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)

Core Insights - Olema Pharmaceuticals reported financial and operational results for Q2 2025, highlighting a focus on advancing its clinical programs for breast cancer therapies [1][5][6]. Recent Progress - The company achieved regulatory alignment on the selected dose for the pivotal palazestrant program and is accelerating enrollment in the OPERA-01 trial, with top-line data expected in the second half of 2026 [2][8]. - Olema is also advancing OP-3136, a KAT6 inhibitor, which is generating strong interest and enrollment in its Phase 1 study [2][9]. Financial Results - As of June 30, 2025, Olema had cash, cash equivalents, and marketable securities totaling $361.9 million [5][19]. - The net loss for Q2 2025 was $43.8 million, an increase from $30.4 million in Q2 2024, primarily due to a one-time milestone payment of $10 million and increased R&D spending [6][20]. - GAAP R&D expenses were $43.9 million for Q2 2025, up from $29.1 million in Q2 2024, reflecting ongoing late-stage clinical trials [7][20]. Anticipated Upcoming Events - Enrollment in the OPERA-01 trial is ongoing, with top-line data expected in the second half of 2026, while the OPERA-02 trial is set to initiate in Q3 2025 [8][9]. - Mature data from the Phase 1b/2 study of palazestrant in combination with ribociclib will be presented at ESMO 2025 [9]. Company Overview - Olema Oncology is focused on developing targeted therapies for breast cancer, with its lead candidate, palazestrant, currently in a pivotal Phase 3 trial [13][14]. - The company is also developing OP-3136, which has shown significant anti-proliferative activity in preclinical studies [15].

Palazestrant (OP-1250) Development - Olema aims to establish Palazestrant as a best-in-class backbone therapy for ER+/HER2- breast cancer, both as a monotherapy and in combination with other anti-tumor agents[8] - The pivotal Phase 3 OPERA-01 clinical trial of Palazestrant as a monotherapy is ongoing, with top-line results expected in 2026[16, 37] - A pivotal Phase 3 OPERA-02 clinical trial of Palazestrant in combination with ribociclib is planned for initiation in 2025[3, 14, 16, 37, 88] - Palazestrant monotherapy Phase 2 data showed a median PFS of 73 months in 2/3L ±CT ESR1-mutant patients and 55 months in 2/3L ±CT ESR1-wild-type patients[45, 46, 47] - Palazestrant, at 120mg in combination with ribociclib, showed a 6-month PFS rate of 74% in all patients and 68% in patients with prior CDK4/6i[75, 80] OP-3136 (KAT6 Inhibitor) Development - Olema is advancing the clinical development of OP-3136, a potential best-in-class KAT6 inhibitor, in breast and other solid tumor cancers[10] - The FDA has cleared the Investigational New Drug (IND) application for OP-3136, and a Phase 1 clinical trial has been initiated[16, 100] - Preclinical data demonstrates that OP-3136 shows synergistic activity in combination with palazestrant[112] Market and Financial Position - The estimated global market for ER+/HER2- metastatic breast cancer is greater than $20 billion[35] - The U S market potential for Palazestrant in the 2/3L setting is estimated at $3-5 billion[63] - Olema has a strong capital position with $3927 million[13]

