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spk01: Thank you, good morning, good afternoon, everybody, and thanks for joining us today for this webcast. Before we begin, as usual, I ask you to please read the disclaimer on slide two, which should appear now, and I want to remind everyone that the various statements that we may make during today's conference or during the Q&A session will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Today, in this call, I'm joined by Jean, Jean Boulatier, our CFO, and by our CFO and co-founder, Pierre Broca. So let me go back to some of the highlights of Lani Fiber Nord development program by starting by 1983. So in January 23, we announced some important changes to the design of the phase three, evaluating Lani inpatient with MASH-NASH. which made the study more attractive for the site and especially more patient-friendly. This new design is based on discussion we had with the FDA and on the alternative approach put forward by the US FDA, which includes two independent phase three, one based on histological outcomes, native three, which would allow us, if our results are positive, to fight for accelerated approval. And the second phase three study in patients with MASH, NASH, and compensatory cirrhosis, which will be our confirmation trial in order to demonstrate clinical outcomes and which would secure a positive full approval. As part of the development of Lani, we were pleased that our partner, Sinobiopharm, received their IND approval by the Chinese and MPA to initiate the clinical development in China. Sinobiopharm is participating to our Global Native III Phase III clinical trial, and we have closed 2023 with the first patient enrolled in China and also a breakthrough therapy designation granted by the NMPA in China, making Lani the first drug candidate, to our knowledge, to receive such designation from both the FDA and the NMPA for the treatment of MASH-NASH. We also published the results, the positive results of a study conducted by Professor Cusi from the University of Florida in 2003, in 2023. The study met its primary endpoint, which demonstrated the reduction of intra-hepatic triglyceride in patients with MAFLD and NAFLD and type 2 diabetes treated with a low dose of Lani for six months. What was key in this study showing the effect on hepatic fat and liver and muscle insulin sensitivity, as well as fat metabolism within just 24 weeks. The effect on insulin sensitivity is an important feature and key differentiator of Lani versus other therapies approved or in development in NASH as insulin resistance is a feature of all NASH patients. We have also been active on licensing. as we also announced the licensing of Lani in Japan and South Korea with the signature of an agreement with the Palace Pharma. This is an exciting milestone and expands our potential footprint. With this agreement, we have received a 10 million up from payment and exercise our right to take a stake ownership in the newly created company. In February, We reported the first SUSAR ever experienced with Lani, and this as we were approaching the end of our screening for N83. Our team has been and is all hands on deck. We have made the changes to our protocol as recommended by our data monitoring committee, and we're today back on track. We have resumed screening, and also we have started randomizing new patients in the majority of our site under central IRB in the US. And we confirmed that we target last patient first visit in first half of 24. Finally, just last week, we announced the positive interim analysis of our proof of concept phase two clinical trial legend, evaluating the combination of NANI with SGLT2 inhibitor and baguette flosing. The study was designed to potentially demonstrate an additive effect of the combination and the management of weight gain that can be observed in some patients treated with lanifibrinoid. The study met its primary endpoint, which was the reduction of HbA1c, and demonstrated that the combination addresses the moderate and metabolically healthy weight gain seen in some patients. The study showed that both Lani alone and in combination with EMPA induce a redistribution of fat from visceral to subcutaneous fat, reflecting a shift from pro-inflammatory visceral fat towards medically, metabolically healthy adipose tissue. This redistribution of fat is consistent with improved insulin sensitivity seen with both Lani alone or the combination. Finally, Lani improved markers of cardiometabolic health. The effect size appears to be further improved when Lani is combined with EMPA. These results further bolster our robust data set, our faith to be native, and from the investor initiative study conducted by Professor Luzi. We plan to present this data in scientific congresses, as well as submit it for publication. We briefly cover several key financial milestones before turning it over to Jean. In 2023, we have secured the financing of approximately $39 million with equity issuance. We also have secured $15 million of non-dilutive. Five, our partner in China following the progress made in the development of Lani. And then an additional 10 million with the signature of the licensing agreement with Epalis Pharma, which also make us eligible up to $231 million of clinical, regulatory and commercial milestones, as well as royalty. And also, as you are aware, at the beginning of the year, thanks to the achievement of key financial and operational milestones, we drew the second tranche of the 50 million euro EIB alone, We're in the second tranche for those 25 million. We are very optimistic for