Inventiva S.A.

Thank you and welcome everybody to this half-year webcast. As usual, some disclaimer, we'll be making forward-looking statements, so please have a look at our regulatory filings that are available on our website. In terms of speakers, I would say we have the classical Infinitiva team, myself and Pierre, the co-founders of the company. We have Michael, our CMO, and Jean, our CFO. But today is a special day for Inventiva, given the very recent partnership we signed with CenoBioPharm online in February. We are very pleased to have with us Philip Duong, head of the investment, who will give us an overview of CenoBioPharm activities. In terms of agenda, I'll give an highlight of the activity over the past six months, and then I will share the floor with Philippe, with Pierre, with Michael, to provide a pipeline update. We will move to the financial section with Jean, near-term catalyst, and then we will open the floor for Q&A. So, moving now to the highlight section, we start first with Lani, our phase three drug in non-alcoholic steroid hepatitis. A lot of key important milestones have been reached in the past six months. In terms of native three, we have expanded in 24 countries, and we have now activated close to 300 sites. And in the presentation, we give you a bit more details on the improvement in terms of cytotoxin. Very pleased, as I mentioned in my introduction, of the very recent collaboration we signed with SinoBioPharm and the expansion of Lani in Greater China, a country that we see is really promising from a commercial point of view, given the prevalence of NASH among the Chinese population. Some of the figures or the key figures of the collaboration are highlighted here, the upfront, the total milestone, the royalties, and we'll get a bit more in detail in the presentation. In terms of recruitment, we have had to announce a delay of the inclusion of the last patient to H22023, despite all the improvement in terms of site opening, country opening, site activation. But we see that all the action that we have launched still have not fully paid out. Especially we are still encountering a screening failure higher than expected and this has led to this delay. As you know, we have two other very important phase two that are ongoing, one that we call Legend, which is a combination of learning with impacted clothing. We started the screening, opening site and randomizing patients as planned first in the United States, but we also secured Regulatory approval in activation in the other countries where this study is taking place. And then we're pleased with Professor Cusi's ability to enroll the last patient in the trial over the summer, a bit later than anticipated. And therefore, results are not expected in H2, but in Q1, 2023. Moving now to Cedirogan, DBBB157. They are now, we say, we're expecting with a lot of excitement the result of this face-to-be in patients with psoriasis, which are expected in H1 2023. This is, I would say, an update for this conference. We have had over the summer an important meeting with the FDA. We're very pleased with the outcome. and the feedback provided with the FDA. We know that we can go directly now into children age of 5 to 14 with MTS6. We know that the design we presented to the FDA, which is a single, six, two, three trials, can potentially support marketing application. This gives us confidence in the search of opportunities to find a new home for the parcel, and really seeing this feedback provided by the FDA really goes into the right direction for this project. Finally, on the financials, we've been continuing to reinforce our cash position, both with dilutive and non-dilutive sources. We've had close to 15 million euros through a combination of the market program, which I remind you is managed by Jefferies, and it's only made of reverse inquiries, and also some non-dilutive funding coming from state-back financing from the French state. We also are very pleased from the European Investment Bank loan that we secured, a $50 million loan and warrant agreement of two tranches of 25 and 35, and we're pleased by the fact that with the upfront that we're expected to receive from our part of the CINO, we will be able to secure the first branch from the IB and this would extend our cash runway to Q4 of 23. And then lastly, also the recognition of being selected by Euronext as part of the Euronext tech leader. So this important index is also a nice recognition of the work that has been done. Let's now move to Lani. I just would like, first, before entering into the detail, give a bit of an overview of the competitive landscape in NASH. It's nice to see that, you know, positive news happening in the field with the recent data from AKIRO and others. Now, when we look at the landscape, I think all eyes are pointed to the part one, phase three results that are expected from West Meteorome. And then you see that from this slide, you see that Lani is really well positioned in terms of timing of when the results will be available, and we're really part of this Limited number of promising compound that are now in phase 3 or planning to enter into phase When we look at, you know, the competitor, I think we can divide them into two sections. We have the oral drugs and the injectables. When we look at the oral drugs, they're really extremely well positioned as the only oral drug that has met the two important endpoints that are considered by the FDA and NEA for approval for national resolution and improvement of fibrosis. There is another section where you have injectables with the recent data from ACCURE where they too managed to secure eating both and boys with a different that we highlight here. Our results are based on ITT population that as you know is a population that is considered by regulatory authority for approval and there we have statistical significance on both endpoints where the results presented by competitors are mostly based on per-protocol population, or even when you consider Acura, some completers. So now let's move to Lani, and before we get into Native 3, I would like just to give some of the highlights of the licensing and commercialization agreement we signed recently, and then I'll give the floor to Philip for the presentation of SILA. Why we were really excited by this opportunity is because China and Greater China is, in terms of NASH population, very attractive. Of course, less population, but also when we look at the prevalence of NASH, there are publications, an increasing number of publications that show that the prevalence of NASH among this population is close or sometimes even superior to what is experienced in the United States. Secondly, we're also excited because when we look at who is currently in development, in China, we see that only semaglutide out of the compound that I described before is present with a compound that you know isn't injectable and that has not been able to show interface to be in preserotic patient, but also in the serotic patient has not been able to show an antifibrotic activity. We really believe Lani, especially with a partner of the quality of Sinobiopharm, It's really well positioned to be potentially a leader in this, in the Nash field in China. In terms of financial, these are the highlights that have been described in the press release, so an upfront, an expected upfront of $20 million. Followed by short term clinical milestone that could potentially. A trigger an additional 5,000,000, and then globally the contemplates. The total of 290 million dollars of clinical regulatory commercial life. In terms of royalties, there is a first period of three years where to sustain, to help on the launch, the royalty will go from high single digit to mid single digit, and starting from the fourth year, from low double digit to mid single digit. Then in terms of regulatory, in terms of development strategy, there are several options that needs to be discussed, especially with regulatory authorities. Two main options seem, you know, viable. One would be for, you know, BioPharm to join the Global Native 3 study, or the other alternative would be to run an independent study. Important to point out, of course, that all the costs linked to the development in Greater China will be borne by our part. So with that, I'll give the floor to Philip, that will give us a quick overview of SinoBioPharm, and therefore I'm moving to page 14 of the presentation.

