Olema Pharmaceuticals, Inc. (NASDAQ:OLMA) is among the best fast money stocks to buy now. During the first quarter, Goldman Sachs Group Inc. expanded its holdings in Olema Pharmaceuticals, Inc. (NASDAQ:OLMA) by 93.6%. Following the purchase of 358,412 shares, the leading bank now owns 741,329 shares of the company’s stock, translating to an investment of $2,787,000 and an ownership of nearly 1.08%. Oppenheimer is among the many research firms bullish on Olema Pharmaceuticals, Inc. (NASDAQ:OLMA). After the ...

Core Insights - Olema Pharmaceuticals (OLMA) shares have increased by 46.5% in September following a collaboration agreement with Pfizer (PFE) for its lead product candidate, palazestrant [1][6] - The collaboration involves a phase Ib/II study to evaluate the safety and potential combinability of palazestrant with Pfizer's atirmociclib in patients with ER+/HER2- metastatic breast cancer (MBC) [2][6] - Year-to-date, OLMA stock has risen by 37.2%, outperforming the industry growth of 4% [3] Collaboration Details - The phase Ib/II study is expected to enroll approximately 35 patients, with initiation anticipated by the end of 2025 [3] - Pfizer will supply atirmociclib for the study, while Olema will lead the study and retain exclusive global commercial rights to palazestrant [4][6] - This marks Olema's second partnership with Pfizer, the first being established in 2020 [7] Pipeline Development - Olema is also conducting a pivotal phase III OPERA-01 study for palazestrant as a monotherapy in second/third-line ER+/HER2- MBC, with top-line data expected in the second half of 2026 [8] - In partnership with Novartis (NVS), Olema is evaluating palazestrant in combination with Kisqali (ribociclib) in an ongoing phase Ib/II study, with a pivotal phase III OPERA-02 study planned [9][10] - Olema is exploring palazestrant in combination with a PI3Ka inhibitor and an mTOR inhibitor in separate phase I/II studies [11] Additional Investigational Candidates - Olema has a second investigational candidate, OP-3136, currently in a phase I study for advanced solid tumors, with initial results anticipated in 2026 [12][13] - The global market opportunity for OP-3136 in second/third-line ER+/HER2- MBC is estimated at around $5 billion [13]

Summary of Olema Pharmaceuticals FY Conference Call Company Overview - Olema Pharmaceuticals is a clinical stage company focused on advancing treatments for metastatic breast cancer, with two clinical stage programs [2][3]. Lead Asset: Palazestrant - Palazestrant is a complete estrogen receptor antagonist, administered as a once-daily oral tablet that fully inhibits estrogen receptor transcriptional activity [2]. - The company is currently conducting two Phase 3 trials for palazestrant: - A frontline metastatic breast cancer study combining palazestrant with Kisqali (ribociclib) [3]. - A second-line trial (OPERA-01) comparing palazestrant monotherapy to standard-of-care monotherapy, expected to read out in the second half of next year [3][5]. Clinical Trial Insights - The frontline trial will involve approximately 1,000 patients, randomized 1:1 between palazestrant with Kisqali and a control arm using an aromatase inhibitor with Kisqali [3]. - The OPERA-01 trial will include about 500 patients, randomized 1:1 between palazestrant monotherapy and standard-of-care [3][10]. - Previous Phase 2 data indicated a seven-month progression-free survival (PFS) benefit in ESR1-mutant patients and a five-month benefit in ESR1 wild-type patients [5][6]. Competitive Landscape - The oral SERD space has seen three positive Phase 3 trials, primarily benefiting ESR1-mutant patients, which constitute about half of the patient population [4]. - Palazestrant aims to differentiate itself by demonstrating efficacy in both ESR1-mutant and wild-type patients, unlike other oral SERDs that have shown limited activity in wild-type patients [6][7]. Combination Therapy - Olema has successfully combined palazestrant with CDK4/6 inhibitors (palbociclib and ribociclib) without significant drug-drug interactions, achieving a median PFS of 13 months in combination studies [13][15]. - The company is also exploring combinations with other agents, including alpelisib and everolimus, and plans to initiate trials with Pfizer's CDK4 inhibitor, atiraciclib [13][19]. Market Opportunity - The current standard of care for frontline hormone receptor-positive HER2-negative metastatic breast cancer is approximately two years, with an annual incidence of about 40,000 women in the U.S. [19]. - Olema aims to extend PFS from two years to three years, potentially increasing the commercial market size from 80,000 patient years to 120,000 patient years [19]. Future Trials and Expectations - Olema is looking forward to results from other frontline oral SERD trials, including Roche's PERSEVERE and AstraZeneca's SERENA-4, which may inform the success of their own trials [22][23]. - The company plans to present data on their CDK4 inhibitor by mid-2025, with ongoing trials in prostate and lung cancer [25][26]. Conclusion - Olema Pharmaceuticals is positioned to make significant advancements in the treatment of metastatic breast cancer through its lead asset, palazestrant, and its strategic focus on combination therapies and clinical trials aimed at improving patient outcomes in both ESR1-mutant and wild-type populations [2][3][19].

