Post-EHA KOL Event June 25, 2019 Forward-Looking Statements Except - - PowerPoint PPT Presentation

Post-EHA KOL Event

June 25, 2019

Forward-Looking Statements

2 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, include, without limitation, those regarding: (i) that the Phase 3 portion of IMerge will be open for patient screening and enrollment in August 2019, with site initiation in July 2019; (ii) that statistical analyses of IMbark data and closely matched RWD suggest favorable overall survival with imetelstat treatment when compared to closely matched RWD from patients treated with BAT in relapsed/refractory MF; (iii) that statistical analyses of IMbark data and closely matched RWD suggest treatment with imetelstat is associated with a lower risk of death compared to BAT; (iv) that imetelstat in lower risk MDS has potential impact on the malignant clone; (v) that imetelstat may have disease-modifying activity; (vi) that there will be an End of Phase 2 meeting with the FDA by the end of Q1 2020; 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, risks and uncertainties related to: (a) whether imetelstat is able to actually demonstrate a

lower risk of death and favorable overall survival compared to BAT in relapsed/refractory MF patients; (b) whether the comparative analyses between RWD and IMbark clinical trial data described in the poster presentation at EHA have limitations and cannot be relied upon as demonstrative; (c) whether the Company

• vercomes all the clinical, safety and efficacy, technical, scientific, manufacturing and regulatory challenges to enable the opening of the Phase 3 portion of

IMerge for screening and enrollment in August 2019 and site initiation in July 2019; (d) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (e) whether imetelstat is safe and efficacious; (f) whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (g) whether the Company 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; (h) the Company’s need for additional capital; and (i) whether imetelstat demonstrates disease-modifying activity. Additional information on the above risks and uncertainties and additional risks, uncertainties 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 Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 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.

Agenda

8:00 am Welcome Suzanne Messere Investor Relations 8:05 am Introductions Aleksandra Rizo, M.D., Ph.D. Chief Medical Officer 8:10 am An Introduction to Myelofibrosis Imetelstat vs. RWD

Comparative analyses of overall survival between IMbark Phase 2 clinical data and real-world data Presented at the 24th Annual Congress of the European Hematology Association

Q&A Rami Komrokji, M.D. Section Head – Leukemia and MDS, Moffitt Cancer Center, Tampa, Florida Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, Tampa, Florida 8:45 am An Introduction to Myelodysplastic Syndromes Imetelstat in Lower Risk MDS

Updated data from Phase 2 portion of the IMerge clinical trial Presented at the 24th Annual Congress of the European Hematology Association

Q&A Uwe Platzbecker, M.D. Head of Medical Department I – Hematology and Cell Therapy, University

• f Leipzig Medical Center, Leipzig,

Germany 9:20 am Closing Remarks John A. Scarlett, M.D. Chairman and Chief Executive Officer

Introductions

Aleksandra Rizo, M.D., Ph.D. Chief Medical Officer

Rami Komrokji, M.D.

5

Current

• Section Head – Leukemia and MDS, Moffitt Cancer Center, Tampa, Florida
• Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, Tampa,

Florida

• Senior Member and Professor of Oncologic Services, Moffitt Cancer Center,

Tampa, FL Previous

• Clinical Director, Malignant Hematology Department Lead Clinical Investigator,

Moffitt Cancer Center, Tampa, Florida

• Director Leukemia & Lymphoma Program, University of Cincinnati, Cincinnati,

Ohio Medical Training

• Jordan University School of Medicine, Amman, Jordan
• Internal Medicine Resident, Case Western University, St. Vincent Program,

Cleveland, Ohio

• Hematology-Oncology Fellow, Strong Memorial Hospital, University of Rochester,

Rochester, New York Expertise

• Clinical trials in hematologic malignancies with a focus on myelodysplastic

syndromes, myeloproliferative neoplasms and acute myeloid leukemia

An Introduction to Myelofibrosis

Rami Komrokji, M.D. Moffitt Cancer Center

Myelofibrosis (MF)

Disease characteristics

7

• 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

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

No approved drug for patients relapsed/refractory to ruxolitinib

8

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

> 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.

