Corporate Presentation October 2019 Forward-Looking Statements - - PowerPoint PPT Presentation

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 determine 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) there 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

• ther 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 under 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

3

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

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

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)

Cash Resources

• As of 6/30/19, $162.3M in cash and marketable securities

Imetelstat Development Highlights

Lower Risk MDS Int-2 or High-risk MF

Non-del(5q), R/R to ESAs, and prior to treatment with lenalidomide or hypomethylating agents

Target Patient Population

Relapsed/Refractory to JAK inhibitors Shorter survival with transfusion dependency No new drugs approved in the U.S. since 2006

Unmet Medical Need

75% discontinue front-line therapy after 5 yrs No approved drugs in relapsed/refractory MF >$500M

U.S. Revenue Potential^

>$500M Imetelstat* 8-week RBC-TI: 42.1% (16/38) Luspatercept** 8-week RBC-TI: 19.6% (21/107)

Imetelstat Data Comparisons

IMbark Trial Data vs. Closely Matched Real-World Data+: Imetelstat# median OS: 30.7 mos Best available therapy (BAT) median OS: 12.0 mos Orphan Drug, Fast Track

FDA Designations

Orphan Drug, Fast Track Phase 3 portion of IMerge clinical trial opened for screening and enrollment in August 2019

Current Status

Planning End of Phase 2 meeting with FDA by end of Q1 2020 to determine potential regulatory path forward

4

^ 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 transfusion 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

Telomerase

Imetelstat directed at a novel molecular target in oncology

5

Telomerase enzyme

• Comprised of an RNA template component (hTR) and a

reverse transcriptase catalytic protein subunit (hTERT)

• If telomerase activity is high, telomere length is

maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life (replicative immortality) +

• In 2009, three Geron collaborators won the Nobel Prize

for Medicine for discovery of telomerase and its relationship with telomeres and cancer

telomeric DNA RNA template (hTR) catalytic subunit (hTERT)

Somatic Cells

Telomerase inactive

Normal Progenitor Cells

Telomerase transiently upregulated to support controlled proliferation of stem cells and progenitor cells

Malignant Progenitor Cells

Telomerase highly upregulated, in over 90% of cancers, enabling continued and uncontrolled proliferation

Telomerase activity in cells

+The Nobel Prize in Physiology or Medicine 2009. Nobel Prize.org. Nobel Media AB 2019.

https://www.nobelprize.org/prizes/medicine/2009/summary/

Imetelstat

A first-in-class telomerase inhibitor

6

• Target: malignant progenitor cell clonal proliferation
• Structure: 13-mer thio-phosphoramidate (NPS)
• ligonucleotide complementary to hTR, with covalently-

bound lipid tail to increase cell permeability/tissue distribution

• Potent competitive inhibitor of telomerase
• Long tissue residence time in bone marrow, spleen, liver
• Clinical experience: more than 600 patients treated in

Phase 1 and 2 trials

• Patent/Market exclusivity: composition of matter U.S.

patent coverage through 2025; methods of use patents for MDS and MF until 2033; potential patent extension with Hatch-Waxman and/or expected market exclusivity associated with orphan drug designations

lipid tail imetelstat telomere Prevents binding by and maintenance of telomeres Imetelstat binds to RNA template

• f telomerase

NPS oligonucleotide

X

Hematologic Myeloid Malignancies

Clinical proof-of-concept in ET, MF and MDS

• Higher telomerase activity expressed

compared to normal cells

• Inhibiting telomerase limits proliferative

capacity of malignant cells, particularly progenitor cells

• Clinical evidence of potential disease-

modifying activity in three hematologic myeloid malignancies: ET, MF, MDS

7

telomerase

Steensma et al, 2018 ASH Presentation Fenaux et al, 2019 EHA Presentation Baerlocher et al, NEJM 2015; 373:920-928 Tefferi et al, NEJM 2015; 373:908-919 Mascarenhas, et al, 2018 ASH Presentation Tefferi Pilot Study, unpublished

Arise from malignant progenitor cells in the bone marrow

Myelodysplastic Syndromes

Lower Risk Myelodysplastic Syndromes (MDS)

Disease characteristics

9 telomerase

• Lower risk MDS is comprised of Low and Intermediate-1

risk patients as defined by the International Prognostic Scoring System

• Lower risk MDS is a heterogenous disease comprised of

numerous subtypes, including refractory anemia with ring-sideroblasts (RARS) and refractory cytopenia with multi-lineage dysplasia-RS (RCMD-RS)