Olema Pharmaceuticals FY Conference Summary Company Overview - **Company**: Olema Pharmaceuticals (NasdaqGS:OLMA) - **Focus**: Development of treatments for hormone receptor-positive, HER2-negative breast cancer, which constitutes 70% of breast cancer cases [4][2] Key Points and Arguments Clinical Trials and Product Pipeline - **Lead Asset**: Palazestrant is currently in two Phase 3 trials: - **Opera-01**: Second and third-line monotherapy trial, results expected in H2 2026, with a market opportunity of $2 to $5 billion [4][5] - **Opera-02**: First-line trial combining palazestrant with ribociclib, expected to enroll before the end of September 2025, with a market opportunity exceeding $10 billion [5][6] - **Phase 2 Data**: Indicated better activity in ESR1 mutant populations compared to wild-type, with median progression-free survival (PFS) of over 7 months in mutants and over 5 months in wild-types [9][10] - **Combination Therapy**: Upcoming data presentation at ESMO in October will focus on the combination of palazestrant with ribociclib, aiming to improve upon the current standard of care [5][6] Market Potential and Competitive Landscape - **Market Opportunity**: The company estimates a $10 billion plus market opportunity for the first-line treatment with palazestrant and ribociclib [5][6] - **Differentiation**: Palazestrant is a complete estrogen receptor antagonist, which may provide a competitive edge over partial agonists like elastastin and vaptogestrin [35][36] Strategic Collaborations - **Collaboration with Pfizer**: A clinical trial collaboration to explore the combination of palazestrant with Pfizer's CDK4/6 inhibitor, Ibrance (palbociclib), is underway, with no financial commitments involved [22][26] - **Focus on Combination Therapies**: Olema is positioning itself as a best-in-class endocrine therapy provider in metastatic breast cancer through various combination trials [30][31] Future Directions - **KAT6 Inhibitor Program (OP-3136)**: Currently in Phase 1, with ongoing dose escalation and combination studies with fulvestrant. The program shows promise in multiple cancer types beyond breast cancer [41][45] - **Business Development**: The company is open to strategic partnerships, especially post-Opera-01, as it seeks to market palazestrant globally [51] Important but Overlooked Content - **Regulatory Alignment**: Olema has aligned with the FDA on a 90 mg daily dosing regimen for palazestrant, which is expected to provide favorable pharmacokinetics [39][40] - **Resistance Mechanisms**: The company is addressing common resistance mechanisms in breast cancer treatment, particularly focusing on ESR1 mutations [15][16] - **Potential in Other Indications**: While the primary focus remains on advanced metastatic breast cancer, there is potential for palazestrant in adjuvant settings and other cancer types, contingent on future collaborations [21][46] This summary encapsulates the critical insights from the Olema Pharmaceuticals FY Conference, highlighting the company's strategic focus, clinical advancements, and market positioning in the oncology sector.

Summary of Olema Pharmaceuticals (OLMA) 2025 Conference Call Company Overview - Olema Pharmaceuticals focuses on breast cancer, specifically ER positive, HER2 negative breast cancer, which accounts for 70% of breast cancer cases and is the second leading cause of cancer death in women globally [2][3] Key Assets - **Lead Asset**: Palisestrant, a complete estrogen receptor antagonist, is currently in a Phase III trial (OPRA-one) and a second trial (Opera two) set to initiate soon. The market opportunity for palisestrant is estimated between $2 billion to $5 billion [3][30] - **Second Asset**: OP-3136, a cat six inhibitor, is in Phase I/IB trials, with ongoing monotherapy dose escalation and combination dosing with fulvestrant and alisestrant [7][8] Clinical Trials and Data - **OPRA-one Trial**: Focuses on palisestrant as a monotherapy in advanced metastatic settings post CDK4/6 and AI treatment. Expected data readout in the second half of next year [3][5] - **Opera two Trial**: A combination trial with ribociclib in the first-line setting, set to initiate soon, with updates expected at ESMO in October [4][41] - **PFS Data**: Previous data showed a median progression-free survival (PFS) of 7.3 months in ESR1 mutant patients and 5.5 months in wild-type patients, indicating potential differentiation in efficacy [23][24] Market Landscape and Strategy - The company aims to improve targeted therapies to extend life and quality of life for patients, emphasizing the importance of combining targeted therapies with endocrine agents [11][12] - Olema believes palisestrant can be the preferred endocrine therapy due to its ability to combine effectively with other agents without significant toxicity [15][16] - The market size for palisestrant is significant, with a potential to treat both mutant and wild-type patients, which could lead to a substantial revenue opportunity [30][31] Competitive Landscape - Olema is closely monitoring competitors like Lilly and Arvinas, with skepticism around the efficacy of treatments in wild-type patients. The company remains confident in palisestrant's potential effectiveness in this group [17][18] - The company is also exploring collaborations, such as with Pfizer's atoramiciclib, to enhance treatment options and potentially reduce side effects associated with current therapies [61][62] Future Outlook - Olema is optimistic about the upcoming data presentations and the potential for palisestrant to establish itself as a leading treatment option in the breast cancer space. The company is focused on execution and collaboration to drive its clinical programs forward [42][43][75] - The anticipated data from the Opera two trial and the combination studies with cat six inhibitors are expected to provide further insights into the efficacy and market positioning of Olema's therapies [73][74]

