Sebetralstat

– Received FDA approval of EKTERLY® (sebetralstat)—the first and only oral on-demand treatment for hereditary angioedema; U.S. launch underway – – Six additional global regulatory submissions under review – – Entered licensing agreements for sebetralstat commercialization in Japan and Canada – – $220.6M in cash, providing runway into 2027 – CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)--Jul. 10, 2025-- KalVista Pharmaceuticals, Inc. (Nasdaq: KALV), today provided an operational update and released financial results for the fiscal year ended April 30, 2025. “The FDA approval of EKTERLY represents a major milestone—not only as the first commercial product for KalVista, but more importantly, as the first and only oral on-demand therapy for people living with HAE,” said Ben Palleiko, CEO of KalVista Pharmaceuticals. “EKTERLY delivers a long-awaited treatment that is safe, effective, and easy to administer. Our commercial team is actively engaging in the field, leveraging their expertise to educate and activate patients and physicians to enable timely access, drive awareness, and support informed treatment decisions around this important new therapy. With commercial partners now in place in Canada and Japan, and six global regulatory submissions under review, we believe EKTERLY is poised to become the foundational therapy for HAE management worldwide.” Recent Business Highlights EKTERLY® (sebetralstat) On July 7, 2025, KalVista announced FDA approval of EKTERLY (sebetralstat), a novel plasma kallikrein inhibitor, for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. KalVista further strengthened the robust body of clinical evidence supporting the efficacy and safety of EKTERLY (sebetralstat) for the treatment of HAE. The Company presented new data at the European Academy of Allergy and Clinical Immunology Congress 2025 (EAACI), the 14th C1-inhibitor Deficiency & Angioedema (C1-INH) Workshop in Budapest, Hungary, and the Eastern Allergy Conference (EAC) in Palm Beach, Florida. Key highlights from these medical congresses are outlined below: EAACI: Data showed the efficacy of EKTERLY (sebetralstat) for the on-demand treatment of HAE attacks among patients receiving long-term prophylaxis (LTP). Real world data highlighted significant challenges with LTP adherence, and ongoing reliance on on-demand medications. In KONFIDENT-S, EKTERLY (sebetralstat) delivered rapid, consistent relief for attacks, regardless of LTP mechanism of action with a median time to beginning of symptom relief of 1.3 hours. C1-INH: Analysis from nearly 1,600 attacks in KONFIDENT-S showed a median time to end of attack progression of 19.8 minutes. These results aligned closely with KONFIDENT, reinforcing the rapid effect of EKTERLY (sebetralstat) after absorption. Interim data from KONFIDENT-S highlighted the role of EKTERLY (sebetralstat) in treating mucosal attacks with a median time to beginning of symptom relief of 1.3 hours for both abdominal and laryngeal attacks. EAC: In KONFIDENT-S, EKTERLY (sebetralstat) was used to treat 76 attacks that had progressed to severe or very severe after a median of 2.16 hours from attack onset, demonstrating its utility in more advanced stages of HAE attacks. The median time to beginning of symptom relief for these attacks was 1.36 hours, with reduction in attack severity and substantial reduction of symptom burden in a median of 1.77 hours and 9.15 hours, respectively. EAACI: Data showed the efficacy of EKTERLY (sebetralstat) for the on-demand treatment of HAE attacks among patients receiving long-term prophylaxis (LTP). Real world data highlighted significant challenges with LTP adherence, and ongoing reliance on on-demand medications. In KONFIDENT-S, EKTERLY (sebetralstat) delivered rapid, consistent relief for attacks, regardless of LTP mechanism of action with a median time to beginning of symptom relief of 1.3 hours. C1-INH: Analysis from nearly 1,600 attacks in KONFIDENT-S showed a median time to end of attack progression of 19.8 minutes. These results aligned closely with KONFIDENT, reinforcing the rapid effect of EKTERLY (sebetralstat) after absorption. Interim data from KONFIDENT-S highlighted the role of EKTERLY (sebetralstat) in treating mucosal attacks with a median time to beginning of symptom relief of 1.3 hours for both abdominal and laryngeal attacks. EAC: In KONFIDENT-S, EKTERLY (sebetralstat) was used to treat 76 attacks that had progressed to severe or very severe after a median of 2.16 hours from attack onset, demonstrating its utility in more advanced stages of HAE attacks. The median time to beginning of symptom relief for these attacks was 1.36 hours, with reduction in attack severity and substantial reduction of symptom burden in a median of 1.77 hours and 9.15 hours, respectively. Organizational