Tipifarnib

– KOMET-001 registrational trial in R/R NPM1-mutant AML achieved primary endpoint – – Alignment reached with FDA and EMA on key aspects of the KOMET-017 protocol including use of MRD-negative CR endpoint for potential U.S. accelerated approval pathway in frontline intensive chemotherapy trial – – Topline MRD-negative CR results from KOMET-017-IC Phase 3 trial anticipated in 2028 – – Multiple data presentations for ziftomenib and pipeline programs expected throughout 2025 – – $727.4 million in cash, together with anticipated collaboration agreement payments, to support ziftomenib commercialization through the frontline AML combination setting – – Management to host webcast and conference call today at 4:30 p.m. ET – SAN DIEGO , Feb. 26, 2025 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported fourth quarter and full year 2024 financial results and provided a corporate update. “We are very pleased the KOMET-001 registrational trial achieved its primary endpoint. We look forward to sharing topline data at an upcoming medical conference and expect to submit a New Drug Application (NDA) in relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) next quarter,” said Troy Wilson , Ph.D., J.D., President and Chief Executive Officer of Kura Oncology . “In parallel, we are advancing ziftomenib into registrational studies in the frontline (1L) setting. Approximately half of patients with newly diagnosed NPM1-mutated (NPM1-m) AML and 80% of patients with KMT2A-rearranged (KMT2A-r) AML will die from the disease within five years. Given this unmet need, we are pleased to have reached alignment with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on key aspects of our Phase 3 trials, including the use of minimum residual disease (MRD)-negative complete response (CR) as a primary endpoint for potential accelerated approval in the U.S. , with topline results anticipated in 2028. Our KOMET-017 trial is breaking new ground, and we and our partners at Kyowa Kirin are working as rapidly as possible to bring ziftomenib to AML patients worldwide.” Recent Highlights Positive topline results from registration-directed trial of ziftomenib in R/R NPM1-m AML – Kura and Kyowa Kirin announced positive topline results from KOMET-001, the Phase 2 registration-directed trial of ziftomenib in patients with R/R NPM1-m AML. The KOMET-001 trial achieved its primary endpoint, consistent with the targeted 20-30% CR/CR with partial hematological recovery (CRh) rate, and data have been submitted for presentation at ASCO. The benefit-risk profile for ziftomenib is highly encouraging, and safety and tolerability were consistent with previous reports. Facilitated by the Breakthrough Therapy Designation status of ziftomenib in R/R NPM1-m AML, the Company completed its pre-NDA meeting with FDA and anticipates submitting an NDA in the second quarter of 2025. Positive feedback from FDA for 1L combination trial designs – Earlier this month, Kura and Kyowa Kirin announced alignment with FDA on the KOMET-017 global trial protocol evaluating ziftomenib in combination with both intensive and non-intensive combination regimens in patients with newly diagnosed NPM1-m and/or KMT2A-r AML. This includes alignment on potential pathways for accelerated approval in the U.S. in both the KOMET-017-IC (intensive chemotherapy) and KOMET-017-NIC (non-intensive chemotherapy) trials by allowing the trials to use MRD-negative CR and CR, as primary endpoints, respectively. The companies also gained alignment with the EMA on the KOMET-017 protocol, and expect to initiate the KOMET-017 Phase 3 trials in the second half of 2025. Positive clinical data for Phase 1 trial of ziftomenib in combination with standards of care – In December 2024 , Kura Oncology and Kyowa Kirin announced encouraging clinical data from KOMET-007, a Phase 1 trial of ziftomenib in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine in patients with NPM1-m and KMT2A-r AML. Among response-evaluable patients enrolled in the 7+3 combination cohort for patients with 1L NPM1-m or KMT2A-r adverse risk AML, 91% achieved a CR (100% for NPM1-m, 83% for KMT2A-r patients). Ziftomenib was generally well tolerated in combination at all dose levels evaluated across all cohorts in the Phase 1a dose-escalation portion of the trial. The positive results from KOMET-007 reported at ASH reinforce the companies’ commitment to evaluating ziftomenib across the continuum of 1L AML treatment options. Global strategic collaboration with Kyowa Kirin to develop and commercialize ziftomenib in acute leukemias – In November 2024 , Kura Oncology and Kyowa Kirin announced they entered into a global strategic collaboration to develop and commercialize ziftomenib (Kyowa Agreement), funding the expansive AML development program through U.S. commercialization in 1L combinations. Under the partnership, Kura retains leadership and key strategic rights to ziftomenib in the U.S. and preserves strategic flexibility, while enabling development and commercialization of ziftomenib across the continuum of care in acute leukemias, including both fit and unfit 1L indications, post-transplant maintenance setting and combinations with targeted therapies. Preclinical data supporting opportunity for ziftomenib in treatment of gastrointestinal stromal tumors (GIST) – In October 2024 , Kura reported preclinical data presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona , supporting the potential for ziftomenib in combination with KIT inhibitors for GIST patients. The combination of ziftomenib and imatinib demonstrated robust and durable antitumor activity in imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST patient-derived xenograft models. Sixty percent of patients develop resistance to imatinib within two years and ziftomenib has the potential to delay the onset of resistance to, or overcome resistance in patients pre-treated with, imatinib. In August 2024 , Kura announced clearance by the FDA of an IND application and the Company remains on track to initiate the KOMET-015 trial evaluating ziftomenib plus imatinib in patients with advanced GIST, in the first half of 2025. Clinical and preclinical data support combinations of farnesyl transferase inhibitors with targeted therapies – Despite multiple advances, innate and adaptive resistance remain a challenge for many classes of targeted therapies in cancer. A growing body of clinical and preclinical data demonstrates the potential of farnesyl transferase inhibitors as companion therapeutic agents to augment the antitumor