CK1α

The global market for AML therapies is expected to be worth $6.62bn in 2031, according to a GlobalData report. Image Credit: LALAKA / Shutterstock. Massachusetts-based company Edgewood Oncology has raised $20m in Series A to advance the clinical development of its lead cancer therapy BTX-A51. The Series A funding round was led by US-based venture fund Alta Partners. Edgewood Oncology expects the funds to finance multiple clinical trials into 2026. BTX-A51 is a multi-kinase inhibitor of casein kinase 1 alpha (CK1α) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9). Edgewood acquired the rights to the therapy from the Hebrew University of Jerusalem in 2023. Edgewood is evaluating BTX-A51 in an open-label Phase I/II trial (NCT04243785) as a monotherapy and in combination with a chemotherapeutic, azacitidine, in patients with relapsed/refractory acute myeloid leukaemia (r/r AML). In Phase Ia, the BTX-A51 monotherapy showed a favourable safety profile along with encouraging antileukemic activity. The combination cohort started enrolment in December 2023. The cohort is expected to enrol up to 30 participants. The cohort aims to evaluate the response rate, safety, toxicity, and pharmacokinetics of the combination therapy of BTX-A51 and azacytidine in patients with r/r AML. See Also: Oncology in 2024: The clinical trial trends reshaping the role of CROs Avenzo Therapeutics secures $150m to progress oncology pipeline The global market for AML therapies is expected to be worth $6.62bn in 2031, according to a GlobalData report . The AML therapy pipeline consists of more than 200 drugs in early development, with the majority of drugs in development being enzyme inhibitors, according to GlobalData Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Edgewood is also investigating BTX-A51 as a treatment for solid tumours and non-Hodgkin lymphoma, open-label Phase I trial (NCT04872166). The study expects to enrol up to 116 participants and is estimated to be completed in May 2027. The company also plans to initiate a Phase II trial evaluating BTX-A51 in breast cancer patients with a genetically defined profile in Q2 2024. Advances in AML therapies include Daiichi Sankyo ’s Vanflyta (quizartinib). In November 2023, the European Commission (EC) approved Vanflyta as an add-on therapy for newly diagnosed fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) positive AML in adults. In September 2023, Mendus’s cancer vaccine, vividencel, received fast-track designation from the US Food and Drug Administration (FDA). A month later, Sellas Life Sciences Group’s CDK9 inhibitor, SLS009, received an orphan drug designation from the FDA. AML therapies in early development include Aptose Biosciences ’ tuspetinib. The company started the Phase I/II APTIVATE trial evaluating the drug’s pharmacodynamics, tolerability, safety, and pharmacokinetics in r/r AML patients in January. In September 2023, Foghorn Therapeutics dosed the first patient in the Phase I trial evaluating the combination therapy of FHD-286 and chemotherapy in patients with r/r AML.

BTX-A51 is a Novel, Small Molecule, Multi-Kinase Inhibitor That Synergistically Co-Targets Master Regulators of Cancer to Promote Cancer Cell Death Enrollment is Underway in Phase 2a Combination Study in Acute Myeloid Leukemia; Enrollment in Phase 2a Targeted Breast Cancer Study to Start in Q2 2024 Financing Enables Company to Fund Multiple Studies to Clinical Proof-of-Concept into 2026 BROOKLINE, Mass.