Healthcare Conference John Scarlett, M.D. President and CEO, Geron - PowerPoint PPT Presentation

Stifel Healthcare Conference John Scarlett, M.D. President and CEO, Geron Corporation November 2018

Forward-Looking Statements Except for statements of historical fact, the statements contained in this presentation are forward-looking statements made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These include, without limitation, statements regarding the expectations, plans, timelines and prospects for imetelstat and Geron, including without limitation: (i) that the imetelstat IND transfers from Janssen to Geron in the second quarter of 2019; (ii) that IMbark and IMerge will continue; (iii) Geron’s plans to initiate the Phase 3 portion of IMerge in mid-2019; (iv) that Geron will outline a decision for myelofibrosis development by the end of the third quarter 2019; (v) that imetelstat for MDS would be prescribed before or in lieu of lenalidomide and/or hypomethylating agents; (vi) financial or operating projections or requirements of Geron; and (vii) other statements that are not historical facts, constitute forward-looking statements. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation: (i) whether contingencies delay or prevent the start of the Phase 3 portion of IMerge by mid-year 2019; (ii) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all; (iii) whether Geron decides for any reason not to develop imetelstat for myelofibrosis; (iv) whether any circumstances arise that prevent a timely transition of the imetelstat program from Janssen; (v) whether Geron’s patents protect the commercial value of imete lstat; (vi) whether imetelstat’s benefit -risk profile for MDS is better than lenalidomide and/or hypomethylating agents; and (vii) whether Geron can obtain sufficient funding to support further development of imetelstat. Additional information and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron's periodic reports filed with the Securities and Exchange Commission un der the heading “Risk Factors,” including Geron's quarterly report on Form 10 -Q for the quarter ending September 30, 2018. Undue reliance should not be placed on forward- looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. 2

Geron Overview Company • A late-stage clinical development biopharmaceutical company with 100% ownership of imetelstat, a Phase 3-ready asset • Sufficient cash ($185M as of 9/30/18) to move imetelstat forward into Phase 3 Imetelstat • A first-in-class telomerase inhibitor, focused on hematologic myeloid malignancies • Clinical evidence of potential disease-modifying activity in three myeloid malignancies: essential thrombocythemia (ET), myelofibrosis (MF) and myelodysplastic syndromes (MDS) • Granted Fast Track designation by FDA for treatment of lower risk MDS patients Current Clinical Trials • IMerge: Phase 2/3 trial in lower risk MDS • IMbark: Phase 2 trial in Intermediate-2 or High-risk MF • Oral presentations of updated data for both trials scheduled at American Society of Hematology (ASH) Annual Meeting Future Plans • Screening and enrollment for Phase 3 portion of IMerge planned to begin by mid-year 2019 • Exploring potential for late-stage development in MF, expect decision by end of third quarter 2019 3

Telomerase A novel molecular target in oncology Telomerase enzyme Malignant Progenitor Cells • Comprised of an RNA template component Telomerase highly upregulated , in over (hTR) and a reverse transcriptase catalytic 90% of cancers, enabling continued and protein subunit (hTERT) uncontrolled proliferation • In 2009, three Geron collaborators won the Nobel Prize for Medicine for discovery of Normal Progenitor Cells telomerase and its relationship with telomeres Telomerase transiently upregulated to support controlled proliferation Somatic Cells RNA template Telomerase inactive (hTR) telomeric DNA catalytic subunit (hTERT) 4

Imetelstat A first-in-class telomerase inhibitor • Target: malignant progenitor cell clonal imetelstat proliferation NPS oligonucleotide • Structure: 13-mer thio-phosphoramidate lipid tail (NPS) oligonucleotide complementary to hTR, with covalently-bound lipid tail to increase cell permeability/tissue distribution Imetelstat binds • Long tissue residence time in bone marrow, to RNA template spleen, liver of telomerase • Potent competitive inhibitor of telomerase • Clinical experience: more than 600 patients X treated in Phase 1 and 2 trials telomere Prevents binding by and maintenance of telomeres 5

