Latest news with #Rezdiffra
Business Insider
11-05-2025
- Health
- Business Insider
Madrigal announces two-year results from Phase 3 MAESTRO-NAFLD-1 trial
Madrigal Pharmaceuticals (MDGL) announced positive two-year results from the open-label compensated MASH cirrhosis arm of the Phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra. Patients in the study achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension, CSPH. Among patients with CSPH at baseline, 65% moved into lower risk categories by year two. Among patients with probable CSPH at baseline, 57% moved into the no/low CSPH category as compared to 14% who moved into the CSPH category by year two. Improvement in CSPH risk was statistically significant compared to baseline. Similar shifts to lower risk categories were observed in an analysis using a more stringent modified Baveno criteria that incorporates magnetic resonance elastography and the Enhanced Liver Fibrosis test as additional evidence for CSPH risk. Safety data were consistent with previous studies and Rezdiffra was well-tolerated with a low rate of discontinuation due to adverse events. The most common adverse events were diarrhea, COVID-19 and nausea. There were two deaths unrelated to Rezdiffra. Protect Your Portfolio Against Market Uncertainty
Yahoo
10-05-2025
- Business
- Yahoo
Madrigal Announces New Clinical Data Demonstrating Rezdiffra™ (resmetirom) Significantly Improved Multiple Noninvasive Tests and Portal Hypertension Risk in Patients with Compensated MASH Cirrhosis
Late-breaking results from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial presented at the EASL Congress 65% of patients with clinically significant portal hypertension (CSPH) at baseline moved into lower risk categories by year two Patients achieved a mean 6.7 kPa reduction in liver stiffness, which was statistically significant compared to baseline CONSHOHOCKEN, Pa., May 10, 2025 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today announced positive two-year results from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra. Patients (n=122) in the study achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (CSPH). 'Rezdiffra demonstrated broad, sustained efficacy across multiple noninvasive parameters at two years of treatment. A high, statistically significant percentage of patients with CSPH or probable CSPH at baseline shifted to lower risk categories,' said Naim Alkhouri, M.D., Chief Academic Officer at Summit Clinical Research and the Director of the Steatotic Liver Disease Program at the Clinical Research Institute of Ohio. 'A larger placebo-controlled study will be needed to confirm Rezdiffra's benefit in F4c, but the totality of data in this high-risk population of patients on the cusp of progressing to liver decompensation is highly encouraging as we await results from the ongoing Phase 3 MAESTRO-NASH OUTCOMES trial of Rezdiffra.' CSPH is a major consequence of cirrhosis and is responsible for its most severe complications, including ascites, variceal bleeding and hepatic encephalopathy. Patients with MASH who progress to cirrhosis face a 42 times higher risk of liver-related mortality. MAESTRO-NAFLD-1 included an open-label active treatment arm of patients with compensated MASH cirrhosis. After one year, patients were given the option to enroll in an open-label extension trial; 122 patients enrolled and 113 completed two years of treatment. At baseline, 35% of patients met Baveno criteria for CSPH, 14% for probable CSPH and 51% for no/low CSPH. The Baveno criteria use a combination of vibration-controlled transient elastography (VCTE) and platelet count to assess CSPH risk. Among patients with CSPH at baseline, 65% moved into lower risk categories by year two (42% to no/low CSPH and 23% to probable CSPH). Among patients with probable CSPH at baseline, 57% moved into the no/low CSPH category as compared to 14% who moved into the CSPH category by year two. Improvement in CSPH risk was statistically significant compared to baseline. Similar shifts to lower risk categories were observed in an analysis using a more stringent modified Baveno criteria that incorporates magnetic resonance elastography (MRE) and the Enhanced Liver Fibrosis (ELF) test as additional evidence for CSPH risk. As previously reported, patients achieved a mean 6.7 kPa reduction in liver stiffness at two years, which was statistically significant compared to baseline. In a responder analysis examining ≥25% improvement or worsening of liver stiffness, 51% of patients achieved improvement. An improvement of this magnitude has been associated with reduced progression to end-stage liver disease.1 Rezdiffra helped 35% of patients achieve liver stiffness measurements consistent with F3 fibrosis, suggesting reversal of cirrhosis. Safety data were consistent with previous studies and Rezdiffra was well-tolerated with a low rate of discontinuation due to adverse events. The most common adverse events were diarrhea, COVID-19 and nausea. There were two deaths unrelated to Rezdiffra. 'Lower thyroid-hormone receptor-beta (THR-β) activity in the liver is predictive of hepatic decompensation2 in patients with MASH, so there is a strong mechanistic rationale supporting the potential of Rezdiffra, a THR-β agonist, to improve outcomes in patients with compensated MASH cirrhosis,' said David Soergel, M.D., Chief Medical Officer of Madrigal. 'These two-year open-label data from MAESTRO-NAFLD-1 add important clinical evidence that supports our confidence in the ongoing, fully enrolled Phase 3 outcomes trial of Rezdiffra in compensated MASH cirrhosis.' Investor Webcast to Review New F4c DataAt 8 a.m. EDT May 13, 2025, Madrigal will host a webcast to review the detailed two-year data from the compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial. To access the webcast, please visit the investor relations section of the Madrigal website or click here to register. About MASHMetabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is expected to become the leading cause of liver transplantation in the U.S. and is already the leading cause of liver transplantation among women. Once patients progress to MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically: these patients have a 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those who progress to cirrhosis face a 42 times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop. MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients. An estimated 1.5 million patients have been diagnosed with MASH in the U.S., and Madrigal is focused on reaching approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists. As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis is expected to grow. About RezdiffraRezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. It is the first approved medication for the treatment of MASH in the U.S. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and MASH resolution primary endpoints, and 91% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of liver stiffness. In the U.S., Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials. Rezdiffra is not approved in Europe for the treatment of patients with MASH with moderate to advanced liver fibrosis and not approved in any geography for the treatment of patients with cirrhosis. The ongoing, fully enrolled MAESTRO-NASH OUTCOMES trial is evaluating progression to liver decompensation events in patients with compensated NASH cirrhosis treated with Rezdiffra versus placebo. A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH and expand the eligible patient population for Rezdiffra with an additional indication in patients with compensated MASH cirrhosis. What is Rezdiffra?Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is not known if Rezdiffra is safe and effective in children (under 18 years old).This indication is approved based on improvement of NASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra. Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you: have any liver problems other than NASH. have gallbladder problems or have been told you have gallbladder problems, including gallstones. are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works. Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, or cyclosporine to suppress your immune system, because Rezdiffra is not recommended in patients taking these medicines. Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. What are the possible side effects of Rezdiffra?Rezdiffra may cause serious side effects, including: liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice), pain or tenderness in the upper middle or upper right area of your stomach (abdomen). gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting. The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, constipation. These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or You may also report side effects to Madrigal at 1-800-905-0324. Please see the full Prescribing Information, including Patient Information, for Rezdiffra. About Madrigal Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need. Madrigal's medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. Rezdiffra is the first and only medication approved by the FDA for the treatment of MASH with moderate to advanced fibrosis (consistent with stages F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (consistent with stage F4c). For more information, visit Forward-Looking StatementsThis press release includes 'forward-looking statements' made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended, including statements related to the potential benefit of Rezdiffra in patients with compensated MASH cirrhosis. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that did not have commercial experience prior to 2024; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of Madrigal's clinical trials, including, but not limited to Madrigal's ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for Madrigal's trials; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra's (resmetirom's) mechanism of action; market demand for and acceptance of Rezdiffra; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financing on acceptable terms; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive trials; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; the uncertainties inherent in clinical testing; uncertainties concerning analyses or assessments outside of a controlled clinical trial; and changes in laws and regulations applicable to our business and our ability to comply with such laws and regulations. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal's submissions filed with the U.S. Securities and Exchange Commission('SEC'), for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied. Madrigal specifically discusses these risks and uncertainties in greater detail in the sections appearing in Part I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on February 26, 2025, and as updated from time to time by Madrigal's other filings with the SEC. 1. Lin H, Lee HW, Yip TC, et al. Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease. JAMA. 2024;331(15):1287–1297.2. Kendall TJ, Jimenez-Ramos M, Turner F, et al. An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease. Nat Med. 2023 Nov;29(11):2939-2953. Investor ContactTina Ventura, IR@ Media ContactChristopher Frates, media@ in to access your portfolio
Health Line
05-05-2025
- Health
- Health Line
Wegovy Reduced Inflammation, Scarring in People with Serious Liver Disease
Wegovy (semaglutide) could offer a new option to treat severe liver disease based on new clinical trial evidence. The GLP-1 drug resolved liver inflammation in nearly two-thirds of participants, twice the rate seen with placebo. Semaglutide had a favorable safety profile, with serious adverse events occurring at the same rate as placebo. Wegovy, a highly effective medication used to treat obesity, shows promise in treating a serious form of liver disease in a new clinical trial. The trial, funded by Novo Nordisk, the manufacturer of Wegovy (semaglutide), found the drug improved liver inflammation, scarring (fibrosis), and sometimes both in people with metabolic dysfunction-associated steatohepatitis (MASH). The results were published on April 30 in The New England Journal of Medicine. MASH is an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), a condition formerly known as nonalcoholic fatty liver disease. MASLD involves the buildup of fat in the liver, which can cause inflammation, liver cell injury, and fibrosis. About one-third of adults in the United States have MASLD. While not all cases lead to liver damage, about 5% of adults develop MASH, a more severe and potentially progressive form of the disease. Untreated, MASH can lead to life threatening complications, including cirrhosis of the liver, liver failure, and liver cancer. Currently, the only FDA-approved treatment for MASH in people with moderate to severe liver fibrosis is Rezdiffra (resmetirom), which received approval in March 2024. With few options available, the study authors note an urgent need for additional treatments. Sun Kim, MD, an associate professor of Endocrinology at Stanford Medicine who wasn't affiliated with the trial, echoed that assessment. 'Patients with diabetes are at high risk for MASLD, especially MASH and advanced fibrosis. Patients with advanced fibrosis are at higher risk for complications, including liver cancer and early death,' Kim told Healthline. 'Thus, we need more treatment options.' The authors also point out that Wegovy may provide added benefits by addressing the comorbidities commonly seen in people with MASH, such as cardiovascular disease and obesity, a cluster of conditions known as cardiovascular-kidney-metabolic syndrome. 'It's definitely exciting to have another therapeutic,' said Kim. Liver inflammation resolved in two-thirds of participants A randomized, double-blind, placebo-controlled study is considered the gold standard in clinical research. The new study was part of an ongoing phase 3 clinical trial involving nearly 1,200 individuals. The interim analysis for these findings included 800 participants, who were mostly white adults evenly split between males and females, with an average age of 56. The majority (72%) were classified as obese based on body mass index (BMI), and more than half were also living with type 2 diabetes. After 72 weeks of treatment, nearly two-thirds of participants who received Wegovy showed resolution of liver inflammation (steatohepatitis) without any worsening of fibrosis, almost twice the rate seen in the placebo group. In addition, 37% of Wegovy users saw a reduction in liver fibrosis without a worsening of MASH, compared to 22% in the placebo group. A smaller subset — just under one-third — experienced both benefits: reduced fibrosis and resolved inflammation. That combined improvement was seen in only 16% of those receiving a placebo. These results underscore the challenge of treating MASH. Inflammation and fibrosis are distinct disease processes, and a drug may improve one without affecting the other. As this trial shows, achieving both outcomes remains difficult. While some participants did achieve both outcomes simultaneously, an ideal therapeutic goal, this combined outcome was less common than improvement in either condition alone. That complexity helps explain why so few medications have received FDA approval for MASH. Targeting both aspects of the disease at once remains a significant challenge. 'There are over 20 drugs in phase 2 and 3. However, it is difficult to reverse liver fibrosis. I describe fibrosis to patients as liver scarring due to inflammation associated with liver steatosis/fat. It's easier to prevent the injury than to reverse the scar,' said Kim. Wegovy also showed a favorable safety profile. By week 72, 88% of participants were able to maintain their target dose. Overall, adverse events were slightly more common in the Wegovy group (86%) than in the placebo group (79%). However, both groups experienced the same rate of serious adverse events (13%). The most common side effects in both groups were gastrointestinal. Participants taking Wegovy more frequently reported: Wegovy improved comorbid health conditions The trial also revealed compelling secondary benefits, with improvements in key comorbidities, including: type 2 diabetes obesity cardiovascular risk markers Most notably, people taking Wegovy lost significantly more weight than those receiving a placebo — an average of 10% of body weight compared to just 2%. Wegovy was also linked to modest improvements in cardiovascular health, including slightly lower blood pressure, triglyceride levels, and cholesterol. In addition, participants taking Wegovy — both with and without type 2 diabetes — saw improvements in hemoglobin A1C, a measure of long-term blood sugar regulation. This effect may not be surprising, as semaglutide is already FDA-approved for diabetes management under Novo Nordisk's other brand name, Ozempic. The authors note that semaglutide had a 'holistic therapeutic approach to both liver disease and associated cardiometabolic illnesses.' 'These results lend further credence that semaglutide is the 'Swiss army knife' of medicine we have been looking for, to treat obesity, cardiovascular disease, type 2 diabetes, and now MASH,' Beverly Tchang, MD, an endocrinologist and assistant professor of clinical medicine at Weill Cornell Medicine, not affiliated with the trial, told Healthline.
