Summary of Sagimet Biosciences FY Conference Call Company Overview - **Company**: Sagimet Biosciences (NasdaqGM:SGMT) - **Focus**: Development of novel therapeutics targeting fatty acid synthesis for diseases such as MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease) and acne [1][2] Key Points on MASH Program - **Lead Molecule**: Denifenstat, a potent FASN (fatty acid synthase) inhibitor, is being developed for MASH and acne [2][3] - **Mechanism of Action**: Denifenstat targets fat, inflammation, and fibrosis, differentiating it from other treatments that primarily focus on fat oxidation or mobilization [3][10] - **Clinical Data**: - Phase IIB study showed a 30% placebo-adjusted improvement in fibrosis [10] - In F4 patients, 11 out of 13 showed a one or two-stage improvement in fibrosis [6][4] - **Combination Therapy**: A combination program with resmetirom is underway, showing enhanced effects on inflammation and fibrosis [6][18] - **Funding Needs**: Approximately $400 million is required to complete the Phase III study for the F2 and F3 populations, with current cash reserves at $125 million [16][30] Key Points on Acne Program - **Partnership**: Collaboration with Ascletis in China for acne studies, showing 20% placebo-adjusted improvements in lesion reduction [8][23] - **Regulatory Pathway**: Plans to seek FDA guidance in early 2026 regarding the use of Ascletis' Phase III data for U.S. regulatory approval [24][25] - **Next-Gen Molecule**: Development of TVB-3567, a more potent follow-on oral FASN product, is in Phase I [25][26] - **Market Potential**: The acne market is significant, with an estimated 50 million Americans affected, and the introduction of effective treatments is expected to increase patient demand [23][24] Financial Considerations - **Royalty Stream**: Expected inflow of approximately $120 million from milestones and royalties related to the acne program in China [29] - **Capitalization Requirements**: The company acknowledges the need for substantial funding to support ongoing and future clinical programs [30] Additional Insights - **Unique Positioning**: Denifenstat is the only FASN inhibitor in development, which is a significant differentiator in the market [11][12] - **Long-Term Strategy**: The company recognizes the necessity for combination therapies in treating patients effectively, indicating a strategic approach to drug development [20][21] - **Intellectual Property**: New IP filed for the combination therapy is expected to provide protection until 2044 [22] This summary encapsulates the critical insights from the Sagimet Biosciences FY conference call, highlighting the company's strategic direction, clinical advancements, and financial outlook.

Financial Data and Key Metrics Changes - The company reported a 15% top-line growth year-to-date and an 11% growth for the quarter, indicating strong momentum in its financial performance [5][21] - The guidance for top-line growth for 2025 has been narrowed to a range of 8%-11%, with corresponding adjustments to operating profit growth [21] Business Line Data and Key Metrics Changes - The diabetes segment experienced a 10% growth, while obesity care saw a remarkable 41% growth, with 83% of this growth coming from international operations (IO) and 24% from the U.S. [11] - Rare disease products returned to normal production levels, growing 13% in a balanced manner between IO and the U.S. [11] Market Data and Key Metrics Changes - The U.S. market for anti-obesity medications continues to expand, with a significant increase in out-of-pocket expenses for patients, rising from 4% to over 10% in just nine months [12] - The company is currently addressing only 3-4 million patients in the obesity market, compared to an estimated 100 million potential patients [12] Company Strategy and Development Direction - The company is sharpening its strategy to focus on treating patients with obesity and diabetes, emphasizing the overlap of these conditions with other comorbidities [8][10] - The acquisition of Akero is part of the strategy to deepen its focus on metabolic diseases, particularly MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease) [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the growth potential in the obesity market, highlighting the significant unmet needs and the company's commitment to expanding its product portfolio [9][14] - The company is preparing for the launch of oral semaglutide, which is expected to capture a significant portion of the market due to its unique profile [96][97] Other Important Information - The company is facing regulatory challenges regarding the Metsera acquisition, but remains confident in the quality of the portfolio and its potential [59][68] - There are ongoing discussions about the competitive landscape in the U.S. for GLP-1 products, with management noting a slight decline in Ozempic scripts but a belief in continued growth potential outside the U.S. [82][84] Q&A Session Summary Question: What do you expect to learn from the amycretin