• RS+ MDS patients associated with better survival

than RS- MDS patients

• Chronic transfusion-dependent anemia is the

predominant clinical feature

• Transfusion dependency is associated with iron
• verload, and shorter survival; 2 units of RBC

monthly may reduce life expectancy by 50%

• Annual transfusions for transfusion dependent

patients cost $29,000-$51,000 per year

• Up to 30% of lower risk MDS patients progress to acute

leukemia (AML)

• Median overall survival is 3.5-5.7 years

High telomerase activity, high expression of hTERT and shorter telomeres are associated with shorter survival in lower risk MDS

Platzbecker, Blood 2019; 133:1096-1107 Sekeres, Natl Compr Canc Netw 2011; 9:57-63 Greenberg et al, Blood 1997; 89:2079-2088 Bejar & Steensma, Blood 2014; 124:2793-2803 Malcovati, Haematologica, 2006:91(12) Lucioni, Am J Blood Res 2013, 3(3):246-259 www.cancer.org/cancer/myelodysplastic-syndromes

Cogle, Curr Hematol Malig Rep; 2015, 10272-10281 Greenberg et al, Blood 1997; 89:2079-2088 Geron Proprietary Market Research

Imetelstat target patient population*

~85%

• f lower risk MDS

> 40,000

Lower risk MDS patients in the U.S.

> 10,000

Lower risk MDS cases diagnosed annually in the U.S.

Lower Risk MDS Patient Population in the U.S.

Addressing a significant unmet need

10

U.S. revenue potential for imetelstat in lower risk MDS could exceed $500M

* Lower risk MDS patients without chromosomal 5q deletion (non-del(5q)), relapsed/refractory to erythropoiesis stimulating agents (ESAs), prior to being treated with lenalidomide or hypomethylating agents (HMAs)

Current Treatment Options Limited

For non-del(5q) lower risk MDS patients R/R to ESAs

11

Fenaux and Adès, Blood 2013; 121:4280-4286 Santini et al, J Clin Oncol 2016; 34:2988-2996 Tobiasson et al, BCJ 2014; 4: e189

Patients relapsed or refractory to ESAs become dependent on red blood cell transfusions

Erythropoiesis Stimulating Agents (ESAs)

• Approved indication

is for anemia

• Transient

improvement in anemia

• Majority of patients

will relapse or become refractory

• Median duration of

response: ~2 years

Hypomethylating Agents (HMAs)

Approved in U.S., but not in Europe

• ≥8-week RBC-TI: 17% for azacitidine

Lenalidomide

Not approved in U.S. or Europe

• ≥8-week RBC-TI: 27%

Proposed Treatment Order for Non-Del(5q) Lower Risk MDS

Planning to sequence imetelstat ahead of current options

12

Imetelstat

≥8-week RBC-TI: 42%

target patient population: non-del(5q), R/R to ESAs, prior to treatment with lenalidomide or HMAs

Fenaux and Adès, Blood 2013; 121:4280-4286 Santini et al, J Clin Oncol 2016; 34:2988-2996 Tobiasson et al, BCJ 2014; 4: e189 EHA 2019 Presentation: Fenaux P, et al for IMerge Phase 2 with data cut-off April 30, 2019

Patients relapsed or refractory to ESAs become dependent on red blood cell transfusions

Hypomethylating Agents (HMAs)

Approved in U.S., but not in Europe

• ≥8-week RBC-TI: 17% for azacitidine

Lenalidomide

Not approved in U.S. or Europe

• ≥8-week RBC-TI: 27%

Erythropoiesis Stimulating Agents (ESAs)

• Approved indication

is for anemia

• Transient

improvement in anemia

• Majority of patients

will relapse or become refractory

• Median duration of

response: ~2 years

IMerge: 2-Part Phase 2/3 Trial

Part 1 – Phase 2 portion

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ClinicalTrials.gov (NCT02598661)

Imetelstat 7.5mg/kg every 4 weeks

• Transfusion dependent is defined as an RBC transfusion requirement of ≥4 units over 8 weeks

prior to trial entry

• ESA R/R following ≥8 weeks of weekly epoetin alfa 40,000 U or darbepoetin alfa 150 mcg (or

equivalent) or serum erythropoietin (sEPO) >500 mU/mL

• Supportive care permitted in both arms: RBC transfusions, myeloid growth factors per investigator

discretion as clinically needed and local guidelines

Transfusion Dependent, Low or Intermediate-1 Risk MDS, non- del(5q), R/R to ESAs, prior to treatment with lenalidomide or HMAs (n=38) 1° Efficacy: Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 weeks 2° Efficacy: RBC-TI ≥24 weeks; time to and duration of RBC-TI; hematologic improvement (HI); reduction in RBC burden

