Hi, all. Thanks for being with us today on the first day of the JPM Healthcare Conference. It's a pleasure to introduce Inventiva to you. We got Frédéric Cren, Pierre Broqua, and Mark Pruzanski. They're going to kick it off. We have some time for questions from the audience afterwards, so feel free to ask those after, and I'll hand it over now.
Thank you. Thank you. I'm Frédéric. I'm the CEO and co-founder. Thank you for taking time on your busy schedule on this last day of JPM. Today, I'll go over the Inventiva and the lanifibranor story. As usual, I'll be making forward-looking statements, so please have a look at our SEC filings that are available on our website. So what I'm going to be trying today to show you, to explain, is that we have with lanifibranor the ideal drug candidate to treat patients with advanced fibrosis and type 2 diabetes. Why we believe this is the case is, first, we have a drug that is oral with, I would say, best-in-class efficacy. We have published Phase IIb data where we have shown an 18% fibrosis placebo-adjusted improvement after only six months of treatment.
And on top of that, we provide a series of cardiometabolic improvements, especially an improvement in insulin sensitivity. And this is particularly true and beneficial to patients, of course, with type 2 diabetes that, as you know, are the most difficult to treat patients. The second one, of course, is that when you look at the tolerability profile where it's an extremely well-tolerated drug. And also, it has an AE profile that makes it compatible with a combination with GLP-1. So we really think that lanifibranor combined to a GLP-1 would be also an ideal combination treatment for patients. The mechanism of action is also very particular. It's a differentiated pan-PPAR profile. And what is great is that we have seen recently two drugs, two PPARs, being approved for liver disease by the FDA.
And so this gives us confidence that when we file for NDA approval after our data is published, you will be in a good situation for approval. And then, of course, where do we stand? We've made tremendous progress over the past months. We have a trial now that is more than 95% enrolled. And I'm very pleased today to share with you that we have sent a message to all of our sites early January to stop screening because we have enough patients randomized or in the screening pool to meet our target. And so we definitely maintain our target for end of having the last patient randomized before the end of this semester and the data the second half of 2026. And then also, most important, we have now a company that is well-capitalized. We did a large raise, more than $400 million.
You see here the lead investor, only top-tier investor. They've done extensive due diligence, and this has given us comfort, you know, that if they've decided to support us, it's because they really believe in the data. We talk about PPAR. There's been a stigma in the industry about PPAR, but it's important to look at data, and what is really crucial is that when we look at the so-called issue of bladder cancer with rosiglitazone, they have been totally removed by meta-analysis. They demonstrated there is no association of bladder cancer with rosiglitazone, and more importantly, pioglitazone has been shown to be actually cardioprotective. And as I mentioned, there have been two drugs approved by the FDA recently that are PPARs. Also, very important, and this is extremely, I think, great news for us and great data.
When you look at what happens in real life, we have in the U.S. alone more than six million scripts of Pio. So it means that in real life, doctors, so in this case, most likely endos, they know they like the drug, they see the benefit of this drug, and can manage the side effects that come with Pio. And this is great news because, of course, you have in the endos office a huge number of patients with MASH. And so when we will come with a drug like Lani, which is an extremely better version than Pio, I think we will have a quick uptake in this population. So that's in real life. And then also, it's important to look at strategically, how do they perceive the PPAR class. And I think the Gilead acquisition of CymaBay for more than $4 billion for a drug.
Actually, at the time, it was not approved, so they had end-of-Phase III data. So $4 billion for a drug in PBCs also bodes well for how strategically it could react to positive data of Lani. So Lani, what is it? It's unique. It's the only pan-PPAR currently in development in NASH. It can activate the three isoforms moderately and at the same dose. It's oral, so it's really clearly differentiated on factors versus other antifibrotic drugs. It's well protected with IP running through 2040. Also, what is really important is why are those three isoforms so important in NASH? NASH is a complex disease. And you see on the bottom of the slide, you know, how each PPAR, why each isoform acts on each of the key features of the disease. If I take, for example, only fibrosis, let's just focus on fibrosis.
We have shown at six weeks strong antifibrotic activity. It's because we have a direct activity and the engagement of PPAR delta and PPAR gamma are able to activate stellate cell and control the fibrogenesis process. If we look only at the bottom of the slide, you know, sometimes we hear, well, your PPAR, it's not fancy as other novel mechanisms of action. True, but there is one advantage: you know what are the potential liabilities that come with this class of drugs, and you can design your molecule to avoid all of these potential liabilities, and that's what we have done with Lani, so all the potential liabilities that are typically seen with a single or dual PPARs have not been seen in all of our tox studies, and we have done one-year monkey and we've done the two-year carcinogenesis study.
