Conference Transcript - MDGL 2026-08-11

Edward Nash, Analyst — Canaccord Genuity

Hi. Good afternoon, everyone. My name is Edward Nash, Senior Biotech Analyst here at Canaccord Genuity. It is my pleasure to have with us today the management team for Magical Pharmaceuticals. Joining us from the company, we have Marty Deer, the Chief Financial Officer, Carol Huntsman, Chief Commercial Officer, and we also have David Sergal, who is the Chief Medical Officer. Thank you all for joining us today. So, at least in the biotech world, usually I would say Madrigal doesn't need any introductions because they were the company that get the first drug approved for a very large indication and out there known as MASH. You know, you've had a really impressive second quarter and, you know, with continued strong growth. Although the company does not provide specific revenue guidance, could you maybe talk to us a little bit about the commercial growth of ResDifera since its launch in April of 24 and how Madrigal positions ResDifera from a perspective of the long-term expectations?

Bill Sibold, CEO

Yeah, great. Thanks, Ed, and thanks for having us. We really appreciate being here. Yeah, I'll take a stab at answering that question. So at Madrigal, we've had excellent commercial growth since our launch in the first quarter of 2024. And we're focused very much on our two type priorities, which is building value for RISDFRA, getting RISDFRA to as many patients as we can, and building our pipeline so we can maintain our leadership position in MASH. And if we talk about the quarter specifically, we announced on 2Q at the end of July, and we had excellent top-line growth. We announced $364 million in revenue, which was 71% increase year over year, looking at the same quarter a year ago. And if you look at our trailing 12 months in revenue, we're on a run rate of approximately $1.3 billion. So that's only after nine quarters of launch. So this is putting us on a trajectory of a mega blockbuster, which is exactly what we think RizDifra is. And we do give KPIs every quarter, and we look at our patient ads and how many patients that we have on ResDifera. And nine quarters in, and we look at this as active patients at the end of each quarter. And at the end of Q2, 2026, we had over 49,000 patients on ResDifera. And we're very excited about achieving a significant threshold. we crossed the 50,000 patient mark in the early July time point. So any launch, specialty or otherwise, that's a significant milestone. So we really think that the growth of the company will continue, and we talked a little bit about what we expect for third and fourth quarter, and we acknowledge that we're comfortable with the consensus growth rate from second quarter to third quarter and then third quarter to fourth quarter 2026, and that will result in robust sales growth for 2026. And we see that growth continuing. So if we look at, so that's sort of the execution of Q2, but a lot of the growth and the future growth is going to be driven by the market dynamics and then the growth of our pipeline. And the market dynamics are just ripe for an exceptional launch and continued growth of RISDFRA. This market is at its infancy. Basically, we are only 10% penetrated into a market that has 10% diagnosis rate. So 10% of 10%, we are just 1% penetrated into what we think can be a significant market. And we're definitely in the leadership position and expect continued growth. And we really liken our growth prospects to some of the, you know, large therapeutic areas in categories such as rheumatoid arthritis or IBD, et cetera, where you see these categories at the $20 billion mark and growing, you know, multiple decades after the first product launch. So we think there's significant growth opportunity for RizDifra, and we think the mash market's going to continue to grow in the future. And we're just at the beginning of seeing where that growth is. And, you know, with that, we want to continue to build on our leadership position within MASH and build out our pipeline. So we've talked about and we have announced that we have IP protection of RISDFRA to 2045. So we're building for the long term. You know, what can we do? We have a once-in-a-lifetime medicine with ResDifera, and what can we do possibly in building out F2, F3, and F4C with ResDifera? What can we do to transform the efficacy of ResDifera through combination therapies? And with that, we've built out our pipeline of potential assets that we can combine with ResDifera and continue to grow the market. So in the last year plus, we've added, we had a pipeline of one drug, RizDifra, you know, in two indications, and we've added now we have a pipeline of 10 assets. And, you know, we're very capital efficient. We spent less than $300 million up front to build out this pipeline, but it's setting us up to really take advantage of our leadership position in MASH, the growing market, our excellent execution, and so we're pretty excited about the long-term prospects for the drug and the company.

Edward Nash, Analyst — Canaccord Genuity

Fantastic. Thank you for that. But so ResDifra has been on the market now for a little bit over two years. Could you talk a little bit about if there's been any real physician evolution in how their sentiment, overall sentiment on ResDifra, especially as we've seen an additional competitor come in the market, and we may likely see another one come next year onto the market. What's been the company's kind of interaction with physicians on that?