--(BUSINESS WIRE)-- Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, today emerged from stealth with $20 million in Series A financing backed by Alta Partners to advance the clinical development of BTX-A51 in acute myeloid leukemia (AML) and a precision medicine approach to breast cancer. BTX-A51 is a first-in-class, small molecule, multi-kinase inhibitor of casein kinase 1 alpha (CK1α), cyclin-dependent kinase 7 (CDK7) and CDK9 that synergistically co-targets master regulators of cancer to promote programmed cell death, or apoptosis. Edgewood acquired the rights to BTX-A51 from Yissum, the technology transfer company of The Hebrew University of Jerusalem, in 2023 and will use the Series A funding to advance efficacy studies in AML and breast cancer. “We formed Edgewood Oncology because of the synergistic mechanism of action and promising safety and anti-tumor data that was observed with BTX-A51 in Phase 1 in AML and solid tumor patients. We look forward to further developing this compound using a precision medicine approach in patient populations who lack effective treatment options,” said David N. Cook, Ph.D., chief executive officer, Edgewood Oncology. “Furthermore, we have taken a virtual approach to drug development, which allows us to remain highly-focused, agile and efficient as we advance this investigational compound in the clinic.” Testing the Use of Combination Therapy in AML There exists a significant unmet need for improved first-line regimens in AML as well as for patients with relapsed or refractory (R/R) disease. In a Phase 1 study in heavily pre-treated R/R AML patients, monotherapy BTX-A51 demonstrated a favorable safety pro encouraging antileukemic activity. As a next step, Edgewood initiated a study of BTX-A51 in combination with azacitidine in R/R AML patients in December 2023. The aim of this Phase 2, multicenter, open-label study is to evaluate the response rate (CR, CRh and CRi) as well as the safety, toxicity and pharmacokinetics of BTX-A51 in combination with azacitidine in patients with R/R AML. “We’re incredibly excited about the potential of BTX-A51in this patient population, and we also have good reason to believe that BTX-A51 could be complementary to standard of care in first-line unfit AML,” said Zung Thai, M.D., Ph.D., chief medical officer, Edgewood Oncology. “In Phase 1 monotherapy, we observed several complete responses and a wide therapeutic window and our preclinical data also suggest that BTX-A51 acts synergistically with both azacitidine and venetoclax in human leukemia cells and animal models.” Edgewood is expecting to initiate a Phase 2 study in breast cancer patients with a genetically-defined pro Q2 2024. Leadership Team Comprised of Seasoned Biotech Veterans “Edgewood’s leadership team not only has a strong track record in company formation and drug development, but Dr. Thai brings an in-depth understanding of BTX-A51, having led all clinical and regulatory efforts for this program during his tenure at BiotheryX,” said Dan Janney, managing partner, Alta Partners. “Moreover, we believe Edgewood’s virtual approach to drug development is the best strategy to get innovative new medicines to patients as quickly and efficiently as possible.” The executive team includes Dr. Cook as chief executive officer, and Dr. Thai as chief medical officer. BTX-A51’s scientific founder is Yinon Ben-Neriah, M.D., Ph.D., professor of Immunology and Cancer Research, The Hebrew University of Jerusalem. The company’s board of directors includes Dr. Cook, Dan Janney, and Isan Chen, M.D., a noted clinical oncologist and co-founder, president and chief executive officer, MBrace Therapeutics, Inc. About Edgewood Oncology Edgewood Oncology is a clinical-stage biotechnology company that was founded to deliver on the promise of BTX-A51 for patients with hematologic malignancies and genetically-defined solid tumors. BTX-A51 is a novel small molecule, multi-kinase inhibitor that synergistically co-targets master regulators of cancer to activate programmed cell death, or apoptosis. BTX-A51 