Imetelstat patient population*

~75%

• f Int-2/High-risk

MF patients

75%

5-year ruxolitinib discontinuation rate

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

Potential for meaningful survival in poor-prognosis patients

9

Ruxolitinib

• Primarily for symptoms or

splenomegaly

• Oral JAK1/JAK2 inhibitor
• Only approved product for

MF in U.S./Europe

• Stay on drug as long as

tolerated

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 *Geron press release: May 16, 2019; clinical cut-off of April 30, 2019

Primary reasons:

• Suboptimal response
• Loss of therapeutic effect

Median Overall Survival is ~14-16 months

After discontinuation of ruxolitinib

Investigational Agent: imetelstat

IMbark Phase 2 Trial: Median Overall Survival of 28.1 months* for 9.4 mg/kg dosing arm

Analyses of IMbark Phase 2 Data vs RWD Presented at the 24th EHA Annual Congress

Rami Komrokji, M.D. Moffitt Cancer Center

Andrew Kuykendall1, Ying Wan2, John Mascarenhas3, Jean-Jacques Kiladjian4, Alessandro Vannucchi5, Julia Wang6, Qi Xia6, Eugene Shu6, Faye Feller2, Aleksandra Rizo2, Jacqueline Bussolari6, Rami Komrokji, MD1

1Moffitt Cancer Institute, Tampa, FL, United States 2Geron Corporation, Menlo Park, CA, United States, 3Icahn School of Medicine at Mount

Sinai, New York, NY, United States, 4Hôpital Saint-Louis, Université Paris, Paris, France 5AOU Careggi, University of Florence, Florence, Italy,

6Janssen Research & Development, LLC, Raritan, NJ, United States

Favorable Overall Survival of Imetelstat-Treated Relapsed/Refractory Myelofibrosis Patients Compared with Closely Matched Real-World Data

Kuykendall et al. EHA 2019 Poster Presentation Abstract# PS1456

Kuykendall et al. EHA 2019 Poster Presentation

• Myelofibrosis (MF), particularly Intermediate-2 (Int-2) or High-Risk disease per

Dynamic International Prognostic Scoring System (DIPSS) criteria, is a life- threatening disease for which the Janus Kinase inhibitor (JAKi), ruxolitinib, is currently the only approved therapy

• Currently, there is no approved or effective therapy for patients who lack or lose

response to ruxolitinib

• These relapsed/refractory (R/R) patients have a notably poor prognosis, with

median overall survival (OS) of 12-14 months 1,2

• Imetelstat, a 13-mer oligonucleotide that specifically targets the RNA template
• f human telomerase, is a potent competitive inhibitor of telomerase

enzymatic activity

• A Phase 2 study, IMbark (MYF2001, NCT02426086), evaluated 2 doses of

imetelstat in JAKi-R/R Int-2 or High-Risk MF3

• Encouraging total symptom score improvements were observed in the 9.4 mg/kg

arm (no appreciable efficacy signal was observed in the 4.7 mg/kg arm)

• Median overall survival (OS) was 29.9 months (95% confidence interval [CI] 22.8,

not evaluable [NE]) in the 9.4 mg/kg arm, with clinical cut-off of 22 Oct 2018

1 Kuykendall AT, et al. Ann Hematol 2018;97:435-441; 2 Newberry KJ, et al. Blood

2017;130:1125-1131; 3 Mascarenhas J, et al. ASH 2018. Abstract & oral presentation #685

Background: Myelofibrosis (MF), Imetelstat and IMbark

imetelstat lipid tail telomere

Prevents binding by and maintenance of telomeres Imetelstat binds to RNA template

• f telomerase

X

NPS oligonucleotide

12

Kuykendall et al. EHA 2019 Poster Presentation

Original Patient Populations

• Int-2/High-risk MF per DIPSS criteria
• Relapsed or refractory to JAKi defined as

documented progressive disease during or after JAKi:

• Subjects must have worsening of splenomegaly-

related abdominal pain at any time after the start

• f JAKi therapy and EITHER:

