Efruxifermin

Published results from the 96-Week Phase 2b SYMMETRY trial in the New England Journal of Medicine Three presentations at the EASL Congress 2025 highlighted data demonstrating statistically significant reversal of compensated cirrhosis (F4) due to MASH and corroborating the anti-fibrotic activity of EFX seen in patients with pre-cirrhotic (F2-F3) MASH Cash, cash equivalents and short and long-term marketable securities of $1,086.2 million at June 30, 2025 SOUTH SAN FRANCISCO, Calif., Aug. 08, 2025 (GLOBE NEWSWIRE) -- Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, today reported second quarter financial results for the period ending June 30, 2025, and provided business updates. “In the second quarter of 2025, we continued to build on the strong momentum established with the announcement of statistically significant reversal of cirrhosis due to MASH in the Phase 2b SYMMETRY study, supported by the peer-reviewed publication of 96-week results in the New England Journal of Medicine and additional data presentations that reinforce the anti-fibrotic activity of EFX across all stages of MASH,” said Andrew Cheng, president and CEO. “We look forward to reporting preliminary results of our first Phase 3 trial, SYNCHRONY Real-World, in the first half of 2026 as well as a readout of SYNCHRONY Histology in the first half of 2027.” Phase 2b SYMMETRY Data Featured in the New England Journal of Medicine In a significant milestone for the EFX clinical program, data from the Phase 2b SYMMETRY study evaluating EFX in patients with compensated cirrhosis (F4) due to MASH was published in the New England Journal of Medicine on May 9, 2025.This peer-reviewed publication reinforces the importance of the SYMMETRY findings and positions EFX as a potential first- and best-in-class therapy with disease-modifying activity in advanced-stage MASH. New 96-Week SYMMETRY Findings Underscore Broad Potential of EFX in Late-Breaking Oral Presentation at EASL 2025 Week 96 data presented during a late-breaking oral session at EASL 2025 demonstrated the potential of EFX 50mg to reverse cirrhosis in high-need MASH subgroups, including patients with cryptogenic cirrhosis and type 2 diabetes.Data suggest EFX may benefit patients at greater risk of progression toward decompensation and end-stage liver disease, showing reversal of cirrhosis for the first time in these groups with high unmet need.The official press program of EASL 2025 highlighted the presentation of SYMMETRY results, underlining the importance of the results within the landscape of liver diseases. New Analyses from Phase 2b HARMONY Study Presented at EASL 2025 Highlight Consistent Fibrosis Improvement with EFX New insights from the Phase 2b HARMONY study demonstrated EFX’s ability to improve fibrosis in pre-cirrhotic MASH (F2-F3) using both conventional pathologist scoring and advanced AI-based analysis of biopsy images.In an oral presentation, analyses of patients treated with 50mg EFX for 96 weeks showed that a majority of individuals achieved improvements across all three measures of antifibrotic response: qFibrosis® staging of biopsy images, ELF score, and liver stiffness by FibroScan®, in stark contrast to placebo patients, none of whom met all three of the same measures.AI-based analysis corroborated the treatment effect observed by conventional pathology scoring.A supporting poster provided evidence that qFibrosis® may detect fibrosis improvement earlier than conventional pathology scoring, manifested