Slide 1: Enhancing the Lives of Patients with Heme Malignancies
Enhancing the Lives of Patients with Heme Malignancies Corporate Presentation November 2023
Slide 2: Forward-Looking Statements and Safe Harbor
Forward-Looking Statements and Safe Harbor Except for the historical information contained herein, this presentation contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements
Slide 3: Geron's Compelling Commercial Value Proposition
Geron’s Compelling Commercial Value Proposition Transforming the Treatment of Heme Malignancies • Imetelstat poised to become a highly differentiated standard of care in lower risk myelodysplastic syndromes (LR MDS)* and relapsed/refractory myelofibrosis (R/R MF) patients ◦ LR MDS Phase 3: Unprecede
Slide 4: Significant Opportunity for Value Creation with First-in-Class Telomerase Inhibitor
Significant Opportunity for Value Creation with First-in-Class Telomerase Inhibitor 2025+ 2025 Expected Phase 3 Final 2024 Analysis in R/R MF 2023 + Expected Phase 3 Potential Additional Interim Analysis Indications US/EU Regulatory Expected US/EU TD in R/R MF Filings Completed • Potential for data
Slide 5: Total Addressable Market for LR MDS and R/R MF >$7B by 2033
Total Addressable Market (TAM) for LR MDS and R/R MF >$7B by 2033 (US/EU4/UK)* Driving to establish imetelstat as standard of care in LR MDS and R/R MF Potential LR MDS Patient Population Potential MF Patient Population ESA Ineligible (RS+ve / RS-ve) JAKi R/R ESA R/R RS+ve ESA R/R RS-ve Become part
Slide 6: Exploring the Broad Potential of Imetelstat and Telomerase Inhibition
Exploring the Broad Potential of Imetelstat and Telomerase Inhibition Indications Discovery Preclinical Phase 1 Phase 2 Phase 3 LR MDS PDUFA: IMerge June 16, 2024 Single Agent R/R MF IMpactMF Single Agent Frontline MF IMproveMF Combination Therapy R/R AML & HR MDS IMpress Single Agent R/R AML TELOME
Slide 7: Imetelstat in Lower Risk MDS
Imetelstat in Lower Risk MDS* U.S. NDA accepted for review by FDA in August 2023; PDUFA target action date of June 16, 2024* *Imetelstat is currently under regulatory review in the U.S. and EU for the treatment of transfusion-dependent anemia in adult patients with low- to intermediate-1 risk myelod
Slide 8: Lower Risk MDS Patient Experience
Lower Risk MDS Patient Experience Frequent transfusions, transfusion dependence, poor quality of life, shortened survival Diagnosis Median age ~70 years Majority treated under Medicare Part B (US) Treat Symptomatic Anemia Lengthy Office Visits Typically blood transfusions, ESAs and in some cases wit
Slide 9: IMerge Phase 3
IMerge Phase 3 Unprecedented durability of transfusion independence along with broad clinical benefit across MDS subgroups and favorable fatigue PROs 9
Slide 10: Compelling Imetelstat Profile from IMerge Phase 3
Compelling Imetelstat Profile from IMerge Phase 3 Durable transfusion Highly statistically significant (p<0.001) and clinically meaningful improvements for imetelstat in 8-week TI, 16-week TI and 24-week TI independence versus placebo Highly statistically significant (p<0.001) and clinically meaning
Slide 11: Significant Long-Term Duration of TI Observed With Imetelstat vs Placebo
Significant Long-Term Duration of TI Observed With Imetelstat vs Placebo P<0.001 50.0 45.0 P<0.001 39.8% P<0.001 Statistically significant 40.0 Represents 63.6% of and clinically meaningful Percentage of patients (%) >24-week TI imetelstat 35.0 responders efficacy with robust 8- 31.4% wk, 16-wk, 24-
Slide 12: Median Duration of 8-Week TI
Median Duration of 8-Week TI* Highly statistically significant and clinically meaningful durability of TI 1 100% Imetelstat Placebo HR P-value* Percentage of patients with 8-week TI 0.9 90% 0.8 80% Median TI duration (weeks)* 51.6 13.3 0.23 <0.001 95% CI 26.9, 83.9 8.0, 24.9 0.7 70% 0.6 60% 0.5 50%
