Inventiva S.A. (NASDAQ:IVA) Q2 2022 Earnings Conference Call September 22, 2022 8:00 AM ET
Company Participants
Frédéric Cren – Co-Founder and CEO
Pierre Broqua – Co-Founder and CSO
Michael Cooreman – Chief Medical Officer
Jean Volatier – Chief Financial Officer
Philip Duong – Head, Investment
Conference Call Participants
Ed Arce – H.C. Wainwright
Jeroen Van den Bossche – KBC Securities
Alex Cogut – Bryan, Garnier
Delphine Le Louët – Société Générale
Operator
Good day and thank you for standing by. Welcome to the Inventiva 2022 Half Year Results and Webcast. At this time, all participants are in listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions]
Please note that today’s conference is being recorded. I would now like to hand over to your speaker, Mr. Frédéric Cren, CEO and Co-Founder. Please go ahead.
Frédéric Cren
Thank you, and welcome, everybody, to this half year webcast. As usual, some disclaimer, we will 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 imperative team, myself and Pierre, the Co-Founder of the company; with Michael, our CMO; and Jean, our CFO. But today, it’s a special day for Inventiva given the recent partnership we signed with Sino Biopharm lanifibranor. We are very pleased to have with us Philip Duong, Head of Investment, who will give us an overview of Sino Biopharm activity.
In terms of agenda, I will give an highlight of the activity over the past six months and then I will share the floor with Philip, 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 will start first with lani, our Phase III drug in non-alcoholic steatohepatitis, NASH. Importantly, a lot of improvement, a lot of key important milestones has been reached in the past six months.
In terms of NATiV3, we have expanded in 24 countries and we have now activated to 300 sites in the trial and in the presentation, we will give you a bit more detail on the improvement in terms of site.
Very pleased, as I mentioned in my introduction of the very recent collaboration with signing with Sino Biopharm 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 I will highlight here, the upfront, the total milestone, the royalties and we will 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 H2 2023, despite all the improvement in terms of site opening, country opening, site activation, but we see that all the actions 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 II that are ongoing, one that we call LEGEND, which is a combination of lani with empagliflozin. We started the screening, opening sites and randomizing patients as planned, first in the United States, but we also secured the regulatory approval and activation in the other countries where this study is taking place.
And then we are pleased with Professor Cusi ability to enroll the last patient in the trial over the summer, a bit later than anticipated. But in terms of results are not expected in H2, but in Q1 2023.
Moving now to cedirogant, ABBV-157, there now, I would say, we — we are expecting with a lot of excitement, the result of the Phase IIb in patients with psoriasis, which are expected in H1 2023.
Odiparcil and this is, I would say, another or really an update on this conference. We have had over the summer an important meeting with the FDA, and we are very pleased with the outcome and the feedback provided with the FDA. We know that we can go directly now into children age of five to 15 — five to 14 with MPS VI. We know that the design we presented to the FDA, which is a single Phase II/III trial can potentially support marketing application. This gives us confidence in the search of opportunities to find a new home for odiparcil and really seeing this feedback provided by the FDA really goes into the right direction for this project.
Finally, on the financials, we have been continuing to reinforce our cash position both with dilutive and non-dilutive sources. We have had close to €50 million through a combination of At-The-Market program, which I will remind you is managed by Jefferies and it’s only made of rigorous inquiries and also some non-dilutive funding coming from state-backed financing from the French — France.
We also are very pleased from the European Investment Bank loan that we secured. €50 million loan award agreement of two tranches of 25% and 25%. And we are pleased by the fact that with the upfront that we are expected to receive from our partner Sino, we will be able to secure the first tranche from EIB and this would extend our cash run way in Q4 of 2023.
And then, lastly, also the recognition of being selected by Euronext as part of the Euronext Tech Leaders. So in this important index is also a nice recognition of the work that has been done so far.
Let’s now move to lani, I just would like first before entering into the details give a bit of an overview of the competitive landscape in NASH. It’s nice to see that positive news happening in the field with recent data from our peer [ph] and others.