Yahoo
02-05-2025
- Business
- Yahoo
Madrigal Pharmaceuticals Inc (MDGL) Q1 2025 Earnings Call Highlights: Strong Sales Growth and ...
Net Sales: $137.3 million in Q1 2025, up 33% from Q4 2024. Patient Growth: Over 17,000 patients on Rezdiffra by end of Q1 2025, up from 11,800 in Q4 2024. Prescriber Penetration: 70% of 6,000 top target prescribers have prescribed Rezdiffra. R&D Expenses: $44.2 million in Q1 2025, down from $71.2 million in Q1 2024. SG&A Expenses: $167.9 million in Q1 2025, up from $80.8 million in Q1 2024. Cash Position: $848.1 million in cash, cash equivalents, restricted cash, and marketable securities at the end of Q1 2025. Warning! GuruFocus has detected 5 Warning Signs with MDGL. Release Date: May 01, 2025 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Madrigal Pharmaceuticals Inc (NASDAQ:MDGL) reported strong first quarter 2025 net sales of $137 million, up 33% quarter over quarter. Rezdiffra, the first FDA-approved treatment for MASH, achieved over 80% commercial payer coverage and treated more than 17,000 patients in its first year. The company has successfully built a strong base of prescribers, with 70% of their top 6,000 targets having prescribed Rezdiffra. Madrigal Pharmaceuticals Inc (NASDAQ:MDGL) is expanding its leadership in MASH with compelling two-year F4c data and ongoing pivotal outcomes trials. The company is well-positioned financially, ending the first quarter with $848.1 million in cash and marketable securities, supporting ongoing and future launches. SG&A expenses increased significantly to $167.9 million in Q1 2025, up from $80.8 million in Q1 2024, primarily due to commercial launch activities. The company anticipates gross-to-net discounts to increase throughout 2025 as they begin contracting with payers. There is uncertainty regarding the impact of potential competition from semaglutide (SEMA) once it gains label expansion for NASH. The European launch of Rezdiffra faces challenges, including responding to regulatory questions and potential differences in non-invasive testing acceptance compared to the FDA. Madrigal Pharmaceuticals Inc (NASDAQ:MDGL) is actively seeking business development opportunities, which may impact cash flow and require careful financial management. Q: Can you elaborate on your expectations for Rezdiffra's growth trajectory, especially with the potential label expansion of SEMA to include NASH? A: We are very excited about our growth momentum and expect it to continue. Our focus has been on the 315,000 diagnosed F2/F3 MASH patients, with only 5% currently treated with Rezdiffra. We anticipate years of growth ahead, and SEMA's approval could further expand the market. We believe our product profile will allow us to grow through any potential market changes. Q: What are your expectations around payer reauthorization requirements and patient persistency on Rezdiffra beyond the first year? A: Reauthorizations are standard and typically require a 12-month re-off. We are not concerned as we are receiving positive feedback from physicians and patients about the drug's efficacy. We expect persistency to be strong due to Rezdiffra's well-tolerated nature and the positive real-world experience. Q: Can you provide an update on the European approval process for Rezdiffra and how non-invasive testing is being approached differently than in the US? A: We are on track for a mid-year action in Europe. The questions from the CHMP are expected, and we are pleased with the review process. Europe is ahead of the US in terms of guidelines and preparation for a MASH product, and we believe there are enough installed NITs to support our launch effectively. Q: What is your confidence in showing an OUTCOMES benefit on hepatic events in F2, F3, versus F4 patients? A: We are confident in our mechanism of action as a liver-directed therapy. Our data shows a significant reduction in liver stiffness, which is a key predictor of adverse liver-related events. We believe this will translate into positive outcomes in our ongoing F4c trial. Q: Can you discuss the impact of your DTC campaign on the launch trajectory and your business development strategy moving forward? A: Our DTC campaign has received positive feedback, helping educate patients and prepare them for discussions with their providers. For business development, we aim to extend our leadership in MASH by exploring complementary assets that could enhance Rezdiffra's efficacy or address different patient segments. We will maintain financial discipline in our approach. For the complete transcript of the earnings call, please refer to the full earnings call transcript. This article first appeared on GuruFocus. Sign in to access your portfolio
Yahoo
02-05-2025
- Business
- Yahoo
Q1 2025 Madrigal Pharmaceuticals Inc Earnings Call
Tina Ventura; Chief Investor Relations Officer; Madrigal Pharmaceuticals, Inc. Bill Sibold; Chief Executive Officer & Director; Madrigal Pharmaceuticals, Inc. Mardi Dier; Chief Financial Officer; Madrigal Pharmaceuticals, Inc. Eliana Merle; Analyst; UBS Andrea Newkirk; Analyst; Goldman Sachs Ritu Baral; Analyst; TD Cowen Akash Tewari; Analyst; Jefferies Yasmeen Rahimi; Analyst; Piper Sandler Liisa Bayko; Analyst; Evercore ISI Jay Olson; Analyst; Oppenheimer & Co. Inc. Mayank Mamtani; Analyst; B. Riley Securities Prakhar Agrawal; Analyst; Cantor Fitzgerald Operator Good day and thank you for standing by. Welcome to Madrigal Pharmaceuticals first quarter 2025 earnings conference call. (Operator Instructions) As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead. Tina Ventura Thank you, Tawana. Good morning, everyone, and thank you for joining us to discuss Madrigal's first quarter 2025 earnings. We issued a press release this morning and I have a slide deck that accompanies this webcast, which we'll post on the investor relations section of our website right after the 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. We plan to keep today's call to about 45 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. With that, I will now turn the call over to Bill on slide 3. Bill Sibold Thanks, Tina. Good morning and thanks for joining. Today I'll provide an update on the significant momentum we continue to build with the US launch of Rezdiffra. I'll briefly recap the impressive two year F4c data we shared on our last earnings call, which has since been selected as a late breaking oral presentation at the EASL Congress in Amsterdam next week. We plan to review this data in an investor webcast following EASL on Tuesday, May 13, and I'll close with the review of our strategy to expand our leadership position in before we move to the quarter, I want to take a moment to recognize Becky Taub, Madrigal's founder and a driving force behind the development and ultimate approval of Rezdiffra. As we announced in April, Becky is taking on the new role of senior scientific and medical advisor, and she will continue to serve on our board of directors. And we are very pleased that Dave Soergel joined us on April 21 as our new Chief Medical Officer succeeding vision, pioneering work, and relentless drive led to the development and approval of the first ever FDA approved medicine for MASH. This is a landmark achievement in our industry and one that has already changed the lives of thousands of patients. It's also changed Madrigal. We've transformed from an R&D focused company to a fully integrated commercial stage brings more than 20 years of leadership experience in metabolic and cardiovascular disease drug development spanning both biotech and large pharma. He was most