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]

Summary of Olema Pharmaceuticals (OLMA) Conference Call - September 02, 2025 Company Overview - **Company**: Olema Pharmaceuticals - **Focus**: Targeted oncology, specifically treatment of ER positive, HER2 negative breast cancer - **Lead Asset**: Palisestrant, a complete estrogen receptor antagonist [4][5] Pipeline and Trials OPERA-One Trial - **Phase**: Three - **Focus**: Second/third line treatment for advanced metastatic breast cancer - **Patient Population**: Patients who have progressed after initial therapy with CDK4/6 and aromatase inhibitors - **Expected Readout**: Second half of next year - **Market Opportunity**: Estimated between $2 billion to $5 billion depending on patient population (mutant only vs. mutant and wild type) [6][5] - **Progression-Free Survival (PFS)**: - ESR1 mutant population: over 7 months median PFS - ESR1 wild type population: 5.5 months median PFS [6] OPERA-Two Trial - **Phase**: Three - **Focus**: First line treatment comparing ribociclib plus palisestrant versus ribociclib plus aromatase inhibitor - **Market Opportunity**: Estimated over $15 billion - **Expected Enrollment Start**: Soon, with updated data presentation at ESMO in October [6][7] - **PFS Data**: Over a year median PFS in the post-CDK4/6 setting, unprecedented [7] Additional Molecules - **OP-3136**: A CAT6 inhibitor in phase one, progressing as a monotherapy and in combination with fulvestrant and palisestrant [8][9] Collaborations and Agreements - **Collaboration with Pfizer**: Clinical trial supply agreement to combine palisestrant with Pfizer's CDK4 selective molecule, atormaciclib [9][10] - **Operational and Financial Impact**: - Total trial cost for OPERA-Two: approximately $500 million - Collaboration with Novartis to provide Kisqali, offsetting costs [63][64] Clinical Strategy and Differentiation - **Treatment Paradigm**: Aim to delay chemotherapy by using targeted agents [10] - **Combination Therapy**: Palisestrant is expected to enhance the efficacy of existing treatments, particularly in the wild type setting [11][12] - **Regulatory Approval Threshold**: Aiming for a 6-month improvement in median PFS compared to current standards [37][91] Safety and Tolerability - **Neutropenia**: Single-digit rates of reversible neutropenia observed, manageable in combination therapies [92][93] - **Tolerability Profile**: Expected to be similar to existing therapies, with no significant new safety concerns [94] Future Directions - **Exploration of Other Indications**: Potential expansion into prostate and lung cancers based on preclinical activity [109][110] - **Upcoming Data**: Anticipated updates from ongoing trials and presentations at medical meetings to generate interest and support enrollment [28][31] Conclusion - Olema Pharmaceuticals is positioned to make significant advancements in the treatment of ER positive, HER2 negative breast cancer with its lead asset, palisestrant, and ongoing clinical trials. The company is leveraging strategic collaborations to enhance its pipeline and reduce operational costs while aiming for regulatory approval through robust clinical data.

Core Viewpoint - Olema Pharmaceuticals has announced a new clinical trial collaboration with Pfizer to evaluate the combination of palazestrant and atirmociclib in treating metastatic breast cancer, aiming to establish palazestrant as a potential backbone endocrine therapy [1][2] Group 1: Clinical Trial Collaboration - The collaboration involves a Phase 1b/2 study to assess the safety and combinability of palazestrant and atirmociclib in patients with ER+/HER2- metastatic breast cancer [1][2] - Pfizer will supply atirmociclib for the study, while Olema will lead the trial [2] - This marks Olema's second clinical trial agreement with Pfizer, following a previous agreement in November 2020 [3] Group 2: Product and Pipeline Information - Olema's lead product candidate, palazestrant (OP-1250), is an orally available complete estrogen receptor antagonist and selective ER degrader, currently in a Phase 3 trial called OPERA-01 [4][5] - Palazestrant has received FDA Fast Track designation for treating ER+/HER2- metastatic breast cancer that has progressed after endocrine therapy [5] - The company is also developing OP-3136, a KAT6 inhibitor, which is in a Phase 1 clinical study [4] Group 3: Future Plans and Expectations - The new study is expected to involve approximately 35 patients, with initiation anticipated in the second half of 2025 [6] - Successful results from this study could inform a pivotal Phase 3 trial for the combination therapy in the frontline metastatic breast cancer setting [6]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _______ to _______ Commission File Number: 001-39712 OLEMA PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in its Charter) Delawar ...

