Inventiva S.A. 2022 Earnings Call
Speaker 1: You you.
Speaker 2: Good day and thank you for standing by. Welcome to the Inventiva 2022 full year results call and webcast. Welcome to the Inventiva 2020 full year results call.
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Speaker 2: Please note that today's conference is being recorded. I would now like to hand over to your speaker, Mr. Frederic Rennes. Please go ahead, sir. Thank you, Pareto, and welcome to everybody to this full year 2022 financial results.
Speaker 3: As usual, I will be making with my colleague forward-looking statements, so please have a look at the regulatory documentation that is available on our website. In terms of speakers today, I'm very happy as usual to have Pierre with us.
Speaker 3: our CSO and co-founder Michael our CMO will go through an update of our three important clinical trials with with lani-fimerner of course the phase three but also the two phase two that are ongoing and then Joe will conclude the presentation with an update on the financials.
Speaker 3: Of course, at the end of the session, we will have a Q&A session. So let me give you, first of all, some highlights for the full year. So let's start with our lead program, Lani, in NASH and start with Native3, where we've been, I would say, very happy to work and extend... So haven't tried to do that.
Speaker 3: developed the phase 3 in 23 countries and now we have more than 350 clinical sites that are active and more than 300 that have screened at least a patient.
Speaker 3: We have throughout the year and we continue to do so implemented a series of measures to boost enrollment.
Speaker 3: And I would say that this continues throughout 2023.
Speaker 3: We've done many things and we're very proud of those and grateful to our team.
Speaker 3: reviewed and implemented the new process.
Speaker 3: to speed up how biopsies are analyzed.
Speaker 3: We have trained site, we have put in place incentives.
Speaker 3: We have included site networks which are specialized, we have a strong NASH expertise, and we also have closed sites that were not performing to our expectations.
Speaker 3: We have developed patient material, including opening recently the patient website.
Speaker 3: We have provided support to prescreening activities to sites, including providing a screening algorithm to better identify patients.
Speaker 3: We are organized and we are currently organizing investigator meetings.
Speaker 3: and also made several protocol improvements.
Speaker 3: All of that, I would say, makes us confident that we will...
Speaker 3: achieve our target to have the last patient first visit.
Speaker 3: have targeted for the second half of 202023.
Speaker 3: We have also, and you know and Michael will go through that, developed a new design for the native 3 which is much more patient-centric. We have started to implement this new protocol. It has been submitted and we're very pleased to see that it has been approved in key countries including the US.
Speaker 3: This morning, Akira announced their design for the Phase 3 and we're very pleased to see that Akira is working on our footsteps with a design which is very close to ours and especially they have selected the same primary endpoint.
Speaker 3: as our primary endpoint in 83. On the other trial, I think it's important to point out that Legend, we have activated the first clinical site in US and in Europe , and of course we are randomizing in all of the countries where Legend is open.
Speaker 3: And then finally, we're looking forward to the result of the investigation study conducted by Professor Cusi from the University of Florida. The last patient was enrolled in September 22. He recently has changed with Professor Cusi. He is going through the database, analyzing the last.
Speaker 3: cleanups and getting ready for the database slot. So we're looking to be able to publish those results by middle of Q2 23.
Speaker 3: The 22 has also been very active in terms of partnership, very proud of having secured a strong partner with CINO BioPharm after an extensive due diligence from their part, which proved that our drug is well positioned in China, which as you know is a very promising market.
Speaker 3: for NASH, given the prevalence of the disease in China. It has allowed us to secure close to 13 million euros of upfront payment and we're eligible to additional milestone that can reach 290 million on top of royalties.
Speaker 3: You know that depending on various discussion and interactions in a biopharm we have with the regulatory authorities, they can join the native three trials. And finally, I would point out that we are very pleased by the strategy of...
Speaker 3: finding partners in Asia. This allows to speed up the development and the entry to market and we continue exploring all the potential commercialization of land fiber and oil nation. And then finally in terms of IP, we are securing in the US a pattern that strengthen our IP estate, especially in patients.
Speaker 3: with especially in neurotic patients.
Speaker 3: Looking at the other program in terms of ABB 157, unfortunately you know that we received, we were notified by ABB that the following unexpected top result, you know, long-term top studies have decided.
Speaker 3: to hold this program. We received a notification in October .
Speaker 3: On the departure, we have a very constructive discussion with the FDA over the summer. They confirm that we can move with this drug in children given the safety profile of the drug. And also have validated that single phase two free trial.