Slide 13: Mean Change in Hemoglobin Levels for All Imetelstat Patients
Mean Change in Hemoglobin Levels for All Imetelstat Patients Highly statistically significant increase in hemoglobin levels over time for imetelstat patients 5 8-week TI Imetelstat Placebo P<0.001 4 responders* n=47 n=9 Median Hgb rise 3.6 0.8 Mean Change in HGB 3 (g/dL) (g/dL; +/- SE) Median Hgb pe
Slide 14: Mean Change in RBC Transfusion Units Over Time
Mean Change in RBC Transfusion Units Over Time Statistically significant decrease in number of RBC units transfused 1 P=0.042 Mean Change in RBC Transfusion 0 -1 (units; +/- SE) -2 -3 -4 -5 1 9 17 25 33 41 49 57 65 73 81 89 97 Weeks Imetelstat Placebo Number of patients Imetelstat 115 104 95 76 60 5
Slide 15: Statistically Significant 8-week TI Rates Across All Subgroups
Statistically Significant 8-week TI Rates (p<0.05) and Comparable Magnitude of Clinical Benefit Across All Subgroups Imetelstat, Placebo, % Difference P-value* -20 -10 0 10 20 30 40 50 60 n (%) n (%) (95% CI) Overall 47/118 (39.8) 9/60 (15.0) 24.8 (9.9, 36.9) <0.001 WHO category^ RS+ 33/73 (45.2) 7/
Slide 16: Durability of RBC-TI for 8-Week TI Responders Across Key LR MDS Subgroups
Durability of RBC-TI for 8-Week TI Responders Across Key LR MDS Subgroups Imetelstat Median, Placebo Median, Hazard Ratio P-value weeks (95% CI) weeks (95% CI) (95% CI) Overall 51.6 (26.9–83.9) 13.3 (8.0–24.9) 0.23 (0.09–0.57) <0.001 WHO category RS+ 46.9 (25.9–83.9) 16.9 (8.0–24.9) 0.32 (0.11–0.95)
Slide 17: More Patients With Imetelstat Had ≥50% VAF Reduction
More Patients Treated With Imetelstat vs Placebo Had ≥50% VAF Reduction in SF3B1, TET2, DNMT3A, and ASXL1 Mutations Imetelstat P=NS Patients with ≥50% VAF reduction, % 40 Placebo P=NS P=0.001 30 20 P=NS 10 29.5 2.6 34.3 8.3 11.1 0 40.0 16.7 0 SF3B1 TET2 DNMT3A ASXL1 23/78 1/38 12/35 1/12 2/18 0/8 4/
Slide 18: VAF Reduction Correlated With Longer TI Duration and Increases in Hgb
VAF Reduction Correlated With Longer TI Duration and Increases in Hgb Levels in Patients Treated With Imetelstat VAF reduction observed in SF3B1, TET2, and DNMT3A Longest RBC-TI Duration vs Maximum Reduction in SF3B1 (left), TET2 (middle), and DNMT3A (right) VAF Fit Imetelstat (N=78) Fit Imetelstat
Slide 19: Sustained Meaningful Improvement in FACIT-Fatigue Score With Imetelstat vs Placebo
Sustained Meaningful Improvement in FACIT-Fatigue Score With Imetelstat vs Placebo Imetelstat-treated patients quicker to report sustained meaningful Higher percentage of imetelstat-treated patients reporting any improvement in fatigue than those receiving placebo episode of sustained meaningful imp
Slide 20: Association of Improvement in Fatigue and Clinical Responses
Association of Improvement in Fatigue and Clinical Responses With Imetelstat vs Placebo Higher proportion of imetelstat-treated patients with 8-week RBC- Majority of the 8-week RBC-TI responders in imetelstat group TI, 24-week RBC-TI, and HI-E response (per IWG 2006) reported consistently had sustai
Slide 21: Consistent With Prior Clinical Experience, the Most Common AEs Were Hematologic
Consistent With Prior Clinical Experience, the Most Common AEs Were Hematologic • Grade 3–4 thrombocytopenia AEs (≥10% of Imetelstat (N=118) Placebo (N=59) and neutropenia were the most patients), n (%) Any Grade Grade 3–4 Any Grade Grade 3–4 Hematologic frequently reported AEs, most often Thrombocy
Slide 22: Grade 3–4 Cytopenias Were of Short Duration and Manageable
