A Phase 1/1b Open-Label, Dose Escalation, First-in- Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-leukemic Activity of the Orally Available CDC-Like Kinase (CLK) Inhibitor, BH-30236, in Adults With Relapsed or Refractory Acute Myelogenous Leukemia (R/R AML) or Higher-Risk Myelodysplastic Syndrome (HR-MDS)

Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/refractory acute myelogenous leukemia (R/R AML) or higher-risk myelodysplastic syndrome (HR-MDS).
Phase 1 (Dose Escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered orally. Approximately 50 participants may be enrolled in Phase 1 of the study.
Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.
The dose expansion part (Phase 1b) will be followed to understand the relationships among dose, exposure, toxicity, tolerability and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

开始日期2024-06-19

申办/合作机构

Blossomhill Therapeutics, Inc.初创企业

100 项与 Blossomhill Therapeutics, Inc. 相关的临床结果

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0 项与 Blossomhill Therapeutics, Inc. 相关的专利（医药）

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项与 Blossomhill Therapeutics, Inc. 相关的文献（医药）

2024-03-22·Cancer Research

Abstract 617: BH-30236, a novel macrocyclic CLK inhibitor modulating RNA splicing, demonstrates potent inhibition of cancer cell growth in a broad panel of cancer cell lines

作者: Jiang, Ping ; Deng, Wei ; Rui, Eugene ; Cui, J. Jean ; Zhai, Dayong ; Ling, Nancy ; Li, Danan

AbstractAlternative splicing (AS) is a primary mechanism for mRNA transcript diversification and protein expression regulation. In cancer, altered mRNA splicing promotes oncogenic transformation, induces metastasis, and confers resistance to cancer treatment. Mutations or imbalanced expression/activity of splicing factors (SF), such as serine-arginine-rich SFs (SRSFs), often result in deregulation of RNA splicing and tumor progression. CDC2-like kinases (CLK) and dual-specificity tyrosine-regulated kinase (DYRK) are key regulators of AS via phosphorylation of SRSFs. BH-30236 is a novel macrocyclic ATP-competitive inhibitor of CLK1/2/4. It also inhibits DYRK1/2, provirus integration site for moloney leukemia virus 3 (PIM3) and FMS-like tyrosine kinase 3 (FLT3) at clinically relevant concentrations. The inhibitory activity of BH-30236 against CLK, DYRK, PIM3 and FLT3 in cancer cells was investigated via the phosphorylation inhibition of SRSFs, Tau, 4EBP1 and FLT3, respectively. A panel of 119 hematological and solid tumor cell lines were used to investigate the spectrum of BH-30236 against cancer cell growth. To understand the mechanism of anti-cancer cell growth, the effect of BH-30236 on AS and protein expression of key tumor related biomarkers were examined. In conclusion, BH-30236 effectively inhibited pSRSF (IC50 40-60 nM in IMR-32 cells), pTau (IC50 ~50 nM in SH-SY5Y cells), p4EBP1 (IC50 ~80 nM in MM1S cells) and pFLT3-ITD (IC50 0.16 nM in MV-4-11 cells). BH-30236 demonstrated broad inhibition of cancer cell growth with a median IC50 of 85.2 nM (range 0.55-393 nM) across 12 tumor types. BH-30236 showed great efficacy against cell lines derived from hematological malignancy (median IC50 23.34 nM), neuroblastoma (median IC50 25.73 nM), breast cancer (median IC50 83.80 nM), colon cancer (median IC50 85.17 nM), and lung cancer (median IC50 102.65 nM). Furthermore, BH-30236 demonstrated synergy with KRAS inhibitors in KRAS mutant cell lines, with EGFR inhibitors in RBM10 mutant H1975 cells, and with BCL2 inhibitor Venetoclax in MOLM-13 cells. Mechanistically, BH-30236 modulated AS by increasing pro-apoptotic and anti-proliferative splicing variants of key factors, such as BCL2L1, S6K, and BCLAF1. Meanwhile, BH-30236 downregulated RNA expression of SRSFs and modulated BCL2 family to increase apoptosis. These results strongly support the clinical applications of the novel multikinase CLK inhibitor BH-30236 in hematological malignancies and solid tumors as a single agent or in combination with other therapies.Citation Format: Ping Jiang, Danan Li, Nancy Ling, Dayong Zhai, Wei Deng, Eugene Rui, J. Jean Cui. BH-30236, a novel macrocyclic CLK inhibitor modulating RNA splicing, demonstrates potent inhibition of cancer cell growth in a broad panel of cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 617.

