Q4 2024 Madrigal Pharmaceuticals Inc Earnings Call
<unk> mode.
After the Speakers' its limitation and there'll be a question and answer session.
A reminder, today's conference call is being recorded.
Speaker Change: I'd like to introduce MS. Tina Ventura, Chief Investor Relations Officer. Please go ahead.
Speaker Change: Thank you Marvin and good morning, everyone and thank you for joining us to discuss Madrigal fourth quarter and full year 2024 earnings. We're also sharing this morning, new two year data from the active treatment open label compensated mash cirrhosis or F. Four C arm.
Speaker Change: Of the phase III Maestro Napoli trial, we issued a press release this morning and have a slide deck that accompanies this webcast, which will post on the Investor Relations section of our website right after the call.
Speaker Change: On the call with me today is bill Civil Chief Executive Officer, and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, and then we'll take your questions. Dr. Michael Charlton our head of clinical development will join us for the Q&A portion of the call. Dr. Charlton has more than 30 years of experience in mass as a leading herpetologist head of the Mayo clinic.
Good day and thank you for standing by. Welcome to Madrigal Pharmaceutical's fourth quarter and full year 2024 earnings conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session.
Speaker Change: 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.
Speaker Change: <unk> group and a treating physician groups.
Speaker Change: We plan to keep today's call to about 45 minutes.
Speaker Change: 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 and with that I will now turn the call over to Bill on slide three well. Thanks, Dana good morning, and thanks for joining today I'll provide an update on the signet.
Speaker Change: Thank you, Marvin. Good morning, everyone, and thank you for joining us to discuss Madrigal's fourth quarter and full year 2024 earnings. We're also sharing this morning new two-year data from the Active Treatment Open Label Compensated MASH Cirrhosis, or F4C, arm.
Speaker Change: of the Phase III maestro NAFLD trial. We issued a press release this morning and have a slide deck that accompanies this webcast, which we'll post on the investor relations section of our website right after the call.
Speaker Change: <unk> momentum we're building with the U S launch of <unk>. We ended 2024 strong and we're pleased with how we've started the year in 2025.
Speaker Change: On the call with me today is Bill Sibold, Chief Executive Officer, and Mardi Dier, Chief Financial Officer. They'll provide prepared remarks, and then we'll take your questions.
Speaker Change: I'll also share an update on new two year data from an open label study for <unk> patients as Tina mentioned the results are very promising and support Reds differs potential to benefit this high risk patient population if approved.
Speaker Change: Dr. Michael Charlton, our head of clinical development, will join us for the Q&A portion of the call. Dr. Charlton has more than 30 years of experience in MASH as a leading hepatologist, head of the Mayo Clinic Hepatology Group, and a treating physician.
Speaker Change: But before we look ahead I want to take a moment to reflect on 2024, a year of remarkable transformation and achievement for the company.
We plan to keep today's call to about 45 minutes.
Speaker Change: I've been in the industry, a long time and I have launched a lot of successful medicines I'll be the first to attest to the tremendous amount of work required for any successful launch let alone a first in disease therapy.
Please note on slide 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.
Speaker Change: And the launch of Red differ is no exception, we work to meet or exceed our high expectations last year and started to lay the foundation for risk differ to potentially become a blockbuster therapy I'm incredibly.
And with that, I will now turn the call over to Bill on slide three. Well, thanks, Tina. Good morning and thanks for joining. Today, I'll provide an update on the significant momentum we're building with the U.S. launch of Res Difra. We ended 2024 strong, and we're pleased with how we've started the year in 2025.
Speaker Change: Really proud of our team's accomplishments highlighted on slide four.
Speaker Change: These are the things that we said that we would do and we did them.
I'll also share an update on new two-year data from an open-label study for F4C patients, as Tina mentioned. The results are very promising and support ResDiffers' potential to benefit this high-risk patient population, if approved.
Speaker Change: We built a world class team to drive the launch of risk differ and support <unk> long term aspirations, our groundbreaking <unk> different phase III trial data were published in the New England Journal of Medicine.
Speaker Change: March 14th we achieved the milestone for the match field the landmark approval of rates differ the first ever treatment approved for this disease.
Speaker Change: But before we look ahead, I want to take a moment to reflect on 2024, a year of remarkable transformation and achievement for the company.
Speaker Change: This achievement was further validated by two top tier liver societies in Europe, and the U S. Both updating their guidelines to include Reds differ as first line therapy for match.
Speaker Change: I've been in the industry a long time and I've launched a lot of successful medicines. I'll be the first to attest to the tremendous amount of work required for any successful launch, let alone a first in disease therapy.
Speaker Change: And we made significant progress expanding Reds differs reach both geographically and clinically submitting reds differ for approval in Europe, and completing enrollment in our maestro Nash outcomes trial.
Speaker Change: and the launch of Res Diffra is no exception. We worked to meet or exceed our high expectations last year and started to lay the foundation for Res Diffra to potentially become a blockbuster therapy.
Speaker Change: Importantly, these accomplishments are translating into thousands of patients now benefiting from riz differ and building a strong foundation for <unk> future as the leader in mass.
Speaker Change: I'm incredibly proud of our team's accomplishments, highlighted on slide 4. These are the things that we said that we would do, and we did them.
Speaker Change: We built a world-class team to drive the launch of Resdipra and support Madrigal's long-term aspirations. Our groundbreaking Resdipra Phase III trial data were published in the New England Journal of Medicine.
Speaker Change: Let's move to the U S res differ launch update on slide five.
Speaker Change: Yeah.
Speaker Change: As we detailed in our earnings release this morning, and first previewed at Jpmorgan in January we generated $103 million in net sales in the fourth quarter of 2024, reflecting 66% quarter over quarter growth.
Speaker Change: On March 14th, we achieved the milestone for the MASH field, the landmark approval of resdifra, the first ever treatment approved for this disease.
Speaker Change: This was another strong demand quarter with inventory well within our expected two to four week range for the full year 2024, we generated $180 million in net sales a remarkable achievement considering we launched in April and these figures represent just three quarters of performance.
Speaker Change: This achievement was further validated by two top-tier liver societies in Europe and the U.S., both updating their guidelines to include res differa as first-line therapy for MASH.
Speaker Change: And, we made significant progress expanding ResDiffer's reach both geographically and clinically, submitting ResDiffer for approval in Europe, and completing enrollment in our Maestro NASH Outcomes Trial.
Speaker Change: Our launch trajectory continues to track in line with some of the most successful specialty medicine launches in the past decade.
Speaker Change: Importantly, these accomplishments are translating into thousands of patients now benefiting from res diffra and building a strong foundation for Madrigal's future as the leader in MASH. Let's move to the U.S. res diffra launch update on slide 5.
Speaker Change: This confirms the urgent need risk for us is addressing in the mass community, it's excellent product profile and the exceptional execution of our team.
Speaker Change: These strong financial results are driven by the key performance indicators critical to any successful drug launch patients on therapy prescribers and access.
Speaker Change: As we detailed in our earnings release this morning, and first previewed at J.P. Morgan in January, we generated $103 million in net sales in the fourth quarter of 2024, reflecting 66% quarter-over-quarter growth.
In the third quarter of 2024 on our payer metric we reached a key milestone one quarter ahead of schedule, achieving greater than 80% commercial coverage for <unk> is different.
Speaker Change: This was another strong demand quarter with inventory well within our expected 2-4 week range.
Speaker Change: Since then we've continued to make great progress on the other two launch metrics.
Speaker Change: For the full year 2024, we generated $180 million in net sales, a remarkable achievement considering we launched in April, and these figures represent just three quarters of performance.
Speaker Change: First on patients as noted on slide six we ended the fourth quarter with more than 11800 patients on res differ and incredible accomplishment in just nine months crossing the 10000 patient threshold is a significant milestone and we continued to steadily add patients at a rate that's consistent with other top tier.
Speaker Change: Our launch trajectory continues to track in line with some of the most successful specialty medicine launches in the past decade. This confirms the urgent need ResGIFRA is addressing in the MASH community, its excellent product profile, and the exceptional execution of our team.
Speaker Change: Your specialty medicine launches <unk>.
Speaker Change: Accordingly, this figure represents patients actively on therapy, meaning it accounts for any discontinuation, making it the most rigorous and meaningful metric to track sustained treatment adoption.
Speaker Change: These strong financial results are driven by the key performance indicators critical to any successful drug launch, patients on therapy, prescribers, and access.
Speaker Change: Yet we're still in the early days, we have penetrated only a fraction of the market with Reds defer less than 4% of the 315000 diagnosed patients with <unk> II <unk> III match.
Speaker Change: In the third quarter of 2024, on our payer metric, we reached a key milestone one quarter ahead of schedule, achieving greater than 80% commercial coverage for RISDFRA. Since then, we've continued to make great progress on the other two launch metrics.
Speaker Change: We remain focused on the 315000 diagnosed patients which represents a highly attractive specialty market.
Speaker Change: First on patients, as noted on slide 6, we ended the fourth quarter with more than 11,800 patients on res diffra, an incredible accomplishment in just nine months.
Speaker Change: Looking ahead. The stated efforts of the next entrant are focused on expanding the market to many multiples of 315000, we believe that the strength of different profile positions. It for leadership in either scenario, creating multiple paths to success for us different in the years ahead.
Speaker Change: Crossing the 10,000 patient threshold is a significant milestone, and we continue to steadily add patients at a rate that's consistent with other top-tier specialty medicine launches.
Speaker Change: Our ability to steadily add red's different patients quarter over quarter is directly tied to increased penetration of our prescriber base.
Speaker Change: Importantly, this figure represents patients actively on therapy, meaning it accounts for any discontinuations, making it the most rigorous and meaningful metric to track sustained treatment adoption.
Speaker Change: From day, one we've talked about wiring the system, how we have been laying the foundation to support the patient volume we expect in the years ahead, and we're seeing real progress as we've engaged providers driven change in clinical practice and helped build the infrastructure necessary for sustained prescription growth on.
Speaker Change: Yet, we're still in the early days. We have penetrated only a fraction of the market with res differa, less than 4% of the 315,000 diagnosed patients with F2-F3 match.
Speaker Change: On slide seven the bar graph on the left illustrates this progress as a reminder, our field team is focused on a total of 14000 target prescribers, primarily herpetologist and gastroenterologists with a concentrated effort on the top 6000 prescribers in the fourth quarter, approximately 60% of our top six.
Speaker Change: We remain focused on the 315,000 diagnosed patients, which represents a highly attractive specialty market.
Speaker Change: Looking ahead, the stated efforts of the next entrant are focused on expanding the market to many multiples of 315,000. We believe that the strength of RISDFRA's profile positions it for leadership in either scenario, creating multiple paths to success for RISDFRA in the years ahead.
Speaker Change: <unk> targets prescribed grids differ up from 40% in the third quarter, we are steadily adding new prescribers and we are seeing increased depth of prescribing from current writers both metrics are tracking exceptionally well with other successful blockbuster launches.
Speaker Change: Our ability to steadily add REZ different patients quarter over quarter is directly tied to increased penetration of our prescriber base.
Speaker Change: As expected our top target prescribers have driven more than 75% of our prescriptions.
Speaker Change: From day one, we've talked about wiring the system, how we have been laying the foundation to support the patient volume we expect in the years ahead. And we're seeing real progress as we've engaged providers, driven change in clinical practice, and helped build the infrastructure necessary for sustained prescription growth.
Speaker Change: Just as we've successfully driven adoption among our top target prescribers, we plan to continue shaping and clinical practice and expanding access across our full prescriber base as we build roads different towards its peak sales potential.
Speaker Change: On slide 7, the bar graph on the left illustrates this progress. As a reminder, our field team is focused on a total of 14,000 target prescribers, primarily hepatologists and gastroenterologists, with a concentrated effort on the top 6,000 prescribers.
Speaker Change: We're already making meaningful progress by year end, approximately 40% of the 14000 had prescribed risk differ reflecting a strong and growing foundation of support.
Speaker Change: In the fourth quarter, approximately 60% of our top 6,000 targets prescribed Rizdifra, up from 40% in the third quarter. We are steadily adding new prescribers, and we are seeing increased depth of prescribing from current writers.
Speaker Change: Whereas differs broad based uptake is being driven by its attractive profile. It's a liver directed therapy that halts or improved liver stiffness are proxy for liver fibrosis in 91% of patients out to three years. It's also a once daily well tolerated pill with simple dosing.
Speaker Change: Both metrics are tracking exceptionally well with other successful blockbuster launches. As expected, our top target prescribers have driven more than 75% of our prescriptions.
Speaker Change: And with the chronic and serious <unk>.
Speaker Change: Liver disease like mash. This favorable profile supports long term adherence with early data continuing to indicate persistency rates comparable to other well tolerated oral therapies.
Speaker Change: Just as we've successfully driven adoption among our top target prescribers, we plan to continue shaping clinical practice and expanding access across our full prescriber base as we build Res Different towards its peak sales potential.
Speaker Change: We're also hearing overwhelmingly positive feedback on <unk> differ from both physicians and patients. They continue to highlight the benefits of the medicine, including improvements in liver function tests and lipid levels reduced fatigue increased physical activity and improvement in fibrosis in these real world outcomes really matter.
Speaker Change: We're already making meaningful progress. By year-end, approximately 40% of the 14,000 had prescribed res diffra, reflecting a strong and growing foundation of support.
Speaker Change: We recently heard from one raise different patient diagnosed with that to mash. She said quote living with mashed felt like having a time bomb in my body, whereas deferred gave me hope and my life back end quote.
Speaker Change: whereas Jifra's broad-based uptake is being driven by its attractive profile.
Speaker Change: It's a liver-directed therapy that halts or improves liver stiffness, a proxy for liver fibrosis, in 91% of patients out to three years. It's also a once-daily well-tolerated pill with simple dosing and with the chronic and serious
Speaker Change: Our goal is to be the leader and mash and help patients for many years to come as noted on slide nine our long term strategy builds on the success of <unk> U S launch.
