ELVN-002

▲8月15-16日 苏州2024生物医药创新者峰会 扫码报名  注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 药融云数据www.pharnexcloud.com显示：2023年2月23日，临床阶段生物制药公司Enliven Therapeutics宣布与生物技术公司Imara完成合并，合并后的公司将以Enliven Therapeutics的名义运营，其股票于次日在纳斯达克全球精选市场交易（NASDAQ:ELVN）。 在合并的同时，Enliven完成了1.65亿美元的私募融资，由新投资者Fairmount和Venrock Healthcare Capital Partners共同领投，其他新投资者参与，包括Fidelity Management & Research Company，RA Capital Management，Frazier Life Sciences和Commodore Capital，以及Enliven所有现有机构投资者的支持。交易完成后，Enliven的现金流跑道延长到2026年，有望实现多个临床里程碑。此次合并完成后，Imara股东持有新公司约16%的股份，Enliven股东（包括私募投资者）持有约84%的股份。 药融云数据www.pharnexcloud.com显示:如今的Enliven Therapeutics是一家精准肿瘤学公司，专注于发现和开发小分子抑制剂，以帮助癌症患者不仅活得更久，而且活得更好。 截图自药融云数据库 Enliven Therapeutics组建了一支经验丰富的猎药人团队，在发现和开发小分子激酶抑制剂方面具有丰富的专业知识，团队中包括20多种临床候选分子的主要或共同发明人，其中4款获FDA批准；以及领导或参与过60多个小分子激酶抑制剂项目的发现、开发或商业化的精准肿瘤学和激酶抑制剂专家。 研发管线 Enliven通过将临床验证的靶点和特定的靶点产品组合与严格的临床试验设计和监管策略相结合，目标是开发具有更高临床成功概率的药物。 目前Enliven Therapeutics正在平行推进两个候选产品。 ELVN-001是一种强效、高选择性小分子激酶抑制剂，旨在特异性靶向断裂点簇集区Abelson白血病病毒（BCR-ABL）融合基因，这是慢性髓系白血病（CML）患者的致癌驱动因素。 尽管BCR-ABL酪氨酸激酶抑制剂（TKIs，例如伊马替尼）的批准显著提高了CML患者的预期寿命，但随着患者治疗时间延长，对生活质量的影响和治疗的耐受性逐渐成为重要的考虑因素。目前市场上绝大多数活性位点TKIs都具有脱靶活性，导致治疗相关的不良事件（AEs）和由于不耐受或耐药性而停药。据统计，有大约20%的患者在治疗的第1年内改变治疗方案，大约40%的患者在治疗的前5年内改变治疗方案，三线治疗及以上患者群体数量逐渐增长（占慢性CML患者的25%以上），但治疗选择有限。77%的医疗专业人员认为需要更有效、更安全、更可耐受的CML药物。 在临床前研究中，ELVN-001与某些领先的和研究性疗法相比，已被证明有更好的基因组选择性、耐受性和强大的肿瘤生长抑制作用。此外，该药物对T315I突变具有高活性，该突变对几乎所有已批准的TKIs都具有抗性。作为一种选择性活性位点抑制剂，ELVN-001的作用机制可能是变构BCR-ABL抑制剂，如第四代BCR-ABL酪氨酸激酶抑制剂Scemblix（Asciminib）的补充选择，这可能在CML的标准治疗方案中发挥越来越重要的作用。 另外，ELVN-001有可能成为对共病患者更有吸引力的一个选择，这些患者希望在严格的用药方案之外获得一些伴随用药方案和更多的用药自由度。ELVN-001目前正在慢性髓系白血病（CML）患者中进行1期临床试验。 2024年4月11日，Enliven Therapeutics宣布了评估ELVN-001在复发、难治或对现有酪氨酸激酶抑制剂（TKIs）不耐受的慢性髓系白血病（CML）患者中的1期临床试验的积极概念验证数据。 截至2024年3月18日，44%（7/16）的可评估反应患者在第12周达到累积主要分子学反应（MMR）率，既往使用过Asciminib和/或TKI耐药的患者也表现出40%的反应率。 在可评估反应的患者中，所有患者在12周时BCR：：ABL1转录水平都有改善或稳定。安全性方面，ELVN-001耐受性良好，无3级或更高级别的非血液学治疗相关不良事件（TRAE），也没有剂量减少的报告。 这些数据与先前批准的BCR：：ABL1 TKI的1期研究的累积MMR率相比具有优势，特别是考虑到该研究的反应评估时间更短，以及许多患者先前接受过多线治疗。 另外，药代动力学数据支持ELVN-001每日一次给药，具有灵活的给药要求（无显著的食物影响，药物与药物相互作用的风险极小）。值得一提的是，鉴于已批准的BCR::ABL1 TKI的靶点覆盖率与一线治疗疗效之间的强相关性，ELVN-001的剂量等于或大于40mg QD时，与第二代活性位点TKI相比，实现了更优的靶点覆盖率；ELVN-001的剂量为80mg QD时，实现了与Asciminib相似的靶点覆盖率。 消息公布当日，Enliven Therapeutics股价大涨20.18%。根据该公司披露，1b期数据预计将于2025年公布，预计将包括约60-100名接受过不同疗法的患者，并进行大量随访。2025年年底计划进行初步的监管互动，目的是明确首次头对头关键试验的监管路径。 截图自雪球 Enliven Therapeutics的第二款候选产品ELVN-002是一种有效的、高选择性的、中枢神经系统渗透性和不可逆的HER2抑制剂，具有抗野生型HER2和各种HER2突变的活性。 该候选药物旨在最大限度地抑制HER2，并实现合理的联合治疗，特别是对于HER2+癌症。该公司认为，Enhertu®（德曲妥珠单抗）颠覆了HER2突变肿瘤的现有治疗模式，对这种新的治疗方案有疾病进展或不耐受的患者又引出了新的未满足治疗需求，因此ELVN-002在HER2扩增和/或过表达的NSCLC（非小细胞肺癌）、CRC（结直肠癌）和MBC（转移性乳腺癌）治疗领域拥有潜在机会。 截图自药融云数据库 美国FDA已批准ELVN-002的IND申请，Enliven Therapeutics启动了第一个研究中心，以评估ELVN-002与曲妥珠单抗+/-化疗药物联合治疗HER2+转移性乳腺癌（MBC）和结直肠癌（CRC）成人患者的疗效。联合治疗研究的首例患者给药计划于2024年第二季度进行。 ELVN-002针对HER2+癌症患者的联合试验得到了正在进行的单药治疗试验的初步数据的支持，其中包括：研究者报告了HER2+和HER2突变肿瘤的反应（包括未经证实），包括使用Enhertu®（德曲妥珠单抗）治疗后疾病进展的患者和脑转移患者，剂量耐受性良好。 重要的是，在临床预测的最佳单药治疗剂量下，ELVN-002基于癌症患者的药代动力学和临床前HER2+疗效，与口服小分子HER2蛋白的酪氨酸激酶抑制剂（TKI）图卡替尼相比，其靶点覆盖率提高了10倍以上。 预计Enliven Therapeutics将于2025年公布ELVN-002的1期单药治疗数据、HER2+ CRC的1a/b期赫赛汀联合疗法数据以及HER2+ MBC的初始1a期联合疗法数据。 财务状况 2024年3月19日，Enliven Therapeutics宣布获得9000万美元的私募股权融资，新老投资者包括Commodore Capital、Fairmount、Venrock Healthcare Capital Partners、一位生物技术投资者、一个大型共同基金、Rock Springs Capital、Logos Capital、Woodline Partners LP和Acuta Capital Partners。