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

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) - P3 | "Clinical Trial Registration Number: NCT06016738 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

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

Olema Oncology Announces New Clinical Trial Collaboration and Supply Agreement with Novartis in Frontline Metastatic Breast Cancer as well as $250 Million Equity Private Placement (GlobeNewswire) - "Under the terms of the agreement, Novartis will provide Olema with ribociclib drug supply for the planned, Olema-sponsored, Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in ER+/HER2- frontline advanced or metastatic breast cancer. All clinical data and inventions from the trial will be jointly owned while Olema maintains global commercial and marketing rights to palazestrant....Olema well capitalized to fund operations beyond key milestones including OPERA-01 Phase 3 top-line data in 2026, initial OP-3136 KAT6 Phase 1/2 monotherapy and combination data, and execution of the Phase 3 OPERA-02 clinical trial."

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

Olema Oncology to Present New Data Combining Palazestrant with Ribociclib at the San Antonio Breast Cancer Symposium (GlobeNewswire) - "Olema Pharmaceuticals...announced that it will present new data from the Phase 1b/2 clinical study of palazestrant (OP-1250) in combination with CDK4/6 inhibitor ribociclib at the San Antonio Breast Cancer Symposium (SABCS 2024)."

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

Olema Oncology Reports Third Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Anticipated Upcoming Milestones :(i) Present updated Phase 2 data showing palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) in December 2024; (ii) Submit the IND application for OP-3136 to the U.S. Food and Drug Administration (FDA) before year-end; initiate the Phase 1 clinical study for OP-3136 in early 2025."

IND • New P1 trial • P2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Olema Oncology Presents Compelling New Preclinical Data Demonstrating Anti-Tumor Activity for OP-3136 with Enhanced Activity of Palazestrant Combinations at ENA 2024 (GlobeNewswire) - "Olema Pharmaceuticals...announced results...presented during poster sessions at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024)....'We look forward to submitting our Investigational New Drug (IND) application for OP-3136 to the US Food and Drug Administration before the end of this year'; Abstract: 230:...Key findings include:...OP-3136 led to either tumor growth inhibition or tumor regression in vivo in xenograft models across all treatment groups. In combination with OP-3136, palazestrant was consistently superior to fulvestrant and led to improved anti-tumor activity and tumor regression. OP-3136 showed robust synergistic anti‑tumor activity when combined with fulvestrant or palazestrant as doublet therapy in breast cancer models."

IND • Preclinical • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Combining palazestrant, a CERAN, and everolimus, an mTOR inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models (GlobeNewswire) - "Olema Pharmaceuticals...announced results...presented during poster sessions at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024); Abstract: 211:...Key findings include: Palazestrant and everolimus demonstrate synergy in vitro and in vivo and resulted in greater anti-proliferative activity than either agent alone. Combining palazestrant with everolimus causes gene signature transcriptional changes, downregulating cell cycle progression and upregulating apoptosis."

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

Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models (GlobeNewswire) - "Olema Pharmaceuticals...announced results...presented during poster sessions at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024); Abstract: 212:...Key findings include: Palazestrant and capivasertib work synergistically to inhibit proliferation of multiple ER+ breast cancer models, both in vitro and in vivo. Palazestrant demonstrates superior anti-tumor efficacy over fulvestrant in combination with capivasertib, significantly inhibiting and repressing tumor growth. Combining palazestrant and capivasertib increases downregulation of genes associated with cell cycle progression."

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

Combining OP-3136, a KAT6 inhibitor, with endocrine therapy and CDK4/6 inhibitor enhances anti-tumor activity in ER+/HER2- breast cancer models (EORTC-NCI-AACR 2024) - "In mouse xenograft studies, OP-3136 showed enhanced, statistically significant tumor growth inhibition with both double and triple combinations involving palazestrant and ribociclib. Notably, the efficacy observed for OP-3136 in combination with palazestrant was statistically superior to that observed for OP-3136 in combination with fulvestrant.OP-3136 displayed favorable combinability with palazestrant and ribociclib across multiple preclinical models, indicating the promise of this drug regimen for the treatment of ER+/HER2- breast cancer patients."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B

Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models (EORTC-NCI-AACR 2024) - "Capivasertib, a pan-AKT inhibitor, was recently approved in combination with fulvestrant for patients with hormone receptor positive locally advanced or metastatic breast cancer whose tumors harbor at least one PIK3CA/AKT1/PTEN-mutation. The combination of palazestrant, a complete estrogen receptor antagonist, and capivasertib, an AKT inhibitor, demonstrated synergy in preclinical ER+/HER2- breast cancer models. These data indicate that combining palazestrant and capivasertib is a promising therapeutic strategy to overcome acquired resistance."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • mTOR • PIK3CA • PTEN

