Olema Pharmaceuticals, Inc. · NASDAQ:OLMA
Olema Pharmaceuticals — Investor Presentation (November 2022)
36 slides from Olema Pharmaceuticals's investor presentation, November 2022
Slide 1: Improving the lives of women with breast cancer
Improving the lives of women with breast cancer November 2022 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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 statements. Such forwar
Slide 3: Aspire to Improve Outcomes for Women Living with Breast Cancer
Aspire to Improve Outcomes for Women Living with Breast Cancer Lead Program, OP-1250*, is an Oral, Small Molecule Complete Estrogen Receptor Antagonist (CERAN) Designed to completely shut-down estrogen pathways in women with ER+/HER- metastatic breast cancer. 1st indication, for 2L/3L+ therapy, coul
Slide 4: Highly Encouraging Preliminary Phase 1/2 Clinical Results
Highly Encouraging Preliminary Phase 1/2 Clinical Results • Over 125 patients treated to date with OP-1250 ‒ Data presented at ENA 2022* across 68 patients at doses of 60 mg and 120 mg • OP-1250 is well tolerated with attractive PK, high drug exposures and strong anti-tumor activity ‒ Majority of TR
Slide 5: Rapidly Advancing OP-1250 into Pivotal Studies Beginning in 2023
Rapidly Advancing OP-1250 into Pivotal Studies Beginning in 2023 Evaluating OP-1250 across a range of ER cohorts in monotherapy and combination trials Preclinical Phase I Phase II Phase III Clinical Collaboration ER+/HER2- Metastatic Breast Cancer 2/3 Line Monotherapy (with and without CNS metastase
Slide 6: OP-1250: Best-in-Class Potential for ER+/HER2- Breast Cancer
OP-1250: Best-in-Class Potential for ER+/HER2- Breast Cancer Clinical dataset with over 125 patients treated with OP-1250 supports opportunity in both monotherapy and combination settings for patients with ER+/HER2- advanced metastatic breast cancer Complete ER CNS Antagonism Penetration Attractive
Slide 7: Breast Cancer is the Second Most Common Diagnosed Cancer Worldwide
Breast Cancer is the Second Most Common Diagnosed Cancer Worldwide Estimated $20B market for endocrine therapies (ET) and targeted agents for ER+ breast cancer In 2022, approximately Majority of All Breast Cancers Current Endocrine Therapy 288K express Estrogen Receptor (ER+) Options Women in the U.
Slide 8: Endocrine Therapy Remains the Backbone of ER+ Breast Cancer Treatment
Endocrine Therapy Remains the Backbone of ER+ Breast Cancer Treatment OP-1250 has the potential to improve upon existing treatments to become the best-in-class ET Illustrative Examples of ER+/HER2- Breast Cancer Treatment Options 2nd/3rd LINE +: ~ 6 months of therapy Relapsed or Oral Fulvestrant PI3
Slide 9: Significant Opportunity Across All Segments of Therapy in ER+/HER2- Breast Cancer
Significant Opportunity Across All Segments of Therapy in ER+/HER2- Breast Cancer = 10K HR+ / HER2-1 HR+ / HER2+2 LINE OF HER2+ 2L/3L+ 1L High-Risk Adjuvant Early Breast Cancer THERAPY w/ CNS Mets PATIENTS ~150K ~115K ~75K ~285K+ ~10K DURATION ~6 ~24 Up to 5 Up to 5 ~12 OF THERAPY3 MONTHS MONTHS YEA
Slide 10: Landscape is Competitive, But Not All SERDs are Created Equal
Landscape is Competitive, But Not All SERDs are Created Equal OP-1250 Has a Promising Profile vs. Competition OP-1250 Giredestrant Elacestrant Camizestrant ARV-471 Imlunestrant Lasofoxifene Amcenestrant Antagonism* SERD (Degrader)* Half Life ~8 days ~1-2 days ~1-2 days ~12 hours ~28 hours 25-30 hour
Slide 11: Understanding OP-1250's Mechanism of Action
Understanding OP-1250’s Mechanism of Action 11
Slide 12: OP-1250: a Complete Estrogen Receptor ANtagonist (CERAN)
OP-1250: a Complete Estrogen Receptor ANtagonist (CERAN) OP-1250 potently and completely inactivates the Estrogen Receptor (ER), blocks ER-driven transcriptional activity, inhibits ER-driven breast cancer cell growth, and strongly induces degradation of ER Partial Antagonists Have a Short Duration o
