Q2 2025 Madrigal Pharmaceuticals Inc Earnings Call

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Demi: Good morning and thank you for standing by. Welcome to Madrigal Pharmaceuticals' second quarter 2025 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

Tina Ventura: Thank you, Demi. Good morning, everyone, and thank you for joining us to discuss Madrigal Pharmaceuticals' second quarter 2025 earnings. We issued a press release this morning and posted a slide deck that accompanies this webcast on the Investor Relations section of our website. On the call with me today is Bill Sibold, Chief Executive Officer; Dave Sorgel, Chief Medical Officer; and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, and then we will take your questions. Please note on slide two, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements. With that, I will now turn the call over to Bill.

Good morning and thank you for standing by. Welcome to Madrigal Pharmaceuticals second quarter, 2025 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Miss Tina Ventura, Chief investor relations officer. Please go ahead.

Thank you, Debbie. Good morning, everyone. And thank you for joining us to discuss madrigal's. Second quarter 2025 earnings.

We issued a press release this morning, and posted a slide deck. That accompanies, this webcast on the investor relations section of our website.

On the call with me today is Bill, sibil chief executive officer.

Dave soral chief medical officer and Marty dear Chief Financial Officer, they'll provide prepared remarks and then we'll take your questions.

Bill Sibold: Thanks, Tina. Good morning and thanks for joining us. We have a lot to cover today. Before we move into this quarter's performance, as you can see on slide three, it's been an incredibly exciting and productive last few months at Madrigal, both driving the launch and building our future. We've accomplished a lot, and each of these milestones reflects the deliberate execution of our long-term strategy to maximize Resdifera's value and expand our leadership in MASH. In a short time, we've transformed Madrigal into a company with a longer runway, a stronger foundation, and greater flexibility to build for the future. Fundamental to our success is our business in the U.S., which continues to outperform. Resdifera's quarterly run rate now exceeds $200 million, well on its way to blockbuster status. We can objectively say it stands among the best specialty launches of the last decade.

Please note on site 2. We will be making certain forward-looking statements. Today we refer you to our SEC filings for a discussion of the risks, that may cause actual results to differ from the forward-looking statements. And with that, I will now turn the call over to Bill. Oh, thanks, Tina. Good morning, and thanks for joining us. Uh, we have a lot to cover today before we move into this quarter's performance. As you can see, on slide 3, it's been an incredibly exciting and productive last few months at Madrid. Go, both driving the launch and building our future

We've accomplished a lot, and each of these milestones reflects the deliberate execution of our long-term strategy to maximize resources, differentiate value, and expand our leadership in Mash. In a short time, we've transformed Madrigal into a company with a longer runway, a stronger foundation, and greater flexibility to build for the future.

Fundamentals to Our Success.

Bill Sibold: Second, we've strengthened the long-term value of Resdifera with our new U.S. patent, providing protection to February 2045. This changes how we think about Resdifera's growth potential and our investment in the business. It's not about years of opportunity, but decades. Third, we're preparing to expand internationally, beginning with Germany later this year. Geographic expansion adds another potential future growth opportunity for Resdifera. Fourth, we're working to expand Resdifera with an indication in compensated MASH cirrhosis, or F4C, where our outcomes trial continues to progress. If positive, it could double Resdifera's market opportunity. Finally, we're building a pipeline for the next phase of leadership in MASH with the addition of a promising oral GLP-1 to combine with Resdifera. We have the capital in place that will allow us to support and scale all of this.

Is our business in the US, which continues to outperform, where differ is quarterly, run rate. Now exceeds $200 million well on its way to Blockbuster status. We can objectively say, it stands among the best specialty launches of the last decade.

Second. We've strengthened the long-term value of resera, with our new US Patent, providing protection to February 2045.

This changes how we think about res Dipper's growth potential and our investment in the business. It's not about years of opportunity, but decades

Third. We're preparing to expand internationally beginning with Germany later. This year, Geographic expansion, adds another potential future growth opportunity for res, differ,

Forth. We're working to expand, red zipper with an indication in compensated mass kouros or f4c, where our outcomes trial continues to progress. If positive it could double risk, differs Market opportunity,

And finally, we're building a pipeline for the next phase of leadership in Mash with the addition of a promising oral glp-1 to combine with red different.

Bill Sibold: Each of these pieces adds value to the foundation we are building for long-term leadership in MASH. Let's move into the call with our agenda on slide four. A lot has happened since our last call. I wanted to take the opportunity first to talk about the new U.S. patent that was issued today. We believe it's a significant contributor to our long-term outlook. As we summarize on slide five, the patent covers claims directed to Resdifera's commercial weight threshold dosing regimen as prescribed in its FDA-approved label and will be listed in the FDA Orange Book. We recently learned some favorable news. The patent reflects an updated expiration date of February 4, 2045, which is extended from the previously noted date of September 30, 2044.

and we have the capital in place that will allow us to support and scale all of this.

Each of these pieces adds value to the foundation. We are building for long-term leadership in Mash.

So, let's move into the call with our agenda on Slide 4. A lot has happened since our last call. I wanted to take the opportunity first to talk about the new U.S. patent that was issued today.

We believe it's a significant contributor to our long-term outlook.

As we summarize on slide 5, the patent covers claims directed to Res differce. Commercial weight threshold dosing regimen as prescribed in its FDA approved label and will be listed in the FDA orange book.

And we recently learned some favorable news.

The patent reflects an updated expiration date of February 4, 2045, which is extended from the previously noted date of September 30, 2044.

Bill Sibold: What gives us such high confidence in the strength of this patent is that it is based on the clear and compelling finding that different Resdifera doses given to two different cohorts of patients, each with different body weights, optimizes the efficacy and safety of Resdifera. This finding is based directly on our clinical team's independent analysis from our Phase 3 MAESTRO-NAFLD trial, which was adopted by the FDA for our label. The bottom line, any potential generic competitor will need to adopt the Resdifera label and would infringe on our patent. Our confidence in this patent is also supported by precedent U.S. case law. This patent changes the game for us in two ways. First, strategically, it gives us the privilege of time. This extension creates a lot of flexibility for us to pursue our long-term strategy.

What gives us such high confidence in the strength of this pattern is that it's based on the clear and compelling findings that different res doses, given to two different cohorts of patients, each with different body weights, optimize the efficacy and safety of res different.

This finding is based directly on our clinical teams independent analysis from our phase 3 Maestro. Nash trial which was adopted by the FDA for our label.

The bottom line, any potential generic competitor will need to adopt the red dip or label and would infringe on our patent.

Our confidence in this patent is also supported by precedent U.S. case law.

Bill Sibold: We can be very thoughtful and deliberate about how we build our future and shape our pipeline. Second, it adds another potential decade of protected revenue and materially increases our value proposition, creates additional opportunity in MASH, and extends our ability to keep innovating to address unmet patient needs. Now let's turn to slide six and Resdifera's second quarter performance, where we delivered net sales of $213 million, up 55% quarter over quarter. U.S. Resdifera net sales are now annualizing at well over $800 million. The significant demand we are generating is driven by strong and consistent execution on two key launch metrics: patients on drug and prescriber penetration. First on patients, as shown on slide seven, we ended the second quarter of 2025 with more than 23,000 patients on Resdifera, up from more than 17,000 patients at the end of the first quarter.

This patent changes the game for us in 2 ways. First strategically, it gives us the privilege of time. This extension creates a lot of flexibility for us to pursue our long-term strategy.

We can be very thoughtful and deliberate about how we build our future and shape our pipeline.

Second, it adds another potential decade of protected revenue and material materially increases. Our value proposition creates additional opportunity in mesh and extends our ability to keep innovating to address unmet patient needs.

Now, let's turn to slide 6 and res. Second quarter performance, where we delivered, net sales of 23 million up 55% quarter over quarter.

Us res different. Net sales are now annualizing at well, over 800 million.

The significant demand we're generating is driven by strong and consistent educ uh execution on 2 key launch metrics patients on drug and prescriber penetration.

Bill Sibold: As we have noted before, this figure represents patients actively on therapy, accounting for any discontinuations. We are encouraged by Resdifera's robust growth, and yet we are still in the early stages of this launch. Only about 7% of the 315,000 diagnosed F2F3 MASH patients under the care of a liver specialist are being treated with Resdifera. There is significant opportunity ahead. Moving to slide eight and our progress on physician penetration. As I have said before, building a strong base of prescribers early in a launch is one of the best indicators of long-term success. That is why the pace of adoption has been so encouraging. In fact, in just over a year since approval, we've achieved another key launch goal. 80% of our 6,000 top targets have prescribed Resdifera.

First on patients as shown on slide 7. We ended the second quarter of 2025 with more than 23,000 patients on resera up, from more than 17,000 patients at the end of the first quarter.

As we've noted before, this figure represents patients actively on therapy accounting for any discontinuation.

We are encouraged by rezz Dipper's robust growth and yet we're still in the early stages of this launch only about 7% of the 315,000 diagnosed f2f. Rematch patients under the care of a liver specialist are being treated with red zipper. There is significant opportunity ahead.

Moving to slide 8 and our progress on physician penetration. As I've said before, building a strong base of prescribers early. In a launch is 1 of the best indicators of long-term success.

