Across 50 treated patients, palazestrant (OP-1250) in combination with ribociclib was well tolerated with no new safety signals or increased toxicity and no clinically meaningful impact on drug exposure of either therapy

在50名接受治疗的患者中，palazestrant（OP-1250）联合ribociclib耐受性良好，没有新的安全信号或毒性增加，对两种疗法的药物暴露均无临床意义的影响

85% clinical benefit rate (CBR) observed to date across all CBR-eligible patients supports promising preliminary efficacy profile of the palazestrant-ribociclib combination

迄今为止，在所有符合CBR条件的患者中观察到的85%的临床获益率（CBR）支持palazestrant-ribociclib组合的有希望的初步疗效

Olema will host an investor conference call today at 8:00 a.m. ET

Olema将于美国东部时间今天上午8:00主持投资者电话会议

SAN FRANCISCO, May 15, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology,” Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, today announced interim results from an ongoing Phase 1b/2 clinical study of palazestrant (OP-1250) in combination with CDK4/6 inhibitor ribociclib for the treatment of ER+/HER2- metastatic breast cancer.

旧金山，2024年5月15日（环球通讯社）--Olema Pharmaceuticals，Inc.（“Olema”或“Olema Oncology”，纳斯达克：OLMA），一家临床阶段的生物制药公司，专注于女性癌症靶向治疗的发现，开发和商业化，今天宣布了palazestrant（OP-1250）正在进行的1b/2期临床研究与CDK4/6抑制剂ribociclib联合治疗ER+/HER2转移性乳腺癌的中期结果。

These results, as of the data cut-off of March 13, 2024, will be presented on May 16, 2024, in a poster session at the 2024 ESMO Breast Cancer Annual Congress in Berlin, Germany (ESMO Breast)..

截至2024年3月13日的数据截止日期，这些结果将于2024年5月16日在德国柏林2024年ESMO乳腺癌年会（ESMO乳腺癌）的海报会议上公布。。

The poster, titled “A Phase 1b/2 Study of Palazestrant (OP-1250) in Combination with Ribociclib in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Advanced and/or Metastatic Breast Cancer”, highlighted that:

该海报题为“Palazestrant（OP-1250）联合Ribociclib治疗雌激素受体阳性，人表皮生长因子受体2阴性，晚期和/或转移性乳腺癌患者的1b/2期研究”，强调：

Across 50 treated patients, the combination of up to 120 mg of palazestrant with the full and approved dose of 600 mg of ribociclib daily was well tolerated, with no new safety signals or enhancement of toxicity and an overall safety profile consistent with the established safety profile of ribociclib plus an endocrine therapy..

在50名接受治疗的患者中，高达120 mg的palazestrant与每日600 mg的完整和批准剂量的ribociclib的组合耐受性良好，没有新的安全信号或毒性增强，总体安全性与已建立的ribociclib加内分泌治疗的安全性相一致。。

Palazestrant did not affect ribociclib drug exposure and ribociclib had no clinically meaningful effect on palazestrant drug exposure.

Palazestrant不影响ribociclib药物暴露，ribociclib对Palazestrant药物暴露没有临床意义。

Promising preliminary efficacy was observed to date with a clinical benefit rate (CBR) of 85% across all CBR-eligible patients (11/13), 83% in ESR1-mutant patients (5/6), 86% in ESR1-wild-type patients (6/7), and 83% in prior CDK4/6 inhibitor patients (10/12).

迄今为止，观察到有希望的初步疗效，所有符合CBR条件的患者的临床获益率（CBR）为85%（11/13），ESR1突变患者为83%（5/6），ESR1野生型患者为86%（6/7），之前的CDK4/6抑制剂患者为83%（10/12）。

Partial responses were observed in five patients through the data cut-off (2 confirmed, 3 unconfirmed) among 23 response-evaluable patients.

通过23名可评估反应的患者中的数据截止（2名确认，3名未确认），在5名患者中观察到部分反应。

Findings from this study support the continued clinical development of palazestrant in combination with ribociclib for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer.

