Ervogastat

前 言   2025 Q4 多家 MNC 财报材料里，“管线移除/降优先级（removed / discontinued / deprioritised）”信息密集出现，且不再局限于早研：从 I 期到 III 期、从肿瘤到免疫/炎症与代谢，均可见项目被直接终止、适应症被撤。本帖仅基于 7 家公司在其季度更新页中明确标注的移除项目做盘点（Pfizer、Lilly、GSK、Sanofi、Roche、BMS、AstraZeneca）。 01  Sanofi SanofiQ4 管线附录更新中，多项中后期项目被标注为 deprioritised 或因结果阴性移出，集中发生在免疫/炎症与神经领域。 II 期，amlitelimab（anti-OX40L单抗，分别用于斑秃、乳糜泻、系统性硬化）均被标注为 deprioritised；此外，Dupixent（溃疡性结肠炎）、eclitasertib（RIPK1抑制剂，溃疡性结肠炎）、frexalimab（anti-CD40L单抗，系统性红斑狼疮）、itepekimab（anti-IL-33单抗，支气管扩张）以及 SAR447873（212Pb标记anti-SSTR多肽偶联核素，胃肠胰神经内分泌肿瘤）均被标注为 deprioritised。 I 期，SAR445514（anti-BCMA×NKp46×CD16三特异抗体，炎症适应症）、SAR446159（anti-IGF-1R×α-synuclein双抗，帕金森病）与 SP0237（流感）被标注为 deprioritised。 02  AstraZeneca AstraZeneca自 2025 Q3 更新以来，披露从 I–III 期均有项目/适应症被移除。 I 期移除包括：AZD0233（CX3CR1拮抗剂）用于扩张型心肌病，以及一项 mRNA-VLP 预防 COVID-19 疫苗。 II 期移除包括：AZD3427（relaxin mimic）用于心力衰竭；并将 ceralasertib（ATR 抑制剂）在实体瘤中的一项 additional indication 从 II 期移除。 III 期移除包括：ceralasertib（ATR抑制剂） + Imfinzi（durvalumab）用于 2L NSCLC（LATIFY）等。 03  BMS BMS“Removed”仅披露在 III 期出现两项移除。移除项包括：SC nivolumab + relatlimab (anti-LAG3单抗) + rHuPH20 用于 1L 黑色素瘤；以及 milvexian (factor XIa抑制剂) 用于 ACS。 04  GSK  GSK相较 2025 Q3，本季度披露从管线中移除 1 个 III 期、1 个 II 期与 4 个 I 期项目，覆盖神经退行、疫苗/感染、免疫与肿瘤早研。 III 期移除为 latozinemab（抗 sortilin 抗体），适应症为额颞叶痴呆（FTD）。 II 期移除为 GSK5101955（MAPS 肺炎球菌 24 价儿科疫苗），适应症为儿科肺炎球菌疾病。 I 期移除项目包括 GSK3888130（抗 IL-7 抗体）用于自身免疫疾病； GSK5462688（RNA-editing 寡核苷酸）用于α1-抗胰蛋白酶缺乏症； GSK4418959（Werner helicase 抑制剂)用于 dMMR/MSI-H 实体瘤 GSK4524101（DNA polymerase theta 抑制剂）用于肿瘤。 05  Eli Lilly  Eli Lilly在 2025 Q4 的“Select Pipeline”更新中，标注了 3 个被移除项目（更新基准为 2025 年 10 月 28 日以来），分别位于 I 期与 II 期。I 期移除项目为 [Ac-225]-PSMA-62（前列腺癌）。II 期移除项目包括：CD19 antibody（适应症：MS 与 RA，LY3541860，non-depleting）以及 GRN gene therapy（适应症：额颞叶痴呆，FTD）。 06  Pfizer Pfizer：自 2025 年 11 月 4 日以来从开发管线中移除 9 个项目，覆盖肿瘤、炎症/IBD 与代谢（MASH）。移除项包括： TUKYSA®（tucatinib，HER2 TKI）用于 HER2+ 转移性乳腺癌 2L/3L（HER2CLIMB-02，III 期，Product Enhancement）； vepdegestrant（ARV-471，ER 靶向 PROTAC）用于 ER+/HER2− 新辅助乳腺癌（II 期，Product Enhancement）； ervogastat（PF-06865571，DGAT2 抑制剂）用于 MASH（II 期，NME）。 prifetrastat（PF-07248144，KAT6 表观遗传调节）+ atirmociclib（PF-07220060，CDK4 抑制剂）用于转移性乳腺癌（I 期，NME）； PF-07899895（SIK 抑制剂）用于溃疡性结肠炎（I 期，NME）； PF-07853578（PNPLA3 调节剂）用于 MASH（I 期，NME）； PF-07054894（CCR6 拮抗剂）用于溃疡性结肠炎（I 期，NME）； PF-06414300（机制未披露）用于溃疡性结肠炎（I 期，NME）； PF-07940369（机制未披露）用于克隆性造血相关贫血 ACH（I 期，NME）。 07  Roche Roche Q4 2025 管线更新中，披露从 I–III 期各有项目被移除，合计 I 期移除 3 个 NME、II 期移除 1 个 NME、III 期移除 1 个AI。 I 期移除包括：RG6120 zifibancimig（nAMD，anti-Ang2×VEGF-A  DutaFab）、RG6221 LTBR agonist（实体瘤）、RG6561（NME）（实体瘤）。 II 期移除为：RG6536 vixarelimab（IPF / SSc-ILD，anti-OSMRβ单抗）。 III 期移除为：RG7446 Tecentriq（atezolizumab）+ 铂类化疗用于 NSCLC 围手术期（peri-adj）。 欢迎大家加入BioPlus Partners微信交流群&Linkedin，共同探讨。 BioPlus Partners Linkedin   微信交流群 入群申请联系人 ：Lisa 邮箱：lisa.li@bp-bioplus.com 电话：18662346610（同微信） 入群申请，请先添加Lisa微信，并分享名片 入群画像 ：Biotech/药厂研发/BD、投资机构、临床医生等 入群福利：不定时行业资料包分享 Upcoming Event  拓展阅读  BioPlus-海外寻找资产系列： 1.AACR复盘：9家CDH17-ADC数据对比 2.自免小众靶点APRIL，正在悄悄火起来了！ 3. STEAP1，会成为ADC与TCE的下一个爆款靶点么？ BioPlus国际大会跟踪系列： 1. 2025 ASCO：ADC、双抗/多抗，有哪些看点？（附一览表） 2. 2025 AACR 双抗与ADC有哪些看点？ 3. 小细胞肺癌领域，下一步将如何“破局”，ADC or TCE？ 4. ELCC 讨论：NSCLC的ADCs最新进展 5. 未来ADC发展方向：新靶点，新载荷，双靶点/双表位... 6. 2025 ASCO 重点项目临床数据：有哪些精彩看点？ 7. 2025 ASCO 重点项目临床数据 8.2025 ESMO 临床数据：有哪些精彩看点？ BioPlus靶点/管线研究系列： 1. “待爆”：CDH17 ADC项目大比拼，谁将脱颖而出? 2. PD-1激动剂在自免疾病项目数据盘点：失败项目的“坑”与启示 3. 上临床就能卖？DLL3 ADC这么好卖？ 4. 胰腺癌三大热门靶点：CLDN18.2、EGFR、RAS 5. TSLP/SCF双抗，下一个自免待爆靶点组合？ 6. GPC3靶点临床屡败，TCE能改写格局么？ 7. 亮相AACR，曾被临床终止的ADC靶点Ly6E，能否卷土重来？ 8. 最高18.45亿美元！赛诺菲为何重金买了两款TL1A双抗？ 9. 