In April, KalVista entered into an exclusive agreement with Kaken Pharmaceutical, Co., Ltd. to commercialize sebetralstat in Japan. Under the terms of the deal, in June 2025 KalVista received an upfront payment of $11 million, and an additional $11 million will be paid upon achieving a regulatory milestone anticipated in early 2026. This agreement also includes potential commercial milestone payments of up to $2 million and royalties based on the Japan National Health Insurance (NHI) price, with royalties expected to be in the mid-twenties as a percentage of sales. In June, KalVista granted Pendopharm, a division of Pharmascience Inc., the exclusive rights to manage the regulatory approval process and commercialization of sebetralstat in Canada. Financial Results for Fiscal Year Ended April 30, 2025: Research and development expenses were $71.7 million and $86.2 million for the fiscal years ended April 30, 2025, and 2024, respectively. The decrease in R&D was primarily attributable to reduced clinical trial expenses, preclinical activities and recognizing expense associated with EKTERLY (sebetralstat) pre-commercial awareness within General & Administrative. General and administrative expenses were $116.3 million and $54.3 million for the fiscal years ended April 30, 2025, and 2024, respectively. The increase in G&A expenses was primarily due to pre-commercial planning expenses related to EKTERLY (sebetralstat). Cash, cash equivalents and marketable securities were $220.6 million on April 30, 2025, compared to $210.4 million on April 30, 2024. About KalVista Pharmaceuticals, Inc. KalVista Pharmaceuticals, Inc., is a global biopharmaceutical company dedicated to developing and delivering life-changing oral therapies for individuals affected by rare diseases with significant unmet needs. In the U.S., KalVista markets EKTERLY®, the first and only oral on-demand treatment for hereditary angioedema (HAE). The Company has multiple regulatory applications under review in key global markets. For more information about KalVista, please visit www.kalvista.com and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, information relating to our business and business plans, the success of our efforts to commercialize EKTERLY® (sebetralstat), our ability to successfully obtain foreign regulatory approvals for sebetralstat, our expectations about the safety and efficacy of sebetralstat and our other product candidates, the timing of clinical trials and their results, our ability to commence clinical studies or complete ongoing clinical studies, including our KONFIDENT-S and KONFIDENT-KID trials, and the ability of EKTERLY to treat HAE , and the future progress and potential success of our oral Factor XIIa program. Further information on potential risk factors that could affect our business and financial results are detailed in our filings with the Securities and Exchange Commission, including in our annual report on Form 10-K for the year ended April 30, 2025, our quarterly reports on Form 10-Q, and our other reports that we may make from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. KALVISTA PHARMACEUTICALS, INC. Consolidated Balance Sheets April 30, 2025 and 2024 (in thousands except share and per share amounts) (Unaudited) 2025 2024 Cash, cash equivalents & Marketable securities $ 220,617 $ 210,401 Other current assets 21,073 15,289 Total current assets 241,690 225,690 Other assets 9,080 9,714 Total assets $ 250,770 $ 235,404 Current liabilities $ 45,167 $ 22,807 Long-term liabilities 110,212 6,015 Total Liabilities 155,379 28,822 Stockholders’ equity 95,391 206,582 Total liabilities and stockholders’ equity $ 250,770 $ 235,404 KALVISTA PHARMACEUTICALS, INC. Consolidated Statements of Operations and Comprehensive Loss Years Ended April 30, 2025 and 2024 (in thousands, except share and per share amounts) (Unaudited) 2025 2024 Research and development $ 71,709 $ 86,167 General and administrative 116,286 54,278 Total operating expenses 187,995 140,445 Operating loss (187,995 ) (140,445 ) Other income: Interest income 6,435 3,896 Interest (expense) (5,785 ) — Foreign currency exchange gain (loss) 2,481 138 Other income (expenses), net 4,812 9,767 Total other income 7,943 13,801 Loss before income taxes (180,052 ) (126,644 ) Income tax (benefit) expense 3,392 — Net loss $ (183,444 ) $ (126,644 ) Net loss per share, basic and diluted $ (3.69 ) $ (3.44 ) Weighted average common shares outstanding, basic and diluted 49,652,878 36,786,575 View source version on businesswire.com: https://www.businesswire.com/news/home/20250710831184/en/ Investors: Ryan Baker Head, Investor Relations (617) 771-5001 ryan.baker@kalvista.com Media: Molly Cameron Director, Corporate Communications (857) 356-0164 molly.cameron@kalvista.com Source: KalVista Pharmaceuticals, Inc.