trials? - Management indicated that they will not progress to phase III trials without clear differentiation in efficacy, safety, or scalability [25] Question: Can you explain the recent pricing trends for GLP-1 products? - Management confirmed that pricing for Ozempic is expected to decline by 10%-15% year-on-year, while Wegovy's pricing has also seen a decrease [27][28] Question: How are you addressing the consumerization of the sales force? - The company is focusing on understanding patient needs and behaviors, emphasizing the importance of direct purchasing channels and expanding product offerings [31][36] Question: What is the outlook for revenue growth in 2026? - Management refrained from providing specific guidance for 2026 but highlighted the potential of the Wegovy pill launch and ongoing pipeline developments as future growth drivers [49][51] Question: What if the FTC blocks the Metsera acquisition? - Management expressed confidence in the acquisition's merits and readiness to discuss its benefits with the FTC [56][59] Question: Are there any supply limitations for the oral semaglutide? - Management reassured that there are no anticipated supply limitations for the oral semaglutide launch [101]

Financial Data and Key Metrics Changes - The company reported a 15% top-line growth year-to-date and an 11% growth for the quarter, indicating strong momentum in its R&D pipeline and business development activities [4][20]. - The guidance for top-line growth for 2025 has been narrowed to a range of 8-11%, with corresponding adjustments to operating profit growth [20]. Business Line Data and Key Metrics Changes - The diabetes segment experienced a 10% growth, while obesity care saw a remarkable 41% growth, with 83% of this growth coming from International Operations (IO) and 24% from the US [10]. - Rare disease products returned to normal production levels, growing 13% in a balanced manner between IO and the US [10]. Market Data and Key Metrics Changes - The US market for anti-obesity medications continues to expand, with a significant increase in out-of-pocket expenses for patients, rising from 4% to over 10% in just nine months [11]. - The company is addressing a market of approximately 100 million patients in the US for obesity treatment, with only 3-4 million currently being treated [11]. Company Strategy and Development Direction - The company is sharpening its strategy to focus on treating patients with obesity and diabetes, emphasizing the overlap with comorbidities such as MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease) [6][7]. - Recent acquisitions, including that of Akero, are aimed at deepening the company's focus on core therapy areas and addressing unmet needs in comorbidities associated with obesity and diabetes [7][15]. Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the growth potential in the obesity market, highlighting the significant unmet needs and the company's strategic focus on expanding its product portfolio [11][13]. - The company acknowledged challenges in the US market, including pricing pressures and competition, but remains committed to leveraging its pipeline and product offerings to drive future growth [20][49]. Other Important Information - The company is preparing for the regulatory submission of new products, including the oral semaglutide and MyMADE for rare diseases, which are expected to contribute to future revenue growth [19][50]. - Management emphasized the importance of understanding patient behaviors and needs in the consumer market, particularly in relation to comorbidities and treatment formats [35][100]. Q&A Session Summary Question: What do you expect to learn from the amycretin trials? - Management stated that they will not progress to phase three without clear differentiation in efficacy, safety, or scalability, and they are awaiting confirmation from phase two data [23]. Question: What are the pricing trends for GLP-1 medications? - Management indicated that pricing for Ozempic is expected to remain stable, with a year-on-year decrease of about 10-15%, while Wegovy's pricing has seen a decline in Q3 [26][27]. Question: How are you addressing the consumerization of the sales force? - The company is focusing on understanding patient needs and behaviors, emphasizing the importance of product formats and direct purchasing channels [30][35]. Question: What is the outlook for the UK market? - Management noted that the UK market is competitive and price-sensitive, but they are seeing strong performance from their products despite pricing pressures [43]. Question: Can you discuss the Metsera acquisition and potential FTC challenges? - Management expressed confidence in the acquisition's merits and their readiness to discuss it with the FTC, emphasizing the quality of the portfolio [52][56]. Question: What is the expected impact of the oral semaglutide launch? - Management believes that the oral market represents a significant opportunity, with expectations of capturing a substantial share due to its unique profile [95][100].