Slide 13: Both CERAN/SERDs and SERM/SERDs Are Strong Degraders of ERα
Both CERAN/SERDs and SERM/SERDs Are Strong Degraders of ER𝝰 MCF-7 MCF-7 BT-474 HCC-1500 HCC-1500 CAMA-1 ECC-1 BT-474 CAMA-1 ECC-1 partial strong partial strong partial strong partial strong partial strong AF1 AF1 partial AF1 strong AF1 AF1 AF1 partial AF1 strong AF1 AF1AF1 strong partial AF1AF1 AF1
Slide 14: CERAN/SERDs Inactivate Both AF1 & AF2 Activity, While SERM/SERDs Only Inactivate AF2
CERAN/SERDs Inactivate Both AF1 & AF2 Activity, While SERM/SERDs Only Inactivate AF2 Agonist Mode Agonist Mode (No (No Estrogen) Estrogen) Antagonist Mode Agonist Mode (+(+ Estrogen) Estrogen) 120 Emax Emax 140 Emax Emax (%E2) (%E2) pIC50 pIC50 (%E2) (%E2) (%E2) Activity (%E2) 100 Lasofoxifene Lasof
Slide 15: Xenograft Efficacy Studies: OP-1250 vs. Fulvestrant
Xenograft Efficacy Studies: OP-1250 vs. Fulvestrant OP-1250 Demonstrates Tumor Shrinkage Across Multiple Xenograft Models MCF-7 (HER2/neu) HCC1500 ST941 HCI-013 15
Slide 16: OP-1250 Has Demonstrated Activity in CNS Metastases Models
OP-1250 Has Demonstrated Activity in CNS Metastases Models AACR 2021: Intracranial Breast Cancer Brain Metastases Xenograft Study 10 mg/kg OP-1250 is superior to tamoxifen, fulvestrant and ovariectomy in shrinking mutant ESR1-Y537S tumors in an intracranial model of ER+ breast cancer brain metastasi
Slide 17: Phase 1/2 Clinical Update from ENA 2022
Phase 1/2 Clinical Update from ENA 2022 17
Slide 18: OP-1250-001 First-in-Human Phase 1/2 Monotherapy Trial: Study Design
OP-1250-001 First-in-Human Phase 1/2 Monotherapy Trial: Study Design Phase 1a Dose Escalation Phase 1b Dose Expansion Phase 2 Cohorts 300 mg Patients with measurable (n=50) disease* 210 mg 60 mg (n=25) Patients with non- 150 mg RP2D (n=15) measurable disease* 120 mg 120 mg (n=25) 90 mg Patients with
Slide 19: OP-1250 Phase 1/2 Dose Expansion
OP-1250 Phase 1/2 Dose Expansion Patients Received Extensive Prior Therapies 60 mg 120 mg Totala Patient characteristics (n=33) (n=35) (N=68) • 69% of patients received Age, median, years 61 61 61 2 or more prior lines of Range 30–81 39–77 30–81 therapy in the advanced ECOG performance status, n (%)
Slide 20: Dose-Proportional PK with Optimal Steady-State Plasma Concentrations
Dose-Proportional PK with Optimal Steady-State Plasma Concentrations OP-1250 Steady-state Plasma Concentration-time Profiles • High oral bioavailability and steady-state plasma levels with minimal peak-to-trough variability allowing complete inhibition of the Mean (+SD) Plasma OP-1250 ER for the ful
Slide 21: OP-1250 Phase 1/2 Monotherapy Dose Expansion Safety Data
OP-1250 Phase 1/2 Monotherapy Dose Expansion Safety Data Well Tolerated at Both 60 mg and 120 mg Doses TRAEs in ≥15% 60 mg 120 mg Total of Patients in Phase 1a/1b (n=33) (n=35) (60 mg & 120 mg, n=68) Grade 1 Grade 2 >Grade 3 Grade 1 Grade 2 >Grade 3 Grade 1/2 >Grade 3 Any TRAE 9 7 1 18 3 6 37 (54%)
Slide 22: OP-1250 Phase 1/2 Dose Expansion: Meaningful Anti-Tumor Activity
OP-1250 Phase 1/2 Dose Expansion Meaningful Anti-Tumor Activity 100 85 Dose Cohort: 80 80 60 mg 120 mg 60 55 Ongoing Best Change From Baseline (%) 40 39 41% of patients had a reduction in target lesion 35 29 25 23 23 22 22 21 21 20 20 18 18 20 14 13 13 13 11 10 10 8 SDa SDa 4 4 SD SD PD SD PD SD PD
Slide 23: OP-1250 Phase 1/2 Dose Expansion: Durable Clinical Benefit
OP-1250 Phase 1/2 Dose Expansion Clear Efficacy and Durable Clinical Benefit in Heavily Pretreated Population Treatment Duration (weeks) and Response by Dose in All Patients (N=68) as of Sept 2, 2022 • Across all patients: 6 PRs out of 57 response-evaluable patients (4 cPRs and 2 uPRs*) 60 mg • In E
Slide 24: Case Study 1: Confirmed Partial Response in Late-Line Patient
Case Study 1: Confirmed Partial Response in Late-Line Patient with Peritoneal Carcinomatosis and Bone Metastasis; Lymph Node Lesion Normalized and Resolution of Peritoneal Stranding and Ascites 41-year-old female Baseline Cycle 5 120 mg OP-1250 QD lymph nodes Peritoneal Confirmed Partial Response Ma