recently the EVP and Global Head of Cardiovascular, Renal, and Metabolism Development at Novartis, where he was overseeing 10 late stage clinical development programs. We believe Dave is the right leader to take the reins at this critical juncture and build on the foundation Becky those lines, I'd also like to highlight the recent addition to our Board of Directors, Jackie Fouse. Jackie brings a depth of experience from her leadership roles at several successful biotechs, including Agios and Celgene. I look forward to working with her as we continue to grow the let's turn to slide 4 and Rezdiffra's first quarter 2025 performance. We're a little more than 12 months into the launch of Rezdiffra and what a difference a year gone from zero approved MASH treatments and no market infrastructure to securing FDA approval in March 2024, launching with the best case label and a world class team, achieving over 80% commercial payer coverage, helping lay the foundation practice by practice to build the infrastructure required for patient treatment, treating more than 17,000 patients who previously had no options, and generating $317 million in net sales in our first 12 months on the any measure, this is an exceptional launch. And we know that because we're benchmarking ourselves against some of the most successful specialty medicine launches in the past decade. Whether it's patient growth, depth, and breadth of prescribing, payer coverage, or net sales, we're performing at or near the top. But the most exciting part, we're just getting started. As we enter year two, we're bringing the same intensity and focus on execution that got us here, and we believe the best is still momentum carried us into another impressive quarter with first quarter 2025 net sales of $137 million up 33% quarter over quarter, despite the typical headwinds we see in Q1 across the patients support and field teams did a great job navigating those dynamics to keep patients on therapy, and we're continuing to generate strong demand and steadily add patients into the second quarter, driven by the urgent need re differ addresses, its compelling product profile, and the exceptional execution of our addition to net sales, we continue to make great progress on key performance indicators that are driving our launch. First on patients as shown on slide 5, we ended the first quarter of 2025 with more than 17,000 patients on Rezdiffra, up from 11,800 patients at the end of the fourth quarter of figure represents patients actively on therapy, accounting for any discontinuations, making it the most rigorous and meaningful metric to track sustained treatment when we compare it to other top tier specialty launches, we're adding patients at a rate that's consistent with those benchmarks. And yet we're still in the very early innings of this launch. Only about 5% of the 315,000 diagnosed F2/F3 MASH patients who are currently under the care of our target prescribers are being treated with also see that awareness is driving action. Our disease and product education efforts are preparing patients to have better conversations with their MASH specialists about their remain focused on those 315,000 patients, which represents a highly attractive specialty market. Looking ahead, the stated efforts of the next entrant are focused on expanding the market to many multiples of our initial target believe that the strength of Rezdiffra's efficacy and attractive real world profile positions it for leadership in either scenario, creating multiple paths to success for Rezdiffra in the years to slide 6 in our progress on physician penetration. Across the many launches I've led, one thing is clear building a strong base of prescribers early in a launch is one of the best indicators of long-term success. That's why the pace at which we've added new prescribers has been so encouraging. In just a year since approval, 70% of our 6,000 top targets have prescribed level of penetration puts us at the high end of the benchmarks we track and shows we've built a strong foundation of healthcare providers who believe in Rezdiffra and are seeing the this type of uptake this quickly is the result of the work we've been doing since day one. Wiring the system for a first in disease launch like Rezdiffra is no small feat. We built and deployed a world class team. We educated physicians on a disease that had no approved partnered with payers to secure broad access and worked hand in hand with practices to help create the infrastructure needed to support sustained prescribing. As a result, more and more practices are integrating red differ into their standard of driving the same momentum as we establish a strong base within our 14,000 total targets to support the significant peak sales potential we the end of the first quarter of 2025, approximately 50% of the 14,000 target prescribers had prescribed Rezdiffra, up from 40% at the end of the fourth quarter of 2024, reflecting a growing and durable foundation. Our in-office support and cross-functional field engagement are not only driving breadth, they're also driving depth. We are steadily turning new writers into repeat prescribers and seeing more prescriptions written per provider. That has consistently increased quarter over quarter as broad uptake is being driven by its attractive real world profile. A medicine's profile often diminishes once it enters real Rezdiffra, we hear the opposite. Physicians and patients continue to highlight meaningful improvements they see on the efficacy measures that matter most to patients, such as liver stiffness, liver fat, liver enzymes, LDL, and our Phase 3 data demonstrate that res differ halts or improved liver stiffness in 91% of patients. As a once daily, well tolerated pill with simple dosing, it's also easy to take. We're seeing strong early signs of adherence with rates that are comparable to other well tolerated oral believe Rezdiffra's liver-directed mechanism, strong efficacy, and attractive real world profile will translate well from F2/F3 MASH patients to those with F4c or compensated mash cirrhosis, as noted on slide MASH progresses, it can lead to cirrhosis marked by significant liver damage, loss of liver function, liver cancer, and death. Many F4c patients are also experiencing clinically significant portal hypertension, or CSPH, a major consequence of cirrhosis that's responsible for its most severe complications, such as ascites, variceal bleeding, and hepatic risk of progression is striking. F2/F3 patients face a 10 to 17-fold increase in liver-related mortality compared to patients without fibrosis. For F4, that number jumps to a 42-fold increase. That's why we are evaluating Rezdiffra in 845 F4c patients in MAESTRO-NASH OUTCOMES, a large Phase 3 double blind placebo controlled trial evaluating progression to liver decompensation. We expect data from this trial in quarter we shared two year data from the open label active treatment arm of our MAESTRO-NAFLD-1 trial in F4c patients. These results demonstrated Rezdiffra's ability to reduce liver stiffness, a key predictor of adverse liver-related to slide 9, let me quickly recap the two primary efficacy findings. Patients saw a mean reduction of 6.7 kilopascals in liver stiffness at two years, which was statistically significant as compared to baseline. For context, physicians use the Baveno Rule of 5 to stratify risk in MASH cirrhosis, so a 6.7 kPa reduction suggests that many patients are moving into a lower risk category.51% of patients achieved a greater than or equal to 25% reduction in liver stiffness. As