Speaker 3: in children would be sufficient to secure this positive, most aid, was made for a lower-amines, mini-
Speaker 3: Financially, we've been very active as well. We secured a 50 million euro loan from the IB, one of the largest for biotech in Europe . Out of those 50, still 25 are to be used and are not included in our cash value.
Speaker 3: On top of the 13 million, or close to 13 million we received from CINO, we also raised close to 10 million from our ATM program and also secure additional facilities backed by the French government. We also raised close to 10 million from our ATM program and also secure additional facilities backed by the French government.
Speaker 3: close to actually a bit more than 5 million euro. At the end of note we were selected.
Speaker 3: There's a very limited number of players to be part of the Euronext Tech Leader segment and also we're very pleased to welcome Dr Lucy Liu, the new board member.
Speaker 3: So let's talk a little bit about lannifibrinor before I...
Speaker 3: give the floor to Michael. Let me just remind you some key features of Lanifibernor. Very importantly, the profile of the drug is really unique. We are to our knowledge the only panpipar occurring in development in NACHE.
Speaker 3: And this profile is really important because the strong results we were able to show during the phase 2B that granted breakthrough therapy, will, according to us, due to the ability to activate the three either form. We also remind you that we are not a TVD.
Speaker 3: and that we have not seen any of the typical liabilities that characterize TZT, especially during the preclinical program. The safety continues to be in our mind very favorable. We recently had the DSMV in our native 3 and the conclusion.
Speaker 3: rules as for the previous SMBs we have had throughout the course of the history of Lani Fibonore that we can continue the trial with no changes.
Speaker 3: I mentioned a very strong result of the FIF2B. I think it's important to try to position Lani Fibburnor compared to the potential competitors. This is of course very difficult because trials are of course different. Also, we have reported our data.
Speaker 3: giving the ITT population because this seems to us the relevant population because this is the one that is considered by regulatory authorities while most of our competitors only reported data for protocol. But I think it gives an idea that Lani Fibburnore, when we look at that resolution and know-working of high-grosses, a very compelling data.
Speaker 3: Certainly, you know, with a profile, very competitive, probably superior to the other oral drug in development and also competitive.
Speaker 3: profile versus injectables.
Speaker 3: This is even more true when we look at fibrosis improvement, which for us remains given the disease and given what we want to achieve, which is that patients with NASH avoid to become cirrhotic. We see that on fibrosis we have a very compelling profile.
Speaker 3: very competitive even with injectables. Lastly, I also would like to show very briefly the primary endpoint we have selected and that also Akera has selected for the phase three. You see that this primary endpoint was met by...
Speaker 3: both our low dose and high dose, 800mg and 1200mg, and that we have 3-4 times more responders.
Speaker 3: Lastly, I also would like to point out that this is a compelling endpoint because it enables to really reduce the placebo. We have 7%, you see that a hero was 5%, so you really see that with this approach we are able to reduce the noise of the placebo effect. Similarly, we have found that the remember step greater to quality than the desired result Bag Community, which begs the question of value value. programme that does notwater effect, what happens if a certain compound Warrior is affected, that safe for the entire Hou-eng you will find thehat887 team at a later time
Speaker 3: Let's talk of the interaction we have had with the FDA, a positive interaction that have led to the new design Michael will present. And I think this is a very good step for all the field with this approach to have a trial.
Speaker 3: based on surrogate histology endpoint in patients with non-cirrhotic NASH and then have the possibility to secure full approval with an outcome trial in patients with compensated cirrhotic NASH.
Speaker 3: I think that makes the development more feasible. Also, from a timing point of view, shorter development to secure full approval, and also in our case, it would expand the population that we could address by also including patients with compensated seros.
Speaker 3: So that's for my brief introduction and I will now turn to Michael that will give you an update on NITIS 3 and also the other two phases that are ongoing.
Speaker 3: Thank you, Frederic, and good morning, good afternoon to everybody.
Speaker 3: I'm on slide 15 now, which summarizes the development program for London Fibrino. On the left in green you have the completed study that was summarized by Frederick just a minute ago, so the phase 2 study and I would just
Speaker 3: highlight also that this was a six-month treatment with a very robust efficacy on histology, both NASH activity and fibrosis, which is a testimony to the frequency of the compound, to have that degree of...
Speaker 3: effect on fibrosis after a short treatment period for fibrosis evaluation. Based on these data, the efficacy and the safety of the compound, the FDA has granted breakthrough therapy designation for vanifibronor Enash.