IMerge Part 1: Phase 2 Portion single arm, open label

IMerge Phase 2 – Recently Reported Data

Meaningful and durable transfusion independence

a Kaplan Meier method

14

Data Reported at European Hematology Association (EHA) Annual Congress in June 2019

• No. of patients

38 Median baseline transfusion burden, units/8 weeks (range) 8 (4-14) Rate of 8-week RBC-TI, % (n) 42% (16/38) Rate of 24-week RBC-TI, % (n) 29% (11/38) Median time to onset of RBC-TI, weeks (range) 8.3 (0.1-40.7) Median duration a of RBC-TI, weeks (range) 85.9 (8.0-140.9) Hematologic improvement – erythroid (HI-E), % (n) ≥1.5 g/dL increase in hemoglobin lasting ≥8 weeks Transfusion reduction by ≥4 units/8 weeks 68% (26/38) 32% (12/38) 68% (26/38) Mean relative reduction of RBC transfusion burden from baseline, %

• 68

EHA 2019 Presentation: Fenaux P, et.al.

ClinicalTrials.gov (NCT02598661)

Safety profile consistent with previous imetelstat clinical trials in hematologic myeloid malignancies

• No new safety signals were identified
• Adverse events with imetelstat (mostly cytopenias) were reversible for most patients

IMerge Phase 2 – Recently Reported Data

Activity across different patient subgroups

15

ClinicalTrials.gov (NCT02598661)

EHA 2019 Presentation: Fenaux P, et.al.

Broadly distributed similar responses observed across different patient subgroups

• Observed 8-week RBC-TI

responses comparable to results for overall patients

IMerge Phase 2 – Recently Reported Data

Potential disease-modifying activity observed

Impact on biomarkers of MDS disease suggest potential effect on the malignant clone and disease modification

➢ 75% (12/16) of patients who achieved an 8-week RBC-TI also had a Hgb rise ≥ 3g/dL

from the pretreatment level, which suggests recovery of normal hematopoiesis

➢ Improvement in cytogenetics of the cells in the bone marrow

• 6/34 (18%) patients had intermediate or poor cytogenetic risk; 4/6 remain on treatment

▪ 5/6 (83%) patients achieved 8-week RBC-TI and all had a ringed-sideroblast WHO subtype ▪ 3/3 patients with trisomy 8 achieved 8-week RBC-TI and 2/3 achieved 24-week RBC-TI ▪ 2/3 patients with available post-treatment cytogenetic data achieved partial cytogenetic

response

➢ Reduction in proportion of cells carrying SF3B1 mutation

• 2/6 patients with baseline SF3B1 mutations had reduction in variant allele frequency and

maintained transfusion independence lasting over a year

16

ClinicalTrials.gov (NCT02598661)

EHA 2019 Presentation: Fenaux P, et.al.

Lower Risk MDS Trial Comparison*

Targeting different disease burdened patient populations

IMerge Part 1 – Phase 2 MEDALIST** – Phase 3

Imetelstat Luspatercept Placebo

38

• No. of patients

153 76 Non-del(5q), R/R to ESAs, prior to treatment with lenalidomide or HMAs Target patient population Non-del(5q), R/R to ESAs, prior to treatment with lenalidomide or HMAs RS+ and RS- MDS subtype Ring-sideroblasts (RS) RS+ only 8 (4-14) Median baseline transfusion burden

# units/8 weeks (range)

5 (1-20) 46 patients had <4 units/8 weeks 42.1% (16/38) 8-week RBC-TI rate, % (n) 37.9% (58/153) 13.2% (10/76) 68.4% (26/38) Rate of transfusion reduction (HI-E), % (n) 52.9% (81/153) 11.8% (9/76) 28.9% (11/38) 24-week RBC-TI rate, % (n) Not assessed 42.1% (16/38) 8-week RBC-TI rate, % (n)

Patients with baseline transfusion burden ≥4 units/8 weeks

19.6% (21/107) 3.6% (2/56)

17

EHA 2019 Presentation: Treatment with Imetelstat Provides Durable Transfusion Independence in Heavily Transfused Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents; Fenaux P, et.al. **MEDALIST sponsor – Celgene/Acceleron. ASH 2018 Presentation: The Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-

• r Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions

*Geron acknowledges that there are limitations when comparing results from an open label Phase 2 trial to a blinded, placebo-controlled Phase 3 trial, and also

that luspatercept has a relatively benign safety profile.

