Olema Pharmaceuticals, Inc. · NASDAQ:OLMA
Olema Pharmaceuticals — Investor Presentation (October 2025)
39 slides from Olema Pharmaceuticals's investor presentation, Oct 20, 2025
Slide 1: Advancing medicines for breast cancer and beyond: Corporate Overview
Advancing medicines for breast cancer and beyond Corporate Overview October 2025
Slide 2: Forward-looking statements and legal disclaimer
Forward-looking statements and legal disclaimer This presentation contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this presentation that are not statements of historical fact are forward-looking st
Slide 3: Olema is focused on transforming the metastatic breast cancer treatment paradigm
Olema is focused on transforming the metastatic breast cancer treatment paradigm Advancing palazestrant with blockbuster potential in 1L MBC with ribociclib and 2/3L MBC as a monotherapy 1L = frontline; 2/3L = second/third-line; KAT6 = lysine acetyltransferase 6; MBC = metastatic breast cancer Progr
Slide 4: The ER+/HER2- global market presents a $20B+ opportunity
The ER+/HER2- global metastatic breast cancer market presents a $20B+ opportunity1 1 2025 opportunity estimates for global endocrine therapy market. Olema internal data. 2National Breast Cancer Foundation, World Health Organization; American Cancer Society. Facts and Figures 2024; SEER database. 3 2
Slide 5: Palazestrant has the potential to become a best-in-class backbone endocrine therapy
Complete ER antagonism Activity in ESR1 wild-type and mutant tumors Well-tolerated and combinable at full doses Optimal PK profile with oral administration Palazestrant has the potential to become a best-in-class, backbone endocrine therapy for metastatic breast cancer AI + CDK4/6i ~6-36+ months ET,
Slide 6: Palazestrant with ribociclib could become the new standard of care in 1L MBC
Emerging resistance mutations, AEs, and suboptimal drug exposure limit the utility of currently approved therapies in 1L MBC Palazestrant in combination with ribociclib has the potential to become the new standard of care in 1L ER+/HER2- MBC 1 Novartis full year earnings reports, 2018-2024. 2ESMO 20
Slide 7: Palazestrant monotherapy in 2/3L MBC offers first market entry in 2027
Palazestrant monotherapy in 2/3L ER+/HER2- MBC offers our first opportunity for market entry in 2027 Promising Safety Well-tolerated Most AEs were low grade (1/2) Differentiated Efficacy Profile Median PFS1 of: 7+ months in 2/3L ±CT ESR1 mutant 5+ months in 2/3L ±CT ESR1 wild-type Favorable Pharmaco
Slide 8: OP-3136 KAT6 inhibitor: promising preclinical data and clinical plans
Potent and selective against KAT6A/B Selective over KAT5/8 with fewer off target effects Synergistic with palazestrant in preclinical models Potential $5B+ global market opportunity2 Promising Preclinical Data in Breast Cancer Synergistic activity with palazestrant and superiority to KAT6 inhibitors
Slide 9: We are rapidly advancing our pipeline of novel therapies through the clinic
We are rapidly advancing our pipeline of novel therapies through the clinic Palazestrant: CERAN/SERD ER+/HER2- metastatic breast cancer OP-3136: KAT6 Inhibitor Breast cancer and other solid tumors Ongoing pivotal Phase 3 trial evaluating palazestrant combination with ribociclib in 1L MBC Ongoing piv
Slide 10: Value-generating catalysts through 2030
Value-generating catalysts through 2030 advance us towards our goal of transforming the treatment paradigm for metastatic breast cancer 2025 EXECUTE GLOBAL REGISTRATIONAL STUDIES 2027 PRODUCT APPROVAL AND LAUNCH FOR PALAZESTRANT IN 2/3L MBC* 2028 PIVOTAL OPERA-02 READOUT IN 1L MBC IN COMBINATION WIT
Slide 11: Palazestrant at a glance
Palazestrant AT A GLANCE Mechanism of Action Complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) Stage of Development Monotherapy: Phase 3 In Combination: Phase 3; multiple studies in Phase 1/2 Special Designations FDA Fast Track* 2025 MILESTONES Advancing p
Slide 12: Palazestrant mechanism of action
Palazestrant mechanism of action Palazestrant is a differentiated oral CERAN/SERD targeting the growth and proliferation mechanism driving ER+ breast cancer Activated ER drives cancer cell growth SERM/SERDs partially inactivate ER (AF2 only) Palazestrant, a CERAN/SERD, not only degrades but also com
Slide 13: Palazestrant has the right properties to become a best-in-class agent
Palazestrant has the right properties to become a best-in-class agent Palazestrant completely inactivates the ER and delivers superior therapeutic exposure Complete ER antagonism is key to shutting off all ER signaling Palazestrant uniquely meets optimal drug-plasma exposure1 * NOTE: This analysis i