Thanks, Federick. Just to check if you can hear me.

Perfectly.

Perfect. Okay. Thanks, Federick. And thank you for the Inventiva team during the collaboration discussions and sort of a fruitful outcome. And we look forward to sort of collaborating with Inventiva in the long term going forward. So, I'll give a quick background on Sano BioPharm. I'm currently looking at page 14. So Sano BioPharm, for those of you that don't know Sano BioPharm, we're one of the largest, actually, if not the largest Chinese pharmaceutical group in China. We're listed in the Hong Kong Stock Exchange since 2003. Currently have a market cap of slightly over $10 billion U.S. dollars. And then last year, we had revenues of $4 billion U.S. dollars. Globally, we're ranked the 40th largest pharmaceutical globally by PharmaExec, which is... which is the largest in China, as I mentioned. So through our subsidiaries, we operate a fully integrated pharmaceutical operations from discovery to clinical development to manufacturing and sales. We started off as generics back in the 80s, and we've moved towards innovation in the last decade. So we have significant R&D capabilities with over 68 innovative assets in the pipeline, and seven of those are focused on liver diseases. We also have US and EU qualified manufacturing capabilities in API, small molecules and biologics. I think from a commercialization perspective for Lani, it's quite important to note that we have the largest sales reps, sales and marketing reps in China with over with almost 14,000 reps covering basically the entire Chinese or the entire China. And we both do it through traditional sales channels, so the hospital sales channels, as well as emerging channels, such as online channels, as well as the pharmacy chains. In hepatology, we have a proven track record with over 17% market share. This is from IMS data, and that's more than double our closest competitor. PhenobioPharm, it's run... Privately owned by the say family. It's currently run by the second generation. So it's a very entrepreneurial and agile organization and Our family the family owners have their backgrounds from Thailand actually and they've been in Chinese market since the 1980s Next page, please page 15 So the way to think about SanobioPharm really is we're a group of operating companies where together we form basically where we provide a comprehensive healthcare ecosystem to the Chinese market. On the top here, we have our pharmaceuticals. So the key partner for Incentiva will be CTTQ, which is on the top left corner. And CTTQ itself is a fully integrated pharmaceutical company with key therapeutic areas in liver health, and in addition to that, oncology and respiratory. We also have a lot of other pharmaceuticals, but we listed our largest ones here. I think importantly for collaboration, we're also very large investors in the online health, for example. We're the largest investors in Medlinker. Medlinker is the leading online platform for chronic disease management in China. And this is a key channel for liver products in China, where we have over 800,000 doctors on our platform or on this platform. We're also present globally through inbox, which was established in 2020, where we our soft health fee on and also associated with the Karolinska Institute group through Karolinska Developments. And we're also present in vaccines where we work closely with Sinovac where they developed the CoronaVac vaccine back in 2020. On to the next page, please. So this is basically an overview of the platform we have. I think there's a couple of important points to note for Lani and how we can bring success to this in China. So one, we have a very large clinical development team of over 500 people in China, which will help accelerate clinical enrollments. We also have a lot of manufacturing sites spread across the country in both API and small molecules. So we're quite confident we can lower the COGS, which is important for countries where pricing is not as high like China. And we also have the largest sales team in China with over 13,000 reps covering the entire China, covering 90% of the hospital channels. And then if we move on to page 17, where I would like to leave off is Sinobiopharm through CTTQ has a very, very long history in the liver space, starting with hepatitis, as well as liver protection, which is quite an Asian concept, but is quite big in China. Like I mentioned, we have market share that's more than double our second largest competitor in the hepatology space. We have a lot of blockbusters in the liver space, two of which is, one is Entegavir, Renjun, which we did $4.6 billion of sales in 2018, which was basically unheard of in this space. We also have an innovative product called Ganmei, which is basically mostly used for hepatitis B patients. But it's an Asian concept of liver protection, which is actually closely quite linked to NASH, where we did $22 billion of sales last year. And it's been consistently growing since we launched this product 10 years ago. We also have a healthy, innovative pipeline within this space where we think there could be potential opportunities to establish or to explore combination treatments in the future. With that being said, I think that's the introduction on sonobiopharm, and I pass it back to Frederick for the rest.