❑ No reduction in spleen volume or size after 12 weeks of

JAKi therapy, or

❑ Worsening splenomegaly* at any time after the start of

JAKi therapy documented by:

– Increase in spleen volume from nadir by 25% measured by MRI or CT, or – Increase in spleen size by palpation, CT, or ultrasound

• Active symptoms of MF
• Baseline measurable splenomegaly (palpable

spleen ≥5 cm below LCM or ≥450 cm3 by MRI)

• Collected from a single-center study at the

Moffitt Cancer Center, patients who had discontinued ruxolitinib

• A closely matched cohort was identified using the

guidelines for inclusion and exclusion criteria as defined in IMbark protocol

• Cohort consisted of patients with MF who had

discontinued JAKi due to lack or loss of response and were subsequently treated with BAT at the Moffitt Cancer Center from January 1998 to August 2018

13

IMbark Criteria Real-World Data (RWD) Criteria

*Adapted from IWG-MRT response criteria definition of progressive disease

Kuykendall et al. EHA 2019 Poster Presentation

Bridging Clinical Trial Data and Real-World Data (RWD)

• Goal of analyses:
• To further assess the potential overall survival (OS) benefit of imetelstat in R/R MF patients treated with

9.4 mg/kg in IMbark

• Analyses performed:
• Main Analysis: OS was measured from the time of JAKi discontinuation to death or censored at last

follow-up

– All patients from the analysis populations of the IMbark and the RWD were included

• Sensitivity Analysis #1: to address the immortal time bias introduced by early deaths post JAKi

discontinuation observed in the RWD (i.e., align more closely with the IMbark clinical trial experience, where such patients would not have completed the screening phase):

– The RWD set excluded 2 patients who died within 1 month post JAKi discontinuation, with OS measured from 1 month post JAKi discontinuation – For IMbark, OS was measured from the randomization date

• Sensitivity Analysis #2: to assess the impact of subsequent hematopoietic stem cell transplant on OS

14

Kuykendall et al. EHA 2019 Poster Presentation

Patient Populations Used in Analyses

The analysis population included:

a) From IMbark:

– 57 patients treated with imetelstat 9.4 mg/kg – Median follow-up, 23 months

b) From RWD:

– 38 patients treated with BAT – Median follow-up, 43 months

15

Kuykendall et al. EHA 2019 Poster Presentation

Statistical Methods Applied to Minimize Biases Arising from Differences in Baseline Characteristics

• To mimic the effect of randomization and improve comparability, a propensity score analysis

approach was taken to match individual patients within each of the data sets to balance the populations with respect to important baseline covariates and prognostic factors that may impact OS outcomes

• Statistical adjustments applied:
• average treatment effect for overlap population (ATO) method
• stabilized inverse probability treatment weighting (sIPTW) method
• Baseline covariates utilized for matching:
• Improved balance in baseline covariates after statistical adjustments applied
• Using the ATO method, all p-values were 1.00 and standardized mean differences were <0.001
• Using the sIPTW method, p-value range was 0.263-0.957 and standardized mean differences were <0.3

16

Kuykendall et al. EHA 2019 Poster Presentation

Statistically Significant Reductions in Death Observed with Imetelstat Treatment Across Analyses

• The data is consistent across the analyses performed
• Median OS of 30.7 months for the imetelstat-treated patients from IMbark is more than double the median OS of 12.0 months using

RWD for patients treated with BAT

• Imetelstat conferred 65-67% lower risk of death compared to BAT in the unweighted analysis and per ATO and sIPTW weighting

methods using hazard ratios

• Results suggest favorable overall survival with imetelstat treatment when compared to closely matched RWD from patients treated

with BAT

17

Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 33.77 (26.87, NE) 12.04 (7.80, 30.53) Hazard ratio (95% CI) 0.35 (0.20, 0.62) P-value 0.0003 Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 30.69 (25.17, NE) 12.04 (7.80, 16.58) Hazard ratio (95% CI) 0.35 (0.18, 0.68) P-value 0.0019 Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 30.69 (25.17, NE) 12.04 (9.51, 16.58) Hazard ratio (95% CI) 0.33 (0.18, 0.61) P-value 0.0003