Summary of Olema Pharmaceuticals (OLMA) FY Conference Call Company Overview - **Company**: Olema Pharmaceuticals (OLMA) - **Date of Conference**: June 11, 2025 - **Key Speaker**: Shane Kovac, COO and CFO Key Points Industry and Company Developments - Olema is at a pivotal moment in drug development, with significant clinical data expected in the next 12 to 18 months [2] - The company is focusing on its phase two ribociclib and palazestrant combination study, with updated data presentation anticipated later this year [2][6] - The cat six program is progressing well, currently in phase one dose escalation, with potential data readouts expected this year [3] - The OPRA o one phase three trial is pivotal, with a potential filing for approval in late 2026 or early 2027 if successful [4] Clinical Trials and Data - Olema has signed a significant agreement with Novartis to support the OPRA two study, which focuses on frontline metastatic breast cancer [4] - The company aims to achieve at least a six-month progression-free survival (PFS) benefit over the control arm in the OPRA two trial, with data expected around late 2028 [5] - Olema believes it has a best-in-class molecule, palazestrant, showing superior efficacy in both mutant and wild-type populations compared to competitors [6][7] Stock Performance and Market Position - Despite positive developments and impressive data presentations, Olema's stock price has fallen below $5, attributed to negative market reactions to competitors' data [18][22] - The company has created significant value over the past year, with successful FDA interactions and trial initiations [20][22] - Olema's stock is currently trading around cash value, indicating a potential buying opportunity for investors [22] Competitor Analysis - Competitors such as AMPER three, Veritec two, and SERENNA six have reported mixed results, impacting market perceptions of Olema [18][19] - Olema differentiates itself by allowing prior fulvestrant use in its trials, potentially leading to a more favorable patient population compared to competitors [35] - The company is optimistic about its competitive edge due to its unique pharmacological profile and dosing strategy [64] Future Outlook - Olema is focused on generating new data and enrolling patients in the coming months, with the next twelve months expected to be critical for the company [67] - The breast cancer market is significant, and Olema aims to compete against major players like Roche and AstraZeneca [68] - The success of upcoming trials, including OPRA o two, is crucial for establishing Olema's position in the market [60] Conclusion - Olema Pharmaceuticals is positioned for potential growth with its innovative drug candidates and strategic partnerships, despite current stock price challenges and competitive pressures [68][69]

Summary of Olema Pharmaceuticals (OLMA) Conference Call Company Overview - **Company**: Olema Pharmaceuticals - **Lead Asset**: Palazestrant, a complete estrogen receptor antagonist - **Current Development Stage**: Enrolling in phase three clinical trials for breast cancer treatment Key Points and Arguments 1. **Clinical Trials**: Olema is currently enrolling a phase three program for palazestrant, focusing on advanced ER-positive, HER2-negative breast cancer that has not received prior treatment in the metastatic setting [2][5] 2. **Efficacy Data**: - Palazestrant has shown a median progression-free survival (PFS) of 13.1 months in patients who progressed on CDK4/6 inhibitors plus an aromatase inhibitor, compared to a standard of care PFS of approximately 5.5 months [7][11] - In a phase two trial, palazestrant demonstrated better activity in the ESR1 mutant subset, achieving 7.3 months PFS [4][17] 3. **Combination Studies**: Olema is also testing palazestrant in combination with ribociclib, showing favorable tolerability and enhanced activity compared to other agents in the same class [6][8] 4. **Market Confusion**: The market is currently confused due to mixed results from other studies in the same class, such as Veritat II and Ember three, which have shown varying PFS outcomes [11][12] 5. **Predictive Confidence**: The CEO emphasized the importance of using prior clinical trial data to predict outcomes, arguing that palazestrant's design addresses weaknesses seen in other agents [13][15] 6. **Upcoming Data**: Olema anticipates a top-line PFS readout from its phase three study next year, with ongoing updates on enrollment data expected later this year [71][72] Additional Important Insights 1. **Regulatory Pathways**: The CEO discussed the complexities of regulatory pathways for competing drugs, particularly highlighting the challenges faced by Lilly's Ember three trial [20][22] 2. **Patient Population**: The discussion highlighted that a significant portion of patients in the Serena six study had already been on therapy for extended periods, which may affect the outcomes of first-line studies [36][38] 3. **Future Studies**: Olema is preparing for upcoming phase three readouts from Roche and AstraZeneca, which could impact market perceptions of the entire class of drugs [57][59] 4. **Cat6 Inhibitor**: Olema is also in phase one dose escalation for a Cat6 inhibitor, with potential data presentation expected next year [94][96] This summary encapsulates the critical aspects of Olema Pharmaceuticals' current position in the breast cancer treatment landscape, focusing on the development and potential of palazestrant, while also addressing market dynamics and future expectations.