项与 Blossomhill Therapeutics, Inc. 相关的新闻（医药）

2024-07-03

·药融圈

中科大校友&美国院士创立Biotech，融资累计1.73亿美元

▲8月15-16日 NDC2024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）监测显示：2024年2月29日，中国科大资深803应用化学校友崔景荣博士（Jean Cui）创立的新药公司BlossomHill Therapeutics，宣布完成了1亿美元的B轮融资。此轮融资由Colt Ventures领衔，Cormorant Asset Management、OrbiMed、维梧资本、Hercules BioVentures Partners、Plaisance Capital Management以及H&D Asset Management在内的新老投资者参与。Colt Ventures 合伙人 Sundeep Agrawal ，维梧资本 Timothy Stubbs 加入董事会。至此，公司累计融资金额总额达1.73亿美元（A轮融资7100万美元；种子轮200万美元）。 2024年2月6日，崔景荣博士因为在SUGEN/辉瑞以及原东家TP（Turning Point Therapeutics后被BMS以41亿美元收购）抗癌新药研发领域的杰出成就而当选美国工程院院士（NAE)，这是货真价实的头衔。曾经主导开发上市的产品有crizotinib (XALKORI®), lorlatinib (LOBRENA®)和 repotrectinib (AUGTYRO®)。 BlossomHill最早成立于2020年6月，重点开发的疾病领域为肿瘤与自身免疫。由崔景荣博士与医药老兵李一山（Y. Peter Li）博士共同创立。值得注意的是，这是一对新药伉俪。此前，崔景荣博士曾在SUGEN, Inc.担任项目负责人和团队领导；2003-2013年，她加入辉瑞，担任Associate Research Fellow，和Senior Principal Scientist。2013年，她加入Turning Point Therapeutics, Inc，担任Turning Point的首席科学官，2013年10月-2020年6月担任董事会成员。药融云数据（www.pharnexcloud.com）监测显示：新公司涉及的专利与激酶和大环策略相关，涵盖的靶点有KRAS（WO2024015262A1）、EGFR、TYK2等等。目标开发出能与阿斯利康的三代FEGFR Tagrisso竞争的候选药物；急性髓性白血病适应症的新分子；目前自身免疫候选分子也尚未公开。参考： NMPA/CDE；药融云数据，www.pharnexcloud.com； FDA/EMA/PMDA；相关公司公开披露； https://bhtherapeutics.com/； https://bhtherapeutics.com/2024/02/blossomhill-therapeutics-closes-100-million-series-b-financing/； https://www.businesswire.com/news/home/20240229403573/en；等等。本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 [ 重磅苏州新药峰会推荐 ] 08/15AM FDA对细胞和基因治疗 (CGT) 产品的监管 09:00-09:10 致辞 09:10-09:30 新兴医疗产品的概述 09:30-10:00 FDA对CGT产品CMC方面的监管。 10:00-10:30 FDA 对 CGT 产品非临床研究的要求 10:30-11:00 CGT 产品临床试验的注意要点 11:00-12:00 小组讨论 12:00-13:30 午餐 08/15PM FDA对核酸和基因编辑产品的监管 13:30-14:00 核酸产品的 CMC 注意要点 14:00-14:30 FDA对核酸产品的非临床要求 14:30-15:00 核酸产品的临床注意要点 15:00-15:30 FDA对溶瘤病毒产品的监管 15:30-16:00 FDA 批准首个基因编辑产品 Casgevy - 案例研究 16:00-17:00 小组讨论以上议程更新中，以会议现场为准... 门票注册通道【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。