That's why the pace of adoption has been so encouraging.

Bill Sibold: This level of penetration exceeds the benchmarks we track and is the direct result of the significant amount of work we've done to wire the system for a first-in-disease launch like Resdifera. We're also seeing strong progress as we expand into our broader 14,000 target prescriber base. By the end of the second quarter, 60% or roughly 8,500 healthcare providers had written a prescription for Resdifera, up from 50% in the first quarter. Looking ahead, more of our focus will be on depth, which is also tracking in line with best-in-class launches. We believe this is largely due to the positive experience that providers are having with Resdifera, and we anticipate that it will continue to drive depth going forward. This positive experience is being driven by Resdifera's compelling profile shown on slide nine.

In fact in just over a year since approval we've achieved another key launch goal. 80% of our 6,000 top targets have prescribed whereas different this level of penetration exceeds the benchmarks we track and is the direct result of the significant amount of work. We've done to wire the system for a first in disease launch. Like Reds, different

We're also seeing strong progress as we expand into our broader 14,000. Target prescriber Bass by the end of the second quarter. 60% were roughly 8,500 Health Care Providers had written a prescription for res, Dara up from 50%, in the first quarter.

Looking ahead, more of our Focus will be on depth which is also tracking in line with best-in-class launches. We believe. This is largely due to the positive experience that providers are having with resera and we anticipate that it will continue to drive depth going forward.

Bill Sibold: Resdifera is the liver-directed medicine with a mechanism of action that improves the critical processes in the liver that drive MASH. It has consistently strong efficacy regardless of patient subtype, including those with type 2 diabetes who have a higher risk of progression and comprise approximately 60% of the MASH population. Additionally, Resdifera works effectively regardless of fibrosis stage, BMI, or genetic makeup. It's very consistent when it comes to treatment effect. It's also easy to prescribe and to take a once-daily, well-tolerated pill with no titration requirement. That simplicity matters to physicians, to patients, and ultimately to adherence. We continue to see strong early signs of adherence consistent with what we see from other well-tolerated oral therapies. As we look ahead to future competition, we believe Resdifera's attractive real-world profile gives us a durable advantage.

And this positive experience is being driven by risk, differs compelling profile shown on slide 9.

Red Dara is the liver directed medicine with a mechanism of action. That improves the critical processes in the liver that drive mash. It has consistently strong efficacy regardless of patient subtype, including those with type 2 diabetes, who have a higher risk of progression, and comprise approximately 60% of the mash population.

Additionally res, Dipper Works, effectively, regardless of fibrosis stage BMI or genetic makeup.

So, it's very consistent when it comes to treatment effect.

It's also easy to prescribe and to take a once daily. Well, tolerated pill with no titration requirements, that Simplicity matters to Physicians to patients and ultimately to adherence

We continue to see strong early signs of adherence, consistent with what we see from other? Well, tolerated, oral Therapies.

Bill Sibold: The next potential entrant in MASH is likely to come from the injectable GLP-1 class. You can see on slide 10, Resdifera compares very favorably across key attributes. For example, while semaglutide demonstrated an improvement in fibrosis, it was less pronounced in patients with type 2 diabetes, whereas Resdifera works consistently across patient subtypes. Another key difference is adherence in the real world. It's low for semaglutide. Most patients struggle to get to and maintain the 2.4 milligram dose. In addition, only approximately 30% of patients with obesity remain on the medicine after one year. This is especially relevant in MASH, where we are talking about a 72-week efficacy endpoint. For a progressive chronic disease like MASH, providers want a medicine that patients will stay on and one that they can administer easily without a titration schedule, and that is where Resdifera stands out.

In Mash is likely to come from the injectable glp1 class.

And you can see on slide 10 whereas different Compares very favorably across key attributes. For example while semaglutide demonstrated an improvement in fibrosis it was less pronounced in patients with type 2 diabetes. Whereas res differer Works consistently across patients subtypes.

Another key difference is adherence in the real world, its low, for some of glutide, most patients struggle to get to and maintain the 2.4 milligram dose.

In addition only approximately 30% of patients with obesity remain on the medicine after 1 year.

This is a specially relevant in Mash, where we're talking about a 72 week efficacy endpoint.

Bill Sibold: Certainly, a key attribute of a GLP-1 is its impact on weight loss. We also know patients with MASH may benefit from a combination approach. Today, about 25% of patients on Resdifera are taking it alongside an injectable GLP-1 to manage their comorbidities. That figure increases to roughly 50% when you include prior GLP-1 users. Combination use is happening in the market today, and we expect it to grow over time. As we look ahead on slide 11 and consider the upcoming GLP-1 launch in MASH, we believe it has the potential to accelerate the growth opportunity for Resdifera. Our focus remains squarely on the 315,000 diagnosed patients with moderate to advanced fibrosis. This is our core specialty market. Novo is targeting a much larger population, many multiples of our 315,000. Their efforts will raise awareness and drive broader screening, diagnosis, and treatment.

For a progressive, chronic disease like mash providers. Want a medicine that patients will stay on and 1 that they can administer easily without a titration schedule and that's where it is. Different stands out.

Certainly a key attribute of a glp-1 is its impact on weight loss. And we also know patients with mash May benefit from a combination approach today about 25% of patients, on res. Dipra are taking it alongside in an injectable glp1 to manage their comorbidities and that figure increases to roughly 50% when you include prior glp1 users.

So combination use is happening in the market today and we expect it to grow over time.

As we look ahead on slide 11 and consider the upcoming GLP-1 launch in Massachusetts, we believe it has the potential to accelerate the growth opportunity for Risk Differer.

Our Focus remains squarely, on the 315,000 diagnosed patients with moderate to Advanced fibrosis. This is our core specialty Market.

Bill Sibold: This will ultimately benefit patients, and we expect it will also benefit Resdifera, both as the foundational therapy in MASH for first-line patients and from the high real-world discontinuation rate of semaglutide. There is clearly a need in this large and underpenetrated market for multiple mechanisms and better combinations to treat this challenging disease. That is why we are excited to study Resdifera in combination with our newly in-licensed oral GLP-1, as noted on slide 12. We are taking a differentiated approach focused on MASH. We are looking to develop a chronic therapy for a chronic disease with Resdifera as the foundation. We want to optimize the efficacy and tolerability in MASH by balancing the right amount of weight loss from a GLP-1 with the fibrosis and lipid reduction of Resdifera in a once-daily, well-tolerated pill. Our data has shown that just 5% weight loss can increase Resdifera's antifibrotic effect.

Novo is targeting a much larger population—many multiples of our 315,000. Their efforts will raise awareness and drive broader screening, diagnosis, and treatment. This will ultimately benefit patients, and we expect it will also benefit Risa both as the foundational therapy in match for first-line patients and from the high real-world discontinuation rate of semaglutide.

And there's clearly a need in this large and underpenetrated market for multiple mechanisms and better combinations to treat this challenging disease.

That's why we're excited to study red zipper in combination with our newly. In-licensed oral glp-1 as noted on slide 12.

We're taking a differentiated approach approach focused on mass. We are looking to develop a chronic therapy for a chronic disease with res differ as the foundation.

We want to optimize the efficacy and tolerability in MASH by balancing the right amount of weight loss from a GLP-1 with the fibrosis and lipid reduction of Resera in a once-daily, well-tolerated pill.

and our data has shown that just 5% weight loss can increase red Dipper's antibiotic effect.

Bill Sibold: As we assessed the oral GLP-1 landscape, we had specific criteria that we were looking for. We wanted an orphaglipron derivative with a favorable stability and pharmacokinetic profile that was amenable to develop as a combination therapy and, of course, an asset that was actionable. We believe XYH2086 from CFPC Pharma is the right oral GLP-1 asset for our program. It gives us the opportunity to develop what we believe could become a best-in-disease, well-tolerated oral combination for MASH. Importantly, we secured this asset with favorable terms. We have exclusive global rights for a $120 million upfront payment and potential future payments based on achievement of development, regulatory, and commercial milestones. We expect the transaction to close in the fourth quarter and expect to enter the clinic in the first half of next year. We will provide additional updates on our clinical development plans on future calls.

And as we assess the oral glp1 landscape, we had specific criteria that we were looking for.

We wanted an orthogonal derivative with a favorable stability and pharmacokinetic profile that was amenable to develop as a combination therapy and, of course, an asset that was actionable.

We believe f, s, s YH2 from CSPC Pharma is the right oral GLP-1 asset for our program.

Gives us the opportunity to develop what we believe to become a best-in-class disease. Well-tolerated oral combinations for MASH.

Importantly, we secured this asset with favorable terms. We have exclusive Global rights for 120 million upfront payment and potential Humor, future payments based on achievement of development Regulatory and Commercial. Milestones, we expect the transaction to close in the in the fourth quarter and expect to enter the clinic in the first.

Half of next year, we will provide additional updates on our clinical development plans on future calls.

Bill Sibold: Let's briefly move on to two additional growth opportunities, starting with the international expansion of Resdifera on slide 13. In June, we received the positive CHMP opinion, a key regulatory milestone that sets the stage for approval across the European Union. We expect a final decision from the European Commission later this month and are preparing to launch in Germany in the second half of this year. As we've discussed, we've made an incredible amount of progress in Germany over the last year. Leadership and our field teams are in place. We understand which providers treat MASH. We're continuing to engage in disease education. We've begun our efforts to wire the system, and importantly, European guidelines already include Resdifera as a first-line treatment for MASH, which positions us well.