Speaker Change: Liver disease like MASH, this favorable profile supports long-term adherence with early data continuing to indicate persistency rates comparable to other well-tolerated oral therapies.
Speaker Change: First we are expanding geographically and remain on track for a mid year regulatory decision for risk differ in Europe, assuming a positive outcome, we plan to take a targeted country by country approach to commercialization beginning with Germany in the second half of the year.
Speaker Change: We're also hearing overwhelmingly positive feedback on resgifra from both physicians and patients.
Speaker Change: Beyond Europe, we are also assessing opportunities to bring rates differ to patients in additional attractive geographies.
Speaker Change: They continue to highlight the benefits of the medicine including improvements in liver function tests and lipid levels, reduced fatigue, increased physical activity, and improvement in fibrosis.
Speaker Change: We're advancing risks differ for patients with compensated Nash cirrhosis.
Speaker Change: Approval in <unk> would represent a major step forward for the mass field and for patients significantly expanding the treatment landscape and effectively doubling risk diverse market opportunity.
Speaker Change: And these real-world outcomes really matter. We recently heard from one res different patient diagnosed with F2MASH. She said, quote, living with MASH felt like having a time bomb in my body. ResDiffer gave me hope and my life back, end quote.
Speaker Change: I will spend some more time on the data we shared this morning in a moment.
Speaker Change: And third we are committed to building a strong pipeline beyond <unk>. We're in the enviable position of providing a highly meaningful medicine to the mash community today and we are now focused on building the right pipeline behind it we're evaluating assets at different stages of development across multiple mechanisms of action all with the goal of strengthening and extending.
Speaker Change: Our goal is to be the leader in MASH and help patients for many years to come. As noted on slide 9, our long-term strategy builds on the success of RISDFAR's U.S. launch.
Speaker Change: First, we are expanding geographically and remain on track for a mid-year regulatory decision for ResDiffer in Europe. Assuming a positive outcome, we plan to take a targeted, country-by-country approach to commercialization beginning with Germany in the second half of the year.
Speaker Change: Our leadership position to mash.
Speaker Change: Moving to slide 10, and the unmet need and compensated mash cirrhosis, it's a chronic progressive liver disease characterized by significant liver damage loss of liver function liver cancer in depth.
Speaker Change: Beyond Europe, we are also assessing opportunities to bring ResDiffer to patients in additional attractive geographies.
Second, we're advancing RISC-Differ for patients with compensated mast cirrhosis.
Speaker Change: A substantial portion of compensated mash cirrhosis patients also suffer from portal hypertension, which often leads to life threatening complications such as hepatic encephalopathy ascites and various youll bleeding.
Speaker Change: Approval in F4C would represent a major step forward for the MASH field and for patients, significantly expanding the treatment landscape and effectively doubling Red Devereux's market opportunity.
Speaker Change: While patients with F. Two F. Three fibrosis face a 10% to 17 times higher risk of liver related mortality.
Speaker Change: I'll spend some more time on the data we shared this morning in a moment.
Speaker Change: And third, we are committed to building a strong pipeline beyond RISDFRA. We're in the enviable position of providing a highly meaningful medicine to the MASH community today, and we are now focused on building the right pipeline behind it.
Speaker Change: Four patients are at a staggering 42 times increased risk.
Speaker Change: And this very sick F. Four patient population preventing progression to adverse clinical outcomes is the central treatment goal.
Speaker Change: We are evaluating assets at different stages of development across multiple mechanisms of action, all with the goal of strengthening and extending our leadership position in MASH.
Speaker Change: This is reflected in FDA guidance, which recommends that clinical trials and compensated Nash cirrhosis use outcomes as an endpoint as opposed to biopsy based surrogate endpoints. This guidance along with data from our open label FRC cohort informed the design of our ongoing Maestro Nash outcomes trial.
Speaker Change: Moving to slide 10 in the Unmet Need and Compensated Mast Cirrhosis, it's a chronic progressive liver disease characterized by significant liver damage, loss of liver function, liver cancer, and death.
Speaker Change: We believe that red different liver directed mechanism of action should deliver a benefit not only in F. Two F three matched patients, but in <unk> patients as well.
Speaker Change: A substantial portion of compensated MASH cirrhosis patients also suffer from portal hypertension, which often leads to life-threatening complications such as hepatic encephalopathy, ascites, and variceal bleeding.
Speaker Change: Therefore as shown on slide 11, we included a separate open label active treatment arm of patients with compensated Nash cirrhosis, and our maestro Napoli one trial to begin evaluating risk depressed safety and efficacy and that foresee.
Speaker Change: While patients with F2-F3 fibrosis face a 10 to 17 times higher risk of liver-related mortality, F4 patients are at a staggering 42 times increased risk.
Speaker Change: As a reminder, maestro Napoli one was a double blind randomized placebo controlled phase III safety trial to support regulatory approval.
Speaker Change: In this very sick F4 patient population, preventing progression to adverse clinical outcomes is the central treatment goal.
Speaker Change: We previously presented positive one year data from the <unk> cohort of this trial and are highlighting new two year V. Cte data and 101 patients on slide 12.
Speaker Change: This is reflected in FDA guidance, which recommends that clinical trials and compensated MASH cirrhosis use outcomes as an endpoint, as opposed to biopsy-based surrogate endpoints.
Speaker Change: This guidance, along with data from our Open Label F4C cohort, informed the design of our ongoing Maestro NASH outcomes trial.
Speaker Change: DCT or vibration or vibration control transient elastography is a widely used noninvasive tests conducted with a fiber scan that measures liver stiffness as a proxy for fibrosis.
Speaker Change: We believe that RISDFR's liver-directed mechanism of action should deliver a benefit not only in F2-F3 MASH patients, but in F4-C MASH patients as well.
Speaker Change: It's also a strong predictor of clinical outcomes.
Speaker Change: The two year results show that patients achieved a mean six seven kpa or kilo Pascal reduction in liver stiffness at two years, which represents the largest mean kpa reduction reported in an F foresee mash patient population today.
Speaker Change: Therefore, as shown on slide 11, we included a separate, open-label, active treatment arm of patients with compensated mast cirrhosis in our Maestro NAPLD1 trial to begin evaluating risk-difference safety and efficacy in F4C.
Speaker Change: As a reminder, Maestro NAPLD 1 was a double-blind, randomized, placebo-controlled Phase 3 safety trial to support regulatory approval.
Speaker Change: While this was a single arm open label trial. This reduction was highly statistically significant versus baseline <unk>.
Speaker Change: <unk> used the Beano rule of five tpa to stratify risk of liver related events in patients with Nash. So a $6 seven reduction suggest that many patients are moving into a lower risk category.
Speaker Change: We previously presented positive one-year data from the F4C cohort of this trial and are highlighting new two-year VCTE data in 101 patients on slide 12.
Speaker Change: 51% of patients achieved a 25% or greater decrease in liver stiffness as measured by V. Cte this level of reduction in liver stiffness has been associated with reduced progression to end stage liver disease moving patients further away from the risks of cirrhosis and its complications.
Speaker Change: VCT, or Vibration Controlled Transient Elastography, is a widely used non-invasive test conducted with a fiber scan that measures liver stiffness as a proxy for fibrosis. It's also a strong predictor of clinical outcomes.
Speaker Change: The two-year results show that patients achieved a mean 6.7 kPa or kilopascal reduction in liver stiffness at two years, which represents the largest mean kPa reduction reported in an F4C MASH patient population to date.
Speaker Change: And we're at a different safety profile was consistent with other risk different clinical trials with a low rate of discontinuation due to adverse events. We look forward to sharing more details from this two year cohort at a future medical meeting.
Speaker Change: These data add to the growing body of evidence supporting <unk> different potential benefit in this high risk patient population and support continued confidence in our fully enrolled cirrhosis outcomes trial.
Speaker Change: While this was a single-arm open-label trial, this reduction was highly statistically significant versus baseline.
Speaker Change: Physicians use the Bobino Rule of 5 KPA to stratify risk of liver-related events in patients with MASH, so a 6.7 reduction suggests that many patients are moving into a lower risk category.
Speaker Change: As noted on slide 13.
Speaker Change: Mr. Nash outcomes as a large phase III double blind placebo controlled trial evaluating progression to liver decompensation events and 845 patients with compensated Nash cirrhosis.
Speaker Change: 51% of patients achieved a 25% or greater decrease in liver stiffness as measured by VCTE. This level of reduction in liver stiffness has been associated with reduced progression to end-stage liver disease, moving patients further away from the risks of cirrhosis and its complications.
Speaker Change: We expect to announce data from this trial in 2027.
Speaker Change: Looking ahead to the opportunity and FRC and assuming today's results translate to maestro Nash outcomes, and whereas differ obtained regulatory approval.
Speaker Change: And Resdifra's safety profile was consistent with other Resdifra clinical trials with a low rate of discontinuations due to adverse events. We look forward to sharing more details from this two-year cohort at a future medical meeting.
Speaker Change: We believe breads differ is and will be the leading therapy in F. Two F foresee period.
Speaker Change: Before I hand, it over to Marty Let me briefly summarize our progress on slide 14.
Speaker Change: These data add to the growing body of evidence supporting res difference potential benefit in this high-risk patient population and support continued confidence in our fully enrolled cirrhosis outcomes trial.
Speaker Change: 2024 was a transformational year for Madrigal, we secured FDA approval for <unk> and are executing on a highly successful launch we see significant runway for growth with less than 4% of the U S target market penetrated and an attractive real world profile Reds differ is well positioned for continued strong.
Speaker Change: As noted on slide 13, Meister-Nash Outcomes is a large Phase III, double-blind, placebo-controlled trial evaluating progression to liver decompensation events in 845 patients with compensated MASH cirrhosis.
Speaker Change: <unk> momentum in 2025 and beyond.
Speaker Change: We are preparing for global expansion.
Speaker Change: We see a significant opportunity in <unk> and believe we will be first to market.
We expect to announce data from this trial in 2027.
Speaker Change: So, looking ahead to the opportunity in F4C and assuming today's results translate to Maestro Nash outcomes and Res Difera obtains regulatory approval.
Speaker Change: And we continue to build for the future as we actively explore opportunities to expand our pipeline with that I'll turn it over to Marty.
Marty: Earlier today, we issued a press release detailing our full financial results I will highlight a few key takeaways for the fourth quarter and full year as noted on slide 15.
Speaker Change: We believe breast different is and will be the leading therapy in F2 to F4C period
Thank you.
Speaker Change: Before I hand it over to Mardi, let me briefly summarize our progress on slide 14.
Speaker Change: Fourth quarter net sales totaled $103 3 million, bringing full year 2020 for net sales to $181 million an impressive achievement. Considering this reflects only nine months of commercialization, we delivered another strong demand quarter with inventory well within the expected two to four week range.
Mardi Dier: 2024 was a transformational year for Madrigal. We secured FDA approval for resdifra and are executing on a highly successful launch.
Speaker Change: We see significant runway for growth, with less than 4% of the U.S. target market penetrated, and an attractive real-world profile. ResDiffer is well-positioned for continued strong momentum in 2025 and beyond.
Speaker Change: Our gross to net discount increased in line with what we previously discussed as we said we expect some variability in gross to net early in the launch looking ahead to 2025 as expected we anticipate an increase in the gross to net discount compared to 2024 as is typical at this stage of the specialty of our specialty.
We are preparing for global expansion.
Speaker Change: We see a significant opportunity in F4C and believe we will be first to market. And we continue to build for the future as we actively explore opportunities to expand our pipeline. With that, I'll turn it over to Mardi.
Speaker Change: Medicine. Much importantly, this is already reflected in our expectations for a robust year over year net sales growth in 2025.
Mardi Dier: Thank you, Bill. Earlier today, we issued a press release detailing our full financial results. I will highlight a few key takeaways for the fourth quarter and full year as noted on slide 15.
Speaker Change: <unk> expenses for the fourth quarter and full year of 2024 by $25 $6 million and $236 7 million, respectively, compared to $76 million and $272 4 million in the prior year period R&D.
Mardi Dier: Fourth quarter net sales totaled $103.3 million, bringing full year 2024 net sales to $180.1 million, an impressive achievement considering this reflects only nine months of commercialization.
Speaker Change: R&D expenses decreased by $35 $6 million in 2024, due primarily to a reduction in clinical trial accruals and the change in accounting for inventory cost following FDA approval.
Speaker Change: We delivered another strong demand quarter with inventory well within the expected two to four week range.
Speaker Change: Our growth to net discount increased in line with what we previously discussed.
Speaker Change: Prove out very steadfast, partially offset by an increase in head count.
Speaker Change: As we said, we expect some variability and growth to net early in the launch.
Speaker Change: Looking ahead, we expect a somewhat higher level of R&D spend in 2025 compared to 2024.
Speaker Change: Looking ahead to 2025, as expected, we anticipate an increase in the gross to net discount compared to 2024, as is typical at this stage of a specialty medicine launch.
Speaker Change: SG&A expenses for the fourth quarter and full year of 2024 were $141 $2 million and $435 $1 million, respectively, compared to $46 $5 million and $108 1 million in the prior year period. This year over year increase was <unk>.
Speaker Change: Importantly, this is already reflected in our expectations for robust year-over-year net sales growth in 2025.
Speaker Change: R&D expenses for the fourth quarter and full year of 2024 were $25.6 million and $236.7 million respectively, compared to $70.6 million and $272.4 million in the prior year periods.
Speaker Change: <unk> and reflects the rapid scale up of our U S commercial operations.
Speaker Change: Following these different approval in March 2024, looking ahead, we expect SG&A expenses to increase in 2025, as we continue to invest in the U S launch and our international expansion.
Speaker Change: R&D expenses decreased by $35.6 million in 2024 due primarily to a reduction in clinical trial accruals and the change in accounting for inventory costs following FDA approval of RISDFRA, partially offset by an increase in headcount.