Carole Huntsman, Other

Great question. Thank you. So we, early on in launch, we built a broad base of prescribers, and actually that is one of the best predictors of long-term success. We actually, last year, announced a milestone of more than 10,000 prescribers, and we've continued to add, on a weekly basis even, new prescribers to that number. So now we're more focused on depth, depth of prescribing. So where we are right now as it relates to our best-in-class specialty launch analogs is we're right aligned with those analogs in terms of depth. And you may ask why we're getting great breadth and depth. It's really how the product is performing and the positive experience that providers are having with the product. We are hearing really on a regular basis that ResDifera is overperforming expectations in the clinic with its best-in-class profile, liver-directed efficacy, well-tolerated, once-daily pill. They're having a great experience with it. So would I say that physician sentiment has changed? No, not really. But I think there may even be more excitement today about the broad efficacy of ResDifera. Dave shared a forest plot during our earnings call that showed how all of the patient subtypes performed on ResDifera. And the efficacy was strong regardless of that patient subtype. And that's actually a really significant competitive advantage for ResDifra relative to the product that's approved and on the market today, as well as to the products that are coming on the market. So that efficacy in each of those patient subtypes. And, you know, speaking of competition in the marketplace, we are now at one year after the approval of Wegovi in MASH. and we continue to steadily add patients. We continue to have very favorable market access positioning for ResDifera. So we're not seeing a significant impact. There is utilization of Wegovi, however, not to the detriment of ResDifera. We see Wegovi more as a background therapy. And in fact, if you look at Wegovi prescriptions on a weekly basis, less than 1% are prescriptions written by hepatologists or GIs for patients or inpatients with MASH. So we welcome competition. Competition helps grow the market. Competition invests more in education of providers and patients. And in the end, that benefits the leader and the foundational therapy that ResDifra is.

Edward Nash, Analyst — Canaccord Genuity

Thank you. And obviously with WAGOI's approval that We obviously know GLP-1s are very effective in the treatment of MASH, and Marty, to your comment about expanding your pipeline, GLP-1 was the first step in that process. Could you talk a little bit about 2086s, the clinical data or the data, I should say, we have to date that would show that a combination of that GLP-1 with ResMediram makes sense?

David Soergel, Other

Yeah, it's a great point. So we licensed in MGL-2086 last July, I think about a year ago. And so 2086 is a orphaglipuron scaffold GLP-1 small molecule agonist. And what we know, the reason why we're interested in this mechanism is because we know from the Meister-Nash study that patients who lose just a little bit of body weight, so 5% body weight loss, see a potentiated effect of resmediram on fibrosis. So you see better antifibrotic efficacy if you can just dial in a little bit of body weight loss. So with 2086, we're not going for 20% weight loss. We're going for just tweaking enough weight loss to be able to get to get more efficacy out of ResMedROM. And so this is sort of consistent with our entire pipeline strategy where ResMedROM, ResDifera is in the middle of that strategy. Everything that we've in license is built around ResDifera and has scientific rationale for it being a combination approach. So that's the existing data with GLP-1 and ResMedROM. And so what we announced just at our last earnings call is that we initiated our first time in human study with 2086. So it's a novel molecular entity. So it requires going first in human. And then next year we'll anticipate running a combination study with Rizmetaram in MASH patients to test its efficacy. So a very exciting time. That was our first in licensing opportunity. But as Carol mentioned, we've got a whole, you know, stable now of agents to combine with ResMedROM and build that next generation of medicines.

Edward Nash, Analyst — Canaccord Genuity

So in addition to the GLP-1 asset, during the past year, you've also taken in Ervogastat, which is a DGAT-2 inhibitor, an SI-RNA targeting PNPLA-3, as well as additional SI and RNAs for six undisclosed targets. Could you maybe highlight briefly the rationale behind this expansion decision? You made these acquisitions very rapidly, probably much quicker than I think of any biotech, not just in MASH, but in general with multiple different mechanisms. And I know the one thing that physicians we've talked to all agree on is that this is going to be a multi-mechanistic approach in MASH. So clearly you guys are on the right path. But maybe you could just talk a little bit behind that rationale and expansion for the exact assets that you acquired.