Corporate Overview This section provides an introductory overview of the company's identity and foundational information [Legal Disclaimer](index=2&type=section&id=Forward-looking%20statements%20and%20legal%20disclaimer) This section outlines legal disclaimers for forward-looking statements, product status, and data interpretation - The presentation contains forward-looking statements regarding research, clinical development, commercial launch, financial sufficiency, and regulatory approvals, which are subject to risks and uncertainties[3](index=3&type=chunk) - Product candidates discussed are under clinical study and not yet approved by the U.S. FDA, with no claims made regarding their safety or effectiveness[4](index=4&type=chunk) - Cross-trial comparisons against third-party data are presented with inherent risks due to differences in study design and should be interpreted with caution[4](index=4&type=chunk) [Strategic Focus & Market Opportunity](index=3&type=section&id=Company%20Focus) This section details the company's strategic focus and significant market opportunities in metastatic breast cancer [Transforming the Treatment Paradigm](index=3&type=section&id=Transforming%20the%20Treatment%20Paradigm) Olema Pharmaceuticals is dedicated to revolutionizing the treatment landscape for metastatic breast cancer (MBC) by advancing two key programs: palazestrant for first-line (1L) and second/third-line (2/3L) MBC, and OP-3136, a potential best-in-class KAT6 inhibitor - Olema is focused on transforming the metastatic breast cancer treatment paradigm[5](index=5&type=chunk) - Advancing palazestrant with blockbuster potential in 1L MBC with ribociclib and 2/3L MBC as a monotherapy[7](index=7&type=chunk) - Progressing OP-3136, a potent and potential best-in-class KAT6 inhibitor[7](index=7&type=chunk) [ER+/HER2- Global Metastatic Breast Cancer Market](index=4&type=section&id=ER%2B%2FHER2-%20Global%20Metastatic%20Breast%20Cancer%20Market) The global ER+/HER2- metastatic breast cancer market represents a significant opportunity, estimated at over $20 billion, with the majority of all breast cancers falling into this subtype. Both 1L and 2/3L settings offer substantial market potential - The ER+/HER2- global metastatic breast cancer market presents a **$20 billion+** opportunity[8](index=8&type=chunk) ER+/HER2- MBC Market Opportunity (2025 Estimates) | Category | Patients (Global) | Duration of Therapy | Global Market Potential (USD) | | :------------------- | :------------------ | :------------------ | :---------------------- | | 1L ER+/HER2- MBC | ~100K+ | ~6-36+ months | $10 billion+ | | 2/3L ER+/HER2- MBC | ~150K+ | ~2-12+ months | $5 billion+ | | **Total Global Market** | | | **~$20 billion+** | - **70%** of all breast cancers are ER+/HER2-[8](index=8&type=chunk) [Palazestrant Program](index=5&type=section&id=Palazestrant%20Program) This section details the Palazestrant program, focusing on its development as a potential best-in-class therapy for MBC [Palazestrant Overview & Best-in-Class Potential](index=5&type=section&id=Palazestrant%20Overview%20%26%20Best-in-Class%20Potential) Palazestrant is positioned as a potential best-in-class, backbone endocrine therapy for metastatic breast cancer, designed to offer complete ER antagonism, activity in both ESR1 wild-type and mutant tumors, good tolerability, and an optimal oral PK profile - Palazestrant has the potential to become a best-in-class, backbone endocrine therapy for metastatic breast cancer[9](index=9&type=chunk) - Key properties include complete ER antagonism, activity in ESR1 wild-type and mutant tumors, good tolerability, combinability at full doses, and optimal oral PK profile[10](index=10&type=chunk) - Designed to help patients feel better, longer[10](index=10&type=chunk) [Palazestrant Mechanism of Action & Properties](index=11&type=section&id=Palazestrant%20Mechanism%20of%20Action%20%26%20Properties) Palazestrant is a differentiated oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD) that completely inactivates the ER by targeting both AF1 and AF2, unlike SERM/SERDs which only partially inactivate ER. This complete antagonism is crucial for shutting off all ER signaling and delivering superior therapeutic exposure - Palazestrant is a Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), currently in Phase 3 for monotherapy and combination[27](index=27&type=chunk) - It completely inactivates the ER (AF1 and AF2) by recruiting N-CoR, preventing transcription of proliferation genes, unlike SERM/SERDs which only partially inactivate ER (AF2 only)[29](index=29&type=chunk) - Palazestrant is a potent ER degrader and uniquely meets optimal drug-plasma exposure, demonstrating potential activity in ESR1 wild-type and mutant tumors[31](index=31&type=chunk) [Palazestrant in Combination with Ribociclib in 1L ER+/HER2- MBC](index=6&type=section&id=Palazestrant%20in%20Combination%20with%20Ribociclib%20in%201L%20ER%2B%2FHER2-%20MBC) Palazestrant, in