Speaker Change: Turning to our balance sheet, we ended 2024 with $931 $3 million in cash cash equivalents restricted cash and marketable securities with a strong cash position, we are well resource to support the ongoing launch of <unk> in both the U S and our planned launch in Europe, I will now turn the call.
Speaker Change: Looking ahead, we expect a somewhat higher level of R&D spend in 2025 compared to 2024.
Speaker Change: SG&A expenses for the fourth quarter and full year of 2024 were $141.2 million and $435.1 million, respectively, compared to $46.5 million and $108.1 million in the prior year period.
Tina Ventura: Back over to Tina.
Tina Ventura: Marty let's move into the Q&A portion of the call. Marvin. Please go ahead and provide instructions for the Q&A session.
Speaker Change: We will now open the lines for questions to open your line.
Tina Ventura: Please press star one one and youll be added to the queue on the call.
Speaker Change: This year-over-year increase was expected and reflects the rapid scale-up of our U.S. commercial operations following Resifera's approval in March 2024. Looking ahead, we expect SG&A expenses to increase in 2025 as we continue to invest in the U.S. launch and our international expansion.
Speaker Change: Our first question comes from the line of Thomas Smith of Leerink Partners. Your line is now open.
Thomas Smith: Hey, guys. Good morning, Thanks for taking the questions and congrats on the strong launch and the new cirrhosis data.
Speaker Change: Turning to our balance sheet, we ended 2024 with $931.3 million dollars in cash, cash equivalents, restricted cash, and marketable securities.
Thomas Smith: Just had a question with respect to the.
Thomas Smith: The ongoing with different launch now that we're roughly two thirds of the way through the quarter. So wondering if you could comment on what you've seen in the first two months of the year in terms of new patient adds.
Speaker Change: With this strong cash position, we are well-resourced to support the ongoing launch of Ruzdifra in both the U.S. and our planned launch in Europe. I'll now turn the call back over to Tina.
Thomas Smith: Any change in the cadence of patients starting on drug or.
Thomas Smith: Anything notable as patients and prescribers kind of work through their insurance or co pay.
Tina Ventura: Thanks, Mardi. Let's move into the Q&A portion of the call. Marvin, please go ahead and provide instructions for the Q&A session.
Thomas Smith: Adjustments and then historically.
Thomas Smith: Given some.
Thomas Smith: High level guidance based on the comp.
Marvin: We will now open the lines for questions. To open your line, please press star 1 1 and you'll be added to the queue on the call.
Thomas Smith: Group, a specialty drug launches.
Speaker Change: I guess any color that you can provide as we think about Q1, and maybe 2025 broadly thanks so much.
Speaker Change: Our first question comes from the line of Thomas Smith of the Ring Partners. Your line is now open.
Tom: Tom Thanks for the question.
Speaker Change: Look.
Speaker Change: Just a couple of points first of all you know 2024 was really.
Thank you for watching!
Speaker Change: Hey guys, good morning. Thanks for taking the questions and congrats on the strong launch and the new cirrhosis data.
Speaker Change: An incredible year, when you think about.
Speaker Change: Going back 12 months from now there wasn't a product on the market for mash and.
Speaker Change: In a very short period of time, we've really done I think a remarkable job of executing and finishing off the year with a $103 million quarter is really.
Speaker Change: Really very impressive by any by any measure you look at as we look at metrics all across the blockbuster launches that you referred to we're tracking extremely well on all fronts. There is no weakness here on any of them.
Speaker Change: anything notable as patients and prescribers kind of work through their insurance or co-pay adjustments, and then historically you've, you know, given some high-level guidance based on the the COMP group of specialty drug launches.
Speaker Change: We carry that I would say the momentum of 24 into 'twenty five of steadily adding patients and prescribers. So that's we've seen more of that in the first quarter of 'twenty five.
Speaker Change: I guess any color that you could provide as we think about Q1 and maybe 2025 broadly. Thanks so much.
Speaker Change: We also do have like everyone else, but Q1 dynamic that is clear.
Speaker Change: Tom, thanks for the question. Look, you know, as just a couple points, first of all, you know, 2024 was really an incredible year. When you think about
Speaker Change: Clearly.
Speaker Change: A phenomenon each year.
Speaker Change: And teams have been well prepared and I think we're managing through that extremely well.
Speaker Change: Going back 12 months from now, there wasn't a product on the market for MASH and, you know, in a very short period of time we've really done, I think, a remarkable job executing and finishing off the year with a 103 million quarters is really very impressive. By any measure you look at, as we look at metrics all across the blockbuster launches that you referred to, we're tracking extremely well on all fronts. There's no weakness here on any of them.
Speaker Change: As I think about what's happening at the prescriber level.
Speaker Change: Each there I would say there isn't a prescriber yet.
Speaker Change: That has.
Speaker Change: Max out or even close to maxing out.
Speaker Change: The patients that exist in their practice or that are being referred into their practice and each practices learning we talk about wiring. The system. That's been a lot of hard work and we've done it on a practice by practice basis and as you can see we continue to add new prescribers and we're now at the 60% penetration into that target group.
Speaker Change: We carried, I would say, the momentum of 24 into 25 of steadily adding patients and prescribers. So we've seen more of that in the first quarter of 25. We also do have, like everyone else, the Q1 dynamic that is clearly a phenomena each year.
Speaker Change: For each of those as they start prescribing theyre doing their wiring. So what we're continuing to do is just bring on.
Speaker Change: Steadily each day each week each month, each quarter prescribers have them get ready to be able to handle the volume of their patients. How they worked through the system et cetera, now from a Q1 dynamic perspective as I said.
Speaker Change: And, you know, teams have been well prepared, and I think we're managing through that extremely well. You know, as I think about what's happening at the prescriber level, you know, each there, I would say there isn't a prescriber yet.
Speaker Change: Certainly that's something that we're seeing like any anyone else I think the team has done a good job.
Speaker Change: Getting ready to manage through that.
Speaker Change: that has maxed out, or even close to maxing out, the patients that exist in their practice or that are being referred into their practice. And each practice is learning. We talk about wiring the system. That's been a lot of hard work, and we've done it on a practice-by-practice basis. And as you can see, we continue to add new prescribers, and we're now at the 60% penetration into that target group. For each of those, as they start prescribing, they're doing their wiring.
Speaker Change: No real other.
Speaker Change: Uh huh.
Speaker Change: Challenges that we've seen with the quarter its pretty standard yes.
Speaker Change: Yes, maybe I'll just add a little bit Tom to answer your question about the analogs. So yes, we do track very closely with our group of 10 specialty launches over the last 10 years.
Speaker Change: It gets a little tricky when you go from Q4 to Q1, so we're not giving specific guidance in that percentage.
Speaker Change: For Q1. It may not go May may not give that guidance going forward that we're really tracking with these analogs, thus far but I will also say if we just look at consensus and Phil said, we're very pleased with what we're seeing going into 2025 and a little commentary there that we believe consensus for Q1 2025 will narrow.
Speaker Change: continuing to do is just bring on, you know, steadily each...
day, each week, each month, each quarter.
Speaker Change: have them get ready to be able to handle the volume of their patients, how they work through the system, et cetera. Now, from a Q1 dynamic perspective, as I said, you know, certainly that's something that we're seeing like anyone else. I think the team has done a good job getting ready to manage through that. No real other
Speaker Change: And go up a little bit.
Speaker Change:
Speaker Change: As a result of what we've been saying so far.
Tom: Thanks, Tom.
Speaker Change: Next question please.
Tom: Thank you ma'am for next question.
challenges that we've seen with the quarter. It's pretty standard.
Speaker Change: Our next question comes from the line of Andrea <unk> of Goldman Sachs. Your line is now open.
Speaker Change: Maybe I'll just add a little bit, Tom, to answer your question about the analogs. So, yeah, we do track very closely with our group of 10 specialty launches over the last 10 years.
Andrea: Thanks for taking the question maybe I can ask you here on this.
Andrea: I know that you shared I was hoping you could speak a little bit more on the clinical meaningfulness of achieving that $6 seven Cal Pascal reduction and I know in the context of your three year data for the <unk> III Nash patient population when you talk about how the Cte measure Malone can kill Pascal was correlated with fewer liver related outcomes just wondering if it seems.
Speaker Change: It gets a little tricky when you go from a Q4 to a Q1, so we're not giving specific guidance in that percentage for Q1 and may not give that guidance going forward, but we're really tracking with these analogs thus far. But I will also say, if we just look at consensus, as Bill said, we're very pleased with what we're seeing going into 2025.
Andrea: Threshold stands for that patient population and then finally, just how are you to today's data change how you're thinking about the Nash outcomes trial.
Speaker Change: And a little commentary there that we believe consensus for Q1 2025 will narrow and go up a little bit as a result of what we've been seeing so far. Great. Thanks, Tom. Marvin, next question, please.
Andrea: At all.
Andrea: Does that change how you think about the powering of the study. Thanks so much.
Speaker Change: Great. Thanks for the question, Andrew I'll turn it over to Michael in a second but as we think about how does it change our view Mr. Nash outcomes look we've been confident about that study. This is just another piece of information, which gives us I would say greater confidence in it.
Thank you. One moment for next question.
Speaker Change: Doing something here, which is really again as we've done with our <unk> three program, we're pioneering the way.
Speaker Change: And we believe that we have designed the right trial for Maestro Nash outcomes.
Speaker Change: This trial that we announced today.
Speaker Change: Actually helped us helped to inform our thinking on Maestro Nash outcomes in would be really exciting news that we presented today as I said it gives us even more confidence, but maybe Michael do you want to answer the first couple of questions that Andrew had.
Speaker Change: liver-related outcomes. Just wondering if that same threshold stands for the F4 cirrhotic patient population? And then finally, just how did today's data change how you're thinking about the NASH outcomes trial, if at all, and does that change how you're thinking about the powering of the study? Thanks so much.
Michael Charlton: Good question.
Speaker Change: The activity of decreases in liver stiffness increases with a higher baseline level. So our baseline levels 25, kilo pascal's to predict <unk> really starts to pick up at around 15 killer Pascal. So there are six seven kilograms reduction.
Speaker Change: Great. Thanks for the question, Andrea. I'll turn it over to Michael in a second, but, you know, as we think about how does it change our
Speaker Change: view on Meister-Nash outcomes. Look, we've been confident about that study. This is just another piece of information which gives us, I would say, greater confidence in it. You know, we're doing something here, which is really, again, as we've done it with our F2-F3 program, we're pioneering the way. And we believe that we have designed the right trial for Meister-Nash outcomes.
Michael Charlton: With the starting point to 25 kilo Pascal's.
Should be highly predictive decreased risk of clinical outcomes.
Speaker Change: Great. Thanks.
Andrea: Thanks Andrea.
Speaker Change: Next question please Martin.
Speaker Change: Thank you one moment for our next question.
Speaker Change: You know, this trial that we announced today actually helped us, helped to inform our thinking on Meister Nash outcomes, and with the, you know, really exciting news that we presented today, as I said, it gives us even more confidence. But maybe, Michael, do you want to answer the first couple of questions that Andrea had? Yes. It's a great question. The productivity of decreases in liver stiffness increases with a higher baseline level.
Our next question comes from the line of <unk> Rahimi of Piper Sandler Your line is now open.
Speaker Change: Good morning team and.
Speaker Change: Thank you so much for all the great updates.
Speaker Change: Is there.
Speaker Change: I guess could you comment on that as we go into 2025, if youll be in a position to provide guidance.
Speaker Change: I think that Marty your commentary was very helpful around that.
Speaker Change: Sensus is kind of a.
Speaker Change: 25 kilopascals, the predictivity really starts to tick up at around 15 kilopascals. So there are 6.7 kilopascal reduction, start with the starting point of 25 kilopascals, should be should be highly predictive of decreased risk of clinical outcomes.
Speaker Change: A little increase tightened a little bit so just maybe help us understand.
Speaker Change: How youre thinking.
Speaker Change: Thinking about moving forward, we understand the dynamics the first quarter.
Speaker Change: And that at what point will you feel comfortable to kind of share with us what the 2025 or 2026 guidance would look like.
Great. Thanks, Andrea. Next question please, Martin.
Speaker Change: That would be really helpful and I'll jump back in the queue.
Thank you. One moment for our next question.
Marty: Great Marty let me pass it over to you yeah. Thanks, yes.
Marty: Yes with respect to guidance, we have been very clear we are not giving guidance right now we consider it internally, but that's not something we're providing at this time, we're just too early in the launch I did provide a little commentary on Q1 2025, and I think the same commentary goes for for the full year 2005, we like what we're seeing in that moment.
Speaker Change: Our next question comes from a line of Yasmin Rahimi of Piper Sandler. Your line is now open.
Yasmin Rahimi: Good morning, team. And thank you so much for all the great updates.
Yasmin Rahimi: Is there, I guess, could you comment on, as we go into 2025, if you will be in a position to provide guidance?
Marty: Tom.
Tom: Going into 2025, we commented on the robust year over year growth, So where consensus sits for 2025, we expect that to narrow as well and go up a little bit based on what we're seeing.
Speaker Change: I think that Mardi, your commentary was very helpful around that the consensus is going to a little increase tighten a little bit. So just maybe help us understand.
Speaker Change: how you're thinking about moving forward. We understand the dynamics of first quarter, but beyond that, at what point will you feel comfortable to kind of share with us what the 2025 or 2026 guidance would look like?
Marty: Good thanks.
Marty: Yes.
Marty: Marvin next question please.
Marty: Thank you for a moment for our next question.
Marty: Yeah.
Speaker Change: Our next question comes from the line of Ellie Merle of UBS. Your line is now open.
Speaker Change: that would be really helpful and I'll jump back in the queue.
Ellie Merle: Hey, guys. Thanks for taking the question.
