palazestrant (OP-1250) / Olema Pharma - LARVOL DELTA

OPERA-02: a phase 3 randomized, double-blind, active-controlled study of palazestrant with ribociclib versus letrozole with ribociclib for the first-line treatment of ER+, HER2- advanced breast cancer (SABCS 2025) - "Secondary endpoints include PFS by a blinded-independent review committee, OS, overall response rate, clinical benefit rate, duration of response, safety, pharmacokinetics and health-related patient-reported outcomes. The study is conducted globally."

Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

OPERA-02: Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

OP-1250-002: A Phase 1 Study of Oral OP-1250 in Combination With Palbociclib in HR+/HER2- Breast Cancer Patients (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Trial completion date: Jul 2025 ➔ Mar 2026 | Trial primary completion date: Jan 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Anticipated Upcoming Events (GlobeNewswire) - "Initiate the Phase 1b/2 study evaluating palazestrant with atirmociclib in ER+/HER2- metastatic breast cancer in Q4 2025; Present trial-in-progress poster entitled 'OPERA-02: a phase 3 randomized, double-blind, active-controlled study of palazestrant with ribociclib versus letrozole with ribociclib for the first-line treatment of ER+, HER2- advanced breast cancer' at the San Antonio Breast Cancer Symposium (SABCS) in December 2025; Report top-line data from OPERA-01 in the second half of 2026."

P3 data: top line • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

OP-1250-003: Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=190 | Recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Sep 2026 ➔ Jan 2028 | Trial primary completion date: Aug 2026 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Palazestrant (OP-1250) plus ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced breast cancer (ABC) (ESMO 2025) - P1 | "75% pts had prior ET, 39% had prior fulvestrant and 71% pts had prior CDK4/6i for ABC (16% had two prior CDK4/6i). Conclusions Palazestrant and ribociclib safety were consistent with the previous reports for each drug in ABC and with robust efficacy in all pts and in those with prior CDK4/6i. A first-line phase 3 trial (OPERA-02) is planned."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Olema Oncology to Present Trial-in-Progress Poster for Phase 3 OPERA-02 Trial of Palazestrant Plus Ribociclib at SABCS 2025 (GlobeNewswire) - "The trial is evaluating palazestrant in combination with ribociclib in frontline estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer."

Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Oncology Announces New Data from the Phase 1b/2 Trial of Palazestrant Plus Ribociclib in ER+/HER2- Metastatic Breast Cancer at ESMO 2025 (GlobeNewswire) - "In the 90 mg palazestrant dose cohort, with a median follow-up of 10.8 months, median progression-free survival (PFS) was not reached; In the 120 mg palazestrant dose cohort, with a median follow-up of more than 19 months, median PFS are mature. Median PFS was 15.5 months for all patients. Median PFS was 12.2 months for those who received prior treatment with CDK4/6i, including 9.2 months for patients with ESR1 wild-type tumors and 13.8 months for patients with tumors with ESR1 mutations...Across 72 patients treated, 90 mg or 120 mg of palazestrant combined with 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity; Palazestrant and ribociclib did not demonstrate any drug-drug interactions and the overall safety profile was consistent with the established safety profile of ribociclib plus an endocrine therapy."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Pharmaceuticals Inc. (OLMA) is gearing up to present mature clinical data from its Phase 1b/2 study of palazestrant or OP-1250 in combination with ribociclib. (RTTNews) - "The data will be featured at the European Society for Medical Oncology (ESMO) Congress, scheduled to take place in Berlin, Germany, from October 17 to 21, 2025."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Oncology Announces New Clinical Trial Agreement with Pfizer to Combine Palazestrant with Atirmociclib in ER+/HER2- Metastatic Breast Cancer (GlobeNewswire) - "The companies will evaluate in a Phase 1b/2 study the safety and combinability of palazestrant plus atirmociclib, Pfizer’s investigational, highly selective-CDK4 inhibitor, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer....Under the terms of the agreement, Pfizer will supply atirmociclib for use in the Phase 1b/2 study and Olema will lead the conduct of the study."

Commercial • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

OP-1250-003: Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, or Everolimus in ER+, HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

OP-1250-001: A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer (clinicaltrials.gov) - P1/2 | N=153 | Completed | Sponsor: Olema Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Phase classification: P2 ➔ P1/2

Monotherapy • Phase classification • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Anticipated Upcoming Events (GlobeNewswire) - "Present mature data from the Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- metastatic breast cancer at the European Society of Medical Oncology (ESMO) Congress 2025...; (ii) Initiate the OPERA-02 trial of palazestrant in combination with ribociclib in frontline metastatic breast cancer in Q3 2025...; (iii) Report top-line data from OPERA-01 in the second half of 2026."

