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 Madrigal Pharmaceuticals. Joining us from the company, we have Mardi Dier, the Chief Financial Officer, Carole Huntsman, Chief Commercial Officer, and we also have David Soergel, who is the Chief Medical Officer. Thank you all for joining us today. Thank you. Thank you. At least in the biotech world, usually I would say Madrigal doesn't need any introductions because they were the company to get the first drug approved for a very large indication and out there known as MASH. You've had a really impressive second quarter, and 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 Rezdiffra since its launch in April of 2024, and how Madrigal positions Rezdiffra from a perspective of the long-term expectations? Yeah. Great. Thanks, Ed, and thanks for having us. We really appreciate being here. I'll take a stab at answering that question. 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 top priorities, which is building value for Rezdiffra, getting Rezdiffra to as many patients as we can, and building our pipeline so we can maintain our leadership position in MASH. 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. If you look at our trailing 12 months in revenue, we're on a run rate of approximately $1.3 billion. That's only after nine quarters of launch. This is putting us on a trajectory of a mega blockbuster, which is exactly what we think Rezdiffra is. We do give KPIs every quarter, and we look at our patient adds and how many patients that we have on Rezdiffra. Nine quarters in, and we look at this as active patients at the end of each quarter. At the end of Q2 2026, we had over 49,000 patients on Rezdiffra. We're very excited about achieving a significant threshold. We crossed the 50,000 patient mark in the early July time point. At any launch, specialty or otherwise, that's a significant milestone. 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. 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. We see that growth continuing. That's sort of the execution of Q2. 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. The market dynamics are just ripe for an exceptional launch and continued growth of Rezdiffra. This market is at its infancy. Basically, we are only 10% penetrated into a market that has 10% diagnosis rate. 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. We really liken our growth prospects to some of the large therapeutic areas in categories such as rheumatoid arthritis or IBD, et c, where you see these categories at the $20 billion mark and growing multiple decades after the first product launch. We think there's significant growth opportunity for Rezdiffra, 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. With that, we want to continue to build on our leadership position within MASH, and build out our pipeline. We've talked about, and we have announced that we have IP protection of Rezdiffra to 2045. We're building for the long term. What can we do? We have a once-in-a-lifetime medicine with Rezdiffra. What can we do possibly in building out F2, F3, and F4c with Rezdiffra? What we could do to transform the efficacy of Rezdiffra through combination therapies. With that, we've built out our pipeline of potential assets that we can combine with Rezdiffra and continue to grow the market. In the last year plus, we had a pipeline of one drug, Rezdiffra, in two indications, and now we have a pipeline of 10 assets. We're very capital efficient. We spent less than $300 million upfront to build out this pipeline. It's setting us up to really take advantage of our leadership position in MASH, the growing market, our excellent execution, so we're pretty excited about the long-term prospects for the drug and the company. Fantastic. Thank you for that. Yeah. Rezdiffra's 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 their sentiment, overall sentiment on Rezdiffra, 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 interaction with physicians on that? Great question. Thank you. 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. Now we're more focused on depth of prescribing. 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. 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 Rezdiffra is over-performing expectations in the clinic with its best-in-class profile. Liver-directed efficacy, well-tolerated once-daily pill, they are having a great experience with it. 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 Rezdiffra. Dave shared a forest plot during our earnings call that showed how all of the patient subtypes performed on Rezdiffra, and the efficacy was strong regardless of that patient subtype. That is actually a really significant competitive advantage for Rezdiffra relative to the product that is approved and on the market today, as well as to the products that are coming on the market. That efficacy in each of those patient subtypes. Speaking of competition in the marketplace, we are now at one year after the approval of Wegovy in MASH, and we continue to steadily add patients. We continue to have very favorable market access positioning for Rezdiffra. We are not seeing a significant impact. There is utilization of Wegovy, however, not to the detriment of Rezdiffra. We see Wegovy more as a background therapy, and in fact, if you look at Wegovy prescriptions on a weekly basis, less than 1% are prescriptions written by hepatologists or GIs for patients or in-patients with MASH. 