Yeah, thank you, Philip. So I think everybody can understand why we are very excited by this partnership and the opportunity that it opened up. So moving back to 1983, so where do we stand? The progress, so now 24 countries are included. operational and we have secured full regulatory approval on 23 out of them. We have productivity in Ukraine and also decided not to move forward in Russia. Where we stand, this is a situation So we have qualified 463 sites and 297 are activated. So really a strong progress there. However, and this follows my introduction, if we look at the impact from the war in Ukraine and Russia, the COVID pandemic, we see that despite the implementation of the measure that have led to the increase of the number of sites, We're still facing, you know, a recruitment that is behind our expectation, and this is mainly due to a screen failure rate that is higher than anticipated. And this really led to the communication last night that we see that now the last patient for the part one is now targeted for the second half of 23 versus H123 as previously communicated. So that's for native, and now we now hand over to Michael, who will give you an update on the two spaces that are ongoing, so the one led by Professor Cusi and the combo study coordination.

Thank you, Frederic. As you mentioned, there are two studies that or in Phase 2. One is on slide 20, a study that aims to provide more information or data on the mechanism of action of lanofibrinol as a fun P-paragonist in patients who have NFLD and type 2 diabetes, conditions that occur often in the same patient. given the similar underlying disease biology. Specifically, this study aims to show that lenofibrinol decreases intrahepatic triglycerides content, improves adipose tissue, specifically the insulin sensitivity thereof, and also insulin sensitivity in hepatic and muscle tissue, which is a core mechanism of action of PPAS signaling. endogenous hepatic glucose production, and markers of cardiometabolic health. The investigation, the principle, it's one side study, and the sponsor and principal investigator is Ken Kuzzi at the University of Florida. The total of 34 patients with NFLD and type 2 diabetes. are enrolled and to have reference values. There are also data from 10 healthy individuals who are non-obese and whose data will serve as reference. These volunteer participants do not receive investigational compounds. Sample size is calculated on an effect size of more than 50% reduction of intrahepatic which is also based on data that are available for how PPR agonists work in this indication or in this finding. The primary endpoint is a change in intrahepatic triglycerides quantified by MR spectroscopy, and so baseline compared to week 24. And in addition, there is a whole wealth of a secondary endpoint that will provide a comprehensive picture on how lenofibrinol improves metabolic health in these patients, starting from insulin resistance, NAFLD resolution, defined as patients with a very low intrahepatic triglyceride content, Changes in hepatic fibrosis measured with allostrography, MRI-based and ultrasound-based, so MRE and FibroScan, as well as biomarkers, and of course also safety and tolerability markers. The results will be expected for early 2023 of patients. or enrolled due to a little delay when the last patient started, the results will be expected in the first quarter of 2023. So for the next slide, 2021, this is the so-called LEGEND study. It's an acronym, and it is essentially a combination of lanofibrinol with an SGLT2 inhibitor, empagliflozin. in patients who have NASH and type 2 diabetes. The rationale for the combination of these two compounds is very strong, as STL2 inhibitors provide additional metabolic benefits to nanofibrinol, and may therefore, you know, or a very attractive way to explore the additional benefits of this combination in a proof-of-concept setting. The study is done with two principal investigators, Drs. Michelle Lai from Harvard and Honor Holleboom from the University of Amsterdam. We have around 40 sites, which are in four countries, in the US, in the UK, in the Netherlands, Belgium and France are five countries. The FDA, the IMD is open, the study has started. The first site was activated in the first half of 2022, and we expect top-line results second half of next year. Patients, adult patients with type 2 diabetes and NASH are to be included in the primary efficacy outcome with HbA1c, which is a marker, of course, of insulin persistence and metabolism, which is also relevant for disease pathway of NASH in addition to type 2 diabetes. And here also we have a broad spectrum of secondary efficacy measures, including imaging, MRI-based imaging, which will give information about the distribution of fat, of adipose tissue, visually in the liver, and also an overall Composition of fat, which is quite important in evaluating to what extent that is related to insulin resistance or insulin sensitivity. In other words, metabolically unhealthy or healthy adipose tissue. Markers of glucose and lipid metabolism, markers of inflammation. body weight and other safety and tolerability issues, of course. Wealth of data, the study will enroll 63 patients, and the treatment is half a year. It's a randomized study, randomized double-blind for lanofibrinol and placebo, open label for the combination. Lanofibrinol plus empagliflozin is one arm, lanofibrinol alone is another arm, and placebo is the third arm. Next slide. I mentioned the site is run in these five countries in Europe and the United States. We have the study approved in France and the US and it's running there and submissions are completed in the remaining countries. So we expect top-line results in 2023, in the second half of 2023. So overall, when you go to slide 23, in the next coming years, we will have a regular announcement of availability of data on the efficacy of lanofibrinol in clinical settings to start with. And in the 1st quarter of next year, the data from the study. Run by a cozy in Florida. Top line results from the phase 2 trial in patients with half of the 2 diabetes. Then the year thereafter in the 2nd half. of 2023, so the same year, in the results, the top-line results from the legend study in patients with NASH and type 2 diabetes, the combination of nanofibrinol with empagliflozin. And then in the second half of 2025, the top-line results of part one of the current pivotal native tree study, currently ongoing, of course, and . in patients with NASH and significant fibrosis, HSF2 and F3. And that's it for me, so.