the future of Lanny Fiebernord and Inventiva, and are focusing on the upcoming important milestone, which is for us, the last patient, first visit of Phase 3, Native 3 clinical trial, which we expect to secure by the first step of this year. Let me give you some figures that make us confident that we can achieve this target. We have more than 75% of the patient targeted to be randomized in the main cohort, and more than 350 are in screening. Importantly, close to 90% of the patient randomized come from North America and EU, which we think bodes well for the quality of the result. From a financial standpoint, and I'm We are, of course, focusing our efforts to expand our cash runway, and we're confident that the recent positive data from Legend, the progress made in 83, and the approval of Resmeteron with no requirement of biopsy for prescribing the drug create a favorable environment for Inventiva. The management of patients with NASH-MASH will require treatment options and potential combination therapies. And we certainly think that given lanifebranor dataset and mechanism of action, there is a significant space for a neural drug with a direct antifibrotic activity and strong insulin sensitizer like lanifebranor. This was clearly highlighted in the recent physician survey we conducted in the U.S. showing prescriber expect to write lanifebranor for approximately 30% of their matched patients. We now turn it over to Jean, We will provide you with an overview of our full year 23 financial reports.
spk00: Thank you, Frederic. Good morning. Good afternoon, everyone. So everything has been said, I may say, and the financials for 23 reflect quite rich activities, as you have heard. Let's start with the profit and loss accounts. So the company's revenues for this year amounted to 17.5 million. I guess a record ever for Inventiva since it has been created. So an increase by more than 40% compared to the 12.2 million recorded in 22. I said the revenues, you know, derived from two things. First, the continuing milestones, two milestones from CTTQ Sinogyo Farm, the Chinese partner. five million dollars and also for the two-thirds of the revenues in 23 from the up front payment of 10,000 million dollars from Mepalis and also a non-cash consideration from the fair value of an option to acquire shares of the JV. The key thing is of course the increasing effort in R&D, so an increase of 82%, reaching 110 million in 23 compared to 60.5 million in 22. Obviously, this reflects the acceleration, planned acceleration in the 23 activities with regard to the clinical development for NATIVE-3, and also in a lesser extent with the LEGEND phase 2a combination trial we have just talked about. GNA expenses amounted to 13.8 million, a slight increase of 7% compared to the 12.9 million in 2022. We consider it's rather under control, considering the growing scope of activities of the company. To be outlined also, a net financial income of 5.1 million, a loss which reflects, we've talked about the EIB first tranche in 23 with interest rates, which would be paid, I remind that end of 26, early 27. But of course, we incur the expense related to this loan and also completed by some interest that we pay for the other existing minor loans. The variation in net financial income is also due to close to zero foreign exchange results in 2023 compared to a greater positive result in 2022. This is obviously related to the euro-dollar context in 2023 compared to last year. We record for the first year our share of net loss for the stake we have in the Japanese JV with a non-cash loss of 12 million, of course, compared to zero in 22. And all things considered, the company's net loss for the full year reached 110.4 million compared to 54.3 million in 22. Let's talk now about cash. If we consider what we call a global cash position, you know, including the pure cash and cash equivalent, the middle-term investment we have that are very liquid and easily mobilizable, and the second trench of the European Investment Bank that we drew mid-January, we started the year with close to 61 million in cash compared to 88.4 at the beginning of the prior year. So it's a decrease of close to 30 million. Obviously, it reflects the higher cash consumed by the operations, 82 million, including, by the way, the 20 million cash in, definitely deriving from the effort in the R&D. By the way, in terms of metrics for the IR&D, we must underline that Lannis-Ibranor is really focused in our financial efforts. R&D in the company represents 87% of overall expense, Of this R&D, of this 87%, Lani Fibrenor represents 85% of this R&D expense. And overall, for the company, 75% of our financial efforts are dedicated to this program. So the negative impact, of course, of the operating cash flow has been partially offset by the operation that Frederic reminded. First end of August, the finance rate of 35.7 growth in regular capital increase. For such an increase, we got the support from existing partners, such as Sofinova and Young Capital. And also, we're very pleased to welcome Qatar Holding LLC, who now holds close to 10% of our shareholder base. The negative operating expense has been also offset, as mentioned, by the $10 million upfront payment from Mepalis and the $5 million related to the two milestones reached with CTTQ, first patient randomized and the attention of the overall. our cash position as of today, we do confirm that this will allow Inventiva to operate until early Q3 2024. I would be glad to answer any question in the Q&A session if needed. I just pass over to Frédéric for the conclusion. Thank you.