Speaker 3: And on the right in orange, the phase three study, which is currently ongoing in the midst of the phase three study, as you know, and I also speak about two earlier phase two studies that Frederick also mentioned. So on slide 16.
Speaker 3: As you heard, we have updated the design of the study to make it more attractive to patients, investigators, removed the seven-year placebo-controlled treatment period and have had very good interactions with the FDA on this change and as you know the FDA has also made...
Speaker 3: every two weeks of treatment has remained unchanged.
Speaker 3: We have two active arms and a placebo arm, and there will be two biopsies, one at baseline, maybe historical, but one biopsy at baseline and one at the end of treatment for a total of about 950 patients.
Speaker 3: After that, patients will remain in the study but they will be re-randomized to an active treatment arm so they will not be receiving placebo beyond that time which is seen by everybody as a very positive approach.
Speaker 3: And the active treatment extension will be at least 48 weeks after that bleed out for the secondary or after the second biopsy.
Speaker 3: So that will provide also data on longer term treatments with lanofibrilar.
Speaker 3: In addition, and this is also a new aspect, we will enable patients who screen fail because of histology but who have NASH and fulfill all the other inclusion criteria to enroll in an exploratory cohort of about 200 patients.
Speaker 3: again using the two doses and placebo controlled. And this exploratory cohort will, for example, enroll patients who are staged for their fibrosis by SF3 by one pathologist, F4 by the second one, and the tiebreaker says F4. These patients would have.
Speaker 3: the exploratory cohort also will not have a second biopsy. So we will go to the next slide, number 17.
Speaker 3: The readout of the histology at 72 weeks is the basis for submission for accelerated approval in the United States with the FDA and the corresponding conditional approval by the European Medicines Agency, the EMA.
Speaker 3: And this is with regard to the FDA corresponding to several communications that they have made and their continued support for accelerated approval in the field of NASH.
Speaker 3: The principal investigators are Dr. Frank from Antwerp and Dr. Sanial from Richmond, Virginia, two very well-known leading experts in the field of NASH. And the main inclusion criteria of course have remained the same. So we're adult patients with a degree of activity based on the SEV scoring, which is a scoring system for a patient.
Speaker 3: the degree of tissue injury, ballooning and inflammation, and fibrosis, stages F2, F3. So patients with advanced fibrosis, but not proceeded to the stage of cirrhosis. We do allow patients who have a stable dose of GLP-1 receptor agonists to have to be at least.
Speaker 3: GLP-1 receptor agonists have become, have an increasing uptake in patients with metabolic disorders. We have randomization according to type 2 diabetes and fibrosis stage. The study is powered based on the phase 2 data which were very positive, so we have 90% power.
Speaker 3: for the primary efficacy endpoint. And then of note, the biopsy reading is very robust. We use three expert pathologists and it's based on the...
Speaker 3: The fact that every biopsy is read by two of them and in case of non-agreement on certain aspects that affect eligibility, the third pathologist is a tie-breaker.
Speaker 3: So the primary efficacy endpoint is again based on the phase 2 data, both NAS resolution and fibrosis improvement, which is of course also related to clinical benefits, which is significant compared to having only one and also corresponds to the mechanism of action of the patient.
Speaker 3: improvement and no worsening of NASH, but we also have a large amount of secondary endpoints that relate to the beneficial effect of NASH on the metabolic immune markers of NASH. And of course also safety and tolerability to have a good benefit-risk ratio, which is the basis for approval.
Speaker 3: Now, going to slide 18, the current native tree update will be updated.
Speaker 3: provide the data for accelerated approval in order to get full approval thereafter. We have to have data on outcome benefit and our plan and this is again in agreement with communications of the FDA will be coming from an study in an outcome study.
Speaker 3: patients with early cirrhosis, in other words when decompensation events will occur so that enables us to predict the sample size of such a study quite well. We plan to have about 900 patients, select one dose of longofibrinor and of course placebo control. The outcome will be event.
Speaker 3: events in the hepatic decompensation events. The first ones that appear in patients with cirrhosis are hepatic encephalopathy, progression of portal hypertension with either bleeding from viruses or the need to prophylactically treat these viruses which is common practice today and the new onset of a site that is symptomatic.
Speaker 3: trial is expected to last up to three years.
Speaker 3: And it is as I mentioned an outcome benefit study for full approval. So going to slide 19. In Native 3 the study is conducted on a worldwide scale as you can see. We have several studies on
Speaker 3: Europe , also some sites in South Africa and Australia. And as Frederick mentioned through our partnership with HDQ, we also have sites in China before the end of involvement.