Thank you.
Ellie Merle: Interesting data I guess whereabouts are risk and benefit seen irrespective of the Atlanta compound at baseline and any color on sort of which patients were more or less likely to shelley's DCT reductions.
Mardi Dier: Great. Mardi, let me pass that over to you. Yeah. Thanks, Yaz.
Speaker Change: Yeah, with respect to guidance, we've been very clear. We're not giving guidance right now. You know, we consider it internally, but that's not something we're providing at this time. We're just too early in the launch.
Speaker Change: I did provide a little commentary on Q1 2025, and I think the same commentary goes for the full year 2025. We like what we're seeing, the momentum.
Ellie Merle: Then just in terms of the study I guess can we expect any further.
Ellie Merle: Long term data from the study like the three year data just curious the timing here since I think the study has been going on.
Speaker Change: Going into 2025, we commented on the robust year-over-year growth, so where consensus sits for 2025, we expect that to narrow as well and go up a little bit based on what we're seeing.
Ellie Merle: Alrighty Thanks, yes.
Speaker Change: Thanks Ali look so more to come. This is just some really top line look at the data.
Speaker Change: Upcoming medical meeting, we'll go into a little bit more detail on things I think there is certainly still a lot left that we can learn from this study just with the data that we have at two years.
Good, thanks Yaz.
Marvin, next question please.
Thank you. One moment for our next question.
Is there anything else Michael to comment on where we're not we're not giving out any more than the top line that we've given today.
Speaker Change: Our next question comes from the line of Ellie Murrell of UPS. Your line is now open.
Ellie Murrell: Hey guys, thanks for taking the question. Interesting F4 data, I guess.
Speaker Change: I think the assumption in the productivity for these results to clinical outcomes and.
Speaker Change: Were those FibroScan benefits seen irrespective of the liver fat content at baseline and any color on sort of which patients were more or less likely to show these?
Speaker Change: With a decline of 25% based on that study of 10 patients forward perspective.
Speaker Change: 30% to 40% decreases likelihood of a liver related clinical events. So that's sort of my takeaway from these results great. Thanks, Alex Thanks Ali Marvin next question. Please.
Speaker Change: VCTE reductions. And then just in terms of the study, I guess, can we expect any further long-term data cuts from this study, like the three-year data? Just curious the timing here since I think the study has been going on for a few years already. Thanks. Yep.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of cost <unk> of Jefferies. Your line is now open.
Speaker Change: Thanks, Ellie. Look, you know, so more to come. This is just some really top-line look at the data at an upcoming medical meeting. We'll go into a little bit more detail on things. I think there's certainly still a lot left that we can learn from this study, just with the data that we have at two years.
Hey, this is Amy answer Carlos Thanks, so much for taking our question.
Speaker Change: Turning off just wanted to get your thoughts on the competitor at G. F. 'twenty, one data in cirrhotic Nash and how that could read across to your S. Four outcome study.
Michael Charlton: Is there anything else Michael to comment on? We're not we're not giving out any more than the top line that we've given today. No, I think you know the assumption in the predictivity for these results the clinical outcomes and with the with the decline of 25% based on that study of 10,000 patients from a perspective that you'd be back to 30 to 40 percent decreased likelihood of a liver related clinical event. So that's our main takeaway from these results.
Speaker Change: Also on part D redesign I think our preliminary math is getting to a potential full year net sales impact of around 3% to 5% for rent deferred going forward just wanted to check. This number with you and will you do any additional discounts ahead of the kind of launch thanks. So much.
Speaker Change: Well Amy Thank you that's a lot of questions again.
Let me see if we can if we can talk through first.
Great. Thanks, Ellie. Thanks, Ellie. Marvin, next question, please.
Speaker Change: First of all.
Speaker Change: As we launch the product from a gross to net perspective, we have been extremely extremely.
Thank you, one moment, for our next question.
Thank you for watching!
Speaker Change: Our next question comes from the line of Akash Tiwari of Jeffries. Your line is now open.
Speaker Change: Diligent about gross to net.
Speaker Change: We werent contracting as we launch the product and when we launched the product.
Speaker Change: Hey, this is Aimee Ansarakosh. Thanks so much for taking our question. Starting off, just wanted to get your thoughts on the competitor FGF21 data in serotic NASH and how that could read across to your F4 outcome study.
Speaker Change: We don't you don't think about launch in a quarter or two or four you think about kind of the years ahead, and we've thought about gross to net.
Akash Tiwari: Also, on Part D redesign, I think our preliminary math is getting to a potential full-year net sales impact of around 3-5% for ResDiffra going forward. Just wanted to check this number with you and will you do any additional discounts ahead of the summer launch? Thanks so much.
Speaker Change: Anticipating that there will be additional competition in the marketplace and time additional indications hopefully for us.
Speaker Change: Et cetera, So we take an extremely disciplined approach here now we will react to market dynamics as any company does you all.
Speaker Change: We have a dynamic in Q1, which we've talked about as it relates to working with the payers and so forth.
Speaker Change: Well, Amy, thank you. That's a that's a lot of questions to get through. Let me see if we can if we can talk through
Speaker Change: Constant dynamic there so we'll continue to react to the market.
You know, first of all,
Speaker Change: As we launched the product, you know, from a gross and net perspective, we have been.
Speaker Change: These dynamics continue to shift.
Speaker Change: extremely, extremely diligent about Gross To Net. We weren't contracting as we launched the product, and when we launched the product, you don't think about launch in a...
Speaker Change: Your other question was on part D. I mean look Marty I think covered it a little bit.
Speaker Change: In some of the opening remarks, but Martin do you want to make any comments, yes, I'll, just say specifically about that part D and how it impacts gross to net remember Medicare patients or about a third of our business.
Speaker Change: you know quarter two or four, you think about kind of the years ahead and you know we thought about gross to net anticipating that there will be additional competition.
Speaker Change: And.
Speaker Change: Part D. We've always said that there will be some impact going into 2025 with the redesign.
Speaker Change: Totally true, but we also had in 2024, we were paying Medicare rebates really send the impact is a little more incremental in 2025 versus a significant step up.
in the marketplace in time, additional indications, hopefully, for us.
Speaker Change: etc. So, you know, we take an extremely disciplined approach here. Now, we will react to market dynamics as any company does. You know, you always have a dynamic in Q1, which we've talked about, as it relates to working with the payers and so forth, you know, there's a constant dynamic there. So, you know, we'll continue to react to the market as these dynamics continue to shift.
Speaker Change: So I think the good news with our gross to net particularly in 2025 is everything.
Speaker Change: It's going as expected right. So we had seen a little bit of increase in our copay assess is as expected and included in our.
Speaker Change: Our expectations for net revenue for the year, Yes, I mean, our.
Speaker Change: Statement and belief in this product and just also where do you think about where we are at the very beginning stages. All of this is taken into account to our enthusiasm and then maybe on the first question that you had early look we're not going to comment on competitive data.
Mardi Dier: I think your other question was on Part D. I mean, look, you know, Mardi, I think, covered it a little bit in some of the opening remarks. But, Mardi, do you want to make any comments? Yeah, I'll just say specifically about that Part D with how it impacts growth to net. Remember, Medicare patients are about a third of our business.
Speaker Change: But what we do believe.
Speaker Change: We're very confident in our data we think that the release of this morning gives us further confidence as I've said in Maestro Nash outcomes, the $6 seven kilo Pascal reduction that really is meaningful.
Mardi Dier: And Part D, we've always said that there will be some impact going into 2025 with the redesign. That's absolutely true. But we also had, in 2024, we were paying Medicare rebates.
Speaker Change: Michael team everyone's really excited.
Mardi Dier: really show the impact is a little more incremental in 2025 versus a significant step up. So I think the good news with our growth to net, particularly in 2025, is everything's
Speaker Change: That we've spoken to in the community as well that's a number that really gets people's attention and we think that translates.
Speaker Change: Into a real meaningful effect for patients and as we said.
Mardi Dier: going as expected, right? So we see a little bit of increase in our co-pay assist is as expected and included in our expectations for net revenue for the year.
Speaker Change: Ours is an outcome study.
Speaker Change: We have followed the FDA guidance and believe that we've designed the right study for approval alright. Thanks Amy.
Speaker Change: Yeah, I mean, our excitement and belief in this product and just also where you think about where we are, we're at the very beginning stages, all of this is taken into account to our enthusiasm. And then, you know, maybe on the first question that you had, Ali, look, we're not going to comment on competitive data, but what we do believe
Speaker Change: Next question Marvin.
Speaker Change: Thank you Mohammed for next question.
Speaker Change: Our next question comes from the line of Lisa <unk> of Evercore ISI. Your line is now open.
Speaker Change: Hi, Thanks for taking my question just two quick ones from me first.
Speaker Change: The killer Pascal change and the changes you talked about today.
Speaker Change: We're very confident in our data. We think that the release of this this morning gives us further confidence, as I said, in Meister Nash outcomes. You know, the 6.7 kilopascal reduction, that really is meaningful. You know, Michael, a team, everyone's really excited, and people that we've spoken to in the community as well. That's a number that really gets people's attention, and we think that translates.
Speaker Change: Could you put that in context of any change in sort of asked for two or three.
Speaker Change: Changes in fibrosis score and then also just wanted to.
Speaker Change: Touch upon some of Glu tide coming to market in Nash and Nash story, and how you think about your.
Speaker Change: Our positioning there in particular with respect to the the pricing differential and how you might handle that thank you.
Speaker Change: into a real meaningful effect for patients. And, you know, as we said, you know, ours is an outcome study. We have followed FDA guidance and believe that we've designed the right study for approval.
Speaker Change: Yes. Thank you for the questions Lisa maybe I'll start off and then ill pass it over to Michael with your first question, but as it relates to some I think look we've been really clear.
Thanks, Amy. Next question, Marvin.
Thank you, one moment, for our next question.
Speaker Change: First of all.
Speaker Change: Or at the very beginning of this market evolution right less than 4% penetration.
Speaker Change: Our next question comes from the line of Lisa Bacow of Evercore ISI. Your line is now open.
Speaker Change: No.
Lisa Bacow: Hi, thanks for taking the question. Just two quick ones for me. First, the kilopascal change and the changes you talked about today,
Speaker Change: We've got many years of growth ahead.
Speaker Change: Then look at the profile of our product we've got a great profile.
Lisa Bacow: Could you put that in context of any change in sort of F4 to F3?
Speaker Change: Look towards the future I don't see any product with the profile of that actually is as good as ours.
changes in fibrosis score.
Speaker Change: Semi <unk>.
Lisa Bacow: And then also just wanted to touch upon semi-glutide coming to market in NASH and NASH story and how you think about your positioning there in particular with respect to the pricing differential and how you might handle that. Thank you.
Speaker Change: Assuming they come to the market. We're planning for that we would assume that is kind of maybe as early as late Q3 beginning of Q4.
Speaker Change: Yes, that's a very different profile a product remember the problem. We're trying to solve here you've got patients that are one to two steps away from cirrhosis.
Speaker Change: Yeah, thank you for the questions Lisa, you know, maybe I'll start off and then I'll pass it over to Michael with your first question But as it relates to some I think look we've been really clear, you know, first of all We're at the very beginning of this market evolution, right? Less than 4% penetration
Speaker Change: And what they can't.
Speaker Change: Afford is time and by that I mean, if youre waiting months to dose titrate and then have a high discontinuation rate you have to be on a drug for it the work and the one thing that we do know is that with our liver directed therapy, it's easy to take it works fast and the results were.
Thank you. Thank you.
Speaker Change: We've got many years of growth ahead. You then look at the profile of our product. We've got a great profile. As I look towards the future, I don't see any product with a profile that actually is as good as ours.
Speaker Change: We're seeing in the real world are extremely promising so what we believe is that actually assuming some it does get approved it's actually going to drive additional.
Speaker Change: Market growth.
Speaker Change: Sema, assuming they come to the market, we're planning for that. We would assume that it's kind of, you know, maybe as early as late Q3, beginning of Q4. You know, that's a very different profile of product. Remember, the problem we're trying to solve here, you've got patients that are one to two steps away from cirrhosis.
Speaker Change: It's something that ultimately is the leader in the space, we're going to benefit from.
Speaker Change: I kind of final point. This is a specialty market that can support multiple products being in it. It then comes down to things like profile, which we have a great profile order of entry where first and have built this market. So we feel extremely extremely confident in our ability to grow.
and what they can't...
Afford
It's time.
Michael Charlton: Through any of the potential competitive entrants so maybe Michael why don't I turn it over to you for the first part of the question.
Speaker Change: And by that, I mean, you know, if you're waiting months to dose titrate and then have a high discontinuation rate, now you have to be on a drug for it to work. And the one thing that we do know is that with our liver-directed therapy, it's easy to take, it works fast.
Michael Charlton: Great question, the literature supports that when compared to baseline change in liver stiffness and reduction in liver stiffness of five kilo pascal's or 25% and a comparable population compensated cirrhosis is highly predictive for a reduction in fibrosis, one stage or more so that's how we look at these days.
Speaker Change: and the results that we're seeing in the real world are extremely promising.
What we believe is that actually...
Speaker Change: Assuming SEMA does get approved, it's actually going to drive additional market growth, which is something that ultimately, as the leader in the space, we're going to benefit from.
Michael Charlton: Over 50% of our patients achieved 25% reduction threshold.
Beth: Great. Thanks, Thank you Beth.
Speaker Change: But a kind of final point, this is a specialty market that can support multiple products being in it.
Speaker Change: Marvin next question please.
Beth: Thank you Omar for next question.
It then comes down to things like profile.
Speaker Change: Our next question comes from the line of David Laboy of Citi. Your line is now open.
which we have a great profile.
Speaker Change: order of entry, we're first, and have built this market so we feel extremely, extremely confident in our ability to grow through any of the potential competitive entrants.
David Laboy: Thank you very much for taking my question.