activities of various targeted therapies and overcome resistance in combination. Enrollment in the FIT-001 trial evaluating our next-generation farnesyl transferase inhibitor KO-2806 continues to progress and the dose-escalation portion of the KURRENT-HN trial with tipifarnib is now complete. Kura expects to present the first clinical data for KO-2806 as a monotherapy and in combination, as well as clinical data from the KURRENT-HN trial, in the second half of 2025. Financial Results Collaboration revenue from our Kyowa Kirin partnership for the fourth quarter and full year 2024 was $53.9 million , compared to no revenue in 2023. Research and development (R&D) expenses for the fourth quarter of 2024 were $52.3 million , compared to $32.5 million for the fourth quarter of 2023. R&D expenses for the full year 2024 were $170.0 million , compared to $115.2 million for the prior year. General and administrative (G&A) expenses for the fourth quarter of 2024 were $24.1 million , compared to $14.2 million for the fourth quarter of 2023. G&A expenses for the full year 2024 were $77.1 million , compared to $50.6 million for the prior year. Net loss for the fourth quarter of 2024 was $19.2 million , compared to a net loss of $42.8 million for the fourth quarter of 2023. Net loss for the full year 2024 was $174.0 million , compared to a net loss of $152.6 million for the prior year. Net loss for the fourth quarter and full year 2024 included non-cash, share-based compensation expense of $8.6 million and $33.9 million , respectively. This compares to $7.2 million and $28.1 million for the same periods in 2023. As of December 31, 2024 , Kura had cash, cash equivalents and short-term investments of $727.4 million , including the upfront payment of $330.0 million from Kyowa Kirin, compared to $424.0 million as of December 31, 2023 . Based on our current plans, we believe our cash, cash equivalents and short-term investments as of December 31, 2024 will be sufficient to enable us to fund our current operating expenses into 2027, and combined with anticipated collaboration funding under the Kyowa Agreement, should support our ziftomenib AML program through commercialization in the 1L combination setting. Forecasted Milestones Submit an NDA for ziftomenib in R/R NPM1-m AML in the second quarter of 2025. Present topline data from KOMET-001 Phase 2 registration-directed trial in R/R NPM1-m AML in the second quarter of 2025. Present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with intensive chemotherapy (7+3) at a medical meeting in the second quarter of 2025. Initiate the KOMET-015 trial evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025. Initiate two independent Phase 3 registration-enabling trials in 1L intensive (KOMET-017-IC) and non-intensive (KOMET-017-NIC) AML in the second half of 2025. Present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with venetoclax and azacitidine at a medical meeting in the second half of 2025. Nominate a development candidate for next-generation menin inhibitor program in diabetes in mid-2025. Initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the first half of 2025. Present data from the Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025. Present data from the Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half of 2025. Present data from the dose escalation portion of KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the second half of 2025. Conference Call and Webcast Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, February 26, 2025 , to discuss the financial results for the fourth quarter and full year 2024 and to provide a corporate update. The live call may be accessed by dialing (800) 579-2543 for domestic callers and (785) 424-1789 for international callers and entering the conference ID: KURAQ4. A live webcast and archived replay of the event will be available here or online from the investor relations section of the company website at www.kuraoncology.com. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates targeting cancer signaling pathways. Ziftomenib, a once-daily, oral menin inhibitor, is the first and only investigational therapy to receive Breakthrough Therapy Designation from the FDA for the treatment of R/R NPM1-m AML. In November 2024 , Kura Oncology entered a global strategic collaboration agreement with Kyowa Kirin Co., Ltd. to develop and commercialize ziftomenib for AML and other hematologic malignancies. Enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-m AML has been completed, and the companies anticipate submission of an NDA to the FDA in the second quarter of 2025. Kura Oncology and Kyowa Kirin are also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-m and KMT2A-r AML. KO-2806, a next-generation farnesyl transferase inhibitor, is being evaluated in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies. Tipifarnib, a potent and selective farnesyl transferase inhibitor, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent HNSCC. For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn. 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 statements regarding, among other things, the efficacy, safety and therapeutic potential of Kura’s product candidates, ziftomenib, tipifarnib and KO-2806; plans, trial designs and expected timing of clinical trials; the expected timing and presentation of results and data from clinical trials; the anticipated timing of submission of an NDA for ziftomenib; the potential for U.S. accelerated approval and full approval of product candidates; and the success and impact of interactions with the FDA; the potential for menin inhibitors to shift the treatment paradigm for GIST; the strength of Kura’s balance sheet and the sufficiency of cash, cash equivalents and short-term investments to fund its current operating plan to 2027, and combined with anticipated collaboration funding under the Kyowa Agreement, to support Kura’s ziftomenib AML program through commercialization in the 1L combination setting. 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, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, 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 the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission , which are available at www.sec.gov. 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. Investors: Patti Bank Managing Director(415) 513-1284patti.bank@icrhealthcare.com Media: Alexandra Weingarten Associate Director, Corporate Communications (858) 500-8822alexandra@kuraoncology.com Source: Kura Oncology, Inc.