Let's briefly move on to 2 additional growth opportunities. Starting with the international expansion of risk, dipra on slide 13 in June, we received a positive chmp opinion, a key regulatory Milestones, that sets the stage for approval across the European Union.

We expect the final decision from the European Commission later this month and are preparing to launch in Germany in the second half of this year.

Bill Sibold: Like the U.S., we've defined our initial target population as patients already diagnosed with F2F3 MASH and under the care of a liver specialist. Based on our research, we estimate that the population is approximately 370,000 patients across Europe. We believe Resdifera can be the first medicine approved for MASH in Europe and the foundational therapy for this population, just as we've established in the U.S. Let's move to slide 14 and the opportunity we see in compensated MASH cirrhosis, or F4C, an important next step in our growth strategy. First, there is a high unmet need with no approved treatments and serious risk of progression. Second, Resdifera's liver-directed mechanism targeting fibrosis is well suited for cirrhosis. Third, our two-year open-label data presented at EASL showed sustained efficacy and supports our confidence in the ongoing MAESTRO-NAFLD trial.

As a first line treatment for MASH, which positions us as well.

Like the US, we've defined our initial target population as patients already diagnosed with F2, F3, and under the care of a liver specialist.

Based on our research, we estimate that the population is approximately 370,000 patients across Europe.

We Believe red zipper. Can be the first medicine approved for Mash in Europe, and the foundational therapy for this population just as we've established in the US.

let's move to slide 14 and the opportunity we see in compensated, Mash cirrhosis or f4c, an important, next step in our growth strategy,

First, there is a high unmet need with no approved treatments and serious risk of progression. Second liver directed mechanism targeting fibrosis is well suited for cirrhosis

Bill Sibold: No other product or mechanism in development has shown this level of reduction in liver stiffness with such an attractive product profile. Finally, we have real-world momentum, a clear first-mover advantage with outcomes data expected in 2027, and what we believe will be a best-in-disease profile in F4C. We have learned what it takes to launch in MASH, and we are ready to extend that leadership from F2 to F4C. Slide 15 outlines the opportunity we see in F4C. We have taken a thoughtful approach to understanding the F4C population. Our research shows there are approximately 245,000 patients in the U.S. with compensated MASH cirrhosis who are already diagnosed and under the care of our target liver specialist.

Third are 2-year open-label data presented at easel shows, sustained efficacy and supports our confidence in the ongoing Maestro, Nash, outcomes, trial.

No other product or mechanism in development. Has shown this level of reduction in liver stiffness with such an attractive product profile.

And finally we have real world momentum a clear first mover Advantage with outcomes data expected in 2027 and what we believe will be a best in disease profile and f4c. We've learned what it takes to launch in mash and we're ready to extend that leadership from F2 to f4c period.

Slide, 15, outlines the opportunity. We see in f4c, we've taken a thoughtful approach to understanding the f4c population. Our research shows there are approximately 200 245 thousand patients in the US.

Bill Sibold: These patients are sicker and further along in disease progression, which typically translates to greater and faster adoption. That is why we believe F4C has the potential to effectively double Resdifera's market opportunity in the U.S. With that, I will hand it over to Dave to walk through the data on slide 60. Thanks, Bill. I will walk through the takeaways now from our two-year open-label extension data in F4C, which we presented at EASL. First, let us look at the liver stiffness data as measured by vibration-controlled transient elastography, or VCTE. Patients experienced a mean reduction of 6.7 kilopascals in liver stiffness at two years, statistically significant versus baseline. Over half achieved at least 25% reduction in liver stiffness. As published in JAMA, that level of improvement is tied to a lower risk of progression to end-stage liver disease.

With compensated MASH cirrhosis who are already diagnosed and under the care of our Target liver specialists.

These patients are sicker and further along in disease, progressed progression, which typically translates to Greater and faster adoption.

That's why we believe f4c has the potential to effectively double Dippers Market opportunity in the US.

With that. I'll hand it over to Dave to walk through the data on slide. 60. Thanks Bill.

I'll walk through the takeaways now from our 2-year open label extension data in f4c, which we presented as easel.

First, let's look at the liver stiffness data as measured by vibration control transient elastography or VCT.

Patients experienced, a mean, reduction of 6.7 kilopascals and liver stiffness at 2 years, statistically significant versus Baseline.

Bill Sibold: 35% of patients met the criteria for regression from F4 to F3, suggesting potential reversal of cirrhosis. Turning to slide 17, another critical point is Resdifera's potential ability to reduce the risk of clinically significant portal hypertension, or CSPH. CSPH is a key driver of the most severe outcomes of cirrhosis, like ascites, variceal bleeding, and hepatic encephalopathy. It marks the tipping point into decompensated disease. In our open-label study, 65% of patients with CSPH at baseline improved to a lower risk category by year two. That movement away from high-risk CSPH suggests Resdifera could help delay or prevent life-threatening complications. Taken together, these data support our confidence in the ongoing phase three MAESTRO-NAFLD trial outcomes trial because the baseline characteristics of the patients in the open-label study align closely with those in our F4C outcomes trial.

Over half achieved at least 25% reduction in liver stiffness as published in Jamma that level of improvement is tied to a lower risk of progression to end-stage liver disease.

And 35% of patients, met the criteria for regression from F4 to F3 suggesting potential reversal of cirrhosis.

Turning to slide 17.

Another critical point is the potential ability to reduce the risk of clinically significant portal hypertension or CPH.

Cph is a key driver of the most severe outcomes of cirrhosis, like a sites, fiscal bleeding and hepatic and sopathi. It marks the Tipping Point into decompensated disease.

In our open label study 65% of patients with cph at Baseline, improved to a lower Risk by year 2.

that, that movement away from high-risk cfph, suggests was, if for could help the layer prevent life-threatening complications,

Bill Sibold: For us, this means Resdifera has the potential to become the first approved treatment for compensated MASH cirrhosis, a very sick segment of the MASH market that currently has no therapeutic options. I will now turn the call over to Mardi.

Taken together these data, support our confidence in the ongoing phase 3 Meister Nash outcomes trial because the Baseline characteristics of the patients in the open. Label study, align closely with those in our f4c outcomes trial.

For us, this means was different. Has the potential to become the first approved treatment for compensated Mash Saros. A very sick segment of the mash Market. That currently has no therapeutic options.

Demi: Yes, thank you, Dave. Second quarter 2025 net sales totaled $212.8 million, up 55% from the first quarter of 2025. This was another strong demand quarter. As we've said, we expected growth to net to be somewhat choppy early in launch, and the team has done an outstanding job managing it to date. As we shared last quarter, we've begun contracting with payers. We saw minimal additional impact from contracting in the second quarter, with an expectation for that to increase our gross net discount in the back half of the year. That's fully expected and consistent with what we typically see with specialty medicines at this point in their launches. We have good visibility into the gross net dynamic this year and are confident that gross net will remain within our expected range through 2025.

I'll now turn the call over to Marty. Yes, thank you. Dave, second quarter 2025, net sales totaled $212.8 million, up 55% from the first quarter of 2025. This was another strong demand quarter, as we said. We expected growth to be somewhat choppy early in the launch, and the team has done an outstanding job managing it. Today, as we shared last quarter, we've begun contracting with payers. We saw minimal additional impact from contracting in the second quarter, with an expectation for that to increase our gross net discount in the back half of the year. That's fully expected and consistent with what we typically see with specialty medicines at this point in their launches.

Demi: R&D expenses for the second quarter of 2025 were $54.1 million compared to $71.1 million in the second quarter of 2024. The decrease was primarily due to lower clinical trial costs. SG&A expenses for the second quarter of 2025 were $196.9 million compared to $105.4 million in the second quarter of 2024. The increase was primarily due to increases in commercial launch activities for Resdifera. Looking ahead, we expect operating expenses in the third and fourth quarters to be modestly higher than the second quarter. Turning to our balance sheet, we ended the second quarter of 2025 with $802 million in cash, cash equivalents, restricted cash, and marketable securities. As Bill mentioned earlier in July, we also entered into an agreement with Blue Owl Capital for up to $500 million in a senior secured credit facility on favorable terms.

Are expected range through 2025.

R&D expenses for the second quarter of 2025 were $54.1 million compared to $71.1 million in the second quarter of 2024. The decrease was primarily due to lower clinical trial costs.

Significant expenses for the second quarter of 2025.

Were 196.9 million compared to 105.4 million in the second quarter of 2024, the increase was primarily due to increases in commercial launch activities for ra.

Looking ahead, we expect operating expenses in the third and fourth quarters to be modestly higher than in the second quarter.

Turning to our balance sheet, we ended the second quarter of 2025 with $802 million in cash, cash equivalents, restricted cash, and marketable securities.

