A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)

This phase 3 clinical trial compares the safety and efficacy of palazestrant (OP-1250) to the standard-of-care options of fulvestrant or an aromatase inhibitor in women and men with breast cancer whose disease has advanced on one endocrine therapy in combination with a CDK4/6 inhibitor.

Start Date16 Nov 2023

Sponsor / Collaborator

Olema Pharmaceuticals, Inc.

NCT05508906 / RecruitingPhase 1

A Phase 1b Open-Label Multicenter Study of OP-1250 in Combination With the CDK4/6 Inhibitor Ribociclib or With the PI3K Inhibitor Alpelisib in Adult Subjects With Advanced and/or Metastatic HR Positive, HER2 Negative Breast Cancer

This is a Phase 1b open-label, 2-part study in 2 treatment groups. The 2 treatment groups are as follows:
Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).
Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation).

Start Date31 Aug 2022

Sponsor / Collaborator

Olema Pharmaceuticals, Inc.

[+1]

ACTRN12621001419853 / RecruitingPhase 1

A Phase 1 Dose Escalation and Dose Expansion Open-label, Multicenter, Study of OP-1250 in Combination with the CDK4/6 Inhibitor Palbociclib in Adult Subjects with Advanced or Metastatic HR-positive, HER2-negative Breast Cancer

Start Date03 Feb 2022

Sponsor / Collaborator

Olema Pharmaceuticals, Inc.

100 Clinical Results associated with Palazestrant

100 Translational Medicine associated with Palazestrant

100 Patents (Medical) associated with Palazestrant

Literatures (Medical) associated with Palazestrant

04 Mar 2024·Molecular cancer therapeutics

Palazestrant (OP-1250), A Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination

Article

Author: Barratt, Susanna A ; Sun, Richard ; Hodges-Gallagher, Leslie ; Peña, Guadalupe ; Myles, David C ; Ortega, Fabian E ; Palanisamy, Gopinath S ; Parisian, Alison D ; Kulp, David ; Robello, Brandon ; Kushner, Peter J ; Harmon, Cyrus L ; Sapugay, Judevin

Abstract:

The estrogen receptor (ER) is a well-established target for the treatment of breast cancer, with the majority of patients presenting as ER-positive (ER+). Endocrine therapy is a mainstay of breast cancer treatment but the development of resistance mutations in response to aromatase inhibitors, poor pharmacokinetic properties of fulvestrant, agonist activity of tamoxifen, and limited benefit for elacestrant leave unmet needs for patients with or without resistance mutations in ESR1, the gene that encodes the ER protein. Here we describe palazestrant (OP-1250), a novel, orally bioavailable complete ER antagonist and selective ER degrader. OP-1250, like fulvestrant, has no agonist activity on the ER and completely blocks estrogen-induced transcriptional activity. In addition, OP-1250 demonstrates favorable biochemical binding affinity, ER degradation, and antiproliferative activity in ER+ breast cancer models that is comparable or superior to other agents of interest. OP-1250 has superior pharmacokinetic properties relative to fulvestrant, including oral bioavailability and brain penetrance, as well as superior performance in wild-type and ESR1-mutant breast cancer xenograft studies. OP-1250 combines well with cyclin-dependent kinase 4 and 6 inhibitors in xenograft studies of ER+ breast cancer models and effectively shrinks intracranially implanted tumors, resulting in prolonged animal survival. With demonstrated preclinical efficacy exceeding fulvestrant in wild-type models, elacestrant in ESR1-mutant models, and tamoxifen in intracranial xenografts, OP-1250 has the potential to benefit patients with ER+ breast cancer.

News (Medical) associated with Palazestrant

15 May 2024

·www.biospace.com

Olema Oncology Announces Promising New Data for Palazestrant in Combination with Ribociclib Presented at the 2024 ESMO Breast Cancer Congress

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 85% clinical benefit rate (CBR) observed to date across all CBR-eligible patients supports promising preliminary efficacy pro the palazestrant-ribociclib combination Olema will host an investor conference call today at 8:00 a.m. ET 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. 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). 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: 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 pro with the established safety pro ribociclib plus an endocrine therapy. Palazestrant did not affect ribociclib drug exposure and ribociclib had no clinically meaningful effect on palazestrant drug exposure. 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). Partial responses were observed in five patients through the data cut-off (2 confirmed, 3 unconfirmed) among 23 response-evaluable patients. 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. “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. 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.” Phase 1b/2 Clinical Study Results Enrollment 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). 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. 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. Pharmacokinetics 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 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. Safety and Tolerability 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 pro ribociclib plus endocrine therapy. 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. Neutropenia was reversible in all patients and the timing was consistent with ribociclib-related neutropenia. Efficacy 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. 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. A copy of the poster will be available on Olema’s website under the Science section. Company Investor Webcast and Conference Call 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. About 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. 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. 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). For more information, please visit . About Olema Oncology 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. 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. For more information, please visit us at . Forward Looking Statements 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. 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. 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. 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. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements. Contact: Geoffrey Mogilner, Vice President, Investor Relations and Communications ir@olema.com