Speaker 3: That is currently ongoing. So quite a global approach. Next slide, number 20. We take out the timelines.
Speaker 3: In the second half of 2023, the last patient first visit target of the CIR-CAD 900 patient is planned. Completion of enrollment essentially at the end of this year.
Speaker 3: And then in the first half of 2025, we'll have the... for the current...
Speaker 3: designer of the study last patient's last visit, and that will bring us to a top line data in the second half of 2025, and an NDA submission for accelerated approval with the FDA at the beginning of 2026.
Speaker 3: I'm going to slide 21. I'll say a few words about
Speaker 3: the two phase two studies. The first one is a patient study in patients with Nefaldi, nonhistologically defined, and who also have type 2 diabetes.
Speaker 3: It is a study that has completed enrollment last year. It is, as Frederick also mentioned, the study that is sponsored by University of Florida and conducted by Dr. Koozie.
Speaker 3: And it is a truly mechanistic study that will provide much more granularity and data on the effects of lanolfibranor as a time people agonist to really address all the metabolic events that
Speaker 3: occur in the cascade of NASH development and also in type 2 diabetes, two conditions which have a very similar and common underlying disease biology, which is really in its upstream mechanism evolving around insulin resistance in multiple tissues and the
Speaker 3: corresponding dysregulation of lipid metabolism and accumulation of toxic lipid intermediaries that lead to the inflammation and tissue injury and fibrosis and deliver but also to an atrogenic lipid profile that causes atherosclerosis etc. So many of these disease biology aspects will be evaluated in this.
Speaker 3: this study and I think therefore it will be giving us a wealth of information about the benefits of lamafibrinor in addition to the hepatic benefits which we have described and published earlier.
Speaker 3: The FLD or NASH and FLD and type 2 diabetes occur very much in parallel as you know and the more advanced the disease becomes and that's true for both that to diabetes and NASH
Speaker 3: the more frequent the overlap becomes, which has to do by the fact that both diseases reinforce one another. So it is a very significant medical issue. And I think therefore studying lanofibrinol in patients with these overlapping conditions helps us understanding the disease and medical value quite a bit.
Speaker 3: So it has to do with insulin resistance and lipid metabolism as I mentioned.
Speaker 3: So, Dr. Koozie has enrolled 30 patients who had type 2 diabetes with a fasting glucose level below 250 milligrams per deciliter and an HbA1c below 9.5, so they were controlled. But with an amount of hepatic steatosis.
Speaker 3: defined by MR spectroscopy of 10% or more and stable weight. The randomization was 1 to 1 active 800 mg versus placebo.
Speaker 3: defined by MR spectroscopy of 10% or more and stable weight. The randomization was one to one active 800 milligram versus placebo and had a
Speaker 3: If you go to the next slide, just mention that in summary, the site uses a spectrum of state-of-the-art imaging technology to evaluate truly the uh
Speaker 3: fat amount in the liver, fat distribution and also inflammation and fibrosis in the liver through various software methods that we have today available based on MRI as well as ultrasound fibroscan and then also very sophisticated ways to measure.
Speaker 3: insulin resistance using the hyperinsulinemic clamp and the use of stable isotopes to measure glucose uptake by muscle etc. So to get really a very detailed picture of
Speaker 3: the effects of lanofibrin R on insulin resistance. And the primary efficacy endpoint that's based to have, just to define the sample size calculation, is based on the reduction of intrahepatic triplicerides measured by mass MR spectroscopy at week 24.
Speaker 3: But there are this really wealth of secondary endpoints that will give us that, I think, profile of lana sibrenar on its...
Speaker 3: with regard to its broad metabolic beneficial effects in MASH.
Speaker 3: As I mentioned, so this study is fully enrolled since September . It's when the last patient was enrolled. And in Q2 2023, in other words, the next weeks we'll have the results, the top-line results of this analysis.
Speaker 3: And then a few words about the combination of lanafibronor and impagliflozin in another phase two study which is run by Inventiva, the so-called legend study.
Speaker 3: It's also in patients with NASH and type 2 diabetes. The rationale for combination treatments in a disease like NASH, of course, has been discussed in many, many fora and there's a strong rationale, given the...
Speaker 3: biology of the disease stretching from metabolism all the way to fibrosis and cancer. So with regard to laminofibrin or based on its mechanism of action, it was a very good rationale to combine it with compounds such as GLP-1 receptor agonist and...
