Welcome, ladies and gentlemen. Welcome to the last day of the JPMorgan Healthcare Conference and today's presentation from Inventiva. It's my pleasure to introduce Andrew Obenshain, CEO of Inventiva. We'll first do the presentation. After that, there's time for some questions, so feel free to save those to the end. And I'll leave it to Andrew to take us through.
Thank you very much, and thank you for having us to this conference, and thank you for ordering up some beautiful weather this week. I'm glad to see there's a sellout crowd of hundreds of people in the audience for those people online. A lot of interest in Inventiva today, so again, I'm Andrew Obenshain. I'm the CEO of Inventiva. Today, I'm going to talk about the company and our lead asset, lanifibranor, which has the potential to be best in disease for MASH as an oral therapy. This is my disclaimer. This presentation contains forward-looking statements. I will not read the whole thing, and I want to start this presentation by just talking about the company a little bit instead of the product, because Inventiva has really gone through a transformation in the last 18 months. We currently have a fully enrolled phase III trial.
That phase III trial design was based off of a phase II-B of well over 200 patients that was published in the New England Journal of Medicine with positive results. And the design of the phase III is largely similar. And we anticipate that readout in the second half of this year. The company itself has received a substantial amount of funding over the last 18 months, starting with a $411 million raise in October of 2024 and supplemented with $172 million in October. That's important because the history of Inventiva has been one of scraping together a couple of pennies to get to the next stage. And now we're actually fully capitalized to realize the full potential of lanifibranor. Along with the first fundraise, Mark Pruzanski, the former CEO of Intercept, joined as the board chairman, bringing a lot of expertise in MASH.
And he has proceeded to build up the management team, starting with addressing the medical and regulatory side. We brought in Jason Campagna, who is the former CMO of Intercept, and Martine Zimmermann, the former head of regulatory at Ipsen, where she got the PPAR approved. So very relevant experience to really shepherd lanifibranor through. We've added commercial expertise from the Nazira Amra from Intercept. And then I've joined. My background is as a public company CEO, transitioning biotech companies from phase three to commercial. So we now have a well-funded company, an experienced management team, a fantastic asset to bring forward into a very exciting MASH space. So I'm going to start by just talking a little bit about MASH and what we think is needed to address the unmet need for these patients. So MASH is a chronic progressive disease. It's the number one cause of liver-related death.
But it's more than just a liver disease. It's more than just liver scarring. It is a cardiometabolic disease. It's really part of the cardiometabolic metabolism. These patients have both a sick liver with scarring, but also a sick body. Over 60% of them have diabetes, obesity is involved. And really, to address the liver issues, you need to address both the sick liver and the sick body. We believe that lanifibranor is a product that is positioned to do just that. In terms of the market, this is a market that's going to grow to $15 billion by 2035, but it's not there yet. It remains a market of a lot of opportunity. There's about 2 million diagnosed MASH patients in the U.S. right now, just under. That's only about 10% of the total population. But that diagnosis rate is increasing very, very quickly.
Our current estimate of 2 million diagnosed represents a growth of about 25% since 2024, and the patient population that we'll target is the F2, F3 patient population. That's about 375,000 patients in the U.S. that are under the care of a physician, and again, that represents growth of about 20% since 2024, but that patient population has been the patient population that's been sufficient to drive the first oral to the market to a run rate of over $1 billion in sales, so this is a market that is growing and a lot of opportunity. Now, one of the reasons the market's growing is because there's been a lot of activity and positive activity. There's been two approvals in this market recently, one GLP-1 and one THR beta, and that has increased the diagnosis rate and the awareness.
But it also presents a question of where does lanifibranor fit in. And so the way we see the treatment of MASH evolving is that any patient that is F1, F2, or F3 will have tried, will soon try, or will be on a GLP-1. That will be the backbone of therapy for these patients because GLP-1s really address the underlying metabolic issues. There's also FGF21s. We view that those therapies are very promising therapies, but really will remain in F4 because they're injectable. They have some overlapping toxicities with GLP-1s. They're probably, and this is speculation, going to be premium priced. So they really will stay in that F4 patient population. And we see the future for F2 and F3 patients as a GLP-1 plus or minus an oral. And that oral will either be Rezdiffra or lanifibranor.
