Ziftomenib

– 87% ORR and 70% CRc in venetoclax-naïve and 48% ORR and 24% CRc in venetoclax-experienced patients at the recommended 600 mg once-daily dose – – Central MRD negativity in 75% of CRc responders with no prior venetoclax exposure; median CRc duration was 9.2 months – – Median OS not reached after median follow up of 10.7 months in patients with no prior venetoclax exposure – – Combination was well tolerated, with low rates of differentiation syndrome and QTc prolongation observed – SAN DIEGO and TOKYO, June 02, 2026 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA, “Kura”) and Kyowa Kirin Co., Ltd. (TSE: 4151, “Kyowa Kirin”) today announced the publication in Blood of updated results from the relapsed/refractory (R/R) NPM1 -mutated acute myeloid leukemia ( NPM1 -m AML) cohort of KOMET-007, a Phase 1a/b trial evaluating ziftomenib in combination with venetoclax and azacitidine (ven/aza). The publication reports nearly two-thirds of patients experienced clinically meaningful, deep and durable responses with a well-tolerated safety pro adults with R/R NPM1 -m AML. KOMZIFTI™ (ziftomenib) is approved by the U.S. Food and Drug Administration as monotherapy for adult patients with relapsed or refractory AML with a susceptible NPM 1 mutation who have no satisfactory alternative treatment options. Ziftomenib in combination with ven/aza is investigational and has not been approved by the FDA. “This analysis provides a more mature evaluation of ziftomenib in combination with venetoclax and azacitidine in patients with NPM1 -mutated AML,” said Eunice S. Wang, M.D., Chief of Leukemia, Roswell Park Comprehensive Cancer Center, and co-first senior author of the publication. “In the relapsed/refractory setting, outcomes with venetoclax-based regimens in patients with NPM1 -mutant AML remain suboptimal, highlighting the substantial need for more effective therapies. These KOMET-007 results are notable for the depth and durability of response observed with the investigational three-drug combination. The favorable safety pro supports the continued evaluation of this combination in a setting where better treatment options are urgently needed.” “As combination approaches become increasingly important in this setting, the data highlighted in this publication strengthen the case for ziftomenib as a backbone in NPM1 -mutant AML,” said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. “Ziftomenib combined with ven/aza demonstrated deep molecular responses, durable remissions, and a generally manageable safety pro R/R NPM1 -m AML. These findings support our ongoing efforts to evaluate ziftomenib-based combinations across the treatment continuum, including in randomized studies designed to define the potential of ziftomenib in newly diagnosed disease.” KOMET-007 Results in R/R NPM1 -m AML The data include 64 response-evaluable patients with R/R NPM1 -m AML from the ongoing KOMET-007 Phase 1a/b trial ( NCT05735184 ), 27 of whom were treated in phase 1a dose escalation and 37 of whom were treated in phase 1b expansion, as of the January 16, 2026 data cutoff date. Patients had received 1 to 8 prior lines of therapy (median of 1), and 37 patients (55%) had prior venetoclax exposure. Robust clinical activity was observed in patients with R/R NPM1 -m AML across all ziftomenib dose levels, with nearly two-thirds of all patients experiencing clinically meaningful, deep, and durable responses. In addition, rapid responses were observed, with a median time to composite complete remission (CRc) of 3.9 weeks. Venetoclax-Naïve Population (600 mg ziftomenib) 70% CRc rate (16/23) with 75% (9/12) central measurable residual disease (MRD) negativity ( 480 msec. Perform an ECG at least once weekly for the first four weeks on treatment, and at least monthly thereafter. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms (Grade 3). In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use of KOMZIFTI with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation, result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsades de Pointes, other serious arrhythmias, and sudden death. Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 3 months after the last dose. ADVERSE REACTIONS Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death. Serious adverse reactions were reported in 79% of patients who received KOMZIFTI. Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%). Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients. Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%). Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients. Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients. Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%). Most common (≥ 20%) adverse reactions, including laboratory abnormalities , were aspartate aminotransferase increased (53%), infection without an identified pathogen (52%), potassium decreased (52%), albumin decreased (51%), alanine aminotransferase increased (50%), sodium decreased (49%), creatinine increased (45%), alkaline phosphatase increased (41%), hemorrhage (38%), diarrhea (36%), nausea (35%), fatigue (34%), edema (30%), bacterial infection (28%), musculoskeletal pain (28%), bilirubin increased (27%), potassium increased (26%), differentiation syndrome (26%), pruritus (23%), febrile neutropenia (22%), and transaminases increased (21%). DRUG INTERACTIONS Drug interactions may occur when KOMZIFTI is concomitantly used with: Strong or Moderate CYP3A4 Inhibitors: Monitor patients more frequently for KOMZIFTI-associated adverse reactions. Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of KOMZIFTI. Gastric Acid Reducing Agents: Avoid concomitant use of KOMZIFTI with proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), or locally acting antacids. If concomitant use with H2RAs or locally acting antacids cannot be avoided, modify KOMZIFTI administration time. Take KOMZIFTI 2 hours before or 10 hours after administration of an H2 receptor antagonist. Take KOMZIFTI 2 hours before or 2 hours after administration of a locally acting antacid. Drugs that Prolong the QTc Interval: Avoid concomitant use of KOMZIFTI. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms. USE IN SPECIFIC POPULATIONS Pregnancy: Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to starting KOMZIFTI. Lactation: Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with KOMZIFTI and for 2 weeks after the last dose. Infertility: Based on findings in animals, KOMZIFTI may impair fertility in females and males of reproductive potential. Please see full Prescribing Information , including Boxed WARNING . Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of ziftomenib to serve as a combination backbone in NPM1 -mutant AML. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, and other interactions with regulatory bodies, the risk that the collaboration with Kyowa Kirin is unsuccessful, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties Kura faces, please refer to Kura’s periodic and other filings with the Securities and Exchange Commission, which are available at . Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Kura Contacts Investors and Media: Greg Mann 858-987-4046 gmann@kuraoncology.com Kyowa Kirin Contacts Investors: Ryohei Kawai ir@kyowakirin.com Media, Global: Sachiko Kido media@kyowakirin.com