点击蓝字 关注我们 【导读】 胰腺癌是导致肿瘤相关死亡的主要原因之一，其特点是患者存活时间短，治疗方案有限。一些靶向疗法未能成功改善患者的预后。肿瘤膜具有潜在的靶向特异性，为提高免疫疗法和药物治疗的疗效带来了希望。 2025年2月19日，广州医科大学第一附属医院的研究团队在期刊《Heliyon》上发表了题为“A novel signature predicts prognosis in pancreatic cancer based on tumor membrane-associated genes”的研究论文。 这项研究 通过scRNA-seq技术揭示了PDAC的瘤内异质性，构建了一个新的预后风险模型（MaGPS），并鉴定了6个与预后相关的膜相关基因，为PDAC的诊断和治疗提供了新的见解和潜在靶点。 https://www-cell-com.libproxy1.nus.edu.sg/heliyon/fulltext/S2405-8440(25)01172-7 01 研究背景 Deng等人在PDAC小鼠模型中证实，糖皮质激素受体（GR）的表达与PD-L1呈正相关，抑制GR会导致肿瘤细胞上的PD-L1下调，从而促进T细胞浸润，增强抗肿瘤免疫力。表皮生长因子受体抑制剂已被批准用于肺腺癌患者的表皮生长因子受体靶向治疗。Alan团队报告称，靶向表皮生长因子受体的多克隆T细胞能有效引导PDAC肿瘤细胞，从而增加T细胞浸润和T细胞介导的抗肿瘤效应。靶向治疗与免疫治疗的结合，主要集中在黑色素瘤和非小细胞肺癌。目前，靶向治疗、化疗或免疫疗法的联合应用在癌症治疗中可能更具潜力。PDAC急需找到新的有效靶点或生物标志物。 02 MaGPS预测PDAC抗肿瘤治疗的潜在益处 为了探索MaGPS相关基因的潜在靶向药物，团队们利用癌症基因组计划（CGP 2014）数据集分析了MaGPS风险组与抗肿瘤药物敏感性之间的相关性。基于TCGA-PAAD数据，团队使用pRRophetic软件包预测了138种药物对PDAC患者的IC50值。样本被分为MaGPS评分高和低两组，并比较了两组之间的差异。两组间有38种药物的IC50值存在显著差异。低风险组中有7种药物的IC50值较低，而高风险组中有31种药物的IC50值较低。低风险组IC50值明显较低的药物包括ATRA、AICAR、EHT-1864、BX-795和CCT007093。MaGPS评分较低的PDAC患者可能对这些药物更敏感。此外，高风险组中IC50值较低的药物包括Tipifarnib、GSK-650394、VX-680、Thapsigargin和Epothilone-B，这些药物可能对MaGPS特征评分较高的PDAC患者更有效。这些结果表明， MaGPS相关基因在指导抗肿瘤药物的选择以及为PDAC患者制定更有针对性、更有效的治疗策略方面具有潜力。 与PDAC药物敏感性相关的MaGPS。 03 总结 1. 关键基因的发现： 研究确定了6个与预后相关的膜相关基因（LMO7、APOL1、SLC2A1、C15orf48、FXYD3和CLDN18），这些基因在PDAC的诊断和治疗中具有潜在价值。 2. 临床潜力： MaGPS模型在预测PDAC患者生存率方面表现出色，并且这些基因的高表达可能为PDAC的诊断和治疗提供新的靶点。例如，Tipifarnib可能对MaGPS评分高的患者有治疗益处。 3. 未来方向： 研究结果为PDAC患者的预后评估和治疗提供了新的生物标志物和潜在治疗靶点，未来的研究应进一步验证这些特征并探索其在联合疗法中的应用。 参考资料： 1.Huang, J. ∙ Lok, V. ∙ Ngai, C.H. ... Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer Gastroenterology. 2021; 160:744-754 2.Siegel, R.L. ∙ Miller, K.D. ∙ Fuchs, H.E. ... Cancer Statistics CA Cancer J Clin. 2021; 71:7-33 2021 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 热门推荐活动 点击免费报名 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛 点击对应文字 查看详情