combination with ribociclib, is being developed for 1L ER+/HER2- MBC, aiming for significant improvement in PFS and OS. Initial Phase 1b/2 data show promising efficacy and a safety profile consistent with ribociclib + ET, with a pivotal Phase 3 OPERA-02 trial initiating in Q3 2025 [Key Properties & Market Potential (1L MBC)](index=6&type=section&id=Key%20Properties%20%26%20Market%20Potential%20(1L%20MBC)) This section highlights palazestrant's unique properties, efficacy potential, and anticipated global market entry in 1L MBC - Palazestrant is the only investigational drug combining with ribociclib in 1L MBC, which is quickly becoming the CDK4/6i of choice[13](index=13&type=chunk)[14](index=14&type=chunk) - Potential for significant improvement in PFS and OS, with activity in ESR1 wild-type and mutant tumors[13](index=13&type=chunk) - Anticipated potential global market opportunity by 2028-2029[13](index=13&type=chunk) [Upcoming Milestones (1L Combo)](index=14&type=section&id=Upcoming%20Milestones%20(1L%20Combo)) This section outlines key upcoming milestones for palazestrant and ribociclib in 1L MBC, including trial initiation, data, and launch - Initiate pivotal Phase 3 OPERA-02 trial in Q3 2025[33](index=33&type=chunk) - Present mature Phase 1b/2 palazestrant + ribociclib data at ESMO 2025[33](index=33&type=chunk) - Anticipated announcement of top-line results from OPERA-02 in 2028, with potential FDA approval and U.S. launch in 2029[33](index=33&type=chunk) [Phase 1b/2 Study Design & Demographics](index=15&type=section&id=Phase%201b%2F2%20Study%20Design%20%26%20Demographics) This section details the design and patient demographics of the Phase 1b/2 study for palazestrant with ribociclib in MBC - Phase 1b/2 study evaluated palazestrant (90 mg / 120 mg) in combination with ribociclib (600 mg) in ER+/HER2- advanced or metastatic breast cancer patients[35](index=35&type=chunk) - Key eligibility included up to 2 prior endocrine therapies ± CDK4/6i and up to 1 prior chemotherapy line[35](index=35&type=chunk) Phase 1b/2 Study Demographics (N=62) | Characteristic | Value | | :---------------------------------- | :---- | | Median age (years) | **61** | | Female sex | **100%** | | Measurable disease at baseline | **68%** | | Visceral disease | **58%** | | Prior CDK4/6 inhibitor | **74%** | | ESR1 mutations at baseline (ctDNA) | **28%** | [Phase 1b/2 Safety Profile](index=17&type=section&id=Phase%201b%2F2%20Safety%20Profile) This section presents the safety profile of palazestrant with ribociclib from the Phase 1b/2 study, highlighting tolerability and adverse events - The combination was well tolerated with no DLTs, and the safety profile was consistent with ribociclib + ET[37](index=37&type=chunk)[38](index=38&type=chunk) - No dose modifications were required for palazestrant, and no patients discontinued palazestrant alone due to TEAEs[14](index=14&type=chunk)[38](index=38&type=chunk) Common TEAEs (≥25%) in Palazestrant + Ribociclib (n=62) | TEAEs (All grades) | Palazestrant + Ribociclib (n=62) (%) | | :----------------- | :------------------------------- | | Neutropenia | **82%** (Grade 3: **45%**, Grade 4: **10%**) | | Nausea | **79%** (Grade 3: **3%**) | | Fatigue | **60%** (Grade 3: **3%**) | | Diarrhea | **50%** (Grade 3: **3%**) | | Anemia | **44%** (Grade 3: **2%**) | | WBC decrease | **42%** (Grade 3: **16%**, Grade 4: **2%**) | [Phase 1b/2 Efficacy Data](index=18&type=section&id=Phase%201b%2F2%20Efficacy%20Data) This section presents efficacy data from the Phase 1b/2 study, including median PFS and competitive benchmarks Median PFS (mPFS) in Phase 1b/2 Study (Data Cutoff: Feb 18, 2025) | Patient Group | Median PFS (months) | | :------------------------------------------ | :------------------ | | All Patients (120 mg palazestrant + ribociclib, n=56) | **13.8** | | Patients with Prior CDK4/6i + ET (n=40) | **13.1** | - The median PFS of **13.1** months in prior CDK4/6i patients compares favorably to competitive benchmarks like MAINTAIN (ET + Ribociclib: **12.0** months, ET + Placebo: **5.3** months) and other SERDs[41](index=41&type=chunk)[42](index=42&type=chunk) - 6-month PFS Rate was **74%** for all patients and **68%** for patients with prior CDK4/6i + ET[40](index=40&type=chunk) [OPERA-02 Phase 3 Pivotal Trial Design](index=20&type=section&id=OPERA-02%20Phase%203%20Pivotal%20Trial%20Design) This section details the design of the OPERA-02 Phase 3 pivotal trial for palazestrant with ribociclib in 1L ER+/HER2- MBC - OPERA-02 is a **~1,000**-patient Phase 3 pivotal trial evaluating palazestrant (90 mg) in combination with ribociclib (600 mg) versus letrozole (2.5 mg) + ribociclib (600 mg) in 1L ER+/HER2- MBC[45](index=45&type=chunk)[46](index=46&type=chunk) - Primary endpoint is PFS (Investigator), with key secondary endpoint OS. Trial initiation is in 2025 in