Slide 14: Palazestrant in combination with ribociclib in 1L ER+/HER2- MBC
Palazestrant in combination with ribociclib in 1L ER+/HER2- metastatic breast cancer MILESTONES 2025: Pivotal Phase 3 OPERA-02 trial ongoing 2025: Presented mature Phase 1b/2 palazestrant + ribociclib data at ESMO 2028: Anticipated announcement of top-line results from OPERA-02 2029: Potential FDA a
Slide 15: Design: Phase 1b/2 study of palazestrant with ribociclib
Design: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Key eligibility criteria Women or men with ER+/HER2– advanced or metastatic breast cancer Up to 2 prior endocrine therapies ± a CDK4/6i for locally advanced or metastatic disease; up to 1 prior line of chemother
Slide 16: Demographics: Phase 1b/2 study of palazestrant with ribociclib
Demographics: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC N=72; N=56 at 120 mg; N=16 at 90 mg 54% with visceral disease 68% with measurable disease 67% received prior endocrine therapy in advanced setting 63% received prior CDK4/6i + ET 36 (50%) patients received
Slide 17: Well tolerated with no DLTs; safety consistent with ribociclib + ET
Well tolerated with no DLTs; safety profile consistent with ribociclib + ET Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Palazestrant 120 mg + Ribociclib Palazestrant 90 mg + Ribociclib MONALEESA-2* Letrozole + Ribociclib† TEAEs in ≥25% of patients (n = 56) (n = 1
Slide 18: Median PFS of 15.5 months for all 120 mg patients
Data cutoff date: July 8, 2025 ; Median follow-up >19 months CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ER+ = estrogen receptor positive; ET = endocrine therapy; HER2- = human epidermal growth factor receptor negative; MBC = metastatic breast cancer; mPFS = median progression free survival; PF
Slide 19: Activity in both ESR1 mutant and wild-type 2L+ patients
Demonstrated activity in both ESR1 mutant and wild-type 2L+ patients Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Data cutoff date: July 8, 2025; Median follow-up >19 months CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ER+ = estrogen receptor positive; HER2- =
Slide 20: Pala + Ribo shows promising activity in 2L+ patients with prior CDK4/6i
Pala + Ribo shows promising activity in 2L+ patients with prior CDK4/6i MAINTAIN study of ribociclib plus ET after CDK4/6i progression serves as best clinical benchmark* * NOTE: This analysis is the aggregation of results across independent studies. There are risks inherent in conducting cross-trial
Slide 21: Design: OPERA-02 pivotal trial in 1L ER+/HER2- MBC
Design: OPERA-02 Phase 3 pivotal trial of palazestrant in combination with ribociclib in 1L ER+/HER2- MBC Ongoing ~1,000-patient trial vs. standard of care Endpoints Primary: PFS (Investigator) Secondary : OS (Key) PFS (BIRC) ORR/CBR/DOR (BIRC, Investigator) Safety PK Health-related PROs n ≈ 1,000 P
Slide 22: Case study: TAGRISSO's path to approval and label expansion
Case study: TAGRISSO’s® path to approval and label expansion by suppressing resistance mutations* * NOTE: This analysis incorporates publicly-available third-party data that we have not independently verified. Results and outcomes presented should be interpreted with caution. Refer to further discla
Slide 23: Palazestrant demonstrates combinability with other targeted agents
Palazestrant demonstrates combinability with other targeted agents Combination with Pfizer’s selective CDK4 inhibitor, atirmociclib (PF-07220060), initiating H2 2025 BID = twice daily; CDK4i = cyclin dependent kinase 4 inhibitor; CDK4/6i = cyclin dependent kinase 4/6 inhibitor; CBR = clinical benefi
Slide 24: Palazestrant as a monotherapy in 2/3L ER+/HER2- MBC
Palazestrant as a monotherapy in 2/3L ER+/HER2- metastatic breast cancer MILESTONES 2025: Pivotal Phase 3 OPERA-01 trial ongoing 2026: Announce top-line results from OPERA-01 in H2 2027: Anticipated submission of New Drug Application for potential approval of palazestrant as a monotherapy in 2/3L ER
Slide 25: Design: Phase 1/2 study of palazestrant as a monotherapy
Design: Phase 1/2 study of palazestrant as a monotherapy In patients with advanced or metastatic ER+/HER2- breast cancer Primary Objectives Pharmacokinetics Safety and Tolerability RP2D Phase 1a: Dose Escalation Phase 1b: Dose Expansion Phase 2 Objectives Efficacy Safety and Tolerability at RP2D * P
Slide 26: Safety: Phase 1/2 study of palazestrant as a monotherapy
Safety: Phase 1/2 study of palazestrant as a monotherapy Palazestrant is well-tolerated, with most TEAEs Grade 1/2 TEAEs in ≥15% of patients Palazestrant 120 mg (n = 83) Grade 1 Grade 2 Grade 3 Grade 4 All (%) Nausea 47 4 3 0 54 (65%) Vomiting 19 2 4 0 25 (30%) Fatigue 13 6 3 0 22 (27%) Neutropenia