All of that has been provided to the FDA, which has come back to us saying that they consider the tox package complete and adequate for a filing of an NDA in MASH patients. So let's talk about the results. So we conducted a Phase IIb, 247 patients treated for six months. Important to retain this, only six months. Two biopsies that were centrally read. The results were published in the New England Journal of Medicine concerning the histology benefit and for the cardiometabolic benefit in the Nature Communications. And on the back of this trial, we received Breakthrough Therapy Designation and Accelerated Approval in F2, F3, and F4 patients. We were the first drug to show statistically effect on the three key endpoints of the FDA: so NASH resolution and fibrosis improvement, fibrosis improvement without NASH worsening, and NASH resolution without worsening of fibrosis.
So the first drug to achieve a statistical effect on all of these three markers. You see here the result of six months on the endpoint that we have retained for our Phase III, statistical effect by both doses. And when you look and you compare to the other drugs that have been approved, such as Madrigal, you see that we have doubled the effect compared to Madrigal after one year of treatment. And to find a similar level of responders, you need to go to the injectable that, if you follow the space, you know, come with some side effects that are not present with Lani. And then, of course, in patients that tend to be, we say in France, polymedicalized, so that receive quite a large number of medications, an oral drug is always better.
Same picture if we only follow, only focus on fibrosis, 18% delta, 12% for Madrigal. You need to go to injectable to find similar or to FGF21 to find similar effect size. Also NASH resolution, both doses being statistically significant, higher effect compared to Madrigal. Then you need to go to the other mechanism to find a similar effect. Importantly, the benefits of Lani do not stop to the histology, but it also comes with cardiometabolic improvement. You have here the liver enzymes. They are normalized after four weeks. If you look at same data, for example, in semaglutide, it's 24 weeks. Not sure you can wait for six months to normalize enzymes in this type of patients. If you look at HDL and triglyceride, also their statistical effect.
And then very important, and we're extremely proud of this data, we had approximately 40% of patients in the trial that had type 2 diabetes. They continued on their treatment during the study. This is the black line. You see that the HbA1c did not change. But for those that were treated with Lani, there were statistically significant improvements seen after 14 weeks. So it means that for those patients that have type 2 diabetes and NASH, we're able to help them control their diabetes, resolve their NASH, reduce their fibrosis. And when you look actually at the effect size in this patient population, it's actually larger than in the larger population.
And that's why, you know, we will come back over and over saying if you have a patient that has NASH and has advanced fibrosis, F2, F3, and type 2 diabetes, there is one drug that is really ideal for this patient population. It's Lani. And this result has also been replicated in a trial that we did in a combination with empagliflozin. And also, we did a clamp study and a tracer study . And there we showed that we actually improve insulin resistance in key organs, including the liver. Weight gain. So of course, we improve insulin resistance. So we have some weight gain with Lani, approximately 2 kilos, 2%. The patients have an average of 100 kilos. Importantly, it happens in only 33% of the patients. So one-third of the patients have a weight gain of approximately 2 kilos.
What is great to see is that this weight gain comes with metabolic improvement. You take a patient in the same trial on placebo that gained weight, all these metabolic parameters worsen. You take a patient on Lani that gained weight, his metabolic profile improves, so it means that we have a metabolically healthy weight gain. It's a shift from the visceral fat that is pro-inflammatory towards the adipose tissue. It's well known. It has been shown by Pio. But that's the mechanism of action. What is important is that so we have a metabolically healthy gain, but we have shown in two different studies, so one in a one-year study in a different patient population that this weight gain plateaus after six months.
And in a blinded analysis of our current Phase III, where we had more than 100 patients that had done the full study, the full 72 weeks, we see once again the weight gain that stabilizes at 24 weeks. This is very different from Pio, where in a study in a NASH population, this study is called PIVENS, went on for several years, 96 weeks. And you see a steady increase of the weight gain. So it's probably due to this pan-PPAR activation with the PPAR delta helping to control the weight increase. And then lastly, if you really have an issue and you really want to control, we have shown that if you combine Lani with SGLT2 inhibitor, you maintain the benefit of both drugs, but weight is totally controlled and it's not different from placebo.
There have been similar studies with Pio and GLP-1 showing that similarly to our combination study, you can control the weight gain by combining Pio and GLP-1. We have in our Phase III approximately 15 patients on GLP-1 on the combination. So we will have data when we release the data, hopefully showing that the same effect happens. So where do we see and how do we compare Lani to the key mechanism of action that are currently in development? I think the fact that we're oral gives us a tremendous advantage versus FGF21. Versus Madrigal, I think there are two important features of Lani that are really also a great advantage for us. It's actually the direct antifibrotic activity. It's visible statistically effect after six months. Madrigal had to wait one year to show it. And then we are direct, you know, we act on insulin resistance.