关注并星标CPHI制药在线2025年7月7日，全球遗传性血管性水肿（HAE）治疗领域迎来里程碑时刻！KalVista Pharmaceuticals研发的Sebetralstat（Ekterly）获FDA批准上市，成为首个用于HAE急性发作按需治疗的口服药物。注射时代目前，全球已有 5 款药物获批用于 HAE 急性发作的治疗，分别是达那唑（赛诺菲）、Berinert（CSL）、艾替班特（武田 / 赛诺菲）、艾卡拉肽（武田 / 赛诺菲）、Ruconest（Pharming）。然而，这些药物均为静脉注射或皮下注射制剂。注射给药方式虽然能够使药物快速进入血液循环，发挥治疗作用，但也存在诸多痛点。在使用场景上，注射给药往往需要在专业的医疗环境下，由医护人员进行操作，或者需要他人协助。这对于 HAE 患者来说，在急性发作时，可能无法及时获得专业的注射服务，从而延误治疗时机。例如，患者在外出旅行、工作或生活中突然发作，很难立即找到合适的场所和人员进行注射。从操作便捷性来看，注射过程相对复杂，需要严格的无菌操作和正确的注射技巧。对于 HAE 患者，在急性发作时，身体不适且情绪紧张，自身难以完成注射操作。另外，注射还可能带来一些不良反应，如注射部位疼痛、红肿、硬结，以及感染等风险。长期频繁注射还可能导致局部组织损伤、脂肪萎缩等问题。这些不良反应不仅增加了患者的痛苦，还可能影响患者对治疗的依从性。患者依从性也是一个重要问题。对于需要频繁用药的 HAE 患者来说，长期的注射治疗可能会给患者带来心理压力和身体负担，导致患者对治疗的依从性下降。一些患者可能会因为害怕注射疼痛、担心不良反应或觉得注射不便等原因，而减少用药次数或中断治疗，从而影响治疗效果。赛诺菲、武田（通过收购 Shire）、CSL Behring、Pharming 等大型跨国药企凭借这些注射产品，占据了主要的 HAE 治疗市场份额，形成了相对稳定的竞争格局。尽管这些药物在一定程度上能够有效治疗 HAE 急性发作，但注射给药方式所带来的种种局限，构成了巨大的未满足临床需求和患者体验痛点，亟待更优的解决方案来打破这一局面。口服破局在 HAE 治疗领域，长期以来注射给药的主导地位终于被打破，KalVista 公司研发的 Sebetralstat 横空出世，带来了革命性的改变。2025 年 7 月 7 日，KalVista Pharmaceuticals 宣布 Sebetralstat（商品名：Ekterly）获 FDA 批准上市，用于治疗 12 岁及以上儿童和成人患者的遗传性血管性水肿（HAE）急性发作，它成为第一个获批用于按需治疗 HAE 的口服药物 。Sebetralstat 是一种新型口服血浆激肽释放酶（PKK）抑制剂。HAE 的发病机制主要是由于 C1 酯酶抑制剂（C1INH）蛋白缺乏或功能障碍，导致 PKK - 激肽系统过度激活，进而引发全身组织肿胀。Sebetralstat 正是通过抑制这一过度激活的系统，减少组织肿胀的发生，从而达到治疗 HAE 的目的。其关键的 III 期 KONFIDENT 研究数据令人瞩目。在症状缓解时间方面，Sebetralstat（300mg 和 600mg）组的症状缓解开始时间显著快于安慰剂组，分别为 1.61h 和 1.79h，而安慰剂组为 6.72h 。在发作严重程度降低时间上，Sebetralstat 组也快于安慰剂组（9.27h vs 7.75h vs >12h）。并且，Sebetralstat 组症状完全消退的时间也更快，300mg 和 600mg 剂量组 24h 内症状完全消退的患者比例分别为 42.5% 和 49.5%，安慰剂组为 27.4% 。在更贴近真实世界的 KONFIDENT-S 开放标签扩展试验中，截至 2024 年 9 月，患者在发作后中位数 10 分钟内即可使用 Sebetralstat 进行治疗。