kol event...2020/06/17 · eha presentation #s183 meaningful and durable transfusion independence...

Geron CorporationNasdaq: GERN

KOL EventJune 17, 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 tothe “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements, include, without limitation, those regarding: (i) that imetelstat has potential disease-modifying activity, and (ii)that Geron has a plan to open for enrollment a Phase 3 clinical trial in Intermediate-2 or High-risk myelofibrosis in the first quarterof 2021. These statements involve risks and uncertainties that can cause actual results to differ materially from those in suchforward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a)whether the COVID-19 pandemic slows or prohibits the Company’s ability to open for enrollment in the first quarter of 2021 theplanned Phase 3 clinical trial in Intermediate-2 or High-risk myelofibrosis; (b) whether regulatory authorities permit the furtherdevelopment of imetelstat on a timely basis, or at all, without any clinical holds; (c) whether imetelstat is safe and efficacious; (d)whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; and (e)whether imetelstat demonstrates disease-modifying activity in clinical trials. Additional information on the above risks anduncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in theforward-looking statements are contained under the heading “Risk Factors” in Geron’s Quarterly Report on Form 10-Q for thequarter 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 underlyingthe 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.


Today’s Agenda8:00 am Welcome Suzanne Messere Investor Relations

8:05 am Introduction Aleksandra Rizo, M.D., Ph.D. Chief Medical Officer

8:10 am Imetelstat in Lower Risk Myelodysplastic Syndromes (MDS)at 25th Annual European Hematology Association Annual Congress

Imetelstat to address significant unmet medical need

EHA Presentation #S183Meaningful and Durable Transfusion Independence

Q&A

Valeria Santini, M.D. Associate Professor of Hematology, University of Florence, Italy

Imetelstat in Intermediate-2 or High-risk Myelofibrosis (MF) at 25th Annual European Hematology Association Annual Congress

8:30 am Imetelstat to address significant unmet medical need

EHA Poster #EP1098Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes

Q&A

John Mascarenhas, M.D. Associate Professor in Myeloproliferative Disorders Program of the Tisch Cancer Institute, Division of Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, New York

8:50 am EHA Poster #EP1101Longer OS in Patients with Higher Risk Triple Negative MF

Q&A

Rami Komrokji, M.D. Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, Tampa, Florida

9:10 am EHA Poster #EP1107Favorable Overall Survival Correlates with Other Clinical Benefits

Q&A

John Mascarenhas, M.D. Associate Professor in Myeloproliferative Disorders Program of the Tisch Cancer Institute, Division of Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, New York

9:30 am Planned Phase 3 Clinical Trial in Refractory MF Aleksandra Rizo, M.D., Ph.D. Chief Medical Officer

9:40 am Closing Remarks John Scarlett, M.D. Chairman and CEO

Introduction

Aleksandra Rizo, M.D., Ph.D.

Chief Medical Officer

Geron

Valeria Santini, M.D.


Current • Associate Professor of Hematology at the University of Florence Medical School, Florence, Italy

• Responsible for the MDS Unit of the Hematology/Clinical and Experimental Medicine Department, AOU Careggi, University of Florence, Italy

Medical Training • University of Florence Medical School, Florence, Italy

• Fellow in Experimental Hematology, Dr. den Hoed Kliniek, Erasmus University, Rotterdam, Netherlands

• Visiting Physician Scientist, Department of Leukemia, M.D. Anderson Cancer Center, University of Texas, Houston, TX

Expertise • Scientific interests and publications are focused on maturation induction and therapeutic targeting of epigenetics modifications in MDS and AML

Imetelstat in Lower Risk

Myelodysplastic Syndromes (MDS)

at 25th Annual European Hematology

Association Annual Congress

Meaningful and Durable Transfusion Independence

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 frequently 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

Patient Population~70% of all MDS patients are lower risk

>100,000 LR MDS worldwide

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

>10,000 LR MDS patients diagnosed each year in the U.S.

*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)

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

TREATMENT WITH IMETELSTAT PROVIDES DURABLE TRANSFUSION INDEPENDENCE (TI) IN HEAVILY TRANSFUSED NON-DEL(5Q) LOWER RISK

MDS (LR-MDS) RELAPSED/REFRACTORY (R/R) TO ERYTHROPOIESIS STIMULATING AGENTS (ESAs)

Uwe Platzbecker1, Pierre Fenaux2, David P. Steensma3, Koen Van Eygen4, Azra Raza5, Ulrich Germing6, Patricia Font7, Maria Diez-Campelo8, Sylvain Thepot9, Edo Vellenga10, Mrinal M. Patnaik11, Jun Ho Jang12, Helen Varsos13, Esther Rose13, Jacqueline Bussolari13, Fei Huang14, Laurie Sherman14, Faye

Feller14, Souria Dougherty14, Libo Sun14, Ying Wan14, Aleksandra Rizo14, Valeria Santini15

1Department of Hematology and Cell Therapy, University Clinic Leipzig, Leipzig, Germany, 2Hospital Saint-Louis, Universiteƴ Paris Diderot, Paris, France, 3Dana-Farber Cancer Institute, Boston, United States, 4Algemeen Ziekenhuis Groeninge, Kortrijk, Belgium, 5Columbia University Medical Center, New York, United States, 6Klinik für Hämatologie, Onkologie and Klinische lmmunologie, Universitätsklinik Düsseldorf, Heinrich-Heine-

Universität, Düsseldorf, Germany, 7Department of Hematology, Hospital General Universitario Gregorio Marañon, 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, 13Janssen Research &

Development, LLC, Raritan, NJ, 14Geron Corporation, Menlo Park, CA, United States, 15MOS Unit, AOU Careggi-University of Florence, Florence, Italy

8Funded by Geron Corporation and Janssen Research & Development Abstract code S183

Telomerase Upregulation

Apoptosis of malignant cells

Recovery of normal RBCs, WBCs,

platelets enabled

X

Mechanism of Action

• Potent competitive inhibitor of telomerase activity

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

• Disease-modifying potential: selective killing of malignant stem and progenitor cells enabling normal blood cell production

Malignant progenitor

cell

Malignant hematopoietic

stem cells

Imetelstat binds to RNA template,preventing maintenance of telomeres

(hTR)

(hTERT)

Imetelstatinhibits telomerase

activity

Imetelstat: First-in-Class Telomerase Inhibitor with Disease-Modifying Potential

9

RBCs, red blood cells; WBCs, white blood cells

Phase 2/3 Study Design

Imetelstat (n~115)7.5 mg/kg IV q4w

R

A

N

D

O

M

I

Z

E

2:1

Placebo (n~55)

Stratification: - Transfusion burden (≤6 vs. >6 units) - IPSS risk category (low vs intermediate-1)

Phase 2single arm, open label

LR MDS R/R to ESA

Phase 3double-blind, placebo-controlled

N~170

• LR MDS patients:o Non-del(5q), IPSS Low or Int-1o Relapsed/Refractory to ESA or EPO >500 mU/ml; HMA/Len naïve o Transfusion dependent: ≥ 4 units RBC/8 weeks over 16 week pre-study period

• Primary Endpoint: 8-week RBC Transfusion Independence (TI)

• Key Secondary Endpoints: 24-week RBC TI/Duration of TI/HI-E

Enrollment Complete Currently Enrolling

EPO, erythropoietin; ESA, erythropoiesis-stimulating agent; HI-E, hematologic improvement-erythroid; HMA, hypomethylating agents; IPSS, International Prognostic Scoring System; Len, lenalidomide; LR, low risk; RBC, red blood cell; R/R, relapsed/refractory

Imetelstat (n=38)7.5 mg/kg IV q4w

10

• 38 patients with non-del(5q) LR MDS R/R to ESA

• Clinical cutoff for analyses: 4 Feb 2020

Treatment Exposure

Parameters N = 38

Median follow-up, months (range) 24.0 (5.6 – 45.5)

Median treatment duration, months (range) 8.5 (0.02 – 38.7)

Median treatment cycles (range) 9 (1 – 40)

Median dose intensity*, % 100

*Median dose intensity of the assigned dose

11

Baseline Patient Characteristics

Parameters N = 38Age, 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)

4-5 units / 8 weeks at baseline, n (%) 6 (16)

≥ 6 units / 8 weeks at baseline, n (%) 32 (84)

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; ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; sEPO, serum erythropoietin;RA, refractory anemia; RAEB1, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RBC, red blood cell; RCMD, refractory cytopenia with multilineage dysplasia; RCMD-RS, refractory cytopenia with multilineage dysplasia and ringed sideroblasts; WHO, World Health Organization

12

Patient Disposition

Parameters N = 38 n (%)

Ongoing on treatment 9 (24)

Discontinued study treatmentLack of EfficacyAdverse EventProgressive DiseaseWithdrawal by Patient DeathPhysician DecisionDisease Relapse

29 (76)12 (32)8 (21)4 (10)2 (5)1 (3)1 (3)1 (3)

Ongoing study participation * 27 (71)

Terminated study participationDeathWithdrawal by Patient

11 (29)8 (21)3 (8)

* Median follow up time: 24 months (5.6 – 45.5)13

a Kaplan Meier method; b Cumulative Duration of TI ≥ 8 weeks is defined as the sum of all periods of TI ≥ 8 weeks during the treatment; c Maximum Hb rise of ≥ 3g/dL from pretreatment level (pretreatment level defined as mean Hb / 8 weeks).CI, confidence interval; Hb, hemoglobin

*Longest TI > 2.7 years

Meaningful and Durable Transfusion Independence (TI) with Imetelstat Treatment

Parameters N = 38

8-week TI, n (%)Time to onset of 8-week TI, weeks, median (range)Duration of TI, weeks, median (95% CI)a

Cumulative duration of TI ≥ 8 weeksb, median (95% CI)a

Hb rise ≥ 3.0 g/dL during TIc, n (%)

16 (42)8.3 (0.1 – 40.7)

88.0 (23.1 – 140.9*)92.3 (42.9 – 140.9)

12 (32)

24-week TI, n (%)Hb rise ≥ 3.0 g/dL during TIc, n (%)

12 (32)11 (29)

1-year TI, n (%) 11 (29)

14

a All patients also achieved 8-week TI b Kaplan Meier methodCI, confidence interval; CR, complete remission; Hb, hemoglobin; HI-E, hematologic improvement-erythroid; IWG 2006, International Working Group Response Criteria 2006; International Working Group Major and Minor Response Criteria 2018; TI, Transfusion Independence

Hematologic Improvement and IWG Response with Imetelstat Treatment

Parameters N = 38

HI-E per IWG 2006, n (%)≥1.5 g/dL increase in Hb lasting ≥ 8 weeksa, n (%)Transfusion reduction by ≥ 4 units/8 weeks, n (%)Duration of HI-E, weeks, median (95% CI)b

26 (68)13 (34)26 (68)

92.7 (37.1 – 149.4)

Major and Minor Response per IWG 2018Major response: 16-week TI, n (%)Minor response: ≥ 50% transfusion reduction/16 weeks, n (%)

14 (37)21 (55)

CR + marrow CR, n (%)CR, n (%)marrow CR, n (%)

9 (24)4 (11)5 (13)

15

Potential Disease-Modifying Activity with Imetelstat Treatment: Durable TI and Substantial Increase in Hb

• 29% of the patients transfusion-free for at least one year• Longest transfusion-free period 2.7 years• 75% of TI responders had a maximum Hb rise of ≥ 3g/dL from pretreatment level

(pretreatment level defined as mean Hb / 8 weeks) 16

Clinical Benefit Observed Across Different Patient Subgroups

Similar HI-E 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

All 8-week TIs (16 patients, 42%) are also HI-E responders in this study

17

Reversible Grade 3/4 Cytopenias without Significant Clinical Consequences

AEAll Grades

N=38n (%)

Grade 3/4N=38 n (%)

Thrombocytopenia 25 (66) 23 (61)Neutropenia 22 (58) 21 (55)Anemia 11 (29) 8 (21)

Frequency of Hematologic AEs

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Neutrophils Platelets

Resolved within 4weeks

Did not resolve within4 weeks**

87%90%

* Resolve to Grade 2 or lower by laboratory assessment** Resolved ≥4 weeks or ongoing at cutoff date

Reversibility of Grade 3/4 Cytopenias*

• 2/38 pts (5%) had febrile neutropenia (Gr3)• 3/38 pts (8%) had Grade 3/4 bleeding

18

Most Frequently Reported Non-Hematologic AEs:no new clinically significant events

TEAE All GradesN=38 n (%)

Grade 3/4N=38n (%)

Back pain 9 (24) 2 (5)

Pyrexia 8 (21) 0

Diarrhea 7 (18) 0

Nasopharyngitis 7 (18) 0

ALT increased 7 (18) 2 (5)*

AST increased 6 (16) 3 (8)*

Bronchitis 6 (16) 3 (8)

Asthenia 6 (16) 1 (3)

Headache 6 (16) 1 (3)

Urinary tract infection 6 (16) 1 (3)

Constipation 6 (16) 0

Edema peripheral 6 (16) 0

Fatigue 6 (16) 0

ALT, alanine aminotransferase; AST, aspartate aminotransferase

*Grade ≥3 AST and ALT were reversible

19

Reduction in hTERT expression correlates with 8- and 24-week TI

On-Target Activity of Imetelstat Correlates with Transfusion Independence

On-Target* activity demonstrated by reduction

in Telomerase Activity (TA) and hTERT expression

*Optimal target activity/PD effect defined as ≥ 50% reduction in TA or hTERT expression based on pre-clinical PK/PD/efficacy experiments PK, pharmacokinetic; PD, pharmacodynamic

80.0%

35.0%

91.7%

34.8%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Yes No Yes No

8-wk TI 24-wk TI

% o

f p

ts a

chie

ve

d >

=5

0%

hT

ER

T

red

uct

ion

Correlation between on-target activity and clinical responses

p=0.002p=0.016

23.1%

54.3%

0%

10%

20%

30%

40%

50%

60%

TA hTERT

% o

f p

ts a

chie

ved

>=5

0%

re

du

ctio

n

in T

A o

r h

TER

T%

pts

wit

h ≥

50

% r

ed

uct

ion

in T

A o

r h

TER

T

% p

ts w

ith

≥5

0%

re

du

ctio

n i

n h

TER

T

20

11 patients had SF3B1 mutations detected at baseline and had paired post-treatment mutation data available:

A. 10/11 had reduction (ranging 10-93%) in SF3B1 variant allele frequency (VAF)

B. The greater reduction of SF3B1 VAF, the longer TI duration patients maintained

C. Significant correlation between greater reduction of SF3B1 VAF and shorter onset time to achieve the longest TI interval (Pearson correlation coefficient r=0.646, p=0.032)

Potential Disease-Modifying Activity with Imetelstat Treatment:Reduction of Malignant Clones Associated with Treatment Response

0%

10%

20%

30%

40%

50%

60%

Baseline Post-imetelstat

% o

f SF

3B1

vari

ant

alle

le f

req

uen

cy (V

AF)

Reduction of SF3B1 VAF by Imetelstat Treatment

# 088-K700E

# 086-H662Q

# 006-E622D

# 095-R625C

# 093-R625L

# 102-K700E

# 080-K700E

# 079-K666R

# 081-R625C

# 078-K700E

# 083-K700E

A

% S

F3B

1 V

AF

Reduction of SF3B1 VAF with Imetelstat treatment A.

-100%

-80%

-60%

-40%

-20%

0%

20%

0 50 100 150

%V

AF

red

uct

ion

of

SF3B

1

Longest transfusion free interval (weeks)

% SF3B1 VAF Reduction vs the Longest TI DurationB

% S

F3B

1 V

AF

Reduction of SF3B1 VAF vs the longest TI durationB.

*Remain on treatment as of 4 Feb 2020

Reduction of SF3B1 VAF vs time to the longest TI

Patient ID

The longest TI

interval (weeks)

Time to the longest

TI interval start

(weeks)

% SF3B1 VAF

reduction

200088* 98.9 6.6 -93.3%

200086* 104 4.3 -91.8%

200006 140.9 9.9 -86.4%

200095 92.4 5.4 -71.9%

200093* 64.6 40.7 -45.5%

200102* 4 32.9 -31.2%

200080 79.9 44.1 -21.9%

200079 3.6 20.7 -11.6%

200081* 76.3 12.1 -10.9%

200078* 89.7 23.1 -9.8%

200083* 68.9 37.1 2.0%

C.

21

• Imetelstat treatment shows meaningful and durable transfusion independence:

• High rates of TI and HI-E: 42% 8-week TI rate and 68% HI-E rate

• Durable TI and HI-E: Median duration of TI is 20 months and median duration of HI-E is 21 months

• TI across multiple patient subtypes: RS+ and RS-, high and very high transfusion burden

• Potential disease-modifying activity:

• 29% of patients transfusion free for ≥1 year

• 75% of TI responders had hemoglobin rise of ≥ 3g/dL from pretreatment level

• Reduction in SF3B1 mutation correlated with shorter onset time to achieve TI

• No new safety signal identified; reversable cytopenias were most frequent AEs, without significant clinical consequences

• Phase 3 trial ongoing: double-blind, placebo-controlled, 2:1 randomization

Imetelstat in LR MDS Key Conclusions

22

Phase 2/3 Study Design

Imetelstat (n~115)7.5 mg/kg IV q4w

R

A

N

D

O

M

I

Z

E

2:1

Placebo (n~55)

Stratification: - Transfusion burden (≤6 vs. >6 units) - IPSS risk category (low vs intermediate-1)

Phase 2single arm, open label

LR MDS R/R to ESA

Phase 3double-blind, placebo-controlled

N~170

• LR MDS patients:o Non-del(5q), IPSS Low or Int-1o Relapsed/Refractory to ESA or EPO >500 mU/ml; HMA/Len naïve o Transfusion dependent: ≥ 4 units RBC/8 weeks over 16 week pre-study period

• Primary Endpoint: 8-week RBC Transfusion Independence (TI)

• Key Secondary Endpoints: 24-week RBC TI/Duration of TI/HI-E

Enrollment Complete Currently Enrolling

EPO, erythropoietin; ESA, erythropoiesis-stimulating agent; HI-E, hematologic improvement-erythroid; HMA, hypomethylating agents; IPSS, International Prognostic Scoring System; RBC, red blood cell; Len, lenalidomide.

Imetelstat (n=38)7.5 mg/kg IV q4w

• Key Elements Same as Phase 2:

▪ Dose and schedule

▪ Primary/secondary endpoints

▪ Patient population as n=38

▪ Continuity of most of the clinical sites

• Current Status/Progress:

▪ First patient dosed in October 2019

▪ Currently enrolling

23

Acknowledgements

Mazure, DominiekMeers, StefBreems, Dimitri

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

of all investigators and their staff

Gourin, Marie-PierreGyan, EmmanuelLegros, LaurenceThepot, Sylvain

Kim, InhoLee, Je-hwan

Klein, SaskiaLangemeijer, Saskiavan de Loosdrecht, Arjan

Oliva, Esther

Pristupa, Alexander

Samoilova, Olga

Udovitsa, Dmitry

De Paz, RaquelEsteve, JordiValcarcel, DavidXicoy, Blanca

Boccia, RalphErba, Harry / DiStasi, AntonioGrunwald, MichaelJacoby, MeganMiller, CaroleSchiller, GarySilverman, LewisStevens, Don

24

Q&A

Valeria Santini, M.D.

University of Florence

Introduction



Geron

John Mascarenhas, M.D.


Current • Associate Professor of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

• Director, Adult Leukemia Program, Icahn School of Medicine at Mount Sinai, New York, NY

• Teaching Faculty, Graduate School of Biomedical Sciences of the Icahn School of Medicine at Mount Sinai, New York, NY

Medical Training • New York Medical College, Valhalla, NY

• Internal Medicine Resident, Brown University School of Medicine, Providence, RI

• Hematology-Oncology Fellow, Mount Sinai School of Medicine, New York, NY

• Clinical Research, Master of Science Program, Mount Sinai Graduate School in Biological Sciences

Expertise • Translational research in malignant hematology and the development of investigator-initiated clinical trials in patients with myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML)

Imetelstat in Intermediate-2 or

High-risk Myelofibrosis (MF)



Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes

Int-2/High-Risk Myelofibrosis


Imetelstat to address significant unmet need with a large market opportunity

Patient Population*

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

>35,000 Int-HR MF patients worldwide

>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.

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

TELOMERASE ACTIVITY, TELOMERE LENGTH AND hTERT EXPRESSION CORRELATE WITH CLINICAL OUTCOMES IN HIGHER-RISK MYELOFIBROSIS (MF)

RELAPSED/REFRACTORY (R/R) TO JANUS KINASE INHIBITOR TREATED WITH IMETELSTAT

Mascarenhas1, R. Komrokji2, M. Cavo3, B. Martino4, D. Niederwieser5, A. Reiter6, B. Scott7, M. Baer8, R. Hoffman9, O. Odenike10, J. Bussolari11, E. Zhu11, E. Rose11, L. Sherman12, S. Dougherty12, F. Feller12, L. Sun12, Y. Wan12, A. Rizo12, F. Huang12, and J. Kiladjian13

1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai; MPN-RC (US), 2H Lee Moffitt Cancer Center (US), 3”Seràgnoli” Institute ofHematology, University of Bologna (IT), 4Grande Ospedale Metropolitano-G.O.M. Bianchi-Melacrino-Morelli (IT), 5University Hospital Leipzig(DE), 6University Hospital Mannheim (DE), 7Fred Hutchinson Cancer Research Center (US), 8University of Maryland GreenebaumComprehensive Cancer Center (US), 9Tisch Cancer Institute, Mount Sinai School of Medicine (US), 10University of Chicago (US), 11JanssenResearch & Development, LLC (US), 12Geron Corporation (US), 13Hôpital Saint-Louis, Université Paris (FR)

30EHA 25 l EP1098

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.

32

Imetelstat Mechanism of ActionOn-target pharmacodynamic (PD) effects and clinical benefits

Source: EHA 2020 Poster: Mascarenhas J, et al

• Imetelstat• A potent, first-in-class competitive inhibitor of telomerase enzymatic activity.• Selectively targets malignant cells with continuously upregulated telomerase, inducing their apoptosis and

thereby enabling potential recovery of normal hematopoiesis.• Currently in clinical development for hematologic malignancies.

• Background• Nonclinical studies demonstrated that imetelstat reduces telomerase activity (TA), human telomerase reverse

transcriptase (hTERT) expression level, and JAK2V617 hematopoietic progenitor cells in MF patient samples,indicative of mechanism based on-target activity.

• Short telomere length (TL), high levels of TA and high expression of hTERT correlated with higher risk, diseaseprogression and shorter OS in patients with myeloid malignancies.

• Cells with short TL, high levels of TA and hTERT represent best target for treatment with telomerase inhibitor.• Optimal PD effect of imetelstat was defined as ≥50% reduction in TA or hTERT from baseline as it correlated

with antitumor activity in preclinical PK/PD/efficacy studies.

• Objectives• Evaluate on-target PD effect of imetelstat and relationship to dose and exposure levels in MF patients.• Assess the correlation of the optimal PD effect with symptom or spleen response and overall survival (OS).• Explore the association between baseline telomere length and hTERT expression level and clinical benefits.• Evaluate the change in allele burden of driver mutation, such as JAK2, CALR, MPL, by imetelstat treatment to

assess disease-modifying activity.

Significantly higher % of pts in 9.4mg/kg arm achieved optimal PD effect* compared to 4.7mg/kg arm

*Optimal PD effect defined as >=50% reduction in telomerase activity (TA) or hTERT expression level.**28 pts had serial (intense) PK samples collected during C1D1; Cmax and AUC0-24h were determined for exposure.

Dose-dependent and Exposure-dependent PD EffectsOn-target activity

Significantly higher % pts with high imetelstat exposure** achieved ≥50% hTERT reduction

33Source: EHA 2020 Poster: Mascarenhas J, et al

p=0.049p=0.033

30.3%

41.7%

57.5%62.5%

0%

10%

20%

30%

40%

50%

60%

70%

≥50% TA reduction ≥50% hTERT reduction

% o

f p

atie

nts

ach

ieve

d >

=50

%

red

uct

ion

in T

A o

r h

TER

T

4.7 mg/kg 9.4 mg/kg

Optimal PD Effects Correlated with Clinical Responses and Longer OS

34

*Optimal PD effect defined as >=50% reduction in telomerase activity (TA) or hTERT expression level.


100.0%

76.1%

93.8%

72.7%

0%

20%

40%

60%

80%

100%

120%

Yes No Yes No

Spleen Response Symptom Response

% o

f p

ts a

chie

ved

op

tim

al P

D e

ffe

ct

AOptimal PD

Median OS (mo)

(95% CI)

HR

(95% CI)

Yes 27.2 (22.2, 34.1)0.54 (0.28, 1.06)

No 18.3 (4.2, 31.6)

B

Patients who achieved optimal PD effect had better OS

Higher % of patients achieved optimal PD effect in responders [spleen response

(SVR ≥35%) or symptom response (TSS reduction ≥50%)] at week 24 than in

non-responders

35

Potential Disease-Modifying Activity

Reduction in malignant clones with imetelstat treatment

0.0%

50.0%

0.0%5.6%

31.3%

100.0% 100.0%

42.1%

0%

20%

40%

60%

80%

100%

120%

JAK2 CALR MPL Any of 3 genes

% p

ts h

ad >

=25

% V

AF

red

uct

ion

4.7 mg/kg 9.4 mg/kg

p=0.019

4.7 mg/kg 9.4 mg/kg

JAK2 N=15 N=16

>=25% Decrease 0 (0%) 5 (31.3%)

CALR N=2 N=2

>=25% Decrease 1 (50%) 2 (100%)

MPL N=1 N=1

>=25% Decrease 0 (0%) 1 (100%)

Any of 3 genes N= 18 N=19

>=25% Decrease 1 (5.6%) 8 (42.1%)

Imetelstat resulted in dose-dependent reduction in variant allele frequency (VAF) of JAK2V617F, CALR and MPL mutations


36

Patients with Short Telomere Length (TL) or Higher hTERT Expression

Improved clinical outcomes when treated with 9.4 mg/kg

Patients with short baseline TL (<=median) had higher rate of responses in 9.4 mg/kg arm

BA

0.0% 0.0%

5.6% 4.5%

17.3%

4.2%

37.9%

25.0%

0%

5%

10%

15%

20%

25%

30%

35%

40%

Shorter TL Longer TL Shorter TL Longer TL


% p

ts a

chie

ve

d r

esp

on

se

Baseline telomere length (TL) vs responses

4.7 mg/kg 9.4 mg/kg

0.0% 0.0%

12.0%

0.0%

7.1%

13.8%

28.6%

37.9%

0%

5%

10%

15%

20%

25%

30%

35%

40%

Lower hTERT Higher hTERT Lower hTERT Higher hTERT


% p

ts a

chie

ve

d r

esp

on

se

Baseline hTERT level vs responses

4.7 mg/kg 9.4 mg/kg


Patients with high baseline hTERT level (>median) had higher rate of responses in 9.4 mg/kg arm

37

Patients with Short Telomere Length (TL) or Higher hTERT Expression

Longer OS when treated with 9.4 mg/kg

9.4 mg/kg4.7 mg/kg

Baseline TLMedian OS (mo)

(95% CI)

HR

(95% CI)

<= Median 20.3 (17.2, 36.6) 0.88 (0.41, 1.88)

> Median 28.6 (16.6, 33.9)

Baseline TLMedian OS (mo)

(95% CI)

HR

(95% CI)

<= Median 30.1 (23.2, NE) 0.70 (0.35, 1.41)

> Median 27.1 (16.2, 33.8)

Patients with shorter baseline TL had a trend of better OS compared to patients with longer TL when treated with 9.4 mg/kg of imetelstat


Conclusions

38

• Imetelstat achieved dose- and exposure-dependent reduction of telomerase activity and hTERT expressionlevel, demonstrating on-target mechanism of action.

• Achieving optimal PD effect (≥50% reduction of telomerase activity or hTERT level) in patients treated withimetelstat is correlated with clinical responses and longer OS. This validates the pre-clinical PD findings.

• Significant, dose-dependent, reduction in VAF of JAK2, CALR and MPL mutations were observed, indicatingthat imetelstat has disease-modifying activity by targeting the underlying MF malignant clones.

• Treatment with 9.4mg/kg imetelstat improved clinical outcomes in patients with short telomeres or highhTERT expression level at baseline. The results are consistent with telomere biology in cancer cells andprovide evidence for on-target mechanism of action of imetelstat through telomerase inhibition.

• This is the first clinical report to systematically evaluate the mechanism of action based PD effect ofimetelstat, and its relationship to exposure and clinical benefits.


Q&A


Icahn School of Medicine at Mount Sinai

Introduction



Geron

Rami Komrokji, M.D.


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





Longer OS in Patients with Higher Risk Triple Negative MF

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)

J. Kiladjian1, J. Mascarenhas2, R. Komrokji3, M. Cavo4, B. Martino5, D. Niederwieser6, A. Reiter7, B. Scott8, M. Baer9, R. Hoffman10, O. Odenike11, J. Bussolari12, E. Zhu12, E. Rose12, L. Sherman13,

S. Dougherty13, F. Feller13, L. Sun13, Y. Wan13, A. Rizo13, F. Huang13, and A. Vannucchi14

1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai; MPN-RC (US), 2H Lee Moffitt Cancer Center (US), 3”Seràgnoli” Institute ofHematology, University of Bologna (IT), 4Grande Ospedale Metropolitano-G.O.M. Bianchi-Melacrino-Morelli (IT), 5University Hospital Leipzig(DE), 6University Hospital Mannheim (DE), 7Fred Hutchinson Cancer Research Center (US), 8University of Maryland GreenebaumComprehensive Cancer Center (US), 9Tisch Cancer Institute, Mount Sinai School of Medicine (US), 10University of Chicago (US), 11JanssenResearch & Development, LLC (US), 12Geron Corporation (US), 13Hôpital Saint-Louis, Université Paris (FR)

43EHA 25 l EP1101

Imetelstat in Triple Negative Patients

44Source: EHA 2020 Poster: Kiladjian J, et al

• Imetelstat• Imetelstat is a telomerase inhibitor that selectively targets malignant cells with continuously upregulated

telomerase, inducing their apoptosis and thereby enabling potential recovery of normal hematopoiesis.

• Background• Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm. JAK2, MPL, and CALR

mutations are considered "driver mutations" and directly contribute to the myeloproliferative phenotypethrough convergent activation of intracellular JAK-STAT signaling, which led to the development of JAKinhibitors (JAKi).

• MF patients negative for JAK2, CALR and MPL mutations are termed Triple Negative (TN), a subpopulationassociated with a higher incidence of leukemic transformation and shorter overall survival (OS) ~2.5-3 yearsfrom diagnosis compared to pts carrying a mutation in JAK2, CALR or MPL gene.

• Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment forMF, but TN MF patients also have worse prognosis and non-relapse mortality vs. non-TN pts after alloHSCT.

• New agents with novel mechanisms of action beyond JAKi are needed to treat TN MF pts.• Reported at ASH 2018, IMbark showed a 32% symptom response rate and median OS of 29.9 months in the

overall population on the 9.4 mg/kg arm, with acceptable safety.

• Objective• To evaluate TN patients enrolled in the IMbark clinical trial for spleen response [spleen volume reduction

(SVR) ≥35%] and symptom response [total symptom score (TSS) reduction ≥50%] at Week 24, fibrosisimprovement and OS to determine if this molecularly defined subset, associated with poor prognosis,benefits from imetelstat treatment.





Trial Population:










Ran

do

miz

e(1

:1) Imetelstat







46

IMbark Phase 2Baseline Frequency of JAK2, CALR, MPL Mutation and TN for Patients

Molecular Subtype4.7 MG/KG,

N=48 9.4 MG/KG,

N=57 Total

N=105

JAK2 V617F 32 (66.7%) 32 (56.1%) 64 (61%)

CALR 2 (4.2%) 7 (12.3%) 9 (8.5%)

MPL 4 (8.3%) 2 (3.5%) 6 (5.7%)

TN 10 (20.8%) 16 (28.1%) 26 (24.8%)

Source: EHA 2020 Poster: Kiladjian J, et al

47

Higher Rates of Spleen and Symptom Response in TN MF PatientsWhen treated with 9.4 mg/kg of imetelstat

0.0%

18.8%

10.0%

50.0%

0.0%

7.3%5.3%

24.4%

0%

10%

20%

30%

40%

50%

60%

4.7 mg/kg 9.4 mg/kg 4.7 mg/kg 9.4 mg/kg


% o

f pat

ient

s ac

hive

d re

spon

se

Higher rates of clinical response in TN vs. Non-TN in 9.4mg/kg

TN Non-TN


48

Longer OS in TN MF PatientsWhen treated with 9.4 mg/kg of imetelstat

4.7 mg/kg 9.4 mg/kg

Imetelstat Dose

(mg/kg)TN vs Non-TN

Percentage of Subjects

Who Died

Median Survival (months)

(95% CI)

HR

(95% CI)

P-value

(Log-rank)

4.7TN 8 / 10 (80.0%) 23.1 (4.2, 36.6) 1.01 (0.46, 2.23) 0.98

Non-TN 27 / 38 (71.1%) 19.4 (16.7, 33.9)

9.4TN 7 / 16 (43.8%) 35.9 (23.2, NE) 0.45 (0.19, 1.03) 0.05

Non-TN 28 / 41 (68.3%) 24.6 (19.6, 29.9)


49

Higher Rate of Bone Marrow Fibrosis Improvement in TN MF Patients When treated with 9.4 mg/kg of imetelstat

0%6%

94%

13%21%

66%

0%

20%

40%

60%

80%

100%

Grade 1 Grade 2 Grade 3

Bone marrow fibrosis grade at baseline

% o

f p

atie

nts

Worse baseline fibrosis grade in TN

TN Non-TN

20.0%

50.0%

20.0%

39.1%

0%

10%

20%

30%

40%

50%

60%

4.7 mg/kg 9.4 mg/kg

% p

ts w

ith

fib

rosi

s im

pro

ven

t

Higher rate of BM fibrosis improvement in TN vs Non-TN in 9.4 mg/kg

TN Non-TN


50

TN MF Patients had Shorter Telomeres and Higher Level of hTERT at Baseline

Representing a suitable target population for imetelstat treatment

79%

60%

46% 48%

0%

20%

40%

60%

80%

100%

Shorter TL Higher hTERT

% o

f p

atie

nts

Higher % of TN pts have shorter TL or higher level of hTERT at baseline compared to Non-TN pts

TN Non-TN

TN MF patients treated with 9.4 mg/kg of imetelstatSource: EHA 2020 Poster: Kiladjian J, et al

Conclusions

51

Overall, TN MF pts R/R to JAKi treated with 9.4 mg/kg imetelstat had better clinical outcomes and prolongedOS compared to non-TN pts, suggesting that imetelstat may improve the poor outcomes expected for TN pts.

• There were 20.8% TN patients in the 4.7 arm and 28.1% in the 9.4 arm, for a total of 24.8% TN patients on thestudy.

• With 9.4 mg/kg imetelstat treatment, clinical response rates were higher in TN vs non-TN patients: spleenresponse rate was 18.8% in TN vs 7.3% in non-TN; and symptom response was 50.0% in TN vs 24.4% in non-TNpatients.

• Imetelstat treatment at 9.4 mg/kg resulted in significantly longer median OS of 35.9 months for TN patients vs24.6 months for non-TN patients.

• Majority (94%) of the TN patients enrolled on the study had Grade 3 fibrosis. Higher rate of bone marrowfibrosis improvement was noted in the TN (50%) vs non-TN (39.1%) patients.

• TN patients enrolled on the study had short telomere length and high hTERT expression level at baseline,representing a suitable target population for imetelstat, a telomerase inhibitor.

These data warrant further investigation of imetelstat in a targeted clinical trial in TN MF patients who havepoor outcomes.


Q&A

Rami Komrokji, M.D.

Moffitt Cancer Center





Favorable Overall Survival Correlates with Other Clinical Benefits

FAVORABLE OVERALL SURVIVAL WITH IMETELSTAT TREATMENT CORRELATES WITH OTHER CLINICAL BENEFITS IN INTERMEDIATE 2 OR HIGH RISK MYELOFIBROSIS

RELAPSED/REFRACTORY TO JANUS KINASE INHIBITOR

J. Mascarenhas1, R. Komrokji2, B. Martino3, D. Niederwieser4, A. Reiter5, B. Scott6, M. Baer7, R. Hoffman8, O. Odenike9, J. Bussolari10, E. Zhu10, E. Rose10, L. Sherman11, S. Dougherty11, F.

Feller11, L. Sun11, Y. Wan11, A. Rizo11, F. Huang11, and J. Kiladjian12

1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai; MPN-RC (US), 2H Lee Moffitt Cancer Center (US), 3Grande Ospedale Metropolitano-G.O.M.Bianchi-Melacrino-Morelli (IT), 4University Hospital Leipzig (DE), 5University Hospital Mannheim (DE), 6Fred Hutchinson Cancer Research Center (US),7University of Maryland Greenebaum Comprehensive Cancer Center (US), 8Tisch Cancer Institute, Mount Sinai School of Medicine (US), 9University ofChicago (US), 10Janssen Research & Development, LLC (US), 11Geron Corporation (US), 12Hôpital Saint-Louis, Université Paris (FR)

54EHA 25 l EP1107





Trial Population:










Ran

do

miz

e(1

:1) Imetelstat







56

Correlation of Overall Survival and Other Clinical BenefitsAnalysis of IMbark Phase 2 data


• Imetelstat• Imetelstat, a 13-mer oligonucleotide that specifically targets the RNA template of human

telomerase, is a potent competitive inhibitor of telomerase enzymatic activity.• Selectively targets malignant cells with continuously upregulated telomerase, inducing their

apoptosis and thereby enabling potential recovery of normal hematopoiesis.

• Background• Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm.• Patients who are relapsed after or refractory to (R/R) therapy with Janus kinase inhibitors (JAKi)

have dismal overall survival (OS) of 13-16 months.• Treatment with imetelstat has demonstrated dose-related clinical benefit, specifically in terms

of symptom response and improvement in OS in IMbark, a phase 2 study in MF patients R/R toa JAKi.

• The improvement in OS for patients treated with 9.4mg/kg imetelstat was further supported byanalyses of IMbark patients with closely matched real world controls.

• Objective• Evaluate the association between OS and spleen volume reduction (SVR) at Week 24, total

symptom score (TSS) reduction at Week 24, and fibrosis improvement.

57

Myelofibrosis Patients Relapsed/Refractory to JAKi OS improvement with 9.4 mg/kg imetelstat treatment

Similar results were observed when sensitivity analyses accounted for confounding factors of

subsequent therapies, including stem cell transplantation and dose escalation from

4.7 mg/kg to 9.4 mg/kg.


Median follow up of 41.7 months

Dose Related Clinical Benefits from Imetelstat Treatment

58

CALR = calreticulin gene, CI = confidence interval, JAK = Janus kinase, IWG-MRT = International Working Group – Myeloproliferative Neoplasms Research and Treatment, MPL = thrombopoietin receptor gene, OS = overall survival, PFS = progression free survival, SVR = spleen volume reduction, TSS = total symptom score, VAF = variant allele frequency


59

Trend of Longer OSCorrelated with reduction in fibrosis

Patients with ≥1 degree of bone marrow fibrosis improvement showed a significantly longer OS than those who had worsening bone marrow fibrosis.

A similar trend was seen in patients with stable vs. worsening fibrosis.


Hazard ratios (HR) and p-values are based on Cox regression models with Imetelstat treatment cohort and bone marrow degree of fibrosis as factors.N: Number of patients in each (reference or non-reference) category. Deaths: Number of deaths in each category.

60

Trend of Longer OS

Correlated with symptom response and spleen response

Patients who achieved symptom and spleen response at week 24 showed trend of longer OS compared to patients who did not achieve a response.

Hazard ratios (HR) and p-values are based on Cox regression models with Imetelstat treatment cohort and TSS reduction, or SVR reduction as factors.N: Number of patients in each (reference or non-reference) category. Deaths: Number of deaths in each category.


61

Prognostic Disease Characteristics for OSIrrespective of treatment dose


• Hazard ratios (HR) and p-values are based on Cox regression models with Imetelstat treatment cohort and demographic or baseline characteristic as factors.

• CI* = Clinical Improvement

Conclusions

62

Imetelstat showed dose-related improvement in OS in patients who are R/R to JAKi. The survival benefit observed with imetelstat was supported by the trend of correlation with other clinical benefits.

• With a median follow-up of 41.7 months, the median OS was 28.1 months for the 9.4 mg/kg arm and 19.9months for the 4.7 mg/kg arm.

• Among 57 patients across both treatment arms that had matching bone marrow samples, 20 patients(35%) had ≥1 degree of bone marrow fibrosis improvement while on study and had a significant longer OSthan those who had worsening bone marrow fibrosis. A similar trend was seen in 29 patients (51%) withstable vs. worsening fibrosis.

• Patients who achieved symptom and spleen response at week 24 showed trend of longer OS compared topatients who did not achieve response.

• Pretreatment DIPSS high risk, ECOG performance status, transfusion dependency, response to last JAKi,higher baseline neutrophils, lower baseline Hb and platelet values correlated with increased risk of death.


Q&A


Icahn School of Medicine at Mount Sinai

Planned Phase 3 in Refractory MF



Geron

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

Principal Investigators: John Mascarenhas, M.D., Icahn School of Medicine, Mt. SinaiSrdan Verstovsek, M.D., MD Anderson Cancer Center

Closing Remarks

John Scarlett, M.D.

Chairman and Chief Executive Officer

Geron

Confidential & Proprietary

Thank YouIf you have any questions, please contact us: [email protected]

kol event...2020/06/17 · eha presentation #s183 meaningful and durable transfusion independence...

Documents