Beth: On the.
David Laboy: The emergence of <unk> once they actually get approved.
Beth: And they can officially getting reimbursed for <unk>.
Michael Charlton: So maybe, Michael, why don't I turn it over to you for the first part of the question. Yeah, it's a great question. The literature supports that when compared to baseline, a change in liver stiffness, a reduction in liver stiffness of 5 kilopascals, or 25% in a comparable population, compensated cirrhosis,
Speaker Change: How do you think that impacts usage.
Beth: Vis vis.
Beth: It is different in terms of combination do you think it makes it easier discussion with payers or do you think it makes it harder discussion.
Beth: Thanks, David look looking at the data and now we've reported this before that about 25% of those different patients are already on a <unk> and when you look at who's already been exposed it's about 50% so.
Michael Charlton: is highly predictive for a reduction in fibrosis of one stage or more. So that's how we would look at these stages. We had about over 50% of our patients achieve that 25% reduction threshold.
Great. Thanks. Thank you, Beth.
Beth: They're already there being used for the Comorbidities and look at the company.
Marvin, next question please.
Thank you. One moment for our next question.
Beth: We are supportive of GOP ones being used in.
Speaker Change: Our next question comes from the line of David Lebois of Citi. The line is now open.
Beth: Comorbidities that can benefit patients such as <unk>.
Thank you very much for taking my question.
Beth: Obesity.
Speaker Change: On the emergence of GLP-1s, once they actually get approved and they can officially get reimbursed for MASH, how do you think that impacts
Beth: So they're already there that's the thing and they've been there for 14 years now we know that at the lower doses. They clearly haven't had an impact on Nash because we're still seeing.
Speaker Change: usage vis-a-vis res diffra in terms of combination? Do you think it makes it an easier discussion with payers or do you think it makes it a harder discussion?
Beth: Hi, diagnosis rates and so forth so that they haven't they can only solve it at the highest doses.
Beth: And we know that that takes time and that there are.
Speaker Change: Oh, thanks David. You know, look, looking at the data now, we've reported this before, that about 25% of res different patients are already on a GLP-1 and when you look at who's already been exposed, it's about 50%.
Beth: Challenges with Tolerability. So we really as we think about the GOP ones coming in.
Beth: It's going to be a market expansion focus that theyre going to have.
Beth: And we believe that given their profile on our profile those patients are going to ultimately the majority of them anyways are going to end up on a red differ anyways, because they are going to still need to.
Speaker Change: So, you know, they're already there being used for the comorbidities. And look, as a company,
Speaker Change: You know, we are supportive of GLP-1s being used in comorbidities that can benefit patients such as obesity. You know,
Beth: Treat the problem that they're having which is now a really severe liver disease right. This is this is not.
Beth: A mild disease, we hear from patients all the time their stories are family members that have died as a result, and how grateful they are to have an opportunity to avoid that so we just we.
Speaker Change: So, they're already there, that's the thing, and they've been there for 14 years. Now, we know that at the lower doses, they clearly haven't had an impact on NASH because we're still seeing high diagnosis rates and so forth. So, they can only solve it at the highest doses.
Beth: We are fully planning on <unk> being here.
Beth: Expect that with our profile, we continue to be the product of choice in this space and as it relates to I think you alluded to from a kind of even payer dynamic perspective.
Speaker Change: And we know that that takes time and that there are challenges with tolerability. So, you know, we really, as we think about the GLP-1s coming in,
Beth: Sure.
Beth: We with our profile and with the.
Speaker Change: it's going to be a market expansion focus that they're going to have and we believe that given their profile and our profile, those patients are going to ultimately, the majority of them anyways, are going to end up on a Red Differ anyways because they're going to still need to
Beth: The.
Beth: Benefit that we've shown to preventing down stream costs, we think that we have an attractive profile. We've had an extremely productive conversations with payers and we believe that will remain the case with or without the introduction of <unk>.
Beth: Thank you very much.
Speaker Change: treat the problem that they're having, which is now a really severe liver disease.
Speaker Change: Marvin next question please.
Beth: Thank you one moment for our next question.
right this is this is not
Speaker Change: a mild disease. We hear from patients all the time their stories of family members that have died as a result.
Speaker Change: Our next question comes from the line of Andy Chien of Wolfe Research. Your line is now open.
Speaker Change: and how grateful they are to have an opportunity to avoid that. So, you know, we are fully planning on GLP-1s being here. We expect that with our profile, we continue to be the product of choice in the space. And as it relates to, I think you alluded to from an even payer dynamic perspective.
Andy Chien: Hey, Thank you for taking the question and congrats on the new data just curious if you can talk about the Europe launch in the second half. So I believe the European regulators that may be less receptive to your U S pricing can you talk about the unique <unk>.
Andy Chien: <unk> and opportunities there have been crafted a strategy to win there and that geography, just curious if you could share some color there. Thank you.
Hey
Speaker Change: We, with our profile and with the benefit that we've shown to preventing downstream costs, we think that we have an attractive profile. We've had extremely productive conversations with payers, and we believe that will remain the case with or without the introduction of GLP-1s.
Andy Chien: Yeah. Thanks, Andy I mean look again remember as we think about Europe is not Europe overall, it's going to be a country by country review and we will be extremely disciplined and we have a.
Andy Chien: <unk> of within two to three years to be positive contribution in any country that we launch and obviously a key piece of that is going to be the pricing. We think from an ERP perspective, there are patients there the unmet need is there and that tends to.
Thank you very much.
Marvin, next question please.
Thank you. One moment for our next question.
Speaker Change: Our next question comes from the line of Andy Chen of Wolf Research. Your line is now open.
Andy Chien: Europe overall kind of approximate.
Andy Chien: U S patient numbers now.
Andy Chen: Hey, thank you for taking the question and congrats on the new data.
Andy Chien: It's on a the regulators arent, obviously involved in the pricing discussion as you go country by country talk to Hca's et cetera, one of the things that I have.
Andy Chen: I'm just curious if you can talk about the Europe launch in the second half. So I believe the European regulators, they may be less receptive to your U.S. pricing. Can you talk about the unique challenges and opportunities there? Have you crafted a strategy to win there in that geography? Just curious if you could share some color there. Thank you.
Andy Chien: Bound in previous launches is that if you have an innovative product that provides value that there is a recognition of that value in Europe.
Andy Chien: Clearly, we will be having discussions with each of the countries and be making our.
Speaker Change: Yeah, thanks, Andy. I mean, look, Amanda, remember, as we think about Europe, it's not Europe overall. It's going to be a country-by-country review, and we will be extremely disciplined, and we have an objective of, within two to three years, to be a positive contribution in any country that we launch in. Obviously, a key piece of that is going to be the pricing. We think from an EPI perspective, there are patients there, the unmet need is there, and
Andy Chien: Argument as to the value of the product. Fortunately, we have really great data and we think that we will ultimately be able to support favorable pricing within Europe. However, as I said, we will be making decisions on a country by country basis.
Andy Chien: And we will pursue the countries, where we believe the value of grids differ is recognized.
Andy Chien: Thanks, Andy.
Europe overall kind of approximate U.S. patient numbers.
Speaker Change: Marvin next question please.
Andy Chien: Thank you for our next question.
Speaker Change: Now, the regulators aren't obviously involved in the pricing discussion as you go country by country, talk to HTAs, etc. One of the things that I have found in previous launches is that if you have an innovative product that provides value, that there is a recognition of that value in Europe.
Andy Chien: Our next question comes from the line of Ritu <unk> of TD Cowen. Your line is now open.
Ritu: Good morning, guys. Thanks for taking the question.
Speaker Change: Just following up on that Bill can you talk a little more to the health technology assessment.
Ritu:
Speaker Change: Clearly, we will be having discussions with each of the countries and be making our argument as to the value of the product. Fortunately, we have really great data, and we think that we will ultimately be able to support favorable pricing within Europe. However, as I said,
Ritu: Algorithms that you are preparing to face what what parts of the dataset that you've generated so far.
Speaker Change: Drive value.
Ritu: At the National plans.
Ritu: Either in writing or meetings indicated they are willing to pay for and then just a quick follow up on the safety of the F. Four open label data set that you presented today.
Speaker Change: We will be making decisions on a country-by-country basis, and we will pursue the countries where we believe the value of Reds Differ is recognized.
Ritu: Given even with compensated patients here more fragile kols focus has been on things like.
Good. Thanks, Andy.
Ritu: Hyperglycemia and suburban it's can you give us the outlines of safety.
Marvin, next question please.
Thank you. One moment for our next question.
Speaker Change: Yes so.
Speaker Change: First of all with the discussions in Europe with DHA is I mean look as you know there is very.
Speaker Change: Our next question comes from a line of Ritu Bhara of TD Cowen. Your line is now open.
Speaker Change: Very formal.
Ritu Bhara: Good morning guys, thanks for taking the question. Just following up on that Bill, can you talk a little more to the health technology assessment algorithms that you are preparing to face, you know, what parts of the data set that you've generated so far?
Speaker Change: Process that you go through and each of the countries.
Speaker Change: You.
Speaker Change: Prepare your value dossier.
Speaker Change: And we're at various stages of that depending on the country.
Speaker Change: But again.
Speaker Change: Lot of this a lot of the evaluation looks at are you offsetting downstream costs et cetera, I mean, I take you back to our ISR analysis, which showed.
drive value.
at the National Plans.
Ritu Bhara: have, either in writing or in meetings, indicated they're willing to pay for. And then just a quick follow-up on the safety of the F4 open label data set that you presented today.
Speaker Change: Or is there going to be a very cost effective therapy.
Speaker Change: Again, they use slightly different tools in each country, but we will be.
Speaker Change: Part of that process, and we feel that the merits the severity of the disease and the merits of the product really do stand on their on their own and we're looking forward to I think productive discussions that we'll have with each of those entities.
Speaker Change: just given, you know, even with compensated patients, they're more fragile. KOL focus has been on things like, you know, hypoglycemia and liver events. Can you give us the outlines of safety?
Michael Charlton: Maybe Michael do you want to comment briefly on the second question is important question. So the same study of course included patients with other arms that had.
Speaker Change: Yeah. So, first of all, with discussions in Europe with the DHTA, I mean, look, as you know, there's a very formal process that you go through in each of the countries. You know, you prepare your value dossier, and, you know, we're at various stages of that, depending on the country. But again, you know, a lot of this, a lot of the evaluation looks at
Speaker Change: Lower degrees of fibrosis and the.
Michael Charlton: Hey.
Michael Charlton: Type and frequency was comparable between patients without foresee non cirrhotic disease. It's a good question.
Speaker Change: Thanks Ritu.
Marvin: Next question please Marvin.
Speaker Change: Thank you Mohammed for next question.
Speaker Change: ICER analysis, which showed Red Zephyr to be a very cost-effective therapy.
Speaker Change: Our next question comes from the line of <unk> of Cantor Fitzgerald. Your line is now open.
So again, they use slightly different tools in each country
Speaker Change: Hi, good morning, and thank you so much.
Speaker Change: My questions. So maybe.
Speaker Change: a part of that process. And we feel that the merit, the severity of the disease and the merits of the product really do stand on their own. And, you know, we're looking forward to, I think, productive discussions that we'll have with each of those entities.
Speaker Change: You'd previously talked about <unk> being a little bit slower to adopt.
But maybe if you can talk about the latest trends what youre seeing in terms of the Gis versus methodologies.
Speaker Change: For instance from thank you great. Thanks.
Speaker Change: Thanks for the thanks for the question.
Michael Charlton: Maybe, Michael, do you want to comment briefly on the second question? Yeah, it's an important question. So the same study, of course, included patients in other arms that had the lower degrees of fibrosis and the AE, the type and frequency was comparable between patients with F4C and non-cirrhotic disease. It's a good question. Good. Thank you.
Speaker Change: <unk>.
Speaker Change: The.
Speaker Change: We're predominantly focused on hepatology and gastroenterology. So if you just look at the numbers.
Speaker Change: Of the.
Speaker Change: Those specialists, there's less than 1000 herpetologist. So when when you start talking about targeting 14000 prescribers.
Speaker Change: The overwhelming majority of Gastroenterologists. So on the backs of the Gastroenterologists, we've really seen this really strong performance to date. So when we talked about them coming on a little bit slower it was a little bit more of the time that it takes to kind of why or their practice.
Next question, please, Marvin.
Thank you. One moment for our next question.
Speaker Change: Our next question comes from the line of Parker Agarwal of Cancer Physiotherapy. Your line is now open.
Parker Agarwal: Hi, good morning, and thank you so much for taking my questions. So maybe, Bill, you previously talked about GI dogs being a little bit slower to adopt, but maybe if you can talk about the latest trends there, what you're seeing in terms of the GIs versus hepatologists for recipro. Thank you.
Speaker Change: It is not a disease that they had been treating so they had to hire staff in some cases, if they wanted access to nics and wanted to have their own. It internally. So that it's just those mechanics to create the pathway within their practice, but they when they come on they come on and by that I mean.
Speaker Change: Thank you. Great. Thanks for the question. Look, we're predominantly focused on hepatologists and gastroenterologists. If you just look at the numbers of those specialists, there's less than 1,000 hepatologists.
Speaker Change: The gastroenterologists.
Speaker Change: <unk> been extremely extremely happy with the way that they have adopted the product and as I said just based upon the numbers. They are really the driving force of the performance that we have seen and we will likely see in the future clearly the herpetologist are I would say.
Speaker Change: So, when we start talking about targeting 14,000 prescribers, you know, the overwhelming majority are gastroenterologists.
Speaker Change: And remain further ahead in most cases, just because the liver is what they are most familiar with they're more familiar with the disease and their practices are probably initially a little better suited but really happy with what we've seen we've seen some of the big Super groups come on and.
Speaker Change: So, on the backs of the gastroenterologists, we've really seen this really strong performance to date.