并购基因疗法细胞疗法高管变更

2024-06-01

·药明康德

脑转移进展风险降低94%！辉瑞抗癌小分子3期试验结果亮眼

▎药明康德内容团队编辑今天，辉瑞（Pfizer）在2024年美国临床肿瘤学会（ASCO）年会公布3期CROWN研究的长期随访结果。这项研究旨在评估第三代间变性淋巴瘤激酶（ALK）抑制剂博瑞纳（洛拉替尼，lorlatinib，英文商品名：Lobrena）在既往未经治疗的ALK阳性晚期非小细胞肺癌（NSCLC）患者中的疗效与安全性。分析显示，与第一代ALK抑制剂相比，使用洛拉替尼治疗患者的疾病进展或死亡风险持续降低81%，脑转移进展风险降低94%。肺癌是世界上导致癌症死亡的首要原因之一。肺癌主要分为小细胞肺癌和NSCLC两种。NSCLC是最常见的肺癌种类，大约占肺癌患者总数的80-85%，ALK阳性肿瘤发生在约3-5%的NSCLC病例中。由于患者基数庞大，ALK阳性NSCLC虽然占比不高，但每年新发病例数仍不容忽视。虽然很多ALK阳性转移性NSCLC患者对最初的酪氨酸激酶抑制剂（TKI）疗法产生应答，但是他们的肿瘤通常会再度恶化。对于那些接受过第二代ALK TKI治疗，但是疾病继续恶化的患者来说，他们的治疗选择非常有限。此外，有约25-40%的ALK阳性晚期NSCLC患者在初诊时已发生脑转移，面临生存期与生存质量的双重挑战。CROWN研究是一项随机、开放标签、平行双臂3期试验。在研究中，296例既往未接受过治疗的ALK阳性晚期NSCLC患者按1:1的比例随机接受洛拉替尼单药（n=149）或第一代ALK抑制剂Xalkori（crizotinib，克唑替尼）单药（n=147）治疗。▲在CROWN研究中，洛拉替尼显著改善患者PFS（图片来源：参考资料[2]）中位随访时间为5年时，根据研究者的评估，洛拉替尼组患者的中位无进展生存期（PFS）仍未达到。其观察到的风险比（HR）为0.19（95% CI：0.13-0.27）。即与第一代ALK抑制剂相比，洛拉替尼将患者的疾病进展或死亡风险降低了81%。此外，洛拉替尼治疗组中有60%的患者五年后仍未见疾病进展或死亡（95% CI：51-68），而对照组仅有8%（3-14）。这些数据也已同步发布在Journal of Clinical Oncology期刊上。此次更新分析显示，洛拉替尼将患者颅内（IC）疾病进展风险降低94%（HR=0.06，95% CI：0.03-0.12）。洛拉替尼治疗组的中位颅内进展时间尚未达到（95% CI：NR-NR），而第一代ALK抑制剂治疗组的这一数据为16.4个月（12.7-21.9）。在基线无脑转移的患者中，接受洛拉替尼治疗的114名患者中仅有4人在治疗最初的16个月内出现脑转移，而接受第一代ALK抑制剂治疗的109名患者中有39人出现这一情况。▲在CROWN研究中，洛拉替尼显著降低患者颅内疾病进展风险（图片来源：参考资料[2]）截至分析时，CROWN研究中洛拉替尼治疗组仍有50%的患者在继续接受治疗，而第一代ALK抑制剂治疗组仅有5%的患者继续接受治疗。五年随访数据显示，第三代ALK抑制剂洛拉替尼与第一代ALK抑制剂在安全性上与既往研究结果一致，未见新的安全性事件。在这项分析中，接受洛拉替尼治疗患者报告的最常见（≥20%）不良事件（AE）与2020年CROWN研究分析一致，包括水肿、体重增加、周围神经病变、认知影响、情绪影响、腹泻、呼吸困难、关节痛、高血压、头痛、咳嗽、发热、高胆固醇血症和高甘油三酯血症。▲CROWN研究的安全性结果摘要（图片来源：参考资料[2]）洛拉替尼是辉瑞开发的一种酪氨酸激酶抑制剂，它在携带ALK重排的临床前肺癌模型中显示出高度活性。该药能够抑制对其它ALK抑制剂耐药的ALK基因突变，并可穿过血脑屏障，治疗脑转移瘤。洛拉替尼曾获得美国FDA授予的突破性疗法认定、优先审评资格，并在2018年获FDA加速批准治疗经治的ALK阳性转移性NSCLC，并在2021年获批一线治疗ALK阳性NSCLC。2022年4月，该疗法也获得中国国家药监局（NMPA）批准用于治疗ALK阳性局部晚期或转移性NSCLC患者。值得一提的是，崔景荣（J. Jean Cui）博士所带领的团队主导开发洛拉替尼与克唑替尼这两款精准抗肿瘤药物。克唑替尼于2011年获美国FDA批准上市，治疗带有ALK突变的NSCLC；洛拉替尼于2018年获FDA批准上市，用于治疗ALK阳性转移性NSCLC。此外，崔景荣博士也是肿瘤药物TPX-0005、TPX-0022、TPX-0046和TPX-0131的主要发明者。崔博士是精准抗癌疗法公司Turning Point Therapeutics的科学创始人，该公司创立于2013年并在2019年完成IPO上市。2022年6月百时美施贵宝（Bristol Myers Squibb）斥资超40亿美元收购该公司。▲崔景荣博士（图片来源：BlossomHill公司官网）崔博士还在2020年6月与生物科技行业资深人士李一山（Y. Peter Li）博士共同创立BlossomHill公司，并担任该公司的总裁兼首席执行官。BlossomHill是一家旨在开发能够解决多种耐药机制新化学实体的小分子药物研发公司。今年2月，该公司宣布完成1亿美元的B轮融资，使该公司筹集的资金总额达到了1.73亿美元。BlossomHill将使用这些资金推进其多个内部发现和开发项目进入临床开发阶段，这些项目针对多种具有高度医疗需求的癌症和自身免疫性疾病。除了洛拉替尼，用以治疗ALK阳性NSCLC的药物还包括由罗氏（Roche）所开发、在上个月甫获FDA批准的Alecensa（alectinib）。新闻稿指出，Alecensa是首个获批用于治疗经手术切除肿瘤的早期ALK阳性NSCLC患者的ALK抑制剂。此外，Nuvalent所开发具有脑部渗透性的潜在“best-in-class”ALK选择性抑制剂NVL-655在今年5月获得美国FDA授予突破性疗法认定。之前公布的试验结果显示，肿瘤带有任何ALK耐药突变患者在接受每日一次的NVL-655治疗后，患者的客观缓解率（ORR）达54%（n=15/28），其中肿瘤带有常见ALK耐药突变G1202R患者的ORR高达71%（n=12/17）。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] 辉瑞公布博瑞纳®CROWN研究最新数据，60%的ALK阳性晚期肺癌受试者无进展生存期超过五年. Retrieved May 31, 2024 from https://www.prnasia.com/story/449167-1.shtml[2] Solomon BJ, Liu G, Felip E, Mok TSK, Soo RA, Mazieres J, Shaw AT, de Marinis F, Goto Y, Wu YL, Kim DW, Martini JF, Messina R, Paolini J, Polli A, Thomaidou D, Toffalorio F, Bauer TM. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. 2024 May 31:JCO2400581. doi: 10.1200/JCO.24.00581. Epub ahead of print. PMID: 38819031.免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