Grade 3–4 Cytopenias Were of Short Duration and Manageable Imetelstat Placebo • Median duration of grade 3–4 Grade 3–4 Cytopenias Per Lab Value (N=118) (N=59) thrombocytopenia and neutropenia was Thrombocytopenia <2 weeks and >80% of events were Median duration, weeks (range) 1.4 (0.1–12.6) 2.0 (0.3
Slide 23: Imetelstat AEs Were Manageable With Dose Modifications
Imetelstat AEs Were Manageable With Dose Modifications Imetelstat Placebo • Most AEs leading to dose modifications Dose Modifications, n (%) (N=118) (N=59) were grade 3–4 neutropenia and thrombocytopenia Patients with any dose delay due to TEAE 81 (68.6) 14 (23.7) • Although 74% of patients treated
Slide 24: Market Opportunity in LR MDS
Market Opportunity in LR MDS 24
Slide 25: Treatment Landscape for LR MDS
Treatment Landscape for LR MDS • Majority of the patients Continuing unmet need presents significant opportunity for imetelstat with symptomatic anemia are treated with ESAs and most will fail treatment in ~2 years* HR MDS Lower Risk MDS (~70%) • Lower risk MDS Complex represents a significant prese
Slide 26: IMerge Phase 3 Data Received Favorably by Practicing Hematologists
IMerge Phase 3 Data Received Favorably by Practicing Hematologists Across U.S./EU Key Markets Key attributes of imetelstat resonated strongly with community and academic hematologists Totality of Meaningful Durability Clinical Benefit of Response EFFICACY Compelling TI rates across RS 16- and 24-wee
Slide 27: Hematologists' Feedback Confirms Imetelstat Opportunity Across RS Subtypes
Hematologists’ Feedback Confirms Imetelstat Opportunity Across RS Subtypes and High Transfusion Burden Patients Imetelstat’s novel mechanism of action Physicians view imetelstat’s novel/first-in-class MOA together with its (MOA) is seen as a key driver for future durability of response as highly com
Slide 28: LR MDS Expected Future Market Evolution (U.S.)
LR MDS Expected Future Market Evolution (U.S.): Imetelstat likely to become new SOC in second line and provide important new option for frontline ESA-ineligible patients Expected Second Expected Second Expected Frontline Usage Expected Second Expected Second Expected Frontline Usage Line Usage Line
Slide 29: Significant Progress On Imetelstat US Launch Preparations
Significant Progress On Imetelstat US Launch Preparations Commercial and medical affairs teams fully-onboarded; field reimbursement and sales onboarding expected 1Q24 Prepare Imetelstat Prepare the Market Prepare Geron REGULATORY SUBMISSIONS & TRADEMARK MARKET INSIGHTS GENERATION COMMERCIAL ORGANIZA
Slide 30: Imetelstat in Relapsed/Refractory MF
Imetelstat in Relapsed/Refractory MF Evaluating potential improved survival 30
Slide 31: Expected MF Market Evolution and Imetelstat Opportunity
Expected MF Market Evolution and Imetelstat Opportunity We expect the future MF market to expand significantly with potential approvals of JAKi-based combination regimens and treatments that address anemia in MF patients. Agents in development today have primary endpoints focused on addressing splee
Slide 32: First and Only Phase 3 Trial in MF with OS as Primary Endpoint
First and Only Phase 3 Trial in MF with OS as Primary Endpoint Actively enrolling global trial • Sites across United States, South America, Europe, Australia and Asia ClincialTrials.gov • Expect 50% enrollment by EOY 2023 (NCT0457615) Planned analyses Primary Endpoint: • Interim Analysis expected in
Slide 33: Phase 3 IMpactMF Trial in Relapsed/Refractory MF
Phase 3 IMpactMF Trial in Relapsed/Refractory MF ClincialTrials.gov (NCT0457615) Trial is >40% enrolled and actively enrolling patients now Imetelstat Primary Endpoint: Intermediate-2 9.4mg/kg every 3 weeks • Overall survival (OS) or High-Risk MF (n ~214) Relapsed/Refractory to 2:1 Key Secondary End
Slide 34: Median OS in IMbark Phase 2 Compares Favorably to Historical Controls