Kuykendall et al. EHA 2019 Poster Presentation

Sensitivity Analyses Consistent with Main Analysis

• Sensitivity Analysis #1 (above): Addressing the immortal time bias introduced by early deaths post JAKi discontinuation observed in the RWD
• Imetelstat conferred a 65% lower risk of death vs BAT in the unweighted analysis and 64% and 66% per ATO and sIPTW, respectively
• Sensitivity Analysis #2: Addressing the impact of subsequent transplant on OS
• Unweighted analysis: median OS with imetelstat vs BAT of 30.69 vs 10.23 months, with a 69% reduction in the risk of death
• ATO and sIPTW: median OS with imetelstat vs BAT of 30.69 vs 12.04 months, with 68% and 70% reductions in the risk of death per ATO and sIPTW, respectively

18

Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 29.86 (23.59, NE) 11.04 (6.80 43.74) Hazard ratio (95% CI) 0.35 (0.19, 0.65) P-value 0.0008 Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 29.86 (21.13, NE) 11.04 (7.13, 19.36) Hazard ratio (95% CI) 0.36 (0.18, 0.73) P-value 0.0044 Imetelstat (IMbark) BAT (Moffitt) Overall survival (months) Median (95% CI) 28.29 (21.13, NE) 11.04 (9.23, 14.03) Hazard ratio (95% CI) 0.34 (0.18, 0.66) P-value 0.0012

Kuykendall et al. EHA 2019 Poster Presentation

Conclusions

• These analyses showed that treatment with imetelstat was associated with

a lower risk of death compared to BAT in closely matched patients from RWD with Int-2 or High-Risk MF after JAKi failure:

• All sensitivity analyses were consistent with the main analysis
• 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

19

Main Analysis Unweighted ATO sIPTW Median OS: Imetelstat BAT 33.77 mos 12.04 mos 30.69 mos 12.04 mos 30.69 mos 12.04 mos Risk of Death 65% 65% 67%

Q&A

Rami Komrokji, M.D. Moffitt Cancer Center

Uwe Platzbecker, M.D.

21

Current

• Head of Medical Department I – Hematology and Cell Therapy, University of

Leipzig Medical Center, Leipzig, Germany Previous Positions

• Professor of Translational Hematology, Department of Internal Medicine and

Section Head of Hematology, University Hospital, Carl Gustav Carus, Dresden, Germany

• Professor of Haematology, Kings College Hospital Medical School, London, Great

Britain Medical Training

• University Hospital, Carl Gustav Carus, Dresden, Germany
• Translation Research, Fred Hutchinson Cancer Center, Seattle, Washington
• Internal Medicine, University Hospital, Carl Gustav Carus, Dresden, Germany
• Hematology/Oncology, University Hospital, Carl Gustav Carus, Dresden, Germany
• Palliative Medicine, University Hospital, Carl Gustav Carus, Dresden, Germany
• Hemostaseology, University Hospital, Carl Gustav Carus, Dresden, Germany

Expertise

• Hematological malignancies with a focus on MDS and AML, including the

translational exploration of innovative treatment options

• Co-founded the European MDS Study Coordinating Office (EMSCO)

An Introduction to Myelodysplastic Syndromes

Uwe Platzbecker, M.D. University of Leipzig Medical Center

Lower Risk Myelodysplastic Syndromes (MDS)

Disease characteristics

23 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 heterogeneous 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

Lower Risk MDS Patient Population in the U.S.

Addressing a significant unmet need

24

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

> 40,000

Lower risk MDS patients in the U.S.