Financial Data and Key Metrics Changes - Third quarter 2025 net sales totaled $287.3 million, up 35% from the second quarter of 2025 [23][24] - R&D expenses for the third quarter of 2025 were $174 million, compared to $68.7 million in the third quarter of 2024, primarily due to a one-time $117 million expense associated with the global licensing agreement for MGL-2086 [24][25] - SG&A expenses for the third quarter of 2025 were $209.1 million, compared to $107.6 million in the third quarter of 2024, reflecting higher commercial investment to support the Rezdiffra launch [25] Business Line Data and Key Metrics Changes - Rezdiffra's sales are annualizing at greater than $1 billion in only its sixth quarter of launch, with over 29,500 patients currently on therapy, up from more than 23,000 at the end of the second quarter [4][6][7] - The number of prescribers for Rezdiffra exceeded 10,000, indicating strong adoption and penetration in the market [8][27] Market Data and Key Metrics Changes - The MASH market is still in its early stages, with Rezdiffra positioned as a first-line therapy, benefiting from a unique profile that surpasses other first-to-market products [9][10] - The company anticipates that the market will expand, driven by increased awareness and diagnosis, particularly with the entry of competitors like Wegovy [10][11] Company Strategy and Development Direction - The company is focused on maximizing the value of Rezdiffra and building its pipeline, with a strong emphasis on payer contracting strategies for first-line access [4][12] - The strategy includes expanding globally, with a recent launch in Germany following European approval, and enhancing targeting efforts towards endocrinologists [15][16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in Rezdiffra's growth potential, citing a strong adherence rate and the drug's well-tolerated profile as key factors for long-term chronic use [11][72] - The company is optimistic about the outcomes of ongoing trials, particularly the Maestro NASH outcomes trial, which is expected to read out in 2027 [16][47] Other Important Information - The company ended the third quarter of 2025 with $1.1 billion in cash and equivalents, providing strong resources to support the ongoing launch of Rezdiffra and advance multiple pipeline programs [25][26] - The gross-to-net impact is expected to be in the high 30% range starting January 1, 2026, consistent with other innovative specialty medicines [24][14] Q&A Session Summary Question: How could AASLD data further de-risk Maestro NASH outcomes? - Management highlighted the positive feedback from gastroenterologists and the foundational therapy status of Rezdiffra, expressing excitement about the upcoming AASLD meeting [31][32] Question: Pros and cons of combining Rezdiffra with MGL-2086 versus other GLP-1s? - Management clarified that MGL-2086 is an orforglipron derivative, emphasizing the rationale for combining it with Rezdiffra to enhance efficacy [37][38] Question: Thoughts on competitive positioning amid recent M&A in the space? - Management views recent M&A as validation of the MASH market and believes it will lead to greater diagnosis and treatment opportunities, favoring Rezdiffra's profile [45][46] Question: Feedback on Rezdiffra's adherence rate and net pricing expectations? - Management confirmed strong adherence rates and indicated that gross-to-net dynamics would likely lead to some future decline in pricing, but they remain optimistic about market access [51][53] Question: Comments on Aetna's formulary coverage decision? - Management stated that Rezdiffra will be available through prior authorization or medical exception, with no expected meaningful impact on patient access [59] Question: Observations on Novo's marketing campaign and its impact on the addressable patient pool? - Management noted that while it is early to quantify the impact, there are signs of increased referrals and diagnosis, which could benefit Rezdiffra [63][64] Question: Path to profitability and focus areas moving forward? - Management emphasized the focus on driving top-line growth and building out the pipeline, indicating that profitability will be considered in the future [68]