collaboration with Novartis[46](index=46&type=chunk) - Eligibility includes ER+/HER2- MBC, any menopausal status, no prior systemic therapy or CDK4/6 inhibitor for MBC[46](index=46&type=chunk) [Strategic Rationale: TAGRISSO Case Study](index=21&type=section&id=Strategic%20Rationale%3A%20TAGRISSO%20Case%20Study) This section provides the strategic rationale for OPERA-02, drawing parallels with the TAGRISSO case study for resistance suppression in MBC - The FLAURA trial for TAGRISSO demonstrated that suppressing common resistance mechanisms (EGFR T790M mutation) led to significant PFS improvement and label expansion into 1L[47](index=47&type=chunk)[48](index=48&type=chunk) - Comparable EGFR mutation rates after 1L TKI to ESR1 mutation rates after 1L CDK4/6i + AI (**~40-50%**) suggest a similar strategic opportunity for OPERA-02[47](index=47&type=chunk) - OPERA-02 is designed to demonstrate greater PFS by suppressing the most common resistance mutation (ESR1) in 1L endocrine sensitive MBC patients, mirroring TAGRISSO's success[48](index=48&type=chunk) [Palazestrant Monotherapy in 2/3L ER+/HER2- MBC](index=7&type=section&id=Palazestrant%20Monotherapy%20in%202%2F3L%20ER%2B%2FHER2-%20MBC) Palazestrant monotherapy offers a first market entry opportunity in 2/3L ER+/HER2- MBC by 2027, aiming to be a best-in-class single agent. Phase 1/2 data show compelling efficacy in ESR1 mutant and wild-type tumors with a well-tolerated safety profile, supporting the ongoing pivotal Phase 3 OPERA-01 trial [Key Properties & Market Entry (2/3L Mono)](index=7&type=section&id=Key%20Properties%20%26%20Market%20Entry%20(2%2F3L%20Mono)) This section highlights palazestrant monotherapy's key properties and anticipated market entry in 2/3L MBC as a best-in-class agent - Palazestrant monotherapy in 2/3L ER+/HER2- MBC offers the first opportunity for market entry in 2027[15](index=15&type=chunk)[17](index=17&type=chunk) - Potential to become the best-in-class single agent endocrine therapy, improving upon current standard of care[15](index=15&type=chunk) - Favorable pharmacokinetic properties include high oral bioavailability, dose-proportional exposure, and a long half-life supporting once-daily dosing[18](index=18&type=chunk) [Upcoming Milestones (2/3L Mono)](index=22&type=section&id=Upcoming%20Milestones%20(2%2F3L%20Mono)) This section outlines key upcoming milestones for palazestrant monotherapy in 2/3L MBC, including trial accrual, results, and launch - Advance patient accrual in pivotal Phase 3 OPERA-01 trial in 2025[51](index=51&type=chunk) - Announce top-line results from OPERA-01 in H2 2026[51](index=51&type=chunk) - Anticipated submission of New Drug Application (NDA) and potential FDA approval and U.S. commercial launch in 2027[51](index=51&type=chunk) [Phase 1/2 Study Design](index=23&type=section&id=Phase%201%2F2%20Study%20Design) This section details the design of the Phase 1/2 study for palazestrant monotherapy in advanced MBC, including objectives - Phase 1/2 study evaluated palazestrant as a monotherapy in patients with advanced or metastatic ER+/HER2- breast cancer[52](index=52&type=chunk)[53](index=53&type=chunk) - Key eligibility criteria included 1-4 prior endocrine therapies for metastatic disease and up to 1 line of prior chemotherapy[53](index=53&type=chunk) - Primary objectives were pharmacokinetics, safety, and tolerability at RP2D, with secondary objectives including efficacy (ORR, CBR, DOR)[53](index=53&type=chunk) [Phase 1/2 Safety Profile](index=24&type=section&id=Phase%201%2F2%20Safety%20Profile) This section presents the safety profile of palazestrant monotherapy from the Phase 1/2 study, highlighting tolerability and adverse events - Palazestrant was well-tolerated, with most treatment-emergent adverse events (TEAEs) being Grade 1/2[55](index=55&type=chunk) Common TEAEs (≥15%) in Palazestrant 120 mg (n=83) | TEAEs (All grades) | Palazestrant 120 mg (n=83) (%) | | :----------------- | :------------------------- | | Nausea | **65%** (Grade 3: **3%**) | | Vomiting | **30%** (Grade 3: **1%**) | | Fatigue | **27%** (Grade 3: **3%**) | | Neutropenia | **25%** (Grade 3: **3%**, Grade 4: **6%**) | | Headache | **20%** | | Constipation | **18%** | | AST increased | **16%** (Grade 3: **1%**) | - Grade 4 neutropenia events were observed in **6** patients, managed with dose interruption/reduction or discontinuation, with recovery[55](index=55&type=chunk) [Phase 1/2 Efficacy Data](index=25&type=section&id=Phase%201%2F2%20Efficacy%20Data) This section presents efficacy data from the Phase 1/2 study, including median PFS in ESR1 mutant and wild-type tumors, showing best-in-class potential Median PFS (mPFS) in Phase 1/2 Study (Data Cutoff: July 7, 2023) | Patient Group (2/3L ±CT) | Median PFS (months) | | :----------------------- | :------------------ | | ESR1 Mutant (n=23) | **7.3** | | ESR1 Wild-Type (n=21) | **5.5** | - Palazestrant shows best-in-class