Demi: This non-dilutive financing consists of a $350 million initial term loan funded at closing, a portion of which was used to repay all outstanding obligations under the Hercules loan facility, and a $150 million delayed draw term available in multiple draws through 2027. We plan to use these funds to pay the upfront payment for the global license of our oral GLP-1. The Blue Owl agreement also provides a mutual option for an additional uncommitted tranche of up to $250 million to support potential additional strategic business development activities. With a strong cash position, we continue to be well-resourced to support the ongoing launch of Resdifera in both the U.S. and our planned launch in Europe in the second half of this year, as well as for business development opportunities to build our pipeline going forward. So with that, let me briefly recap our second quarter progress on slide 19.

As Bill mentioned earlier in July earlier in July, we also entered into an agreement with Blue Owl capital for up to $500 million in in a senior secured credit facility on favorable terms. This non-diluted financing consists of a 350 million initial term loan funded at closing, a portion of which was used to repay all outstanding obligations under the Hercules loan facility and a 150 million delayed draw term available in multiple draws through 2027.

We plan to use these funds to pay the upfront payment for the global license of our oral GLP-1.

the blue agreement also provides a mutual provide the mutual option for an additional uncommitted tranche of up to 250 million dollars to support potential additional strategic Business Development, activity,

With this strong cash position. We continue to be well, resourced to support the ongoing launch of a different in both us and our PL planned launch in Europe. In the second half of this year as well as for business development opportunities, to build our pipeline going forward.

Demi: We continue to drive strong momentum in the fifth quarter of our launch with a medicine that is now annualizing at well over $800 million. We have more than 23,000 patients on therapy and expect to continue to steadily add patients going forward. Physician adoption continues to build. We hit a key launch goal with 80% of our 6,000 top targets now prescribing Resdifera. We are expanding our leadership in F2 to F4C MASH with our new patent confirming Resdifera protection to February 2045, our progress in F4C, our expected expansion into Europe, and our exciting new oral GLP-1 global licensing agreement. Now I will turn the call back to Tina Ventura to open up the Q&A session.

So, with that, let me briefly recap our second quarter of progress on slide 19.

We continue to drive strong momentum in the fifth quarter of our launch with a medicine that's now annualizing at well over 800 million dollars.

We have more than 23,000 patients on therapy and expect to continue to steadily. Add patients going forward.

Physician adoption continues to build. We hit a key launch goal with 80% of our 6,000 top targets. Now, prescribing Risa

and we're expanding our leadership in F2 to f4c. Mash with our new patent, confirming different protection to February, 2045 our progress in f4c, our expected expansion, into Europe, and our exciting new oral glp-1 Global licensing agreement.

Tina Ventura: Thanks, Mardi. Let's move into the Q&A portion of the call. Demi, please go ahead and provide instructions for the Q&A session.

And now, I'll turn the call back to Tina to open up the Q&A session. Thanks, Marty. Let's move into the Q&A portion of the call. Demi, please go ahead and provide instructions for the Q&A session.

Speaker 5: We will now open the lines for questions. To open your line, please press star and you will be added to the queue on the call. Our first question comes from Thomas Smith with Leerink Partners.

We will now open the lines for questions to open your line. Please press star and you will be added to the queue on the call.

Our first question comes from Thomas Smith with Ling Partners.

Speaker 6: Hey, guys. Good morning. Thanks for taking the questions and congrats on the really strong quarter here. I was wondering if you could just expand on the comments regarding gross net and the inventory dynamic in the quarter. I know you guided to there being a little bit of choppiness, but it looks like you may have benefited perhaps from a better net pricing in the quarter versus Q1. If you could just help us kind of frame where you see this going for the rest of the year, and then if you could just comment on inventory stocking in the quarter, that would be really helpful. Thanks so much.

Bill Sibold: Hey, Tom. Thanks very much. Mardi, I am going to turn it over to you to talk about gross net.

Hey guys, good morning. Thanks for taking the questions and, uh, congrats on the really strong quarter here. Um, I was wondering if you could just expand on the comments regarding gross to net and the, uh, inventory dynamics in the quarter. I know you guided to, uh, there being a little bit of choppiness, but it looks like you may have benefited, perhaps, from better net pricing in the quarter versus Q1. If you could just help us, uh, kind of frame where you see this going for the rest of the year. And then, if you could just comment on inventory stocking in the quarter, that would be really helpful. Thanks so much.

Tina Ventura: Yep. Great. Hi, Thomas Smith, and thank you for the question. Let us just start with saying that this was a really strong demand quarter and the team executed so well once again. With respect to gross net that we addressed in the call, we have been very disciplined and will remain disciplined when it comes to gross net. We have been very consistent with our messages quarter to quarter. We said from the start of launch that gross net will be choppy early in the launch, and we are still just five quarters in. That is the case what we have seen here in this quarter. We did say last quarter that we began contracting in April, and we also anticipated that we would have minimal additional impact from contracting this quarter and expect to see more of that impact in the second half of the year.

Thank you, Tom. Thanks very much. Uh, Marty, I'm going to turn it over to you to talk about gross net. Yep, great. Hi. Tom and thank you for the question. Um let's just start with saying that this was a really strong demand quarter and the team executed so well. Uh, once again now with respect to gross net, that we addressed in the call that we've been very disciplined and will remain disciplined. Um, when it comes to gross net and we've been very consistent with our messages, quarter to quarter. We said, from the start of launch that gross, net will be choppy early in the launch and we're still just 5.

Tina Ventura: So we have explained that we are very focused on gross net. We have very good visibility and that we plan to stay within the range that we have discussed previously. That is very typical for specialty pharma launches at this point in their launch.

Bill Sibold: Yeah, thanks, Mardi. Look, Tom, as you heard me say, we've been extremely diligent about gross net from the beginning, and we don't think about it in terms of a quarter to quarter. We've taken a very long-term view looking over multiple years. We know that Resdifera is going to be a big product, and gross net's really important. You want to watch it and work very carefully on it and make sure that you preserve it. So our team's done just an outstanding job on it. We feel really good about where we're at. As Mardi said, we've got a real strong sense of how it will evolve and where we're going.

Plan to stay within the the range that we discussed previously. That's very typical for specialty Pharma launches at this point in their launch.

yeah, thanks Marty, you're looking Tom as you heard me say,

Tina Ventura: Great. Thanks, Tom. Next question, please.

We've been extremely diligent about gross, net from the beginning and we don't think about it in terms of, you know, a quarter to quarter, we've taken a very long-term view looking over multiple years. You know, we know that there's different is going to be a big product and gross and that's really important. So you want to watch it. Uh, and uh, work, uh, very carefully on it and make sure that, you know, you uh preserve it. So our team's done an assistant outstanding job on it. And so we feel really good about where we're at. And as Marty said, we've got a, a, a real strong sense of of how it will evolve and where we're going.

Great. Thanks. Tom next question, please.

Speaker 5: Question comes from Yasmeen Rahimi with Piper Sandler.

Question comes from yes. Me rahimi with Piper Sandler.

Speaker 7: Good morning, team. Congrats to an outstanding quarter. Team, one of the questions that I think seems to be investors asking us with the entrance of GLP-1 to the market, let's say you maintain your pricing strategy and don't aggressively rebate to the level of matching semaglutide. How do you foresee sort of maintaining the strong growth curve that you have shown so far? I think it's very clear that hepatologists are going to prefer liver-directed therapies, but if there is a sort of a prior authorization of GLP-1, if edits needed due to pricing differences, how do you foresee how soon that could play sort of flatten out and not become as important? If you could just talk about that dynamic, we get that question quite a bit, and I'm sure so do you.

Um, good morning team. Congrats on outstanding quarter. I guess team, um, 1 of the questions that I think seems to be investors asking us with the entrance of glp1, to the market. Let's say, you maintain your pricing strategy, and don't aggressively rebate to the level of matching semaglutide. How do you foresee sort of maintaining the strong growth curve that you have shown so far? Um, uh, and and, and, and

and I think it's very clear that hepatologists are going to

Bill Sibold: Okay, there is a lot of questions and nuance in there. Let me just kind of roll through a little bit of, provide a little bit of context here. As we said, we are coming off an outstanding second quarter, which was driven by strong demand. That is number one. We have been steadily adding patients since launch, and that does not change. We expect this trend will continue through the semaglutide launch in the second half of the year. In addition to the strong demand, in Q2, we also benefited a bit from the Q1 effect. We would expect our quarter-over-quarter growth rates to continue to track right in line with other successful specialty launches with similar dynamics. You heard Mardi Dier talk about gross net that is being choppy quarter to quarter.

prefer liver directed therapies. But if there is a sort of a prior authorization of the glp1 Step At Its needed due to pricing differences, how do you foresee how soon that could play sort of flat? Now to not become as important. So, if you could just talk about that Dynamic, we get that question quite a bit and I'm sure. So, do you

okay. Yeah, there's a lot of, there's a lot of questions and Nuance in there. So let me just kind of roll through uh a little bit of provide a little bit of context here. I mean as we said we're coming off an outstanding second quarter which was driven by strong demand so number and we've been steadily adding patients since launch and that doesn't change. We expect this trend will continue through the SEMA launch in the second half of the year.

Now, in addition to the strong demand, you know, with our, uh, in Q2, we also benefited from the Q1 effect.

So we would expect our quarter over quarter growth rates to continue to track right in line with other successful, specially launches with similar Dynamics.