> 10,000

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

Imetelstat target patient population*

~85%

• f lower risk MDS

Current Treatment Options Limited

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

25

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

• Median duration of

response: ~2 years

• Majority of patients

will relapse or become refractory

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%

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

Data from Phase 2 Portion of IMerge Presented at the 24th EHA Annual Congress

Uwe Platzbecker, M.D. University of Leipzig Medical Center

Treatment with Imetelstat Provides Durable Transfusion Independence in Heavily Transfused Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents

Pierre Fenaux1, David P. Steensma2 , Koen Van Eygen3 , Azra Raza4, Valeria Santini5, Ulrich Germing6, Patricia Font7, Maria Diez-Campelo8 , Sylvain Thepot9 , Edo Vellenga10, Mrinal M. Patnaik11, Jun Ho Jang12, Laurie Sherman13, Libo Sun14, Helen Varsos14, Aleksandra Rizo13, Ying Wan13, Fei Huang13, Jacqueline Bussolari14, Esther Rose14, Uwe Platzbecker 15

1Hො

• pital Saint-Louis, Universit ƴ

e Paris Diderot, Paris, France, 2Dana-Farber Cancer Institute, Boston, United States, 3Algemeen Ziekenhuis Groeninge, Kortrijk, Belgium, 4Columbia University Medical Center, New York, United States, 5 MOS Unit, AOU Careggi-University of Florence, Florence, Italy, 6Klinik f ሷ ur H ሷ amatologie, Onkologie and Klinische lmmunologie, Universit ሷ atsklinik D ሷ usseldorf, Heinrich-Heine-Universit ሷ at, D ሷ usseldorf, Germany, 7Department of Hematology, Hospital General Universitario Gregorio Mara෤ non, Madrid, 8Hematology Department, The University Hospital of Salamanca, Salamanca, Spain, 9CHU Angers, Angers, France, 10Department of Hematology, University Medical Center Groningen, Groningen, Netherlands, 11Division of Hematology, Mayo Clinic, Department of Internal Medicine, Rochester, MN, United States, 12Department of Hematology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic Of, 13Geron Corporation, Menlo Park, CA, United States, 14Janssen Research & Development, LLC, Raritan, NJ, 15Department of Hematology and Cell Therapy, University Clinic Leipzig, Leipzig, Germany

Funded by Geron Corporation and Janssen Research & Development Abstract code S837 27

• Patients with TD LR-MDS (low or intermediate 1 by IPSS) that

has relapsed or is refractory to ESA therapy have limited treatment options

• Higher telomerase activity, expression of human telomerase

reverse transcriptase (hTERT) and shorter telomeres predict for shorter overall survival in lower risk MDS1

• Imetelstat is a first-in-class telomerase inhibitor that targets

cells with short telomere lengths and active telomerase and has clinical activity in myeloid malignancies2-4

➢ FDA granted Fast Track designation for LR-MDS (Oct 2017)

• IMerge is an ongoing global phase 2/3 study of imetelstat in

RBC TD patients with LR-MDS with a primary endpoint of 8- week TI

1- Gurkan E, et al Leuk Res 2005; 29:1131-9; 2- Baerlocher GM, et al. N Engl J Med 2015;373:920-928, 3-Tefferi A, et al. N Engl J Med 2015;373:908-919, 4- Tefferi A, et al. Blood Cancer J 2016;6:e405 ESA, erythropoiesis-stimulating agent; hTERT, human telomerase reverse transcriptase; IPSS, International Prognostic Scoring System; Int-1, Intermediate-1; LR, lower risk; RBC, red blood cell; TD, transfusion dependent; TI, transfusion independence.

Background: Myelodysplastic Syndromes (MDS) and Imetelstat

imetelstat lipid tail telomere

Prevents binding by and maintenance of telomeres Imetelstat binds to RNA template

• f telomerase

X

NPS oligonucleotide

28

Fenaux et al. EHA 2019 Oral Presentation

(n = 38)

MDS patients:

• IPSS Low or Int-1
• Relapsed/Refractory

to ESA or EPO >500 mU/ml

• Transfusion

dependent: ≥ 4 units RBC/8 weeks over 16 week pre-study period

expand

All patients (n = 32) 8-week TI = 34% Initial Cohort (n = 13) non-del(5q) HMA/len naïve 8-week TI = 54% Expansion Cohort (n = 25) non-del(5q) HMA/len naïve

HMA, hypomethylating agent; len, lenalidomide 29

Primary Endpoint: 8-week RBC Transfusion Independence (TI) Key Secondary Endpoints: 24-week RBC TI/Duration of TI/HI-E

IMerge Phase 2/3 Study: Phase 2 Portion

Imetelstat 7.5 mg/kg IV q4w (2-hr infusion)

Fenaux et al. EHA 2019 Oral Presentation

• Data from 38 patients with non-del(5q) HMA/len naïve transfusion dependent

lower risk MDS is presented

• Data Cutoff Date: 30 April 2019

Treatment Exposure

Parameters n = 38 Median Follow-up, months (range) Initial cohort (n=13) Expansion cohort (n=25) 15.7 (5.6 – 37.5) 33.7 (5.6 – 37.5) 14.3 (10.9 – 16.5) Median treatment duration, months (range) 8.5 (0.02 – 37.5) Median treatment cycles (range) 9 (1 – 39) Median dose intensity, % 95.2

30

Fenaux et al. EHA 2019 Oral Presentation

Patient Treatment Disposition

Parameters n = 38 (n, %) Ongoing on Treatment 12 (32) Discontinued from Treatment Reason: Lack of Efficacy Adverse Event (AE) Withdrawal by Subject Progressive Disease Relapse Physician Decision 26 (68) 12 (32) 8 (21) 2 (5) 2 (5) 1 (3) 1 (3)

31

Fenaux et al. EHA 2019 Oral Presentation

Baseline Patient Characteristics

Parameters

n = 38

Age, years, median (range) 71.5 (46 – 83) Male, n (%) 25 (66) ECOG PS 0-1, n (%) 34 (89) IPSS risk, n (%) Low Intermediate-1 24 (63) 14 (37) RBC transfusion burden, units / 8 weeks, median (range) 8 (4 – 14) >4 units / 8 weeks at baseline, n (%) 35 (92) WHO 2001 category, n (%) RARS or RCMD-RS RA, RCMD or RAEB-1 27 (71) 11 (29) Prior ESA use, n (%) 34 (89) sEPO > 500 mU/mL, n (%) 12 (32)

(from 37 patients with baseline sEPO levels)

ECOG PS, Eastern Cooperative Oncology Group Performance Status; sEPO, serum erythropoietin; RA, refractory anemia; RAEB1, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; RCMD-RS, refractory cytopenia with multilineage dysplasia and ringed sideroblasts; WHO, World Health Organization 3 2

Fenaux et al. EHA 2019 Oral Presentation

a Kaplan Meier method

Meaningful and Durable Transfusion Independence with Imetelstat Treatment

Parameters n = 38

8-week TI, n (%) Time to onset, weeks, median (range) Duration of TIa, weeks, median (range) 16 (42) 8.3 (0.1 – 40.7) 85.9 (8.0 – 140.9) 24-week TI, n (%) 11 (29) HI-E per IWG 2006, n (%) ≥1.5 g/dL increase in Hgb lasting ≥ 8 weeks Transfusion reduction by ≥ 4 units/8 weeks 26 (68) 12 (32) 26 (68) CR + marrow CR + PR (per IWG 2006, central path review), n (%) CR marrow CR PR 9 (24) 5 (13) 4 (10)

CR, complete remission; IWG, International Working Group, PR, partial remission. 33

Fenaux et al. EHA 2019 Oral Presentation

8-week TI Observed Across Different Subgroups

34

Fenaux et al. EHA 2019 Oral Presentation

Durable Transfusion Independence with Imetelstat Treatment (median follow up 15.7 months; median treatment duration 8.5 months)

Of the 16 patients who achieved 8-week TI

• Median duration of TI is 86 weeks,

ranging from 8 - 141 weeks

• 11/16 (69%) achieved 24-week TI rate
• 12/16 (75%) had a Hgb rise ≥ 3g/dL

from the pretreatment level

35

Fenaux et al. EHA 2019 Oral Presentation

Reductions in Transfusion Burden in Majority of Patients Mean relative reduction of RBC transfusion burden from baseline was 68%