If there is one common feature of all patients with MASH, it's the fact that they have insulin resistance. And also in terms of tolerability, no GI side effects. So when we talk about combination, we're clearly, you know, an ideal candidate to be combined with GLP-1. It's all for this reason that we really believe that we have a key spot that is patients with advanced fibrosis and type 2 diabetes. In terms of market, we focus on F2, F3. You have here in orange, you know, the percentage, the estimated percentage of patients with type 2 diabetes. It's approximately 40%-50%. In our trial, we have approximately 60% of patients with type 2 diabetes. So we're talking here quite a large size of the NASH population.
You see here that, you know, when you are F2, F3, you have a 10-fold or 17-fold risk to increase your liver-related mortality, and that patient with type 2 diabetes and NASH, you know, type 2 diabetes is an independent predictor of fibrosis progression, and actually, patients with NASH and type 2 diabetes have a faster progression of their fibrosis, and that type 2 diabetes alone is an independent risk factor of mortality, so when we discussed with, you know, we conduct marketing studies and where do these pathologists and GIs see where Lani fits with the other mechanism of action. You see here where, you know, Lani's position. It's really patients that have an advanced fibrosis and type 2 diabetes, whether they have obesity or not. It's really clear that this is a key spot for us.
And also, I would say once again that the combination Lani, oral Lani, with the GLP-1 is also an ideal product or treatment for patients with NASH. So where do we stand in terms of progression in the NATiV3, which is our Phase III? So very pleased to, you know, to communicate, as I did in the intro, that we have stopped screening because we have enough patients enrolled in the study. Importantly, as I mentioned, we have patients on GLP-1, approximately 15%, well-powered, above 90%. And also over the summer, we ran a blinded analysis comparing the Phase II-B results with NATiV3. We confirmed that the baseline values are similar. It means that the patients we're recruiting are similar, have similar characteristics than the one of the Phase II-B. So that's encouraging, of course.
And more importantly, the magnitude of changes that we saw in relevant biomarker are consistent between the two studies. And so with this good news on recruitment, we confirm our target to have the last patient randomized for the first half of 2025. And as it is an 18-month study, we will have the result for the second half of 2026. And we are already preparing for filing in 2027. We have, thanks to the recent raise, we are well capitalized to execute on our clinical trial. And with all this, we, you know, we are putting in place all the actions to be sure we are the second oral drug approved in MASH, with a target of approval in 2028. So with that, I think we can move to the Q&A. Thanks a lot, Fred. Any questions from the room? Otherwise, I can kick it off maybe with Mark.
Let's start with you. Can you comment on your appointment as chairman of the board and what made you decide Inventiva?
Sure. Is this on?
Yes.
Yeah. So as you know, I recently joined the board as chair. You know, I was long a leader, I guess, in this space, having put NASH, now MASH on the map all the way back in the aughts to find the regulatory path. And of course, you know, unfortunately, didn't get the first drug to patients. But now that's happened. But there's still clearly a huge unmet need. And I've been following the Inventiva and lanifibranor program for many years. As Frédéric showed, it's demonstrated in Phase II-B in a relatively short course of treatment, six months, best in category, best in oral category efficacy with a fairly clean profile.
And you've got the precedent molecule pioglitazone, which is a top 20 selling drug by volume in the United States, still despite the fact that no one's promoting it and despite whatever lingering concerns there might be about the class. So you know, I view this as a great opportunity to position the next oral drug that I hope will get to patients for, as Frédéric mentioned, the most difficult, the most at-risk patient segment, specifically type 2 diabetics with advanced fibrosis. And there you've got a uniquely differentiated profile represented by this drug. So I'm very happy to be involved with the story.
Thank you. Just checking. As you mentioned already, but we're as well extremely excited by the recent financing of up to 348 million in equity financing to advance the trial further and additional 30 million of milestone payments relating to your agreement with CTTQ.
This financing follows a look at blinded data from around 500 patients on treatment for six months and 100 patients for 18 months. Can you elaborate a bit more on that data?
Sorry. You said what are the difference between six months or 18 months?
Yes. Yeah. Can you elaborate on the data available at this blinded look? The blinded analysis.
Yeah. Sorry. Maybe Pierre, you want to answer that?
Yeah, sure. So yeah, we did a blinded analysis on 500 patients, 200 of which had completed week 72. So you know the principle of blinded analysis. We pull all the data and we follow several markers, including ALT, AST, glycemic control, lipid metabolism, some liver-related, fibrosis-related NITs such as FAST and ELF. We follow that over time.
