, thank you very much for attending and the good level of question and discussion. Next event for us is EASL in June, in person, because we were very much looking forward to do that. As you can imagine, we have submitted the new data abstract, we hope that that will get accepted. And we will organize an off the KOL webcast to go over the NASH base, the key data presented, and also the new data that will be presented at the EASL in June in London. And so I really hope to see all of you in London in June. Thank you very much and have a great day.

Thank you. This does conclude the conference for today. Thank you for participating. You may now disconnect.