Thank you, Michael. We'll give you a very brief update on EBPV157, the Dirogan-B, our gamma reverse agonist that is currently in phase 2b with our partner, ALVE. We were last week in Chicago, and we are extremely pleased with the progress of this molecule, you know that we're excited by this mechanism of action, where gamma has a possibility really to suppress IL-17 expression, but as you know, is a validated target in the clinic. Clearly, the potential of the once daily, already available, our gamma with a target profile that, as you know, as we have said in the past, what we're targeting in the Eumera-like efficacy with better safety in the end of a company like AbbVie that has such a strong expertise in autoimmune disease is really something that really excites us. And we really think we have a little jewel here in our pipeline. The meeting of the day in Chicago was really great. We really see that there is excitement around this molecule. Now we have to wait for the fifth-to-be trial that is currently ongoing. This is 200 patients, 16 weeks, a trial in patients with moderate to severe psoriasis. And at the primary endpoint, there is It's a measurement of 575 also worthwhile noting that. In parallel, we have launched the phase 1 that is needed to start phase 3. so. So positive to see that the plants are in place to in case of success. And then I would say that for us now, just. We just need to wait for the results of this phase to be, which, as indicated in clinicaltrial.gov, the results of the trial is expected to end in Q1 2023. So we should have the results in the first half of next year. We also, of course, why we're excited is also because we are financially rewarded by the mix of milestones, but especially royalties that start from each single digit and can reach double-digit levels. And, of course, this drug is approved, and we are convinced, given the mechanism of action, given the potential of the market in the autoimmune space and the capabilities of our partner AbbVie, that this product has the potential to really be a meaningful source of revenue in the future for Invalida. So that was a very quick update, and now let's move to Audit Parcel, and Pierre will give you the latest on this program.

Yeah, thank you, Frédéric. So yes, we're very excited to update you on the Audit Parcel program, but I'd just like to start with a recap on MPS and Audit Parcel media interaction on page 27. So, as you know, MPS are inherited disorders that are characterized by the dysfunction of lysomal enzymes, which are required for the breakdown of decosaminoglycans, the GAGs. Within this family of disorders, MPS6 is caused by mutation in the RSPG, which encodes the enzyme leading or responsible for the degradation of DS and CS. So, MPS6 is actually an accumulation of DS, dermatosulfate, and choroidine sulfate in all cells of the body. So then, of course, MPSS is a devastating multisystem disease, which is actually leading to a reduced life expectancy up to only the teens or early 20s in the more rapidly advancing cases, and up to 40 or 50s in slower progressing cases. So today, there is one treatment approved. and enzyme replacement therapy, niglazime, which, however, has several limitations due to its poor distribution in the body. And there is, therefore, still a very important medical need for treatment of MPS6, even in patients that are actually treated with ERT. So, next slide, please. So, we're getting up on the d-parcyl. So, d-parcyl is a small, already available molecule. that decreases the CS and ES type of GACs accumulation in disease cells. And this, as you recall, a very unique GAC clearance mechanism of action. On top of that, the is, of course, already available, well distributed, and can penetrate difficult-to-reach tissues, including cartilages, bone, and cornea. offering, therefore, an opportunity to address the clinical manifestations that are currently not treated by ERT. So, in Madhya, I've conducted a phase two study called IMPROVE in adult MPS6 patients that were at an advanced stage of disease. And in this study, UDIVAR-T was found to be safe and to provide beneficial effects in both ERT-treated and ERT-naive MPS6 patients, and this only after a short treatment duration of six months. Therefore, we believe that there is a good rationale for further assessment of Oedipacil efficacy in younger patients. Next slide, please. So, overall, Oedipacil has a favorable safety profile shown in multiple clinical trials. As you maybe remember, the combined developing previous indication where more than 1,500 patients have been exposed to the drug. Very clear efficacy data in MPS6 patients are nice model that we have also published. We see Dipartida really as a potential game changer, as being the first oral therapy with the ability to broadly address a wide range of clinical manifestations in MPS6 patients. This market, as you know, is close to a $400 million market. In addition to that, Odiparseal has also the potential to treat other MPS, where CS, RDS accumulate, such as MPS1, MPS2, MPS4A, and MPS7. So in MPS6, next slide, Odiparseal aims at improving the treatment options for both ERT-eligible and ineligible patients, either as an add-on to ERT or as a monotherapy we could potentially see the treatment as potential first-line therapy in combination with ERT in ERT-eligible patients, but also as immunotherapy in ERT-eligible patients. So now let's dive into the recent FDA discussion. As you recall, also, from a regulatory perspective, we have obtained Zolibaxil often drug, fast-track, and rare pediatric designations. And today I would like to report on the recently held FDA meeting that took place last month to discuss the regulatory path for approval, including study objectives, patient population, endpoints, a clarification that we believe will be helpful for future partnership discussions. Next slide, please. The feedback from FDA was that the single phase 2-3 study of one-year duration in MPS-6 patients 5 to 15 years of age could support a fight. This pivotal study that we call POSIGY would be double-blind, randomized, placebo-controlled, evaluating the ability of one dose of adipacil administered in combination with ERT versus placebo in combination with ERT. to enhance mobility is the primary objective, and to improve endurance while reducing fatigue and pain. These are secondary objectives. Primary endpoint will therefore be a six-minute walk distance, and secondary endpoint would be a three-minute stair climb and pain assessments through questionnaire. This first part will be followed by a 12-month safety expansion with all patients under Oedipaxil plus CRT. The study contemplates to enroll 50 pediatric patients for 12 months, potentially leading to the filing of ODPARCEL approval as ERT or in combination with ERT in patients five years of age 12. So following this feedback from FDA, we believe that ODPARCEL will present an attractive partnering opportunity. Thank you.