Financial Data and Key Metrics Changes - In Q3 2025, net sales totaled $287.3 million, representing a 35% increase quarter over quarter [22][24] - R&D expenses increased to $174 million from $68.7 million in Q3 2024, primarily due to a one-time $117 million expense for a global licensing agreement [23][24] - SG&A expenses rose to $209.1 million compared to $107.6 million in Q3 2024, reflecting higher commercial investment for the Rezdiffra launch [24] Business Line Data and Key Metrics Changes - Rezdiffra's sales are annualizing at over $1 billion within six quarters of launch, with over 29,500 patients currently on therapy, up from over 23,000 at the end of Q2 2025 [3][5][25] - The number of prescribers for Rezdiffra exceeded 10,000, indicating strong adoption and penetration in the market [6][25] Market Data and Key Metrics Changes - The MASH market is still in its early stages, with Rezdiffra positioned as a first-line therapy, benefiting from a unique profile that surpasses other first-to-market products [8][10] - The company anticipates that the market will expand, driven by increased awareness and diagnosis, particularly with the entry of competitors like Novo [61] Company Strategy and Development Direction - The company is focused on maximizing the value of Rezdiffra and expanding its pipeline, with a strong emphasis on payer contracting for first-line access in 2026 [3][11] - The strategy includes a thoughtful approach to pipeline development, aiming to combine Rezdiffra with other mechanisms like GLP-1s to enhance treatment efficacy [15][16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in Rezdiffra's growth potential, citing a strong adherence rate and a favorable market position [10][68] - The company is optimistic about the upcoming data presentations at AASLD, which are expected to bolster confidence in the Maestro NASH outcomes trial [32][19] Other Important Information - The company ended Q3 2025 with $1.1 billion in cash and equivalents, providing a strong financial position to support ongoing operations and pipeline advancements [25] - The gross-to-net impact is expected to rise to the high 30% range in 2026, consistent with other innovative specialty medicines [23][12] Q&A Session Summary Question: How could AASLD data further de-risk Maestro NASH outcomes? - Management highlighted the positive feedback from gastroenterologists and the foundational role of Rezdiffra in treatment, expressing excitement for the upcoming AASLD data [29][31] Question: Pros and cons of combining Rezdiffra with MGL-2086 versus other GLP-1s? - The company clarified that MGL-2086 is an orforglipron derivative, emphasizing the rationale for combining it with Rezdiffra to enhance efficacy [35][36] Question: Thoughts on competitive positioning amid recent M&A in the space? - Management views recent M&A as validation of the MASH market, believing it will lead to increased diagnosis and treatment opportunities for Rezdiffra [41][43] Question: Feedback on Rezdiffra's adherence rates and net pricing expectations? - Management confirmed strong adherence rates and indicated that while some gross-to-net decline is expected, they are well-positioned for stable pricing [49][51] Question: Insights on Aetna's formulary coverage decision? - Management stated that Aetna's non-coverage will not significantly impact access, as Rezdiffra will still be available through prior authorization [55][56] Question: Observations on Novo's marketing campaign and its impact on patient numbers? - Management noted that while it is early to quantify, there are signs of increased referrals and diagnosis, which could benefit Rezdiffra [60][62] Question: Path to profitability and future growth strategies? - The focus remains on driving top-line growth and expanding the pipeline, with profitability being a longer-term goal [63][68]