Speaker 3: S32 receptor agonist, S32 inhibitor, sorry. Lanofibrinol in itself, of course, addresses all aspects of the disease, and so in many patients, it will probably be adequate as a treatment, but some patients may have an additional benefit from the-
Speaker 3: combination treatment. And the other aspect is that with lamafibrinol, a certain percentage, roughly about one third if you define it as five percent or more of patients will have an increase in weight. We know that weight increase with lamafibrinol is metabolically healthy.
Speaker 3: you know, clear from all the data that we have from native and that we have published. Yet, it is maybe an issue for some patients and therefore I think it is important to show that with a combination such as with an SGL2 inhibitor that weight gain can be...
Speaker 3: balanced out. Go to the next slide, number 26. So we know from at least four randomized trials that have been published that when you combine glithosome with an SGLT2 inhibitor.
Speaker 3: that you do see an improvement of metabolic markers, a further improvement, such as lowering of HbA1c, and that the weight gain that you see with pyglutazole, which is Hama agonist, as I mentioned before.
Speaker 3: disappearing. So there's no weight increase which may be an important aspect for some patients. And these data are quite robust. They are robust. They are based on four large studies, as I mentioned, about 1400 patients in different parts of the world. So this is
Speaker 3: a good foundation for our approach and there has been no safety concerns for the combination of PPAR agonists with an FCR2 inhibitor.
Speaker 3: Slide 27 gives some more information about the legend trial. I summarized the rationale. We will have information from that study which is currently ongoing as well about the distribution of ancient
Speaker 3: fat because we use imaging as well, so multi-scan. And we will have information about the additional metabolic benefits and the effect that the combination has on the weight change.
Speaker 3: So, the study is based on the effect of lana fibrinor on HPA1C that is used for the sample size calculation and we have those data from native. HPA1C of course is also as it underlies insulin resistance an important marker for NASH as well as for type 2 diabetes that provides a good rationale to use.
Speaker 3: as well as the hepatic health markers assessed non-invasively.
Speaker 3: On slide 28, some more details, we run this study in four countries. The principal investigators are Dr. Holobom from the Academic Medical Center in Amsterdam.
Speaker 3: and Dr. Lai from Harvard, but Israel in Boston. And it's an ongoing study, so top-line results are planned to be available this year. As you can see, it's a half year treatment as well. We have one dose of...
Speaker 3: Lamofibranor and one dose of Empagliflozin, that's the SGR2 inhibitor that we choose, and in one arm, another arm is Lamofibranor 800 mg and it's a placebo controlled study. I covered the endpoints already, so I can go to slides.
Speaker 3: 29 which filled in.
Speaker 4: will be covered by Jean. Good morning, good afternoon everyone. So we will get to the key information on our financial landscape. Happy to answer your questions later on if you have further questions.
Speaker 4: So first of all in terms of shell debate, no significant change, it's rather stable and therefore still robust with our key partners. We have recently extended our coverage, our nice coverage.
Speaker 4: I wouldn't like to elaborate too much about our market cap which appears disconnected from what is the potential of the land-free runoff assets.
Speaker 4: But at least at the moment the consensus is still positive and the significant spread versus the current market cap. In terms of financial statements, three...
Speaker 4: three takeaways to remind First of all in terms of revenues, I guess it's the first time we reach
Speaker 4: This level of 12 million point two in sales and the good thing is it's the same cash wise because we recorded also this amount with the upfront from the CTTQ Sinobio Farm Partnership in China where we were talking about. Second point is the continuous effort
Speaker 4: We will continue this trend to reach a plateau, a cruise speed in 23 expected, to match again our objective by the end of the year.
Speaker 4: And then third point in a very difficult market, here in the financial feed, we have securized a short term close to 80 million euro, principally with the European Investment Bank deal to twice of 25 million.
Speaker 4: One has been raised in the fourth quarter and we have also used our at the market program with 9 million plus also in June remaining $58 million on the shelf. And we have optimized the store.
Speaker 4: kind of state backed loan niche with the 5 million plus also cashing this year.
Speaker 4: All in all we finished the year with close to €88 million without considering the cartridge of a 25 millisecond transfer EAV which allows us to operate until the end of 23.
Speaker 3: All right, thank you Jean. So on the catalyst of the near term, so it's, as you understood for us, is closing and obtaining the data from Professor Cusi on the faith II. We're looking, you know, with relatively confidence on this trial and we think it's going to be an important data for positioning learning patients with type 2 diabetes.
Speaker 3: And of course, I mentioned all the efforts that we're doing and we continue to target an end of enrollment for NEDI 3 for the second half of this year. That will be also, I think, very important.