And to put this into the context of our Phase II-B data, which you have seen here, we have performed the exact same blinded analysis on the pool of 247 patients from the Phase II-B. And what we saw, this was really a magic moment because, firstly, we observed that the baseline data for all these markers, with the exception of HbA1c, because we have a higher population, a higher percentage of diabetic patients in the Phase III. Besides that, all the baseline values of those markers were exactly the same. And that indicates that we have really succeeded in enrolling the same kind of patients that we had in our Phase II-B. And when we followed the trends for change on these different markers for the first six months, it was really great to see a parallel decrease.
So the curves were actually overlapping between the Phase II-B blinded analysis and the Phase III blinded analysis. On top of that, what we saw on certain fibrosis-related markers such as ELF, after 18 months, we had a greater decrease than after six months. So that means the way we interpret that is that we are confident or we are, you know, confident that we are going to replicate the Phase II-B data. And that because the treatment duration is longer, we may expect a greater benefit on fibrosis with lanifibranor in NATiV3. Thank you. And if we dig in a little bit more on Lani's therapeutic profile and potential, can you compare and contrast Lani with Rezdiffra, especially in terms of efficacy, impact on fibrosis, tolerability, and other biomarkers? Yeah, with other mechanism of action. So you've seen the slide.
I think the key differentiating factor is the fact that we have direct antifibrotic activity visible after six months. And this insulin sensitivity activity, this is clearly, you know, a key advantage, a key differentiator. Oral also is important. And that's important to highlight because the other mechanism of action that I've shown, you know, direct antifibrotic activity are all injectable. So that's, you know, in a population that, you know, might be under GLP-1, if you ask them to take another second shot, that might not go down very well.
All right. One more. Can you comment on the weight gain with Lani, including its magnitude and plateau, especially in combinations with SGLT2? T2. T2.
Right. Yeah. No, actually, the weight gain is due to insulin sensitization. So you improve insulin sensitivity in all patients.
Some patients will pick up on weight because you will increase their ability to store fat in the adipose tissue. That comes with an improvement of all cardiometabolic disorders because instead of insulin-resistant patients actually store fat in the liver, this is why we have steatosis, but also in the heart and also in the muscle. When you treat those patients with an insulin sensitizer, you remove fat from all these organs and you get it back to the adipose tissue. We did studies comparing the metabolic profile of patients having gained weight on Lani versus patients having gained weight on placebo in the Phase II-B trial. We clearly see that weight gain in Lani comes with an improvement of metabolic cardiovascular parameters, which is not the case with the placebo patients gaining weight.
And lastly, as you have seen, there is a plateau indeed after six months, which we believe, personally, I think that we have achieved maximum insulin sensitization in those patients. And then we have also the PPAR delta component, which is not in PIO, it's only in Lani, which can improve insulin sensitivity in the muscle and improves energy expenditure. Okay? So all in all, this is the way I explain this plateau after six months.
Perfect. Thank you. Just checking if any questions. Maybe last one on Lani. What do you view as the future treatment landscape of MASH and how do you see Lani fitting into that treatment landscape? Mark? Future treatment landscape of MASH and how do you see Lani fitting into that landscape?
Well, yeah, I mean, I think as we've been saying, the drug will be ideally positioned to treat type 2 diabetics with advanced fibrosis either as a monotherapy or in combination with a GLP-1. I mean, I think another point of differentiation, as Frédéric mentioned, is that the two mechanisms play very well together. So you get additive metabolic benefits starting with HbA1c lowering. And I think also, you know, it was generally viewed as very good news that Novo demonstrated with semaglutide efficacy on both endpoints and that they're going ahead and seeking approval because they will greatly expand the market. And specifically, they'll mobilize endocrinologists to really care about these patients. And that will be a great tailwind for when hopefully lanifibranor will be approved. But just to note, you know, as is true in other metabolic diseases, there's room here for a number of different modalities.
But the landscape where, you know, thinking a few years ahead, we're launching lanifibranor in the context of Rezdiffra, THR-beta agonist, GLP-1, ± an FGF21, there is a huge opportunity, I think, for lanifibranor. Thank you, and maybe to conclude, what are you most excited about heading into 2025? Who wants to start? I'll start. I'm most excited that I, you know, given we just did this large array, I can, you know, put my mind on other things than talking only to investors and focus on, you know, things like, you know, commercial activity where, you know, where do we fit, get more data, preparing for the NDA filing. Its work is already done. As we mentioned, all the preclinical packages are finalized so we can start writing. So that, I think, for us is exciting.
And then I would add the Madrigal presentation before, you know, when you see, you know, their launch curve, the fact that they confirmed this is a large market. I think this is exciting. So I just want to follow, you know, that Rezdiffra sales, just, you know, just go to the $1 billion. And then when you come back after that with a better drug, it's just, you know, a dream. So that's good.
Perfect. Thanks to all of you. Unless any other questions? Thanks. Then we can conclude. Thank you. Thanks.