最新数据还显示，对于涉及喉部、腹部的发作以及接受长期预防治疗患者的突破性发作，症状开始缓解的中位数时间为 1.3 小时。“口服按需” 的治疗模式带来了诸多颠覆性的价值。从患者自主性角度来看，患者可以随身携带药物，在急性发作时随时服用，无需依赖他人或特定的医疗场所，极大地增强了患者对疾病的自我管理能力。这对于提高患者的生活质量有着显著的意义，患者不再需要时刻担忧发作时无法及时获得治疗，能够更加自由地参与日常生活和社交活动。快速响应急性发作也是一大优势，中位10分钟的等待用药时间，相较于以往寻找注射场所和人员的过程，大大缩短了治疗的延误时间，使患者能够在发作初期就及时得到药物治疗，有效减轻症状和降低严重并发症的风险。与现有的注射药物相比，Sebetralstat 的定位明确，它既可以直接替代现有的急性发作注射治疗药物，为患者提供一种更为便捷的选择；也可以作为补充，与其他治疗方式联合使用。在一些患者对注射治疗存在恐惧、依从性差或者在无法及时获得注射治疗的情况下，Sebetralstat 的口服剂型就成为了理想的替代方案 。预防战场在 HAE 治疗领域，除了 KalVista 公司在急性发作治疗方面取得突破外，BioCryst 公司也凭借其口服药物 Berotralstat（商品名：Orladeyo）在预防领域占据了重要地位。BioCryst 是一家全球性的生物技术公司，致力于改善补体介导疾病和其他罕见疾病患者的生活。Berotralstat 是一种口服的血浆激肽释放酶抑制剂，主要用于预防 12 岁以上成人和儿科患者的遗传性血管性水肿发作 。其作用机制是通过抑制血浆激肽释放酶的活性，阻断其将高分子量激肽原裂解为缓激肽的过程，从而减少因缓激肽增多导致的血管通透性增加和组织水肿，降低 HAE 发作的频率和严重程度。在 Sebetralstat 获批之前，Berotralstat 是全球唯一获批的口服 HAE 治疗药物，不过它仅用于预防 HAE 发作。从市场格局来看，BioCryst 在口服预防药物领域处于相对独立的地位，在一定程度上填补了 HAE 预防治疗的空白。然而，它也存在一定的局限性。尽管 Berotralstat 能够显著减少患者的发作次数，如在关键的 3 期 APeX - 2 试验中，Berotralstat（150mg，每日 1 次）可显著减少患者 24 周内 HAE 发作次数，并且这种效果持续至第 48 周，完成 48 周试验的患者的 HAE 发作频率从基线平均 2.9 次 / 月，降至平均 1 次 / 月 。但大多数 HAE 患者在长期预防治疗后，仍会在不可预测的情况下发作，并且需要接受按需治疗药物治疗。这意味着单纯的预防治疗无法完全满足 HAE 患者的需求，患者在接受 Berotralstat 预防治疗的同时，仍需有应对急性发作的有效手段。与主要用于急性发作按需治疗的 Sebetralstat 相比，Berotralstat 和 Sebetralstat 在治疗策略上存在本质差异，这也决定了它们之间并非竞争关系，而是具有潜在的互补性。未来，可能会出现这样一种治疗模式：部分患者采用 “Berotralstat 长期预防 + Sebetralstat 按需应对突破性发作” 的组合策略。这种组合策略能够充分发挥两种药物的优势，既通过长期预防减少发作次数，又能在急性发作时及时有效地进行治疗，为患者提供更全面、更个性化的治疗方案，进一步改善患者的生活质量和疾病管理效果。巨头应对与未来战场Sebetralstat 的获批上市，无疑在 HAE 治疗领域投下了一颗重磅炸弹，对现有的巨头格局产生了巨大的冲击 。赛诺菲、武田、CSL、Pharming 等公司，长期凭借注射类 HAE 治疗药物占据着主要市场份额，但 Sebetralstat 口服按需治疗的优势，使其在市场竞争中脱颖而出，成为这些巨头不可忽视的竞争对手。