Imetelstat Key differentiating features Targeting telomerase to tackle the underlying disease Unique • Telomerase activity is high in patients with myeloproliferative neoplasms • Inhibiting telomerase expression limits the proliferation of malignant progenitor cell clones Mechanism that drive the disease of Action Trial eligibility criteria emphasizes difficult-to-treat patients Challenging • IMerge – open to all MDS subtypes, minimum transfusion burden of 4.0 units/8 weeks, pre- transfusion hemoglobin ≤ 9.0 g/dL Patient • IMbark – must show objective evidence of disease progression during or after treatment with Populations a JAK inhibitor (JAKi) or never responded to JAKi treatment plus active symptoms of MF Tested Activity within multiple outcome measures suggest clinical benefit • IMerge – ≥8 -week red blood cell (RBC) transfusion independence (TI) achieved across MDS Broad subtypes (ring-sideroblast, RS +/-) and erythropoietin (EPO) levels, reductions in transfusion Clinical burden in all patients • IMbark – range of reductions in Total Symptom Score, potential improvement in overall Activity survival for 9.4 mg/kg arm, including patients with at least one high-risk mutation and triple negative mutation patients 6

Hematologic Myeloid Malignancies Clinical evidence of potential disease modifying activity All arise from malignant progenitor cell clones in the bone marrow telomerase Baerlocher et al, NEJM 2015; 373:920-928 Steensma et al, 2018 ASH Abstract #463 Tefferi Pilot Study, unpublished Tefferi et al, NEJM 2015; 373:908-919 7

Myelodysplastic Syndromes (MDS) Disease characteristics • MDS is a diverse group of clonal hematologic malignancies • Comprised of numerous subtypes, including refractory anemia with ring-sideroblasts (RARS) and refractory cytopenia with multi-lineage dysplasia-RS (RCMD-RS) • RS+ MDS associated with lower risk of AML transformation and better survival than RS- patients telomerase • Median age at diagnosis is 70 • Up to 30% of patients progress to acute leukemia (AML) Lower Risk MDS • Median overall-survival is 3.5-5.7 years • Chronic anemia is the predominant clinical problem, many patients are dependent on RBC transfusions • Transfusion dependency is associated with iron overload, and shorter survival - 2 units of RBC monthly may reduce life expectancy by 50% and increase risk of progression to AML Sekeres, Natl Compr Canc Netw 2011; 9:57-63 Bejar & Steensma, Blood 2014; 124:2793-2803 Greenberg et al, Blood 1997; 89:2079-2088 Malcovati et al, JCO 2007; 25:3503-3510 www.cancer.org/cancer/myelodysplastic-syndromes 8

MDS Patient Population in the U.S. Addressing a large unmet need 60,000 ~70% MDS patients in the U.S. of MDS patients have Lower Risk MDS 16,000 Cases diagnosed annually in the U.S. Cogle, Curr Hematol Malig Rep; 2015, 10272-10281 Greenberg et al, Blood 1997; 89:2079-2088 9

Treatment Landscape for Lower Risk MDS Chronic anemia remains an unmet need Erythropoiesis Lenalidomide Stimulating Not approved in U.S. or Europe for Agents (ESAs) Patients non-del(5q) patients • ≥8 -week RBC-TI: 27% refractory to • Improvement in ESAs become anemia in ~50% of patients dependent on • Median treatment red blood cell duration: ~2 years transfusions Hypomethylating Agents (HMAs) Approved in U.S. for all patients, including del(5q) and non-del(5q) Not approved in Europe • ≥8 -week RBC-TI: ~17% Fenaux and Adès, Blood 2013; 121:4280-4286 Santini et al, J Clin Oncol 2016; 34:2988-2996 10 Tobiasson et al, BCJ 2014; 4: e189