Corporate Presentation October 2019
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 forward-looking statements include statements regarding the expectations, plans, timelines and prospects . for imetelstat and Geron, including, without limitation, statements related to: (i) the therapeutic and commercial potential of imetelstat, including that imetelstat may have disease-modifying activity; (ii) that Geron will have top-line results from the IMerge MDS clinical trial in mid-2022; (iii ) Geron’s planned activities and the timing thereof, including Geron’s plan to conduct an End of Phase 2 meeting with the FDA by the end of Q1 2020 to potentially determ ine regulatory strategy for imetelstat in relapsed/refractory MF and thereafter decide whether to proceed with development in MF; (iv) Geron’s potential for future growth, including the potential for Geron to partner and/or expand its development pipeline through a license or acquisition; (v) the U.S. revenue potential of >$500 million for imetelstat in each of MF and MDS, respectively; (vi) that the IMbark results suggest favorable overall survival with imetelstat treatment based on comparative analyses between real-world data (RWD) and the IMbark clinical data; (vii) that there is potential patent life extension under Hatch-Waxman or market exclusivity under orphan drug regulations; (viii) that Geron expects that fedratinib will be marketed for only frontline Int-2/High-risk MF; and (ix) other statements that are not historical facts. 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, risks and uncertainties related to whether: (a) regulatory authorities permit the further development and approve the commercialization of imetelstat for MF or MDS and/or potential additional indications on a timely basis, or at all, without any clinical holds; (b) t here is a delay in Geron’s decision regarding further development of imetelstat for MF; (c) imetelstat demonstrates successful efficacy and safety in clinical trials; (d) Geron will be able to successfully retain or recruit key personnel to support its current and future development plans or to otherwise successfully manage its growth; (e) there are failures or delays in manufacturing sufficient quantities of imetelstat, or other clinical trial materials, in a manner that meets the quality standards of the FDA and other regulatory authorities; (f) Geron’s patents protect the commercial opportunity of imetelstat; (g) whether imetelstat’s benefit -risk profile for MDS will actually be superior to other drugs such as lenalidomide, hypomethylating agents and/or luspatercept; (h) that the fedratinib label permits marketing for only frontline Int-2/High-risk MF; (i) the inherent limitations of comparative analyses between RWD and clinical trial data, result in such analyses not being relied upon as demonstrative; (j) Geron will be able to identify and acquire and/or in-license other hematology-oncology product candidates; and (k) Geron can obtain sufficient funding to support further development of imetelstat and any/or additional product candidates. 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 in Geron's quarterly report on Form 10-Q for the quarter ended June 30, 2019. 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
Company Snapshot Imetelstat, a Novel Drug with a Unique Target • Proprietary drug targeting telomerase-driven, uncontrolled progenitor cell proliferation in hematologic malignancies • Development focused on MDS and MF; both have significant unmet medical need and market opportunity • Fast Track designation for both lower risk MDS and Int-2/High-risk MF • Issued patent coverage until 2033 and orphan drug designation for both MDS and MF Late-Stage Clinical Development • IMerge Phase 3 clinical trial opened August 2019 in lower risk myelodysplastic syndromes (MDS) with top-line results expected by mid-year 2022 • Planning an IMbark End of Phase 2 meeting with the FDA by end of Q1 2020 to determine whether there is a potential regulatory path forward in relapsed/refractory myelofibrosis (MF) In-House Leadership and Expertise Establishes a Foundation for Potential Future Growth • Highly-experienced, multi-functional, in-house hematology-oncology and late-stage drug development team Cash Resources • As of 6/30/19, $162.3M in cash and marketable securities 3