Let's move to the last slide before we wrap up, so we can move with Jean to the update on financials.

So let's go through the key financial figures. So as you will see, it's quite straightforward and in continuity of the prior financial period. I will be happy to answer your question at the end of the meeting. On this slide, one important information is the cash position. So as you can see, we maintain a reasonable level of cash versus the end of 21. So we are at 87 million versus 95 million at the end of last year. Prior to the consequences of the Chinese deal, allowing us to operate until Q2 2023, and as disclosed and explained, the deal with the Sinobio farm to gather the conditions for reaching the first tranche of the EIB and therefore allow us to extend the cash runway through Q423. Let's go through the next slide with the evolution of the profit and loss accounts and cash flow. As I said, no revenues for this semester. As a reminder, Inventiva recorded four million milestones from AbbVie in the accounts of last year. But we have been paid early this year and then have a positive effect on our cash flow for this semester. As usual, the key and stable information with regard to R&D investments, which represents more than 80%, still of our total OPEX is the increase in the R&D, plus 56%, and it's still due to the acceleration of the NATIVE III studies, priorly, and as you have seen, some additional studies, plus, in a lesser extent, if you remember, we have this year a full semester of operation of our U.S. affiliates versus only one quarter in 2021. Reasonable increase due to the increase in personal cost, but due to the charge related to the share-based payment, which is non-cash, and also a full semester The most important impression, as you know, is the cash position, as I said. So, 87.2 million without the consequence, as I said, of the Sinovio Farm Deed and EIB first tranche. So, the net operating cash flow reflects the evolution of the R&D expense, essentially, and in a lesser extended G&A evolution. The net financial cash flow is very important for the semester. We have succeeded in activating for the third time our ATM program with close to 15 million, and we have been able to mobilize soft loan, back state loans for 5.3 million. And we also took benefit of the favorable evolution of the dollar versus euro with a positive cash impact of 2.4 million. I think this is the key information. Again, if you have other questions at the end, I'd be happy to answer.

Thank you. The last slide before we open to Q and A. So, what are the next milestones? The list of what has been achieved so far. And I would say that we have in front of us two important clinical readouts. One concerning LAMY, beginning of the year, Q1. The results from the study led by Professor Cusin, patient with type 2 diabetes and NAFLD. And then, of course, the data from the phase 2B that is currently carried out by our partner, AbbVie, with Cedric. This really, I would say, will be a very important event for our company next year. With that, let's move to Q&A. The operator will provide you how to ask your question, both via the platform or via the telephone.

Thank you. As a reminder, to ask a question from the phone line, you will need to slowly press star 1 and then 1 on your telephone. You will then hear an automated message advising that your hand is raised. Once again, it's star one and then one on your telephone. If you wish to ask a question via the webcast, please use the Q&A box available on the webcast link during this call. We are going to proceed with the phone question. We have the first questions coming from the line of Ed Ark from H.C. Wainwright. Please ask a question. Your line is open.

Hi, good morning. Can you hear me?

Perfectly, yes.