as statistically significant fibrosis regression in peri-portal and peri-sinusoidal zones. Second Quarter 2025 Financial Results Akero's cash, cash equivalents and short and long-term marketable securities as of June 30, 2025, were $1,086.2 million.Akero believes that its cash, cash equivalents and short and long-term marketable securities will be sufficient to fund its current operating plan into 2028.Research and development expenses for the three-month period ended June 30, 2025 were $69.3 million, compared to $55.3 million for the comparable period in 2024. These increases were attributable to higher expenses associated with the ongoing Phase 3 SYNCHRONY Histology, Real-World, and Outcomes studies, and manufacture of clinical supplies for Phase 3 and potential marketing applications, as well as higher expenses for personnel.General and administrative expenses for the three-month period ended June 30, 2025 were $11.6 million, compared to $10.4 million for the comparable period in 2024. These increases are attributable to higher expenses for personnel, professional services and other costs associated with operating as a public company.Total operating expenses were $80.9 million for the three-month period ended June 30, 2025, compared to $65.7 million for the comparable period in 2024. About MASHMASH is a serious form of MASLD that is estimated to affect 17 million Americans. MASH is characterized by an excessive accumulation of fat in the liver that causes stress and injury to liver cells, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer and eventually death. Approximately 20% of patients with MASH are expected to progress to cirrhosis, which has a higher risk of mortality. There are no approved treatments for compensated cirrhosis due to MASH, one of the fastest growing causes of liver transplants and liver cancer in the US and Europe. About Cirrhosis Due to MASH Cirrhosis due to MASH (metabolic dysfunction-associated steatohepatitis) is a life-threatening disease with high risk of liver failure, cancer, and death. By 2030, an estimated 3 million Americans are projected to have cirrhosis due to MASH. About EFX Efruxifermin (EFX), Akero’s lead product candidate for MASH, is currently being evaluated in three ongoing Phase 3 studies. In multiple Phase 2 studies, EFX has been observed to reverse fibrosis (including compensated cirrhosis due to MASH), resolve MASH, reduce non-invasive markers of fibrosis and liver injury, and improve insulin sensitivity and lipoprotein profile. This holistic profile offers the potential to address the complex, multi-system disease state of all stages of MASH, including improvements in lipoprotein risk factors linked to cardiovascular disease – the leading cause of death among MASH patients. Engineered to mimic the biological activity profile of native FGF21, EFX is designed to offer convenient once-weekly dosing and has been generally well-tolerated in clinical trials to date. About Akero Therapeutics Akero Therapeutics is a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including metabolic dysfunction-associated steatohepatitis (MASH). Akero’s lead product candidate, efruxifermin (EFX), is currently being evaluated in three Phase 3 clinical studies: SYNCHRONY Histology in patients with pre-cirrhotic (F2-F3 fibrosis) MASH, SYNCHRONY Outcomes in patients with compensated cirrhosis (F4) due to MASH, and SYNCHRONY Real-World in patients with MASH or MASLD (metabolic dysfunction-associated steatotic liver disease). The Phase 3 SYNCHRONY program builds on the results of two Phase 2b clinical trials, the HARMONY study in patients with pre-cirrhotic MASH and the SYMMETRY study in patients with compensated cirrhosis due to MASH. Akero is headquartered in South San Francisco. Visit us at akerotx.com and follow us on LinkedIn and X for more information. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements'' within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, statements regarding Akero’s business plans and objectives; the potential therapeutic effects of EFX, as well as the dosing, safety and tolerability of EFX, the future potential of EFX as a therapy with disease-modifying activity in advanced-stage MASH; upcoming milestones, including the results, and expected timing to report results from the SYNCHRONY Phase 3 program; and Akero's growth as a company and expectations regarding its uses of capital, expenses, and financial results, including the expected cash runway. Any forward-looking statements in this press release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Akero’s product candidate development activities and planned clinical trials; Akero’s ability to execute on its strategy; positive results from any of its clinical studies may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States and foreign countries; Akero’s ability to fund operations; as well as those risks and uncertainties set forth more fully under the caption "Risk Factors'' in Akero’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission (SEC) as well as discussions of potential risks, uncertainties and other important factors in Akero’s other filings and reports with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Akero undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Contact:Christina Tartaglia332.322.7430christina.tartaglia@precisonaq.com Media Contact:Peg Rusconi617.910.6217peg.rusconi@deerfieldgroup.com Akero Therapeutics, Inc.Condensed Consolidated Balance Sheets(Unaudited)(In thousands) June 30, 2025 December 31, 2024Assets Cash, cash equivalents and short-term marketable securities$742,315 $743,078 Other current assets 22,285 27,302 Non-current assets 344,552 55,506 Total assets$1,109,152 $825,886 Liabilities and Stockholders’ Equity Current liabilities$60,401 $39,754 Non-current liabilities 22,932 36,020 Stockholders’ equity 1,025,819 750,112 Total liabilities and stockholders’ equity$1,109,152 $825,886 Akero Therapeutics, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(Unaudited)(In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024Operating expenses: Research and development$69,254 $55,322 $138,821 $105,972 General and administrative 11,619 10,419 22,934 19,723 Total operating expenses 80,873 65,741 161,755 125,695 Loss from operations (80,873) (65,741) (161,755) (125,695)Interest expense (1,172) (1,231) (2,326) (2,222)Interest and other income, net 11,540 10,985 22,851 18,586 Net loss$(70,505) $(55,987) $(141,230) $(109,331)Comprehensive loss$(70,602) $(56,169) $(141,190) $(109,862)Net loss per common share, basic and diluted$(0.86) $(0.81) $(1.76) $(1.70)Weighted-average number of shares used in computing net loss per common share, basic and diluted 81,721,387 69,160,484 80,197,494 64,234,122