Bill Sibold: We have good visibility and expect for that gross net discount to step up in 2025, but stay within the specialty product range that we have discussed. Everything I have said there is in the context of expecting a semaglutide approval and launch. You asked a very specific question about step edits and so forth. Look, right now it is just a little too early to tell. Product has not approved yet. We do not know what the label looks like, and those are going to be taken into consideration in the discussions that we have with payers. We have been actively talking with payers. We think that we have established a good partnership and planning with payers, but we are waiting to see ultimately what happens with the label and approval of semaglutide. Either way, we plan for all scenarios.

And you heard Marty talk about gross in net, that is being choppy quarter to quarter. We have good visibility and expect for that growth. To net, discount to step up in, uh, 2025 but stay within the specialty product range, that we've discussed. So, everything I've said there is in the context of, uh, expecting a SEMA approval, and

now, uh, you asked a very specific question about, uh, step edits and so forth, you know, look right now it's just a little too early to tell

The product hasn't been approved yet. We don't know what the label looks like, and those are going to be taken into consideration in the discussions that we have with payers. We've been actively talking with payers, and we think that we've established a good partnership and planning with payers. But we're waiting to see ultimately what happens with the label and approval of some of the glue type.

Bill Sibold: A step edit here in this space, though, is somewhat complicated, and I think that that is going to be one of the things to take into consideration because these patients have other comorbid conditions such as type 2 diabetes or cardiovascular disease. So, think about it. If a patient is well controlled on a different GLP-1, would a payer disrupt their current therapy to put them on semaglutide for MASH? There is a lot of nuance and complications here. We do not have all the data yet, but we have planned for all eventualities, and it does not change our excitement for the opportunity that exists.

Either way, we plan for all scenarios, and a step edit here in this space, though, is somewhat complicated. I think that’s going to be one of the things to take into consideration because these patients have other comorbid conditions such as type 2 diabetes or cardiovascular disease. So, you know, think about it: if a patient's well controlled on a different GLP-1, would it appear disruptive to their current therapy to put them on semaglutide?

Tina Ventura: Bill, I would just add one more thing. Remember, GLP-1s have been on the market for a long time. Our data has been pretty consistent in what we've seen to date that of the patients that we've treated, about 50% are either on or have exposure to GLP-1s already, and probably 25% are on at any given time. There's a lot of familiarity in the market already, and clearly combination use is already established.

So, you know, there's a lot of nuance and complications here. We don't have all the data yet, but we have planned for all eventualities and, you know, it doesn't change our excitement for the opportunity that exists. Yeah. Bill and yes, I would just add 1. More thing is, remember, glp ones have been on the market for a long time. And our data has been pretty consistent what we've seen today that of the patients that we've treated about 50% or either on

Bill Sibold: Yeah, it's a really great point, Mardi, because this isn't as though it's a new product that's entering the market that's never been used. I mean, this has been used everywhere. There's nobody who hasn't heard of it or has the ability to get it for some indication now. This is just an extension. So, that's a very different setup than if you have a brand new mechanism of action entering a market which has more potential to disrupt.

Tina Ventura: Great, thanks, yeah. Thank you. Thank you very much. Next question.

Now, this is just an extension. So, you know, that's a very different setup than if you have a brand new mechanism of action entering a market which has more potential to disrupt.

Great, thanks. Yeah, thank you. Thank you. Thank you. Next question.

Speaker 5: Next question comes from John Wolloben with Citizens.

Next question comes from John wibben with citizens.

Speaker 6: Hi, this is Catherine on for John. I just have a quick question about your new GLP, oral GLP-1, and just how many did you look at, and how did you go about picking it? I know you kind of said that the orphaglipron backbone was kind of a deciding factor, but just to provide a little bit of color on that.

Hi. Um, this is Katherine on for John. I just have a quick question about, um, your new jlp world glp1 and um, just how many did you look at kind of and how did you go about picking? I know you kind of said that the orphan backbone was was kind of uh side and Factor but just to provide a little bit of color on.

Bill Sibold: Yeah, look, thanks for the question. As we have said for a long time, business development is a part of our strategy, and we are looking to add the right assets to our pipeline to extend our leadership in MASH. Oral GLP-1s are something that we have been interested in for a long time. Like with any business development process, you look at a lot of different things before you find the one that is just right. That is what we did. We laid out what we were looking for. We were looking for an orphaglipron derivative. We wanted favorable stability and a CK profile that is amenable to combo. We found that in this asset. So, it was a very systematic approach.

Yeah look uh, thanks for the question, you know?

As we've said, uh, for a long time uh, you know, BD is a part of our uh, strategy and we're looking to add the right assets to our pipeline uh, to extend our leadership in Mash, uh, oral GLT ones or something that we've been interested, uh, for a long time, um, you know, like with any BD, uh, process, you look at a lot of different things before you find the 1, that's just right? And, you know, that's what we did. We laid out, what we were looking for, we were looking for an orphan lip Ron derivative, uh, we wanted favorable stability and a CK profile. That's amenable to combo. Uh, and you know, we found that, uh, in this asset. So, you know, it was

Bill Sibold: Yeah, we looked at a lot of things before deciding and coming upon the one that we think is just right to create that product, which we think is going to be a nice advancement in MASH. Now, just the one thing I will say, there are a lot of oral GLP-1s out there. There are a lot of GLP-1s, triple Gs, et cetera, but there is only one that is going to be combined with Resdifera in this form. That is how we differentiate in this market. That is something which is special to Madrigal Pharmaceuticals, and that is something that we see a huge opportunity for.

A very systematic approach. Yeah, we looked at a lot of things before deciding, and coming upon the 1 that we think, is just right to create that product, which we think is going to be a nice advancement in that is now just the 1 thing, I'll say there are a lot of oral glp. Ones out there. There are a lot of glp 1's. Triple G's Etc but there's only 1.

That's going to be combined with different in this form and that's how we differentiate in this market that's something which is special to uh managable. And that's something that we see a huge opportunity for

Tina Ventura: Great. All right. Thank you. Thanks. Next question, please.

Right.

All right. Thank you, thanks. Um, next question, please.

Speaker 5: Next question comes from Eliana Merle with UBS.

next question, comes from Eliana, mu with UBS

Speaker 7: Hey, guys. Congrats on the quarter and thanks for taking the question. In terms of next year, how are you thinking about sequential quarterly growth once Resdifera is available? Specifically on gross net, can you give us a little bit more color on how you are thinking about how that could trend next year? Lastly, feel free to just not answer this question, but what is your latest thinking around when you might be in a position to issue revenue guidance? Thanks.

Speaker 6: Do you want to take the revenue guidance or anything?

Hey guys. Congrats on the quarter and thanks for taking the question. Um, in terms of next year, how are you thinking about sequential quarterly growth? Once Sam is available and specifically on growth tonight. Um, can you give us a little bit more color on how you're thinking about how that could Trend next year? Um, and lastly and feel free to just not answer this question but what's your latest thinking around when you might be in a position to issue Revenue guidance. Thanks

Tina Ventura: Thanks, Ellie. Thanks for the question. Revenue guidance is easy. We haven't discussed that publicly, and we have no plans in the near term to give guidance. In terms of growth, you are asking about 2026 already, but we are in Q2 of 2025. We are focused on the rest of the year of 2025. We have discussed on the call, and we will say it again now, that we believe that we will be steadily adding patients through the rest of the year and continue our growth trend. As you know, we follow a basket of analogs of specialty medicines that have launched successfully over the last 10 years, and we are tracking right along that growth rate of those top analogs in this basket. We feel very good about the growth in the rest of the year.

Tina Ventura: Gross net, I think we made those comments in 2025, and we feel good and have good predictability. As the year goes on, then we will start focusing on 2026 and discussing that more. Great. Thanks, Ellie. Next question, please.

Do you want to take the revenue guidance or anything? Any, any part of it? Yeah, thanks Ellie. Thanks for the question. Um, so, Ron guidance is easy. We we haven't just, uh, uh, discussed that publicly and we have no plans in the near term to, uh, give guidance. Um, in terms of growth, you know, you're asking about 2026 already. But we're in Q2 of 2025. So, we're focused on the rest of the year of 2025, and we've discussed on the call and we'll say it again. Now that we believe that we'll be steadily adding patients through the the rest of the year. Um, and and, you know, continue our growth Trend and, you know, as you know, we follow uh, a basket of analogs of specialty medicines that have launched successfully over the last 10 years and we are tracking right along that growth rate of those top analogs um, in in this basket. So we feel very good about the growth in the rest of the year and then grow tonight. I think we made those comments in 2025. Um, and

We feel good and have good predictability. And as the year goes on, then we'll start focusing on 2026 And discussing that more.

Great. Thanks. Ellie next question, please.

Speaker 5: Next question comes from Andrea Newkirk with Goldman Sachs.

Speaker 7: Good morning. Thanks for taking the question and congratulations on the quarter. Bill, just as you think to a potential EU approval next month, just curious how you're thinking about the shape of a potential launch curve there versus what you've seen in the U.S., and when might you expect to recognize first revenue?

Next question comes from Andrea. Newberg with Goldman Sachs.