2025 Q1：BMS、Sanofi和Roche管线调整，哪些项目被砍？ 10. 现场！2025AACR：KRAS抑制剂的百花齐放 11. IL-17小分子抑制剂，能否杀出重围？ 12.全球首款：华东医药申报MUC17 ADC药物 13.荨麻疹 first-in-class双抗提交临床试验申请 14.绝非 “越低越好”：CD3 亲和力的权衡之道 15.重磅！罗氏披露BBB穿越Aβ药物最新临床数据（附详细资料） 16.阿斯利康C5纳米双抗：重症肌无力III期临床达主要终点 17.从口服到吸入和外用制剂，PDE4还有哪些可能？ BioPlus技术平台深入剖析系列： 1. TCE 免疫共刺激信号之选：CD2，一颗冉冉升起的新星 2. BD爆发前夜！6家TCE Probody技术平台深度盘点 3. TCE Probody：Amgen携重磅技术“破局“，改写行业格局？ 4. 有人放弃，有人前行！自免TCE全球管线大盘点 5. Immunocore将TCR疗法照进现实，向自免疾病迈进 6. B细胞清除免疫重置：SLE等疾病长效缓解终成现实！ 7. 国内50家CD3平台序列来源汇总 8. CD28共刺激最终章？ZW209 DLL3/CD3/CD28 三抗剑指 Amgen 9. TCE 结构之争落幕：行业用行动给出 “标准答案” 10. CD3 VHH猴交叉：重要吗？ 11.Genentech创新前沿：口服VHH抗体，靶向IL-23R 12.AbbVie专利公开：靶向PSMA/STEAP1 双抗ADC 13.In vivo CAR-T： MNC 还在看？ BioPlus人物专访： 1. 专访肖亮：卖青苗不一定是坏事，这是中国Biotech长成参天大树的必经之路 2. 专访王刚，恺佧生物这些年的“出海”之旅？   3.专访熊安稳教授：NSCLC，PD-1/VEGF之后，PD-1/IL2会是下一个双抗之王么？ BioPlus视频访谈： 1.对话余强，迫界者第一讲！医药圈原创视频访谈栏目 2.迫界者第二讲！对话丁元华、赵春林 3.BioPlus Talks海外上线！把中国创新讲给全球听

Fourth -quarter and full-year 2025 Rezdiffra ® (resmetirom) net sales of $321.1 million and $958.4 million, respectively As of year-end 2025 , more than 36,250 patients on Rezdiffra Built industry-leading MASH pipeline with more than 10 programs at multiple stages of development Reports cash, cash equivalents, restricted cash and marketable securities of $988.6 million as of Dec. 31, 2025 Company to host conference call today, Feb. 19, 2026, at 8 a.m. EST CONSHOHOCKEN, Pa., Feb. 19, 2026 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today reports fourth-quarter and year-end 2025 financial results and provides corporate updates. Bill Sibold, Chief Executive Officer of Madrigal, stated: “2025 marked a defining year for Madrigal. We solidified our position as the undisputed leader in MASH highlighted by nearly $1 billion in Rezdiffra sales in its first full year of launch. And we’re just getting started – having penetrated only a fraction of a market that we believe has decades of growth ahead. We believe 2026 will be even more exciting where we expect another year of robust net sales growth driven by broad first-line access, increasing disease awareness and the outstanding real-world experience with Rezdiffra reported by patients and providers.” Sibold continued: “We are shaping the future of MASH by advancing the science to deliver new innovations for patients. Just a year ago, we were a single-product company, and today we have a pipeline with more than 10 programs that we believe will define the future of MASH treatment. Our priorities are clear – deliver first-to-market outcomes data in F4c, further characterize the benefits of Rezdiffra through evidence generation and usher in an era of combination medicines anchored by Rezdiffra as the foundation that address the full spectrum of patient needs.” Recent Corporate Updates Licensed global rights to six pre-clinical siRNA programs, providing potential for an effective, genetically targeted treatment approach for patients with MASH Small interfering RNAs (siRNAs) offer a precision approach to gene silencing in MASH by selectively reducing the production of disease-driving proteins. By pairing this precise gene-silencing approach with Rezdiffra, Madrigal aims to explore whether reducing key drivers of disease at the genetic level can complement Rezdiffra’s therapeutic effects. IND-enabling activities in initial candidates will begin in 2026. Expanded MASH pipeline with exclusive global license agreement for ervogastat, a phase 2 oral DGAT-2 inhibitor DGAT-2 inhibition represents a complementary