Mevrometostat

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Oct. 27, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, presented posters at the 2025 EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics highlighting preclinical data that further illustrate the potential for ORIC-944, a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the embryonic ectoderm development (EED) subunit, to treat prostate cancer and various other solid tumors. “These preclinical data underscore the potential of ORIC-944 to overcome resistance not only in prostate cancer but in other solid tumors and highlight that the therapeutic potential of PRC2 inhibition may be maximized in combination with inhibitors of key tumor drivers, including AR inhibitors and KRAS inhibitors,” said Lori Friedman, PhD, chief scientific officer. “Based on these data and clinical findings to date, we continue to believe ORIC-944 is a potential best-in-class PRC2 inhibitor with potential in both castration-resistant and castration-sensitive prostate cancer, as well as multiple other tumor types.” Key findings of posters presented at the 2025 EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics: PRC2 inhibition enhances AR inhibitor response to delay treatment relapse in castration-sensitive prostate cancer by restricting adaptation of tumor cells in preclinical studies ORIC-944 is a potential best-in-class PRC2 inhibitor that, when combined with androgen receptor (AR) inhibition, synergistically impaired tumor growth, significantly improved survival and extended the duration of response to AR inhibitors in vivo by restricting cellular plasticity and delaying prostate tumor adaptation in castration-sensitive prostate cancer (CSPC). Transcriptional effects induced by combining ORIC-944 and AR inhibitors were comparable across all AR inhibitors tested (i.e., darolutamide, apalutamide or enzalutamide), and consistent with transcriptional effects of mevrometostat and AR inhibitor combination. Mechanistically, ORIC-944 in combination with AR inhibition in CSPC was linked to increased luminal cell state, and the restriction of lineage adaptation through reduced chromatin accessibility at binding sites of transcription factors associated with lineage diversification and cell plasticity such as FOXA, HNF1A and ONECUT2. These results were reproduced with mevrometostat and AR inhibitor combination and are consistent with what was previously reported in preclinical studies of CRPC. PRC2 inhibition enhances KRAS inhibitor response to delay treatment relapse in KRAS-mutant preclinical lung and colorectal cancer models ORIC-944 is a potential best-in-class PRC2 inhibitor that, when combined with KRAS inhibition, significantly improved efficacy and progression-free survival in KRAS G12C mutant non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) models, demonstrating that PRC2 inhibition can deepen and extend responses by preventing or delaying resistance to KRAS inhibition. PRC2 activity is increased in tumors from KRAS-mutant NSCLC and CRC patients, and transcriptional analysis from in vivo studies of CRC demonstrated that PRC2 inhibition drives tumor cell differentiation. ORIC-944 combined with the KRAS inhibitor adagrasib, regressed 100% of tumors in KRAS-mutant adenocarcinoma and squamous NSCLC xenograft models in vivo. The combination also prevented adagrasib tumor relapse and extended progression-free survival in a KRAS G12C adenocarcinoma NSCLC xenograft model. About ORIC-944 ORIC-944 is a potent and selective allosteric PRC2 inhibitor via EED subunit that demonstrates best-in-class drug properties in preclinical studies, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including clinical half-life of approximately 20 hours, robust target engagement, and a favorable safety profile. ORIC-944 continues to further demonstrate a potential best-in-class profile with positive interim PSA response data generated in an ongoing Phase 1b trial in combination with ERLEADA® (apalutamide) and in combination with NUBEQA® (darolutamide) for prostate cancer (NCT05413421). About ORIC Pharmaceuticals, Inc. ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the embryonic ectoderm development (EED) subunit, being developed for prostate cancer, and (2) enozertinib (ORIC-114), a brain penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the continued clinical development of ORIC-944 and its best-in-class potential; the potential advantages of ORIC-944, including in combination with KRAS inhibitors in lung and colorectal cancers; the development plans and timelines for ORIC-944; plans underlying ORIC’s clinical trials and development; and statements by the company’s chief scientific officer . Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC’s product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements; the potential market for our product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on August 12, 2025, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Contact: Dominic Piscitelli, Chief Financial Officer dominic.piscitelli@oricpharma.com info@oricpharma.com

根据美国Clinicaltrial数据库数据，今年9月份，全球新开由企业资本主导的临床试验总数为826项，数量较8月份上升18.51%；单月新开临床试验数量高于去年同期水平，同比上升28.46%。 热门领域分布 从9月份新开临床试验热门适应证来看，乳腺癌为最主要的热门研发领域，新开临床试验31项，环比上涨72.22%，同比上涨93.75%。其次为非小细胞肺癌，新开临床试验22项，与去年同期相比上涨10.00%。值得注意的是，9月份新开临床试验数量上升幅度最大的热门适应证为结肠炎，由8月份的3项上升至9项，上升幅度为200.00%；数量下降幅度最大的适应证为卵巢癌，由8月份的13项下降到9项，下降幅度为30.77%。 对新开临床试验的发起企业进行统计后发现，9月份发起临床试验最多的企业为阿斯利康，新开临床试验16项，环比上升6.67%，同比上升45.45%。其次为辉瑞，新开临床试验11项，环比下降21.42%，同比增长83.33%。值得注意的是，9月份我国药企齐鲁制药和康诺亚生物进入新开临床试验数量排名前十榜单，分别新开8项和5项临床试验。其中，齐鲁制药为新开临床试验数量上升幅度最大的企业，与8月份相比上升了7倍。 对临床试验的申请国家和地区进行统计后发现，9月份美国仍为临床试验开展最为主要的国家，新开临床试验227项，相较8月份上涨了1.79%。其次是中国，新开临床试验数量为113项，与8月份相比下降了21.53%。 头部企业表现 9月份新开临床试验数量排名前三的企业分别为阿斯利康、辉瑞和百时美施贵宝，数量分别为16项、11项、10项。 阿斯利康9月份新开的16项临床试验中，有两项为Ⅲ期临床试验，适应证均为肿瘤。其中一项的适应证为尿路上皮癌（NCT07205822），试验药物为Dato-DXd（德达博妥单抗）。该药是一种靶向TROP2的抗体偶联药物（ADC），主要用于治疗乳腺癌和非小细胞肺癌。另一款进入Ⅲ期临床试验的药物为Durvalumab，适应证为硬纤维瘤（NCT06992609）。Durvalumab是一种人源化的抗PD-L1蛋白单克隆抗体，可阻断PD-L1与PD-1和CD80结合的能力。 辉瑞9月份新开的11项临床试验中，有3项为Ⅲ期临床试验，其中两项的适应证均为肿瘤，分别为泛晚期肿瘤（NCT06103734）和广泛性小细胞肺癌（NCT07028853）。其中，泛晚期肿瘤的试验药物为Zavegepant，该药属于第三代高选择性降钙素基因相关肽（CGRP）受体拮抗剂，通过阻断CGRP信号通路发挥治疗作用；广泛性小细胞肺癌的试验药物为Mevrometostat，是一款选择性EZH2抑制剂。另一项Ⅲ期临床试验的适应证为体外膜氧合并发症（NCT07029828），试验药物为Ritlecitinib，该药是一种口服选择性JAK3抑制剂。 百时美施贵宝9月份新开的10项临床试验中，有3项为Ⅲ期临床试验，适应证分别为多发性硬化症（NCT07140913）、肾结石（NCT07116967）和克罗恩病（NCT06979453）。以多发性硬化症为适应证的试验药物为Xanomeline/Trospium Chloride，这是一款复方药物。其中，Xanomeline通过激活中枢神经系统的M1/M4受体，改善精神分裂症的阳性（如幻觉）、阴性（如情感淡漠）及认知症状；Trospium Chloride作为外周拮抗剂，抑制Xanomeline对胃肠道的副作用（如恶心、呕吐），提高机体耐受性。以肾结石和克罗恩病为适应证的试验药物均为Deucravacitinib，该药是一种选择性酪氨酸激酶2（TYK2）变构抑制剂，通过选择性结合TYK2假激酶结构域，抑制IL-12/23和Ⅰ型干扰素信号通路，从而调节免疫反应。 齐鲁制药9月份新开8项临床试验，其中3项为Ⅲ期临床试验，适应证分别为周围神经病变（NCT07162883）、胰腺癌（NCT07079228）和特应性皮炎（NCT06732323）。以周围神经病变为适应证的试验药物为QL2107，这是一款PD-1抑制剂生物类似药。以胰腺癌为适应证的试验药物为QLS31905，该药是齐鲁制药自主研发的靶向Claudin18.2（CLDN18.2）和CD3的双特异性T细胞衔接器（BiTE），通过结合肿瘤细胞表面的CLDN18.2和T细胞表面的CD3，激活T细胞，从而杀伤肿瘤细胞。以特应性皮炎为适应证的试验药物为ESG401，该药是一款靶向 CLDN18.2的单克隆抗体，主要用于治疗CLDN18.2阳性实体瘤。 康诺亚生物9月份新开的5项临床试验中，包括两项Ⅲ期临床试验，适应证分别为多发性硬化症（NCT07181239）和特应性皮炎（NCT07106372）。多发性硬化症的试验药物为CM336，该药是康诺亚生物自主研发的一款靶向BCMA和CD3的双特异性抗体，通过同时结合靶细胞上的BCMA和T细胞上的CD3，激活T细胞介导的细胞毒性（TDCC）作用，从而清除靶细胞。以特应性皮炎为适应证的试验药物为Stapokibatrt，该药是一款靶向I L-4Rα的单克隆抗体，主要用于治疗2型炎症性疾病。 （数据来源于美国Clinicaltrial数据库，统计时间为10月9日） 来源/ 中国医药报 文/ 陈宇哲 新媒体编辑：李佳欢 统筹策划：何红梅 中国医药报社版权所有，未经许可不得转载使用。