Speaker 3: all the efforts that we are doing and we continue to target an end of enrollment for native 3 for the second half of this year. That will be also a very important achievement.
Speaker 3: news. And then the last one is of course the work we are doing on legend with the data expected in the second half. So this is for a quick update of the 2022 financials and the achievement. I give now the floor to the operator that will provide instructions.
Speaker 2: and wait for your name to be announced. If you wish to ask a question via the webcast, please type them in the question box and click submit.
Speaker 2: name to be announced. If you wish to ask a question via the webcast, please type them in the question box and click submit. We are now going to proceed with our first question.
Speaker 5: And the questions come from the line of same is Fernandez from Guggenheim Securities. Please ask a question. Great. Thanks so much for the question. So a couple of quick questions. The first one is really hoping to know if there will be a disclosure of baseline characteristics of the patients now that the next or the first phase three trial that's going to read out in 2025 is likely if those are likely to be presented and shared with.
Speaker 5: from the Phase II clinical studies. I think, Michael, you provided a lot of detail in your prepared remarks, just hoping to better understand, you know, what or how those results are likely to be presented, whether it's in a press release with a...
Speaker 5: sort of formal primary endpoint assessment, you know, or if it's more kind of exploratory analyses that will be provided and perhaps presented at a medical meeting specifically. Thanks. Thank you, Seamus. So, maybe I'll take the first question and then…
Speaker 3: It's actually a good suggestion. Honestly, we have not thought about that and we're not able to answer, but yes, this is feasible, that could be interesting to do.
Speaker 3: Of course, we have looked at the patient that has been enrolled, and Michael maybe can correct me, but from what we have seen is that, of course, we're not changing patient population from the previous phase to B, and so we're really looking for patient, of course, F2F3 with moderate to severe level of inflammation and...
Speaker 3: I don't know what it is due to. I don't think it means anything. We have seen that the drug is as efficacious.
Speaker 3: in both populations, so patients with NARSH or patients with NARSH and type 2 diabetes. But otherwise, yeah, good suggestion maybe to disclose the baseline characteristic once we are fully enrolled. Maybe Michael or Pierre, you want to talk about communication strategy for the phase 2.
Speaker 3: Yes, sure. For the study that is sponsored by the University of Florida, we will have once the data are available and press reason on the top-line results and then of course the data.
Speaker 3: the details of the data, the primary efficacy endpoint and all the secondary efficacy endpoints will be presented made public at scientific conferences in the first place by Dr. Kousis's team.
And maybe this is one follow up. Should we anticipate those results likely in terms of the medical meetings that you would be targeting? Is that more of an EASD conference just because this is a diabetic patient population or a little bit more along the lines of AASLD remaining focused on the liver focused patient population? I know there's a blend of endocrinologists and liver specialists.
So stay.
active with the liver conferences.
I think there is enough material to cover both conferences. Okay, thank you.
about the FACES trials that you're conducting, is the intention to potentially make lannifib nor available to all patients who you're trying to gear it towards a type two diabetic patient, which it seems to have some tremendous benefit for.
And then also on the Legend trial, so you're looking at it in combination with Impeil-Losen, but it seems that a number of these patients or a number of the physicians believe that these patients will already be on some kind of background with one. So I'm just wondering, again, bigger picture, how do you envision a new trial?
some of these combinations to play out, you know, in real world, and are you intending to try to find another combination treatment to optimize Lenny, or is it to, you know, that's maybe oral and more suitable for the population that you're targeting, or is it just to potentially manage some of the weight gain issues?
or whatever, you know, optimizes the profile in general. So I guess I'm trying to understand how it works out with the GLIP ones as well as the combination trials that you're looking at right now. Thanks.
Okay, so maybe on the Phase III. So currently, of course, we have patient F2F3 and we stratify for patient with NASH N-type 2 diabetes.
Clearly our intention and belief that ALANI presses both populations, so and that has been shown in the face-to-be, it's effective in patients with NASH, and it's also effective in patients with NASH anti-dietiabetes. Where and why we work a lot.
on the anti-diabetic properties of Lani is because we look at competition and when we look at competitors we believe we are the only one that has this direct...
insulin sensitizer properties and so if you position yourself from the patient perspective and you have NASH and type 2 diabetes
If you are treated with LANI, not only you would improve your NASH, reduce your...
but on top of that, you will, Lanny would help further control your HbA1c. So it's really a perfect, perfect drug for this patient. And we also have published that when we look at patients with prediabetes treated with Lanny during the phase 2b, those patients during the course of the trial are seen there.
diabetes stop progression. So clearly it's a patient population that we like. And then ultimately when we talk to endocrinologists, we realize that they have huge amount of patients that are sitting in their offices that have NASH. And so developing and producing the type of a...
the data we will be generating with Professor Cusi I think will help position the drug among endocrinologists.