published in JAMA, This level of reduction is associated with a lower risk of progression to end-stage liver disease, essentially a reversal of results and additional insights will be presented at the upcoming EASL Congress on May 10 by Dr. Naim Alkhouri, Chief Academic Officer at Summit Clinical Research and the director of the Steatotic Liver Disease Program at the Clinical Research Institute of abstract was accepted as a late breaking oral presentation, and one of the most important findings will highlight is Rezdiffra's impact to reduce liver stiffness measures and other biomarkers that are linked to a reduction in risk of CSPH. Importantly, CSPH is the cause of many adverse liver-related OUTCOMES that mark the progression from compensated to decompensated cirrhosis. Preventing these devastating outcomes is the central goal of treating liver I mentioned earlier, we'll also be hosting a brief investor webcast on May 13 to review the data and discuss the evolving MASH cirrhosis landscape. Dr. Alkhouri will join us for that discussion, and we hope many of you will tune expansion to treatment of F4c is a key pillar of our long-term MASH leadership strategy, as shown on slide 10. While we continue to execute a successful US launch in F2, F3, we're advancing efforts to expand Rezdiffra's indication to F4c. Our Phase 3 MAESTRO-NASH OUTCOMES trial is in alignment with FDA guidance for clinical trial design in cirrhosis expect to have data years ahead of the competition and first mover advantage in this segment of the market as well. If approved, this could potentially double Rezdiffra's market opportunity. We're also preparing to bring red differ to patients outside the US. We remain on track for a mid-year regulatory decision in Europe. And if we receive a positive outcome, we plan to launch in Germany in the second half of the Europe, we're evaluating additional high priority global markets. At the same time, we're focused on building the right pipeline beyond Rezdiffra. We're in the enviable position of delivering a first in disease medicine to patients today, and now we're looking to extend that leadership with a portfolio of differentiated actively evaluating opportunities across multiple mechanisms and stages of development, and as I mentioned earlier, we're excited to have Dave Soergel on board as our new Chief Medical Officer to help lead our pipeline development that, let me briefly recap our first quarter progress on slide 11. We're off to a great start in year two of our launch. We generated $317 million in net sales over the last 12 months and are seeing continued momentum into the second quarter. Physician adoption continues to build with 70% of our 6,000 top targets now prescribing expanding our leadership in MASH. With compelling two year F4c data, two pivotal OUTCOMES trial underway, and a potential EMA approval on the horizon, we believe Rezdiffra is well on its way to becoming the foundational therapy across F2 to F4c. With that, I'd like to turn it over to Mardi. Mardi Dier Yeah, thank you, Bill. Good morning. I just want to take a moment to comment on how Madrigal is positioned in the current macroeconomic environment. We're positioned extremely well. As a commercial stage biotech with a first in disease medicine addressing a serious unmet need, we've built a US-based supply chain. Rezdiffra is manufactured in the US and its intellectual property is also US to our financial results as noted on slide 12. First quarter of 2025 net sales totaled $137.3 million, up 33% from the fourth quarter of 2024. This was another strong demand quarter with inventory levels well within our expected two to four week we said, we expect gross net to be choppy in the early in the launch, and the team managed through our first quarter very well. In 2025, we expect gross to net discount to increase and step up as we move through the year and as we begun to contract with payers, which is in line with our expectations. Importantly, this is already reflected in our expectations for robust year over year net sales growth in 2025.R&D expenses for the first quarter of 2025 were $44.2 million compared to $71.2 million for the first quarter of 2024. The decrease was primarily due to the change in accounting for inventory costs following FDA approval of Rezdiffra in March 2024 and lower clinical trial cost. Looking ahead, we expect a similar level of R&D spend in 2025 compared to expenses for the first quarter of 2025 were $167.9 million compared to $80.8 million in the first quarter of 2024. SG&A expenses increased by $87.1 million primarily due to increases in commercial launch activities for Rezdiffra, including a corresponding increase in headcount and stock compensation expense. Looking ahead, we expect SG&A expenses to increase in 2025, including a step up into the second quarter as we continue to invest in the US launch and prepare for our launch in to our balance sheet, we ended the first quarter of 2025 with $848.1 million in cash, cash equivalents, restricted cash, and marketable securities. With this strong cash position, we continue to be well resourced to support the ongoing launch of Rezdiffra both in the US and our planned launch in Europe in the second half of this year. I'll now turn the call back over to Tina. Tina Ventura Thanks, Mardi. Let's move into the Q&A portion of the call. Tawana, please go ahead and provide instructions for the Q&A session. Operator (Operator Instructions)Eliana Merle, UBS. Eliana Merle Hey guys, thanks for taking the question and congratulations on the quarter. I'm just curious to go a little bit more in depth on your expectations for the growth trajectory for Rezdiffra, particularly when SEMA's label is expanded to include NASH. Do you expect to see new patients at a similar rate, and can you just elaborate on sort of how you see the growth from there? Thanks. Bill Sibold Yeah, it was a great quarter. We're really excited about it and as we said, we've continued that momentum into Q2. As we look towards the potential approval of SEMA, as we pointed out on one of the slides here, we have a couple of different views of how the market's going to they're talking about a market which is multiples the size of our 315,000 patients. Our efforts to date have really been focused on the 315,000. So there's plenty of patients when you consider where they're at about 5% penetration today. So we see, really years of growth in this market ahead. SEMA is only going to accelerate diagnosis and add to that 315, I said, our efforts are on the 315,000. We believe there's a great market there. There's even a greater market if what they do happens which makes, as I said, multiples of the 315,000. So long way of saying, we feel really comfortable with our profile. We believe ours is the winning profile and we believe that we can grow through their potential approval and launch. Mardi Dier Yeah, and maybe Ellie I'll jump in here and just add a little bit, as Bill said, we expect this momentum of growth to continue into Q2. So we do expect, good quarter-over-quarter growth and also the same for 2025, robust growth for 2025, and I would just, give the commentary here for both the quarter and for the year we expect consensus to narrow and move up a little bit. Operator Andrea Newkirk, Goldman Sachs. Andrea Newkirk Hi everyone, good morning and congratulations on the quarter. Bill, could you just talk us through your expectations around payer reauthorization requirements that you might be seeing right now and how are you thinking about the persistency of these patients to continue