Median OS in IMbark Phase 2 Compares Favorably to Historical Controls ClincialTrials.gov (NCT02426086) Improvement in overall Imetelstat 9.4 mg/kg survival (OS) observed for JAKi relapsed/refractory MF patients in IMbark Phase 2 • 14 – 16 mos median OS for 29.9 mos historical controls for JAKi relap
Slide 35: Median OS More than Double vs BAT Treatment in RWD Study
Median OS More than Double vs BAT Treatment in RWD Study Evaluating imetelstat vs BAT in IMbark Phase 2 data compared to real world data (RWD) from a closely-matched JAKi relapsed/refractory MF cohort of patients at the Moffitt Cancer Center who had discontinued ruxolitinib and were subsequently tre
Slide 36: Manageable Imetelstat Safety Results in IMbark Phase 2
Manageable Imetelstat Safety Results in IMbark Phase 2 Limited clinical consequences of 9.4 mg/kg (n=59) reversible, on target cytopenias n (%) All Grades Grade ≥ 3 ClincialTrials.gov (NCT02426086) • Thrombocytopenia and neutropenia Hematologic (≥10% in either arm)§ characterization: Thrombocytopeni
Slide 37: Financials
Financials 37
Slide 38: Financial Resources to Support Potential Commercial Launch of Imetelstat
Financial Resources to Support Potential Commercial Launch of Imetelstat Financial resources Up to ~$48M ~$382M $210M expected to support Q3 2023 Cash and 2023 expected projected level of operating marketable GAAP operating expenses securities as of 9/30/23 expenses operations through third quarter
Slide 39: Significant Opportunity for Value Creation with First-in-Class Telomerase Inhibitor
Significant Opportunity for Value Creation with First-in-Class Telomerase Inhibitor 2025+ 2025 Expected Phase 3 Final 2024 Analysis in R/R MF 2023 + Expected Phase 3 Potential Additional Interim Analysis Indications US/EU Regulatory Expected US/EU TD in R/R MF Filings Completed • Potential for data
Slide 40: Thank you!
Thank you! Contact: Investor Relations ir@geron.com
Slide 41: References
References Slide # Reference Slide # Reference Slide # Reference Slide # Reference 3, 4, 10, Zeidan et al, ASCO 2023; Platzbecker et al, EHA 2023; 26, 27 Geron Market Research, US/EU3 Jan 2023 65 Steensma et al, JCO 2020; Platzbecker et al, ASH 83 Bruedigam et al, Cell Stem Cell 2014; 39, 44, 45 San
Slide 42: Appendix 1
Appendix 1* Additional information and data from IMerge Phase 3 *To view and/or download Geron scientific and medical presentations and publications please visit: 42 https://www.geron.com/research-and-development/publications/
Slide 43: IMerge Phase 3 Trial Design & Patient Population
IMerge Phase 3 Trial Design & Patient Population 43
Slide 44: Phase 3 IMerge Trial Design
Phase 3 IMerge Trial Design Phase 3 Double blind, randomized Imetelstat 118 clinical sites in 17 countries 7.5mg/kg every 4 weeks Primary Endpoint: (n=118) 8-week RBC Transfusion Independence (TI)** Patient Population ( ITT n=178): R Stratification: A • Transfusion burden (4 - 6 vs >6 units) Key Sec
Slide 45: Key Trial Metrics
Key Trial Metrics Balanced time on study and treatment time between two arms Imetelstat Placebo (n=118) (n=60) Median time on study, months (range) 19.5 (1.4-36.2) 17.5 (0.7-34.3) Median time on treatment, months (range) 7.8 (0.03-32.5) 6.5 (0.03-26.7) Median time on treatment for 8-week TI responde
Slide 46: Baseline Patient Demographics and Disease Characteristics
Baseline Patient Demographics and Disease Characteristics Comparable between both arms Imetelstat Placebo (n=118) (n=60) Age, years, median (range) 71.5 (44-87) 73.0 (39-85) WHO 2001 category, n (%) RS+ 73 (61.9) 37 (61.7) RS- 44 (37.3) 23 (38.3) RBC transfusion burden, units/8 weeks, median (range)
Slide 47: Risk Categorization by IPSS-R or IPSS-M Was Consistent With Baseline IPSS Risk