Now when we look at the landscape, I think all eyes are pointed to the part one of Phase III results that are expected from the waste material and then you see that from this slide, you see that lani really well positioned in terms of timing of when the results will be available and were really part of this limited number of promising compounds that are now in Phase III or planning to enter into Phase III.
When we look at the competitor, actually we can divide them into two sections. We have the oral drug and the injectables. When we look at the oral drug, we are really extremely well positioned as the only oral drug that has met really the two important endpoints that are considered by FDA and NDA for approval for NASH resolution and improvement of fibrosis.
And there is another section where you have injectables with recent data from Cure, where they too have managed to secure hitting both end points with the difference 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 are going statistical significance on both endpoints, where the results presented by competitors are mostly based on per protocol population or even when you consider Europe from competitors.
So now let’s move to lani, and before we get into NATiV3, I would like just to give some of the highlights of the licensing and commercialization agreement we signed recently and then I give the floor to Philip for the presentation of that.
Why we decided buy this opportunity is because China and Greater China is in terms of national position very attractive. Of course, vast population, but it also when we look at the prevalence of NASH, there are publication and 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 are also excited because we — 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 is an injectable and that has not been able to show their Phase IIb in pre-cirrhotic patients, but also in the cirrhotic patients have not been able to show an anti-fibrotic activity. We really believe lani, especially with the partner of the quality of Sino Biopharm is really well positioned to be potentially a leader in this — in the NASH field in China.
In terms of financials, so these are the highlights that have been described in the press release, an upfront and expected upfront of $20 million, followed by short-term clinical milestone that could potentially trigger an additional $5 million. And then globally, the deal contemplates a total of $290 million of clinical, regulatory and 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 large terms that needs to discussed, especially with regulatory authorities. Two main obviously we see viable. One would be for Sino Biopharm to join the global NATiV3study or the other alternative will be to run an independent study. Important to point out, of course, that all the costs lead to the development in Greater China will be borne by our partners.
So, with that, I will give the floor to Philip that will give us a quick overview of Sino Biopharma and then, therefore, moving to page 14 of the presentation.
Philip Duong
Thanks, Frédéric. Just to check if you can hear me.
Frédéric Cren
Perfectly.
Philip Duong
Perfect. Okay. Thanks, Frédéric, 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 will give a quick background on Sino Biopharm and I am currently looking at page 14. So Sino Biopharm, for those of you that don’t know Sino Biopharm, we are one of the largest, actually, if not the largest Chinese pharmaceutical group in China.
We are listed in the Hong Kong Stock Exchange since 2003. We currently have a market cap of slightly over US$10 billion and then last year, we had revenues of US$4 billion. Globally, we are ranked the 40th largest pharmaceutical globally by Pharm Exec’s, 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 up as generics back in the ‘80s and we have 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 U.S. 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, and this is from IMS data, and that’s more than double our closest competitor.
Sino Biopharm, it’s run — it’s a — it’s privately owned by the Tse 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 have been in the Chinese market since the 1980s.
Next page, please, page 15. So the way to think about Sino Biopharm really is, we are 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 Inventiva 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 are also very large investors in the online health, for example, we are 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 are also present globally through invoX, which we established in 2020, where we have done recent acquisitions in F-star, Softhale, Fion [ph] and also associated with the Karolinska Institute Group through Karolinska Development. And we are also present in vaccines where we work closely with Sinovac where they developed the corona back 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 are quite confident we can lower the COGS, which is important for countries where pricing is not as high like China. And we also have one of — we have the largest sales team in China with over 13,000 reps covering the entire China, covering about 90% of the hospital channels.
And then if we move on to page 17. What I’d like to leave off is, Sino Biopharm 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, which is, one is Entecavir Runzhong, which we did $4.6 billion of sales in 2018, which was basically unheard of for in this space. We also have an innovative product called Ganme [ph], which is basically — mostly used against — usually for hepatitis B patients, but it’s the nation concept of liver protection, which is actually closely quite linked to NASH, where we did $20 — $2 billion of sales last year and has been consistently growing since we have 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 Sino Biopharm and I will pass it back to Frédéric for the rest.