IMerge Phase 3 in Lower Risk MDS

Screening and enrollment opened August 2019

18

Imetelstat (n = ~115) 7.5mg/kg every 4 weeks Placebo (n = ~55) Randomize (2:1) Double-blind Transfusion Dependent, Low or Intermediate-1 Risk MDS, non-del(5q), R/R to ESAs, prior to treatment with lenalidomide or HMAs (n = ~170) 1° Efficacy: Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 weeks 2° Efficacy: RBC-TI ≥24 weeks; time to and duration of RBC-TI; hematologic improvement (HI); reduction in RBC burden

Clinical Trial Design for IMerge Part 2: Phase 3 Portion

ClinicalTrials.gov (NCT02598661)

Considerations for potential Phase 3 execution and success

• Phase 3 trial design:
• Same starting dose and schedule as Phase 2
• Same target patient population as Phase 2
• Same primary and secondary endpoints as Phase 2
• Many of the clinical sites participated in Phase 2
• Many of the key imetelstat Phase 2 clinical team members will be managing Phase 3

➢ Countries expected to participate in Phase 3 include: U.S., Canada, United Kingdom, Israel, Russia, South Korea, Belgium, Netherlands, Italy, France, Spain, Germany and Czech Republic ➢ Top-line results expected mid-year 2022

Myelofibrosis

Myelofibrosis (MF)

Disease characteristics

20

• Malignant clonal proliferation and atypical megakaryocytic

hyperplasia leads to bone marrow fibrosis and impaired hematopoiesis

– Constitutional symptoms (e.g., fever, weight loss, night sweats,

pruritus) present in approximately 35% of patients also thought to be due to cytokines produced by malignant megakaryocytes

– Impaired bone marrow hematopoiesis shifts blood production to

spleen and liver (palpable splenomegaly in approximately 80% of patients)

– Fibrosis thought to be induced by inflammatory cytokines

produced by megakaryocytes originating from the malignant progenitor cell clone

• Serious and life-threatening illness

− Leukemic transformation to AML (blast-phase MF) − Thrombohemorrhagic complications associated with dysfunctional

hematopoiesis

− Median survival: ~1-3 years for Intermediate-2 or High-risk disease

telomerase

Tefferi, JCO 2005; 23:8520-8530 Tefferi, Mayo Clin Proc 2012; 87:25-33 Gangat et al, JCO 2011; 29:392-397 Ferraris, Blood; 2005a; 105(5):2138–2140 Harley, Nat Rev. 2008;8:167–179

Higher telomerase activity and shorter telomere length in patients with myeloproliferative neoplasms Inhibition of neoplastic progenitor cell growth

• bserved with telomerase

inhibition

Imetelstat patient population*

~75%

• f Int-2/High-risk

MF patients

> 9,000

Int-2/High-risk MF patients in the U.S.

> 2,000

Int-2/High-risk MF cases diagnosed annually in the U.S.

Int-2/High-Risk MF Patient Population in the U.S.

A large unmet need creates demand for alternative therapies

21

U.S. revenue potential for imetelstat in Int-2/High-risk MF, relapsed/refractory to JAKi could exceed $500M

Mehta et al, Leuk Lymphoma 2014; 55:595-600 Gangat et al, JCO 2011; 29:392-397 Geron Proprietary Market Research

* Intermediate-2/High-risk MF patients relapsed/refractory to JAK inhibitors

75%

5-year ruxolitinib discontinuation rate

Unmet Medical Need in Int-2/High-Risk MF

No approved therapies in relapsed/refractory MF

22

Two JAK inhibitors (JAKi) Ruxolitinib – Approved 2011

• Primarily for symptoms or splenomegaly
• Oral JAK1/JAK2 inhibitor
• Stay on drug as long as tolerated

Fedratinib – Approved 2019

• Primarily for symptoms or splenomegaly
• Oral JAK2 inhibitor
• Black box warning for Wernicke’s

Encephalopathy

Front Line MF Approved Products

Harrison et al, ASH 2015; Gupta et al, ASCO 2016 Newberry et al, Blood 2017; 130:1125-1131 Kuykendall et al, Ann Hematol 2018; 97:435-441 Spiegel et al, Blood Advances 2017; 1:1729-1738 *Fedratinib approved for Int-2/High-risk MF--since the label contains no second-line, R/R MF efficacy information, or specific approval for such indications, we expect that it will be marketed for only Int-2/High-risk MF.