Risk Categorization by IPSS-R or IPSS-M Was Consistent With Baseline IPSS Risk Imetelstat Placebo Total Imetelstat Placebo Total (N=118) (N=60) (N=178) (N=103) (N=52) (N=155) IPSS-R, n (%)a IPSS-M, n (%)b Very Low 3 (2.5) 2 (3.3) 5 (2.8) Very Low 4 (3.9) 0 4 (2.6) Low 87 (73.7) 46 (76.7) 133 (74.7)
Slide 48: Patient Disposition After 18 Months Median Follow Up
Patient Disposition After 18 Months Median Follow Up Imetelstat Placebo (n=118) (n=59) Treatment ongoing, n (%) 27 (22.9) 14 (23.7) Treatment discontinued, n (%) 91 (77.1) 45 (76.3) Lack of efficacy 28 (23.7) 25 (42.4) Adverse event 19 (16.1) 0 Cytopenias 11 (9.3) 0 Unrelated 8 (6.8) 0 Disease relap
Slide 49: IMerge Phase 3 Efficacy
IMerge Phase 3 Efficacy ——————
Slide 50: Primary End Point of 8-Week RBC-TI Rate Significantly Higher With Imetelstat
Primary End Point of 8-Week RBC-TI Rate Was Significantly Higher With Imetelstat vs Placebo Imetelstat Placebo 50 P<0.001 40 Imetelstat Placebo 8-Week TI Responders (N=118) (N=60) 30 n (%) 47 (39.8) 9 (15.0) Patients, % 95% CIa 30.93–49.25 7.10–26.57 20 % Difference (95% CI)b 24.8 (9.9–36.9) P-value
Slide 51: Continuous Sustained TI with Imetelstat Treatment
Continuous Sustained TI with Imetelstat Treatment 83% of imetelstat 8-week TI responders had a single continuous TI period * * * Pre-treatment hemoglobin was 6.2 g/dL with transfusion burden of 5 units/8 weeks before study start; on-study hemoglobin was <6.5 g/dL during majority of TI period, yet no
Slide 52: Secondary Endpoint: Hematologic Improvement-Erythroid (HI-E)
Secondary Endpoint: Hematologic Improvement-Erythroid (HI-E) Highly statistically significant HI-E using updated IWG 2018 criteria Most recent HI-E criteria (IWG 2018) puts greater emphasis on durability by measuring response at >16 weeks Imetelstat Placebo P-value * (n=118) (n=60) HI-E per IWG 2018
Slide 53: Improvement in HI-E Rates With Imetelstat vs Placebo
Improvement in HI-E Rates With Imetelstat vs Placebo Imetelstat Placebo % Difference Hematologic Improvement (n=118) (n=60) P-valuea HI-E (IWG 20181), n (%) 50 (42.4) 8 (13.3) 29.0 95% CIb (33.3, 51.8) (5.9, 24.6) <0.001 Patients with LTB, nc 21 18 HI-E response (16-week RBC-TI), n (%) 7 (33.3) 4 (2
Slide 54: Primary and Secondary Endpoint by RS Status
Primary (8-Week TI) and Secondary Endpoint (24-Week TI) by RS Status RS+ and RS- demonstrate statistically significant improvement in both 8-week and 24-week TI RS+ RS- 60 P=0.016 Percentage of patients (%) 50 45.2% P=0.003 P=0.038 40 32.9% 31.8% P=0.019 30 18.9% 20.5% 20 8.7% 10 5.4% Imetelstat 0%
Slide 55: Comparable 24-Week RBC-TI Rate Across Key LR-MDS Subgroups
Comparable 24-Week RBC-TI Rate Across Key LR-MDS Subgroups Imetelstat Placebo, % Difference P-value n/N (%) n/N (%) (95% CI) Overall 33/118 (28.0) 2/60 (3.3) 24.6 (12.64–34.18) <0.001 WHO category RS+ 24/73 (32.9) 2/37 (5.4) 27.5 (10.00–40.37) 0.003 RS− 9/44 (20.5) 0/23 (0.0) 20.5 (−0.03–35.75) 0.01
Slide 56: Comparable 24-Week RBC-TI Rate Regardless of Baseline Mutation Status
Comparable 24-Week RBC-TI Rate Regardless of Baseline Mutation Status Imetelstat Placebo % Difference P-value n/N (%) n/N (%) (95% CI) Overall 29/110 (26.4) 1/55 (1.8) 24.5 (12.55–34.11) <0.001 Yes 29/107 (27.1) 1/54 (1.9) 25.3 (13.01–35.01) <0.001 Mutation status No 0/3 0/1 NE (NE–NE) NE Yes 20/75
Slide 57: Comparable 24-Week RBC-TI Rate Regardless of Baseline TA, TL or hTERT Level
Comparable 24-Week RBC-TI Rate Regardless of Baseline TA, TL or hTERT Level Imetelstat Placebo % Difference P-value n/N (%) n/N (%) (95% CI) Baseline TAa ≤Median 5/17 (29.4) 0/17 29.4 (0.25–55.95) 0.074 >Median 12/24 (50.0) 0/9 50.0 (7.67–70.35) 0.018 Baseline TLb ≤Median 13/40 (32.5) 1/32 (3.1) 29.