这项研究的结果支持palazestrant联合ribociclib用于ER+/HER2晚期或转移性乳腺癌的一线治疗的持续临床开发。

“The data we are presenting at the ESMO Breast Cancer Annual Congress in Berlin add further support to our thesis that palazestrant possesses key characteristics that make it a potential backbone endocrine therapy of preference for ER+/HER2- breast cancer, both as a monotherapy and in combination with other targeted agents,” said Sean P.

“我们在柏林ESMO乳腺癌年会上提供的数据进一步支持了我们的论点，即palazestrant具有关键特征，使其成为ER+/HER2乳腺癌首选的潜在骨干内分泌治疗方法，既可以作为单一疗法，也可以与其他靶向药物联合使用，”Sean P。

Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “We are grateful to the approximately 300 women to date that have participated across our clinical trials. We are excited with the progress we are making, and we look forward to advancing toward our goal of transforming the endocrine therapy standard of care for breast cancer.”.

博恩，医学博士，博士，Olema Oncology总裁兼首席执行官。“我们感谢迄今为止约300名女性参与了我们的临床试验。我们对正在取得的进展感到兴奋，并期待着朝着改变乳腺癌内分泌治疗标准的目标前进。”。

Phase 1b/2 Clinical Study Results

1b/2期临床研究结果

Enrollment

注册

As of the data cut-off of March 13, 2024, 50 patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer with at least four weeks of follow-up were treated with palazestrant (3 patients each at 30 mg once daily and 60 mg once daily, 44 patients at the palazestrant recommended Phase 2 dose (RP2D) of 120 mg once daily) plus ribociclib 600 mg once daily (three weeks followed by one week off treatment).

截至2024年3月13日的数据截止日期，50例复发性，局部晚期或转移性ER+/HER2-乳腺癌患者接受了至少四周的随访（3例患者各30 mg，每日一次，60 mg，44例患者在palazestrant推荐的2期剂量（RP2D）为120 mg，每日一次）加上ribociclib 600 mg，每日一次（三周后停止治疗一周）。

The majority of patients (37 or 74%) were 2nd/3rd line+, with 37 (74%) patients having received prior endocrine therapy for metastatic breast cancer, 35 (70%) patients having received prior CDK4/6 inhibitors (11 or 22% having received two prior lines of CDK4/6 inhibitors), and nine (18%) patients having received chemotherapy for metastatic breast cancer.

大多数患者（37%或74%）为二线/三线+，其中37例（74%）患者接受过转移性乳腺癌的内分泌治疗，35例（70%）患者接受过CDK4/6抑制剂治疗（11%或22%）接受过两次CDK4/6抑制剂治疗，9例（18%）患者接受过转移性乳腺癌化疗。

Of 48 patients whose circulating tumor DNA (ctDNA) was assessed as of the data cut-off, 27% had activating mutations in ESR1 at baseline. The study is now fully enrolled with 60 patients..

在截止数据时评估了48例循环肿瘤DNA（ctDNA）的患者中，有27%的患者在基线时ESR1发生了激活突变。这项研究目前已全部纳入60名患者。。

Pharmacokinetics

药代动力学

Palazestrant demonstrated favorable pharmacokinetics characterized by high oral bioavailability, dose proportional exposure and a half-life of eight days as a single agent, with steady-state plasma levels showing minimal peak-to-trough variability enabling consistent inhibition of ER for the full dosing interval.

Palazestrant表现出良好的药代动力学，其特征在于高口服生物利用度，剂量比例暴露和作为单一药剂的八天半衰期，稳态血浆水平显示最小的峰谷变化，使得在整个给药间隔内能够一致抑制ER。

Palazestrant did not affect ribociclib 600 mg drug exposure when compared with published exposure data for single-agent ribociclib. Steady-state trough values showed no clinically significant difference between the combination and single-agent palazestrant..