mechanism that offers the potential for additive clinical benefit when combined with Rezdiffra, a thyroid hormone receptor-β (THR-β) agonist. Data from Phase 2 trials of ervogastat demonstrated impressive reductions in MRI-PDFF with 72% of patients treated with ervogastat (150mg) achieving at least a 30% reduction in liver fat, and 61% achieving at least a 50% reduction. Madrigal plans to conduct a drug-to-drug interaction study with Rezdiffra and consult with the FDA on design of a Phase 2 combination trial this year. 2025 Highlights Secured Orange Book listed Rezdiffra patent, providing protection into 2045 Patent entitled, “Methods for treating a fatty liver disease” (U.S. Patent No. 12,377,104) that covers the FDA-approved use of Rezdiffra with claims directed to Rezdiffra’s commercial weight-threshold dosing regimen as prescribed in the FDA-approved label was listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book, in August 2025. Licensed global rights to oral GLP-1 (MGL-2086) to combine with Rezdiffra Madrigal licensed global rights to an oral glucagon-like peptide-1 (GLP-1) receptor agonist and orforglipron derivative in September 2025. The global license agreement supports Madrigal’s strategy to develop innovative combination treatments for MASH, anchored by its foundational therapy, Rezdiffra. MGL-2086 is expected to enter the clinic in the second quarter of 2026. Presented two-year data at EASL and AASLD from the active-treatment open-label extension (OLE) F4c cohort of the NAFLD-1 trial Rezdiffra treatment significantly improved liver stiffness, fibrosis biomarkers, and markers of clinically significant portal hypertension (CSPH) risk in patients with compensated MASH cirrhosis (F4c). 65% of patients with CSPH at baseline moved into lower risk categories by year two. Baseline characteristics of patients from the OLE F4c cohort are similar to patients enrolled in the ongoing MAESTRO-NASH OUTCOMES trial which is expected to read out topline data in 2027. Presented poster of distinction at AASLD supporting importance of staying on Rezdiffra to prevent disease progression New analysis examining effects of Rezdiffra treatment demonstrated that patients who paused therapy experienced a reversal of earlier gains; findings underscored the need for sustained therapy. Launched Rezdiffra in Germany following European Commission approval Following European Commission (EC) conditional marketing authorization in August 2025, Madrigal launched Rezdiffra in Germany in September 2025. The EC conditional marketing authorization was based on positive results from Madrigal’s pivotal Phase 3 MAESTRO-NASH trial demonstrating that Rezdiffra reduced fibrosis, resolved MASH and improved key noninvasive tests. Rezdiffra is the first and only approved therapy in the European Union for MASH. Secured up to $500 million in senior secured credit to advance MASH pipeline In July, Madrigal entered into a senior secured credit facility with funds managed by Blue Owl Capital that provides up to $500 million to advance Madrigal’s pipeline to further extend its leadership position in MASH. Fourth -Quarter and Full-Year 2025 Financial Results Total Revenues: Madrigal generated fourth-quarter and full-year 2025 net revenues of $321.1 million and $958.4 million, respectively. Net revenues in the comparable prior year periods were $103.3 million and $180.1 million, respectively. Operating Expenses: Fourth-quarter and full-year 2025 operating expenses