on Rezdiffra beyond this first year? Thanks so much. Bill Sibold Thanks, Andrea. So you know reauthorizations are part of the process for every medicine, so we're not really concerned about that. Most of the policies, as we said in the past, require a 12 month re-off, and that's in line with most it ends up being at kind of provider discretion or requires stabilization or some kind of measure on one of the NITs, so we don't see that as an issue specifically because we're hearing such great results from physicians and patients that have been on the fact, I said a lot of products when they launch, they typically don't live up to the well-controlled clinical trial environment that may show a certain level of efficacy. They end up declining a little bit. We're seeing absolutely the opposite in our have physicians and patients coming back and saying we're really seeing efficacy across a bunch of parameters and exceeding expectations in that sense, which leads to the persistency piece, which is because it's a well-tolerated oral, we would expect persistency to be, very good like other well-tolerated orals. So you know we feel we're in a really great spot because of the profile of the product and what the one year results are of seeing such strong real world experience. Operator Ritu Baral, TD Cowen. Ritu Baral Good morning, guys. Thanks for taking the question and congratulations on this quarter. My question has to do with Europe. I believe you guys are well on your way for the CHMP documents as they post, but can I ask where you are on responding to their questions? I believe you requested an extension of the clock the I guess the driver for the extra time needed to respond and as you go through these discussions for the Rezdiffra label, can you talk to how maybe Europe is approaching non-invasive testing different than FDA? It looks like they may be on accelerated acceptance, and does this factor into what label Rezdiffra may get in Europe? Thanks. Bill Sibold Okay, Ritu, that's a lot there. I'm going to try to remember it all. Look, the questions we're getting, I think, are, all expected. We're still on track for our mid-year action we would expect, this is, you have to remember, just like with the FDA, this is the first MASH product ever approved in I think agencies want to take their time and make sure that they understand and that they are putting forth kind of the best label that they can that is going to be really the foundation for all other MASH labels. So you know we're really happy with how the review is going and as I said, we're expecting approval and we'll expect to launch later this question on NITs, yeah, look, so it's interesting, Europe's had a year plus to digest the fact that there's going to be a mash product, as we talked about last year, physicians in the US until the product was approved almost didn't believe there was going to be a product approved because of, the over 2 dozen or almost 2 dozen failures before on the other hand, with the approval in the US has much more certainty, so the actions they've taken, starting with the EASL guidelines last year, are actually quite far ahead of the US. Now from an NIT perspective, we believe that there are there's enough installed NITs that will allow us to launch effectively, but just like the US, there's going to have to be additional NITs added as you have a new product that is approved and you actually have to start thinking about now how are you going to die. And stage patients a little bit in many ways the EU is ahead of the US from an action perspective, and we think that's probably more important than anything right we have EASL next week. We're really excited to talk directly to a lot of the physicians and hear firsthand from them how their prep is going, but I was impressed last year as well, so I'm sure they're that much further ahead, and that's certainly what our teams are telling us now. Operator Akash Tewari, Jefferies. Akash Tewari Hey, thanks so much. Can you talk about your relative confidence in showing an OUTCOMES benefit on hepatic events in F2, F3, versus F4? We're digging this internally and there's some clear encouraging signals, whether it's the INTERCEPT trial or even SEMA in F2/F3. There's almost no correlation we're seeing in F4 between liver fat reduction and actual hepatic events. So what gives your team confidence the liver stiffness data will actually translate? I really appreciate it. Bill Sibold Thanks for the question. Nice to hear from you. Look, I think that as we showed in the slides today, this 6.7 kPa reduction in two years, we think is actually quite meaningful. I think the literature supports that. But if we take even a step back our MOA a liver directed therapy. It's really looked at as kind of the master regulator of fibrosis, and we believe that starting from that point we have great confidence in the mechanism. Now the data to date with the reduction in liver stiffness in this cohort of patients, and we're going to explain more about it next week, I would encourage you to listen gives us further confidence that that is getting at the heart of the problem and therefore we won't have the events that you would without treatment. So I think you know everything from the biology to what we've seen early gives us great confidence in our F4c trial that's ongoing know, we have 845 patients. It's a well-sized trial and we're more encouraged, as I said, by the data that we've talked about today and we're going to talk about at EASL next week. So yeah, look, like anything else, that's why you do the trials, right? And we'll have to see what results ultimately look like, but so far we remain, extremely confident in the outcome. Operator Yasmeen Rahimi, Piper Sandler. Yasmeen Rahimi Good morning team. Congrats on a great quarter. My question is just now that you've had patients for over a year on therapy, have you been able to quantify sort of what the compliance rate is and sort of as patients are, kind of talking like, do they feel function better as they're on the drug? So what is the adherence rate that you're seeing and how do you think it will be projected moving forward? And I'll jump back in the queue. Bill Sibold Yeah, thanks for the question. It's a little early to be making a call on ultimately what does adherence look like. However, all the early signs are very promising, and I think again it goes back to the well-tolerated nature of the product and the overall profile of the of the questions that I think people were asking was this is an asymptomatic disease, is why would someone stay on? Well, the physicians have been able to give really positive feedback to patients because they're seeing these results across a number of parameters, and that always gives people a reason to stay on, especially if they're not feeling any really significant tolerability issues along the had talked to a lot of patients and anecdotally we hear, some patients that are saying as well that, they feel better, and I think it's a little bit of a hope. They're worried about the consequences of severe liver disease, right?They've seen some of them have family members that have gone through transplant. Some family members have died from MASH, and it's, I hadn't expected this as much, but the hope that they now have because there's a once a day pill, that's really kind of astonishing, and that's giving people as well, I think the reason to stay on. So we're really optimistic it's early, but all signs right now suggest that we will have an adherence rate very consistent with well-tolerated orals. Operator