与单药ribociclib公布的暴露数据相比，Palazestrant不影响ribociclib 600 mg药物暴露。稳态谷值显示联合用药和单药palazestrant之间没有临床显着差异。。

Safety and Tolerability

安全性和耐受性

Treatment with palazestrant up to the RP2D of 120 mg was well tolerated with no dose-limiting toxicities, and the maximum tolerated dose (MTD) was not reached. The majority of treatment-emergent adverse events (TEAEs) were Grade 1 or 2, and the severity and incidence of adverse events were consistent with the expected safety profile of ribociclib plus endocrine therapy.

palazestrant治疗至RP2D为120 mg，耐受性良好，无剂量限制性毒性，未达到最大耐受剂量（MTD）。大多数治疗紧急不良事件（TEAE）为1级或2级，不良事件的严重程度和发生率与ribociclib加内分泌治疗的预期安全性一致。

Ten patients had dose reduction of ribociclib only, due to QTcF prolongation (n=4), neutropenia (n=4), or fatigue (n=2). No patients discontinued palazestrant due to a treatment-related adverse event, and two patients discontinued ribociclib for neutropenia without discontinuation of palazestrant in the 120 mg cohort.

由于QTcF延长（n=4），中性粒细胞减少（n=4）或疲劳（n=2），10名患者仅减少了ribociclib的剂量。没有患者因治疗相关的不良事件而停用帕拉西坦，两名患者因中性粒细胞减少而停用了ribociclib，而在120 mg队列中没有停用帕拉西坦。

Neutropenia was reversible in all patients and the timing was consistent with ribociclib-related neutropenia..

中性粒细胞减少症在所有患者中都是可逆的，并且时间与ribociclib相关的中性粒细胞减少症一致。。

Efficacy

功效

In a maturing dataset, palazestrant showed anti-tumor activity and prolonged disease stabilization in patients both with ESR1 wild-type and ESR1 activating mutations at baseline, and in those previously treated with one or two lines of CDK4/6 inhibitors. Partial responses were observed in five patients (two confirmed, three unconfirmed as of data cut-off) out of 23 response-evaluable patients.

在一个成熟的数据集中，palazestrant在基线时具有ESR1野生型和ESR1激活突变的患者以及先前用一种或两种CDK4/6抑制剂治疗的患者中均显示出抗肿瘤活性和延长的疾病稳定期。在23名可评估反应的患者中，有5名患者（截至数据截止，2名已确认，3名未确认）观察到部分反应。

Across patients who were CBR-eligible, the CBR was 85% (11/13) for all patients, 83% (5/6) for patients with ESR1 mutations, 86% (6/7) for patients that were ESR1 wild-type, and for CDK4/6i-pretreated patients the CBR was 83% (10/12). The longest duration on treatment is 44 weeks through the data cut-off, and 66% (33/50) of patients in this data set remain on treatment as of the data cut-off date..

在符合CBR条件的患者中，所有患者的CBR为85%（11/13），ESR1突变患者为83%（5/6），ESR1野生型患者为86%（6/7），CDK4/6i预处理患者的CBR为83%（10/12）。截至数据截止日期，治疗的最长持续时间为44周，截至数据截止日期，该数据集中66%（33/50）的患者仍在接受治疗。。

A copy of the poster will be available on Olema’s website under the Science section.

海报的副本将在Olema的网站上的科学部分下提供。

Company Investor Webcast and Conference Call

公司投资者网络广播和电话会议

Olema will host a webcast and conference call for analysts and investors to review the data being presented at ESMO Breast Cancer Annual Congress 2024 today, Wednesday, May 15, 2024, at 8:00 a.m. ET (2:00 p.m. CEST). Please register for the webcast by visiting the Investors & Media section of Olema’s website at olema.com..

Olema将于今天，2024年5月15日星期三，美国东部时间上午8:00（CEST下午2:00），为分析师和投资者举办一次网络广播和电话会议，审查在2024年ESMO乳腺癌年会上提交的数据。请访问Olema网站Olema.com的投资者和媒体部分注册网络广播。。

About Palazestrant (OP-1250)

关于Palazestrant（OP-1250）

Palazestrant (OP-1250) is a novel, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

Palazestrant（OP-1250）是一种新型的口服小分子，具有完全雌激素受体（ER）拮抗剂（CERAN）和选择性ER降解剂（SERD）的双重活性。目前正在对复发性，局部晚期或转移性ER阳性（ER+），人表皮生长因子受体2阴性（HER2-）乳腺癌患者进行研究。

In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors.