Slide 58: IMerge Phase 3 Patient-Reported Fatigue
IMerge Phase 3 Patient-Reported Fatigue 58
Slide 59: Methods
Methods Patient-Reported Outcome (PRO) • Previous research, including a literature review of qualitative research on the experience of patients with LR MDS and input from expert clinicians in LR MDS, led to the identification of a set of PRO concepts relevant to patients with LR MDS • The PRO items
Slide 60: PRO Fatigue Endpoint
PRO Fatigue Endpoint • Proportion of patients in each treatment group reporting any episode of sustained meaningful deterioration or improvement in fatigue (Fig. 2)1,2 • Sensitivity analyses were performed in alternate populations and with alternate definitions of meaningful deterioration and improv
Slide 61: PRO Population Demographics and Disease Characteristics
PRO Population Demographics and Disease Characteristics Imetelstat Placebo (n=118) (n=57) Completion rates3 for FACIT- Fatigue questionnaire were Median age, years (range) 72 (44-87) 73 (39-85) good throughout the study, Gender, n (%) >85% at most cycles Male 71 (60) 38 (67) Female 47 (40) 19 (33) R
Slide 62: Lower Deterioration in FACIT-Fatigue Score for Imetelstat vs Placebo
Lower Deterioration in FACIT-Fatigue Score for Imetelstat vs Placebo • In the ITT population, the sensitivity analysis showed that 43% of patients in either group experienced any episode of meaningful deterioration in fatigue for ≥2 consecutive cycles • In the PRO population, 67% of patients in eith
Slide 63: Improvement in FACIT-Fatigue Score Over Time With Imetelstat vs Placebo
Improvement in FACIT-Fatigue Score Over Time With Imetelstat vs Placebo • A repeated measurement mixed model (RMMM) analysis showed an overall change in FACIT-Fatigue score from baseline of 1.08 (by LSM with 95% CI, −0.36 to 2.53) with imetelstat vs −2.48 (by LS M with 95% CI, −4.48 to −0.5) with pl
Slide 64: Appendix 2
Appendix 2 Strong evidence for potential disease modification 64
Slide 65: Strong Evidence of Imetelstat Disease Modification Potential in Phase 3 and Phase 2 Trials
Strong Evidence of Imetelstat Disease Modification Potential in Phase 3 and Phase 2 Trials Killing of Recovery of Bone Reduced Telomerase Activity Malignant Stem and Marrow and Blood Clinical Benefits Progenitor Cells Cell Production Correlated with Depletion of mutated and Highly statistically Dept
Slide 66: IMerge Phase 3 – Evidence of Disease Modification Potential with Imetelstat in LR MDS
IMerge Phase 3 – Evidence of Disease Modification Potential with Imetelstat in LR MDS 66
Slide 67: Higher Percentage of Patients Achieved a Cytogenetic Response With Imetelstat
Higher Percentage of Patients Achieved a Cytogenetic Response With Imetelstat vs Placebo • Among patients with cytogenetic abnormalities at baseline, the Imetelstat Cytogenetic responsea Placebo (N=60) (N=118) cytogenetic response rate was 35% Patients with baseline cytogenetic abnormality (9/26) in
Slide 68: More Patients With Imetelstat Had ≥50% Reduction in Central Bone Marrow RS
More Patients Treated With Imetelstat vs Placebo Had ≥50% Reduction in Central Bone Marrow RS, Which Associated With TI Responses • A higher percentage of patients treated with imetelstat vs placebo had a ≥50% reduction in central bone marrow RS • RBC-TI responders enriched in patients achieving a 1
Slide 69: Reductions in VAF of Genes Frequently Mutated in MDS Greater With Imetelstat
Reductions in VAF of Genes Frequently Mutated in MDS Were Greater With Imetelstat vs Placebo • Mutations on 36 genes associated with MDS were tested by NGS on samples taken from baseline and post-treatment • Among patients with evaluable mutation data, the maximum reductions in VAF of the SF3B1, TET
Slide 70: Imetelstat Treatment Resulted in Sustained Reduction of SF3B1 VAF Over Time