potential, being the only CERAN/SERD with potential for approval in both ESR1 mutant and wild-type tumors[58](index=58&type=chunk) - The mPFS of **7.3** months in ESR1 mutant patients and **5.5** months in ESR1 wild-type patients compares favorably to other SERDs in CDK4/6i-experienced patients[57](index=57&type=chunk)[59](index=59&type=chunk) [OPERA-01 Phase 3 Monotherapy Trial Design](index=27&type=section&id=OPERA-01%20Phase%203%20Monotherapy%20Trial%20Design) This section details the design of the OPERA-01 Phase 3 monotherapy trial, aiming for superior efficacy in ESR1 mutant and wild-type tumors - OPERA-01 is a Phase 3 monotherapy trial designed to show superior efficacy in ESR1 mutant and ESR1 wild-type tumors[60](index=60&type=chunk)[61](index=61&type=chunk) - The trial includes a dose selection part (Palazestrant 120 mg vs 90 mg) and a dose assessment part (Palazestrant vs. SOC Endocrine Therapy) with **~510** patients[61](index=61&type=chunk) - Primary endpoint is PFS (BIRC) in ESR1 mutant and ESR1 mut-nd, with top-line results expected in H2 2026[61](index=61&type=chunk) [Commercial Launch Planning (2/3L Mono)](index=28&type=section&id=Commercial%20Launch%20Planning%20(2%2F3L%20Mono)) This section outlines commercial launch planning for palazestrant monotherapy in 2/3L MBC, including market potential and preparations - Planning for commercial launch of palazestrant as a monotherapy in 2/3L ER+/HER2- MBC is anticipated in 2027[62](index=62&type=chunk) - The annual U.S. incidence is estimated at **~40,000** patients, with a U.S. market potential of **~$3-5 billion** in the 2/3L setting[62](index=62&type=chunk) - Preparatory work includes establishing manufacturing supply and distribution, and building a targeted field force of **~75–100** reps to cover U.S. breast oncologists[62](index=62&type=chunk) [OP-3136 Program](index=8&type=section&id=OP-3136%20Program) This section introduces the OP-3136 program, highlighting its development as a novel KAT6 inhibitor for breast cancer and solid tumors [OP-3136 Overview & Value Potential](index=8&type=section&id=OP-3136%20Overview%20%26%20Value%20Potential) OP-3136, Olema's potent and selective KAT6A/B inhibitor, represents an exciting new target in breast cancer with the potential to generate further value and meaningfully impact the MBC treatment landscape. Preclinical data show synergistic activity with palazestrant and CDK4/6 inhibitors, with a Phase 1 study currently enrolling - OP-3136 has the potential to generate further value and meaningfully impact the MBC treatment landscape[19](index=19&type=chunk) - KAT6 is an exciting new target in breast cancer, with promising preclinical data in breast cancer and other solid tumors[20](index=20&type=chunk) - OP-3136 is potent and selective against KAT6A/B, synergizes with palazestrant in preclinical models, and has a potential global market opportunity of **$5 billion+**[20](index=20&type=chunk) [OP-3136 at a Glance](index=29&type=section&id=OP-3136%20at%20a%20Glance) OP-3136 is a KAT6A/B inhibitor currently in Phase 1 development, with an initial development indication for 2/3L ER+/HER2- MBC. Initial monotherapy and combination data from the Phase 1 study are anticipated in 2026 - Mechanism of Action: KAT6A/B inhibitor[65](index=65&type=chunk) - Stage of Development: Phase 1, with initial development indication for 2/3L ER+/HER2- MBC[65](index=65&type=chunk) - Upcoming Milestone: Initial monotherapy and combination data from the Phase 1 study expected in 2026[64](index=64&type=chunk) [Mechanism of Action & Target Validation](index=30&type=section&id=Mechanism%20of%20Action%20%26%20Target%20Validation) OP-3136 targets KAT6, an exciting and validated target in ER+/HER2- MBC. KAT6 acetylates chromatin, enabling transcription and proliferation, and OP-3136 prevents this by blocking histone acetylation. Clinical proof of concept for KAT6 inhibitors has been demonstrated by Pfizer, validating KAT6 as an active new target and highlighting the potential for synergistic combination therapies - OP-3136 is a potent and selective KAT6A/B inhibitor, orally bioavailable with high free drug exposure, and synergizes with palazestrant and CDK4/6 inhibitors in preclinical models[66](index=66&type=chunk) - KAT6 acetylates chromatin, enabling transcription and proliferation; OP-3136 inhibits KAT6, stopping histone acetylation and blocking transcription of proliferation-associated genes[68](index=68&type=chunk) - KAT6 is a clinically validated target, with overexpression correlated with worse clinical outcomes in ER+ breast cancer. Pfizer's first-in-human data for a KAT6 inhibitor validates it as an active new target and shows synergistic activity with ET[69](index=69&type=chunk)[72](index=72&type=chunk) [Preclinical Data & Selectivity](index=33&type=section&id=Preclinical%20Data%20%26%20Selectivity) OP-3136 demonstrates high potency and superior selectivity