Olema Pharmaceuticals, Inc. · NASDAQ:OLMA
Olema Pharmaceuticals — Investor Presentation (August 2026)
40 slides from Olema Pharmaceuticals's investor presentation, August 2026
Slide 1: Advancing medicines for breast cancer and beyond
Corporate Overview Advancing medicines for breast cancer and beyond August 2026
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
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 2/3L MBC as a monotherapy and in 1L MBC in combination with ribociclib Progressing OP-3136, our potent and potential best-in-class KAT6 inhibitor 1L = frontline; 2/
Slide 4: The ER+/HER2- global metastatic breast cancer market presents a $20B+ opportunity
— The ER+/HER2- global metastatic breast cancer market presents a $20B+ opportunity1 The majority of all breast cancers Adjuvant ER+/ Patients3 ~200K+ are ER+/HER2-2 HER2- MBC Duration of Therapy4 Up to 5 years Global Market Potential5 $20B+ 11% ER-/HER2- 1L ER+/ Patients3 ~100K+ 9% ER+/HER2+ HER2-
Slide 5: Palazestrant has the potential to become a best-in-class, backbone endocrine therapy
— Palazestrant has the potential to become a best-in-class, backbone endocrine therapy for metastatic breast cancer Current Duration of Line Standard of Care Therapy1 Palazestrant has the right properties to succeed Low Risk Tamoxifen Up to 5 years Adjuvant Complete ER antagonism Moderate to High-Ri
Slide 6: Palazestrant monotherapy in 2/3L ER+/HER2- MBC offers our first opportunity for market entry
— Palazestrant monotherapy in 2/3L ER+/HER2- MBC offers our first opportunity for market entry in 2028 Palazestrant has the potential to become the best-in-class single agent endocrine therapy and improve upon current standard of care Differentiated Efficacy Profile Promising Safety Favorable Pharma
Slide 7: Palazestrant in combination with ribociclib has the potential to become the new standard
— Palazestrant in combination with ribociclib has the potential to become the 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 Combination Partner of Choice Differentiated Efficacy Pr
Slide 8: OP-3136 has the potential to generate further value and impact the MBC landscape
— OP-3136 has the potential to generate further value and meaningfully impact the MBC treatment landscape KAT6 is an exciting new target in breast cancer and initial results from the Phase 1 clinical study of OP-3136 are encouraging Promising Anti-Tumor Activity1 Manageable Safety1 Favorable Pharmac
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 OP-3136: KAT6 Inhibitor ER+/HER2- metastatic breast cancer Breast cancer and other solid tumors Ongoing Phase 1 study 02 evaluating OP-3136 monotherapy and combination IN COLLABORATION WITH NOVARTI
Slide 10: Value-generating catalysts advance us towards transforming the treatment paradigm
— Value-generating catalysts advance us towards our goal of transforming the treatment paradigm for metastatic breast cancer Corporate Priorities and Anticipated Milestones Q2 2026 MID 2027 2028 WELL-CAPITALIZED WITH INITIAL OP-3136 COMBINATION POTENTIAL APPROVAL AND LAUNCH ~$461M IN CASH1 DATA IN E
Slide 11: Palazestrant at a glance
AT A GLANCE • Mechanism of Action Complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) • Stage of Development Palazestrant Monotherapy: Phase 3 In Combination: Phase 3; multiple studies in Phase 1/2 • Special Designations FDA Fast Track* MILESTONES • Complete
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 Palazestrant, a CERAN/SERD, SERM/SERDs Activated ER not only degrades but also partially inactivate ER drives cancer cell growth completely i
