Olema Pharmaceuticals Conference Call Summary Company Overview - **Company**: Olema Pharmaceuticals (NasdaqGS:OLMA) - **Mission**: To improve treatment options for individuals living with breast cancer [1] Clinical Programs Palazestrant - **Type**: Complete estrogen receptor antagonist - **Current Trials**: - **OPERA-02**: Phase three trial in combination with ribociclib versus ribociclib and an aromatase inhibitor (AI) for first-line treatment of ER-positive, HER2-negative breast cancer - **OPERA-01**: Phase three trial as monotherapy for patients post-progression on first-line therapy [2][3] - **Market Size**: Approximately $20 billion for ER-positive, HER2-negative breast cancer treatments, with a $5 billion market for second and third-line therapies [3][4] - **Median Progression-Free Survival (PFS)**: - OPERA-02 trial shows a median PFS of 15.5 months, significantly higher than the standard of care [8] - OPERA-01 trial shows a PFS of 12 months, compared to 5 months in the standard of care [8][12] OP-3136 - **Type**: KAT6 inhibitor - **Current Status**: In phase one/two trials, with ongoing monotherapy dose escalation [3][21] - **Combination Therapy**: Expected to combine with palazestrant and fulvestrant to enhance efficacy [23] Market Dynamics - **Unmet Medical Need**: Approximately 320,000 breast cancer diagnoses in the U.S. annually, with 70% being ER-positive, HER2-negative [3] - **Treatment Duration**: First-line therapies have longer treatment durations, contributing to market size [4] - **Resistance Mechanisms**: Palazestrant shows potential to address resistance mechanisms in both ESR1 mutant and wild-type populations [10][11] Competitive Landscape - **Comparison with Competitors**: - Giredestrant (Roche) and camizestrant (AstraZeneca) are in similar trials but have shown less efficacy compared to palazestrant [26][29] - Palazestrant is positioned to outperform competitors in both mutant and wild-type settings [15][28] Future Outlook - **Commercialization Plans**: - Expected product approval and launch filing for palazestrant in 2027 [24] - Ongoing commercial planning and manufacturing setup [20] - **Upcoming Data Releases**: - First pivotal trial readout for OP-3136 expected in the second half of next year [24] - Continued enrollment in OPERA-01 and OPERA-02 trials [19] Key Takeaways - Olema Pharmaceuticals is focused on addressing significant unmet needs in breast cancer treatment through innovative therapies - The company is well-positioned in a large market with promising clinical data supporting its lead product, palazestrant - Future trials and data releases will be critical in establishing the efficacy and market potential of both palazestrant and OP-3136 [24][33]

Financial Data and Key Metrics Changes - The company is currently conducting a phase three pivotal trial focused on hormone receptor positive, HER2 negative breast cancer, with the lead asset being palisestrant [2][3] - The ongoing phase three trial is a monotherapy trial in the second and third line setting, with top-line results expected next year [3] - The company plans to initiate a first-line trial in the second half of the year, which will include ribociclib [3][4] Business Line Data and Key Metrics Changes - The company has two clinical stage assets: palisestrant in phase three and OP3136, a CAT6 inhibitor, in phase one dose escalation [4] - The phase two data for palisestrant showed a progression-free survival (PFS) of 7.3 months in the ESR1 mutant population, which is significantly better than the control arm [13] - The combination of ribociclib and palisestrant is expected to show favorable results compared to other combinations, with a median PFS of 15 months reported [20][21] Market Data and Key Metrics Changes - The company is competing in a rapidly evolving market for oral SERDs, with recent trials showing benefits primarily in ESR1 mutant patients [6][7] - The company aims to differentiate palisestrant by demonstrating its efficacy in both mutant and wild-type populations [13][18] Company Strategy and Development Direction - The company is focused on advancing its clinical trials and establishing palisestrant as a competitive treatment option in the breast cancer market [2][3] - The strategy includes a combination approach with ribociclib and palisestrant, which is expected to enhance treatment outcomes [20][21] - The company is also exploring the potential of OP3136 in various cancer types, including castration-resistant prostate cancer and non-small cell lung cancer [42][43] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the efficacy of palisestrant in the first-line setting, particularly for treatment-naive patients [25] - The company anticipates that the upcoming data updates will provide further insights into the performance of its assets and their potential market impact [33][34] Other Important Information - The company has a clinical collaboration with Novartis for the supply of ribociclib, which is a key component of its trials [30] - The company is preparing for potential data updates and has several catalysts expected later this year [34][46] Q&A Session Summary Question: How does palisestrant differentiate from other oral SERDs? - Management highlighted that palisestrant is a complete estrogen receptor antagonist, unlike others that are partial agonists, which may limit their efficacy in certain populations [6][7] Question: What are the expectations for the OPERA one trial design? - The trial is designed to test both mutant and wild-type populations separately, allowing for a more targeted statistical analysis [18] Question: How does the combination of ribociclib and palisestrant compare to other treatments? - The combination is expected to show significantly better results than existing treatments, with a median PFS of 15 months compared to 5 months in previous studies [20][21]