Olema Pharmaceuticals FY Conference Summary Company Overview - **Company**: Olema Pharmaceuticals (NasdaqGS:OLMA) - **Focus**: Improving treatments for patients with ER-positive, HER2-negative breast cancer, addressing significant unmet needs in this common cancer indication [1][2] Key Programs and Trials - **Lead Asset**: Palazestrant, a complete estrogen receptor antagonist, currently in two phase III trials and one phase I trial [1][2] - **Trial Details**: - **OPERA-02**: First-line trial in combination with ribociclib, targeting a market opportunity of over $10 billion [3] - **OPERA-01**: Second/third-line trial as a monotherapy, with a potential market opportunity of $5 billion [3][9] - **OP3136**: KAT6 inhibitor in phase I, exploring combination studies with endocrine agents [2][14] Market Opportunity - **Adjuvant Setting**: Potential market opportunity approaching $20 billion globally [3] - **First-Line Treatment**: OPERA-02 targeting a $10 billion market opportunity [3] - **Later Lines of Treatment**: OPERA-01 targeting a $5 billion market opportunity [3] - **Overall Market Potential for Palazestrant**: Estimated at $3 billion to $5 billion, depending on patient population [10][13] Clinical Data and Efficacy - **Palazestrant's Mechanism**: Complete estrogen receptor antagonism with a long half-life of eight days, allowing continuous receptor occupation [4][5] - **Progression-Free Survival (PFS)**: - OPERA-01 aims for a two-month additional PFS benefit over current standards [23] - Data suggests a median PFS of 5.5 months in the ESR1 wild-type setting, which has not been achieved by other agents [11][24] - **Combination with Ribociclib**: Demonstrated a year of median PFS in patients previously treated with CDK4/6 inhibitors [7][10] Competitive Landscape - **Differentiation Strategy**: Emphasis on the properties of palazestrant and its potential to provide better outcomes than existing therapies [36][37] - **Regulatory Strategy**: Separate analyses for ESR1 mutant and wild-type populations in trials to meet regulatory requirements [22][23] Future Plans - **NDA Filing**: Anticipated filing for palazestrant in 2027 following positive trial results [10][12] - **Commercialization Strategy**: Plans to market palazestrant in the U.S. and seek a collaborator for international markets [12][30] - **KAT6 Inhibitor Development**: OP3136 is expected to enter phase III trials in breast cancer by 2028, with potential applications in other cancers [15][16][41] Additional Insights - **KAT6 Inhibitor Profile**: OP3136 aims for better tolerability compared to existing KAT6 inhibitors, with a focus on minimizing cytopenias [39][41] - **Collaboration with Pfizer**: Exploring combination therapies with Pfizer's atirmociclib, targeting improved outcomes in breast cancer treatment [33][34] Conclusion Olema Pharmaceuticals is positioned to address significant unmet needs in the treatment of ER-positive, HER2-negative breast cancer through innovative therapies like palazestrant and OP3136, with substantial market opportunities and a clear strategy for clinical development and commercialization.