口服药物的便捷性是其最大的竞争优势，这将显著分流注射药物的市场份额。患者对于治疗方式的选择，往往会受到便捷性的影响，尤其是在 HAE 这种需要随时应对急性发作的疾病中，口服药物能够让患者更加自主地进行治疗，减少对医疗场所和专业人员的依赖，这对于提高患者的生活质量和治疗依从性具有重要意义。面对这一挑战，这些巨头药企需要重新评估其产品组合和市场策略。降价可能是一种应对方式，通过降低药物价格来提高产品的竞争力，但这也可能会影响到企业的利润空间；加强服务也是一种策略，例如提供更加完善的患者教育、随访服务等，以提高患者的满意度和忠诚度；开发下一代产品则是从根本上提升竞争力的方法，通过研发更有效、更便捷的治疗药物，来满足患者的需求。KalVista 公司凭借 Sebetralstat 这一突破性产品，从一家 Biotech 公司迅速跃升为 HAE 治疗领域的重要参与者，市场地位得到了显著提升 。在此之前，KalVista 作为一家专注于生物医药研发的公司，虽然在 HAE 治疗领域进行了深入的研究，但在市场上的影响力相对较小。Sebetralstat 的成功获批上市，不仅为公司带来了巨大的商业机会，也使其在行业内的知名度和声誉大幅提高。公司的市值可能会因此而增长，吸引更多的投资者关注；同时，也能够吸引更多的优秀人才加入，进一步提升公司的研发实力和创新能力。展望未来，HAE 药物的研发方向将呈现出多元化的趋势。随着 Sebetralstat 的成功上市，口服按需治疗药物的市场前景变得更加广阔，这将吸引更多的药企投入研发，预计未来会有更多、更优的口服按需药物涌现，市场竞争也将更加激烈 。口服预防药物的进一步优化也是一个重要的研发方向，目前 BioCryst 的 Berotralstat 虽然在预防领域取得了一定的成果，但仍有改进的空间，如提高疗效、减少副作用等，以更好地满足患者的需求。组合疗法研究也将成为未来的热点，探索口服预防和口服按需药物的联用效果，有望为患者提供更全面、更个性化的治疗方案。例如，对于一些病情较为复杂的患者，可能需要同时使用预防药物和按需治疗药物，以达到最佳的治疗效果。针对不同 HAE 分型的靶向治疗也是一个重要的研发方向，HAE 存在多种分型，不同分型的发病机制和临床表现可能存在差异，因此开发针对不同分型的靶向治疗药物，能够提高治疗的精准性和有效性。随着基因治疗技术的不断发展，未来也可能会出现针对 HAE 的基因治疗方法，从根本上治愈这种疾病，但目前基因治疗仍面临着技术、安全性和伦理等多方面的挑战，需要进一步的研究和探索。“口服化” 和 “患者友好型” 将成为未来 HAE 药物研发的核心趋势 。随着医疗技术的不断进步和患者需求的不断提高，研发更加便捷、有效、安全的治疗药物，将是药企在 HAE 治疗领域取得成功的关键。只有不断创新，满足患者的未满足需求，才能在激烈的市场竞争中立于不败之地。结语从长期依赖注射治疗到口服药物的出现，HAE 治疗领域正经历着一场意义深远的变革。口服药物 Sebetralstat 和 Berotralstat 的相继问世，不仅为患者带来了更便捷、更个性化的治疗选择，显著改善了患者的生活质量和疾病管理体验，也对 HAE 治疗市场格局产生了巨大的冲击，促使行业竞争更加多元化。我们期待未来能有更多创新药物和治疗方式出现，进一步优化 HAE 的治疗策略，为全球 HAE 患者带来更多希望，彻底改变他们与疾病相伴的生活轨迹。参考来源：Investors & NewsKalVista Pharmaceuticals官网END智药研习社近期直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~