spk01: Thank you, Jean. Before we move to the conclusion, let's open it up for the Q&A. I see that there are some questions already.
spk04: Thank you. As a reminder, to ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To answer your question, please press star 1 1 again. We will now take the first question. coming of the line of Simon Fernandez from Guggenheim Securities. Please go ahead.
spk07: Oh, thanks so much for the question. So, you know, Frederic, I just wanted to follow up on some of the data that was just presented, you know, and comments from Dr. Harrison on the call that were certainly very interesting. You know, we've got the ResMedAROM data, not a lot of changes that we see in HbA1c in a diabetic patient population, whereas we very clearly see substantial changes in HbA1c with Lani. And then also the incremental benefits of adding an SGLT2 would suggest that this opportunity is quite substantial. Just wanted to confirm your view of the market his comments that he would much prefer to give his product to or give this product to diabetic patients and then also just the confirmation that depending on the timing of the completion of last patient when if you would strongly expect this to be the next oral mash therapy available in the market. And I have one additional follow-up question.
spk01: Thank you. Thank you, Seamus. Yes, we were actually very pleased by a comment made by Steve Harrison who said that for him, once Lani will be approved, if he sees a patient entering his clinic with MASH and type 2 diabetes, he would prescribe Lani over any other compound he has seen. That for us is a very nice comment because we know that there is a large proportion of patients with NASH and type 2 diabetes, you know, between 40 to 50. We have 60% in our phase 3 study without, you know, looking to recruit more patients with type 2 diabetes. And these patients with type 2 diabetes actually have a form of NASH that is more severe, you tend to have a higher proportion in patients with F2, F3, and also they tend to have a more progressive fibrosis. So that was great. And when we look at the competitors, we really think that this activity on HbA1c, the insulin sensitivities property that we have, that were clearly illustrated by the study we did with Professor Cusi, where we saw statistical impact on insulin sensitivity in the liver and the muscle is really a feature we really want to put forward and really work on stressing the importance of these properties. And we should not also not forget one piece of work that we did where we saw that a patient with prediabetes treated in the face-to-be So their diabetes stopped and their progression towards diabetes stopped when treated with Lani. So it's really a compound Lani that has a great profile for patients with type 2 diabetes and also with prediabetes. And then to your question about, do we think we are the next orally approved drug? Yes, I can confirm that because we are close to finish the recruitment. the first half of 26. the other oral drug that we know would be the i think sagimet but it has to start phase three and the other drug in development in phase three are injectables and all the studies we have done with payers and especially prescriber really put oral drug as a preferred very well positioned in this field.
spk07: Great. And just as a follow-up question, as it relates to the phase three, you commented that I think you've already kind of added a further 5% of patients recruited officially into the study and then have an additional 15% to 20%. So, It sounds like the conviction that the last patient first visit will occur by the end of the first half of this year or during the second quarter is extremely high. You know, is there sort of a sooner rather than later aspect to that that you have higher conviction in? And then just secondarily, Maybe you can update us on the progress towards sort of F4 patients that I believe are more exploratory as part of the study.