Summary of Aligos Therapeutics Conference Call Company Overview - **Company**: Aligos Therapeutics (NasdaqCM:ALGS) - **Focus**: Development of therapies for liver and viral diseases, specifically targeting chronic hepatitis B virus (HBV) and metabolic dysfunction-associated steatohepatitis (MASH) [1][2] Key Points on Chronic Hepatitis B Virus (HBV) - **Prevalence**: HBV is the largest chronic viral infection globally, affecting approximately three times more people than HIV [3] - **Current Treatments**: Standard care involves nucleoside and nucleotide analogs, which block virus replication but do not eliminate the long-lived cccDNA form of the virus [3][4] - **Clinical Outcomes**: A study in Taiwan showed that after five years of treatment with nucleoside analogs, 4% of patients developed liver cancer, and 5% experienced liver decompensation [4] - **Need for Better Therapies**: Deep and rapid suppression of HBV is essential to prevent liver disease and cancer, highlighting the limitations of current therapies [5] PEVI/PHOSCOVIR Development - **Lead Program**: PEVI is a next-generation capsid assembly modulator designed to treat chronic HBV [2] - **Mechanism of Action**: PEVI blocks the encapsulation of pre-genomic RNA and reduces cccDNA levels, which is a significant advancement over first-generation capsid assembly modulators [10][11] - **Clinical Data**: In a 96-week study, 100% of E antigen negative patients achieved HBV DNA levels below 10 international units, compared to only 20% in traditional treatments [16][22] - **Resistance**: PEVI has shown effectiveness against resistant variants of HBV, which is a significant advantage over previous treatments that led to drug resistance [17][18] B Supreme Phase II Study - **Study Design**: The B Supreme study will compare PEVI with nucleoside analogs in both E positive and E negative patient populations, focusing on achieving HBV DNA levels below 10 [21][22] - **Endpoints**: The study will measure antigen reductions and cccDNA levels, with paired biopsies to assess integration events related to HBV lifecycle [24][26] - **Regulatory Approval**: The study has received approval from regulatory agencies in 14 countries, indicating broad acceptance of its design [19][24] Future Milestones and Commercial Opportunity - **Upcoming Data**: Key data from the B Supreme study will be presented at the AASLD meeting, including post-treatment effects and interim analyses [46][47] - **Market Opportunity**: With 94% of HBV patients needing better chronic suppressive therapy, PEVI is positioned to become the standard of care, potentially increasing the rate of functional cures in combination therapies [39][42][44] MASH and ALG-055009 Development - **Overview**: ALG-055009 is a thyroid hormone receptor beta agonist aimed at treating MASH, showing improved potency and reduced side effects compared to existing therapies [50][52] - **Clinical Results**: In Phase IIa studies, ALG-055009 demonstrated a 46% reduction in liver fat, outperforming similar drugs [54] - **Partnership Discussions**: Aligos is in discussions with potential partners for ALG-055009, aiming to leverage its capabilities in cardiometabolic diseases [56] Conclusion - Aligos Therapeutics is advancing innovative therapies for HBV and MASH, with promising clinical data and a clear regulatory pathway for its lead programs. The company is well-positioned to address significant unmet needs in these areas, with a focus on improving patient outcomes and reducing healthcare costs associated with liver diseases [57][58]

Core Insights - Pharmaceutical companies are heavily investing in drugs for MASH, a liver disease associated with obesity and metabolic issues, with significant acquisitions occurring this year [1] - Magical Pharmaceuticals has launched Resifa, the first FDA-approved drug for MASH, which is expected to drive market growth and awareness [1][2] Industry Overview - The MASH market has approximately 315,000 diagnosed patients in the U.S., with only 7% currently treated, indicating substantial room for growth [4][5] - The diagnosis rate for MASH is estimated at 10%, suggesting many patients remain undiagnosed and untreated [5] - The market is anticipated to evolve into a significant specialty market, similar to established markets like rheumatoid arthritis and psoriasis, which have multiple products and substantial revenue [6][7] Company Positioning - Magical Pharmaceuticals has reported an $800 million run rate, indicating strong initial market performance with only 7% penetration [7] - The company believes that increased competition will enhance awareness and treatment options, benefiting all players in the market [6][10] - The company is confident in its ability to compete against larger firms due to its strong product profile and experienced team [9][10]