Summary of Olema Pharmaceuticals Conference Call Company Overview - **Company**: Olema Pharmaceuticals - **Focus**: Development of treatment options for breast cancer, specifically targeting estrogen receptor positive, HER2 negative breast cancer, which constitutes about 70% of breast cancer cases [3][4] Lead Asset - **Lead Molecule**: Palazestrant - **Mechanism**: Complete estrogen receptor antagonist, effectively shutting down growth signals [3] - **Clinical Trials**: - **OPERA-01**: Phase 3 trial for second/third-line treatment, readout expected in late 2026 [4] - **OPERA-02**: Phase 3 trial for first-line metastatic treatment in combination with ribociclib, readout expected in late 2028 [4][5] - **OP3136**: KAT6 inhibitor in Phase 1 trials for breast cancer, prostate cancer, and non-small cell lung cancer [5] Industry Context - **Market Size**: - Current global market for CDK4/6 inhibitors is approximately $15 billion, expected to grow to $15 billion-$20 billion by 2030 [20] - First-line breast cancer treatment market estimated at $10 billion-$15 billion, with second/third-line market at about $5 billion in the U.S. [34] Competitive Landscape - **Roche's LIDARA Trial**: Positive interim results reported, indicating improved disease-free survival with giredestrant [9][10] - **Comparison with Roche**: Olema's palazestrant shows better progression-free survival (PFS) in both ESR1 mutant and wild type populations compared to Roche's data [12][21] Key Findings from Recent Data - **ESMO Presentation**: Olema's phase 2 data showed approximately 10 months PFS in ESR1 wild type, compared to 5.5 months in Roche's control arm [12] - **Regulatory Considerations**: OPERA-01 and OPERA-02 trials are designed to separately analyze ESR1 mutant and wild type populations, enhancing regulatory clarity [24][26] Collaborations - **Novartis**: Collaboration for ribociclib supply in OPERA-02 trial [29] - **Pfizer**: Collaboration for atirmociclib, aiming to explore next-generation endocrine therapies [30][32] Future Expectations - **Upcoming Data**: Phase 1 data for OP3136 expected in the first half of 2026, focusing on safety and preliminary efficacy [41] - **Potential Indications**: Besides breast cancer, OP3136 is being explored for prostate cancer and non-small cell lung cancer, with preclinical activity observed [42][43] Conclusion - Olema Pharmaceuticals is positioned to capitalize on significant market opportunities in breast cancer treatment, with promising clinical data and strategic collaborations enhancing its competitive edge in the industry [20][34]

Financial Data and Key Metrics Changes - The company is focused on developing targeted therapeutics for breast cancer, particularly ER positive HER2 negative breast cancer, which represents approximately 70% of breast cancer cases [2][3] - The lead asset, palazestrant, is in a first-line trial with a CDK4/6 inhibitor, ribociclib, and is expected to read out results in the second half of next year [4][13] - The market potential for the combination of these assets is estimated to be between $15 billion to $20 billion [6] Business Line Data and Key Metrics Changes - The company has two clinical stage assets: palazestrant and OP3136, targeting different mechanisms in breast cancer treatment [4][5] - The first-line market opportunity with ribociclib and palazestrant is projected to exceed $10 billion [20] - The second and third-line market opportunity is estimated to be over $5 billion, focusing on both ESR1 mutation positive and wild-type patients [9][33] Market Data and Key Metrics Changes - The company is uniquely positioned as the only next-generation endocrine therapy combining with ribociclib, following a shift in the standard of care due to compelling survival data [6][7] - The competitive landscape includes other agents like palbociclib and camazestrant, which have shown limitations in terms of toxicity and efficacy [19][20] Company Strategy and Development Direction - The company aims to differentiate its products by demonstrating superior progression-free survival (PFS) in both mutant and wild-type populations [32][49] - A new collaboration with Pfizer aims to explore the combination of palazestrant with atoramiciclib, a CDK4 selective inhibitor, to enhance treatment options [27][30] - The company is focused on executing pivotal trials and generating data to support its market position and future product launches [44][46] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readouts and the potential for positive outcomes in pivotal trials, which could lead to regulatory filings and product launches [46][47] - There is an acknowledgment of market fatigue regarding new data, but management believes that compelling evidence from upcoming trials will help regain investor confidence [50][52] Other Important Information - The company has a fast track designation from the FDA for palazestrant, indicating the potential for expedited review and approval [13] - Upcoming data presentations at ESMO are expected to provide further insights into the efficacy of the company's therapies [44][56] Q&A Session Summary Question: What will the company communicate going forward? - The company plans to highlight the compelling phase two data, particularly focusing on the wild-type population post CDK4/6 treatment [49] Question: How does the company view market perception? - Management noted that the market may not fully value the potential of their therapies, but they believe that upcoming data will clarify their efficacy [50][51] Question: What are the expectations for the Roche pivotal trial? - Management expressed hope for positive outcomes from Roche's trial, which could validate their approach and enhance market confidence [55][56]