spk01: So we're starting to rescreen. We started rescreening in the U.S. with the site that are under central IRB. And the opening of our site is following the plan. There is one . One item we don't control will be the strain failure rate following the introduction of these autoimmune antibodies that we put in place following the recommendation of the data monitoring committee. We believe the impact will be limited, but only The future months will confirm that. But if the screen failure doesn't change significantly compared to what we have experienced in the past, we should be able to meet this end of recruitment as planned for the end of H1. We have had many webinar meetings called with all our sites. They understand the situation. motivated to restart screening. So we really got positive feedback from how we handled this user. Then on the next phase three, which is a phase three that is requested to secure full approval and that we plan to conduct in patient with compensated cirrhosis. We need to have this trial ongoing when we file for NDA. We are including patients with F4 compensated cirrhosis in the exploratory arm. We currently, out of those 200 patients, we will have approximately 30% with F4. We are not doing a second biopsy, but we have a very large set of non-invasive tests planned to be used in this patient that are stratified one-to-one-to-one in the exploratory core. So that will give us, I think, valuable information on how Lani performs in this patient and will help us finalize the discussion we have with the FDA on the design of this confirmatory trial.
spk07: Great, thank you so much and good luck with the continued progress and congrats on the recent updates.
spk04: Thank you. Thank you. We will now take the next question. From the line of Rami Katkouda from LifeSci Capital, please go ahead.
spk06: Hey, guys. Thanks for taking my questions as well. Just a couple of quick ones from me. First, I guess, when do you expect SQS sites to begin enrolling patients again? And then, secondly, what milestones do you need to hit to draw additional tranches from the EIV loan, and could that occur before the third quarter?
spk01: Okay, so the second question is easy. We have met all the requirements of the EIV. And that allowed us to draw the second tranche of 25 million. And then if we want to put in place a new loan with the EIB, we need to discuss that with them. I think they're not close to it, but they are open to do such a thing, but we have not started discussing on that. And then when we plan to open XUS, site so canada there are sites under central irb so those we plan to open those soon and then the other countries we start opening them starting from april with a focus for us on europe what i mentioned in my introductory that you know most of our patients come from the us or north america close to 70%, and an additional 21% come from EU. So they're really a focus from our team to focus our effort in these two geographic areas.
spk06: Got it. And I know it's a bit early, but would you look to partner Lani in Europe as well? And would that partnership come before or after the Native 3 readout?
spk01: Well, our strategy concerning Lani is is that we see that there are two strategic regions for NASH that are Europe and the US. We want to keep those rights, I would say, bundled together as one. And so we're more looking at partnering Europe and the US together rather than splitting those. We think that an appropriate moment will be post phase three because we are confident in the data we will generate post phase three and the ability to get approval based on the native three data.
spk05: Got it. Thanks so much. Thank you. We will now take the next question.
spk04: from the line of Lucy Codrington from Jefferies. Please go ahead.
spk03: Thank you for taking my questions. Sorry, I didn't quite catch in a prepared remark. Could you just repeat the state of random, the kind of randomization post the screening resuming? And also just whether you had a set amount already in screening when the when the recruitment was halted, has that number changed within that screening pool given the kind of safety concerns is probably overstating it, but since that incident and then the required additional monitoring that the trial will entail, has that meant you've lost any patients within screening? And then just on the partnership kind of commentary, I guess, I was going to ask if you're in any active discussions with potential partners and whether interest had increased since your recent data and the ResMeta and approval. I guess your comment just then suggesting you'd prefer to wait till after phase three might suggest that's no. But I guess, can you afford to wait till after phase three given the cash constraints that you have? And could you explore other options kind of roots in terms of a potential option agreement? Are these types of things being considered in order to get you to that data, which seems to be the most important thing? And then I guess related to that, you mentioned about potentially another EIB loan. How long do those loans take to negotiate? Just promise that we've only got a limited amount of time before that the cash runway expires. Thank you.