36

Fenaux et al. EHA 2019 Oral Presentation

Sustained Improvement in Hgb with Imetelstat Treatment

37

Hgb mean (+/-SE) change from baseline

Fenaux et al. EHA 2019 Oral Presentation

Activity in Patients with Intermediate or Poor Cytogenetic Risk

Among 34 patients with baseline cytogenetic data available:

• 6/34 (18%) had intermediate or poor cytogenetic risk

─ 5/6 (83%) achieved 8-week TI and all had a ringed-sideroblast WHO subtype ─ 3/3 with trisomy 8 achieved 8-week TI and 2/3 achieved 24-week TI ─ 4/6 remain on treatment

• 2/3 patients with available post-treatment cytogenetic data achieved partial cytogenetic response

Subject Karyotype ~24 wks post-imetelstat ~48 wks post-imetelstat 8-wk TI WHO Classification

200083* 47,XX,+8 [9] (45%) 47,XX,+8 [1] (5%)

X RCMD-RS

200088* 47,XY,+8 [20] (100%) 47,XY,+8 [5] (25%) 47,XX,+8 [1] (5%)

X RCMD-RS

200061 47,XX,+8 [20] (100%)

X RARS

200040 46,XY,DEL(7)(Q22) [5] (25%)

X RCMD-RS

200093* 46,XX,Dup/Tri/Qtp(9)(P13P24) [20] (100%) 46,XX,Dup/Tri/Qtp(9)(P13P24) [19] (95%) 46,XX,Dup/Tri/Qtp(9)(P13P24) [19] (95%)

X RCMD-RS

200102* 46,XY,T(3;3)(Q21;Q26.2) (100%)

RA

38

*remain on treatment

Fenaux et al. EHA 2019 Oral Presentation SF3B1 mutated Patient ID TI duration in SF3B1 patients (weeks)

200078* 48.7 200079 3.6 200081* 52 200083* 32 200088* 56.7 200095* 62.9

2/6 patients with baseline SF3B1 mutations had reduction in variant allele frequency and maintained TI lasting over a year Potential Impact on the Malignant Clone with Imetelstat Treatment

39 Confirmed partial cytogenetic response (from 100% to 5% abnormal karyotype)

*remain on treatment

Fenaux et al. EHA 2019 Oral Presentation

No New Safety Signals Identified

ALT, alanine aminotransferase; AST, aspartate aminotransferase; LFT, liver function test

TEAE All Grades

N=38 (n, %)

Grade 3/4

N=38 (n, %)

Thrombocytopenia 25 (66) 23 (61) Neutropenia 22 (58) 21 (55) Anemia 10 (26) 8 (21)

• Grade 3 LFT elevations were

reversible

TEAE All Grades

N=38 (n, %)

Grade 3/4

N=38 (n, %)

Back paina 7 (18) ALT increased 7 (18) 2 (5) AST increased 6 (16) 3 (8) Bronchitis 6 (16) 3 (8) Other AEsb 6 (16) Headache 6 (16) 1 (3)

Hematologic AEs Non-hematologic AEs

a In 3/7 (43%) patients back pain was an AE associated

with infusion related reaction

b nasopharyngitis, diarrhea, constipation, edema

peripheral and asthenia

40

Fenaux et al. EHA 2019 Oral Presentation

Reversible Grade 3/4 Cytopenias without Significant Clinical Consequences

• 2/38 patients (5%) had febrile neutropenia
• 4/38 patients (10%) had bleeding events, 2/38 (5%) were Grade 3/4

41

91% 92%

10 20 30 40 50 60 70 80 90 100

Neutrophils Platelets

%

Recovery of Grade 3/4 Cytopenia by Laboratory Value

Did not resolve within 4 weeks Resolved within 4 weeks

Fenaux et al. EHA 2019 Oral Presentation

8- and 24-week TI correlate with a reduction in hTERT expression

* In preclinical xenograft models, a 50% reduction in hTERT expression is the threshold correlated with anti- tumor activity hTERT expression 8-wk TI No 8- wk TI 24- wk TI No 24- wk TI