Frédéric Cren
Yes. Yeah. Thank you, Philip. So I think everybody can understand why we are very excited by this partnership and the opportunity that it opens up. So moving back to NATiV3. So where do we stand? The progress now, 24 countries are included in operation and we have secured full regulatory approval on 23 out of that. We have closed activities in Ukraine and also decided not to move forward in Russia.
Where we stand if this is a situation at the end of August? So we have qualified 463 sites and 297 are activated. So really strong progress there. However, if you follow 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 has led to the increase of the number of sites, we are still facing a recruitment that is behind our expectation and this is mainly due to a little of ray [ph] that is higher than anticipated and this really led to the communication last night that we see that now the last patient first visit for the Part 1 is now targeted for the second half of 2023 versus H1 2023 as previously commuted.
That for NATiV3 and now — I will now hand over to Michael, who will give you an update on the two phases that are ongoing, so the one led by Professor Cusi in the combo static called LEGEND.
Michael Cooreman
Thank you, Frédéric. As you mentioned, there are two studies that are in Phase II. One is on slide 20, a study that aims to provide more information on data on the mechanism of action of lanifibranor as a fund agonist in patients who have not only have type 2 diabetes to conditions that occur often in the same patient, given the similar underlying disease biology.
Specifically, this study aims to show that lanifibranor decreases intrahepatic triglyceride content, improves any cirrhosis, specifically the insulin sensitivity thereof and also insulin sensitivity in hepatic and muscle tissue, which is a core mechanism of action of Hippo signaling, endogenous hepatic glucose production and markers of cardiometabolic health. The investing the principle is one type study and sponsor and principal investigators, Ken Cusi at University of Florida.
The total of 34 patients with that of the 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 the effect size of more than 50% reduction of intrahepatic fat, which is also based on data that are available for how [inaudible] work in this indication — in this finding.
The primary endpoint is a change in intrahepatic triglyceride 25 by MR spectroscopy and so baseline compared to 24. And in addition, there’s a lot of secondary endpoint that will provide a kind of a comprehensive picture on how lanifibranor improves metabolic health in these patients, starting from insilicosystems, NAFLD solution defined as patients with a very low intrahepatic triglyceride content, change in hepatic fibrosis measured with elastography, MRI-based and ultrasound based MRE and FibroScan, as well as biomarkers, and of course, also safety and tolerability markers. The results will be expected for early 2023. All patients are enrolled. Due to a little delay the last patient started, the results will be expected in the first quarter of 2023.
So go to the next slide, slide 21. This is the so-called LEGEND study is an acronym and it is essentially a combination of lanifibranor and 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 SGLT2 inhibitors provide additional metabolic benefits to lanifibranor. And we, therefore, are a very attractive way to explore the additional benefits of this combination in the proof-of-concept setting.
The study is done with two principal investigators, Dr. Dr. Michelle Lai, Harvard and Onno Holleboom from the University of Amsterdam. We have around 40 sites, which are in four countries in the U.S., in the U.K., in the Netherlands, Belgium or France of five countries. The FDA — the IND is open. The study has started. The first site was activated in the first half of 2022 and we expect topline results in the second half of next year.
Patients — adult patients with type 2 diabetes and NASH are to be included in the primary efficacy outcome is HbA1c, which is a mark, of course, of insilicosystems and metabolism, which is also relevant for — in the 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 that adipose tissue naturally 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 of glucose and lipid metabolism markers of inflammation, body weight and other safety and tolerability issues, of course.
So wealth of data. The study will enroll 63 patients and the treatment is half a year. So randomized study, randomized double blind for lanifibranor and placebo, open label for the composition, lanifibranor plus empagliflozin is one ARM, lanifibranor alone is another arm and placebo is the third arm.
Next slide, mentioned aside, run in these five countries in Europe and the United States. We have the study approved in France and U.S. and its running better and submissions are completed in the remaining countries. So we expect topline 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 lanifibranor in clinical settings to start with in the first quarter of next year, the data from the study run by Cusi in Florida, topline results from the Phase II trial in patients with NAFLD type 2 diabetes.