Clinical ResultPhase 3Fast TrackPhase 2

08 May 2024

·www.globenewswire.com

Olema Oncology Reports First Quarter 2024 Financial Results and Provides Corporate Update

Completed enrollment in 60-patient Phase 1b/2 clinical studies of palazestrant in combination with each of ribociclib and palbociclibNew clinical data from palazestrant-ribociclib combination study to be presented at the ESMO Breast Cancer Annual Congress 2024 in Berlin, Germany. Olema will host an investor conference call on May 15, 2024, at 8:00 a.m. ET to review the dataInvestigational New Drug (IND) application for OP-3136, a novel KAT6 inhibitor, expected to be filed with FDA in late 2024Cash, cash equivalents and marketable securities of $249.0 million as of March 31, 2024 SAN FRANCISCO, May 08, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema”, “Olema Oncology”, Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, today reported financial results for the first quarter ended March 31, 2024, and provided a corporate update. “Our mission at Olema is uniquely focused on advancing the standard of care for women living with cancer,” said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “We are excited for the achievements we are making both with palazestrant, our oral complete ER antagonist program, and now with our KAT6 inhibitor program, OP-3136. We believe palazestrant has the potential to become the backbone endocrine therapy-of-choice for advanced or metastatic breast cancer, and we look forward to presenting new clinical data in combination with ribociclib at the 2024 ESMO Breast Cancer Annual Congress later this month.” First Quarter 2024 Highlights Completed enrollment of 60-patient Phase 1b/2 studies of palazestrant (OP-1250) in combination with each of ribociclib and palbociclib.Nominated OP-3136, an orally bioavailable KAT6 inhibitor, as a development candidate. OP-3136 demonstrated potent anti-tumor activity alone and in combination with both palazestrant and CDK4/6 inhibitors in preclinical ER+ breast cancer models.Announced publication of data in Molecular Cancer Therapeutics describing the design, discovery and optimization of palazestrant. Upcoming Milestones Present interim Phase 1b/2 clinical results of palazestrant in combination with ribociclib at ESMO Breast Cancer Annual Congress 2024, May 15-17, 2024, in Berlin, Germany.Present trial-in-progress poster on OPERA-01, a pivotal Phase 3 monotherapy clinical trial in the second- and third-line setting of ER+/HER2- advanced or metastatic breast cancer, at the 2024 ASCO Annual Meeting, May 31-June 4, 2024, in Chicago, IL.Initiate Phase 1b/2 clinical study of palazestrant in combination with mTOR inhibitor, everolimus, in Q3 2024.File an Investigational New Drug (IND), application with the U.S. Food and Drug Administration (FDA) for OP-3136 in late 2024 and advance clinical development. First Quarter 2024 Financial Results Cash, cash equivalents and marketable securities as of March 31, 2024, were $249.0 million. Net loss for the quarter ended March 31, 2024, was $31.0 million, as compared to $28.3 million for the quarter March 31, 2023. The increase in net loss for the first quarter was primarily related to increased spending on research and clinical development-related activities as a result of late-stage clinical trials for palazestrant and the advancement of our KAT6 inhibitor program. This increase was offset by decreased spending on general and administrative activities and higher interest income earned from marketable securities. GAAP research and development (R&D) expenses were $29.9 million for the quarter ended March 31, 2024, as compared to $22.8 million for the quarter ended March 31, 2023. The increase in R&D expenses was primarily related to a $5.0 million milestone payment incurred in connection with the exclusive global license agreement entered into in June 2022 between Olema and Aurigene (Aurigene Agreement) associated with the advancement of our KAT6 inhibitor program, and increased spending on clinical development-related activities, as we continue to advance palazestrant into late-stage clinical trials. The increase was offset by decreased spending on clinical pharmacology studies and nonclinical research programs and a one-time restructuring charge recorded in the first quarter of 2023. Non-GAAP R&D expenses were $26.5 million for the quarter ended March 31, 2024, which included a $5.0 million milestone payment in connection to the Aurigene Agreement and excluded $3.4 million non-cash stock-based compensation expense. Non-GAAP R&D expenses were $19.7 million for the quarter ended March 31, 2023, excluding $3.1 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release. GAAP G&A expenses were $4.5 million for the quarter ended March 31, 2024, as compared to $6.8 million for the quarter ended March 31, 2023. The decrease in G&A expenses was primarily due to decreased spending on corporate- and legal-related costs, and personnel-related expenses, including a one-time restructuring charge recorded in the first quarter of 2023. Non-GAAP G&A expenses were $3.0 million for the quarter ended March 31, 2024, excluding $1.5 million non-cash stock-based compensation expense. Non-GAAP G&A expenses were $5.2 million for the quarter ended March 31, 2023, excluding $1.5 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release. ESMO Breast Cancer Investor Conference Call 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 on 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. About 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. 