Liisa Bayko, Evercore. Liisa Bayko Hi, thanks for taking the question and congratulations on a strong quarter. I just want to drill a little bit more into, two topics. One is if you get any more granular and grows to net for the quarter, and then, the project, the trajectory from here, I know you said it was it would be kind of, a little bit, up and down, but just curious, on more then on in terms of like GLP-1s and this whole concept, I guess today. What is your estimate of what percentage of your patients are on GLP-1s? How do you expect this to change as semaglutide gains label expansion into MASH, and do you expect any kind of step through or any payers to kind of lean that way as that comes on board later on this year? Bill Sibold Thanks, Lisa. It's a couple of questions, but those are ones that I'm sure are on people's minds, so maybe we'll go with that. Maybe starting with the GLP-1 combo. So as we reported previously, 25% of patients are on a GLP-1 that are on our estimate right now, and it jumps to about 50% that have been exposed previously. So GLP-1s, we have to remember they're not new. They've been here for over a decade. Despite them being here for over a decade, there's still this MASH challenge that exists. People are still diagnosing and seeing MASH and patients are GLP-1s and the question of is there a step through, look, it's early, they haven't been approved yet. We have to see what the label looks like and ultimately what their approval looks like. However, we've planned for all scenarios and as I said on a question earlier, we feel very confident that we can grow through all part of that has to do with the fact that, A, 5his is a high unmet need. B, we've got a great profile. We're a liver directed once a day pill. You've heard me call it the holy grail of profiles. Profiles matter at the end of the got to take a drug for it to work. It's controlled, well-controlled studies are great, but in the real world you've got to take a drug for it to work, and we feel like we're in a really good place. Now from a gross to net perspective, we've been extremely diligent about gross to net. You've heard me say from the beginning. We have planned for years ahead, not a single quarter, but we've really looked towards the evolving looking at different products coming into the market thinking about new indications for us. And as you know, we started in a really great position. We really preserved gross to net out of the gate by not contracting, largely because of the innovative nature of the product, right?You know this has been the graveyard of drug development and Rezdiffra really broke through and we take that into consideration. However, you can't escape the dynamics of the market. Payers are always evaluating the landscape evolves, whether it's a new calendar year or you get a competitive entrant. So we've thought about gross to net anticipating that there will be additional competition, we've had good partnerships with payers. We're going to keep those good partnerships, but in line with that, we started contracting in Q2. And it's not everywhere and it's not all at once. It's an evolution. It's going to take we are right where we thought we would be. We're executing kind of our plan for the short, medium, and long term, and feel we're in a really strong position. But maybe Mardi, perhaps you could comment a little bit more on the [GLP] dynamic in '25. Mardi Dier I'm happy to. As Bill said, we've been very disciplined with our growth to net, but it is absolutely part of our business going also said it continues to be choppy and that's going to be the case as we continue to launch, but our team did a fantastic job from fourth quarter into first quarter and managed the dynamics really well. I would say specifically for Q1, we are a little favorable across the board for (inaudible), but we're really staying within the range that's typical for specialty pharmacy we do see, as we said last quarter, that this will continue to step up throughout the year in 2025, particularly with some of the contracting as Bill said, not everywhere, not all at once, but as that continues to take effect throughout the year. So anyway, we're in really great shape with our gross in that and right as part of our expectations moving forward. Operator Jay Olson, Oppenheimer. Jay Olson Oh hey, congrats on the impressive launch progress and thanks to Becky for her pioneering efforts successfully bringing Rezdiffra to you talk about any feedback on the key messages in your DTC campaign and how that's impacted the launch trajectory? And then with regards to business development, as you look ahead to extending your leadership position in MASH, what sort of complementary assets would you like to add to Rezdiffra? Bill Sibold Great, Jay, thanks for the question. First of all, on DTC, yeah, feedback is very positive about our DTC. The idea is to get to mostly diagnose patients and have them prepared to take action when they go to see their from the whole community has actually been very strong, and we're really encouraged by it, and we think it's an important piece of the mix because this is a disease that people don't know a lot about. We still know that the biggest issue is taking action, and we hear every day of tragic stories of patients where physicians haven't taken action or where patients didn't know what fatty liver disease meant and came back years later to find out if they need a transplant. That is something that we as a company, our purpose is really to fight against take it seriously. Education through DTC is important. As our DTC continues to evolve, I would direct you to a new campaign that we have at [ This really gets to the heart of this is a serious disease and action is required. That's once again feel like I know that it sounds like I'm doing a commercial myself right there. That wasn't the intent, but I wanted to make sure that Jay you got the website to go to. Your second question was on business development. I look, we've been really clear all are in this really enviable position. Most position, most companies have a pipeline looking for a great asset. We have a great asset and now we have the luxury of building a pipeline to sustain our leadership position. You don't get many opportunities like this in the industry where you're the first to launch in a very significant disease that has had a checkered past in development because it's been such a difficult disease to first, we've done it, and it's really with a product that is very specific to the problem. It's liver directed. And is a great profile, but in order for us to extend our leadership, we think it is important to have additional products focus will be in MASH, and we're looking at next mechanisms of action that are compelling or products that could be combined with Rezdiffra to make Rezdiffra and the new entity that much better. So that allows us to either extend efficacy work in new different pardon me, segments of the population, we're looking across the entire pipeline early stage to late stage. We're going to base it on mechanisms that we're interested in, mechanisms that we think could be helpful for patients, and we will then be very diligent in the way that we actually go about doing our deals, we're not going to do a bet the company strategy on any of don't have to. So we'll maintain that financial discipline. We'll do good deals. We'll do deals that are going to make a difference ultimately for patients and sustain our leadership in the future. So more to come on that when we have something to present. Operator [Mayank Mamtani, B. Riley Securities]. Mayank Mamtani Thanks for taking our questions and congrats on strong quarter. Digging into the Novo's New England publication from last night on a sense, it seems that the SEMA benefit is coming in interestingly low to mid BMI F2 patients rather than F3 more advanced. It would be great to hear though your thoughts on how maybe you're thinking about patient your benefit seems more pronounced in the more advanced [FCF4] and just quickly on going back to the comments on EU approval launch strategy mid-year. Curious the implications of this F4 data coming in at EASL, but also on pricing given macro discussions on, innovation being possibly better rewarded in in EU countries. Thanks again for taking our questions. Bill Sibold Right, okay, thank you very much for the question. Look, we didn't see anything new actually. We just, we got it last night like everyone else, so we're looking through it, but really nothing new there, well-controlled trial, you get results from a well-controlled trial.I think that the real question is what's the applicability to the real world and I think, we know that in the real world, GLP-1a, there's a challenge specifically of, keeping people on drugs and getting them to the highest you know nothing's changed from our perspective looking at looking at that news now you know where right now where we're used, it's about 50/50 F2/F3 patients and you know what happens is physicians, pardon me, a patient comes into their into the see the 6 months, 12 months, and the physicians looking at that patient at that moment, and if they have F2, they say, well, let's wait a year, they could go to F3, they could, who knows where they're going to go. They're making that decision at the moment and that's why we're seeing that they're often choosing to it be F2 or F3, so we expect that that mix to continue, as we have hopes to move into F4c as well, and we think that, we will be the product F2 to F4c period, which is, I think, an ambitious but ultimately realistic feel really comfortable with our with our positioning and our profile. Regarding Europe and thinking about pricing and so forth, I mean, look, we're going through our pricing analysis now. Our belief is we have a very innovative product and that the innovation will be recognized in Europe. I think that the dynamics of GL1-s look, as we said. And a lot of patients are already have already been exposed to a GLP1 and still have 50% of our patients have already been exposed, but they still have this problem. So, we think that the two can co-exist, we are only going to be focusing on those patients that we think are most in need, those that need a liver directed therapy, and we think that there's, plenty of room for us in at the very beginning of a market. You know what my experience is that every time you have a new entrant enter a market, the market growth increases pretty significantly, and clearly that's a stated goal by Novo. So there's going to be lots of patients that are going to be available for us regardless of how the dynamics evolve. Operator Prakhar Agrawal, Cantor Fitzgerald. Prakhar Agrawal Hi, thank you so much for bringing my questions and congratulations on the strong quarter. So, I had a couple, follow up on growth to net as well, but maybe longer term for 2026 and beyond as you are having the initial payer contracting discussions for next year. What do you expect in terms of the net pricing evolution for 2026?Do you expect a big step up compared to 2025 given the summer launch and just curious as to what you're hearing from the payers, especially given the pricing differential. And secondly, maybe quickly on BD clearly seems to be a priority, but what exactly is the BD capacity given the ongoing investments in the launch in the US and later Europe? Thank you so much. Bill Sibold All right, thanks for the question. Maybe I'll start with just a comment on gross net, and then Mardi can provide a little bit more. I mean, look, as I said, you heard me answer earlier, we've taken a long term view of gross net. We know with, pretty good certainty what the potential market evolution looks like with new entrants just looking at the pipeline and so forth. It's a little early to comment on ' to net only goes in one direction. And we've been very disciplined about it. We'll continue to be, we have a very significant value proposition with the product that we have, so we think that we'll continue to be in a very favorable place from a gross from that perspective. But maybe, Marty, do you want to comment any more on that, or it's still early? Yeah. Mardi Dier It's really too early Prakhar, so on 2026, but it's all part of our business, it's all part of our expectations. We have ongoing dialogue and good relationships with the payers, and we'll talk about that more as the year progresses. Bill Sibold Yeah. And then regarding BD, as I said, we're not doing a bet the company strategy. We're going to be very diligent and disciplined about the way we do deals. And Mardi, do you want to comment? Yeah. Mardi Dier Yeah, you talked about the capacity, and I think Bill's point is right. We're not vetting the company here. We're in a great position from a cash standpoint, and that cash is we're focused on building, out the US launch and the ex US launch. If we do BD that may put a different lens on our cash flow, but right now we're in a very good position with our cash. Operator Andy Chen, Wolfe Research. Hi, this is Emma on for Andy. Thanks for taking our question and congrats on the quarter. You mentioned six abstracts will be presented at EASL next week. I guess just aside from the late breaker, which is more focused on, the F4c data, what are other key findings to look out for F4? Thank you. Bill Sibold Well, look, that's going to be the big data that we're going to be presenting there. We think it's really important, especially, we've seen that there's been this kind of gravitation and interest in FGF21 in F4c. We have data which we think is just really impressive, and you're going to see that in the late breaker. We have, as you said, we have six different posters, etc. covers really a large gamut, everything from some of the unmet need to more specific results that we're seeing in Germany, for instance, from claims analysis that we've done, etc. So it's a little bit of an evolution of the data that we have and some more details about the severity of the disease and what you're seeing in the real world from, incidents of things like HCC, it's a pretty exciting meeting for us, the presentations we're going to be doing are great. I'd say probably more than anything we're looking forward to just the interaction with the community there and what we're hearing is there's a lot of anticipation about the dialogue that we're going to be having with. Various physicians from literally around the world that attend. So it's a great meeting for big news is the late breaker and thus therefore it's a late breaker because it is of such interest. So stay tuned. Hope to see some of you over there and certainly hope that you will join us on our call looking at that F4c data after EASL. Tina Ventura Great. Emma, thanks for that question. And Tawana, thanks for your time and thank you all for your interest today. This is now the time we're going to conclude the call. A replay of this webcast will be available on our website in approximately two hours. So thank you so much for joining us. Operator That concludes today's conference call. Thank you for your participation. You may now disconnect.