ASCO会议临床结果临床3期

2024-03-26

·Firstwordpharma

Months after in-licensing first programme, Avenzo raises $150M

Another pair of former Turning Point team members has raised a megaround this year. Avenzo Therapeutics closed a $150-million series A-1 on Tuesday to build a cancer company via licensing deals and acquisitions. The financing comes a month after Turning Point co-founders Jean Cui and Y. Peter Li nabbed a $100-million Series B for their small molecule oncology venture, BlossomHill. The A-1 round, which brings Avenzo’s total fundraising to $347 million, was led by New Enterprise Associates, Deep Track Capital, Sofinnova Investments, and Sands Capital. Other new investors also participated in the financing, including INCE Capital, TF Capital, Delos Capital, and Quan Capital.On the hunt for dealsAthena Countouriotis and Mohammad Hirmand, Turning Point’s former CEO and CMO, respectively, formed Avenzo in 2022 shortly after Bristol Myers Squibb acquired the biotech for $4 billion. Their mission was to build a best-in-class oncology pipeline through strategic partnerships.“We’ve been focused on partnering with early-stage companies that may not necessarily have the clinical development capabilities or expertise that we have at Avenzo, to progress important potential new therapies through clinical development,” Countouriotis told FirstWord. She serves as president and CEO of Avenzo. Avenzo gained its first candidate in January when it in-licensed AVZO-021 (formerly ARTS-021) from Allorion Therapeutics, along with an exclusive option for an undisclosed preclinical programme, for $40 million upfront. The latter is eligible for up to $1 billion in milestones.AVZO-021, which is being studied in a Phase I trial for HR+/HER2- metastatic breast cancer and other advanced solid tumours, has the potential to be a best-in-class selective CDK2 inhibitor, according to Countouriotis. CDK2 is a well-known target of interest for cancer given its role as a key resistance mechanism to approved CDK4/6 agents, but compounds targeting the kinase have struggled in the clinic, including programmes from Nuvation Bio and Blueprint Medicine, which both received partial holds from the FDA due to a safety signal. AVZO-021’s selectivity could give it an edge over other programmes in development, particularly on safety.“There have been multiple assets that were designed as CDK2/4/6 inhibitors that we believe had too much off-target toxicity, hence why we believe a best-in-class CDK2 selective agent can have transformational potential in HR+/HER2- breast cancer,” Countouriotis said. Tuesday’s financing will help Avenzo continue bulking out its pipeline with dealmaking. While Countouriotis declined to disclose any other targets of interest, she said the company is on the lookout for small molecule programmes and antibody-drug conjugates.

临床1期并购抗体药物偶联物蛋白降解靶向嵌合体引进/卖出

100 项与 Blossomhill Therapeutics, Inc. 相关的药物交易

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100 项与 Blossomhill Therapeutics, Inc. 相关的转化医学

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