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. 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). For more information, please visit www.opera01study.com. About Olema Oncology 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. 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. For more information, please visit us at www.olema.com. Non-GAAP Financial Information The results presented in this press release include both GAAP information and non-GAAP information. As used in this release, non-GAAP R&D expense is defined by Olema as GAAP R&D expense excluding stock-based compensation expense, and non-GAAP G&A expense is defined by Olema as GAAP G&A expense excluding stock-based compensation expense. We use these non-GAAP financial measures to evaluate our ongoing operations and for internal planning and forecasting purposes. We believe that non-GAAP financial information, when taken collectively, may be helpful to investors because it provides consistency and comparability with past financial performance. However, non-GAAP financial information is presented for supplemental informational purposes only, has limitations as an analytical tool, and should not be considered in isolation or as a substitute for financial information presented in accordance with GAAP. Other companies, including companies in our industry, may calculate similarly titled non-GAAP measures differently or may use other measures to evaluate their performance, all of which could reduce the usefulness of our non-GAAP financial measures as tools for comparison. Investors are encouraged to review the related GAAP financial measures and the reconciliation of these non-GAAP financial measures to their most directly comparable GAAP financial measures and not rely on any single financial measure to evaluate our business. Forward-Looking Statements 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,” "believe,” “could,” “expect,” “goal,” “may,” “potential,” "upcoming," “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to the timelines for initiation and enrollment for potential clinical studies and for results of clinical trials of palazestrant (OP-1250) as a monotherapy and in combination trials, timings of presentations at conferences and conference calls, Olema’s financial condition and resources, results of operations, cash position, potential beneficial characteristics, including but not limited to safety, tolerability, activity, efficacy and therapeutic effects of palazestrant, the potential of palazestrant to advance the standard of care for women living with cancer or become the backbone endocrine therapy-of-choice for advanced or metastatic breast cancer, palazestrant’s combinability with other drugs, the initiation of a phase 1b/2 clinical study of palazestrant in combination with everolimus and timing thereof, and the sufficiency and timing of Olema’s preclinical program, including the potential beneficial characteristics of its KAT6 inhibitor compounds and the timing of a potential IND application for OP-3136. 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. 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 future filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements. Olema Pharmaceuticals, Inc.Condensed Consolidated Balance Sheets Data(in thousands) March 31,December 31, 2024 2023 Cash, cash equivalents and marketable securities $248,977 $261,807 Total assets 263,694 276,945 Total current liabilities 26,224 21,621 Total liabilities 27,376 23,050 Total stockholders’ equity 236,318 253,895 Total liabilities and stockholders’ equity $263,694 $276,945 Olema Pharmaceuticals, Inc.Condensed Consolidated Statements of Operations(In thousands, except share and per share data) Three Months Ended March 31, 2024 2023 Operating expenses: Research and development (1) $29,883 $22,826 General and administrative (2) 4,456 6,776 Total operating expenses 34,339 29,602 Loss from operations (34,339) (29,602)Other income: Interest income 3,352 1,305 Other income 17 11 Total other income 3,369 1,316 Net loss $(30,970)$(28,286)Net loss per share, basic and diluted $(0.56)$(0.70)Weighted average shares used to compute net loss per share, basic and diluted 55,574,324 40,354,493 Reconciliation of GAAP to Non-GAAP Information(In thousands) Three Months Ended March 31, 2024 2023 (1) Research and development reconciliation GAAP research and development (3) $29,883 $22,826 Less: share-based compensation expense 3,412 3,088 Non-GAAP research and development $26,471 $19,738 (2) General and administrative reconciliation GAAP general and administrative $4,456 $6,776 Less: share-based compensation expense 1,497 1,542 Non-GAAP general and administrative $2,959 $5,234 (3) Research and development expenses for the three-months ended March 31, 2024 include a $5.0 million milestone payment in connection to the Aurigene Agreement. IR and Media Contact:Geoffrey Mogilner, Vice President, Investor Relations and Communicationsir@olema.com