Now, maybe for the GLP-1, I'll let Michael up here answer. Just one comment, just to point out that in the current native 3, the phase 3, we are allowing patient under GLP-1, under a stable dose of GLP-1 for three months.
And so we are including patients with EGLP1 in the trial, and that will help us, of course, generate data about combining Lani and EGLP1. Maybe Michael or Pierre, do you wanna add something about the legend and...
including patients with EGLP1 in the trial. And that will help us, of course, generate data about combining Lani and EGLP1. Maybe Michael or Pierre, do you want to add something about the legend and combination with the GLP1?
Yeah, so I think the, you know, in these diseases, it's also known in cardiovascular disease and diabetes treatment, treatment paradigms change as new treatments become available and semaglutide specifically is a GLP-1 receptor agonist suddenly have or changing that paradigm and now that GLP-1 receptor agonists are becoming, have become first line treatment in type 2 diabetes.
So I think that's something that we adapt to. I don't think that's actually an opportunity. I mean, we do allow patients who are on a stable dose to be enrolled in native 3. We may also, since Frederick referred to that, consider to use that opportunity to update legend, if you wish. And that's something that we are.
you know, for a disease like NASH and type 2 diabetes that go hand in hand or approval will be for NASH, but many patients will have type 2 diabetes and even those who don't have over type 2 diabetes, many of those have more have pre-diabetes which the...
the diabetology community also recommends to treat. So this is an advantage I think that we have in the NASH field. And the fact that the treatment field for type 2 diabetes is changing is something that we use to our advantage to position.
lana fibrinor in combination with these newer treatments as well. So I think that's how our studies are currently designed and I think that lana fibrinor will have an attractive position in this field.
fibrinor in combination with these newer treatments as well. So I think that's how our studies are currently designed and I think that lana fibrinor will have an attractive position in this field. Okay great, thank you.
We're now going to proceed with our next question.
We are now going to proceed with our next question.
The questions come from the line of eight from H. C. Wayne Wright. Please ask a question. Great. Thanks for taking my questions and congrats on the continued progress. A few for me. Firstly, just wanted to ask if you can disclose how many patients are currently enrolled in the
Native 3. And then turning to the outcomes trial, I think you mentioned 900 patients is the total target, but I think there's 800 on the slide. Just wanted to confirm the total number there. And then lastly, also with outcomes, which are 600
dose of planning to use for that trial? And then I have a couple follow-ups. OK, so the first two, I think, of the outcome trials is correct. Here is the next one. I hope we make like that. And do we disclose the number of patients that we have randomized and enrolled? No, we have not.
We look at the practice. Of course, we monitor the situation daily and we're very pleased with the enrollment, with the screen failure I mentioned.
we have let's say battled or anyway had to concentrate in improving the screen failure which was earlier than what we expected. That is something general in the industry but we've been you know really working hard and we see the screen failure going down for the past regularly for the past several months so that's very positive.
As I mentioned, we have quite a large number of sites that are screening, inactivity screening, so we, you know, that gives us confidence that we can meet our target of endoverrollment for the second half of this year. And on the third question, on the dose, maybe Michael, you want to...
give an highlight of the discussion with FDA? Yeah, if I understand the question correctly, correct me if I'm wrong, it was about the total number of patients that we enrolled in the outcome study. So our estimate is 800, about 800, with two arms, one dose of Lomafibrinor.
placebo. And the 950 or 960 is for the native tree, the study that you are currently running that is providing the
So did I answer your question? Actually Michael, the other part of the question was which dose would you be using, intend to use for the outcomes study, which dose of laminar? We have not decided yet, but we will choose one dose. I think when we finalize the design we will take all information into consideration.
your remarks.
some work that's been done more recently on speeding up biopsies. I wondered if you could expand upon those activities and what you've done and how that's helped the study. And then lastly, I just wanted to ask about the financials. I think you said cash right now is a runway to the end of the year.
if you could confirm that and also what's the remaining amount on the ATM. Thanks so much. Okay, so on the bioptic process there have been many activities going on and improving that process that helped in improving the screening process by speeding up the
And then secondly, the big change we made is that you know that we follow, say, the FDA guidelines to have a biopsy reviewed by three pathologies.
with a tiebreaker. We started the trial with two pathologists involved. And if one of these two pathologists disagreed or did not evaluate in the same way as the other one, the biopsy of the patient would be excluded. And now we have introduced a tiebreaker also for the baseline.