Speaker Change: So when we talked about them coming on a little bit slower, it was a little bit more of the time that it takes to kind of wire their practice.
Speaker Change: It's not a disease that they had been treating, so they had to hire staff in some cases if they wanted access to NITs and wanted to have their own NIT internally. So it's just those mechanics to create the pathway within their practice.
Speaker Change: And we've seen them go from.
Speaker Change: I would call more or less dabbling two full on.
Speaker Change: Nash treatment and literally treating hundreds and hundreds of patients with many more to come so we're feeling that the.
Speaker Change: Elution of the prescriber base is in a really great place and I would say that the breadth of prescription that we're seeing in this launch is a true standout and something which is a great prognosticator for future uptake of the product unique prescribers you need patients and we have both of those.
but when they come on, they come on.
Speaker Change: And by that I mean, the gastroenterologists, I've been extremely, extremely happy with the way that they have adopted the product, and as I said, just based upon the numbers, they are really the driving force of the performance that we have seen and will likely see in the future.
Speaker Change: Okay. Thanks broker.
Speaker Change: Marvin It looks like we've got time for one more question. Please.
are, I would say...
Speaker Change: Thank you one moment our next question.
Speaker Change: and remain further ahead in most cases just because, you know, the liver is what they are most familiar with. They're more familiar with the disease and their practices are probably initially a little better suited, but I'm really happy with what we've seen. We've seen some of the big super groups come on and we've seen them go from, you know, I would call more or less dabbling to full-on NASH treatment and, you know, literally treating hundreds and hundreds of patients with many more to come.
Speaker Change: Our next question comes from the line of Catherine a pony of citizens. Your line is now open.
Speaker Change: Hi, Katherine on for John.
Speaker Change: Quick question about dose adjustment in the open label two year open label extension, where did all patients 50 milligram dose and also just as far as patient retention, how many patients how many swatek started the study how many continued through the two year time point. Thank you.
Speaker Change: So, you know, we're feeling that the evolution of the prescriber base is in a really great place. And I would say that the breadth of prescription that we're seeing in this launch
Speaker Change: Okay great.
Speaker Change: Maybe I'll turn this one over to you for those specific 122 patients entered the second year.
Speaker Change: is a true standout and something which is a great prognosticator for future uptake of the product. You need prescribers, you need patients, and we have both of those.
Speaker Change: The open label extension.
Speaker Change: State or from 101 that had a second PCT.
Speaker Change: Thank you.
Marvin: Good. Thanks, Prakhar. Marvin, it looks like we've got time for one more question, please.
Speaker Change: And then just one.
Speaker Change: Yes, yes.
Speaker Change: Yes, everybody.
Speaker Change: Great. Okay. Thanks, Katherine 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 approximately two hours. Thanks for joining.
Thank you. One moment for our next question.
Speaker Change: Our next question comes from line of Catherine O'Coney of Citizens Alliance Now Open.
Speaker Change: Yeah.
Speaker Change: Ladies and gentlemen, thank you for your participation in today's conference you May now disconnect have a wonderful day.
Catherine O'Coney: Hi, this is Catherine, Anika, John. I just have a quick question about dose adjustment in the open label, two-year open label extension. Will do all patients stay at the 80 milligram dose and also just as far as patient retention dose, how many patients, how many sterotics started the study and how many continued through the two-year time point? Thank you.
Michael Charlton: Okay, great. Michael, maybe I'll turn this one over to you for those specifics. 122 patients entered the second year of the Open Label Extension and these data are from 101 that had a second BCT.
Thank you.
Thank you for joining.
Michael Charlton: 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 approximately two hours. So thanks for joining.
Michael Charlton: Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.
OK, are you ready?
Thank you for watching!
Speaker Change: A film by A film by A film by A film by A film by A film by A film by A film by A film by A film by
Part 2
I'm I'm I'm I'm I'm I'm I'm I'm I'm
[music]
Thank you very much.
Speaker Change: This video footage was made between 2020 and March 18, 2001 from VA parking lot.
Sibold, Mardi Dier, Tina Ventura
Speaker Change: [music].
Speaker Change: Good day, and thank you for standing by.
Speaker Change: Two magical pharmaceuticals fourth quarter and full year 2024 earnings conference call.
Speaker Change: At this time, all participants are a listen only mode.
Speaker Change: After the Speakers' presentation, there'll be a question and answer session.
Speaker Change: Today's conference call is being recorded I would now like.
Speaker Change: To introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.
Speaker Change: Thank you Marvin.
Speaker Change: Everyone and thank you for joining us to discuss madrigals fourth quarter and full year 2024 earnings. We're also sharing this morning, new two year data from the active treatment open label compensated mash cirrhosis or at four C arm.
Speaker Change: The phase III Maestro Napoli trial, we issued a press release this morning and have a slide deck that accompanies this webcast, which were posted on the Investor Relations section of our website right after the call.
On the call with me today is built the boat Chief Executive Officer, and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, and then we'll take your questions. Dr. Michael Charlton our head of clinical development will join us for the Q&A portion of the call. Dr. Charlton has more than 30 years of experience in mass as a leading herpetologist out of the Mayo Quinn.
Speaker Change: I kept pathology group and a treating physician.
Speaker Change: We plan to keep today's call to about 45 minutes.
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 and with that I will now turn the call over to Bill on slide three well. Thanks, Dana good morning, and thanks for joining today I'll provide an update on the Cigna.
Speaker Change: <unk> momentum we're building with the U S launch of <unk>. We ended 2024 strong and we're pleased with how we've started the year in 2025.
Tina Ventura: I'll also share an update on new two year data from an open label study for <unk> patients as Tina mentioned the results are very promising and support Reds different potential to benefit this high risk patient population if approved.
Tina Ventura: But before we look ahead I want to take a moment to reflect on 2024, a year of remarkable transformation and achievement for the company.
Speaker Change: I've been in the industry, a long time and I've launched a lot of successful medicines I'll be the first to attest to the tremendous amount of work required for any successful launch let alone a first in disease therapy.
Speaker Change: And the launch of breath differ is no exception, we work to meet or exceed our high expectations last year and started to lay the foundation for rent deferral to potentially become a blockbuster therapy I'm incredibly.
Speaker Change: Billy proud of our team's accomplishments highlighted on slide four these are the things that we said that we would do and we did.
Speaker Change: We built a world class team to drive the launch of rent deferral and support madrigals long term aspirations are groundbreaking or at a different phase III trial data were published in the New England Journal of Medicine.
Speaker Change: March 14th we achieved a milestone for the match field the landmark approval of rates differ the first ever treatment approved for this disease.
Speaker Change: This achievement was further validated by two top tier liver societies in Europe, and the U S. Both updating their guidelines to include brands differ as first line therapy for match.
Speaker Change: And we made significant progress expanding red differs reach both geographically and clinically submitting reds different for approval in Europe, and completing enrollment in our maestro Nash outcomes trial.
Speaker Change: Importantly, these accomplishments are translating into thousands of patients now benefiting from rates differ and building a strong foundation for <unk> future as the leader in mass.
Speaker Change: Let's move to the U S res differ launch update on slide five.
Speaker Change: Yeah.
Speaker Change: As we detailed in our earnings release this morning, and first previewed at Jpmorgan in January we generated $103 million in net sales in the fourth quarter of 2024, reflecting 66% quarter over quarter growth.
Speaker Change: This was another strong demand quarter with inventory well within our expected two to four week range for the full year 2024, we generated $180 million in net sales a remarkable achievement considering we launched in April and these figures represent just three quarters of performance.
Speaker Change: Our launch trajectory continues to track in line with some of the most successful specialty medicine launches in the past decade.
Speaker Change: This confirms the urgent need rich, Jeff Brad is addressing in the mass community, it's excellent product profile and the exceptional execution of our team.
Speaker Change: These strong financial results are driven by the key performance indicators critical to any successful drug launch patients on therapy prescribers and access.
Speaker Change: In the third quarter of 2024 on our parametric we reached a key milestone one quarter ahead of schedule, achieving greater than 80% commercial coverage for <unk> is different since then we've continued to make great progress on the other two launch metrics.
Speaker Change: First on patients as noted on slide six we ended the fourth quarter with more than 11800 patients on res differ an incredible accomplishment in just nine months crossing the 10000 patient threshold is a significant milestone and we continued to steadily add patients at a rate that's consistent with other top.
Speaker Change: Peer specialty medicine launches importantly, this figure represents patients actively on therapy, meaning it accounts for any discontinuation, making it the most rigorous and meaningful metric to track sustained treatment adoption.
Speaker Change: Yes, we're still in the early days, we have penetrated only a fraction of the market with Reds defer less than 4% of the 315000 diagnosed patients with F. Two F three match.
Speaker Change: We remain focused on the 315000 diagnosed patients which represents a highly attractive specialty market.
Speaker Change: Looking ahead. The stated efforts of the next dendron are focused on expanding the market to many multiples of 315000, we believe that the strength of brands differs profile positions. It for leadership in either scenario, creating multiple paths to success for us different in the years ahead.
Speaker Change: Our ability to steadily add red's different patients quarter over quarter is directly tied to increased penetration of our prescriber base.
Speaker Change: From day, one we've talked about wiring the system, how we have been laying the foundation to support the patient volume we expect in the years ahead, and we are seeing real progress as we've engaged providers driven.
Speaker Change: <unk> change in clinical practice and helped build the infrastructure necessary for sustained prescription growth.
Speaker Change: On slide seven the bar graph on the left illustrates this progress as a reminder, our field team is focused on a total of 14000 target prescribers, primarily hepatology and gastroenterology us with a concentrated effort on the top 6000 prescribers in the fourth quarter, approximately 60% of our top six.
Speaker Change: <unk> thousand targets prescribed grids differ up from 40% in the third quarter, we are steadily adding new prescribers and we are seeing increased depth of prescribing from current writers both metrics are tracking exceptionally well with other successful blockbuster launches as.
Speaker Change: As expected our top target prescribers have driven more than 75% of our prescriptions.
Speaker Change: Just as we've successfully driven adoption among our top target prescribers, we plan to continue shaping clinical practice and expanding access across our full prescriber base as we build roads different towards the peak sales potential.
Speaker Change: We're already making meaningful progress by year end, approximately 40% of the 14000 had prescribed reds differ reflecting a strong and growing foundation of support.
Speaker Change: Whereas differs broad based uptick is being driven by its attractive profile. It's a liver directed therapy that halts or improved liver stiffness are proxy for liver fibrosis in 91% of patients out to three years. It's also once daily well tolerated pill with simple dosing and with the chronic and Sir.
Speaker Change: <unk>.
Speaker Change: Liver disease like mash. This favorable profile supports long term adherence with early data continuing to indicate persistency rates comparable to other well tolerated oral therapies.
Speaker Change: We're also hearing overwhelmingly positive feedback on <unk> differ from both physicians and patients. They continue to highlight the benefits of the medicine, including improvements in liver function tests and lipid levels reduced fatigue increased physical activity and improvement in fibrosis and these real world outcomes really.
Speaker Change: We recently heard from one whereas different patient diagnosed with that to mash. She said quote living with <unk> felt like having a time bomb in my body, whereas deferred gave me hope and my life back end quote.
Speaker Change: Our goal is to be the leader and mash and help patients for many years to come as noted on slide nine our long term strategy builds on the success of <unk> U S launch.
Speaker Change: First we are expanding geographically and remain on track for a midyear regulatory decision for is different in Europe.
Speaker Change: Sumit a positive outcome, we plan to take a targeted country by country approach to commercialization beginning with Germany in the second half of the year.
Speaker Change: Beyond Europe, we are also assessing opportunities to bring whereas different to patients in additional attractive geographies.
Speaker Change: Second we're advancing risks differ for patients with compensated mash cirrhosis.
Speaker Change: Approval and FRC would represent a major step forward for the mass field and for patients significantly expanding the treatment landscape and effectively doubling risk diverse market opportunity.
Speaker Change: I will spend some more time on the data we shared this morning in a moment.
Speaker Change: And third we are committed to building a strong pipeline beyond <unk>. We are in the enviable position of providing a highly meaningful medicine to the mash community today and we are now focused on building the right pipeline behind it we are evaluating assets at different stages of development across multiple mechanisms of action all with the goal of strengthening and extending our.
Speaker Change: Our leadership position to mash.
Speaker Change: Moving to slide 10, and the unmet need and compensated mash cirrhosis, it's a chronic progressive liver disease characterized by significant liver damage loss of liver function liver cancer and death.
Speaker Change: Substantial portion of compensated mash cirrhosis patients also suffer from portal hypertension, which often leads to life threatening complications such as hepatic encephalopathy ascites and various field bleeding.
Speaker Change: While patients with F. Two F. Three fibrosis face a 10% to 17 times higher risk of liver related mortality.
Speaker Change: Four patients are at a staggering 42 times increased risk.
Speaker Change: And this very sick F. Four patient population preventing progression to adverse clinical outcomes is the central treatment goal.
Speaker Change: This is reflected in FDA guidance, which recommends that clinical trials and compensated mash cirrhosis use outcomes as an endpoint as opposed to biopsy based surrogate endpoints. This guidance along with data from our open label FRC cohort informed the design of our ongoing Maestro Nash outcomes trial.
Speaker Change: We believe that red different liver directed mechanism of action should deliver a benefit not only in F. Two F. Three matched patients, but in FRC mass patients as well.
Speaker Change: Therefore as shown on slide 11, we included a separate open label active treatment arm of patients with compensated mash cirrhosis and our maestro Napoli one trial to begin evaluating <unk> safety and efficacy and FRC.
Speaker Change: As a reminder, maestro Napoli one was a double blind randomized placebo controlled phase III safety trial to support regulatory approval.
Speaker Change: We previously presented positive one year data from the <unk> cohort of this trial and are highlighting new two year V. Cte data and 101 patients on slide 12.