Financial StatementPhase 3License out/inPhase 1Fast Track

08 May 2024

·www.globenewswire.com

Olema Oncology Announces New Clinical Data for Palazestrant in Combination with Ribociclib to be Presented at the 2024 ESMO Breast Cancer Annual Congress

Olema will host an investor conference call at 8:00 a.m. ET on May 15, 2024SAN FRANCISCO, May 08, 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 that it will present new clinical data from the Company’s ongoing Phase 1b/2 clinical study of palazestrant in combination with CDK4/6 inhibitor ribociclib in a poster presentation at the upcoming European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress 2024 taking place May 15-17, 2023, in Berlin, Germany. Details of the ESMO Breast Cancer Annual Congress 2024 poster presentation are: Title: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 (ER+, HER2-), advanced and/or metastatic breast cancer (ID 407)Presentation #:212PDate:Thursday, May 16, 2024Time:12:00 p.m. CEST (6:00 a.m. ET) A copy of the poster will be made available on Olema’s website under the Science section when it is presented at the congress. Abstracts for the posters will be found on the ESMO Breast Cancer Annual Congress website here. Company Investor Webcast and Conference Call 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 on 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. About 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. 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. 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). For more information, please visit www.opera01study.com. About Olema Oncology 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. 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. For more information, please visit us at www.olema.com. IR and Media Contact:Geoffrey Mogilner, Vice President, Investor Relations and Communicationsir@olema.com

Fast TrackPhase 3

100 Deals associated with Palazestrant

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
ER-positive/HER2-negative Breast Cancer	Phase 3	US	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	AR	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	AU	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	BE	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	CZ	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	DE	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	HK	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	IT	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	MY	Olema Pharmaceuticals, Inc.	16 Nov 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	MX	Olema Pharmaceuticals, Inc.	16 Nov 2023

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05508906 (ESMO_BC2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer First line HER2 Negative \| ER Positive	33	palazestrant+ribociclib	tlxytpbabo(gougrxzcsg) = The most common (≥25%) were nausea, neutropenia (G4: 2 pts; 6%), WBC count decreased, fatigue, anemia, and diarrhea. Most TEAEs were grade 1-2 and consistent with the known safety profiles of each drug. lyjxljptpy (rmnlwescdt )	Positive	16 May 2024
GlobeNewswire Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer ER Positive \| HER2 Negative	19	Ribociclib 600 mg+Palazestrant 120 mg	wbabxcqofs(yutypbzqev) = well tolerated, with no safety signals or enhancement of toxicity and an overall safety profile remains consistent with the expected safety profile of ribociclib plus an endocrine therapy. sumogrxzqp (awszjdrojb ) View more	Positive	05 Dec 2023
GlobeNewswire Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer ESR1 Mutation \| ER Positive \| HER2 Negative	46	palbociclib 125 mg+palazestrant 120 mg	ugwaqgbxjg(sudgzdtjbk) = There was no observed drug-drug interaction between palazestrant and palbociclib, and there was no induced metabolism or increase in exposure of either palbociclib or palazestrant when administered in combination. hkkhkmbtnq (azyocwlmtz ) View more	Positive	05 Dec 2023
				palbociclib 125 mg+palazestrant 120 mg (ESR1 mutation)
NCT04505826 (ESMO2023) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer HER2 Negative \| ER Positive	86	OP-1250 120 mg	ktrggepbht(fnyqbqfsew) = nausea, vomiting, neutropenia, fatigue, headache, constipation, and diarrhea rvsdssljty (vnrhlcclkn ) View more	Positive	22 Oct 2023
				OP-1250 120 mg (ESR1 mutation)
NCT04505826 (ENA2022) Manual	Phase 1	ER-positive/HER2-negative Breast Cancer ER positive \| HER2 negative	37	OP-1250 (60mg)	sobzizcnhx(zvjnqfjxji) = The most common treatment emergent adverse events reported (≥10%) in Phase 1b in the 60 mg/120 mg cohorts were nausea (28%/21%), vomiting (17%/16%), fatigue (17%/5%) and headache (11%/ 11%). kynqsbrmkk (latpzndgov ) View more	Positive	28 Oct 2022
				OP-1250 (120mg)
NCT04505826 (Biospace) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer ER positive \| HER2 negative	-	OP-1250	kyqbnkprcm(xqrvdzxmyt) = xgawgycfbg rsfuhrrxde (tbkisurmva ) View more	Positive	30 Nov 2021

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