融资完成之后，截至2024年3月31日，该公司拥有总计3.205亿美元的现金、现金等价物和有价证券，预计现金流跑道将延长至2026年底。该公司累计赤字为1.772亿美元。 Enliven Therapeutics公司2023全年研发费用为6460万美元，而2022年全年为3100万美元；一般和行政（G&A）费用为1900万美元，2022年全年为780万美元；2023年全年净亏损总额为7160万美元，而2022年全年为3770万美元。 2024年第一季度，该公司研发费用为2000万美元，去年同期为1190万美元；一般和行政费用为600万美元，去年同期为450万美元；2024年第一季度净亏损2270万美元，去年同期为1470万美元。 以下为Enliven Therapeutics股东情况（截至2024年4月8日）： 截至2024年6月25日，Enliven Therapeutics公司市值约为10.3亿美元。截止发文前，市值为11.59亿美元，每股24.65美元。 美“生物安全法案”事件影响 鉴于目前Enliven Therapeutics没有任何制造设施，该公司依赖第三方制造和生产候选药物。根据Enliven财报，康龙化成为该公司提供原料药，且是临床前研究和临床研究的合作方。Endpoints今年4月报道，指出美国“生物安全法案”事件可能会波及到更多中国的医药外包公司，Enliven Therapeutics在该文中表示，若与康龙化成的合作被限制，Enliven的一款针对癌症的小分子激酶抑制剂的研发和生产可能会被迫中止。如果中美相关政策发生变化，Enliven可能会面临产品供应中断和成本增加的风险。 不管美国所谓此类安全法是否通过，地缘zz已经不可避免。影响互相之间合作的信心。不过，中国企业的高质量/快速的服务，想必仍然能获取不少制药企业信任。 此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 参考： NMPA/CDE； 药融云数据www.pharnexcloud.com FDA/EMA/PMDA； 相关公司公开披露（正文图片均来自企业官方，除非另有说明）； https://www.enliventherapeutics.com/； https://www.globenewswire.com/news-release/2023/02/23/2614889/0/en/Enliven-Therapeutics-Closes-Merger-with-Imara-and-Private-Placement-of-165-Million.html； https://endpts.com/us-china-tensions-threaten-to-ensnare-additional-chinese-biopharma-contractors/； https://www.globenewswire.com/news-release/2023/02/23/2614889/0/en/Enliven-Therapeutics-Closes-Merger-with-Imara-and-Private-Placement-of-165-Million.html；等等。 8月15日  苏州国际博览中心C馆C101  FDA对新兴医疗产品的监管 策划人：杜新，埃格林，副总裁；FDA协会秘书长 联合主办：FDA专家协会 会议日程 09:00-09:05 致辞 李  宁｜上海君实生物，首席执行官；FDA专家协会会长 09:05-09:20 新兴医疗产品的概述 杜  新｜埃格林医药，联合创始人&CEO 09:20-09:45 新兴医疗产品的发展趋势和监管挑战 陆金华｜星尘生物，CSO 09:45-10:10 CGT 产品临床试验的注意要点 李长青｜埃格林医药，联合创始人&CMO 10:10-10:35 CGT产品的临床药理学考量 杨   劲｜中国药科大学，教授 10:35-11:00 新兴医疗产品的GMP合规考量 孙志刚｜绿叶制药集团，高级副总裁 11:00-12:00 小组讨论：新兴医疗产品的国际化 12:00-13:30 午餐 13:30-13:55 小核酸药物的开发与监管考量 杨永胜｜海昶生物，高级副总裁&核酸创新研究院院长 13:55-14:20 FDA对溶瘤病毒产品的的监管 张   静｜武汉朗来科技，首席医学官 14:20-14:45 首个DMD基因疗法的FDA审评审批争议-案例研究 王亚宁｜武汉朗来科技，首席医学官 14:45-15:10 FDA对人工智能相关药品研发的监管概况 15:10-15:35 FDA对人工智能在药物器械的监管及案例分析 胡云富｜泛生子，首席医疗官 15:35-16:00 中国药企和新兴产品进入美国的商务，法务，和药政考量 陈少羽｜泛生子，美国安诺波特律师事务所驻上海代表处，管理合伙人 16:00-16:45 小组讨论：新兴医疗产品监管的进一步深化    FDA如何更新其监管框架以适应核酸和基因编辑技术     FDA对于核酸和基因编辑产品临床试验设计的新指导     FDA关于核酸和基因编辑产品生产变更的监管要求     FDA如何平衡创新与安全     FDA与其他政府机构在基因治疗监管方面的合作 扫码报名参会 【关于药融圈】 药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

Announced positive proof of concept data from Phase 1 clinical trial of ELVN-001 in CML, achieving an initial cumulative MMR rate of 44% (7/16) by 12 weeks in response-evaluable patients Strong balance sheet with $321 million in cash, cash equivalents and marketable securities, which is expected to provide cash runway into late 2026 BOULDER, Colo., May 14, 2024 (GLOBE NEWSWIRE) -- Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage precision oncology company focused on the discovery and development of next-generation small molecule kinase inhibitors, today reported financial results for the first quarter ended March 31, 2024, and provided a business update, including highlights of pipeline progress. “The first quarter of 2024 was a pivotal quarter for Enliven. We released positive proof of concept data from our Phase 1 clinical trial of ELVN-001, which was a