And so now when there is a disagreement between the two biologists, there is a tiebreaker, a serpathology that has the tiebreaker. So that also has been introduced. And all along the way also, we have introduced training, alignment training between these three pathologies so that they really...
So, 88 million as we have seen, end of 23 and very important without considering the second tranche of the EIB which presents a cartridge of 25 million euro.
And we have still $58 million on the shelf for the market program. Great, thanks so much. We are now going to proceed with our next question.
And the questions come from line of Frederick Gomez from Farmium Securities. Please ask your question. Frederick Gomez, the line is open. Thanks for taking my questions. One of the underlegends studied the... Yes, can you hear me? Yes. Yes. Yes, I can hear you.
Yes, I'm not on mute. No, no, we hear you very well. Can you hear me? Yes. Yes, yes. Yes.
Okay, perfect. Yeah, perfect. So the first question is on the legend study. The primary will be the HBA1AAC. Can you maybe clarify a little bit the statistical analysis plan or you will perform the analysis between the combo arm and the landing arm? I'm just wondering how you will...
Does it, I'm curious to hear you about the potential impact on the outcome and and also the baseline data because this shift may have an impact of a role on the trial itself if more patients have been looked by three pathologies.
versus two. Can you maybe elaborate a little bit more on the potential impact of this change? Sure, so for the legend we can start with that and maybe even for the tiebreaker, maybe Michael you can address that. Sure, yes I think to start with legend we actually have based the sample size calculation on the
and the power on the data that we have from native 2, on the effect on HbA1c, I don't have it in my head now, but those numbers we have, and also on the additional benefit that you expect when you combine pyblithosone with one of the S32 inhibitors. And as I mentioned, there are four large randomized trials.
give actually a consistent picture that you have an additional benefit on the decrease of HbA1c after half a year of treatment or longer. But most of these studies was half a year. And that provides the basis to define an effect size that we should see and and power calculation to have on the...
a p-value that is adequate. That's what it's based on. Now it is a proof of concept study so I like to point out that this is really because we this is the way we do it but the main importance of the study is really to show that there is an additional benefit of the combination on metabolic markers for those patients who may need it and also on
have two, diabetes or obese. So it will actually not be an issue for all patients, for some may be. And this is what it's based on.
So we really see the value of this study in providing that set of data on the additional benefits that the combination may have in certain patients for whom this may be important. And it's in line also with how metabolic treatments, sorry, metabolic diseases are treated, such as type 2 diabetes. The physician will start with an...
and then see how the patient evolves and may add another treatment if necessary in certain patients. So with regard to the biopsy, it was always our intention to start with three expert pathologists. And we have started with two and have as soon as the third one was onboard contractually made the time breaker process, and put it in place.
That does not really affect the patients that we enroll as eligible. In fact, we have looked at patients who screen failed based on the initial two biopsies and see which patients would be eligible if they were eligible.
or when the third one comes in as a tiebreaker and some of these patients would then be eligible again, or would become eligible. But the key point is that the tiebreaker system gives a degree of stability, I think, in the histology scoring. That's an important aspect, of course.
but for the evaluation of efficacy at the end of the 72-week treatment period, all histology will be re-read. So the histology at inclusion and the histology at the end of treatment will be evaluated again by the three pathologists according to this.
So for the entire study, if you look at the evaluation of efficacy, the reading will be consistent. We have no further questions at this time. I'll hand back the conference to Mr. Grant.
for closing remarks. Thank you. Yes, well thank you very much for attending. We have in front of us a very exciting 2023. Thank you very much.
The very exciting space, it was not the case last year and we see now much more renewed interest. There are going to be quite a lot of events this year, especially with the FDA, the anti-sep and the milder goal submission and concerning you know Lani Fibarno will remain.
confident we have in our hands a drug that can make it to the finish line. And this year, operationally, we know we have to deliver on Native 3. And as I mentioned, it seems that we are on the right track. And then we also be looking forward with optimism, let's say, to go further optimism to...
to the data that will be generated by Professor Cusi in the Type 2 Diabetes Study and also of course in the Legend Study. I think that will keep us busy. And as usual, thank you very much for attending and I look forward to seeing all of you in future meetings.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect your lines. Thank you.