spk01: Yeah, okay. So I'll take the first two questions about the status of the trial and the partnering, and I'll let you answer the question about the European Investment Bank and how long that takes. On screening, what I said is that we have more than 75% of the patients needed for the main cohort that are randomized. And that we have more than 350 patients in screening. So the pool of patients in screening is diminishing, but it's not due to pushback or the change of attitude of the sites towards Lani Sieberner. To the contrary, as I said, we have had meetings, calls, webinars, a face-to-face meeting with the sites, and the excitement remains, especially after the legend data. The patients in screening are diminishing. It's just because at a certain moment, there is a date of, let's call it a date of validity for the lab test and for the biopsy. And so at a certain moment, we lose those patients. And then also I mentioned, you know, I gave some data about where this is and what is important is that the countries which we will reopen first as really those countries that matter, which is North America and Europe. When I say that matters, it's that they are providing the most, the country providing more patients in the trial. Now concerning our cash runway, yes, we have a cash runway until early Q3. Luckily for us, we are in a, in a good moment with positive data in the nash field due to the madrigal approval which has lifted a regulatory hurdle the need that patients do not need to go under biopsy all options are on the table it could be um as you mentioned uh working with uh with a big pharma Or it could be to go back to the capital market. We have, I think, a strong shareholder base that has been supportive for the past 12 years. And so we think we are in a positive trend. So maybe I'll let Jean answer your question about the timing of the EIB.
spk00: Sure. We have continued discussion with the EIB. By the way, they have asked to come visit us on the site in a couple of weeks. There are two ways. One way, the short circuit would be below 10 million. This could be managed within the existing loans. And generally, it could be within two or three months. And the second option is a greater tranche, which would be managed through a new finance agreement. Obviously, both would go with cash injections. Frédéric was talking about the potential capital increase, so this could be managed together with this operation. And for the second option, I guess that Within six months to one year, this could be possible to discuss a sub tranche. But again, everything is depending on the future cash injection on which we are working actively.
spk04: Thank you. Thank you. As a reminder, if you wish to ask a question, please press star 1 and 1. We will now take the next question from the line of Jacob McHale from KVC Securities. Please go ahead.
spk02: Hi there. Can you please provide some guidance on how we should look at R&D for 2024? And do you expect R&D to decrease once you have completed enrollment in the trial? And just perhaps maybe to go back on the target of 950 patients, Do you think that target is achievable only with US sites, or will you need the additional sites in order to reach that? And also perhaps a second question on that is, do you need to meet certain thresholds in terms of patient numbers from each region?
spk01: So in terms of giving you the highlights for the coming years and with our hypothesis, our planning. So when we say we plan to reach enrollment at the end of each one, this include the contribution that are outside of North America, so mostly from Europe. In terms of minimum numbers to achieve, the only requirement And if I'm wrong, I'll ask Pierre to intervene, but I think it came from the FDA. They wanted a certain percentage to come from the US, and we have largely achieved that target.
spk05: OK, thank you.
spk00: So maybe for your question about the trend of the R&D expense, We should increase slightly in 2024, you know, something around 10% plus 10%. But then, as you mentioned, the year after 25 should decrease, of course, due to the end of the recruitment and, you know, the investment to finish up the recruitment.
spk02: Okay. Thank you very much. Very clear.
spk04: Thank you. There are no further questions.
spk01: I think we lost the operator, but so I'll just make the conclusion. Just to mention that 23 was a busy year for our team at Menteva, and 2024 will be another busy year with many milestones to achieve. What I think is really great for Inventiva is that we have an incredible asset. We have an oral compound with a very attractive and competitive profile. And clearly the data we've generated makes Lani a compound that is very well placed to make it through the finish line in MASH-NASH. And we're convinced that Lani will play a key role in the treatment of patients with MASH-NASH. So thank you very much for attending. Thank you for your support. And I look to continue the open dialogue throughout 2024. Thank you very much.
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