significant milestone for the Company,” said Sam Kintz, MBA, Enliven’s Co-founder and Chief Executive Officer. “We are thrilled by the initial ELVN-001 data, particularly the tolerability profile and evidence of activity in heavily pre-treated patients, including in patients with asciminib-resistant chronic myeloid leukemia. We also continued to advance our trials of ELVN-002, including the activation of the first site to evaluate ELVN-002 in combination with trastuzumab in patients with HER2+ cancers, which we believe is an area of significant unmet need for patients. Additionally, we extended our cash runway into late 2026 thanks to the support of new and existing investors.” Corporate Updates Entered into a securities purchase agreement for a private investment in public equity (PIPE) financing resulting in gross proceeds of $90 million. The financing, from both new and existing investors, is expected to extend the Company’s cash runway into late 2026 and through multiple key milestones for ELVN-001 and ELVN-002.Appointed to the Board of Directors, Lori Kunkel, MD, an accomplished industry executive and board member with a track record of success in corporate strategy, clinical development and commercialization. Pipeline Updates ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with chronic myeloid leukemia (CML). Announced positive proof of concept data from the Phase 1 clinical trial evaluating ELVN-001 in patients with CML who are relapsed, refractory or intolerant to available tyrosine kinase inhibitors (TKIs). As of the cutoff date of March 18, 2024, 44% (7/16) of response-evaluable patients achieved a cumulative major molecular response (MMR) rate by week 12, and patients with prior exposure to asciminib and/or who were TKI-resistant also demonstrated responses, with a 44% and 40% cumulative MMR rate, respectively. Among response-evaluable patients, all had improved or stable BCR::ABL1 transcript levels by 12 weeks. ELVN-001 was well tolerated with no Grade 3 or higher non-hematologic treatment-related adverse events and no dose reductions reported.These data compare favorably to precedent Phase 1 cumulative MMR rates for approved BCR::ABL1 TKIs, particularly given the more heavily pre-treated patient population. Further details can be found here.Phase 1b data is expected in 2025 and is expected to include between approximately 60-100 patients across various lines of therapy with significant follow-up. ELVN-002 is a potent, highly selective, central nervous system penetrant and irreversible HER2 inhibitor with activity against wild type HER2 and various HER2 mutations. Following U.S. Food and Drug Administration approval of its Investigational New Drug application, the Company activated the first site to evaluate ELVN-002 in combination with trastuzumab +/- chemotherapeutic agents in HER2+ metastatic breast cancer (MBC) and colorectal cancer (CRC). First patient dosing for the combination trial is expected in Q2 2024.The combination trial in patients with HER2+ cancers is supported by the initial data from the ongoing monotherapy trial, which includes: Investigator reported responses (including unconfirmed) in both HER2+ and HER2 mutant tumors, including in patients who have progressed