Speaker Change: DCT or by basically the vibration control of Trans again, Elastography is a widely used noninvasive tests conducted with a fiber scan that measures liver stiffness as a proxy for fibrosis.
Speaker Change: It's also a strong predictor of clinical outcomes.
Speaker Change: The two year results show that patients achieved a mean six seven kpa or kilo Pascal reduction in liver stiffness at two years, which represents the largest mean kpa reduction reported in enough foresee matched patient population to date.
Speaker Change: While this was a single arm open label trial. This reduction was highly statistically significant versus baseline.
Speaker Change: <unk> used the Beano rule of five kpa to stratify risk of liver related events in patients with Nash. So a $6 seven reduction suggest that many patients are moving into a lower risk category.
Speaker Change: 51% of patients achieved a 25% or greater decrease in liver stiffness as measured IV Cte.
Speaker Change: This level of reduction in liver stiffness has been associated with reduced progression to end stage liver disease moving patients further away from the risks of cirrhosis and its complications.
Speaker Change: And read a different safety profile was consistent with other reg different clinical trials with a low rate of discontinuation due to adverse events.
Speaker Change: We look forward to sharing more details from this two year cohort at a future medical meeting.
Speaker Change: These data add to the growing body of evidence supporting <unk> potential benefit in this high risk patient population and support continued confidence in our fully enrolled cirrhosis outcomes trial.
Speaker Change: As noted on slide 13, Maestro Nash outcomes as a large phase III double blind placebo controlled trial evaluating progression to liver decompensation events and 845 patients with compensated Nash cirrhosis.
Speaker Change: We expect to announce data from this trial in 2027.
Speaker Change: So looking ahead to the opportunity and FRC and assuming today's results translate to maestro Nash outcomes and Reds differ obtained regulatory approval. We believe brad's differ is and will be the leading therapy in F. Two F foresee period.
Speaker Change: Before I hand, it over to Marty Let me briefly summarize our progress on slide 14.
Speaker Change: 24 was a transformational year for Madrigal, we secured FDA approval for our Red Zebra and are executing on a highly successful launch we see significant runway for growth with less than 4% of the U S target market penetrated and an attractive real world profile Reds differ is well positioned for continued strong.
Speaker Change: Momentum in 2025 and beyond.
Speaker Change: We are preparing for global expansion we.
Speaker Change: We see a significant opportunity and FRC and believe we will be first to market.
Speaker Change: And we continue to build for the future as we actively explore opportunities to expand our pipeline with that I'll turn it over to Marty.
Thank you Bill earlier today, we issued a press release detailing our full financial results I will highlight a few key takeaways for the fourth quarter and full year as noted on slide 15 fourth quarter net sales totaled $103 3 million, bringing full year 2020 for net sales to $181 million.
Speaker Change: An impressive achievement considering this reflects only nine months of commercialization, we delivered another strong demand quarter with inventory well within the expected two to four week range. Our gross to net discount increased in line with what we previously discussed as we said we expect some variability in gross to net early in them.
Speaker Change: Looking ahead to 2025 as expected we anticipate an increase in the gross to net discount compared to 2024 as is typical at this stage of the special specialty medicine. Much importantly, this is already reflected in our expectations for a robust year over year net sales growth in 2025.
Speaker Change: R&D expenses for the fourth quarter and full year at 2024 by $25 $6 million and $236 7 million, respectively, compared to $76 million and $272 4 million in the prior year period R&D expenses decreased by <unk> <unk>.
$35 $6 million in 2024, due primarily to a reduction in clinical trial accruals and the change in accounting for inventory cost following FDA approval of risk Deborah partially offset by an increase in head count looking ahead, we expect a somewhat higher level of R&D spend in 'twenty.
Speaker Change: 25 compared to 2024.
Speaker Change: SG&A expenses for the fourth quarter and full year of 2024 were $141 $2 million and $435 $1 million, respectively, compared to $46 $5 million and $108 1 million in the prior year periods. This year over year increase was <unk>.
Speaker Change: <unk> and reflects the rapid scale up of our U S. Commercial operations. Following following <unk> approval in March 2024, looking ahead, we expect SG&A expenses to increase in 2025 as we continue to invest in the U S launch and our international expansion.
Speaker Change: Turning to our balance sheet, we ended 2024 with $931 $3 million in cash cash equivalents restricted cash and marketable securities with a strong cash position, we are well resource to support the ongoing launch of <unk> in both the U S and our planned launch in Europe, I will now turn the call.
Tina Ventura: Back over to Tina.
Tina Ventura: Thanks, Marty let's move into the Q&A portion of the call. Marvin. Please go ahead and provide instructions for the Q&A session.
Tina Ventura: We will now open the lines for questions to open your line.
Tina Ventura: Please press star one one and youll be added to the queue on the call.
Speaker Change: Our first question comes from the line of Thomas Smith of Leerink Partners. Your line is now open.
Thomas Smith: Hey, guys. Good morning, Thanks for taking the questions and congrats on the strong launch spend.
Speaker Change: New cirrhosis data.
Speaker Change: Just had a question with respect to.
Speaker Change: The ongoing with different launch now that we're roughly two thirds of the way through the quarter. So wondering if you could comment on what you've seen in the first two months of the year in terms of new patient adds or any change in the cadence of patients starting on drug or.
Speaker Change: Anything notable as patients and prescribers kind of worked through their insurance or co pay.
Speaker Change: Adjustments and then historically.
Speaker Change: Given some.
Speaker Change: High level guidance based on the comp.
Speaker Change: Group of specialty drug launches.
Speaker Change: I guess any color that you can provide as we think about Q1, and maybe 2025 broadly thanks so much.
Tom: Tom Thanks for the question.
Speaker Change: Look.
Speaker Change: Just a couple of points first of all you know 2024 was really.
Speaker Change: An incredible year, when you think about.
Going back 12 months from now there wasn't a product on the market for mash and.
Speaker Change: In a very short period of time, we've really done I think a remarkable job of executing and finishing off the year with a $103 million quarter is really.
Speaker Change: Really very impressive by any by any measure you look at as we look at metrics all across the blockbuster launches that you referred to we're tracking extremely well on all fronts. There is no weakness here on any of them.
Speaker Change: We carry that I would say the momentum of 24 into 'twenty five of steadily adding patients and prescribers. So that's we've seen more of that in the first quarter of 'twenty five.
Speaker Change: We also do have like everyone else for Q1 dynamic that is clear.
Speaker Change: Clearly.
Speaker Change: A phenomenon each year.
Speaker Change: And no teams have been well prepared and I think we're managing through that extremely well.
Speaker Change: As I think about what's happening at the prescriber level.
Speaker Change: Each there I would say there isn't a prescriber yet.
Speaker Change: That has.
Speaker Change: Max out or even close to maxing out.
Speaker Change: The patients that exist in their practice or that are being referred into their practice and each practices learning we talk about wiring. The system. That's been a lot of hard work and we've done it on a practice by practice basis and as you can see we continue to add new prescribers and we're now at the 60% penetration into that target group.
Speaker Change: For each of those as they start prescribing theyre doing their wiring. So what we're continuing to do is just bring on.
Speaker Change: Steadily each day each week each month, each quarter prescribers have them get ready to be able to handle the volume of their patients. How they worked through the system et cetera, now from a Q1 dynamic perspective as I said.
Speaker Change: Certainly that's something that we're seeing like any anyone else I think the teams have done a good job.
Speaker Change: Getting ready to manage through that.
Speaker Change: No real other.
Speaker Change: Uh huh.
Speaker Change: Challenges that we've seen with the quarter its pretty standard yes.
Speaker Change: Yes, maybe I'll just add a little bit Tom to answer your question about the analogs. So yes, we do track very closely with our group of 10 specialty launches over the last 10 years.
Speaker Change: It gets a little tricky when you go from our Q4 and Q1, so we're not giving specific guidance in that percentage.
Speaker Change: For Q1, it may not may or may not give that guidance going forward that we're really tracking with these analogs, thus far but I will also say if we just look at consensus as Bill said, we're very pleased with what we're seeing going into 2025 and a little commentary there that we believe consensus for Q1 2025 will narrow.
Speaker Change: And go up a little bit.
Speaker Change:
Speaker Change: As a result of what we've been saying so far.
Tom: Thanks, Tom.
Speaker Change: Next question please.
Speaker Change: Thank you gentlemen for next question.
Speaker Change: Our next question comes from the line of Andrea <unk> of Goldman Sachs. Your line is now open.
Speaker Change: Thanks for taking the question maybe I can ask you here on the cirrhosis data that you shared I was hoping you could speak a little bit more on the clinical meaningfulness of achieving that $6 seven Cal Pascal reduction and I know in the context of your three year data for the <unk> III Nash patient population, we had talked about how V. Cte measure below 10 kilo Pascal.
Speaker Change: <unk> correlated with fewer liver related outcomes I'm, just wondering if that seems threshold stands for that patient population and then finally, just how do you to today's data change how you're thinking about the Nash outcomes trial.
Speaker Change: At all and does that change how you think about the powering of the study. Thanks so much.
Speaker Change: Great. Thanks for the question, Andrew I'll turn it over to Michael in a second but.
Speaker Change: As we think about how does it change our view Mr. Nash outcomes look we've been confident about that study. This is just another piece of information, which gives us I would say greater confidence in it.
Speaker Change: Doing something here, which is really again as we've done with our <unk> three program, we're pioneering the way.
Speaker Change: And we believe that we have designed the right trial for Maestro Nash outcomes.
Speaker Change: This trial that we announced today.
Michael Charlton: Actually helped us helped to inform our thinking on Maestro Nash outcomes in would be really exciting news that we presented today as I said it gives us even more confidence, but maybe Michael do you want to answer the first couple of questions that Andrew had its a great question.
Speaker Change: Activity.
Speaker Change: Decreases in liver stiffness increases with a higher baseline level. So our baseline level is 25 kilo pascal's productivity really starts to pick up at around 15 killer Pascal. So there are six seven kilo pass grow production.
Speaker Change: With the starting point to 25 kilo pascal's it.
Speaker Change: It should be should be highly predictive decreased risk of clinical outcomes.
Speaker Change: Great.
Speaker Change: Thanks Andrea.
Speaker Change: Next question please Martin.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of <unk> Rahimi of Piper Sandler Your line is now open.
Speaker Change: Good morning team.
Speaker Change: And thank you so much for all the great updates.
Speaker Change: Is there.
Speaker Change: Could you comment on as we go into 2025, if youll be in a position to provide guidance.
Speaker Change: I think that part of your commentary was very helpful around that.
Speaker Change: Consensus has gone up.
Speaker Change: Little increase tightened a little bit so just maybe help us understand.
Speaker Change: How youre thinking of.
Speaker Change: And thinking about moving forward, we understand the dynamics of the first quarter, but beyond that at what point will you feel comfortable to kind of share with us what the 2025 or 2026 guidance would look like.
Speaker Change: That would be really helpful I'll jump back in the queue.
Speaker Change: Great Marty let me pass it over to you yeah. Thanks, yes.
Speaker Change: Yes with respect to guidance, we have been very clear, we're not giving guidance right now we consider it internally, but that's not something we're providing at this time, we're just too early in the launch.
I did provide a little commentary on on Q1, 2025, and I think the same commentary goes for the full year 2005, we like what we're seeing that momentum.
Speaker Change: Into 2025, we commented on the robust year over year growth, So where consensus sits for 2025, we expect that to narrow as well and go up a little bit based on what we're seeing.
Speaker Change: Good thanks.
Speaker Change: Yes.
Speaker Change: Marvin next question please.
Speaker Change: Thank you for a moment for our next question.
Speaker Change: Yeah.
Speaker Change: Our next question comes from the line of Ellie Merle of UBS. Your line is now open.
Ellie Murrell: Hey, guys. Thanks for taking the question.
Ellie Murrell: <unk> four data I guess, we're about risks and benefits seen irrespective of the comp.
Ellie Murrell: <unk> at baseline and any color on sort of which patients were more or less likely to shelley's CCTV reductions.
Ellie Murrell: And then just in terms of the study I guess can we expect any further long term datacom.
Ellie Murrell: Like the three year data just curious.
Ellie Murrell: Timing curious as I think the study has been going on.
Ellie Murrell: A few years already yes. Thanks Ali look so more to come. This is just some really top line look at the data.
Ellie Murrell: Upcoming medical meeting, we'll go into a little bit more detail on things I think there is certainly still a lot left that we can learn from this study just with the data that we have at two years.
Michael Charlton: Is there anything else Michael to comment on where we're not we're not giving out any more than the top line that we've given today.
Ellie Murrell: I think the.
Ellie Murrell: Simpson and productivity for these results to clinical outcomes and with.
Ellie Murrell: The decline of 25% based on that study of 10000 patients forward perspective.
Speaker Change: 30% to 40% decreased likelihood of a liberal related clinical events. So that's sort of my takeaways from these results great. Thanks, Alex Thanks Ali Marvin next question. Please.
Speaker Change: Thank you one woman for next question.
Akash Tiwari: Our next question comes from the line of our cash to worry of Jefferies. Your line is now open.
Speaker Change: Hey, this is Amy on your car. Thanks, so much for taking our question.
Speaker Change: Turning off just wanted to get your thoughts on the competitor at key F. 'twenty, one data in cirrhotic Nash and that how that could read across to your S. Four outcome study.
Speaker Change: Also on part D redesign I think our preliminary math is getting to a potential full year net sales impact of around 3% to 5% for rent deferral going forward just wanted to check this number with you and will you do any additional discount ahead of the kind of launch thanks. So much.
Speaker Change: Well Amy Thank you that's a lot of questions again.
Speaker Change: Let me see if we can if we can talk through.
Speaker Change: First of all.
Speaker Change: As we launch the product from a gross to net perspective, we have been extremely extremely.
Speaker Change: Diligent about gross to net.
Speaker Change: We werent contracting as we launch the product and when we launch the product.