for KAT6A/B over other essential KAT family members (KAT5 and KAT8) compared to PF-8144, suggesting a potential safety advantage. Preclinical studies also show strong synergistic anti-tumor activity when combined with palazestrant, leading to significant tumor regression Biochemical Potency (IC50 nM) and Selectivity | Target | OP-3136 | PF-8144 | | :----- | :------ | :------ | | KAT6A | **9** | **7** | | KAT6B | **1** | **1** | | KAT7 | **108** | **88** | | KAT5 | **6792** | **1288** | | KAT8 | **4490** | **1372** | - OP-3136 showed **>500-fold** selectivity over KAT5 and KAT8, which may confer a safety advantage over alternative products like PF-8144[74](index=74&type=chunk) - OP-3136 demonstrated synergistic activity in combination with palazestrant in preclinical breast cancer models, resulting in strong tumor regression and improved anti-tumor efficacy compared to PF-8144 combinations[75](index=75&type=chunk)[77](index=77&type=chunk) [Phase 1 Study Design](index=35&type=section&id=Phase%201%20Study%20Design) The OP-3136 Phase 1 study, with IND cleared by FDA, is currently recruiting patients. It includes dose escalation for monotherapy and combination, followed by dose expansion cohorts for OP-3136 with fulvestrant, palazestrant, and a triple combination with palazestrant + ribociclib - The IND for OP-3136 has been cleared by the FDA, and the Phase 1 study is actively recruiting patients[78](index=78&type=chunk)[79](index=79&type=chunk) - The study design includes dose escalation (monotherapy and combination) and dose expansion cohorts for OP-3136 + Fulvestrant, OP-3136 + Palazestrant, and OP-3136 + Palazestrant + Ribociclib[79](index=79&type=chunk) - Key eligibility criteria include ER+/HER2- MBC (or MCRPC or MNSCLC for Part 1A) and at least one prior line with CDK4/6i + ET for combination cohorts[79](index=79&type=chunk) [Overall Pipeline & Strategic Milestones](index=9&type=section&id=Overall%20Pipeline%20%26%20Strategic%20Milestones) This section provides an overview of the company's pipeline and outlines key strategic milestones for advancing programs and generating value [Pipeline Overview](index=9&type=section&id=Pipeline%20Overview) Olema is rapidly advancing its pipeline of novel therapies, including Palazestrant (CERAN/SERD) for ER+/HER2- metastatic breast cancer and OP-3136 (KAT6 Inhibitor) for breast cancer and other solid tumors, targeting significant global market opportunities - Olema is rapidly advancing its pipeline of novel therapies through the clinic[22](index=22&type=chunk) Olema Pipeline and Market Opportunities | Product Candidate | Mechanism/Target | Indication | Stage | Potential Global Market Opportunity* (USD) | | :---------------- | :--------------- | :--------- | :---- | :--------------------------------- | | Palazestrant | CERAN/SERD | ER+/HER2- metastatic breast cancer | Planned pivotal Phase 3 trial evaluating palazestrant combination with ribociclib in 1L MBC; Ongoing pivotal Phase 3 trial evaluating palazestrant as a monotherapy in 2/3L MBC | $10 billion+ (1L), $5 billion+ (2/3L) | | OP-3136 | KAT6 Inhibitor | Breast cancer and other solid tumors | Ongoing Phase 1 study evaluating OP-3136 monotherapy and combination in advanced or metastatic: ER+/HER2- breast cancer, Castrate-resistant prostate cancer, Non-small cell lung cancer | $5 billion+ | [Value-Generating Catalysts & Corporate Priorities](index=10&type=section&id=Value-Generating%20Catalysts%20%26%20Corporate%20Priorities) Olema has a clear roadmap of value-generating catalysts through 2030, focusing on advancing global registrational studies, achieving product approvals and launches for Palazestrant in both 2/3L and 1L MBC, and progressing the OP-3136 program with initial clinical data. These milestones are aimed at transforming the MBC treatment paradigm and generating significant shareholder value - Olema aims to transform the metastatic breast cancer treatment paradigm and generate significant shareholder value by 2030[80](index=80&type=chunk) - Key milestones include executing global registrational studies (2025), product approval and launch for Palazestrant in 2/3L MBC (2027), pivotal OPERA-02 readout in 1L MBC (2028), OP-3136 clinical data and OPERA-01 readout in 2/3L MBC (2026), and label expansion in 1L MBC (2029)[23](index=23&type=chunk)[81](index=81&type=chunk) - Palazestrant is highly differentiated with activity in ESR1 mutant and wild-type tumors, with OPERA-01 and OPERA-02 trials on track. OP-3136 is an exciting new target, synergizes with Palazestrant, and its Phase 1 study is enrolling with initial data expected in 2026[82](index=82&type=chunk) [Conclusion](index=37&type=section&id=Thank%20You) This section concludes with the company's commitment to advancing therapeutic solutions for breast cancer and beyond - Olema Pharmaceuticals is committed to advancing medicines for breast cancer and beyond[83](index=83&type=chunk)