were $380.7 million and $1,258.5 million, respectively, compared to $170.3 million and $678.0 million in the comparable prior year periods. Cost of Sales: Fourth quarter and full-year 2025 cost of sales were $24.4 million and $56.1 million, respectively, compared to $3.4 million and $6.2 million in the comparable prior year periods. R&D Expense: Fourth quarter and full-year 2025 R&D expense was $116.3 million and $388.5 million, respectively, compared to $25.6 million and $236.7 million in the comparable prior year periods. The full-year increase was primarily due to upfront payments for business development transactions, partially offset by a reduction in expenses related to clinical trials. SG&A Expense: Fourth quarter and full-year 2025 SG&A expense was $240.0 million and $813.8 million, respectively, compared to $141.2 million and $435.1 million in the comparable prior year periods. The full-year increase was primarily due to increases in commercial activities for Rezdiffra including corresponding increases in headcount. Interest Income: Fourth quarter and full-year 2025 interest income was $9.5 million and $37.4 million, respectively, compared to $11.1 million and $46.7 million in the comparable prior year periods. The full-year decrease was primarily due to higher principal balances and interest rates in 2024. Interest Expense: Fourth quarter and full-year 2025 interest expense was $8.3 million and $22.3 million, respectively, compared to $3.5 million and $14.7 million in the comparable prior year periods. The full-year increase was primarily due to a higher average outstanding principal balance after entering into the new credit facility in July 2025. Cash, Cash Equivalents, Restricted Cash and Marketable Securities: As of Dec. 31, 2025, Madrigal had cash, cash equivalents, restricted cash, and marketable securities of $988.6 million, compared to $931.3 million as of Dec. 31, 2024. The increase was primarily due to entering into a new credit facility in July 2025 that consisted of a $350 million initial term loan funded at closing, a portion of which was used to repay all outstanding obligations under Madrigal’s then-outstanding loan facility, offset by funding of operations. Conference Call and Webcast At 8 a.m. EST today, Feb. 19, Madrigal will host a webcast to review its financial and operating results and provide a general business update. To access the webcast, please visit the investor relations section of the Madrigal website or click here to register. An archived webcast will be available on the Madrigal website following the event. About MASH Metabolic 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 the leading cause of liver transplantation in women and the second leading cause of all liver transplantation in the U.S. It is the fastest-growing indication for liver transplantation in Europe. 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 to 17 times higher risk of liver-related mortality as compared to patients without fibrosis. Madrigal is focused on reaching approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists in the U.S. Patients with MASH 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. An estimated 245,000 patients with compensated MASH cirrhosis (consistent with F4c fibrosis) are currently under the care of liver specialists in the U.S. As disease awareness improves and disease prevalence increases, the number of diagnosed patients with F2 to F4c MASH is growing. 