Then the year thereafter in the second half of 2023, so the same year, in the results — the topline results from the LEGEND study in patients with NASH and type 2 diabetes, the combination of lanifibranor with impact lymphoid and then in the second half of 2025, the topline results of Part 1 of the current pivotal NATiV3 study currently ongoing, of course, and wells in its way in patients with NASH and significant fibrosis F2 and F3. And that’s it for me. So…
Frédéric Cren
Thank you, Michael. And I will give a very brief update on ABBV-157, here again the — our again [inaudible] security in Phase IIb with our partner AbbVie. We were last week in Chicago and we are extremely pleased with the progress of this molecule. You know that we are extremely excited by this mechanic of action. We are again has a possibility really to suppress IL-17F gene expression, but as you know, is a validated target in clinic.
Clearly, the potential of a once-daily orally available ROR gamma with a target product profile that, as you know, that we have said in the past, what we are targeting is the Humira efficacy with better safety in the end of a company like AbbVie that has such a strong expertise in optimal disease, really something that really excites us and we really think we have a little to do here in our pipeline.
The meeting with other day in Chicago was really great. We see that the real excitement around this molecule. Now we have to wait for the Phase IIb trial that is currently ongoing. This is 200 patients, 15 weeks, a trial in patients with moderate to severe psoriasis and that the primary end point, there is a measurement of 75.
Also worthwhile noting that in parallel, AbbVie has launched a Phase I that is needed to start Phase III, so too positive to see that plans are in place to in the case of success. And then I would say that for us now just need to wait for the results of the Phase IIb, which as indicated in clinicaltrials.gov, the results — the trial is expected to end in Q1 2023, so result — we should have the results in the first half of next year.
We also, of course, we are excited is also because we are financially rewarded by the mix of milestone, but especially royalties that start from mid-single digits and can reach double-digit level. And of course, this drug is approved. We are convinced, given making 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 Inventiva.
So that was the very AbbVie update and let’s move to odiparcil and Pierre will give you latest on this program.
Pierre Broqua
Yeah. Thank you, Frédéric. So, yes, we are very excited to update you on the odiparcil program. But I just like to start with a recap on MPS and [inaudible] action on Page 27. So as you know, MPS are innovative disorders that are characterized by the dysfunction of lysosomal enzymes, which are required for the breakdown of glycosaminoglycans, the GAGs. Within this family of disorders, MPS VI is caused by mutation in ERT SBT [ph], which encodes the enzyme leading or responsible for the degradation of DS and CS. So MPS is actually an accumulation of DS, dermatan sulfate and chondroitin sulfate in all cells of the body.
So then, of course, MPS 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 up to 40 or 50 in slower progressing cases. So today, there is one treatment approved, an enzyme replacement therapy, Naglazyme, 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 MPS VI, even in patients that are actually treated with ERT.
So the next slide, please. So we have odiparcil, odiparcil is a small orally available molecule that decreases the CS and DS type of GAGs accumulation in disease cells. And this, as you recall, a very unique GAG clearance mechanism of action.
On top of that, odiparcil is, of course, all available, well distributed and can penetrate difficult to meet tissues including cartilage bone and cornea, offering, therefore, an opportunity to address the clinical manifestations that are currently not treated by ERT.
So we now have conducted a Phase III study called iMProveS in adult MPS VI patients that were at an advanced stage of disease. And in this study, odiparcil found to be safe and to provide beneficial effects in both ERT treated and ERT-naive MPS VI patients and this only after a short treatment duration of six months. Therefore, we believe that there is a conversional for further assessment of odiparcil efficacy in younger patients.
Next slide, please. So, overall, odiparcil has a favorable safety profile shown in multiple clinical trials. As you maybe remember, the component is developing previous indication where more than 1,500 patients have been exposed to the drug.
On top of the, I would say, very clear efficacy data in MPS VI patients or mice model that we have also published. We see odiparcil will be a potential game changer, has being the first oral therapy with the ability to broadly address a wide range of clinical manifestations in MPS VI patients. This market, as you know, is close to a $400 million market. In addition to that, odiparcil has also the potential to treat other MPS, where CS and DS accumulate such as MPS I, MPS II, MPS IVA and MPS VII.
So in MPS VI, next slide, odiparcil 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, also as a monotherapy in ineligible patients.