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 Palazestrant uniquely meets Palazestrant is a potent shutting off all ER signaling optimal drug-plasma exposu
Slide 14: Palazestrant as a monotherapy in 2/3L ER+/HER2- metastatic breast cancer
MILESTONES Palazestrant as a • 2027: Announce top-line results from OPERA-01 in Q1 monotherapy in 2/3L • 2027: Anticipated submission of New Drug Application for potential approval of palazestrant as a ER+/HER2- metastatic monotherapy in 2/3L ER+/HER2-MBC and preparations for commercial launch breas
Slide 15: 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 Phase 1A: Dose Escalation Phase 1B: Dose Expansion Phase 2 300 mg Key Eligibility Criteria* • ER+/HER2- advanced breast cancer • 1–4 prior endocrine therapies for metastatic 210
Slide 16: Safety: Phase 1/2 study of palazestrant as a monotherapy
— Safety: Phase 1/2 study of palazestrant as a monotherapy Palazestrant was well-tolerated, with most TEAEs Grade 1/2 Palazestrant TEAEs in ≥15% of patients 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%) Neutropen
Slide 17: Efficacy: Phase 1/2 data supports ongoing OPERA-01 trial
— 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* Patients with ESR1 Mutation1 Patients with ESR1 Wild-Type2 All ESR1 mut 2/3L ±CT All ESR1 WT 2/3L ±CT n=36 n=23 n=39 n=21 Median PFS,
Slide 18: 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 PFS (months) in ESR1 Wild-Type Median PFS (months) in ESR1 Mutant Patients* CDK4/6i-Experienced Patients* 8.0 8.0 7.3 7.0 7.0
Slide 19: 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 PART 1: DOSE SELECTION PART 2: DOSE ASSESSMENT n = 40 Palazestrant ELIGIBILITY CRITERIA n = 195 (total 235) 120 mg • 1-2 prior lines of endocrine therapy Palazestrant • Prior treatment wi
Slide 20: 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 2028 Annual U.S. Commercial Early Establishing Anticipated U.S. market incidence launch commercial manufacturing targeted field potential of estimated at planning leadership supply and force of ~$3
Slide 21: Palazestrant in combination with ribociclib in 1L ER+/HER2- metastatic breast cancer
Palazestrant in combination with ribociclib in 1L ER+/HER2- metastatic breast cancer 1L = frontline; ER+ = estrogen receptor positive; ESMO = European Society for Medical Oncology Congress; HER2- = human epidermal growth factor receptor 2 negative;
Slide 22: Design: Phase 1b/2 study of palazestrant in combination with ribociclib
— Design: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC ER+/HER2- advanced or metastatic breast cancer (CDK4/6i-naïve or previously treated) Part 1: Dose Escalation Part 2: Dose Expansion Key eligibility criteria 120 mg Palazestrant • Women or men with ER+/HER2– ad
Slide 23: Demographics: Phase 1b/2 study of palazestrant with ribociclib
— Demographics: Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC Patient Characteristics 90 mg (N=16) 120 mg (N=56) Total (N=72) • N=72; N=56 at 120 mg; N=16 at 90 mg Median age (years) 60 61 61 Range 25-76 28-85 25–85 • 54% with visceral disease Female sex 16 (100%)
Slide 24: 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 MONALEESA-2* Palazestrant 120 mg + Ribociclib Palazestrant 90 mg + Ribociclib Letrozole + Ribociclib† (n = 56) (n = 16) (n = 334) TEAEs in ≥2
Slide 25: Median PFS of 15.5 months for all 120 mg patients
— Median PFS of 15.5 months for all 120 mg patients Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- MBC All Patients Patients with Prior CDK4/6i + ET 120 mg palazestrant + 600 mg ribociclib (n=56) 120 mg palazestrant + 600 mg ribociclib (n=40) mPFS: 15.5 months mPFS: 12.