Lanifibranor's Potential and Mechanism - Lanifibranor is a promising oral small molecule designed to treat MASH by targeting intrahepatic fibrosis progression and extrahepatic manifestations, delivering anti-inflammatory & metabolic benefits[13] - Lanifibranor is a differentiated pan-PPAR agonist with moderate and well-balanced activity on the three PPAR isoforms[34] - Phase 2b data showed an 18% improvement in fibrosis with no worsening of MASH vs placebo at 6 months (42% vs 24%, p=001) and improved cardiovascular, glycemic, and metabolic markers[14] - Lanifibranor observed to induce a decrease in key serum biomarkers consistent with histologic endpoints, with a 139% decrease in Pro-C3 (p=0005) and a 411% decrease in CK18-M30 (p<0001) compared to placebo[81] Market and Clinical Trial Landscape - The US has approximately 19 million diagnosed MASH patients[9] - Analysis shows significantly more than ~315K MASH patients are under treater care[10] - 85% of specialists in the US described the greatest unmet needs as lack of effective, liver directed therapies[12] - In the Phase 2b NATIVE trial, 24% of patients on lanifibranor 1200mg achieved resolution of MASH and improvement of fibrosis, compared to 3% on placebo[76] - NATiV3 is fully recruited with 1009 patients in the main cohort and 410 in the exploratory cohort[95] Inventiva's Strategy and Timeline - Inventiva raised $411 million in a successful PIPE financing in October 2024[7] - Inventiva aims to re-define MASH treatment with lanifibranor, with targeted launch in 2028[16, 17] - Topline results for NATiV3 are expected in H2 2026[7, 17]

Core Points - Inventiva has appointed Andrew Obenshain as the new CEO, succeeding co-founder Frédéric Cren, who has led the company since its inception in 2012 [1][2][3] - The leadership transition is part of a strategic decision to support Inventiva's growth, particularly in preparing for potential commercialization in the U.S. market for metabolic dysfunction-associated steatohepatitis (MASH) [2][3] - The company is currently evaluating lanifibranor in a pivotal Phase 3 clinical trial, which is crucial for its future development and potential market entry [4] Company Overview - Inventiva is a clinical-stage biopharmaceutical company focused on developing oral therapies for MASH, a progressive chronic liver disease [4] - The company is publicly listed on Euronext Paris and Nasdaq, indicating its established presence in the financial markets [5] Leadership Insights - Andrew Obenshain brings over 20 years of experience in drug development and commercialization, having previously served as CEO of bluebird bio and held senior roles at Shire and Genzyme/Sanofi [3][4] - Frédéric Cren expressed pride in the company's transformation from a private biotech to a recognized leader in the MASH field, highlighting the achievements made under his leadership [3]

Core Points - Roche has signed a definitive merger agreement to acquire 89bio for a total equity value of approximately $2.4 billion, with a potential total deal value of up to $3.5 billion [1][2] - The acquisition includes a tender offer to purchase all outstanding shares of 89bio at $14.50 per share in cash, along with a contingent value right (CVR) that could yield payments of up to $6 per share based on specific milestones [1][2] - The deal is expected to close in Q4 2025, pending customary closing conditions and regulatory approvals [2] Company Strategy - Roche aims to strengthen its portfolio in cardiovascular, renal, and metabolic diseases through this acquisition, particularly focusing on the potential of pegozafermin as a transformative treatment for metabolic dysfunction-associated steatohepatitis (MASH) [3][4] - The lead product, pegozafermin, is a fibroblast growth factor 21 (FGF21) analogue currently in late-stage trials for MASH with advanced fibrosis, which could offer best-in-disease efficacy for moderate to severe patients [4][5] Regulatory and Advisory Details - Pegozafermin has received priority medicines (PRIME) status from the European Medicines Agency (EMA) [5] - Citi acted as the financial adviser for Roche, while Sidley Austin served as legal adviser; Moelis & Company and Centerview Partners were financial advisers for 89bio, with Gibson, Dunn & Crutcher as legal adviser [5]