So now let’s dive into the recent FDA discussion. As you recall also from a regulatory perspective, we have obtained odiparcil orphan 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 many objectives, patient population, endpoints, a clarification that we believe will be helpful for future partnership discussions.
Next slide, please. So in short, the feedback from FDA was that the single Phase II/III study of one year duration in MPS VI patients five years to 15 years of age would support five-year filing. This pivotal study that we call Prodigy [ph] would be double-blind, randomized, placebo-controlled, evaluating the ability of one dose of odiparcil administered in combination with ERT versus placebo in combination with ERT and this to enhance mobility is a primary objective and to improve entrance while reducing fatigue and pay. These are secondary objectives. Primary endpoint will therefore be a 6-minute resistance and secondary endpoints would be 3 minutes per line and pain assessment through a questionnaire.
This first part will be followed by a 12-month safety expansion with all patients under odiparcil plus ERT. The study contemplates to enroll 15 pediatric patients for 12 months, potentially leading to the filing of odiparcil approval as ERT or in combination with ERT in patients five years of age 12. So following this feedback from FDA, we believe that odiparcil will represent an attractive partnering opportunity. Thank you.
Frédéric Cren
Thank you, Pierre. Let’s move to the last slide before we wrap up. So we can move with Jean to the update on financials.
Jean Volatier
So let’s go through the key financial figures. So — and you will see it’s quite straightforward 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, obviously, information is the cash position. So as you can see, we maintained a reasonable level of cash versus the end of 2021. So we are at €87 million versus €95 million at the end of last year. So this prior to the consequences of the Chinese deal was allowing us to operate until Q2 2023, and as disclosed and explained the deal with the Sino Biopharm allowed to gather the conditions for reaching the first tranche of the EIB, and therefore, allow us to extend the cash runway through Q4 2023.
Let’s go through next slide with the key evolution of the profit and loss account and cash flow. As I said, so no revenues for this semester. As a reminder, Inventiva recorded €4 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 usually, the key and stable information with regards to R&D investments, which represent 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 NATiV3 studies primarily 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. affiliate versus only one quarter in 2021, a reasonable increase [Technical Difficulty] due to the increase in personnel cost by due to the charge related to the share-based payment, which is non-cash payment and also a full semester [Technical Difficulty] last year.
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 Sino Biopharm deal and EIB first tranche. So the net operating cash flow reflects the evolution of the R&D expense essentially, and in a lesser extent, the G&A evolution.
The net financing 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 — what was soft loan in the back stage loans for €5.3 million. 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.
Frédéric Cren
Thank you, Jean. The last slide before we open to Q&A. So what are the next milestone, here is the list of what have been achieved so far. And I would say that we have in front of us two important clinical readouts, one concerning lani, at the beginning of the year, Q1, the results from the study led by Professor Cusi patients with type 2 diabetes in NAFLD and then, of course, the data from the Phase IIb that is currently carried out by our partner AbbVie this year is really, I would say, will be the — very important event for our company next year.
With that, let’s move to Q&A, as the operator will provide you the — how to ask your question both via the platform or via the telephone.
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] We have the first question coming from the line of Ed Arce from H.C. Wainwright. Please ask your question. Your line is open.
Ed Arce
Hi. Good morning. Can you hear me?
Frédéric Cren
Perfectly Ed.
Ed Arce
Wonderful. Thanks for taking my questions and congratulations on the deal with Sino Biopharm. I have three questions. First, you mentioned the recent results of Akero 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 Sino Biopharm deal that they could either join NATiV3 or decide to conduct its own Phase III trial. And I wanted to know if they — if you and Sino decided to have that joined to NATiV3 trial, would that have any impact on the time line? And then lastly, the top line NASH results from NATiV3 looks like it’s still about three years away, second half of 2025, which based on your most recent runway creates about a two-year funding gap. So I am wondering if there are any additional opportunities for funding say from the results from AbbVie or perhaps initial funding from a future partnership on odiparcil? Thanks so much.
Frédéric Cren
Thank you, Ed. So very, very cumulative question so oh I got to take off sorry. I will try again, sorry, can you hear me?
Ed Arce
Yes. I can hear you fine.