Imetelstat Development Highlights Lower Risk MDS Int-2 or High-risk MF Target Patient Non-del(5q), R/R to ESAs, and prior to treatment Relapsed/Refractory to JAK inhibitors with lenalidomide or hypomethylating agents Population Shorter survival with transfusion dependency 75% discontinue front-line therapy after 5 yrs Unmet Medical Need No new drugs approved in the U.S. since 2006 No approved drugs in relapsed/refractory MF U.S. Revenue Potential ^ >$500M >$500M IMbark Trial Data vs. Closely Matched Real-World Data + : Imetelstat * 8-week RBC-TI: 42.1% (16/38) Imetelstat Data Imetelstat # median OS: 30.7 mos Luspatercept ** 8-week RBC-TI: 19.6% (21/107) Comparisons Best available therapy (BAT) median OS: 12.0 mos FDA Designations Orphan Drug, Fast Track Orphan Drug, Fast Track Phase 3 portion of IMerge clinical trial opened for Planning End of Phase 2 meeting with FDA by end of Q1 Current Status screening and enrollment in August 2019 2020 to determine potential regulatory path forward ^ Based on Geron proprietary market research * Recent data from Phase 2 portion of IMerge using a clinical cut-off of April 30, 2019 reported at European Hematology Association (EHA) meeting in June 2019 ** As reported at 2018 American Society of Hematology (ASH) meeting for Phase 3 Medalist trial in patients with baseline trans fusion burden ≥4 units/8 weeks + Statistical analyses comparing Phase 2 IMbark clinical data to closely matched real-world data presented at EHA meeting in June 2019 # Starting dose of 9.4 mg/kg every three weeks 4
Telomerase Imetelstat directed at a novel molecular target in oncology Telomerase enzyme Telomerase activity in cells • Comprised of an RNA template component (hTR) and a reverse transcriptase catalytic protein subunit (hTERT) Somatic Cells • If telomerase activity is high, telomere length is Telomerase inactive maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life (replicative immortality) + Normal Progenitor Cells • In 2009, three Geron collaborators won the Nobel Prize Telomerase transiently upregulated to for Medicine for discovery of telomerase and its support controlled proliferation of relationship with telomeres and cancer stem cells and progenitor cells Malignant Progenitor Cells Telomerase highly upregulated , in over RNA 90% of cancers, enabling continued and template uncontrolled proliferation telomeric DNA (hTR) catalytic subunit (hTERT) + The Nobel Prize in Physiology or Medicine 2009. Nobel Prize.org. Nobel Media AB 2019. https://www.nobelprize.org/prizes/medicine/2009/summary/ 5
Imetelstat A first-in-class telomerase inhibitor imetelstat • Target: malignant progenitor cell clonal proliferation • Structure: 13-mer thio-phosphoramidate (NPS) NPS oligonucleotide lipid tail oligonucleotide complementary to hTR, with covalently- bound lipid tail to increase cell permeability/tissue distribution • Potent competitive inhibitor of telomerase Imetelstat binds to RNA template • Long tissue residence time in bone marrow, spleen, liver of telomerase • Clinical experience: more than 600 patients treated in Phase 1 and 2 trials X • Patent/Market exclusivity: composition of matter U.S. patent coverage through 2025; methods of use patents telomere Prevents binding by for MDS and MF until 2033; potential patent extension and maintenance of with Hatch-Waxman and/or expected market exclusivity telomeres associated with orphan drug designations 6
Hematologic Myeloid Malignancies Clinical proof-of-concept in ET, MF and MDS Arise from malignant progenitor cells in the bone marrow • Higher telomerase activity expressed compared to normal cells telomerase • Inhibiting telomerase limits proliferative Baerlocher et al, NEJM 2015; 373:920-928 capacity of malignant cells, particularly progenitor cells Steensma et al, 2018 ASH Presentation Fenaux et al, 2019 EHA Presentation • Clinical evidence of potential disease- modifying activity in three hematologic myeloid malignancies: ET, MF, MDS Tefferi Pilot Study, unpublished Tefferi et al, NEJM 2015; 373:908-919 Mascarenhas, et al, 2018 ASH Presentation 7
Myelodysplastic Syndromes
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