Wonderful. Thanks for taking my questions, and congratulations on the deal with CINO Biopharma. I have three questions. First, you mentioned the recent results of ACARA were a protocol versus ITT. which is more of a standard and the basis for your results in the Phase IIb. I was wondering if you could talk about how you view the differences of that data, and as well, your perspective on how the regulatory agencies view the differences of those two. That's first. Second is, I wanted to ask if, You mentioned with the Sinobiopharma deal that they could either join Native 3 or decide to conduct its own Phase 3 trial. And I wanted to know if you and Sino decided to have them join the Native 3 trial, would that have any impact on the timeline? And then lastly, The top line NASH results from Native 3 looks like it's still about three years away, second half of 25, which, based on your most recent runway, creates about a two-year funding gap. So I'm wondering if there are any additional opportunities for funding, say, from the results from AbbVie or perhaps initial funding from a future partnership on OD Parcels. Thanks so much.

Thank you, Ed. Thank you, Ed. So very, very interesting. Any questions? I've got echo, sorry. Let's try again. Yeah, okay. Sorry? Oh, sorry, can you hear me?

Yes, I can hear you fine.

Okay, sorry, we just had a terrible echo here. So on the first question, maybe Pierre and Michael complete for me, the different protocol versus ITT. You know, I just think it's important just because I care produce some slides where, you know, they use and compare the face to data. I think it's important also to, you know, to have a complete picture. And from what they said in their presentation is that if they had used an ITT approach, it would have lost the statistical significance on, I think, on the NASH resolution one. And therefore, in that case, we could claim to be the only drug that has met both regulatory points. But nevertheless, I just think it's important that we retain that because on the phase three, what the regulatory authorities will be looking is the data from the ITP and the fact that we were able in the phase two B to B on that population gives us more confidence or even greater confidence that, you know, we will succeed in our phase three. Then I will ask the second question, and Philippe, don't hesitate to complete my answer. So your question was, you know, in the event Sinobiopharm would that have an impact on the timeline? I would say that it's too soon to mention that. It will certainly contribute and help in our recruitment effort because the patient that would be recruited in China would account in the patient needed for part one, but we're prudent and therefore we, you know, we do not, we don't take this upside in our project. And then, I don't know, Philippe, anything you would like to add to this?

Yeah, thanks, Frederick, and thanks for the question, Ed. I think in terms of our clinical enrollment capabilities, I think we can quite quickly enroll patients. Obviously, it's subject to multiple factors, such as CDE regulatory approval and such, but I think once or if we do go down the route of a global multicenter trial, I think we're quite confident in our capabilities to sort of quickly

Thank you. And then the last question about the two-year funding gap until Part 1 readout. I think there are two ways to read it. It's a glass half empty. We can also read it as, given the difficult times in the market, Inventiva secured financing until Q4 23. And also, as you mentioned, I think we have several opportunities that are both dilutive and non-dilutive. On the dilutive, we have an APM open, and we have always benefited from the support of a strong shareholder. And then on the non-dilutive side, yes, we are excited by the discussion with the FDA for this feedback, which according to us, reinforces a rationale for the parcel to continue developing in MTS6. And we have not changed our strategy. We do not want to develop a departure on our on our own we we think it's a good candidate for partnering will we succeed it's too soon to say but the idea feedback gave us give us confidence and then also i think lani is a very attractive uh And there are other geographic areas beyond China where partnering would make a lot of sense. And then finally, as the partnership in the short term, if they decide to move into phase three, of course, this will trigger milestones. always nice to receive it, but you know that we have always said that in this contract, what is really material are the royalties and not the milestone. But, you know, if next year, this program moving to phase three, Inventiva will have a very promising asset like Lani Nash and a drug in phase three, hypsoriasis, maybe potentially other autoimmune disease the finance and carried out by AbbVie. So I really think an interesting value proposition to investors.

Great. That's all Craig. Thank you. Thank you. Thank you.

And I think we were assessing a question from Jerome that we don't hear him. Hello? Hello, yeah, we can hear you now.

Hi, sorry, there seems to be echo here on the line. Congrats also from KDC with regards to the Sharna Farm deal and with the results for OBD Parcel. Maybe from my end and following up on the Akira results a little bit, Um, you know, Nash clearly has been a little bit more of a challenge over the past year. You see renewed interest from investors. Do you believe that also with more and more people refocusing on it, there will be non-invasive, um, let's say, uh, like our diagnostics methods coming online. and maybe one last question you guys can give me or us an estimate of the Nash size in China all right on the first question I would say yes in the sense that

Good news from other competitors, like Akiro and others, are a positive for the space. the failures of other compounds have, and I don't think it was justified, shed a negative light on the successes of others and then include that, landing that. So yes, it's very positive to see other companies succeeding because this provides a positive sentiment on the space and I really hope that continues. This is why we're looking and cheering for madrigal success in their faces. On the non-invasive, maybe, Michael, do you want to just give an update on the recent progress there?