Frédéric Cren
Okay. Sorry, we just had a terrible echo here. So, on the first question, maybe Pierre and Michael will complete for me, the difference protocol versus ITT. I just think it’s important just because of Akero produce some slides where they used and compared the Phase II data, I think it’s important also to have a complete picture. And from what they said in their own presentation is that if they had used an ITT approach, they would have lost 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 made will lead to both a regulatory endpoint. But nevertheless, I just think it’s important that we retain that because on the Phase III, what the regulatory authorities will be looking is the data from the ITT and the fact that we were able in the Phase IIb to be sustained on that population give us more confident or even greater confidence that we will succeed in our Phase III.
Then I will ask the second question and Philip don’t hesitate to complete my answer. So your question was, in the event biopharm joins the NATiV3 would that have an impact on the time line. 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 1. But we are prudent and therefore, we do not — we don’t take this upside in our projection. And then last, I don’t know, Philip, anything you would like to add to this?
Philip Duong
Yes. Thanks, Frédéric, 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, simply CD regulatory approval and such.
But I think once or if we do go down the route of a global multicenter trial. I think we are quite confident that our capabilities to sort of quickly open sites as well as leverage scale networks to sort of recruit the patients quite quickly to sort of not delay the timetable from Inventiva site.
Frédéric Cren
Thanks Philip and then last question about the two-year funding gap until the Part 1 read out. I think there are two ways to read it — it’s a glass of LT. We can also read given the difficult times in the market if Inventiva secured financing until Q4 2023.
And also as you mentioned, I think we have several opportunities so that are both dilutive and non-dilutive — on the dilutive, we have an APM open, and we have always benefited from the support of front enrollment.
And then on the non-dilutive side yes, we are excited by the discussion with the FDA for the feedback, which according to us reinforces the rationale for odiparcil, continue develop in MPS VI and we have not changed our strategy. We do not want to develop odiparcil on our own. We think it’s a good candidate for partnering. Will we succeed it too soon to say, but the FDA feedback gave us confidence.
And then also, I think lani is a very attractive compound, and there are other geographic areas beyond China where the bartering would make a lot of sense. And then finally, as the partnership in the short-term, we — if they decide to move into Phase III, of course, this will trigger a milestone. But always like 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 if next year, the program moving to Phase III, Inventiva will have a very promising asset like lani NASH and the drug in Phase III in psoriasis, maybe potentially other [inaudible] disease indication finance and carried out by AbbVie, so I really think an interesting value proposition to investors.
Ed Arce
Great. That’s all right. Thank you.
Frédéric Cren
Thank you. And I think we were expecting a question from Jeroen and we don’t hear him?
Jeroen Van den Bossche
Hello.
Frédéric Cren
Yes. We can hear you now.
Jeroen Van den Bossche
Hi. Sorry, there seems to be echo here on the line. Congrats also from KBC with regards to the Sino Biopharma deal and with the results for odiparcil, maybe from my end and following up on the Akero a little bit. NASH clearly has been a little bit more of a challenge over the past years? Do you see renewed interest from investors, do you believe that also with more and more people refocusing on it, there will be non-invasive, let’s say, like diagnostic methods coming online? And maybe one last question — you guys can give me or us an estimate of the NASH size in China?
Frédéric Cren
All right. On the first question, I would say yes, in the sense that good news from other competitors like Akero and other are a positive for the space. I think we — the failures of other compounds have — and I don’t think it was justified shed a negative light on the successes of other and include that learning that.
So yes, it’s very positive to see other companies succeeding because this provides a positive sentiment on the space and they really hope that continues. And this is why we are looking and cheering for Madrigal success in their face. On the non-invasive, maybe, Michael, do you want to just give an update on the recent progress there?
Michael Cooreman
Absolutely. So, yes, and our focus on the FDA, the FDA this data requires histology as the target efficacy endpoint. I should say then that in the past, [inaudible] been quite some progress in the — 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 replacement for histology.