Matched baseline / post baseline data available 15/16 20/22 11/11 24/27 ≥50% reduction from baseline* 73% 35% 82% 38%

42

On Target Activity Demonstrated by Reduction in Telomerase Activity and hTERT Expression

Biomarker TA hTERT Matched baseline / post baseline data available 12/38 35/38 Reduction from baseline 6/12 (50%) 26/35 (74%)

Fenaux et al. EHA 2019 Oral Presentation

• Imetelstat treatment shows meaningful and durable transfusion independence

in heavily transfusion dependent non-del(5q) and HMA/len naïve lower risk MDS patients – 8-week TI rate 42% – 24-week TI rate 29% – Median TI duration approximately 20 months – HI-E rate 68%

Conclusions

43

Fenaux et al. EHA 2019 Oral Presentation

• Transfusion independence observed across different clinical subgroups,

including patients with int/poor cytogenetic risk

• Biomarker data suggest potential effect on the malignant clone and disease

modification

• No new safety signal was identified; reversable cytopenias were most

frequent AEs, without significant clinical consequences

• These results support initiation of the Phase 3 double-blind, placebo-

controlled (2:1) portion of the study, expected to open this summer

Conclusions

44

Fenaux et al. EHA 2019 Oral Presentation

Acknowledgements

Mazure, Dominiek Meers, Stef Breems, Dimitri

The authors thank all the patients for their participation in this study and acknowledge the collaboration and commitment

• f all investigators and their staff

Gourin, Marie-Pierre Gyan, Emmanuel Legros, Laurence Thepot, Sylvain Kim, Inho Lee, Je-hwan Klein, Saskia Langemeijer, Saskia van de Loosdrecht, Arjan Oliva, Esther Pristupa, Alexander Samoilova, Olga Udovitsa, Dmitry De Paz, Raquel Esteve, Jordi Valcarcel, David Xicoy, Blanca Boccia, Ralph Erba, Harry / DiStasi, Antonio Grunwald, Michael Jacoby, Megan Miller, Carole Schiller, Gary Silverman, Lewis Stevens, Don

45

Q&A

Uwe Platzbecker, M.D University of Leipzig Medical Center

Imetelstat Program Update

John A. Scarlett, M.D. Chairman and CEO

Geron Overview

48

Imetelstat, a Novel Drug with Unique Target

• Proprietary drug targeting telomerase-driven, uncontrolled progenitor cell proliferation in hematologic malignancies
• Development currently focused on two indications; both have significant unmet medical need and market opportunity
• Issued patent coverage until 2033 and orphan drug designation for MDS and MF

In-House Leadership and Expertise Establishes a Foundation for Potential Future Growth

• Highly-experienced in-house hematology-oncology and late-stage drug development team

Phase 3 Clinical Trial Starting August 2019 in Lower Risk Myelodysplastic Syndromes (MDS)

• Recently reported imetelstat Phase 2 efficacy data (8-week RBC-TI) compares favorably to data from the Phase 3 MEDALIST trial of

luspatercept in high transfusion burden, lower risk MDS patients

• Randomized, placebo-controlled Phase 3 clinical trial planned to open for screening and enrollment in August 2019
• Fast Track designation granted

Preparing for End of Phase 2 Meeting for Relapsed/Refractory Myelofibrosis (MF)

• Recently reported statistical analyses suggest favorable overall survival for imetelstat-treated relapsed/refractory MF patients compared to

best available therapy (BAT) in closely matched patients from real-world data

• End of Phase 2 meeting with FDA to potentially determine regulatory strategy for relapsed/refractory MF is planned by the end of Q1 2020

2019 Development Plans

49

Complete Transition of Imetelstat Development Program

❑ Transfer IND sponsorship by the end of the second 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 ❑ Senior Leadership in 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 regulatory strategies for End of Phase 2 meeting with the FDA in the second half of 2019 ❑ Schedule an End of Phase 2 meeting in the first quarter of 2020

✓ ✓ ✓ ✓ ✓

Thank you

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