Imetelstat Treatment Resulted in Sustained Reduction of SF3B1 VAF Over Time 50 SF3B1 Gene Mutation Frequency Over Time 40 Mean value (±SE) 30 20 Imetelstat Placebo 10 Baseline Week 12 Week 24 Week 36 Week 48 Week 60 Week 72 Week 84 Week 96 Visit Imetelstat 78 42 33 22 22 16 13 11 7 Placebo 38 36 26
Slide 71: RBC-TI Responders Enriched in Patients Achieving ≥50% Reduction in SF3B1 VAF
RBC-TI Responders Enriched in Patients Achieving ≥50% Reduction in SF3B1 VAF in the Imetelstat Group Imetelstat SF3B1 VAF SF3B1 VAF ≥50% Reduction Imetelstat Placebo N=78 N=38 Patients, n (%) P Value Yes No Total Maximum % reduction from baseline in SF3B1 VAF 30 30 (Fisher 20 20 (N=23) (N=55) (N=78)
Slide 72: RBC-TI Responders Enriched in Patients Achieving ≥50% Reduction in TET2 VAF
RBC-TI Responders Enriched in Patients Achieving ≥50% Reduction in TET2 VAF in the Imetelstat Group TET2 VAF Imetelstat Imetelstat Placebo TET2 VAF ≥50% Reduction N=35 N=12 Patients, n (%) Maximum % reduction from baseline in TET2 VAF 60 60 P Value 50 50 Yes No Total (Fisher 40 40 (N=12) (N=23) (N=3
Slide 73: 8-Week and 24-Week RBC-TI Correlated With Reduction in RS+ Cells and VAF
8-Week and 24-Week RBC-TI Correlated With Reduction in RS+ Cells, Cytogenetic Responses, and VAF Reduction in Patients Treated With Imetelstat 8-Week RBC-TI Correlations 24-Week RBC-TI Correlations 110 Yes No 110 Yes No P=0.098 P=0.065 100 100 P=0.014 90 P=0.034 90 P<0.001 P=0.003 24-week RBC-TI rat
Slide 74: IMbark Phase 2 – Evidence of Disease Modification Potential in R/R MF
IMbark Phase 2 – Evidence of Disease Modification Potential with Imetelstat in R/R MF 74
Slide 75: Strong Evidence of Disease Modification Potential: Bone Marrow Fibrosis
Strong Evidence of Disease Modification Potential ClincialTrials.gov (NCT02426086) Improved bone marrow fibrosis correlated to improved survival in IMbark Phase 2 Significant Dose-Dependent Fibrosis Longer Median OS and Higher Survival Rate Improvement with Imetelstat Treatment in Patients with Impr
Slide 76: Strong Evidence of Disease Modification Potential: VAF Reduction
Strong Evidence of Disease Modification Potential ClincialTrials.gov (NCT02426086) Reduction in key MF driver mutations correlated to improved survival in IMbark Phase 2 Significant Dose-Dependent ≥20% VAF Longer Median OS and Higher Survival Rate in Patients Reduction with Imetelstat Treatment Who
Slide 77: Strong Evidence of Disease Modification Potential: Malignant Clones Reduced
Strong Evidence of Disease Modification Potential ClincialTrials.gov (NCT02426086) Malignant clones reduced in imetelstat-treated patients in IMbark Phase 2 Dose-Dependent Complete Elimination of Mutation Burden from Multiple Driver- and Non-Driver Genes 9.4 mg/kg 9.4 mg/kg 4.7 mg/kg 4.7 mg/kg Compl
Slide 78: Appendix 3: Imetelstat mechanism of action
Appendix 3 Imetelstat mechanism of action 78
Slide 79: Telomerase, a Unique Oncology Target
Telomerase, a Unique Oncology Target Malignant HSCs are the malignant Heme source of disease in heme hematopoietic malignancies stem cells malignancies • Malignant hematopoietic Myelodysplastic stem cells (HSCs) give rise Syndromes (MDS) to uncontrolled proliferation of malignant blood cells • Malig
Slide 80: Novel Drug, Novel Target
Novel Drug, Novel Target Imetelstat, First-in-Class Telomerase Inhibitor Imetelstat enables recovery of bone marrow Imetelstat binds to and blood cell production telomerase and inhibits its activity Evidence for potential disease modification: • Clinical efficacy results: durable TI (LR MDS); improv
Slide 81: Appendix 4: Pipeline expansion programs
Appendix 4 Pipeline expansion programs 81
Slide 82: Phase 1 IMproveMF Study Evaluating Combination Therapy in Frontline MF