氨基观察-创新药组原创出品 作者 | 沙晓威 MASH市场继续大爆发。 Madrigal的MASH新药Rezdiffra从去年上市以来，季度销售额一路高涨，上市满一年销售额达3.17亿美元，其中，今年一季度销售额则高达1.37亿美元。 这是市场对于MASH“第一人”的回报。当然，尽管Rezdiffra仅开发了5%的目标市场，空间依然巨大，但更激烈的竞争早已在酝酿之中。 除了与Rezdiffra同靶点的THRβ激动剂，还有GLP-1、FGF21、PPAR等靶点激动剂正在加速中后期临床，意图在MASH这个蓝海中分一杯羹。就在不久前，GSK以20亿美元买下了FGF21激动剂Efimosfermin alfa，后者目前已进入3期临床。 面对这种情况，意图打造一个MASH帝国的Madrigal，显然不能坐以待毙。 7月30日，Madrigal发布公告，以以1.2 亿美元的预付款、最高可达20亿美元的总交易额，与石药集团达成授权合作，获得其口服GLP-1小分子激动剂SYH2086的中国以外全球权益。 Madrigal引进SYH2086目的在于，与Rezdiffra进行联用，通过抗纤维化+减重来优化MASH 治疗。 这笔交易也释放出一个信号，那就是MASH的下一个阶段，将不再是单一靶点的较量，而是围绕THR-β、GLP-1、FGF21等多靶点、多机制的协同战。这场技术军备赛，正在不断升温。 / 01 / 超预期的“第一人” 自1980年MASH（原NASH）被提出以来，全球药企累计投入超千亿美元，超百款药物折戟。 MASH研发黑洞的称号并不是说说而已。而Madrigal成为了第一个吃螃蟹的人。2024年3月1日，Rezdiffra正式获得FDA批准，成为首款获批用于治疗MASH伴纤维化的口服小分子药物。 从撕开一道口子，到让市场看到MASH赛道的爆发力，Madrigal只用了几个月的时间，远超市场预期。 如下图所示，自商业化以来，Rezdiffra销售额持续攀升：2024年二季度为1460万美元，三季度达到6220万美元，四季度突破1亿美元，今年一季度更是达到1.37亿美元。 上市满一年，Rezdiffra销售额达到3.17亿美元。这样的成绩，超出市场预期。 而Rezdiffra之所以放量迅速，除了“首药效应”，还离不开以下几个关键因素：  首先是疗效，这款THR-β受体选择性激动剂，在一项针对F1B-F4全阶段MASH纤维化患者的3期MAESTRO-NASH研究中展现出明确临床获益。 与安慰剂相比，80mg组和100mg组25.9%的患者和29.9%的患者实现了MASH消退且纤维化没有恶化。 其次，作为小分子药物，每日一次的口服剂型带来了依从性优势。 最大的推动则是Madrigal的商业化举措。在美国获得了80%的商业保险覆盖，且95%的支付可以接受无创检测而并不要求穿刺活检诊断，这对于提高患者依从性帮助极大。 而这可能还只是开始。根据公司财报，使用Rezdiffra的患者人数不断攀升，2025年一季度超过1.7万例，相比于31.5万例目标人群，渗透率仅5%，意味着潜在增长空间巨大。 此外，处方医生的渗透率也一路高升。公司CEO Bill Sibold此前直言，自己职业生涯中从来没看到过一个新药上市如此受到专家的重视。Bill Sibold曾在赛诺菲工作了12年，其中6年主要负责Dupixent的销售。 与此同时，Rezdiffra也在积极拓展适应症。从目前的数据来看，Rezdiffra对F4阶段的MASH肝硬化患者同样具有治疗潜力。结合Rezdiffra的先发优势，一旦适应症拓展成功，商业化表现将进一步超预期。 当然，尽管Rezdiffra势头正猛，但考虑到未来激烈的市场竞争，尤其GLP-1等对手的虎视眈眈，Madrigal也在加紧布局，尤其是联合疗法。 / 02 / 强敌变队友 MASH正在从GLP-1“受害者”变成“受益者”。 此前，由于替尔泊肽等GLP-1在MASH临床中展现出过分优秀的数据，导致市场担心，大部分MASH玩家，可能都要活在GLP-1的阴影之下。 替尔泊肽的2期临床数据非常突出，甚至在肝纤维化改善患者比例上优于Rezdiffra。去年11月，司美格鲁肽治疗MASH的三期临床ESSENCE研究的初步结果，让市场松了一口气。 更重要的是，Madrigal指出，在真实世界使用中，已有不少患者联合使用Rezdiffra和GLP-1。 Madrigal在此前财报电话会议上表示，这个庞大而未被充分渗透的市场中，显然有多种机制来治疗这种具有挑战性的疾病。我们期待联合治疗成为治疗范式的一部分。 也正在这一背景之下，其于7月底宣布与石药集团达成授权合作，引入其口服GLP-1小分子激动剂SYH2086，并明确目标是将其与Rezdiffra联用，打造“双口服”的长期治疗方案。 尽管SYH2086还处于早期，但Madrigal认为其“展现出优异的体外激动活性，以及体内降糖和减重效果，在多种动物模型中，在广泛的剂量范围内具有线性药代动力学特征，且未观察到显著的安全风险。” 公司首席医疗官David Soergel 医学博士也给出了开发Rezdiffra与口服GLP-1联合疗法的临床理由，即希望通过每日一次口服药丸，平衡GLP-1带来的减重效果、与Rezdiffra的抗纤维化+降脂作用，以优化MASH治疗的疗效和耐受性。 考虑到Rezdiffra与GLP-1的联合接受度高，有利于进一步扩大现有的治疗人群。 而在Madrigal看来，SYH2086虽尚处在临床早期，但在动物体内显示出较好的减重效果以及口服吸收性能。这也是Madrigal看中的：双口服药物的组合，打造“疗效更佳、依从性更强”的新方案。 尽管小分子GLP-1开发难度系数极高，包括辉瑞等大药企也曾多次折戟，但为了患者依从性，Madrigal还是决定押注这一彩票。毕竟，其曾公开指出GLP-1不如Rezdiffra之处，比如耐受性差、给药方式不友好等等。 考虑到MASH药物的治疗，需要同时缓解纤维化并降低肝脂肪含量，涉及到的代谢通路复杂，其最终治疗方案可能需要联合多个药物进行治疗。 就未来而言，联合疗法的构建，将会是应对激烈竞争的一种方式。这也与Madrigal在电话会上的期待一致，希望联合治疗成为治疗范式的一部分。 / 03 / 更加激烈的角逐 Rezdiffra获批上市，开启MASH元年，也正式拉开了这一百亿美金市场的激烈角逐。 在治疗药物方面，诸多药企还在不断探索。除了THR-β与GLP-1，FGF21也成为全球MASH治疗中最受关注的新机制。 Akero的Efruxifermin是一款Fc-FGF21融合蛋白，在F4期肝硬化患者中表现亮眼。2b期研究数据显示，39%（46/134）实现了肝硬化逆转，且MASH无恶化。有趣的是，Efruxifermin的肝硬化逆转效果预期收益与GLP-1治疗无关：在基线未服用GLP-1的97名患者亚组中，45%的患者肝硬化得到逆转（安慰剂组为17%）。 如此超预期的临床结果，使Efruxifermin有望填补Rezdiffra在F4期MASH肝硬化患者治疗中的空白。 也正是对MASH市场及这个靶点的看重，今年5月，GSK以最高20亿美元收购Boston Pharmaceuticals的Efimosfermin alfa，这是一款具有调脂、抗炎、逆转纤维化多重作用的FGF21类似物，即将进入3期临床。 尽管此前的临床结果显示Efimosfermin alfa的MASH缓解率不如Efruxifermin，但是经过工程化改造的Efimosfermin alfa，其半衰期可以延长到21天，可实现每月给药1次。 显然，Rezdiffra虽率先上市，但药企对MASH的机制仍在探索，治疗药物机制较多，必然会产生更多的变数。 在这个过程中，中国企业也在深度参与其中，包括中国生物制药、歌礼制药、正大天晴、东阳光药、歌礼制药、康哲药业等药企，均在MASH领域投入了极大的资源。 仅针对FGF12这个靶点，就有10余家企业布局，其中正大天晴的TQA2225、华东医药的DR10624等产品均已进入中后期临床阶段。也有企业已不满足于这一单靶点的探索。 去年11月，Apollo与东阳光药达成接近10亿美元的BD合作，以开发FGF21/GLP-1双靶点融合蛋白HEC88473，用于减肥和MASH。 正大天晴的lanifibranor则是国内第一个进入临床3期的MASH口服药物。该药物以PPAR为靶点，在体内实现抗纤维化和抗炎症双通路调节。此前，FDA已授予lanifibranor用于MASH的突破性疗法认证和快速通道资格。 回看过去几年，MASH治疗从无药可用到首药破冰，再到如今的新机制、联用博弈，药企全方位出击、加速推进。而对所有入局者来说，都会面临疗效、患者依从性以及商业化的多方考验。 MASH这盘大棋，才刚刚落子。 PS：欢迎扫描下方二维码，添加氨基君微信号交流。