STTT重磅 | 瑞金医院团队解锁AML分化治疗新靶点，Opera Phenix助力3D类器官药效验证 急性髓系白血病（AML）是一类恶性程度极高的血液肿瘤，分化阻滞是其核心致病特征，尽管AML的亚型之一急性早幼粒细胞白血病（APL）已依靠分化疗法实现临床治愈，但占绝大多数的非APL型AML，长期缺乏有效的分化治疗方案，现有靶向药仅针对少数基因突变亚型，且难以清除白血病干细胞，预后改善有限。 2026年5月，上海交通大学附属瑞金医院的研究团队在《Signal Transduction and Targeted Therapy》发表重磅研究成果，首次鉴定出ZMIZ1是维持AML分化阻滞的关键表观调控因子，并研发出靶向抑制ZMIZ1小分子化合物，可有效解除AML分化阻滞，诱导白血病细胞成熟分化、削弱干性、重塑抗肿瘤免疫。该研究为非APL型AML提供了全新、可转化的分化治疗靶点与候选药物。在这项从机制到转化的研究中，Opera Phenix高内涵成像分析系统成为3D骨髓类器官药效验证的关键技术支撑。 研究思路与实验 该研究的整体思路是：靶点筛选—机制解析—药物研发—药效验证，层层递进地完成了从靶点发现到临床转化的验证。下表展示了各阶段核心实验方法与结论。 研究阶段 核心实验方法 核心结论 靶点筛选 基于CRISPR‑Cas9转录与表观调控功能缺失文库，对512个基因进行筛选； 临床大量样本的相关性验证； shRNA敲低AML细胞系的表型验证：细胞增殖/凋亡/分化检测； 小鼠AML模型体内敲除ZMIZ1进行生存分析、白血病负荷检测 鉴定ZMIZ1为AML分化阻滞关键调控因子； ZMIZ1在患者中高表达且与不良预后显著相关； 敲低/敲除ZMIZ1可诱导髓系分化、抑制白血病细胞生长； 小鼠体内缺失ZMIZ1可显著降低白血病负荷、延长小鼠生存期 机制解析 免疫荧光共定位；相分离与FRAP实验验证；ChIP‑seq/Re‑ChIP‑seq；Hi‑C三维基因组；TurboID互作质谱；Co‑IP；scRNA‑seq与RNA velocity ZMIZ1形成核相分离凝聚体，富集结合超级增强子；与MEF2D协同稳定增强子‑启动子环；维持癌基因转录、阻滞分化、保留白血病干细胞干性 药物研发 利用ZMIZ1的结构信息和AlphaFold模型进行结构引导的小分子筛选：5万个化合物； 生物物理活性验证（SPR、MST亲和力检测）； 药物特异性验证（CETSA突变验证）； 体外细胞药效验证（单药/联合用药细胞表型、转录组分析） 获得SIH‑001/SIH‑002高亲和力先导化合物； 特异性结合ZMIZ1并降解蛋白； 可诱导AML分化、降低干性，与venetoclax/Ziftomenib协同增效 药效验证 小鼠AML移植模型生存期观察； 人iPSC诱导分化形成的3D骨髓类器官用Opera Phenix高内涵成像定量； 原代AML细胞药效； 单细胞转录组 体内抑制ZMIZ1显著延长小鼠生存期、减轻器官浸润； 3D类器官证实药物抑制AML定植浸润与增殖； 恢复抗原呈递，具备临床转化潜力 Opera Phenix高内涵成像系统在研究中承担的任务 在该研究中，Opera Phenix高内涵成像分析系统主要用于完成人iPSC来源AML骨髓类器官（BMO）的三维成像与定量分析，是用于3D骨髓类器官可视化与定量药效学验证的核心技术，针对ZMIZ1抑制剂单药、venetoclax、Ziftomenib及联合用药组，高通量、高精度评估三维立体肿瘤模型中的药物治疗效果。 Opera Phenix具体开展实验内容 将植入人原代急性髓系白血病（AML）细胞的骨髓类器官进行固定、透化、免疫荧光染色（DAPI细胞核、FITC标记CD33+AML白血病细胞、APC-Cy7标记CD45+人造血细胞），经透明化处理后，利用Opera Phenix高内涵系统对96孔板中的骨髓类器官样本进行三荧光通道同步采集，进行骨髓类器官的全自动Z-stack层扫与三维重构。 图注：对植入急性髓系白血病（AML）细胞的骨髓类器官进行全景共聚焦成像与三维重构；样本经Hoechst（蓝色/细胞核）、CD33（FITC绿色/AML白血病细胞）、CellTrace（黄色/细胞示踪）及CD45（APC-Cy7红色/人造血干细胞）荧光标记。 通过高内涵软件在三维重构的视觉效果下进行如下的数据分析： - 细胞计数：类器官内总细胞数、CD33+AML阳性白血病细胞数量、CD33+细胞占总细胞比例； - 细胞增殖/抑制率：各组AML细胞增殖抑制率、单药/联合用药细胞清除效率对比； - 细胞空间分布参数：AML细胞在类器官内部的浸润深度、空间定植范围、细胞分布密度； - 分化及表型指标：药物干预后白血病细胞形态变化、细胞干性相关表型量化评估； - 药效协同性：SIH-001分别联合venetoclax、Ziftomenib药物时干预效果标准化对比与统计学差异分析。 实验结论 通过系统定量分析证实：靶向ZMIZ1的SIH-001可显著抑制AML细胞在人骨髓类器官内的定植、浸润与增殖，有效降低白血病细胞干性；且SIH-001与venetoclax、Ziftomenib具有显著协同增效作用，联合用药可最大程度清除类器官内白血病细胞、抑制肿瘤恶性增殖，从三维人源化模型层面，直观、定量验证了ZMIZ1抑制剂的安全性与高效性，为药物后续临床转化提供了真实可靠的可视化数据支撑。 总结 该研究创新性证实ZMIZ1是AML分化阻滞的核心表观调控靶点，阐明了其通过相分离凝聚体、超级增强子调控、MEF2D协同轴驱动AML恶性进展的全新机制，开发出高特异性ZMIZ1小分子抑制剂，突破了非APL型AML缺乏广谱分化治疗方案的临床难题，为难治复发AML提供了全新的治疗方向。而瑞孚迪（Revvity） Opera Phenix高内涵成像系统凭借优异的3D厚样本成像、多通道精准定量、高通量药物筛选能力，成功实现了人源骨髓类器官的可视化药效评估，精准验证了靶向ZMIZ1药物的单药及联合用药价值，弥补了传统二维实验与动物模型的局限性，是本研究从基础机制走向临床转化的关键核心技术支撑。 Opera Phenix PLUS和Operetta CLS两个型号的高内涵成像分析系统，以高通量方式完成类器官的3D层扫、深层成像、AI定量，精准读取类器官表型与功能变化。 瑞孚迪explorer G3类器官全流程无人值守自动化平台：从种胶、传代、换液、加药，生长动态监测，药敏测试、多维度表型功能筛选等，全流程自动化标准化运行，大幅降低批次差异，对接合规要求，重新定义类器官研发流程与效率。 参考文献 Li, H., Liu, Y., Cui, J. et al. Targeting ZMIZ1 induces differentiation in acute myeloid leukemia via chromatin remodeling. Sig Transduct Target Ther 11, 189 (2026). https://doi.org/10.1038/s41392-026-02766-6  研究思路与实验