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 Rezdiffra is. Thank you. Obviously with Wegovy's approval, we obviously know GLP-1s are very effective in the treatment of MASH. Mardi, to your comment about expanding your pipeline, GLP-1 was the first step in that process. Could you talk a little bit about MGL- 2086, the clinical data or the data, I should say, we have to date that would show that a combination of that GLP-1 with resmetirom makes sense? Yeah. It is a great point. We licensed in MGL-2086 last July, I think about a year ago. MGL-2086 is an orforglipron scaffold GLP-1 small molecule agonist. The reason why we were interested in this mechanism is because we know from the MAESTRO-NASH study that patients who lose just a little bit of body weight, so 5% body weight loss, see a potentiated effect of resmetirom on fibrosis. You see better anti-fibrotic efficacy if you can just dial in a little bit of body weight loss. With MGL-2086, we are not going for 20% weight loss. We are going for just tweaking enough weight loss to be able to get more efficacy out of resmetirom. This is sort of consistent with our entire pipeline strategy, where resmetirom, Rezdiffra is in the middle of that strategy. Everything that we've in-licensed is built around Rezdiffra and has scientific rationale for being a combination approach. That's the existing data with GLP-1 and resmetirom. What we announced just at our last earnings call is that we initiated our first time in human study with MGL-2086. It's a novel molecular entity, so it requires going first in human. Next year we'll anticipate running a combination study with resmetirom in MASH patients to test its efficacy. A very exciting time. That was our first in-licensing opportunity, but as Carole mentioned, we've got a whole stable now of agents to combine with resmetirom and build that next generation of medicines. In addition to the GLP-1 asset, during the past year, you've also taken in ervogastat, which is a DGAT-2 inhibitor, an siRNA targeting PNPLA3, as well as additional siRNAs 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. 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. Clearly, you guys are on the right path. Maybe you could just talk us a little bit behind that rationale and expansion for the exact assets that you acquired. Well, we moved quickly because the opportunity was there- Yeah. ...to do a really good deal and get a great asset. Ervogastat first, as you pointed out, we licensed in from Pfizer last year. They had actually run this medicine up through phase II-B, so we had already some very good evidence, Pfizer quality evidence, showing that ervogastat 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. The feeling, the other thing that we know about resmetirom is that the more you can reduce liver fat, the more that you can reduce PDFF, the more anti-fibrotic efficacy you get with resmetirom. The combination of these two mechanisms, THR-β with resmetirom and a de novo lipogenesis inhibitor with the DGAT-2 inhibitor, gives us an opportunity to boost resmetirom's efficacy in terms of anti-fibrosis as well. Two approaches, GLP-1 and DGAT, with the same sort of foundational strategy, right? Looking to combine another mechanism, complementary mechanism with resmetirom and deliver a better profile, better efficacy with the great safety and tolerability we've already seen with resmetirom. So that's the approach that we've taken with ervogastat. That'll be entering a phase I study, drug-drug interaction study later this year, and then a phase II program anticipated next year. PNPLA3 was licensed in earlier this year. We licensed it in from Arrowhead Pharmaceuticals, and they had been previously partnered with J &J. There was actually quite a bit of work done in early phase development with this siRNA therapy. As you probably are all well aware, siRNAs are great because they're highly specific to the target, and they're very durable. You can give them quarterly or semi-annually, and sometimes even annually for some of these medicines. The science has really progressed substantially with siRNAs, and they're sort of a great modality for chronic diseases like MASH. The rationale for combining these two mechanisms with resmetirom plus PNPLA3 is PNPLA3 is known to be one of the major genetic drivers of MASH severity, especially in Hispanic patients. Up to 30% of Hispanic patients have PNPLA3 mutations that are amenable to down-regulation or silencing with an siRNA. Again, in these higher-risk patients with PNPLA mutation, delivering better efficacy might be an important clinical benefit for those individuals. That combination rationale is to basically deliver PNPLA3 siRNA quarterly or semi-annually, and then have as a baseline therapy resmetirom. So developing as a combination regimen as opposed to a fixed-dose combination. 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, "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 we get them in and whatever shows the most robust. I know that fits hand in hand, but- Yeah. ...just kind of curious how you guys are thinking about a mechanism. Yeah. I would say the near-term priority is to generate the data, right? Run the combination trial. We'll have three combination studies in phase II starting next year, we anticipate, and we have to talk to the agency about that first, but that's the plan. Once we see those data, we'll have a decision to make about which ones we bring forward into phase III. As we've talked about, resmetirom is already a great drug. It delivers great broad efficacy across all subgroups. The bar for us is actually quite high. This is not a situation where we have to develop a pipeline of assets because we're running up against a constraint, like IP constraint, because we have IP out to 2045 with resmetirom. But it really is an opportunity that's been created by the success of resmetirom 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. Yeah. 