Slide 25: Case Study 2: Confirmed Partial Response with Multiple Liver Metastasis
Case Study 2: Confirmed Partial Response in Late-Line Patient with Multiple Liver Metastasis 61-year-old female Baseline Cycle 7 60 mg OP-1250 QD Confirmed Partial Response Maintained ≥12 months Right liver lobe lesion Prior Therapy in Advanced / Metastatic Setting CDK4/6i: • Ribociclib Endocrine Th
Slide 26: OP-1250 Phase 1/2 Monotherapy Dose Expansion Summary
OP-1250 Phase 1/2 Monotherapy Dose Expansion Summary OP-1250 is a complete ER-antagonist with attractive PK, high drug exposures and a long-half life Heavily Pre-treated Patients Best-in-Class Emerging Profile 82% of patients had visceral disease at baseline 84% of TRAEs were Grade 1 / 2 in severity
Slide 27: Ongoing Phase 1/2 Combination Studies
Ongoing Phase 1/2 Combination Studies 27
Slide 28: Phase 1b Combination Study with Palbociclib: Study Design
Phase 1b Combination Study with Palbociclib: Study Design Initiated January 2022 Dose Escalation Dose Expansion 120 mg Palbociclib RP2D OP-1250 + OP-1250 90 mg + 125 mg Palbociclib 125 mg 60 mg • 3+3 design 30 mg • N=12-18 patients • N=12-18 patients Primary objectives: Pharmacokinetics, safety and
Slide 29: Phase 1b Combination Study with Ribociclib and Alpelisib
Phase 1b Combination Study with Ribociclib and Alpelisib Initiated Q3 2022 Dose Escalation Dose Expansion 120 mg 1L+ ER+ MBC OP-1250 (CDK4/6 naïve 90 mg Ribociclib RP2D OP-1250 + or previously + 600 mg Ribociclib 600 mg 60 mg treated) 30 mg • N=30 patients • 3+3 design 120 mg OP-1250 Patients with 9
Slide 30: Rapidly Advancing Toward Phase 3
Rapidly Advancing Toward Phase 3 30
Slide 31: Key Learnings From Recent Pivotal Readouts Impact Study Design for OP-1250
Key Learnings From Recent Pivotal Readouts Impact Study Design for OP-1250 Pharmacology and Trial Design Negatively Impacted Trial Outcomes SABCS’21: EMERALD Q2’22: acelERA Q2’22: AMEERA-3 Q3’22: AMEERA-5 Elacestrant Giredestrant Amcenestrant Amcenestrant MOA: SERM/SERD MOA: CERAN MOA: CERAN MOA: CE
Slide 32: EMERALD Results Validate Opportunity in 2L+ Setting for OP-1250
Key Learnings From Recent Pivotal Readouts Impact Study Design for OP-1250 EMERALD Results Validate Opportunity in 2L+ Setting for OP-1250 • EMERALD study demonstrated that elacestrant, a SERM/SERD, could improve upon standard of care in 2L+ patients ~40% of patients are endocrine resistant and • Ab
Slide 33: Rapidly Advancing OP-1250 Toward Pivotal Phase Studies
Rapidly Advancing OP-1250 Toward Pivotal Phase 3 Studies Dose Range of 30 mg to 300 mg Phase 1a Dose Escalation Completed n=42 RP2D Selection Dose Expansion at 60 mg and 120 mg Phase 1b Dose Expansion Completed Enrollment n=56 Monotherapy Measurable Completed Enrollment n=50 Disease (incl. P1b patie
Slide 34: Developing a Potential Best-in-Class Agent to Improve Breast Cancer Outcomes
Developing a Potential Best-in-Class Agent to Improve Breast Cancer Outcomes OP-1250 completely blocks transcriptional activity in both wild-type and mutant ER with highly favorable PK Highly differentiated program amongst a competitive new class of compounds Demonstrated combinability with CDK 4/6
Slide 35: Delivering on Value Creating Milestones
Delivering on Value Creating Milestones H1 2022 Q4 2022 2023 Initiated Phase 1b Presented initial Present additional combination with P1 / 2 monotherapy monotherapy and palbociclib expansion data combination data ✓ ✓ ✓ V Q3 2022 Q4 2022 Mid-2023 Initiated Phase 1b study Present initial Initiate pivo
Slide 36: Investor Relations / Media / Business Development / Careers
Investor Relations Media Business Development Careers [email protected] [email protected] [email protected] [email protected] 36
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