on Enhertu and patients with brain metastases, at doses that have been well tolerated.Importantly, at the clinically predicted optimal monotherapy dose, ELVN-002 had >10x target coverage based on pharmacokinetics in cancer patients and preclinical HER2+ efficacy compared to tucatinib. Phase 1 monotherapy data, Phase 1a/b Herceptin combination data in HER2+ CRC, and initial Phase 1a combination data in HER2+ MBC are expected in 2025. First Quarter 2024 Financial Results Cash Position: As of March 31, 2024, the Company had cash, cash equivalents and marketable securities totaling $320.5 million, which is expected to provide cash runway into late 2026.Research and development (R&D) expenses: R&D expenses were $20.0 million for the first quarter of 2024, compared to $11.9 million for the first quarter of 2023.General and administrative (G&A) expenses: G&A expenses for the first quarter of 2024 were $6.0 million, compared to $4.5 million for the first quarter of 2023.Net Loss: Enliven reported a net loss of $22.7 million for the first quarter of 2024, compared to a net loss of $14.7 million for the first quarter of 2023. About Enliven TherapeuticsEnliven Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule inhibitors to help people with cancer not only live longer, but live better. Enliven aims to address existing and emerging unmet needs with a precision oncology approach that improves survival and enhances overall well-being. Enliven’s discovery process combines deep insights in clinically validated biological targets and differentiated chemistry to design potentially first-in-class or best-in-class therapies. Enliven is based in Boulder, Colorado. Forward-Looking StatementsThis press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended) concerning Enliven and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Enliven, as well as assumptions made by, and information currently available to, management of Enliven. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements in this press release include, but are not limited to, statements regarding the potential of, and plans and expectations regarding Enliven’s programs, including ELVN-001 and ELVN-002; Enliven’s pipeline of product candidates; expected milestones for ELVN-001 and ELVN-002, including the expected timing of dosing of ELVN-002 for the combination trial and of data from the clinical trials of ELVN-001 and ELVN-002; statements relating to Enliven’s expected cash runway; and the anticipated use of proceeds from the PIPE financing; and statements by Enliven’s Co-founder and Chief Executive Officer. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various risks and uncertainties, including, without limitation: the limited operating history of Enliven; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, product candidates; the outcome of preclinical testing and early clinical trials for product candidates and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; Enliven’s limited resources; the risk of failing to demonstrate safety and efficacy of product candidates; Enliven’s limited experience as a company in designing and conducting clinical trials; the potential for interim, topline and preliminary data from Enliven’s