Phase 1 IMproveMF Study Evaluating Combination Therapy in Frontline MF Preclinical data for ruxolitinib followed by October 2023: Study Started imetelstat: • Additive inhibitory effect on MF Escalated to second May 2022 stem cells in vivo dose cohort Rationale • Synergistically depletes stem cells f
Slide 83: IMpress Phase 2 Study in Post-HMA Relapsed/Refractory AML
IMpress –Phase 2 Investigator-Led Study of Single Agent Imetelstat in Post-HMA Relapsed/Refractory AML Lead PrincipaI Investigator: Dr. Uwe Platzbecker, University Hospital, Leipzig, Germany In preclinical models, imetelstat: First Patient Dosed: • Prevented expansion of human AML leukemic stem cell
Slide 84: TELOMERE Pending Phase 1/2 Study in Relapsed/Refractory AML
The Tisch TELOMERE – Pending Phase 1/2 Investigator-Led Study of Imetelstat in Cancer Institute Combination with Venetoclax or Azacitidine in Relapsed/Refractory AML Lead Principal Investigator: Dr. John Mascarenhas, Mt. Sinai Hospital, New York, New York In preclinical models, imetelstat + venetocl
Slide 85: Ongoing and Planned Preclinical Experiments in Lymphoid Malignancies
Ongoing and Planned Preclinical Experiments to Define the Role of Imetelstat in Lymphoid Malignancies Lead Principal Investigator: Dr. Swaminathan Iyer, MD Anderson Cancer Center, Houston, Texas T-Cell lymphoma cell lines in vitro have shown: • Short telomere length (Sezary syndrome; transformed myc
Slide 86: Next Generation Telomerase Inhibitor Program Update
Next Generation Telomerase Inhibitor Program Update Status • Expect completion of Program goal current discovery effort in 2023, at which time Discover and develop novel small molecules based on chemistry Geron plans to potentially advance platforms proprietary to Geron that bind to the active site
Slide 87: Appendix 5: TAM
_ Appendix 5 ———— TAM
Slide 88: Total Addressable Market for LR MDS and R/R MF >$7B by 2033
Total Addressable Market (TAM) for LR MDS and R/R MF >$7B by 2033 (US/EU4/UK)* Establishing imetelstat as standard of care in LR MDS and R/R MF Potential LR MDS Patient Population Potential MF Patient Population ESA Ineligible (RS+ve / RS-ve): ~4k ESA R/R RS+ve: ~8k JAKi treated: ~24k ESA R/R RS-ve:
Slide 89: Appendix 6: ASH 2023 Accepted Abstracts
Appendix 6 ASH 2023 Accepted Abstracts 89
Slide 90: ASH 2023: Consistent Efficacy Across MDS Risk Subgroups
ASH 2023: Consistent Efficacy Across MDS Risk Abstract #194 Subgroups using Different IPSS Risk Classifications Conclusion • IMerge Phase 3 Oral presentation on Saturday, December 9, 2023 at 2:15 pm PT results indicate that the clinical efficacy of imetelstat is Subgroup analysis demonstrated that i
Slide 91: ASH 2023: Consistent Efficacy Regardless of Underlying MDS Mutations
ASH 2023: Consistent Efficacy Across MDS Subgroups Abstract #4603 Regardless of Underlying MDS Mutations Conclusion Poster presentation on Monday, December 11, 2023 from 6-8 pm PT Imetelstat showed comparable TI rates across TI responses in imetelstat-treated patients occurred regardless of the pres
Slide 92: ASH 2023: Unprecedented Durable Continuous TI
Abstract #4605 ASH 2023: Unprecedented Durable Continuous TI Conclusion Poster presentation on Monday, December 11, 2023 from 6-8 pm PT Patients who achieve continuous TI: 17.8% of imetelstat-treated patients achieved ≥1-year sustained TI with a median • With a median TI TI duration of 123 weeks. du
Slide 93: ASH 2023: Durable TI Associated with Better Survival (RWD)
ASH 2023: Durable TI Associated with Better Survival Abstract #2440 (RWD)* Conclusion For transfusion dependent Poster presentation on Monday, December 11, 2023 from 6-8 pm PT patients achievement of TI with second line An analysis of US health insurance claims database of 5662 LR MDS patients treat