Good morning. Thanks for taking the question and congratulations on the quarter. Um, bill, just a few things to a potential EU approval next month. Um, just curious how you're thinking about the shape of a potential launch curve there. Um, versus what you've seen in the US and when might you expect to recognize first Revenue?

Bill Sibold: Thanks, Andrea. Look, I think, you know, we've got a very good view on what curves can look like having just gone through the U.S. launch. You know, it all starts with how do you wire the system? How do you prepare? How do you educate? How do you create pathways for patients there? The benefit in Europe is they've had more time to prepare for this launch than the U.S. did. Because remember, in the U.S., since we were the first product ever approved in MASH, the community had been met with disappointment over 20 times. There's the guidelines in Europe that exist already. With the U.S. getting approved, Europe's had a little bit longer to prepare. But like any other launch, and especially when it's a first-in-disease, it takes time. We have some really good first-hand experience with that in the U.S.

Thanks Andrea. Uh, look, I think, you know, we've got a

Very good view on what curves can look like, having just gone through the uh, us launch. You know, it all starts with

Bill Sibold: We're taking essentially all the learnings from the U.S. and transferring them to the really outstanding team that we've hired in Europe and specifically Germany. I just want to put a fine point on that. It's Germany that we're launching in first. We're not going everywhere all at once. We put extremely rigid guidelines in place for what we need to see in a market for it to launch. So, you know, more to come. When will we start recognizing revenue? I would say it's really not much of a, there's not much happening in 2025. We're going to be starting in the second half of the year in order to get the teams deployed, etc. It takes a little time. So really, it's more of a 2026 and on story.

The, uh, there's the uh, e the guidelines in Europe that exists already and with the US getting approved. Europe's had a little bit longer to prepare but like any other launch and especially when it's a first in disease, it takes time and you know, we have some really good firsthand experience with that in the us. And we're taking essentially all the learnings from the US and transferring them to the really outstanding team that we've hired uh in uh Europe and specifically Germany and and and I just want to, you know, put a fine point on that.

Tina Ventura: Great. Thanks, Andrea Newkirk. Next question, please.

It's Germany that we're launching in first, we're not going everywhere. All at once we put extremely, rigid guidelines in place for what we need to see in a market for it to launch. So, you know, more to come. Uh, when will we start recognizing Revenue? Look, I would say it's it's really not much of a, there's not much happening in 25. We're going to be starting in the second half of the year, uh, in order to get the, the teams deployed, uh, Etc. It takes a little time. So, uh, really, it's more of a, a 26 and on story.

Great thanks. Andrea. Next question, please.

Speaker 5: Next question comes from Andy Chen with Wolfe Research.

Next question comes from Andy Chen, with Wolfe research.

Speaker 6: Hey, thank you for taking the question. Mardi, you talked about this basket of specialty drugs. Can you give some numbers around what this gross net range is in that basket that you are analyzing? This 20% to 30% that the gross net that you are guiding to, is that an educated guess and prediction, or is that already a largely known fact given your existing contracting negotiations that you know that it is going to end up in the 20% to 30% range? Thank you.

Bill Sibold: Hey, Andy, thanks for that. I will turn it over to Mardi in a second. Just to be clear on that, we are very, very clear on the 20% to 30%. That is based on decades of experience and knowledge and how our conversations have gone with the payer community. You know, like everything else that we talked about in this launch, we have been very accurate in our comments that we make to all of you. So maybe I will turn it over to Mardi for any other comment that you have, Mardi. But you know, look, we do not say things just to say things. We say things because we are confident in them.

Hey, uh, thank you for taking the question. Uh, Marty, you talk. You talked about this basket of, uh, specialty uh, drugs. Can you give some numbers around with this gross to net? Range is like in that basket that you're analyzing. Um and then this 20 to 30% that uh that the gross to net that you're uh that you're guiding to is that an educated guess or and prediction or is that already a largely known fact given your existing Contracting negotiation should negotiations and you know that it's going to end up in the 20 30% range. Um thank you.

Hey Andy, thanks for that. Um, I'll turn it over to Marty in a second, just just to be clear on that.

Yeah.

We are very, very clear on the 20 to 30%.

Uh, that is based on, you know, decades of experience and knowledge and.

how our conversations have gone with the payer community.

Tina Ventura: Right. Just to reiterate that, Andy, we have good visibility for the rest of the year. We have talked about this range since, I think, our first launch quarter. We feel very strong that we are tracking along with typical specialty medicines and that the gross net for 2025 falls within that range. There are a lot of components to gross net, many components of which contracting is just one. We did say we started contracting in April and that you would see more of that in the second half. That is just sort of the natural dynamics in this marketplace, launching in the U.S., all very predictable for 2025 as we move forward. So we feel good about that.

So you know, like everything else that we talked about in this launch, you know, we've been very accurate in our uh comments that we make uh to all of you. So um, maybe I'll I'll turn it over to Marty for any other comment that you have Marty but, you know, look, we, you know, we don't say things, just to say things, we say things, because we're confident in them, right? Yeah. Yeah. Just to reiterate that Andy, we have good visibility for the rest of the year. We've talked about this range since I think that our first launch quarter and

Tina Ventura: Just to reiterate a point that Eliana Merle asked too, we have not commented on 2026, but we see this drug, its continued growth and robust growth as we move forward and as we steadily add patients. Good. Thanks, Andy. Next question, please.

And uh, you know, we feel very strong that we're tracking along with typical specialty medicines and that the gross net for 2025 Falls within that range. And, you know, there's a lot of components to gross net. Many components of which Contracting is just 1. Uh, and we did say, we started Contracting in April and that you'd see more of that in the second half that just sort of a natural, uh, Dynamics in this Marketplace. You know, in launching in the US, all very predictable for 2025, as we move forward. So we feel good about that and, and just to reiterate a point but alas, too, you know, we, we haven't commented on 2026, but you know, we see this drug as continued growth and robust growth as we move forward, and as we steadily, add patients

Good. Thanks. Andy next question, please.

Speaker 5: Next question comes from Ritu Baral with TD Cowen.

Next question comes from Reed to barrel with TD Cowen.

Speaker 7: Hi, guys. Thanks for taking the question. I wanted to ask about some of your underlying plans, Bill Sibold, as far as continuing this growth momentum into the potential Resdifera label expansion. You hit your target of 80% prescribers in that top tier. What is the next target and how does that overlap with your understanding of Novo's potential detailing target for that label expansion? As part of that answer, could you address the sort of growing awareness of NASH in the diabetic population and amongst endocrinologists? Are they part of that next tier? Thanks.

Hi guys, thanks for taking the question. Um, I wanted to ask about some of your underlying plans um bill as far as continuing this growth momentum. Um into the potential wigga. Be label expansion. You you hit your target of 80%? Um uh prescribers. Um in that top tier, what's the next Target? And how does that overlap with your understanding of novo's potential? Detailing Target for that label expansion and as part of that answer, could you?

Address the sort of growing awareness of math in the diabetic population, and amongst endocrinologists. Are they part of that next tier? Thanks.

Bill Sibold: Thanks, Ritu. Look, we do not have a next target that we are going to talk about. Really, what happens now is it is a focus on depth. We have the breadth of prescribing that we are seeing is, as we said, it is leading the other products that we are looking at, the analogs. So we have done just an outstanding job there. So it really becomes a depth story now, and we are seeing all the signs that we are tracking right with those analogs as well. So that is the next, the first leading indicator is really the breadth. Now you go to depth, and we are seeing more of that. And why do people use more? Because they see the results. The real-world experience that we are seeing is actually very impressive.

Thanks for you. Um, look, we don't have a next Target that we're going to talk about. Um, really, what happens now is it's a focus on depth. I mean, we have the breadth of prescribing that we're seeing is uh,

as, as we said it, it's leading the, um,

Bill Sibold: We have physicians, every physician I speak with talks about just what they are seeing in the real world is impressive and exceeding expectations. So you talked about kind of where do we go from here from an endocrinology perspective? Yep, endocrinology, there is some, it is not all of endocrinology, but some endocrinologists are very excited about Resdifera, and we have started spending a little bit more time with those physicians and will continue to do so. As I said, the key focus is hepatologists and gastroenterologists, and we also talked about endocrinologists, but we will continue to pursue additional endocrinologists that have an interest. You know, endocrinologists are super interested in mechanism of action.

Those analogs as well. So that's the next. Uh, the first leading indicator is really the breadth. Now, you go to depth and we're seeing more of that. And why do people use more? Because they see the results, The Real World experience that we're seeing, uh, is actually, uh, very impressive. We have positions every position I speak with talks about, just how what they're seeing in the real world.

Is impressive and exceeding expectations.

Bill Sibold: And this being a THR beta, their eyes light up saying, look, this is in our alley to be talking about something with a cool mechanism like this, albeit very specific to the liver in our case. And so yeah, we have those targets that will increase as well. Anything else, Ritu, with that, or does that answer it for you?

So, uh, you talked about kind of, Where Do We Go From Here? Uh, from an Endocrinology perspective. Yep. Endocrinology. There's some, it's not all a Endocrinology, but some endocrinologists are very excited about red, Dara. And we've started spending a little bit more time with those Physicians and we'll continue to do so. Uh, as I said, the key focus is hepatologists and gastroenterologists and we also talked about endocrinologists but we'll continue to pursue additional endocrinologists. That have an interest. You know, interesting endocrinologists are super interested in mechanism of action and this being a th are beta their eyes light up saying look this is in our Ally to be talking about something with a cool mechanism like this albeit very specific to the liver in our case

Speaker 7: That covers it. Thank you so much.