We are all active part of that discussion, including our academic colleagues, R&D industry as well as the FDA, and I think that’s very good news. I think with regard to lanifibranor specifically, what gives us confidence is that lanifibranor given this mechanism of action has shown strong efficacy on the histology endpoint, but also in a broad range of biomarkers that reflect the disease as well. So I think in — for both histology and IT, I think, lanifibranor has a very strong position.
Frédéric Cren
Thank you. And the last question on the NASH size market in Greater China. Personally, I have not seen any forecast or any public data. The only data I have seen is what we mentioned before is about the prevalence that seems to be like 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, Philip on your side, have you seen anything public on the market potential or anything you can disclose?
Philip Duong
Yes. Sure. So, as you know, whenever we improved NASH treatments, a bit of an echo I will just go ahead. Yes, so without any NASH treatments, I think there’s quite a large range of numbers that we have seen from as low as sort of 2% to even as high as 6%, 7%.
But like Frédéric, like he 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 have 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.
Frédéric Cren
Well, thank you. And then we have a question from Alex from Bryan, Garnier. The floor is yours.
Alex Cogut
I hope you can hear me well. Yes thanks for taking my questions. So I was just wondering if you could share a bit more on the screening failure in the Phase III. Like what would be the rate of failure you are 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?
Frédéric Cren
Yes. Enrollment, thank you. The screen failure rate is high, and we have seen that, first of all, happening across the type field of NASH clinical studies. So I don’t think what I know actually that all data are not in aberration with others, which is reassuring.
So NASH is as many other indications challenging. Having said that, we actually have advanced a lot of efforts to detail the reasons for the screen failure rates — and basically from satisfied every individual case.
And overall, there are a couple of reasons, which I have to do with lab values of course, and also with the histology reading, which as you know, seen quantitative scoring system. And we have three expert pathologists. I think they are among the very best, if not the best in the field. We spent a lot of time bringing it together in the formal sessions that they can align the reading before we start looking at biopsy in our part of the study.
And we have now also vented 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, a system whereby each biopsy is set by two of these pathologists independent of each other. And if there is a non-alignment, say one scores fibrosis stage 3 and the other one at 4 or at 2 and at 1, then there’s a tiebreak. When tiebreak automatically will then define what score is align.
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 prescreen patients so that the likelihood that when a patient enters the screening process that the patient ends up being a screen 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 it’s not — it’s well known that aminotransferase, specifically as C phase [ph] we call 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.
Alex Cogut
Got it. That’s very helpful color. Thank you. And just a question on cedirogant if I may it seems like AbbVie is pretty excited about the compound given the speed of recruitment in the Phase IIb. But I don’t believe they have actually released Phase Ib results, which makes me believe there may be waiting it for AAD in March, but then they might also have the Phase IIb data. So do you have any insights into kind of their plan for releasing Phase Ib or Phase IIb data next year?
Frédéric Cren
Well, you are right, the Phase Ib data has not been that if they share. The next important congress is in the early AAD in March opposite of March. That could be a date where they could publish for the results until the abstract is available is difficult to confirm that. And in terms of plan of it look more education of the Phase IIb, I don’t think this has been decided yet.
Alex Cogut
Got it. And on the back of the Phase IIb, 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 III? How can we think about that?
Frédéric Cren
No. It’s related — the milestones are — directly combined for us will be beginning the initiation of the Phase III.
Alex Cogut
Okay. Okay. That’s all from me.
Frédéric Cren
In any indication — we don’t need to be psoriasis if we — first patient enrolled in the first Phase III.
Alex Cogut
Okay. Understood. Thank you. That’s it from me.
Frédéric Cren
Thank you. And then Delphine Le Louët from Société Générale is also online, and so very happy to.
Delphine Le Louët
Yes. Hello. Hi. Good afternoon, good morning, everyone. Different question from my side, can you Fred, 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 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 towards 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 add up ramp for Chinese patient within the NATiV trial? And finally, I was wondering, can you remind us the other condition that you have from the EIB to unlock the other €25 million envelope? Thank you very much.
Frédéric Cren
All right. To your first question about figures in terms of number of screen, screen failure 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 others, 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 we have 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. So that was not the case. So that how that has been sort. And now clearly, for our team and ICON, is to go back to what Michael said is, we need to improve this screen failure rate that is high for us it’s high for everybody in the market, but we are fully care about them and we need to bring it down.