Combining palazestrant, a CERAN, and everolimus, an mTOR inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models (EORTC-NCI-AACR 2024) - "This data indicates that combining palazestrant and everolimus is a promising therapeutic strategy for treating patients with ER+/HER2- breast cancer. This combination is currently being evaluated in a phase 1b clinical study."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Olema Oncology Announces New Preclinical Combination Data to be Presented at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Olema Pharmaceuticals...announced that it will be presenting multiple posters during the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024)....Poster presentations include new preclinical data demonstrating activity for palazestrant in combination with capivasertib and everolimus, and OP-3136, Olema’s KAT6 inhibitor, in combination with palazestrant and other targeted agents."

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

Phase 1b Combo w/ Ribociclib, Alpelisib, or Everolimus (clinicaltrials.gov) - P1 | N=155 | Recruiting | Sponsor: Olema Pharmaceuticals, Inc. | N=90 ➔ 155 | Trial completion date: Aug 2024 ➔ Jun 2026 | Trial primary completion date: Aug 2024 ➔ May 2026

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • 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 • HER-2

OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) vs standard-of-care for patients with ER+, HER2- advanced or metastatic breast cancer after endocrine therapy and CDK4/6 inhibitors. (ASCOBT 2024) - 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 patietns 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, patient-reported outcomes, and PK in patients with and without ESR1 mutations. The study started recruitment in November 2023."

Clinical • Metastases • P3 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

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. | Recruiting ➔ Active, not recruiting | N=30 ➔ 60 | Trial completion date: Dec 2023 ➔ Jul 2025 | Trial primary completion date: Jan 2023 ➔ Jan 2025

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) vs standard-of-care for ER+, HER2- advanced or metastatic breast cancer patients after endocrine therapy and CDK4/6 inhibitors. (ASCO 2024) - 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. Lin et al. ESMO 2023 MO382."

Clinical • Metastases • P3 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

A phase Ib/II study of palazestrant (OP-1250) in combination with ribociclib in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer (ESMO-BC 2024) - P1 | "Twenty-seven pts (82%) received prior CDK4/6i: 24 prior palbociclib, 5 prior ribociclib and 4 prior abemaciclib; 7 pts (21%) received two prior lines of CDK4/6i. Antitumor activity and clinical benefit, including in heavily pretreated patients, were observed. Updated data will be presented."

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

Olema Oncology Announces Promising New Data for Palazestrant in Combination with Ribociclib Presented at the 2024 ESMO Breast Cancer Congress (GlobeNewswire) - P1b | N=90 | NCT05508906 | Sponsor: Olema Pharmaceuticals, Inc. | "Olema Pharmaceuticals, Inc...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....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....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)."

P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Olema Oncology Reports First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Upcoming Milestones:...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."

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

Olema Oncology Announces New Clinical Data for Palazestrant in Combination with Ribociclib to be Presented at the 2024 ESMO Breast Cancer Annual Congress (GlobeNewswire) - "Olema Pharmaceuticals... 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."

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

Olema Oncology Reports Fourth Quarter and Full-Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Upcoming Milestones: Present interim Phase 2 clinical results of palazestrant in combination with ribociclib at ESMO Breast Cancer Annual Congress 2024, May 15-17, 2024, in Berlin, Germany; Initiate Phase 1b/2 clinical study of palazestrant in combination with mTOR inhibitor, everolimus, in Q3 2024."

New P1/2 trial • P2 data • Breast Cancer • Oncology • Solid Tumor

Olema Oncology Announces Publication of Data Highlighting Palazestrant’s Ability to Inhibit Wild-Type and Mutant ER+ Breast Cancer Both as Monotherapy and in Combination with CDK4/6 Inhibitors (GlobeNewswire) - "Olema Pharmaceuticals, Inc...announced that Molecular Cancer Therapeutics, an American Association for Cancer Research journal, has selected as a featured article a data publication that describes the distinct properties of palazestrant (OP-1250)....In mouse xenograft models, palazestrant demonstrated excellent pharmacokinetics, was well tolerated, showed synergy with CDK4/6 inhibitors, and was highly effective at reducing tumor growth in both wild-type and ESR1-mutant ER+ breast cancer. In addition, in an ESR1-mutant intercranial xenograft model, palazestrant inhibited tumor growth and improved survival of animals with CNS metastases, even after stopping drug treatment."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Oncology • Solid Tumor