So let me go into lanifibranor and specifically how it was designed and the mechanism of action. So lanifibranor is a Pan-PPAR agonist. It was rationally designed based on over a decade of PPAR biology and understanding. It was not made on the old TZD backbones. Rather, it's a new chemical entity, so it has its own properties. And really, it was designed with two goals in mind. First of all, to be a low-potency binder across all three isoforms. Now, why is low potency? Why? We usually, in drug development, we like high potency. We like tight binders. But it's been shown that especially for the gamma isoform, if it binds tightly and has a high-potency binder, it leads to adverse events that we want to avoid. For example, peripheral edema.
And this was the case with rosiglitazone, which was a tight gamma binder that was withdrawn from the market in Europe. We also want it to be balanced across all the isoforms. We want to recruit not only the liver effects, but the body effects. And also the balance actually helps to mitigate. These are networked receptors. And hitting them all together leads to a much more balanced profile and safe profile. And one of the reasons we wanted to be balanced across all three isoforms was we wanted to recruit both the liver effects, and each isoform has different impacts in the body. So we wanted to address steatosis, PPAR gamma, fibrosis, PPAR gamma and alpha, inflammation and ballooning, PPAR, all the three PPARs, and vascular gamma and delta. And then we also, for MASH, especially want to address the metabolism. And a pan-PPAR addresses insulin sensitivity.
It lowers HbA1c, increases HDL, and lowers triglycerides. So that was the goal of the design of lanifibranor. So let's turn to the clinical data. This was the goal of the design. How did the drug actually perform in patients? Well, in a phase II-B study, which these were published in the New England Journal of Medicine, with only six months of treatment, so 24 weeks, lanifibranor improved fibrosis and key metabolic markers. So we saw an 18% effect size on fibrosis. And if we looked at both fibrosis and MASH resolution, that actually grew to 24%. In addition to that, it improved the cardiometabolic, glycemic, and metabolic markers. So it delivered as promised in the clinic. Now, that phase II trial was, again, six weeks, and it was two doses, 800 and 1200. It included F1, F2, and F3 patients.
The primary endpoint was an SAF score, so a steatosis activity fibrosis score as a measure. This is not what our phase III is going to look very similar to this, but not quite identical. I'm going to go through a couple of differences and maybe what impact those will have. Let's start. Let's reground ourselves in the efficacy. On the dual endpoint, the resolution of MASH and improvement in fibrosis, that is what's going to be our primary endpoint, not the SAF score. That is where we had that 24% effect size in the phase II. Now, our phase III is going to include no F1 patients. It's just F2 and F3. How do we do on effect size in that population? Well, roughly the same, slightly better.
So we're confident that the elimination of the F1 patient population from the phase III has either no or positive impact. Also, we're running the study, or the study was run more in the U.S. than the phase II, and therefore there was more type 2 diabetes. So the patient population is slightly enriched for type 2 diabetes. And again, you see that the effect size remains similar, actually slightly better. So that phase III patient population has looked, we're confident that we can duplicate that phase II data. Now, these are the histological findings from the study, but the biomarkers also support the same efficacy that we saw. So we saw a statistically significant decrease in liver enzymes, ALT, AST, gamma GT, and this was rapid and sustained improvement.
And we also saw a number of extrahepatic benefits, including the lipid profile improving with HDL going up, triglycerides going down. There was no change in LDL. There was significant reduction in HbA1c. In fact, it went down by just over half a point. That would have been an approval diabetes product back in the day. We saw significant improvements in hepatic and muscular insulin sensitivity. We saw a decrease in diastolic blood pressure. That was not statistically significant, but something we'll be measuring. And we saw increases in adiponectin levels as well, up to threefold and over threefold at the higher dose. Now, that's how we did on efficacy, which was quite compelling and really led the company to start that phase III. And on safety, how did the rational design impact the safety of the molecule? So overall, the concern about PPARs is peripheral edema.
If you look at the peripheral edema rates and drug-related peripheral edema rates in our phase II, it was just at 2%. It appears that the design seems to have mitigated some of the worst impacts of PPAR gamma. We did also have weight gain in the study, as has been reported with other PPAR agonists. That weight gain appears to have been milder than previous PPAR agonists. Half of patients gained no weight, so there was no impact. 20% gained less than 5%, and 30% gained 5% or more. And this profile, so remember the profile of really robust fibrosis efficacy, cardiometabolic benefits, when we talk to physicians, we think this is a very competitive profile in the MASH market. Let me move to the phase III. Again, this is a fully recruited trial. The last patient was enrolled in April of last year.
As opposed to being a six-month trial, it is an 18-month trial, so a full extra year of follow-up, and we do hope for a deepening of effect over that extra one year. The main cohort has over 1,000 patients enrolled, so a very large trial. Again, two doses, and the key differences between the phase II and the phase III are, as I mentioned, the Type 2 diabetes, again, no F1s, and there are a number of patients, 14%, that actually started the trial on a baseline of GLP-1, a stabilized dose of GLP-1, as opposed to we had no patients in the phase II as real GLP-1s were really not used that much at that time, so importantly from this as well, we have an exploratory cohort where any screen fails, F1 or F4, go into an exploratory cohort.
So we will have a population of F4s coming out of this where we should have some data. And that is particularly important because the next step for Inventiva is an outcomes trial. So because we are using a histological endpoint, which is used as a surrogate endpoint by the FDA and the EMA, we do need to do a confirmatory trial. And we are going to start an outcome study in patients with compensated cirrhosis MASH to confirm the clinical benefits. We have to measure either the prevention of progression to cirrhosis or a reduction in associated clinical outcomes, such as decompensation, cancer, or liver transplant. So we're actively designing that trial now.
Some early thoughts on it are that we need to have a patient population that is sick enough so they can progress to get events, but not so sick that we cannot reverse the pathology of it. Right? So there's got to be this Goldilocks patient population that we can study. Otherwise, we're doing a 10-year outcomes trial, which no one wants. We do believe that there is a patient population of compensated advanced chronic liver disease, or CACLD, that meets that criteria. These are patients that have advanced fibrosis or cirrhosis, but no outward signs of liver disease. However, you can identify them through non-invasive tests. One of the key hallmarks is they have portal hypertension. In other words, the blood flowing into the liver is not flowing out as quickly.
It's backing up into the circulation system of the body and leading to varices in the esophagus and other places. And importantly, preclinical data suggests that lanifibranor can address the etiology of that CACLD patient, that portal hypertension. So we'll be exploring this more and giving more details on this as we go through the year. All right. So what can you expect from Inventiva in the next 24 months? Well, we will report out data this year. We will start our F4 outcomes trial at the beginning of next year sometime, and then file with the FDA as well and the EMA. And we anticipate a potential market launch for lanifibranor in 2028. And we do so from a position of strength.
We have a cash balance that runs us out to Q3 2027, and that assumes the positive data and the third tranche from the pipe that we did in October 2024 coming in and funding the company. Just as a reminder, we own this asset fully with the exception of outlicensed in China, Japan, and South Korea, with a very low royalty burden. So this is a fully owned asset by Inventiva. So to summarize, we have an asset that has a therapy that has the potential to have real clinical benefit in a very large unmet need patient population with a large potential. We have a company that is well-funded with a really strong management team, and we're looking forward to giving you updates throughout the course of the year and having a very successful 2026.
And with that, I will hand it over to you, to our questions in the audience. Thank you.
Thank you. Any questions from the audience here? Otherwise, I would like to kick it off. I mean, I sat here a year ago. It's great to see the progress since you started the job in October. Any first impressions? And how has it been going?
So I would say that this is a French innovation company that has done a wonderful job of progressing this asset as far as it has. I think it was a real pleasure and surprise to come in and to see how well this trial had been executed and just the potential impact on patients that it has. This is in terms of actually reversing stages of fibrosis.
I did not, as first time in the MASH market, appreciate just the damage that liver disease does to these patients and the impact that you can have by reversing it. So very impressed with what the company has done so far.
Great. And with the recent management changes, is Inventiva planning to become a U.S. company?
No, we are going to stay France-based. We will build up our U.S. commercial infrastructure in the future, but we will be I think we'll move from a French innovation company to a transatlantic international company that's still based in France.
Great. That's pleased to hear. I see we got one question from the webcast, which is, is there any I mean, you commented on the planned filing of the data. Do you see any risk factors, limiting factors that could result in a later filing?
I always say that we're not Pfizer. We're not going to file an NDA in one day with a COVID vaccine. No, but we have I think right now we are building up such a very strong team that has experience prosecuting these types of trials, collecting the data, cleaning the data, moving from last patient, last visit to top-line data, moving from top-line data to NDA filing. So I think we're going to move very efficiently going forward.
And what's the company currently doing to prepare for commercialization?
So this 2026 is a year of strategic preparation, doing a lot of market research, preparing some market access, thinking strategically about which geographies we want to be in at what point, probably building up a little bit of presence in medical affairs for 2026, really with the preparation to scale robustly in 2027 after data.
Good.
Any further questions in the room? I think we're all right. Keep it there.
Thank you.
Yep. Well, thank you, everyone, for coming today. Don't jostle on the way out, and we look forward to giving updates for the course of the year. Thank you.
Thank you.