Core Insights - Olema Pharmaceuticals has aligned with the FDA to select a 90 mg dose of palazestrant for the Phase 3 OPERA-01 trial in ER+/HER2- metastatic breast cancer [1][2] - The OPERA-01 trial results are expected to be presented at the ASCO Annual Meeting from May 30 to June 3, 2025, with top-line data anticipated in 2026 and a potential commercial launch in 2027 [2][4] Company Overview - Olema Oncology is a clinical-stage biopharmaceutical company focused on developing targeted therapies for breast cancer, particularly through its lead product candidate, palazestrant (OP-1250) [4][5] - Palazestrant is a novel small molecule that acts as both a complete estrogen receptor antagonist and a selective estrogen receptor degrader, currently being evaluated in multiple clinical trials [3][5] Clinical Trials - The OPERA-01 trial is a randomized, open-label Phase 3 study comparing palazestrant monotherapy to standard endocrine therapy for patients with advanced ER+/HER2- breast cancer [2][4] - Palazestrant has received FDA Fast Track designation for treating ER+/HER2- metastatic breast cancer that has progressed after endocrine therapy and at least one line of treatment with a CDK4/6 inhibitor [3][4]

Summary of Olema Pharmaceuticals (OLMA) FY Conference Call - May 27, 2025 Company Overview - **Company**: Olema Pharmaceuticals (OLMA) - **Focus**: Development of palazestrant, a complete estrogen receptor antagonist, for the treatment of breast cancer Key Points Clinical Trials and Data - **OPRA O1 Trial**: - Focuses on palazestrant for second and third line HER2 negative metastatic breast cancer - Enrollment for the dose-ranging part completed late last year, with data collection ongoing [6][8] - Top-line data expected in 2026, with more precise timelines to be provided in the second half of 2025 [8][10] - **ASCO Presentation**: - A trial progress poster will be presented, focusing on part two of the OPRA O1 trial, which may attract interest from investors and potential trial participants [12][14] - **Comparison with Other Trials**: - Data from EMBER three and Veritec two trials will be analyzed to assess palazestrant's potential for success [16][18] - OPRA O1 aims to show better progression-free survival (PFS) in ESR1 mutant and wild-type populations compared to existing therapies [19][20] Market Potential - **Market Opportunity**: - The second and third line treatment market for wild-type patients is estimated at $5 billion, depending on PFS duration [49] - Differentiation in the mutant population could enhance market capture [49] Cat 6 Inhibitor Program - **Mechanism**: - Cat 6 is an epigenetic target that affects chromatin structure, potentially enhancing the efficacy of anti-estrogen therapies [52][53] - **Preclinical Data**: - Olema's Cat 6 inhibitor shows promising preclinical results, particularly in combination with palazestrant, which may enhance anti-tumor activity [54][58] - **Future Data**: - Data from monotherapy dose escalation may be available by the end of 2025, with ongoing trials in various solid tumors [57][59] Differentiation and Competitive Landscape - **Molecular Characteristics**: - Palazestrant is positioned as a complete estrogen receptor antagonist, distinguishing it from other SERDs and SERMs in the market [24][25] - **Investor Perception**: - The company believes that investors may overlook the unique molecular properties and potential of palazestrant compared to other drugs in the same class [61][62] Pipeline and Future Directions - **Upcoming Trials**: - The initiation of the OPRA O2 trial is expected in the second half of 2025, contingent on data from OPRA O1 [44][48] - **Broader Applications**: - Interest in exploring Cat 6 inhibitors in non-small cell lung cancer and castration-resistant prostate cancer [59] Conclusion - Olema Pharmaceuticals is advancing its clinical trials for palazestrant, with significant market potential in breast cancer treatment. The company is also exploring innovative approaches with its Cat 6 inhibitor program, positioning itself as a key player in the oncology space. Investors are encouraged to consider the unique attributes of Olema's therapies as they differentiate from competitors.