On your second question about what the feedback from the China regulatory authorities will be on the approach. I frankly do not know because I have no experience with them. Maybe, Philip, you want to comment on that, but maybe right now, it might be a bit too speculative I don’t know – what would you say?
Philip Duong
Yes. Thanks, Frédéric, 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 as well.
Delphine Le Louët
Yes. I can imagine. But the idea is to know if Sino Biopharm 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 partnering out-licensing, I mean licensing the right for Chinese market?
Philip Duong
Apologies, I didn’t quite get the question. Is it how you would?
Delphine Le Louët
No. I was wondering if Sino Biopharm already shared with you some of their experience from the past from other licensing deal they may have or any view that they have or any confidence that they have towards the regulatory passing in China?
Philip Duong
Yes. Sure. So I think global multi-centers are joining our Phase III 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 risk — it’s done well.
But unfortunately for NASH, not that it’s never — not that it’s been done before, but it’s new. So I think it will be the first global multicenter trial in NASH where if we do it, I think it will be a landmark situation. So for other therapeutics there is — it’s been done before we have experience with that.
Delphine Le Louët
Okay. And Frédéric the last question regarding the financing, yes?
Frédéric Cren
Yes. For AAD the second tranche I will let Jean describe the competition.
Jean Volatier
Good afternoon, Delphine.
Delphine Le Louët
Hi, Jean.
Jean Volatier
Yes. We have disclosed all information with regards to the CPs and the — CPs condition precedent. I will not go in state, 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 second tranche one year after the first one is to get a cash injection of €70 million, okay including the initial cash injection that is required for the first tranche.
Clearly speaking, we match we are on the way to match — we have matched €9.5 million with ATM. We will match the $12 million euro with China. So mathematically, we missed €50 million to bridge.
And as we have explained in terms of financial strategy, we will get other opportunities to bridge this €50 million. There are also other CPs like, as you may know, the warrant side of the deal because there are some issuance — of warrants for each tranche.
And there are some operational conditions also relating to mix of — activated sites at the time of the raising, or a number of randomized patients, which is quite first reasonable in terms of negotiation with AAD and attainable within the current plan of development.
Frédéric Cren
The last CP, which we have met, was to sign a partnering that we have done or as we entering Phase III. And I think we are [inaudible]. We hope that we will be — able to meet the second potential condition.
Delphine Le Louët
Thank you.
Frédéric Cren
Very good. And then we have no more question on the phone, but we have some questions on the platform. Some have been covered, one has not been covered — that can we disclose what, are the milestones beyond the €5 million [inaudible] this unfortunately we can. And then there is a question about the YAP-TEAD program, where do we stand there? And then I will turn to Pierre for our…
Pierre Broqua
Yes. Sure. Thank you for the question. So yes, we are also very excited with the progress made with this project. We are actually working on very specific molecules, three compounds that are now into — in vivo evaluation phase. And this compound differentiates quite well from other competitors like from Viva, Akina [ph], even Novartis in the middle inspection and the outcome being that those compounds are capable of inhibiting the proliferation of sales, the proliferation of which is dependent on the update.
But also tested, and that makes a big difference our profiling and as it is something that’s communicated earlier this year. We have demonstrated that our Akina compounds acting on the small pockets of FTs are actually preventing the FTs association and preventing the proliferation of FT dependent sales, but are capable of preventing the proliferation of past-dependent sales. Our lead compounds do both, which opens the opportunity to address many more cancers and those are contact currently in vivo testing and looking forward for the in vivo data.
Frédéric Cren
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 Philip for staying up late now because it’s — more than 9 p.m. in China.
Thank you and thank you for making yourself available. I think it was important to describe the capabilities Sino Biopharma. Otherwise of course, we will 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 are actually just after this conference run to the celebration of the 10-year anniversary of Inventiva. We started this adventure 27th of August, 2012.
And today, we are really pleased to be in a position to celebrate this important landmark for Inventiva on the back of positive news for lanifibranor and for odiparcil and also for cedirogant. Thank all of you for your participation, and I look forward to seeing you very soon. Thank you.
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