Slide 27: Efficacy: Compelling Phase 1/2 data supports ongoing OPERA-01 trial
All 36 21 18 12 4 0 0 2/3L ±CT 23 14 13 10 2 0 0 Efficacy: Compelling Phase 1/2 data supports ongoing OPERA-01 trial 7.3 months mPFS in ESR1 mutant; 5.5 months in wild-type for EMERALD-eligible 2/3L ± CT patients* * NOTE: This analysis is the aggregation of results across independent studies. There
Slide 28: Palazestrant in the competitive landscape: best-in-class potential
Palazestrant in the competitive landscape: best-in-class potential* Palazestrant is the only CERAN/SERD with potential for approval in both ESR1 mutant and wild-type Median Progression Free Survival (months) EMERALD Control Arm(1) (n=103) Gired estrant Phase 1a/b(3) (n=17) Elacestrant (EMERALD)(2) (
Slide 29: OPERA-01 Phase 3 monotherapy trial design
OPERA-01 Phase 3 monotherapy trial designed to show superior efficacy in ESR1 mutant and ESR1 wild-type tumors For more details on this trial, please visit www.opera01study.com. BIRC = blinded independent review committee; CBR = clinical benefit rate; CDK4/6i = cyclin dependent kinase 4/6 inhibitor;
Slide 30: Planning for commercial launch of palazestrant in 2/3L ER+/HER2- MBC
Planning for commercial launch of palazestrant as a monotherapy in 2/3L ER+/HER2- MBC anticipated in 2027 Annual U.S. incidence estimated at ~40K* patients Commercial launch planning beginning in 2025 Early commercial leadership build expected to begin in 2026 Establishing manufacturing supply and d
Slide 31: OP-3136 at a glance
OP-3136 AT A GLANCE Mechanism of Action KAT6A/B inhibitor Stage of Development Phase 1 Initial Development Indication 2/3L ER+/HER2- MBC MILESTONES 2026: Anticipated initial monotherapy and combination data from the Phase 1 study 2/3L = second/third-line; ER+ = estrogen receptor positive; KAT6 = lys
Slide 32: OP-3136: Olema's KAT6 inhibitor
OP-3136: Olema’s KAT6 inhibitor* An exciting new and validated target** for the treatment of ER+/HER2- metastatic breast cancer Potent and selective against KAT6A/B Orally bioavailable with high levels of free drug exposure OP-3136 synergizes with palazestrant and CDK4/6 inhibitors in preclinical mo
Slide 33: OP-3136 mechanism of action
OP-3136 mechanism of action KAT6 is a clinically validated target1 and overexpression correlated with worse clinical outcomes in ER+ breast cancer2 KAT6 inhibition downregulates genes involved in estrogen receptor signaling and other signaling pathways3 Inhibition regulated gene expression through b
Slide 34: KAT6 validated as an active new target in breast cancer
KAT6 validated as an active new target in metastatic breast cancer* * NOTE: Incorporates publicly-available third-party data that we have not independently verified. These results should be interpreted with caution. Such third-party data has been pulled by us from publicly-available sources for supp
Slide 35: OP-3136 preclinical data demonstrated specificity for KAT6A/B
OP-3136 preclinical data demonstrated specificity for KAT6A/B OP-3136 is potent and selective against KAT6A/B Note: Olema KAT6 inhibitors discovered in collaboration with Aurigene 1 Mukohara T, et al. Inhibition of lysine acetyltransferase KAT6 in ER+ HER2- metastatic breast cancer: a phase 1 trial.
Slide 36: OP-3136 synergistic activity with palazestrant in preclinical models
OP-3136 demonstrated synergistic activity in combination with palazestrant in preclinical breast cancer models Waterfall Plot (T47D CDX Model) Palazestrant in combination with either OP-3136 or PF-8144 resulted in strong tumor regression relative to fulvestrant combinations OP-3136 and palazestrant
Slide 37: OP-3136 Phase 1 study design
OP-3136 Phase 1 study design IND cleared by FDA and Phase 1 study is recruiting patients Primary objectives: Safety and tolerability, RDE (monotherapy + combination) Secondary objectives: PK, ORR (CR + PR), CBR (CR + PR + SD ≥24 weeks), DOR PART 1: DOSE ESCALATION DL1 DL2 DL3 DL4 Mono RDE ER+/HER2-
Slide 38: Olema: a late-stage opportunity in breast cancer and beyond
Olema: a compelling late-stage opportunity in breast cancer and beyond Focused on transforming the metastatic breast cancer treatment paradigm and the potential to generate significant shareholder value by 2030 1L = frontline; 2/3L = second/third-line; CDK4/6 = cyclin dependent kinase 4/6; ESMO = Eu
Slide 39: Advancing medicines for breast cancer and beyond
— Advancing medicines for breast cancer and beyond
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