And uh, so yeah, we have some, we have those targets that will uh, increase uh, as well. Um, anything else we do with that? Or is that does that answer it for you?

Bill Sibold: Great. Okay, thanks.

Tina Ventura: Thanks, Ritu. Next question, please.

That covers it. Thank you so much. Great, okay, thanks, thanks for you too. Next question, please.

Speaker 5: Next question comes from Akash Tewari with Jefferies.

Next question comes from Akash tewari with Jeffries.

Speaker 7: Hi, this is Cathy on for Akash. To follow on the gross net question from before, I know you said you will see more of the contracting happen in the second half of the year, but based on our math, it looks like the gross net for this quarter roughly returned to Q4 levels. We also anticipated a potentially higher Part D impact from this quarter versus last quarter. So what are the biggest drivers behind this price improvement for the quarter? Can you give us some color on the Part D redesign impact this quarter, as well as the stocking contribution and the driving factors behind that increase? Thank you.

Hi. This is Kathy on for a cause to follow on the growth to net question from before, I know you said you'll see more of the Contracting happen in um the second half of the year. But based on our math, it looks like the gross to net. For this quarter, roughly returned to Q4 levels. And then we also anticipated a potentially higher Part. D impact from this quarter versus last quarter. So what are the biggest drivers behind this price Improvement for the quarter? And can you give us some color on the part? D, redesign impact Discord as well as the stocking contribution in the driving. Factors behind that increase. Thank you.

Bill Sibold: Thanks for the question. There was a couple thrown in at the end there. I am not sure we can get to, but Mardi, what on the comments?

Tina Ventura: Let's start on the easy one on stocking, which was not part of gross net, as you know, but let's reiterate what we said in the script as well. It was a strong demand quarter. Inventory is not, we do not need to discuss that anymore, strong demand quarter. With respect to gross net, a lot of focus here. Let's reiterate. The range that has been brought up on this call already for typical specialty medicines at this point in the launch for this year is 20% to 30%. What we said is that contracting, which is one component of many components in gross net, will see a bigger start in April, normal part of our business, and will continue to widen that through the end of the year. That is all predictable in that 20% to 30% range and expected.

Thank you. Thanks, for the question. There was a lot a couple thrown in at the end there. I'm not sure we can get to, but Marty went. Yeah. Well, let's start on the easy 1 on Stocking, which was not part of gross net, as you know. But, uh, let's reiterate what we said in the script as well. It was a strong demand quarter. Um, and so inventory is, is not in. Not, uh, you know, we don't need to discuss that anymore. Strong demand quarter, uh, with, with respect to gross net. A lot of focus here. Uh, let's reiterate, uh, so, uh, again the range

That has been brought up on this. Call already for a typical specialty medicine at this point in the launch for this year is 20 to 30%. What we've said is that Contracting which is 1 component of uh many components in Gross to net. Will see a bigger started in April, normal normal part of our business and we'll continue to uh, widen

Tina Ventura: In Part D, I thought we kind of put this to bed, but the Part D impact was, we discussed this on the Q4, and I believe the Q1 call was just incremental to what we saw in the Q4. That is because we had rebates in the Q4 given the timing of our launch. The new IRA Part D impact was pretty minimal going into 2025, given the base from which we started in the Q4 of 2024. All in all, gross net again, falls within the range and will continue to do so through the rest of 2025.

Bill Sibold: Yeah, and look, I mean, we were clear on our first approval call that we would have choppy gross net for a period of time. That is just what happens in a launch. Just to reiterate again, there are a number of components of gross net, including copay assistance. We have a $0 copay assistance program as well, which is getting greater and greater utilization. It is really important. We want patients on copay assistance because that just makes it more affordable, which leads to better persistency, leads to better outcomes for patients. Next question.

That through the end of the year. So that's all predictable in that 20 to 30% range and expected in part the, um, I thought we kind of put this to bed, but the part the impact was was, uh, we discussed this on the fourth quarter and I believe, the first quarter call was just incremental to what we saw in the fourth quarter. And that's because we had rebates in the fourth quarter, given the timing of our launch. So the new Ira Part D impact was pretty minimal going into 2025, um, given the base from which we started in the fourth quarter of 2024. Um, all in all, um, you know, so gross to net again calls within the range and we'll continue to do so through the rest of 2025. Yeah. And look, I mean, we were clear on our first approval call that we would have choppy growth to net for a period of time. That's just what happens in a launch. And, you know, just to reiterate again, there are a number of components of gross net including co-pay assistance. I mean, we have a we have

Tina Ventura: Good. Thanks. Next question, please.

A 0 copay assistance program as well. Um, which is getting, uh, you know, greater and greater utilization. It's really important. We want patients on co-pay assistance because that just makes it more affordable, which leads to better persistency leads to better outcomes for patients. Next question. Good, thanks. Next question, please.

Speaker 5: Next question comes from Ayank Mamtani with B. Riley Securities.

Next question, comes from my aunt Montana with dyd securities.

Speaker 6: Yes, good morning, team. Thanks for taking your questions and congrats on a very strong quarter. Could you give us a little more detail on the claims of this newly issued patent with 2045 XPERI? I guess it is related to the method of treating NASH, where those findings work in humans was a non-obvious finding. Also, was curious if there is a plan to further build on this with the F4C outcomes data emerging. Then, I have a quick follow-up.

Bill Sibold: Sorry, what was the F4C question? I missed that.

And also was curious, if there's planned to further build on this, with the f4c outcomes data emerging, and then I have a quick follow-up.

Speaker 6: Yeah, if there's additional patent work you may do as the F4C and the outcomes data still kind of emerging there.

Sorry, what was the F4C question? I missed that.

Bill Sibold: Yeah, great. That is something, look, we do not have as a trial outcome yet. We do not have approval yet. Certainly, there will be, we will look for opportunities with the F4C indication, we hope, in the future. But look, I think the patent you saw this morning or it is available now. As we have said, it is based on clear and compelling evidence that different Resdifera doses given to two different cohorts of patients, each comprising different body weights, optimizes the efficacy and safety of Resdifera. That is, you know, that is the headline for it. We think this is a very strong patent. This is something that has become our base case now. As we think about all of our planning in the company and how we are thinking about our plans for everything from BD to just investment, etc., 2045 is our base case.

Yeah, it's there's additional pattern, uh, work. You may do as the f4c and the outcomes data, uh, you know, still kind of emerging there. Yeah, great, that's something. Look, you know, we don't have, uh, as a trial outcome, yet we don't have approval yet. Uh, certainly, uh, there will be, uh, uh, we'll look for opportunities with the, uh, f4c indication, we hope in the future.

Bill Sibold: Look, I think I am going to let you all spend a little bit more time reading it and so forth, but we think all the facts are very clear. We think that there is good precedent as well in case law, and you know, we are really excited about this. This is a really, really, really important development for us as a company.

Um, but look, you know, I think the the, the, the the the patent you saw this morning or you are, it's it's available now. Um, and as we said, it's based on clear and compelling evidence, uh, that uh, different res different doses, given to 2 different cohorts of patients, each comprising, different body weights, optimizes the efficacy of safety of, uh, efficacy and safety of different. So that's, you know, that's the, the, the, the headline for it. We think this is a very strong patent. Um, this is something that is become our, uh, base case. Now, as we think about all of our planning in the company and how we're thinking about uh our plans for everything from BD to just investment, Etc. 2045 is our base case. So look, I think I'm going to let the let you all spend a little bit more time uh reading it and so forth. But we think all the facts are

Tina Ventura: Great. Thanks, Ayank. Next question, please, Demi.

Are very clear. We think that there's good precedent as well uh in uh uh case law and uh you know we're really excited about this. This is an really, really really important uh, development for us as a company.

Speaker 5: Next question comes from Jay Olson with Oppenheimer.

Great. Thanks Maya. Next question, please demie.

Next question comes from G alson with open Heimer.

Speaker 6: Oh, hey, congrats on the quarter and all the impressive progress, especially with life cycle planning. In your due diligence process, can you talk about any preclinical or clinical work done to support a fixed dose combination of SYH2086 with Resdifera? Now that you have an oral GLP-1, what other mechanisms are you considering and how are you thinking about future business development deals in terms of timing and priority? Thank you.

Oh, hey, congrats on the quarter and all the impressive progress, especially with life cycle planning.

Bill Sibold: Great, thanks, Jay. Maybe I will start with just the last bit, then I will turn it over to Dave. Look, BD is still very much a part of our strategy. We think this is a great first step, but we will continue to look at next best mechanisms of action that are going to add potential value to MASH patients, either as a standalone or in combination with Resdifera. We really believe that the market is going to move towards combination therapy and that Resdifera is going to be the foundational therapy. It already is. It is the standard of care today. What you see in a lot of different diseases is that you add to that standard of care, whether it be for a different effect you are looking for, a subpopulation, etc.