David Soergel, Other

Yeah, well, we moved quickly because the opportunity was there to do a really good deal and get a great asset. So Avergostat first, as you pointed out, we licensed in from Pfizer last year. They had actually run this medicine up through phase 2B. So we had already some very good evidence, you know, Pfizer quality evidence showing that avirgastat has efficacy in patients with MASH, very effective reducer on its own of liver fat, which, of course, is one of the substrates for the development of MASH. And so the feeling, the other thing that we know about resmediram is that the more you can reduce liver fat, more you can reduce PDFF, the more antifibrotic efficacy you get with resmediram. And so the combination of these two mechanisms, THR-beta with resmediram and a de novo lipogenesis inhibitor with the DGAT2 inhibitor, gives us an opportunity to boost resmediram's efficacy in terms of antifibrosis as well. So two approaches, GLP-1 and DGAT, with the same sort of foundational strategy, right, looking to combine another mechanism, complementary mechanism with RizMedROM and deliver a better profile, better efficacy with the great safety and tolerability we've already seen with RizMedROM. So that's the approach that we've taken with Arvergastat, and that'll be entering a phase one study, drug-drug interaction study later this year, and then a phase two program anticipated next year. PNPLA-3 was licensed in earlier this year. We licensed it in from Arrowhead Pharmaceuticals, and they had been previously partnered with J&J. So there was actually quite a bit of work done in early phase development with this sRNA therapy. As you probably are all well aware, sRNAs are great because they're highly specific to the target and they're very durable. So you can give them quarterly or semi-annually and sometimes even annually for some of these medicines. So the science has really progressed substantially with that CRNAs, and they're sort of a great modality for chronic diseases like MASH. And so the rationale for combining these two mechanisms with resmediron plus PNPLA-3 is PNPLA-3 is known to be one of the major genetic drivers of MASH severity, especially in Hispanic patients. Up to 30% of Hispanic patients have PNPLA-3 mutations that are amenable to downregulation or silencing with an sRNA. So, again, in these higher-risk patients with PNPLA mutation, delivering better efficacy might be an important clinical benefit for those individuals. So that combination rationale is to basically deliver PNPLA-3 siRNA quarterly or semiannually, and then have as a baseline therapy res metaram. So developing as a combination regimen as opposed to a fixed-dose combination.

Edward Nash, Analyst — Canaccord Genuity

So will the prioritization of these programs really be driven by the clinical data themselves or it will be, as opposed to you guys don't internally think, you know, this is really where things are going to move and this is the one that we're really kind of crossing our fingers and hoping works out? Or is it just a matter of, you know, we get them in and whatever shows the most robust I know that fits hand in hand, but, you know, I'm just kind of curious how you guys are thinking about it, Mick.

David Soergel, Other

Yeah, I mean, I would say the priority, the near-term priority is to generate the data, So run the combination trial. So we'll have three combination studies in phase two starting next year. We anticipate. And we have to talk to the agency about that first. But that's the plan. And once we see those data, we'll have, you know, a decision to make about which ones we bring forward into phase three. And, you know, as we've talked about, resmederam is already a great drug. I mean, it delivers great, broad efficacy across all subgroups. And so the bar for us is actually quite high. So this is not a situation where we have to develop a pipeline of assets because we're running up against, you know, a constraint, you know, like IP constraint, because we have IP out to 2045 with ResMedROM. But it really is an opportunity that's been created by the success of ResMedROM that allows us to build a pipeline and deliver the next generation of treatments. But the bar is high for us. It's got to be a transformative medicine for us to bring it forward.

Bill Sibold, CEO

Just one comment on that. We're very cost-effective in building the pipeline, and it's creating the optionality to move the whole sector forward. That's the underlying strategy with RBD.

Edward Nash, Analyst — Canaccord Genuity

So the cardiometabolic effects of MASH treatment have been clearly received a lot of attention even well before RISDFER was approved. And that's something in our conversation with the KOLs that gets brought up a lot is that, you know, they're looking beyond some of the other, the direct clinical impacts more towards cardiometabolic factors as well. You know, this year at major medical conferences, we've been hearing a lot about this. So could you maybe talk to us a little bit about how important you think in MASH therapy it is to show a benefit beyond just MASH resolution and fibrosis improvement?

David Soergel, Other

Well, I guess I would sort of quibble a little bit with just MASH resolution. And the reason is because MASH is known to be a risk factor for cardiovascular morbidity and mortality. So if you can improve MASH, if you can improve the liver disease, the possibility is that you reduce cardiovascular risk as well in these patients. But we also know that resmediram is a cardiometabolic drug. So it reduces atherogenic lipids, it reduces LDL-C, it reduces LP little a, actually quite effectively, as well as triglycerides. So we know that it has systemic anti-lipid effects that could potentially lead to a cardiovascular benefit in patients with MASH. So, yes, I mean, MASH at its root is stimulated by cardiovascular risk factors like diabetes, obesity, hypertension, et cetera. But there's a trigger in MASH that leads some patients to develop liver fibrosis and experience the worst outcomes. And so the disease, you know, it's not just a constellation of metabolic findings. findings, it's the metabolic findings that lead to some worse pathophysiology. And that's science that's really not as well understood yet, what that trigger is. So our thesis is that treating with resmediram and maybe with other of our pipeline assets will be able to deliver even a better profile for patients and improve their risk.