在临床研究中，palazestrant完全阻断了野生型和突变型转移性ER+乳腺癌中ER驱动的转录活性，并且已经证明了抗肿瘤功效以及有吸引力的药代动力学和暴露，有利的耐受性，中枢神经系统穿透性以及与CDK4/6抑制剂的组合性。

Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus).

Palazestrant已获得美国食品和药物管理局（FDA）的快速通道指定，用于治疗ER+/HER2转移性乳腺癌，该乳腺癌在一种或多种内分泌治疗后进展，其中至少一种与CDK4/6抑制剂联合使用。它正在进行的3期临床试验OPERA-01中作为单一药物进行评估，并在CDK4/6抑制剂（palbociclib和ribociclib），PI3Ka抑制剂（alpelisib）和mTOR抑制剂（依维莫司）的1/2期联合研究中进行评估。

For more information, please visit www.opera01study.com..

有关更多信息，请访问www.opera01study.com。。

About Olema Oncology

关于Olema肿瘤学

Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for women living with cancer. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance.

Olema Oncology是一家临床阶段的生物制药公司，致力于改变癌症患者的护理标准并改善其预后。Olema通过利用我们对内分泌驱动的癌症，核受体和获得性耐药机制的深入了解，正在推进一系列新疗法。

In addition to our lead product candidate, palazestrant (OP-1250), a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), Olema is developing a potent KAT6 inhibitor (OP-3136). Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts.

除了我们的主要候选产品palazestrant（OP-1250），一种专有的口服完全雌激素受体（ER）拮抗剂（CERAN）和选择性ER降解剂（SERD），Olema正在开发一种有效的KAT6抑制剂（OP-3136）。Olema总部位于旧金山，在马萨诸塞州的剑桥市有业务。

For more information, please visit us at www.olema.com..

欲了解更多信息，请访问www.olema.com。。

Forward Looking Statements

前瞻性声明

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Words such as “anticipate,” “expect,” “will,” “may,” “goal,” “potential” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements.

本新闻稿中关于非历史事实的声明是1933年《证券法》第27A节和1934年《证券交易法》第21E节所指的“前瞻性声明”。诸如“预期”、“期望”、“意志”、“可能”、“目标”、“潜力”等词语和类似表达（以及其他涉及未来事件、条件或情况的词语或表达）旨在识别前瞻性陈述。

These statements include those related to the potential beneficial characteristics, safety, tolerability, efficacy, and therapeutic effects of palazestrant, the development of palazestrant, the initiation and timing of clinical trials, palazestrant’s combinability with other drugs, the potential of palazestrant to become a backbone endocrine therapy in the treatment of ER+/HER2- metastatic breast cancer, and Olema’s potential to transform the endocrine therapy standard of care treatments for women living with ER+/HER2- metastatic breast cancer.

这些声明包括与palazestrant的潜在有益特征，安全性，耐受性，有效性和治疗效果，palazestrant的发展，临床试验的开始和时间，palazestrant与其他药物的组合性，palazestrant成为治疗ER+/HER2转移性乳腺癌的骨干内分泌治疗的潜力，以及Olema改变ER+/HER2转移性乳腺癌患者内分泌治疗护理标准的潜力。

Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release.

由于此类声明涉及未来事件，并基于Olema当前的预期，因此会面临各种风险和不确定性，Olema的实际结果、表现或成就可能与本新闻稿中所述或暗示的结果、表现或成就存在重大差异。

These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and other filings and reports that Olema makes from time to time with the U.S.

这些前瞻性声明具有风险和不确定性，包括但不限于Olema截至2024年3月31日的季度报告表10-Q中题为“风险因素”的部分中讨论的风险和不确定性，以及Olema不时向美国提交的其他文件和报告。

Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, inclu.

证券交易委员会。除法律要求外，Olema不承担更新这些前瞻性声明的义务，包括。

Contact:

联系人：

Geoffrey Mogilner, Vice President, Investor Relations and Communications

Geoffrey Mogilner，投资者关系与沟通副总裁

ir@olema.com

ir@olema.com