Absolutely. So, yeah, you know, and I'll focus on the FDA. The FDA, to this date, requires histology as the end point. I should say that in the past years there has been quite some progress on data that are being generated both from imaging and biomarkers and algorithms based on those as non-invasive markers for the disease and for response to treatment. And in these discussions, to what extent they will be complementary to or in the future be a replacement for histology, You know, we are all active part of that discussion, including our academic colleagues, R&D and industry, as well as the FDA. And I think that's very good news. I think with regard to lanifibrinol specifically, what gives us confidence is that lanifibrinol, given its mechanism of action, has shown strong efficacy on the histology endpoint, but also in the broad range of biomarkers that reflect the disease as well. So I think for both histology and IT, I think, has a very strong position.

Thank you. And the last question is the large-sized market in Greater China. Personally, I have not seen any forecast or any public data. The only data I've seen is what we mentioned before is about the prevalence that seems to be higher or similar to the one in the U.S. and then given the size of the Chinese population, that makes it a very attractive market. I don't know, Philippe, on your side, have you seen anything public on the market potential or anything you can disclose?

Yeah, sure. So, as you know, without any NASH treatments, I think there's quite a large range of numbers that we've seen from as low as sort of two to even as high as six, seven percent. But like Frederick, like you mentioned, I think it's just the sheer size of the population with over 1.3 billion population. That translates to quite a high potential NASH patients. We've seen numbers being thrown about 50 million patients or so. But again, without sort of any approved treatments, those numbers are hard to verify. But it is quite a large market in China for NASH.

Thank you. And then I see we have a question from Alex from Brian Garnier. The floor is yours.

I hope you can hear me well. Thanks for taking my question. So I was just wondering if you could share a bit more on the screening failure in the phase three. Like what would be the rate of failure you're seeing and kind of what measures are you introducing to reduce that failure? And are you already seeing kind of results in terms of faster enrollment on the back of those measures.

Thank you. The screen failure rate is high, and we've seen that, first of all, happening across the entire field of NASH clinical studies. So I don't think, or I know actually, that our data are not in aberration with others, which is reassuring. So NASH has many other indications, challenges. Having said that, we actually have a lot of effort to detail the reasons for the screen failure rates in basically from site to site, every individual case. And overall, there are a couple of reasons which have to do with lab values, of course, and also with the histology reading, which is, as you know, semi-quantitative, the scoring system, and we have three expert histopathologists. I think they are among the very best, if not the best in the field. We spend a lot of time bringing them together in formal sessions where they can align their reading before they start looking at biopsies as part of the study. And we have now also invented, that's recent, so it's not possible to say what the impact will be, but I can estimate that from our previous results, of course, on a system whereby each biopsy is read by two of these pathologists independent of each other. And if there is a non-alignment, say one scores fibrosis stage three and the other one F4, or F2 and F1, then there's a tiebreaker. And the tiebreaker automatically will then define what score is aligned. And if I look back to the data that we had previously, that will alleviate or increase the screen failure rate to a certain extent. In addition to that, we pay a lot of attention to providing guidance to sites to diagnose pre-screened patients so that the likelihood that when a patient enters the screening process, that the patient ends up being a screening failure is reduced. And with that, I think we have looked at published data as well as our own data, what are the criteria that would have the highest effect And, you know, it's well known that aminotransferase specifically, ASP, can be called that. So we have adapted our inclusion criteria accordingly and will implement that as an amendment. And we can anticipate that these measures will have a measurable effect on the screen failure rate going forward.

Got it. That's very helpful, Collard. Thank you. And just some questions on the Sudiro ground, if I may. So it seems like AbbVie is pretty excited about the compound given the speed of recruitment in the Phase 2b. But I don't believe they've actually released the Phase 1b results, which makes me believe they may be waiting for AAD in March. But then they might also have the Phase 2b data. So do you have any insights into kind of their plan for releasing Phase 1b or Phase 2b data next year?

You're right, the Phase 1b data has not been publicly shared. The next important Congress is in New Orleans in March, the first of March. That could be a date where they could publish the results. Until the abstract is available, it's difficult to confirm that. And in terms of plan of the phase to be, I don't think this has been decided yet.

Got it. And on the back of the phase to be, are there any specific milestones you would expect in 2023, let's say, maybe related to finalizing the study or relating to good results, obviously, or is it related then to a start of phase three? How can we think about that?

So it's related. The next clinical milestone for us would be the beginning, the initiation of the phase three. Okay. In any indication. So it doesn't need to be psoriasis if the first patient enrolled in the first phase three.

Okay. Understood. Thank you. That's it for me.

Thank you, and then Bethin from Societe Generale is also online, and we're very happy to... Yes, hello, hi, good afternoon, good morning, everyone.

A different question from my side. Can you let us know exactly how many patients have been screened and enrolled so far, or as of end of August, just for us to get an idea of the rapidity of the inclusion and what sort of... effectively ramp up, we can expect, till the end of the last patient's first visit in order to prevent any further delay or just to get an idea of what's your goal and how we position ourselves toward that. Second question deals with according to your knowledge of your Chinese partner and the Chinese market, can you give us a sort of a probability of what would be the scenario choose by the let's say by the Chinese would that be to go for a Chinese study or to come up and adapt harm for Chinese patient within the native trial and finally I was wondering if Can you remind us the other condition that you have from the EIB to unlock the other 25 million envelope? Thank you very much.