In your due diligence process. Can you talk about any preclinical or clinical work done to support a fixed dose combination of syh 2086 with res Dara. And now that you have an oral glp1, what other mechanisms are you considering? And how are you thinking about future? Business Development deals in terms of timing and priority? Thank you, great. Thanks. Jay. Maybe I'll start with just the, uh, the, the last bit and then I'll, uh, turn it over to Dave. Look, biddies of still very much a part of our strategy. Now, we think this is a great first step, uh, but we will continue to look at next best mechanisms of action that are going to add potential value to, uh, Mash patients either as a standalone or in combination with res different. Now, you know, we really believe that the market is going to move towards combination therapy and the rest difference.

Bill Sibold: Remember, we are at the absolute very beginning, 7% penetrated into this 315,000 population with decades, I would say, of growth in this marketplace ahead of us. It is going to support multiple mechanisms of action, multiple products, and as the leader with the foundational product, looking for those next white spaces or areas of opportunity is something that we are going to be a part of, and more than that, we are going to drive. So Dave, maybe do you want to talk a little bit about this asset? Yeah, sure. I think first of all, let us touch on two things. First of all, the scientific rationale for combining a GLP-1 with resmetirome. Second, we can talk about this molecule in particular. We already know, based on our experience in MAESTRO-NAFLD trial, that as little as 5% weight loss will enhance the efficacy of resmetirome in NASH.

The foundational therapy. It already is it's the standard of care today. And what you see in a lot of different diseases is that you add to that standard of care, whether it be for a different effect, you're looking for a subpopulation, etc. Remember, we are at the absolute, very beginning 7% penetrated into this 315,000 population with decades. I would say of growth in this Marketplace ahead of us. It's going to support multiple mechanisms of action multiple products. And as the leader with the foundational products, looking for those next white spaces, or areas of opportunity is something that we are going to be a part of and more than that, we are going to drive. So, uh, Dave, maybe, do you want to talk a little bit about, um, this asset? Yeah sure. Um, so I think, first of all, let's let's touch on 2 things. First of all, the scientific rationale, for combining a glp 1, with first meter on. And then second, we can talk about this molecule in particular.

Bill Sibold: So we see better biopsy results in patients who achieve as little as 5% weight loss. As we talked about, we can achieve that more effectively and in more patients, that level of weight loss by adding a GLP-1 mechanism drug to Resdifera. So the scientific rationale, I think, is very, very strong for combining the mechanisms. Second, with respect to this molecule in particular, Bill touched on some of the properties that we were looking for. We were looking for chemical properties like the structure. We wanted to make sure that it came with a de-risked structure like an orphaglipron backbone. We wanted to make sure that the pharmacokinetics and sort of initial pharmacology were consistent with what we were seeing with other molecules in this class. That gave us that assessment.

So, you know, we already know um, you know based on our experience in Maestro Nash that as little as 5% weight loss will enhance the efficacy of rest meter on in Nash. So we see better biopsy results in patients who achieve um as little as 5% weight loss.

so um as as we talked about um we can achieve uh that more effectively and in more patients that level of weight loss with by adding a glp-1 mechanism drug uh to wrest it from

Bill Sibold: I think it is important to mention that this is still a preclinical asset and there is still work to be done before we get into the clinic. From what we have seen, we are very excited about combining 2086 with Resdifera. Maybe just one final point on that, Jay. Fixed dose combo would be great, but it is not completely necessary. I think you have to go back to when you have got the runway that we have got at 2045. We have the time to do things in a very thoughtful, precise way. Ideally, it is a fixed dose combo, but it does not have to be. It would just be more convenient for patients. We like the properties that would make that a good probability.

from a

would be great, but it's not completely necessary.

right, and again, I think this, you have to go back to

When you've got the runway that we've got to 2045,

Right, we have the time to do things in a very thoughtful. Precise way.

Ideally, it's a fixed dose combo but doesn't have to be. It would just be more convenient for patients, but we like the properties that would make that uh uh a good probability.

Tina Ventura: Great. Thanks so much, Jay. Demi, it looks like we have time for one more question, please.

Great. Thanks so much. J and Demi. It looks like we have time for 1 more question, please.

Speaker 5: Next question comes from Cavalier Pullman with Clearstreet.

Next question comes from Cavalry palmen with clear Street.

Speaker 6: Hi, good morning. Congrats on the progress and thanks for taking my question. I just want to kind of understand a little bit about the competitive landscape, and your rationale for choosing GLP-1 over there are a lot of dual and triple agonists going on and how you are thinking about whether, with increase in weight loss, if you can see more benefit to MASH patients and you expect any kind of off-label use there as this space grows, as well as, with the combination specifically for the oral drug you have. Any concerns related to kind of overlapping toxicities and based on that, how you are thinking about developing it, whether you plan to, when you like test different doses and scheduling of both drugs or GLP-1 will be adjusted according to the approved regimen for Resdifera?

Hi, uh, good morning. Congrats on the progress and thanks for taking my question. I just want to kind of understand a little bit about the competitive landscape, you know, and your rationale, for choosing glp1 over, there are a lot of dual and triple Agonist uh going on and how you are thinking about whether you know, in with increased

Reason weight loss. If you can see more benefit to mash patients and you expect any kind of off label use their as this space grows, as well as you know, with the combination specifically for the oral drug, you have

Any concerns related to kind of overlapping toxicities? Based on that, how are you thinking about developing it? Will you plan to test different doses and scheduling of both drugs, or will GLP-1 be adjusted according to the approved regimen for Reservoir?

Bill Sibold: Great. Thank you. I appreciate the question. There is a lot there. Let me just take a couple of things really quickly. First of all, we like oral GLP-1 for the reasons Dave mentioned and that we mentioned in the call. With as little as a 5% weight loss in combination with Resdifera, we see a better effect on fibrosis from Resdifera. That makes it better. Now, you are talking about a whole group of products, triple Gs, etc., where their fundamental approach is the battle of who can show the greatest weight loss. There are comparisons of a percent, 2% in the teens and beyond, and that becomes a competitive set. That is not the game we are playing.

Great. Well, thank you. There's uh, appreciate the questions. Uh, there there's a lot there. Let me just take a, a couple things really quickly. First of all, we like, uh, oral glp1 for the reasons, Dave mentioned, and that we mentioned in the call.

With as little as a 5%.

Weight loss.

In association with red DARA, we see a better effect on fibrosis from res diffe, so that makes it better now.

you're, you're, you're talking about a whole group of products, triple G's Etc, where they're fundamental approach is, you know, the Battle of who can show the greatest weight loss and, you know, uh, there's uh, comparisons of a percent 2% in the teams and Beyond and you know, that becomes a competitive set

Bill Sibold: We need an oral GLP-1 that gets us past that 5%, but it is well tolerated. It is something that people can stay on so that the overall profile of the new product with Resdifera remains what it is, which is really as good as it gets in a profile of a drug. It is a holy grail profile. Once-a-day pill, something we have been looking for my whole career are products like this. We have a very different approach on how we are thinking about this. The primary objective is not for massive weight loss. The primary objective is to get to this threshold weight loss that makes Resdifera perhaps an even better drug. That is a different frame, and I think people have got to get their head around that because that is how we very thoughtfully approach this.

That's not the game. We're playing.

we need an oral glp-1 that gets us past that 5% but it's, well, tolerated, it's something that people can stay on, so that the overall profile of the new product with red, Dara remains what it is, which is

really As Good As It Gets in a profile of a drug. It's a Holy Grail profile. Once a day pills something we've been looking for my whole career, our products like this. So we have a very different approach on how we're thinking about this. The primary objective isn't for massive weight loss,

Bill Sibold: As it relates to what is the impact on the product profile? As I said, we are trying to make it a well-tolerated profile and not give up anything on it. That is how we hope to satisfy that with dosing, etc., but it is premature to talk about our development plan. We are going to come back at a later time. As I said as well, BD remains part of our strategy, and it is something that we will be continuing to be very thoughtful about how we might extend our leadership in MASH. Dave.

The primary objective is to get to this threshold weight loss. That makes res differ, perhaps an even better drug. So that's a different frame and I think people got to get their head around that, uh, because you know, that's how we very thoughtfully approach. This, um, as it relates to, you know, what's the impact on the on the product profile? As I said, we're trying to make it a well tolerated, uh, profile and not give up anything on it. And that's how we hope to satisfy that with dosing Etc. But it's premature to talk about our development plan. We're going to come back at a at a later time. And as I said as well, you know, uh BD uh, remains part of our strategy and it's something that will be uh, continue to be very thoughtful about how we might extend, uh, our leadership in Mash.

Speaker 6: Yeah, just add one thing with respect to the diligence on the molecule. So, of course, one of the things that we were looking at was the preclinical profile and ensuring that this molecule would be, at least from a preclinical standpoint, compatible with resmetirome. So we were reassured by our diligence process. We are very excited to have this and to test it in the clinic.

Tina Ventura: Great. Thanks, Dave. And thanks, everyone. Thanks, Demi. And thank you all for your time and interest today. This now concludes our call. A replay of this webcast will be available on our website in about two hours. Thank you for joining us.

Speaker 5: Gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.

Gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.

Demi: Please wait. The conference will begin shortly.

Please wait; the conference will begin shortly.