Speaker Change: We don't you don't think about launch in a.
Speaker Change: Quarter two were for you think about kind of the years ahead, and we've thought about gross to net.
Speaker Change: Anticipating that there will be additional competition in the marketplace and time additional indications hopefully for us.
Speaker Change: Et cetera, So we take an extremely disciplined approach here now we will react to market dynamics as any company does you always have a dynamic in Q1, which we've talked about as it relates to working with the payers and so forth.
Speaker Change: Constant dynamic there. So we will continue to react to the market.
Speaker Change: These dynamics continue to shift.
Speaker Change: Your other question was on part D. I mean look Marty I think covered it a little bit.
Speaker Change: In some of the opening remarks, but Martin do you want to make any comments, yes, I will just say specifically about the part D and how it impacts gross to net remember Medicare patients or about a third of our business.
Speaker Change: And.
Speaker Change: Part D. We've always said that there will be some impact going into 2025 with the redesign.
Speaker Change: Totally true, but we also had in 2024, we replaced paying Medicare rebates really send the impact is a little more incremental in 2025 versus a significant step up.
Speaker Change: So I think the good news with our gross to net particularly in 2025, it's everything.
Speaker Change: It's going as expected right. So we had seen a little bit of increase in our copay assess is as expected and included in our.
Speaker Change: Our expectations for net revenue for the year.
Speaker Change: Our.
Speaker Change: Statement and belief in this product and just also where do you think about where we are at the very beginning stages of all of this is taken into account to our enthusiasm and then maybe on the first question that you had earlier look we're not going to comment on competitive data.
Speaker Change: But what we do believe.
Speaker Change: We're very confident in our data we think that the release of this this morning gives us further confidence as I've said in Maestro Nash outcomes.
Speaker Change: $6 seven kilo Pascal reduction that really is meaningful.
Speaker Change: <unk> team everyone's really excited.
Speaker Change: People that we've spoken to in the community as well that's a number that really gets people's attention and we think that translates into a real meaningful effect for patients and as we said ours is an outcome study.
Speaker Change: We have followed FDA guidance and believe that we've designed the right study for approval alright. Thanks Amy.
Speaker Change: Question Marvin.
Speaker Change: One woman for next question.
Speaker Change: Okay.
Speaker Change: Our next question comes from the line of Lisa <unk> of Evercore ISI. Your line is now open.
Speaker Change: Hi, Thanks for taking my question just two quick ones from me first.
Speaker Change: The killer Pascal change and the changes you talked about today.
Speaker Change: Could you put that in context of any change in sort of a four to us.
Speaker Change: Three.
Speaker Change: Changes in fibrosis score and then also just wanted to.
Speaker Change: Touch upon some of Glu tide coming to market in Nash and Nash story, and how you think about your.
Our positioning there in particular with respect to the the pricing differential and how you might handle that thank you.
Yes. Thank you for the questions Lisa maybe I'll start off and then ill pass it over to Michael with your FERC question, but as it relates to some I think look we've been really clear.
Speaker Change: First of all.
Speaker Change: At the very beginning of this market evolution right less than 4% penetration.
Speaker Change: No.
Speaker Change: We've got many years of growth ahead.
Speaker Change: Then look at the profile of our product we've got a great profile.
Speaker Change: Look towards the future I don't see any product with the profile that actually is as good as ours.
Speaker Change: Semi <unk>.
Speaker Change: Assuming they come to the market. We're planning for that we would assume that is kind of maybe as early as late Q3 beginning of Q4.
Speaker Change: Yes, that's a very different profile a product remember the problem. We're trying to solve here you've got patients that are one to two steps away from cirrhosis.
Speaker Change: And what they can't.
Speaker Change: Afford is time and by that I mean, if youre waiting months to dose titrate and then have a high discontinuation rate you have to be on a drug for it to work and the one thing that we do know is that with our liver directed therapy, it's easy to take it works fast and the results were.
Speaker Change: Or seeing in the real world are extremely promising so what we believe is that actually assuming some of that does get approved it's actually going to drive additional.
Speaker Change: Market growth.
Speaker Change: It's something that ultimately is the leader in the space, we're going to benefit from.
Speaker Change: I kind of final point. This is a specialty market that can support multiple products being in it. It then comes down to things like profile, which we have a great profile order of entry where first and have built this market. So we feel extremely extremely confident in our ability to grow.
Michael Charlton: Through any of the potential competitive entrants so maybe Michael why don't I turn it over to you for the first part of the question.
Michael Charlton: Great question, the literature supports that when compared to baseline change in liver stiffness and reduction in liver stiffness of five kilo pascal's or 25% and a comparable population compensated cirrhosis is highly predictive for a reduction in fibrosis, one stage or more so that's how we look at these days.
Michael Charlton: Over 50% of our patients achieve that 25% reduction threshold.
Beth: Great. Thanks, Thank you Beth.
Speaker Change: Marvin next question please.
Beth: Thank you Manuel for next question.
Speaker Change: Our next question comes from the line of David Laboy of Citi. Your line is now open.
David Laboy: Thank you very much for taking my question.
Beth: On the.
Beth: The emergence of GOP once once they actually get approved.
Beth: And they can officially getting reimbursed for <unk>.
Beth: How do you think that impacts usage.
Beth: These are the diff.
Beth: Yes.
Beth: In terms of combination do you think it makes it an easier discussion with payers or do you think it makes it harder discussion.
Beth: Oh, Thanks, David look looking at the data and now we've reported this before that about 25% of our is different patients are already on a <unk> and when you look at who's already been exposed it's about 50%.
Beth: So.
They're already there being used for the Comorbidities and look as a company.
Beth: No.
Beth: We are supportive of GOP ones being used in.
Beth: Comorbidities that can benefit patients such as <unk>.
Beth: Obesity.
<unk>.
Beth: So they're already there that's the thing and they've been there for 14 years now we know that at the lower doses. They clearly haven't had an impact on Nash because we're still seeing.
Beth: Hi, diagnosis rates and so forth so that they haven't they can only solve it at the highest doses.
Beth: And we know that that takes time and that there are.
Beth: Challenges with Tolerability. So we really as we think about the GOP ones coming in.
Beth: It is going to be a market expansion focus that theyre going to have.
Beth: And we believe that given their profile on our profile those patients are going to ultimately the majority of them anyways are going to end up on a red differ anyways, because they are going to still need to.
Beth: Treat the problem that they're having which is now a really severe liver disease right. This is this is not.
Beth: A mild disease, we hear from patients all the time their stories are family members that have died as a result, and how grateful they are to have an opportunity to avoid that so we just we.
Beth: We are fully planning on <unk> being here.
Beth: Expect that with our profile, we continue to be the product of choice in this space and as it relates to I think you alluded to from a kind of a even payer dynamic perspective.
Beth: <unk>.
Beth: We with our profile and with the.
Beth: The.
Beth: Benefit that we've shown to preventing down stream costs, we think that we have an attractive profile. We've had an extremely productive conversations with payers and we believe that will remain the case with or without the introduction of <unk>.
Beth: Thank you very much.
Speaker Change: Marvin next question please.
Beth: Thank you one moment for our next question.
Beth: Our next question comes from the line of Andy Chien with Wolfe Research. Your line is now open.
Andy Chien: Hey, Thank you for taking the question and congrats on the new data just curious if you can talk about the Europe launch in the second half. So I believe European regulators that may be less receptive to your U S pricing can you talk about the unique <unk>.
Andy Chien: <unk> and opportunities there have you craft a strategy to win there and that geography, just curious if you could share some color there. Thank you.
Speaker Change: Yeah. Thanks, Andy I mean look again remember as we think about Europe is not Europe overall, it's going to be a country by country review and we will be extremely disciplined and we have a.
Speaker Change: <unk> of within two to three years to be positive contribution in any country that we launch and obviously a key piece of that is going to be the pricing. We think from an abbvie perspective, there are patients there the unmet need is there and that tends to.
Speaker Change: Europe overall kind of approximate.
Speaker Change: U S patient numbers now it's on.
Speaker Change: The regulators arent, obviously involved in the pricing discussion as you go country by country talk to Hca's et cetera, one of the things that I.
Speaker Change: Found in previous launches is that if you have an innovative product that provides value that there is a recognition of that value in Europe.
Speaker Change: We will be having discussions with.
Speaker Change: Each of the countries and be making our.
Speaker Change: Argument as to the value of the product. Fortunately, we have really great data and we think that we will ultimately be able to support favorable pricing within Europe. However, as I said, we will be making decisions on a country by country basis, and we will pursue the countries, where we believe the value of Reds differ is.
Andy: Okay. Thanks, Andy.
Speaker Change: Marvin next question please.
Speaker Change: Thank you for our next question.
Speaker Change: Our next question comes from the line of Ritu <unk> of TD Cowen. Your line is now open.
Ritu Bhara: Good morning, guys. Thanks for taking the question.
Following up on that Bill can you talk a little more to the health technology assessment.
Ritu Bhara:
Ritu Bhara: Algorithms that are preparing to face what what parts of the dataset that you've generated so far.
Ritu Bhara: Drive value.
Ritu Bhara: Is that the national plans.
Ritu Bhara: Either in writing or meetings indicated they are willing to pay for it and then just a quick follow up on the safety of the <unk>.
Ritu Bhara: Four open label dataset that you presented today.
Speaker Change: Given even with compensated patients theyre more fragile kols focus has been on things like.
Speaker Change: Hyperglycemia and suburban it's can you give us the outlines of safety.
Speaker Change: Yes so.
Speaker Change: First of all with the discussions in Europe with DHA is I mean look as you know there is a very.
Speaker Change: Very formal.
Speaker Change: Process that you go through and each of the countries.
Speaker Change: You.
Speaker Change: Prepare your value dossier.
Speaker Change: And we're at various stages of that depending on the country.
Speaker Change: But again.
Speaker Change: Lot of this a lot of the evaluation looks at are you offsetting downstream costs et cetera, I mean, I take you back to our ISR analysis, which showed.
Speaker Change: Or is there going to be a very cost effective therapy.
Speaker Change: Again, they use slightly different tools in each country, but we will be.
Speaker Change: Part of that process, and we feel that the merits the severity of the disease and the merits of the product really do stand on their on their own and we're looking forward to I think productive discussions that we'll have with each of those entities.
Michael Charlton: Maybe Michael do you want to comment briefly on the second question is an important question. So the same study of course included patients with other arms that had.
Speaker Change: Lower degrees of fibrosis and the.
Speaker Change: Hey.
Speaker Change: Type and frequency was comparable between patients with FERC, so that non cirrhotic disease. It's a good question.
Ritu Bhara: Thanks Ritu.
Marvin: Next question please Marvin.
Ritu Bhara: Thank you Margaret for next question.
Speaker Change: Our next question comes from the line of <unk> <unk> of Cantor Fitzgerald. Your line is now open.
Speaker Change: Hi, good morning, and thank you so much for taking my questions. So maybe.
Speaker Change: You'd previously talked about Gi dogs, being a little bit slower to adopt.
Speaker Change: But maybe if you can talk about the latest trends there what youre seeing in terms of the Gis versus kind of advantages.
Speaker Change: Okay, great. Thanks.
Speaker Change: Thanks for the thanks for the question.
Speaker Change: <unk>.
Speaker Change: Be.
We're predominantly focused on hepatology and gastroenterology. So if you just look at the numbers.
Speaker Change: Of those.
Speaker Change: Those specialists, there's less than 1000 herpetologist. So when when you start talking about targeting 14000 prescribers.
Speaker Change: The overwhelming majority of Gastroenterologists. So on the backs of the Gastroenterologists, we've really seen this really strong performance to date. So when we talked about them coming on a little bit slower it was a little bit more of the time that it takes to kind of why or their practice.
Speaker Change: It's not a disease that they had been treating so they had to hire staff in some cases, if they wanted access to nics and wanted to have their own. It internally. So that it's just those mechanics to create the pathway within their practice, but they when they come on they come on and by that I mean.
Speaker Change: <unk> Gastroenterologists I have been extremely extremely happy with the way that they have adopted the product and as I said just based upon the numbers. They are really the driving force of the performance that we have seen and we will likely see in the future clearly the herpetologist are I would say.
Speaker Change: And remain further ahead in most cases, just because the liver is what they are most familiar with they're more familiar with the disease and their practices are probably initially a little better suited but really happy with what we've seen we've seen some of the big Super groups come on.
Speaker Change: And we've seen them go from you know.
Speaker Change: I would call more or less dabbling two full on.
Speaker Change: Nash treatment and literally treating hundreds and hundreds of patients with many more to come. So we're feeling that the evolution of the prescriber base is in a really great place and I would say that the breadth of prescription that we're seeing in this launch is a true standout and something which is a.
Speaker Change: Great Prognosticator for future uptake of the product unique prescribers you need patients and we have both of those okay. Thanks broker.
Speaker Change: Marvin It looks like we've got time for one more question. Please.
Speaker Change: Thank you one moment our next question.
Catherine O'Coney: Our next question comes from the line of Catherine the Kony of citizens. Your line is now open.
Speaker Change: Hi, Catherine onto Jon.
Speaker Change: Quick question about dose adjustment in the open label two year open label extension, where do all P&C at the 80 milligram dose and also just as far as patient retention dose how many patients how many swatek started the study how many continued through the two year time point. Thank you.
Michael Charlton: Okay, Great Michael maybe I'll turn this one over to you for those specific 122 patients entered the second year.
Speaker Change: The open label extension.
Speaker Change: These data are from 101 second.
Speaker Change: Second PCT.
Speaker Change: Thank you.
Speaker Change: And then yes.
Speaker Change: Yes.
Speaker Change: Everyone have a great. Okay. Thanks, Katherine 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 approximately two hours. So thanks for joining.
Speaker Change: Okay.
Speaker Change: Ladies and gentlemen, thank you for your participation in today's conference you May now disconnect have a wonderful day.