preclinical studies and clinical trials to materially change from the final data; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; developments relating to Enliven’s competitors and its industry, including competing product candidates and therapies; the decision to develop or seek strategic collaborations to develop Enliven’s current or future product candidates in combination with other therapies and the cost of combination therapies; the ability to attract, hire, and retain highly skilled executive officers and employees; the ability of Enliven to protect its intellectual property and proprietary technologies; the scope of any patent protection Enliven obtains or the loss of any of Enliven’s patent protection; reliance on third parties, including contract manufacturing organizations, contract research organizations and strategic partners; general market or macroeconomic conditions; Enliven’s ability to obtain additional capital to fund Enliven’s general corporate activities and to fund Enliven’s research and development; and other risks and uncertainties, including those more fully described in Enliven’s filings with the Securities and Exchange Commission (SEC), which may be found in the section titled “Risk Factors” in Enliven’s Annual and Quarterly Reports on Form 10-K and 10-Q filed with the SEC and in Enliven’s future reports to be filed with the SEC. Except as required by applicable law, Enliven undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. Head-to-Head ComparisonsThe Company has not performed any head-to-head trials for ELVN-001. As a result, the data referenced in this press release is derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, conclusions from cross-trial comparisons cannot be made. Contact:Investorsir@enliventherapeutics.com Mediamedia@enliventherapeutics.com Enliven Therapeutics, Inc.Selected Condensed Consolidated Financial Information(in thousands, except per share data)(unaudited) Statements of OperationsThree Months Ended March 31, 2024 2023 Operating expenses: Research and development$19,970 $11,880 General and administrative 6,017 4,538 Total operating expenses 25,987 16,418 Loss from operations (25,987) (16,418)Other income (expense), net 3,249 1,694 Net loss$(22,738) $(14,724)Net loss per share, basic and diluted$(0.54) $(0.80)Weighted-average shares outstanding, basic and diluted 42,046 18,515 Balance SheetsMarch 31, December 31, 2024 2023 Assets Current assets: Cash, cash equivalents and marketable securities$320,504 $253,148 Restricted cash 54 54 Prepaid expenses and other current assets 6,641 2,949 Contingent value right asset 10,000 10,000 Total current assets 337,199 266,151 Property and equipment, net 683 742 Operating lease right-of-use assets 241 320 Deferred offering costs 563 563 Other long-term assets 4,091 4,091 Total assets$342,777 $271,867 Liabilities and Stockholders' Equity Current liabilities: Accounts payable$2,727 $532 Accrued expenses and other current liabilities 12,304 15,362 Contingent value right liability 10,000 10,000 Total current liabilities 25,031 25,894 Long-term liabilities 34 67 Total liabilities 25,065 25,961 Stockholders' equity 317,712 245,906 Total liabilities and stockholders' equity$342,777 $271,867