Slide 26: Demonstrated 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 ESR1 Mutant Patients with Prior CDK4/6i ESR1 Wild-Type Patients with Prior CDK4/6i 120 mg palazestrant + 600 mg ribociclib (n=14) 120 mg palazestran
Slide 27: 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* Comparison of Median PFS (months)* in CDK4/6i Pre-Treated Patients Olema: 120 mg Palazestrant + Ribociclib 12.2 months (n = 40)
Slide 28: Design: OPERA-02 Phase 3 pivotal trial with ribociclib in 1L 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 02 ELIGIBILITY CRITERIA • ER+/HER2- MBC • Any menopausal status Palazestrant 90 mg Endpoints • No prior systemic therapy for MBC + Primary: PF
Slide 29: Palazestrant demonstrates combinability with other targeted agents
— Palazestrant demonstrates combinability with other targeted agents Working to establish palazestrant as the potential combination agent of choice in breast cancer DOSE ESCALATION DOSE EXPANSION Palazestrant ER+/HER2- MBC 90 mg Palazestrant Atirmociclib (CDK4/6i naïve or 60 mg + 300 mg BID + previo
Slide 30: OP-3136 at a glance
AT A GLANCE • Mechanism of Action KAT6A/B inhibitor • Stage of Development Phase 1 OP-3136 • Initial Development Indication 2/3L ER+/HER2- MBC MILESTONES • May 2026: Announced CTCSA with Bayer to combine OP-3136 with darolutamide in MCRPC; combo to initiate in Q4 2026 • ASCO 2026: Presented initial
Slide 31: OP-3136: Olema's KAT6 inhibitor
— OP-3136: Olema’s KAT6 inhibitor* An exciting new and validated target** for the treatment of ER+/HER2- MBC and beyond 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 models1,
Slide 32: OP-3136 mechanism of action
— OP-3136 mechanism of action KAT6 acetylates chromatin, OP-136 inhibits KAT6, stopping acetylation of histones and enabling transcription and proliferation preventing transcription of proliferation-associated genes • KAT6 is a clinically validated target1 and overexpression correlated with worse cl
Slide 33: KAT6 validated as an active new target in metastatic breast cancer
— KAT6 validated as an active new target in metastatic breast cancer* PF-8144 Median PFS with ET1 First-in-human clinical proof of concept for KAT6 inhibitor 15 13.7 from Pfizer has important implications: 12 10.7 10.9 10.7 • Validates KAT6 as an active new target for the treatment 9 7.3 of metastat
Slide 34: 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 Biochemical Potency and Selectivity IC50 (nM) OP-3136 PF-8144 • OP-3136 showed >500-fold selectivity over other KAT6A 9 7 essential KAT family members: KAT5 and KAT8 KAT6B 1 1 • OP-3136 ha
Slide 35: OP-3136 synergistic activity with palazestrant in preclinical models
— OP-3136 demonstrated synergistic activity in combination with palazestrant in preclinical breast cancer models1 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 palaze
Slide 36: OP-3136 Phase 1 study design
— OP-3136 Phase 1 study design Enrollment in palazestrant and fulvestrant combination arms ongoing, data expected in mid-2027; darolutamide combination expected to initiate in Q4 2026 PART 1: DOSE ESCALATION PART 1A DL5+ Mono RDE (n=32) PART 2: DOSE EXPANSION DL4 PART 1B OP-3136 + Fulvestrant MBC DL
Slide 37: OP-3136 monotherapy was well tolerated with no DLTs observed
— OP-3136 monotherapy was well tolerated with no DLTs observed across evaluated dose levels up to 45 mg daily1 Preliminary safety from Part 1A of the Phase 1 study of OP-3136 in multiple solid tumor types TRAE Any Grade, n (%) Grade 3, n (%) • Most TRAEs were grade 1 or 2; no grade 4 or 5 TRAEs were
Slide 38: OP-3136 monotherapy demonstrated tumor shrinkage across tumor types
— OP-3136 monotherapy demonstrated tumor shrinkage in over 2/3 of patients across dose levels in various advanced solid tumor types1 Durable responses and evidence of on-target engagement reinforce best-in-class potential • Among 19 response-evaluable patients Responses across dose levels and tumor
Slide 39: 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 Palazestrant OP-3136 • Highly differentiated with activity in ESR1 mutant and wild-type
Slide 40: Thank You
Thank Youmedicines Advancing for breast cancer and beyond
Olema Pharmaceuticals — Investor Presentation (August 2026) on 6ix