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 R&D. Understood. Yeah. The cardiometabolic effects of MASH treatment have been clearly received a lot of attention, even well before Rezdiffra was approved. That's something in our conversation with the KOLs that gets brought up a lot is that they're looking beyond some of the other, the direct clinical impacts more towards cardiometabolic factors as well. This year at major medical conferences, we've been hearing a lot about this. 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? Well, I guess I would quibble a little bit with just MASH resolution. Yeah. No, it's true. The reason is because MASH is known to be a risk factor for cardiovascular morbidity and mortality. Yeah. 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. We also know that resmetirom is a cardiometabolic drug. It reduces atherogenic lipids, it reduces LDL-C, it reduces Lp(a) actually quite effectively, as well as triglycerides. We know that it has systemic anti-lipid effects that could potentially lead to a cardiovascular benefit in patients with MASH. Yes, MASH at its root is stimulated by cardiovascular risk factors like diabetes, obesity, hypertension, et c. But there's a trigger in MASH that leads some patients to develop liver fibrosis and experience the worst outcomes. The disease, it's not just a constellation of metabolic 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. Our thesis is that treating with resmetirom and maybe with other of our pipeline assets will be able to deliver even a better profile for patients and improve their risk. 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. Assuming positive results from these trials, how do you anticipate these readouts will impact the potential for expansion, the commercial opportunity for Rezdiffra, especially with regards to the outcome study in F4? Sure. I'll talk about the phase III studies- Okay. ...and then I'll hand it to Carole to talk about commercial. We have two phase III studies ongoing, as you pointed out. The 54 months data from MAESTRO-NASH is the continuation of the trial that led to accelerated approval. MAESTRO-NASH 52 week was what led to MAESTRO-NASH's initial accelerated approval, and then confirmation of benefit will happen at 54 months in 2028, as you pointed out. That's the F2, F3 population. Yeah. The MAESTRO 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. 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. That would be a label update with a new indication. Yeah. Maybe I'll hand it to Carole. Yeah, as Dave said, outcomes are very important. So whether outcomes come from F2, F3 study, the F4 study, that is going to be very important to us commercially and provides even more opportunity to continue a very strong launch. As it relates specifically to F4c, there are 245,000 F4c patients diagnosed in the U.S., and because this is a much more severe condition, we feel that there is 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 Rezdiffra in F2 through F4c. So do you feel, based on, the F4 has obviously been one of the areas we know the agency, that was really a big focus for them early on because those patients were at the most need of a treatment. As we saw with all of the FGF21s having been acquired by big pharma companies, or three big pharma companies acquiring the three that were out there. How do you see the FGF21s playing in versus the Rezdiffra in the F4? So I will talk about it- Sure. ...I guess from a scientific standpoint, and then you can. So FGF21 is an interesting mechanism. We have 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 is an on-target issue with this target, bone mineral density loss. That's sort of been known for quite a while. We'll have to see how the phase III studies land, what the profile is when they actually complete their phase III program. But the way we've thought about this mechanism is really as an induction therapy where you treat patients with advanced fibrosis, especially F4, for 6-12 months on a background of resmetirom, and then you continue resmetirom after that. And that way, you sort of mitigate some of the challenges, especially with bone mineral density loss. Yeah. I would just go back to the story about outcomes and the importance of outcomes. Rezdiffra 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. 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 execute a very successful launch. Could you maybe talk a little bit about the EU strategy and how that's really been contributing to overall Rezdiffra uptake? Yeah, I'll answer that. We're approved in the EU. Which is fantastic, and we launched in Germany last September, and we just got approval in the U.K. as well. Listen, MASH is a global disease. It is not just a U.S. disease. So the opportunity outside the U.S. is significant. Right now, with respect to Rezdiffra in Europe in particular, the market setup is great. We have guidelines. In fact, 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 Rezdiffra. Market access and reimbursement is an issue. It presents challenges, particularly with the most favored nations, the MFN strategy that is coming out of the U.S. administration. Until we figure out and have clarity on MFN, you will not see a big uptake, most likely in Europe for Rezdiffra. But we are at the ready, and we are working on it. It is a big focus of ours. But in 2026, we have said that sales will likely be negligible until we work our way through the MFN strategy. Thank you very much. Obviously, this is still very early days for Rezdiffra, and you have 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. Great. Thanks, Ed. Thanks Ed.