holds promise in acute myeloid leukemia and genetically-defined solid tumors, which are the focus of ongoing clinical programs. For more information, please visit , and follow us on LinkedIn. About Alta Partners Founded in 1996, Alta Partners is one of the nation's premier healthcare venture capital firms. Alta has raised $2.6 billion in capital through 11 venture funds and invests in healthcare companies across the development continuum, from company formation to later-stage opportunities, and has funded more than 175 companies in the sector to date. In August 2022, Stat Reports recognized Alta as the country's top performing biotech venture fund. Alta has offices in the San Francisco Bay Area, Denver, and Jackson, WY. For more information, please visit . View source version on businesswire.com: Contacts Tracy Lessor TLOW Communications, LLC 617-519-9827 tracy@tlowcommunications.com Source: Edgewood Oncology View this news release online at:

根据中国国家药监局药品审评中心（CDE）官网数据，本周有十余款1类新药首次在中国获批临床，这些新药来自罗氏（Roche）、默沙东（MSD）、赛诺菲（Sanofi）、海创药业、金唯科生物、格博生物等公司，涉及细胞与基因疗法(CGT)、抗体偶联药物（ADC）、蛋白降解疗法等多种药物类型。本文将介绍部分1类新药信息，仅供读者参阅（排名不分先后）。 作用机制：使用HSV-1载体的基因治疗药物 适应症：营养不良型大疱性表皮松解症 WG1025是唯源立康自主研发的一款使用I型单纯疱疹病毒（HSV-1）载体作为基因治疗递送工具的1类生物新药，活性成分是携带编码VII型胶原蛋白（COL7）的COL7A1基因的复制缺陷型HSV-1载体。该产品获批临床，拟开发用于营养不良型大疱性表皮松解症（DEB）。DEB是一种临床症状严重的遗传性皮肤病，由COL7A1基因发生突变所致COL7蛋白表达缺乏，从而使得患者皮肤非常脆弱。 作用机制：AAV基因治疗药物 适应症：新生血管性年龄相关性黄斑变性 JWK001是金唯科生物自主研发的一款采用“两质粒包装系统”的腺相关病毒（AAV）基因治疗新药。其通过将携带全新自主设计的抗VEGF蛋白表达框的AAV载体，可在视网膜细胞中持续高效表达抗血管内皮生长因子（VEGF）蛋白。VEGF已被证实在新生血管性年龄相关性黄斑变性（nAMD）新生血管形成中具有重要作用。该产品获批临床，拟开发用于治疗nAMD。 作用机制：表达CD19的自体T细胞 适应症：急性淋巴细胞白血病 aT19是永泰生物旗下永泰瑞科正在开发的一款经过基因改造而强制表达CD19的自体T细胞。靶向CD19的CAR-T细胞治疗B细胞急性淋巴细胞白血病（B-ALL）后复发患者中约有50%为CD19阳性复发。aT19注射液在CAR-T-19注射液给药后回输，具有再度激活CAR-T细胞，再次启动CAR-T细胞的增殖，增加免疫记忆细胞的潜力。该产品获批临床，拟开发用于25岁（含）以下复发/难治B-ALL，在靶向CD19的CAR-T细胞治疗后临床获益的患者，以增强治疗效应、减少复发。 作用机制：IL-13/TSLP双特异性纳米抗体 适应症：哮喘 SAR443765是赛诺菲正在开发的一款靶向胸腺基质淋巴细胞生成素（TSLP）和白细胞介素-13（IL-13）通路的双特异性纳米抗体。赛诺菲在2023年美国胸科学会（ATS）年会上展示的临床数据显示：在一项关键的哮喘测量中，与单独使用TSLP 或IL13相比，SAR443765展现出更好的疗效，显示有协同作用。该产品在中国获批临床，拟开发用于治疗成人中重度哮喘。 上海生物制品研究所：注射用SIBP-A17 作用机制：ADC 适应症：晚期恶性实体瘤 SIBP-A17是上海生物制品研究所自主研发的创新型抗体偶联药物（ADC），具有连接子可裂解、载荷活性强、抗肿瘤“旁观者效应”等药物优势。临床前研究数据显示：SIBP-A17对乳腺癌、胃癌、肺癌、胰腺癌等具有较好的治疗潜力；在动物体内稳定性良好，游离小分子水平显著低于同类产品，具有较好的安全性及耐受性。该产品获批临床拟开发用于难治的或复发的对标准治疗无效的晚期恶性实体瘤。 作用机制：靶向PTK7的ADC 适应症：实体瘤 PRO1107是普方生物正在开发的一款以蛋白酪氨酸激酶7（PTK7）为靶点的ADC，以MMAE作为有效载荷，采用普方生物自主研发的新型亲水性载荷连接子LD343，DAR值为8。PTK7是一种存在于细胞表面的受体蛋白，在肿瘤发生发展中的重要作用，且在肿瘤中的特异表达。PRO1107获批临床拟开发用于实体瘤患者。 作用机制：靶向TL1A的人源化单抗 适应症：溃疡性结肠炎 MK-7240是Prometheus Biosciences开发的一款针对肿瘤坏死因子（TNF）-样配体1A（TL1A）的人源化单克隆抗体。2023年6月，默沙东以总额达108亿美元的款项完成对Prometheus的收购，从而获得这款免疫领域的产品。TL1A是一个与肠炎和纤维化有关的靶标，在免疫调节及炎症性疾病中发挥重要作用。MK-7240在中国获批临床，拟开发用于中度至重度活动性溃疡性结肠炎。 作用机制：CK1α分子胶蛋白降解剂 适应症：髓系恶性肿瘤 GLB-001为格博生物自主研发的一款高选择性的酪蛋白激酶1α（CK1α）口服分子胶蛋白降解剂。CK1α是一种由CSNK1A1基因编码的丝氨酸/苏氨酸蛋白激酶，已被证实对许多不同类型的恶性血液肿瘤和实体瘤的生长和存活至关重要。GLB-001可通过与CRL4CRBN E3泛素连接酶复合物中的底物蛋白受体CRBN相结合，靶向降解CK1α，并触发p53的稳定与蓄积及其下游信号传导通路的激活，导致肿瘤细胞周期停滞和凋亡，发挥抑制肿瘤生长的作用。GLB-001获批临床拟开发用于髓系恶性肿瘤。 作用机制：钾离子竞争性酸阻滞剂 适应症：反流性食管炎 JP-1366（zastaprzan）是由韩国Onconic Therapeutics公司研发的一款创新钾离子竞争性酸阻滞剂（P-CAB），已在韩国提交上市申请。丽珠医药于2023年3月与Onconic达成合作，获得授权可在中国大陆、香港、澳门及台湾地区开发、制造和商业化该产品。JP-1366在中国获批临床拟开发用于治疗反流性食管炎。 作用机制：p300/CBP小分子抑制剂 适应症：血液系统恶性肿瘤 HP537是海创药业自主研发的p300/CBP抑制剂小分子抗肿瘤药物。p300/CBP参与细胞周期进展和细胞生长、分化和发展，在肿瘤中高度表达和激活，是肿瘤细胞生长的关键调控因子。HP537获批临床，拟开发用于血液系统恶性肿瘤，包括但不限于多发性骨髓瘤（MM）、非霍奇金淋巴瘤（NHL）、急性髓系白血病（AML）、骨髓增生异常综合征（MDS）患者。 作用机制：ATR抑制剂 适应症：实体瘤 Camonsertib是Repare公司开发的一款选择性口服ATR抑制剂。ATR全称为共济失调毛细血管扩张突变Rad3相关蛋白，是DNA损伤修复的关键酶之一。研究显示，在ATM缺失的肿瘤细胞中，ATR抑制剂可以产生合成致死效应，在导致ATM缺失肿瘤细胞死亡的同时，并不影响正常细胞。 此外，ATR抑制剂还能与PARP抑制剂联合以增强治疗敏感性。Camonsertib在中国获批临床，拟开发用于实体瘤。除了上述药物，还有一些其它药物也于本周在中国获批临床，限于篇幅，本文不再一一介绍。希望这些药物后续研究顺利进行，早日惠及广大病患。 参考资料： [1]中国国家药监局药品审评中心（CDE）官网.Retrieved Feb 24，2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]各公司官网及公开资料 内容来源于网络，如有侵权，请联系删除。