Olema Pharmaceuticals, Inc. · NASDAQ:OLMA
Olema Pharmaceuticals — Investor Presentation (August 2025)
37 slides from Olema Pharmaceuticals's investor presentation, Aug 11, 2025
Slide 1: Advancing medicines for breast cancer and beyond: Corporate Overview
Advancing medicines for breast cancer and beyond Corporate Overview August 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 plus ribociclib could become new standard of care in 1L ER+/HER2- 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. 2 Data c
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: potent, selective, synergistic with palazestrant
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 Planned 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 initiating in Q3 2025; multiple studies in Phase 1/2 Special Designations FDA Fast Track* 2025
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 UPCOMING MILESTONES 2025: Initiate pivotal Phase 3 OPERA-02 trial in Q3 2025: Present mature Phase 1b/2 palazestrant + ribociclib data at ESMO 2028: Anticipated announcement of top-line results from OPERA-02 2029: P
Slide 15: Design: Phase 1b/2 study of palazestrant plus 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 plus ribociclib
Demographics: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC N=62; N=56 at 120 mg 58% with visceral disease 68% with measurable disease 77% received prior endocrine therapy in advanced setting 74% received prior CDK4/6i + ET 34 (55%) patients received 1 prior line o
Slide 17: Safety: Phase 1b/2 study of palazestrant plus ribociclib
Safety: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Well tolerated with no DLTs; safety profile consistent with ribociclib + ET Palazestrant + Ribociclib** MONALEESA-2* Letrozole + Ribociclib† TEAEs in ≥25% of patients (n = 62) (n = 334) All grades‡ Grade 3 Grade
Slide 18: Efficacy as of February 18, 2025 cutoff: palazestrant plus ribociclib
Efficacy as of February 18, 2025 cutoff date: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Data cutoff date: February 18, 2025 * Follow up was calculated from first dose date to data cutoff date regardless of disease progression status. CDK4/6i = cyclin-dependent
Slide 19: Efficacy comparison in 2/3L patients vs. competitive landscape
Efficacy comparison in 2/3L patients vs. competitive landscape MAINTAIN study of ribociclib plus ET after CDK4/6i progression serves as best clinical benchmark* Interim efficacy signals for palazestrant (120 mg) in combination with ribociclib (600 mg) * NOTE: This analysis is the aggregation of resu
Slide 20: Design: OPERA-02 Phase 3 trial of palazestrant plus ribociclib
Design: OPERA-02 Phase 3 pivotal trial of palazestrant in combination with ribociclib in 1L ER+/HER2- MBC ~1,000-patient trial vs. standard of care; initiation in 2025 Endpoints Primary: PFS (Investigator) Secondary : OS (Key) PFS (BIRC) ORR/CBR/DOR (BIRC, Investigator) Safety PK Health-related PROs
Slide 21: 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 22: Palazestrant as a monotherapy in 2/3L ER+/HER2- MBC
Palazestrant as a monotherapy in 2/3L ER+/HER2- metastatic breast cancer UPCOMING MILESTONES 2025: Advance patient accrual in pivotal Phase 3 OPERA-01 trial 2026: Announce top-line results from OPERA-01 in H2 2027: Anticipated submission of New Drug Application for potential approval of palazestrant
Slide 23: 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 24: 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 25: Efficacy: 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 26: 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 27: 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 28: Planning for commercial launch of palazestrant in 2/3L 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 29: 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 UPCOMING MILESTONES 2026: Anticipated initial monotherapy and combination data from the Phase 1 study 2/3L = second/third-line; ER+ = estrogen receptor positive; K
Slide 30: 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 31: 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 32: 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 33: 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 34: 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 35: 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 36: 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 37: Advancing medicines for breast cancer and beyond
— Advancing medicines for breast cancer and beyond
Olema Pharmaceuticals — Investor Presentation (August 2025) on 6ix