Clinical data • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

OPERA-02: Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=1000 | Not yet recruiting | Sponsor: Olema Pharmaceuticals, Inc.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Palazestrant, a novel oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in patients with ER+/HER2− advanced or metastatic breast cancer: phase 1/2 study results (Breast Cancer Res) - P1/2 | N=153 | NCT04505826 | Sponsor: Olema Pharmaceuticals, Inc. | "This study enrolled 146 patients. No dose-limiting toxicities were observed at doses up to 300 mg/day palazestrant. Confirmed partial responses were observed with 60 and 120 mg/day palazestrant. Both doses showed similar and tolerable safety profiles, favorable pharmacokinetics, and steady-state plasma concentrations above the predicted threshold for complete ER inhibition. Greater clinical benefit at palazestrant 120 mg/day (46%) versus 60 mg/day (19%) led to selection of 120 mg/day as RP2D and study expansion dose. At 120 mg/day, the median progression-free survival was 4.8 months (95% CI, 3.5–7.1) overall and 5.6 months (95% CI, 4.8–NE) among patients with cancers with ESR1 mutations. Most treatment-emergent adverse events (TEAEs) were grade 1–2."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Discovery of Palazestrant (OP-1250), a Potent and Orally Bioavailable Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD). (PubMed, ACS Omega) - "OP-1250 is a potent complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that is active in both WT and mutESR1 breast cancer tumors. OP-1250's effective induction of tumor regression either as a single agent or in combination with a CDK4/6 inhibitor has led to the rapid advancement of this compound into a Phase 3 clinical trial (OPERA-01)."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) monotherapy vs standard-of-care for ER+, HER2- advanced or metastatic breast cancer patients after endocrine therapy and CDK4/6 inhibitors. (ASCO 2025) - P2, P3 | " OPERA-01 (NCT06016738) is a multicenter, randomized, open-label, phase 3 clinical trial comparing the efficacy and safety of palazestrant as a single agent to SOC ET (fulvestrant, anastrozole, letrozole, or exemestane) in patients with ER+, HER2– MBC that relapsed or progressed on 1-2 prior lines of ET, including a CDK4/6i. Secondary endpoints include overall survival, antitumor activity (objective response rate, clinical benefit rate, and duration of response), safety, exposure and patient-reported outcomes in patients with and without ESR1 mutations. Study recruitment began in November 2023."

Clinical • Metastases • Monotherapy • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Discovery of Palazestrant (OP-1250), a Potent and Orally Bioavailable Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD) (ACS Omega) - "OP-1250 is a potent complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that is active in both WT and mutESR1 breast cancer tumors. OP-1250's effective induction of tumor regression either as a single agent or in combination with a CDK4/6 inhibitor has led to the rapid advancement of this compound into a Phase 3 clinical trial (OPERA-01)."

Clinical • Breast Cancer

OPERA-01: OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Monotherapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Olema Oncology Announces Palazestrant Dose Selection and Trial-in-Progress Poster at ASCO 2025 Annual Meeting (GlobeNewswire) - "Olema Pharmaceuticals, Inc....announced it has aligned with the U.S. Food and Drug Administration (FDA) to select 90 mg of palazestrant as the dose for Part 2 of the ongoing registrational Phase 3 OPERA-01 trial in second- and third-line estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer....The FDA also selected 90 mg of palazestrant in combination with the approved dose of CDK4/6 inhibitor ribociclib for the pivotal Phase 3 OPERA-02 trial in frontline ER+/HER2- metastatic breast cancer....'We remain steadfast in our commitment to these patients, and with 90 mg of palazestrant confirmed as the selected dose, we are focused on rapidly advancing our OPERA-01 and OPERA-02 pivotal trials with top-line data from OPERA-01 anticipated in 2026 and a potential commercial launch in 2027'."

P3 data: top line • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Oncology Reports First Quarter 2025 Financial and Operating Results (GlobeNewswire) - "Anticipated Upcoming Events: (i) Present trial-in-progress poster, 'OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) monotherapy vs standard-of-care endocrine therapy for patients with ER+, HER2- advanced breast cancer after endocrine and CDK4/6 inhibitor therapy,' at the American Society of Clinical Oncology (ASCO) Annual Meeting in June; report top-line data from OPERA-01 in 2026; (ii) Initiate the pivotal Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in frontline metastatic breast cancer in 2025; (iii) Present mature data from the Phase 1b/2 trial of palazestrant in combination with ribociclib at an upcoming medical meeting."

Clinical data • New P3 trial • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Oncology Reports Fourth Quarter and Full Year 2024 Financial and Operating Results (GlobeNewswire) - "Pivotal Phase 3 OPERA-01 trial of palazestrant as a monotherapy in patients with 2/3L metastatic breast cancer on track for top-line data in 2026. Pivotal Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in patients with frontline metastatic breast cancer enabled by new Novartis collaboration and $250 million equity private placement; trial on track for initiation this year....Updated results from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib in patients with ER+/HER2- advanced or metastatic breast cancer...expected to be presented this year at a major medical meeting."

New P3 trial • P1/2 data • P3 data: top line • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

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 or metastatic breast cancer (SABCS 2024) - P1, P2 | "Among them, 34 (74%) pts received one prior treatment and 12 (26%) received two prior treatments with CDK4/6i; 34 (74%) pts received prior palbociclib, 11 (24%) prior abemaciclib and 8 (17%) prior ribociclib. Palazestrant in combination with ribociclib was well tolerated and safety was consistent with the known profiles of each drug and similar to combinations of ribociclib with ET. Encouraging preliminary efficacy from the combined agents, including in pts with prior CDK4/6i treatment was observed. Updated data will be presented."

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

OPERA-01: OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=510 | Active, not recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Monotherapy • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Olema Oncology Presents Updated Clinical Results for Palazestrant in Combination with Ribociclib at the San Antonio Breast Cancer Symposium (GlobeNewswire) - P1b/2 | N=155 | NCT05508906 | Sponsor: Olema Pharmaceuticals, Inc. | "Olema Pharmaceuticals, Inc...announced updated clinical results from the ongoing Phase 1b/2 study of palazestrant in combination with CDK4/6 inhibitor, ribociclib, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer....With a median follow-up of 12 months, the median PFS was not reached as of the data cutoff date. Across all patients, the 6-month PFS rate was 73%. In those who received prior treatment with a CDK4/6i plus an endocrine therapy, the 6-month PFS rate was 68%. The 6-month PFS rate in ESR1 mutant patients was 81% and in ESR1 wild-type patients it was 70%. In those who were clinical benefit rate (CBR)-eligible, the CBR was 76% (37/49) in all patients, 81% (13/16) in patients with ESR1 mutations, and 74% (23/31) in ESR1 wild-type patients."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer