corporate presentation · imerge: 2-part phase 2/3 trial ©2020, geron corporation | nasdaq: gern |...

Geron CorporationNasdaq: GERN

Corporate Presentation

May 2020

Forward Looking Statements

©2020, Geron Corporation | Nasdaq: GERN | 2

Except for the historical information contained herein, this presentation contains forward-looking statements made pursuant to the “safe harbor” provisions of the PrivateSecurities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements, include, without limitation, those regarding: (i) that Geron expects tocomplete IMerge enrollment in the first quarter of 2021 and have top-line results in the second half of 2022; (ii) Geron’s plans to start enrollment in the refractory MF Phase3 trial in the first quarter of 2021, have enrollment completed in the second half of 2022, have results from an interim analysis in the first half of 2023, and have final top-lineresults in the first half of 2024; (iii) the therapeutic and commercial potential of imetelstat, including that imetelstat has potential disease-modifying activity; (iv) expectedimetelstat patent coverage in the EU and U.S. and expected market exclusivity related to orphan drug designation in the EU and U.S.; (v) that imetelstat has potential futureopportunities in High Risk Myelodysplastic Syndromes/Acute Myeloid Leukemia (HR MDS/AML), Polycythemia Vera (PV), and Essential Thrombocythemia (ET); (vi) that theU.S. and worldwide annual revenue potential for imetelstat in lower risk MDS (LR MDS) could exceed $500 million and $1 billion, respectively, and for refractory MF couldexceed $750 million and $1.5 billion, respectively; (vii) that in LR MDS, imetelstat has the ability to treat both ring sideroblast positive (RS+) and ring sideroblast negative (RS-)patients; (viii) that imetelstat treatment for MF has a potential survival benefit compared to best available treatment (from real world data); and (ix) other statements thatare 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: (a) whether Geron overcomes all the potential delays, added expense and otheradverse impacts caused by the evolving effects of the novel coronavirus (COVID-19) pandemic, and overcomes the clinical, safety, efficacy, technical, scientific, intellectualproperty, manufacturing and regulatory challenges in order to meet the expected timelines and planned milestones in (i) and (ii) above; (b) whether Geron’s existing capitalresources will be sufficient to enable Geron to meet the expected timelines and planned milestones in (i) and (ii) above; (c) whether regulatory authorities permit the furtherdevelopment of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether imetelstat is demonstrated to be safe and efficacious in clinical trials; (e) whetherany future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (f) whether imetelstat actually demonstrates disease-modifyingactivity in patients; (g) that imetelstat may not achieve the revenue potential in (vi) above because: Geron may not have the expertise to successfully market imetelstat,competition could cause imetelstat not to achieve the revenue potential in (vi) above and/or that Geron may not have sufficient funds to successfully commercializeimetelstat; (h) whether imetelstat is able to maintain the patent protection and obtain and maintain the orphan drug exclusivity referenced in (iv) above and have freedom tooperate; (i) Geron may decide not to pursue development of imetelstat in HR MDS/AML, PV or ET; and (j) Geron will need to raise substantial additional capital to completethe Phase 3 clinical trial in refractory MF and begin the commercialization of imetelstat. 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 under the heading “Risk Factors” inGeron’s quarterly report on Form 10-Q for the quarter ended March 31, 2020 filed with the Securities and Exchange Commission (the “SEC”). Undue reliance should not beplaced 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.

Geron Snapshot


Compelling and Differentiating Phase 2 Data

Unique mechanism of action inhibiting telomerase, an upregulated target in hematologic myeloid malignancies

Evidence of potential disease-modifying activity across a spectrum of hematologic malignancies

100% owned by Geron

Imetelstat: First-In-Class Telomerase Inhibitor

Clinical/regulatory team highly experienced in developing therapeutics for hematologic malignancies

Includes employees in clinical, regulatory, statistics, translational science and commercial who guided earlier imetelstat development at Janssen

Highly Experienced Development Team

Ongoing, randomized, placebo-controlled Phase 3 in LR MDS relapsed/refractory to ESAs; top-line results expected 2H 2022

Planned randomized, overall survival Phase 3 in Int-2/High-risk MF patients refractory to JAKi vs. BAT; expected milestones: open trial 1Q 2021, completion of enrollment 2H 2022, interim analysis 1H 2023, final top-line results 1H 2024

Two Phase 3 Trials with Registration Intent

LR MDS: Meaningful and durable transfusion independence, and increase in hemoglobin levels

MF: 28.1 mos.a median OS in Int-2/High-risk MF patients relapsed/refractory to JAKi compares favorably to historical controls of 14-16b

mos. and 12 mos.c from RWD analyses of best available therapy (BAT)

aEHA 2020 Abstract: Mascarenhas J, et al bKuykendall et al, Ann Hematol 2018; 97:435-441; Newberry et al, Blood 2017; 130:1125-1131; Spiegel et al, Blood Advances 2017; 1:1729-1738 cEHA 2019 Poster: Kuykendall A, et al LR MDS, lower risk myelodysplastic syndromes; MF, myelofibrosis; OS, overall survival; JAKi, janus kinase inhibitor; ESAs, erythropoiesis stimulating agents

About Imetelstat

• Structure: Proprietary 13-mer thio-phosphoramidate (NPS) oligonucleotide, with covalently-bound lipid tail to increase cell permeability/tissue distribution

• Potent competitive inhibitor of telomerase activity

• FDA has granted Fast Track and Orphan Drug designations for both lower risk MDS and Int-2/High-risk MF

• Clinical experience: more than 600 patients treated in Phase 1 and 2 trials

• Phase 3 clinical trial in lower risk MDS currently enrolling

• Patent/Market exclusivity:

➢ Composition of matter patent coverage expires in 2024 in EU and 2025 in U.S.

➢ Patent term extension includes potential five-years in EU, until2029 and until 2030 in U.S.

➢ Methods of use patents until 2033 for MF in EU and until 2033 for both MDS and MF in U.S.

➢ Expected market exclusivity extension related to orphan drug designation in EU for up to ten years and in U.S. for up to seven years

A novel telomerase inhibitor discovered and developed by Geron

Imetelstat


Telomerase Continuously Upregulated

Imetelstat Mechanism of Action in Hematologic Malignancies


In normal stem and progenitor cells, telomerase is transiently upregulated, enabling maintenance of normal hematopoiesis

Normal Hematopoiesis Malignant Hematopoiesis

Malignant hematopoietic progenitor cells

Malignant blood cells

Malignanthematopoietic

stem cells

Hematopoietic progenitor cells

Mature blood cells

Hematopoietic stem cells

The accumulation of these malignant cells is associated with clinical manifestations of disease

*Data on file

Telomerase Transiently Upregulated

In malignant stem, progenitor and blood cells, telomerase is continuously upregulated, resulting in malignant hematopoiesis

Imetelstat selectively targets malignant cells with continuously upregulated telomerase, inducing their apoptosis (cell death), and enabling potential recovery of normal hematopoiesis*

Imetelstat Indications in Hematologic Myeloid Malignancies


Potential to benefit patients across multiple indications

Lower Risk MyelodysplasticSyndromes (LR MDS)

Unmet Need

Patients lose transfusion independence and need more durable transfusion independence

Program Status

IMerge Phase 3 ongoing. Top-line results expected 2H 2022

Imetelstat target patient population is non-del(5q), LR MDS patients relapsed/refractory to ESAs

U.S. Annual Revenue Potential**

$500M+

Int-2 / High-Risk Myelofibrosis (MF)

Polycythemia Vera (PV)

Essential Thrombocythemia(ET)

~25,0002nd line

U.S. Patients

~40,0002nd line

U.S. Patients

Unmet Need

Patients are non-responsive to hydroxyurea (HU) and have a sub-optimal response to JAKi in HU failures

Unmet Need

Patients who have failed standard therapy have limited options

~5,0002nd line+

U.S. Patients

Unmet Need

Patients fail HMA and/or BCL-2 treatments

Potential Future Opportunities

Other diseases characterized by telomerase upregulation, associated with malignant stem and progenitor cell proliferation

ImetelstatPhase 2 ClinicalData

Anti-leukemic activity in blast phase MF (n=9)Company data


100% hematologic response (n=2) Company data


100% hematologic response (n=18)NEJM 2015

~12,500Int-2/HR MF U.S. Patients

Unmet Need

75% of patients discontinue ruxolitinib after five years, and have poor survival of ~14-16 mosa

No specifically approved therapies for JAKi refractory patients

Program Status

Plan to start Phase 3 1Q 2021

Imetelstat target patient populationis Int-2/HR MF patients who are refractory to JAKi treatment

U.S. Annual Revenue Potential**

$750M+

HR MDS / Acute Myeloid Leukemia (AML)

Phase 3 Development

Source: MDS: Zeidan Blood 2019; MF: Decision Resources 2019; AML/HR-MDS: Smart Analyst 2020; ET/PV NORD est.** Company estimates; Geron Proprietary Market ResearchaKuykendall et al, Ann Hematol 2018; 97:435-441; Newberry et al, Blood 2017; 130:1125-1131; Spiegel et al, Blood Advances 2017; 1:1729-1738HMA, hypomethylating agent; BCL-2, b-cell lymphoma-2

~40,000LR MDS

U.S. Patients

Lower Risk

Myelodysplastic Syndromes (MDS)

Lower Risk Myelodysplastic Syndromes (LR MDS)


Imetelstat to address significant unmet need with a large market opportunity

Disease Characteristics• Ineffective production of RBCs, WBCs, and platelets (hematopoiesis)

• Chronic anemia

• Patient subgroups include Ring Sideroblast Positive (RS+) and Ring Sideroblast Negative (RS-)

Current Treatment Paradigm• Treated initially with erythropoiesis stimulating agents (ESAs)

• Patients relapsed/refractory to ESAs are RBC transfusion dependent

• Serial RBC transfusions result in lower quality of life, significant costs, lengthy office visits, iron overload, shorter survival and higher risk of transformation to AML

Opportunity*

~70% of all MDS patients are lower risk

>40,000 LR MDS U.S. patients today

>10,000 LR MDS U.S. patients diagnosed annually

Imetelstat U.S. annual revenue potential >$500M**

*Lower risk MDS patients without chromosomal 5q deletion (non-del(5q)), relapsed/refractory to ESAs prior to being treated with lenalidomide or hypomethylating agents (HMAs)Source: SEER; Greenberg 2012 Revised IPSS MDS; Platzbecker, Treatment of MDS 2019 Blood; Cogle, Curr Hematol Malig Rep; 2015; Greenberg, et al, Blood 1997;89:2079-2088**Company Estimates; Geron Proprietary Market Research.

The Unmet NeedHigher rate of transfusion independence than currently available options

Durable transfusion independence

Ability to treat both RS+ and RS- patients

Disease-modifying therapy

RBCs, red blood cells; WBCs, white blood cells; AML, acute myeloid leukemia

ClinicalTrials.gov (NCT02598661)

IMerge: 2-Part Phase 2/3 Trial


Part 1 – Phase 2 portion

Imetelstat

7.5mg/kg every 4weeks

• Transfusion dependent is defined as an RBC transfusion requirement of ≥4 units over 8-week period during the 16

weeks prior to trial entry

• Relapsed/Refractory to Erythropoiesis Stimulating Agents (ESAs) following ≥8 weeks of weekly epoetin alfa 40,000

units or darbepoetin alfa 150 mcg (or equivalent) or serum erythropoietin (sEPO) >500 mU/mL

• Both RS+ and RS- MDS subgroups permitted

• Supportive care permitted: 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, no prior treatment with lenalidomide or HMAs(n=38)

1° Efficacy:

Red Blood Cell (RBC) TransfusionIndependence (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 Data: Efficacy


1-Year RBC-TI rate now reported

a Kaplan Meier method

All data is from EHA 2019 Presentation: Fenaux P, et al, unless otherwise noted*EHA 2020 Abstract: Platzbecker U, et al, published May 14, 2020; oral presentation to occur at EHA 2020

75% of TI responders had hemoglobin rise of > 3g/dL from pretreatment level, suggesting potential recovery of normal hematopoiesis

No. of patients 38

Median baseline transfusion burden, units/8 weeks (range) 8 (4-14)

Rate of 8-week RBC-TI, % (n)Median durationa of RBC-TI, weeksMedian time to onset of RBC-TI, weeks (range)

42% (16/38)88*

8.3 (0.1-40.7)

Rate of 24-week RBC-TI, % (n) 32% (12/38)*

Rate of 1-year RBC-TI, % (n) 29% (11/38)*

Hematologic improvement-erythroid (HI-E), % (n)

≥1.5 g/dL increase in hemoglobin lasting ≥8 weeks

Transfusion reduction by ≥4 units/8 weeks

Median durationa of HI-E, weeks

68% (26/38)

32% (12/38)

68% (26/38)

93*

Mean relative reduction of RBC transfusion burden from baseline, % -68%

Confidential & Proprietary


IMerge Phase 2 Data


Similar activity across different patient subgroups

Similar 8-week TI responses across different patient subgroups

• RS Subgroups:

RS+ (RARS/RCMD- RS) vs. RS- (Other)

• Baseline transfusion burden:

High (4-6 units) vs. Very High (>6 units)

• Serum EPO level:

≤ 500 mU/mL vs. > 500 mU/mL

Source: EHA 2019 Presentation: Fenaux P, et.al.


IMerge Phase 2 Data: Safety


Most frequent hematologic and non-hematologic adverse events (AEs)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; LFT, liver function testGrade 3 LFT elevations were reversible

aIn 3/7 (43%) patients back pain was an AE associated with infusion related reaction

bnasopharyngitis, diarrhea, constipation, edema peripheral and asthenia

Hematologic AEs

TEAEAll GradesN=38 (n, %)

Grade 3/4N=38 (n, %)

Thrombocytopenia 25 (66) 23 (61)

Neutropenia 22 (58) 21 (55)

Anemia 10 (26) 8 (21)

Non-Hematologic AEs

TEAEAll GradesN=38 (n, %)

Grade 3/4N=38 (n, %)

Back paina 7 (18) 0

ALT increased 7 (18) 2 (5)

AST increased 6 (16) 3 (8)

Bronchitis 6 (16) 3 (8)

Other AEsb 6 (16) 0

Headache 6 (16) 1 (3)

Source: EHA 2019 Presentation: Fenaux P, et al


IMerge Phase 2 Data: Safety


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

91% 92%

0

10

20

30

40

50

60

70

80

90

100

Neutrophils Platelets

%

Recovery of Grade 3/4 Cytopenia by Laboratory Value

Did not resolvewithin 4 weeks

Resolved within 4weeks

Source: EHA 2019 Presentation: Fenaux P, et al


IMerge Part 1 – Phase 2 MEDALIST1 - Phase 3**

Imetelstat Luspatercept Placebo

38 No. of patients 153 76

Non-del(5q) R/R to ESAs Target patient population Non-del(5q) R/R to ESAs

RS+ and RS- MDS ring sideroblast (RS) subgroups RS+ only

8 (4-14) Median baseline transfusion burden# units/8 weeks (range)

5 (2-20)66 (29%) < 4U / 8 wks

42% (16/38) ≥8-week RBC-TI rate, % (n) 48% (73/153) 16% (12/76)

42% (16/38)≥8-week RBC-TI rate, % (n)

Patients with baseline transfusion burden ≥ 4 units / 8weeks

32% (34/107) 7% (4/56)

32% (12/38)* ≥24-week RBC-TI rate, % (n) Not reported/assessed

29% (11/38)* ≥1-year RBC-TI rate, % (n) Not reported/assessed

88 weeks* Median duration of RBC-TI 31 weeks 14 weeks

Key Imetelstat Efficacy Results in LR MDS


Breadth (RS+/RS-), depth (RBC-TI Rate) and durability of response

1 Comparative MEDALIST Phase 3 data provided for informational purposes only and should not be relied upon as demonstrative or indicative of imetelstat’s potential in LR MDS. There are several limitations when comparing results from an open-label Phase 2 trial to a blinded, placebo-controlled Phase 3 trial with a significantly greater patient population, and also, luspatercept is an approved treatment with a relatively benign safety profile.All IMerge Phase 2 data is from EHA 2019 Presentation: Fenaux P, et al, unless otherwise noted. *EHA 2020 Abstract: Platzbecker U, et al, published May 14, 2020; oral presentation to occur at EHA 2020.

**MEDALIST sponsor – Celgene/Acceleron. ASH 2019 Presentation: Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in IPSS-R Very Low-, Low-, or Int-Risk RBC Transfusion-Dependent MDS with Ring Sideroblasts; Fenaux P, et al; NEJM 2020 Supplementary Appendix 2020; 382:140-51.

Lower Risk Myelodysplastic Syndromes (LR MDS)


A significant addressable market opportunity

Source: SEER; Zeidan Blood 2019 ** Company Estimates; Geron Proprietary Market Research; Worldwide revenue estimates: EU revenue potential ~45% of U.S., additional markets ex-U.S./ex-EU ~ 20% of U.S. revenue potential

>100,000LR MDS patients worldwide

>40,000LR MDS patients in the U.S.

>10,000LR MDS cases diagnosed

annually in the U.S.

$500M+U.S. annual revenue potential for

Imetelstat in LR MDS**

$1.0B+Worldwide annual revenue potential

for imetelstat in LR MDS**

Imetelstat target patient population

is non-del(5q) LR MDS patients

relapsed/refractory to ESAs

Imetelstat in LR MDS*


Highly differentiated therapy designed to address unmet need in patients R/R to ESAs

Novel Mechanism of ActionFirst-in-class Telomerase Inhibitor

Selectively targets malignant stem, progenitor and blood cells with continuously upregulated telomerase, inducing their apoptosis (cell death), enabling potential recovery of normal hematopoiesis1

Ability to Treat Both RS+ and RS- PatientsTI similar in both RS+ and RS- patients

High Rates of Transfusion Independence (TI)42% of patients achieved 8-week TI and 68% achieved hematologic improvement (HI-E)

Potential Disease-Modifying Activity29% of patients were transfusion free for ≥1 year**

75% of TI responders had hemoglobin rise of > 3g/dL from pretreatment level, which suggests potential recovery of normal hematopoiesis

Durability of Transfusion Independence29% of patients were transfusion free for ≥1 year**

Median duration of TI was 88 weeks**

*Imetelstat target patient population is non-del(5q)LR MDS patients relapsed/refractory to ESAs

R/R, relapsed/refractoryAll data is from EHA 2019 Presentation: Fenaux P, et al, unless otherwise noted**EHA 2020 Abstract: Platzbecker U, et al published May 14, 2020 1Data on file


IMerge Phase 3 in LR MDS


Currently enrolling

Imetelstat(n = ~115)

7.5mg/kg every 4 weeks

Placebo(n = ~55)R

and

om

ize

(2

:1)

Do

ub

le-b

lind

Transfusion Dependent, Low or Intermediate-1 Risk MDS, non-del(5q), R/R to ESAs, no prior 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

Phase 3 Trial Design• Same dose and schedule as Phase 2

• Same primary and secondary endpoints as Phase 2

• Same target patient population as Phase 2, including both RS+ and RS- patient subgroups

• Many of the clinical sites participated in Phase 2

• Many of the key imetelstat Phase 2 clinical team members are managing Phase 3

Current Status/Progress➢ First patient was dosed in October 2019

➢ As of the end of April 2020, 68% of planned clinical sites were opened for enrollment

➢ Targeting completion of enrollment in 1Q 2021

➢ Top-line results expected 2H 2022

Intermediate-2 or High-Risk Myelofibrosis (MF)

Int-2/High-Risk Myelofibrosis


Imetelstat to address significant unmet need with a large market opportunity

Source: Decision resources**Company estimates

Opportunity*

~70% of all MF patients are Int-2 or HR

>12,500 Int-2/HR MF patients in the U.S.

>2,100 Int-2/HR MF patients diagnosed each year in the U.S.

Imetelstat U.S. annual revenue potential > $750M**

The Unmet NeedTherapies that can extend survival

Treatment options for patients who are refractory to JAKi therapy

Disease-modifying therapy

Non-JAKi mechanism of action

Disease Characteristics• Malignant stem and progenitor cell proliferation give rise to malignant

megakaryocytes, bone marrow fibrosis and impaired hematopoiesis

• Splenomegaly: normal blood production shifts to other organs, such as the spleen, which can cause the spleen to enlarge

• Symptoms: fever, weight loss, night sweats)

• Fibrosis: thought to be induced by inflammatory cytokines produced by megakaryocytes originating from malignant progenitor cell clones

Current Treatment Paradigm for Int-2/HR MF• Only approved therapies in the U.S. are JAKi (ruxolitinib and fedratinib)

• Most patients lose response to ruxolitinib

• ~50% patients discontinue ruxolitinib within 3 years and 75% within 5 years

• Poor survival of 14-16a months for patients who discontinue ruxolitinib

* Int-2/HR MF patients who are refractory to JAKi treatment

aKuykendall et al, Ann Hematol 2018; Newberry et al, Blood 2017; 130:1125-1131; 97:435-441; Spiegel et al, Blood Advances 2017; 1:1729-1738

ClincialTrials.gov (NCT02426086)

IMbark Phase 2 Trial


Clinical activity in relapsed/refractory MF patients

Trial Population:

• Patients with Intermediate-2 or High-risk MF (Int-2/High-risk) patients who have relapsed after or are refractory to prior treatment with a janus kinase inhibitor (JAKi)

• Relapsed or refractory to JAKi defined as documented progressive disease during or after JAKi:

o Patients must have worsening of splenomegaly-related abdominal pain at any time after the start of 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

Intermediate-2 or High-risk MF

R/R to JAKi treatment

Ran

do

miz

e(1

:1) Imetelstat

9.4 mg/kgevery 3 weeksn=59

Imetelstat4.7 mg/kgevery 3 weeksn=48

Co-primary endpoints:Spleen response rate and symptom response rate

Secondary endpoints:CR, PR and CI, anemia response per 2013 IWG-MRTcriteria, duration of responses,and overall survival (OS)

Exploratory endpoints:Cytogenetic and molecular responses, leukemia free survival

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




IMbark Phase 2: Symptom Response at Week 24

19 (32%) patients in the 9.4 mg/kg arm had ≥ 50% decrease in TSS from baseline at Week 24

TSS, total symptom score.

31 (52%) patients in the 9.4 mg/kg arm had ≥ 50% symptom response at any time **

** Data on file

3 symptom respondersin 4.7 mg/kg

19 symptom responders in 9.4 mg/kg

Source: ASH 2018 Presentation: Mascarenhas J, et al




IMbark Phase 2: Spleen Volume Reduction (SVR) at Week 24

6 (10%) patients in the 9.4 mg/kg arm had ≥ 35% SVR at Week 24

22 (37%) patients in the 9.4 mg/kg arm had ≥ 10% SVR at Week 24

0 SVR responder in4.7 mg/kg

6 SVR responders in 9.4 mg/kg

SVR, spleen volume reduction.



IMbark Phase 2 Data: Safety


Most frequent hematologic* and non-hematologic adverse events (AEs)

*Treatment emergent, per reported AEs (not laboratory values). Frequency of reported Grade 3/4 hematologic AEs were consistent with cytopenias reported through lab values.

4.7 mg/kg (n=48)

9.4 mg/kg (n=59)

n (%) All Grades Grade ≥ 3 All Grades Grade ≥ 3

Hematologic (≥ 10% in either arm)

Thrombocytopenia 11 (23) 11 (23) 29 (49) 24 (41)

Anemia 15 (31) 15 (31) 26 (44) 23 (39)

Neutropenia 5 (10) 5 (10) 21 (36) 19 (32)

Leukopenia 3 (6) 3 (6) 8 (14) 8 (14)

Non-hematologic (≥ 20% in either arm)

Nausea 15 (31) 1 (2) 20 (34) 2 (3)

Vomiting 10 (21) 1 (2) 8 (14) 1 (2)

Diarrhea 18 (38) 2 (4) 18 (31) 0

Fatigue 10 (21) 3 (6) 16 (27) 4 (7)

Cough 11 (23) 0 9 (15) 0

Dyspnea 9 (19) 6 (13) 14 (24) 3 (5)

Abdominal Pain 10 (21) 2 (4) 14 (24) 3 (5)

Asthenia 9 (19) 3 (6) 14 (24) 6 (10)

Pyrexia 8 (17) 1 (2) 13 (22) 3 (5)

Edema peripheral 13 (27) 0 11 (19) 0



IMbark Phase 2 Data: Safety


Reversible grade 3/4 cytopenias and no observed hepatic toxicities

Grade 3/4 Liver Function Test (LFT) elevations were observed in 7 patients on study

• An independent Hepatic Review Committee reviewed all LFT and hepatic data

• Imetelstat-related hepatic toxicities were not observed

Most grade 3/4 cytopenias were reversible within 4 weeks

Clinical consequences of cytopenias

n(%)4.7 mg/kg

(n=48)9.4 mg/kg

(n=59)

Grade 3 Febrile Neutropenia 1 (2) 1 (2)

Grade ≥ 3 Hemorrhagic events 2 (4) 3 (5)

Grade ≥ 3 Infections 10 (21) 6 (10)



IMbark Phase 2 Data: Survival


Data suggest potential improvement in survival

Clinical cut-off (Feb 19, 2020):

Median follow-up: 41.7 months

Median overall survival:

28.1 mos. (95% CI 22.8-31.6)

** Kuykendall et al, Ann Hematol 2018; 97:435-441; Newberry et al, Blood 2017; 130:1125-1131; Spiegel et al, Blood Advances 2017; 1:1729-1738

All data is from EHA 2020 abstract: Mascarenhas J, et al, unless otherwise noted; published May 14; poster available at EHA 2020

After discontinuation of ruxolitinib:**

Median overall survival is ~14-16 mos.

28.1mos


IMbark Phase 2 Data vs. Real World Data


Further evidence of potential survival benefit

IMbark Phase 2 Data vs. Real-World Data(RWD)

Source: Kuykendall A., et al, EHA 2019 Poster

Purpose: Assess potential overall survival benefit withimetelstat 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 withineach dataset to mimic the effect of randomization and improve comparability

Results: Analyses suggest potential survival benefit and lower risk of death for imetelstat vs. BAT fromRWD

• In an unweighted analysis prior to statistical adjustments comparing the two patientcohorts:

o 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

o Imetelstat conferred 65% lower risk of death compared to BAT from RWD

o 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 outcomes to the unweighted analysis (imetelstat: 30.7 mos; BAT: 12.0 mos)

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

12.0 mos33.8 mos


Three Abstracts to be Presented at EHA 2020


Abstracts support overall survival observed in IMbark

EHA 2020 Abstracts published May 14, 2020; posters available at EHA 2020

Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes in Higher-RiskMyelofibrosis (MF) Relapsed/Refractory (R/R) to Janus Kinase Inhibitor Treated with Imetelstat; Mascarenhas J, et. al.

▪ Provides evidence for on-target mechanism of action of imetelstat through telomerase inhibition

Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor; Mascarenhas J, et. al.

▪ The potential survival benefit observed with imetelstat was supported by the trend of correlations with other clinicalbenefits, such as symptom and spleen response, as well as fibrosis improvement

Imetelstat Treatment Results in Clinical Benefits, Including Improved Overall Survival, in Patients with Higher-Risk Triple-Negative Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitors (JAKi); Kiladjian, et. al.

▪ Triple Negative (TN) patients treated with imetelstat 9.4 mg/kg had better clinical outcomes and OS vs. non-TNpatients, suggesting that treatment with imetelstat may overcome the poor outcomes expected with TN patients

Int-2/High-Risk Myelofibrosis


A significant addressable market opportunity

Source: Decision Resources 2019** Company estimates; Worldwide revenue estimates: EU revenue potential ~45% of U.S., additional markets ex-U.S./ex-EU ~ 20% of U.S. revenue potential

~70% Intemediate-2/High-risk; ~50% patients discontinue Rux within 3 years and 75% within 5 years; Tefferi, JCO 2005; 23:8520-8530; Tefferi, Mayo Clin Proc 2012; 87:25-33; Gangat et al, JCO 2011; 29:392-397

>35,000Int-2/HR MF patients

worldwide

>12,500 Int-2/HR MF patients in

the U.S.

>2,100 Int-2/HR MF cases diagnosed

annually in the U.S.

$750M+U.S. annual revenue potential for imetelstat

in JAKi Refractory MF**

$1.5B+Worldwide annual revenue potential for

imetelstat in Refractory MF**

Imetelstat target patient population

is Int-2/HR MF patients who are refractory to JAKi

treatment

Imetelstat in Int-2/High-Risk Myelofibrosis*


Highly differentiated therapy designed to address current unmet need

Novel Mechanism of Action

First-in-class Telomerase Inhibitor

Selectively targets malignant stem, progenitor and blood cells with continuously upregulated telomerase, inducing their apoptosis (cell death), enabling potential recovery of normal hematopoiesis1

Non-JAKi Treatment Option75% of patients discontinue ruxolitinib after five yearsc

There is no non-JAKi therapy approved for Int-2/HR MF

Improvement in Overall Survival28.1 mos.a median OS in Int-2/High-risk MF patients relapsed/refractory to JAKi compares favorably to historical controls of 14-16c mos. and 12 mos.b from RWD analyses of best available therapy (BAT)

Planned randomized Phase 3 trial in Int-2/HR refractory MF patients with overall survival as primary endpoint planned to open 1Q 2021 for enrollment

Potential Disease-Modifying ActivityPotential improvement in overall survival

Improvement in MF Symptoms 32%d of patients achieved symptom response (>50% reduction in TSS from baseline) at 24 wks; 52%1 of patients achieved symptom response at any time

aEHA 2020 abstract: Mascarenhas J, et al; published May 14; poster available at EHA 2020

b Kuykendall A, et al, EHA 2019 Posterc Kuykendall et al, Ann Hematol 2018; 97:435-441; Newberry et al, Blood

2017; 130:1125-1131; Spiegel et al, Blood Advances 2017; 1:1729-1738dASH 2018 Presentation: Mascarenhas J, etal

*Imetelstat target patient population is Int-2/HR MF patients who are refractory to JAKi treatment 1Data on file

Population: Int-2/High-risk MF refractory to a JAKi

– Inadequate spleen or symptom response after treatment with JAKi for ≥ 6 months, including an optimal dose of JAKi for at least 2 months

Primary endpoint: Overall Survival (OS; HR=0.6)

– Secondary endpoints include: symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of responses, safety, pharmacokinetics, patient reported outcomes

Statistical Design and Methods

Comparator arm: Best Available Therapy (BAT), excluding JAKi

Imetelstat treatment arm: 9.4 mg/kg every 3 weeks

Phase 3 Trial Design in Int-2/HR MF with OS as Primary Endpoint


Plan to open for enrollment 1Q 2021

Imetelstat(9.4 mg/kg q3 wks)

BAT (excl. JAKi)

Refractory MFInt2/High-risk (n=320)

Final Analysis for OSEvent-driven

Est timing: 1H 2024

OS

2:1

Interim Analysis for OS

Event-drivenEst timing: 1H 2023

Closing Remarks

Planned Development Priorities


2020 2021+

Data UpdatesEHA 2020 Annual CongressJune 11-14

More mature IMerge Phase 2 data, including durability of transfusion independence

Abstract Online: May 2020

Oral Presentation: June 2020

Three new analyses of IMbark Phase 2 data supporting observed potential improvement in OS as indicator of disease-modifying activity

Abstracts Online: May 2020

Three Posters: June 2020

Lower Risk MDSIMerge Phase 3 Clinical TrialLower risk MDS R/R to ESAs

Complete enrollment 1Q 2021

Top-line results 2H 2022

Refractory MFPhase 3 Clinical Trial Int-2/High-risk MF Refractory to JAKi

FDA accepted Phase 3 trial design May 2020

Open Phase 3 Refractory MF clinical trial 1Q 2021

Complete enrollment 2H 2022

Interim analysis 1H 2023

Final top-line results 1H 2024

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