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 both the FDA and European Commission for the treatment of MASH with moderate to advanced fibrosis (F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (F4c). For more information, visit . Forward Looking Statements This 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 expected growth of Rezdiffra sales in 2026, expected commercial insurance coverage for Rezdiffra in 2026, the expected benefit of Madrigal’s recently issued patent, Madrigal’s clinical development plans and timelines for its pipeline, Madrigal’s leadership position in the MASH sector, the potential size of the MASH market and 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; our ability to successfully commercialize Rezdiffra in the U.S. and Europe; risks related to obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of our clinical trials, including, but not limited to our ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for our 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 or of any other product candidate; market demand for and acceptance of Rezdiffra; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitors; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; our ability to protect our intellectual property rights; 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 1A of its Annual Report on Form 10-K for the year ended December 31, 2024, and as updated from time to time by Madrigal’s other filings with the SEC. Madrigal may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor Madrigal’s website in addition to following its press releases, filings with the SEC, public conference calls, and webcasts. Madrigal Pharmaceuticals, Rezdiffra™ and associated logos are trademarks of Madrigal Pharmaceuticals, Inc. Investor Contact Tina Ventura, IR@madrigalpharma.com Media Contact Christopher Frates, media@madrigalpharma.com (tables follow) Madrigal Pharmaceuticals, Inc. Condensed Consolidated Statement of Operations (in thousands, except share and per share amounts) Three Months Ended Twelve Months Ended December 31, December 31, 2025 2024 2025 2024 Revenues: Product revenue, net $ 321,083 $ 103,320 $ 958,403 $ 180,133 Operating expenses: Cost of sales 24,448 3,445 56,148 6,233 Research and development 116,268 25,648 388,525 236,718 Selling, general and administrative 239,976 141,224 813,827 435,057 Total operating expenses 380,692 170,317 1,258,500 678,008 Loss from operations (59,609 ) (66,997 ) (300,097 ) (497,875 ) Interest income 9,459 11,079 37,364 46,654 Interest expense (8,297 ) (3,498 ) (22,309 ) (14,671 ) Loss on extinguishment of debt - - (2,779 ) - Other income, net (128 ) - (463 ) - Net loss $ (58,575 ) $ (59,416 ) $ (288,284 ) $ (465,892 ) Basic and diluted net loss per common share $ (2.57 ) $ (2.71 ) $ (12.85 ) $ (21.90 ) Basic and diluted weighted average number of common shares outstanding 22,829,067 21,929,425 22,434,310 21,272,962 Madrigal Pharmaceuticals, Inc. Condensed Consolidated Balance Sheets (in thousands) December 31, December 31, 2025 2024 Cash, cash equivalents, restricted cash and marketable securities $ 988,649 $ 931,251 Trade receivables, net 134,476 53,822 Other current assets 122,645 47,854 Other non-current assets 13,819 9,320 Total assets $ 1,259,589 $ 1,042,247 Liabilities and Equity Current liabilities $ 310,288 $ 169,277 Long-term liabilities 346,612 118,587 Stockholders’ equity 602,689 754,383 Total liabilities and stockholders’ equity $ 1,259,589 $ 1,042,247