Edward Nash, Analyst — Canaccord Genuity

So in addition to the recent expansion of the pipeline, we're also expecting data from the Phase III Maestro Nash Outcomes Study, which was anticipated for next year, as well as the 54-month long-term data from the Maestro Nash Study are expected in 2028. So, assuming positive results from these trials, how do you anticipate these readouts will impact the potential for expansion, the commercial opportunity for res different, especially with regards to the outcome study in F4.

David Soergel, Other

Sure. Yeah. I mean, I'll, I'll, I'll talk about the phase three studies. I'll hand it to Carol. I'll talk about commercial. Um, so, so we have two phase three studies ongoing, as you pointed out. So the, the 54 months data from Maestro Nash is the continuation of the trial that led to accelerated approval. So Maestro Nash 52 week was, uh, what led to, uh, Maestro Nash's initial accelerated approval. And then confirmation of benefit will happen at 54 months, um, in 20, as you pointed out. So that's the F2, F3 population. And then the Meister outcome study is the F4 population. And that's an event-driven outcome study, which means that we have to get to a certain target number of events to complete the trial. And at that point, we would unblind and determine whether or not we were successful. So what we've talked to the agency about is that either of these two trials, positive results from either of these two trials could lead to full approval in F2, F3. Of course, a positive study in F4 would lead to an indication expansion into F4. So that would, you know, be a label update with a new indication. And so maybe I'll hand it to Carol.

Carole Huntsman, Other

Yeah, and so, I mean, as Dave said, outcomes are very, very important. So whether outcomes come from F2, F3 study, the F4 study, that's going to be very important to us commercially and provides even more opportunity to continue a very, very strong launch. As it relates specifically to F4C, there are 245,000 F4C patients diagnosed in the United States. And because this is a much more severe condition, we feel that there's going to be a lot more urgency to treat. So penetration of that population will happen a lot more quickly and actually has the opportunity to double our overall opportunity with ResDifera and F2 through F4C.

Edward Nash, Analyst — Canaccord Genuity

So do you feel based on, I mean, the F4 has obviously been one of the areas we know the agency, that was really kind of a big focus for them early on because those patients were at the most need of a treatment. But as we saw with all of the FGF21s having been acquired by big pharma companies, all three big pharma companies acquiring the three that were out there. How do you see the FGF21s kind of playing in versus the ResDifera in the F4?

David Soergel, Other

So I'll talk about it, I guess, from a scientific standpoint. So FGF21 is an interesting mechanism. We've seen some data from Phase II in both F2, F3, and in F4, small data set in F4 that shows anti-fibrotic efficacy with these medicines. Now, they also have other effects. So they have GI side effects, and there's an on-target issue with this target, bone mineral density loss. So that's sort of been known for quite a while. So we'll have to see how the phase three studies land, you know, what the profile is when they actually complete their phase three program. But the way we've thought about this, this mechanism is really as an induction therapy, where you treat patients with advanced fibrosis, especially for, for six to 12 months, on a background of resmediram, and then you continue resmediram after that. So, and that way you sort of mitigate some of the challenges, especially with, especially with mineral density loss.

Carole Huntsman, Other

And I would just go back to the story about outcomes and the importance of outcomes, ResDiffer will be the first with outcomes. And really all of the products that are coming along will start with an accelerated approval and they'll have to get to their outcomes. So just as we were first to the market in F2, F3, we'll be first with outcomes and that gives us a real opportunity to continue to, you know, execute a very successful launch.

Edward Nash, Analyst — Canaccord Genuity

So could you maybe talk a little bit about the EU strategy and how that's really been contributing to overall RISDFRA uptake?

Bill Sibold, CEO

Yeah, I'll answer that. So we're approved in the EU, which is fantastic. And we launched in Germany last September, and we just got approval in the UK as well. So listen, the MASH is a global disease. It's not just a U.S. disease. So the opportunity outside the U.S. is significant. Right now, with respect to RISDFRA in Europe in particular, the market setup is great. We have guidelines. In fact, we had guidelines. We were on the guidelines from EASL before we even had them in the U.S. The patient population is significant. So the epidemiology is ripe for the need for RISDFRA. Market access and reimbursement is an issue. It presents challenges, particularly with the most favored nations, the MFN strategy that's coming out of the U.S. administration. So until we figure out and have clarity on MFN, you won't see a big uptake, most likely in Europe, of ResDifera. But we're kind of at the ready, and we're working on it. It's a big focus of ours. But, you know, in 2026, we've said that sales will likely be negligible until we work our way through the MFN strategy.

Edward Nash, Analyst — Canaccord Genuity

Thank you very much. Obviously, this is still very early days for ResDifera, and you've been off to a fantastic start with it. So look forward to continued strong growth there and obviously the evolution of the pipeline as well. Thank you very much for joining us.

Bill Sibold, CEO

Thank you.