All right. To your first question about figures in terms of number of screen, screen failure and all of that, we are not communicating on that. This is not done by our competitors, so we want to preserve our competitive advantage versus versus other because the competitive market what we can say that if you look at the number of sites countries so that we are we say online with our expectation and that was not the case The last time we had a webcast where we were facing a delay in terms of regulatory approval and in terms of opening of sites. That was not the case. So that's how that has been solved. And now clearly for our team and ICON, to go back to what Michael said, we need to improve this screen failure rate that is high for us, is high for everybody in the market, but we only care about us and we need to bring it down. On your second question about what feedback from the China regulatory authorities will be on the approach, I frankly do not know because I have no experience with them. Maybe, Philippe, you want to comment on that? Maybe right now it might be a bit too speculative. I don't know. What would you say?

Yeah, thanks, Patrick, and thanks for the question. I think it's a bit too early to tell, but I think we will do what's best for the quickest launch in China.

Yeah, I can imagine. But the idea is to know if Sinobiopharm has already been involved in such a deal, and so what was the solution chosen for the other company if they were involved in such a deal and partnering together? I mean, licensing the right for Chinese market.

Apologies, I didn't quite get the question. Is it how you would do it?

No, I was wondering if, you know, SinoBioPharm already shared with you some of their experience from the past, from other licensing deals they may have, or any view that they have or any confidence that they have toward the regulatory passing in China?

Yeah, sure. So I think global multicenters are joining a phase three trial in China is in other therapeutic areas has been done before and it's, I won't say it's common, but it's done before and it's resulted in sort of good, it's done well. But unfortunately for NASH, Not that it's been done before, but it's new. So I think it'll be the first global multicenter trial in Nash where if we do it, I think it'll be a landmark situation. So for other therapeutic areas, it's been done before and we have experience with that.

Okay. And Frederic, and the last question regarding the financing, yes.

Yeah, for AB for the second trial to let you all describe the condition.

Good afternoon, Delphine. We have disclosed all the information with regards to the CPs and the family CPs conditions precedence. I will not go in detail, but you can go in the disclosures that have been made. The total condition to reach the second tranche in one year, more than one year from now, because the objective is to raise the second tranche one year after the first one, is to get a cash injection of 70 million, including the initial cash injection that is required for the first tranche. Clearly speaking, we match – we're on the way to match the – we have matched 9.5 million with the ATM. We will match the $12 million euro with the China deal. So mathematically, we miss 50 million to 20 million. And as we have explained in terms of financial strategy, we will get other opportunities to bridge this $50 million. There are also other SEPs like, as you may know, the warrants side of the deal, because there are some issuance of warrants for each tranche. And there are some operational conditions also relating to the mix of activated sites, activated sites at the time of the rating, or a number of randomized patients, which is quite, first, reasonable in terms of negotiation with the AAB, and attainable within the current plan of development.

and the last cp which we have met was to sign the partnering that we have done or at the entering phase three and uh i think we are uh or we hope that we will be also able to meet the second potential condition thank you very good and then we have no more questions on the on the phone but we have some questions on the On the platform, some have been covered. One that's not been covered is that can we disclose, you know, what are the milestones beyond the 5 million a year term milestone? This, unfortunately, we can't. And then there is a question about the YAPT program. Where do we stand there? And they are returned to Pierre for questions.

Yeah, sure. Thank you for the question. So, yeah, we're also very excited with the progress made with this project. We're actually working on very specific molecules, lead compounds that are now into in vivo evaluation phase. And these compounds differentiate quite well from other competitors, like from Vivace or Ikena, even Novartis. in the mechanism of action and the outcome being that those compounds are capable of inhibiting the proliferation of cells, the proliferation of which is dependent on the update, but also tested. And that makes a big difference in our profiling. And I think this is something we have communicated earlier this year. We have demonstrated that Divacir or Ikena compounds acting on the small pockets of teeth are actually preventing YAPT association and preventing the proliferation of YAPT-dependent cells, but are incapable of preventing the proliferation of TAS-T-dependent cells. Our lead compounds do both, which opens the opportunity to advise many more cancers. And those compounds are currently in in vivo testing and looking forward for the in vivo data.

Thank you, Pierre. I think we have no more questions. Therefore, I would like to thank all of you for participating for your question. I would like to thank Philippe for staying up late now because it's more than 9 p.m. in China. Thank you for making yourself available. I think it was important to describe the capabilities of Oxino BioPharm. Otherwise, of course, we'll continue working and we look forward to the next meeting. I would also like to point out that today for us is a special day because we're actually just after this conference run to the celebration of the 10-year anniversary of to Inventiva. We started this adventure 27 of August of 2012 and today we're really pleased to be in a position to celebrate this important landmark for Inventiva on the back of positive news for Lani Fibonor and for the parcel and also for Cedric. Thank all of you for your participation and I look forward to seeing you very soon. Thank you.