Primary reasons:

• Suboptimal response
• Loss of therapeutic effect

Median Overall Survival is ~14-16 months

After discontinuation of ruxolitinib

Relapsed/Refractory MF No Approved Products*

Unmet Medical Need in Int-2/High-Risk MF

Potential for meaningful survival in poor-prognosis patients

23

Harrison et al, ASH 2015; Gupta et al, ASCO 2016 Newberry et al, Blood 2017; 130:1125-1131 Kuykendall et al, Ann Hematol 2018; 97:435-441 Spiegel et al, Blood Advances 2017; 1:1729-1738 *Fedratinib approved for Int-2/High-risk MF– since label contains no second-line, **9.4 mg/kg dosing arm as reported at ASH 2018 R/R MF efficacy information, or specific approval for such indications, we expect that it will be marketed for only Int-2/High-risk MF.

Imetelstat

First-in-class telomerase inhibitor

Relapsed/Refractory MF Investigational Agent IMbark Phase 2 Trial: Median Overall Survival 29.9 months**

Differentiators:

• Non-JAKi targeted approach
• Potential disease-modifying activity

75%

5-year ruxolitinib discontinuation rate Primary reasons:

• Suboptimal response
• Loss of therapeutic effect

Median Overall Survival is ~14-16 months

After discontinuation of ruxolitinib

Relapsed/Refractory MF No Approved Products* Front Line MF

IMbark Phase 2 Results

Data suggest potential improvement in survival

24

Clinical cut-off (10/22/2018):

• Median follow-up: 27.4 (0.2-33.0) mos

Median overall survival:

• 29.9 mos (95% CI: 22.8, NE)

ASH 2018 Presentation: Mascarenhas J, et. al.

29.9 mos

IMbark Phase 2 Statistical Analyses

Corroborate potential survival benefit

25

Kuykendall A., et al, EHA 2019 Poster

IMbark Phase 2 Data vs. Real-World Data (RWD) Results: Analyses suggest potential survival benefit and lower risk of death for imetelstat vs. BAT from RWD

• In an unweighted analysis comparing the two patient cohorts:
• Median OS of 33.8 months for imetelstat-treated patients from IMbark is

more than double the median OS of 12.0 months for BAT from RWD

• Imetelstat conferred 65% lower risk of death compared to BAT from RWD
• Results suggest favorable OS with imetelstat treatment when compared to

closely-matched RWD from patients treated with BAT

• Analyses using two statistical adjustment methods resulted in similar
• utcomes to the unweighted analysis (imetelstat: 30.7 mos; BAT: 12.0 mos)

Purpose: Assess potential overall survival benefit with imetelstat treatment

• IMbark data compared to RWD of a closely-matched cohort of patients from

Moffitt Cancer Center who had discontinued ruxolitinib and were subsequently treated with best available therapy (BAT)

• Propensity score analysis approach taken to match individual patients within

each dataset to mimic the effect of randomization and improve comparability

Acknowledging the limitations of such comparative analyses between RWD and clinical trial data, favorable OS of imetelstat treatment in this very poor- prognosis patient population warrants further evaluation

33.8 mos 12.0 mos

Potential Late-Stage Development in MF

Preparing for discussions to determine regulatory path forward

26

2019 2020 Q4 Q1 Q3 Q2 Expect EOP2 Meeting by end

• f Q1 2020

Expect a decision on late-stage development in relapsed/refractory MF after EOP2 Meeting Preparing for End of Phase 2 (EOP2) Meeting

• Analyses supporting regulatory strategy
• Feedback from KOLs on OS results
• Designs for potential registration trials

Granted Fast Track designation by the FDA for relapsed/refractory MF

Upcoming Milestones

2019 Development Plans

28

Complete Transition of Imetelstat Development Program

❑ Transfer IND sponsorship by the end of the second quarter ❑ Transition of imetelstat program back to Geron by end of third quarter ❑ Actively recruit hematology-oncology research and development expertise throughout 2019 ❑ Chief Medical Officer ❑ Senior Leadership in Pharmacovigilance and Safety, Clinical Sciences/Operations, Clinical Development, Biostatistics, Quality, Manufacturing, Regulatory Affairs

MDS Development

❑ Updated data from the Phase 2 portion of IMerge presented at EHA in June 2019 ❑ Site initiation for Phase 3 portion of IMerge in July 2019 ❑ Commence screening and enrollment for Phase 3 portion of IMerge in August 2019

Prepare for End of Phase 2 Meeting with the FDA for Relapsed/Refractory MF

❑ Initiate discussions with MF KOLs ❑ Prepare analyses and develop regulatory strategies for FDA meeting ❑ Conduct an End of Phase 2 meeting by the end of the first quarter of 2020

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

Thank you

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