Geron Corporation · NASDAQ:GERN
Geron — ASH 2013 Analyst & Investor Event
45 slides from Geron's conference presentation, Dec 10, 2013
Slide 1: ASH 2013 Analyst & Investor Event
= geron ASH 2013 Analyst & Investor Event December 9, 2013 John A. Scarlett, MD President & CEO. geron
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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 without limitation, the follow
Slide 3: Background: myelofibrosis and imetelstat
* Background: myelofibrosis and imetelstat * Preliminary results from Mayo Clinic investigator-sponsored trial (IST) of imetelstat in myelofibrosis presented at ASH Annual Meeting (abstract #662) * Geron’s independent efficacy analysis of the first 22 MF patients enrolled in the study = Investigator
Slide 4: Top Line Observations
Top Line Observations * Geron’s independent review of the data from the first 22 patients in the Mayo Clinic IST suggests that imetelstat has disease-modifying activity in MF + Unprecedented remissions (CR+PR) by IWG-MRT criteria observed in 5/22 patients * Clinical improvement (Cl) by WG-MRT criter
Slide 5: Myelofibrosis and Imetelstat
Myelofibrosis and Imetelstat Disease Characteristics and Unmet Medical Need geron
Slide 6: Myelofibrosis: Disease in the Bone Marrow
g in the Bone Marrow Malignant clonal myeloproliferation and atypical megakaryocytic hyperplasia leads to bone marrow fibrosis and impaired hematopoiesis Fibrosis thought to be induced by cytokines produced by the malignant progenitor cell clone? Impaired bone marrow hematopoiesis shifts blood produ
Slide 7: The Unmet Medical Need
The Unmet Medical Nee: + Allo-HCT (allogeneic hematopoietic cell transplantation) only current treatment that can result in complete remission of disease = Generally limited to <10% patients due to lack of suitable donors, older age and co-morbidities = Though improved regimens available, still asso
Slide 8: Resolution of Bone Marrow Fibrosis
in of Bone Marrow Fibro: Remi * MF: Sequential analysis in Allo-HCT patients with grade 2 or grade 3 fibrosis at baseline showed near or complete resolution (to grade 1 or 0): = 69% at day 100; 93% at day 365 * CML: Bone marrow fibrosis occurs in 20-40% of patients? and is associated with significan
Slide 9: Imetelstat: A Telomerase Inhibitor
Imetelstat: A Telomerase Inhibitor chromosome imetelstat binds to RNA template preventing maintenance of telomeres RNA Template (hTR) Telomere telomere Telomerase pu Imetelstat Telomerase enzyme: + Reverse transcriptase comprised of an RNA component {hTR) and a reverse transcriptase catalytic protei
Slide 10: Preliminary efficacy results from Mayo Clinic investigator-sponsored trial
Preliminary efficacy results from Mayo Clinic investigator-sponsored trial of imetelstat in myelofibrosis Geron’s independent efficacy analysis of the first 22 MF patients enrolled in the study . geron
Slide 11: Investigator-Sponsored Single Center Study in Myelofibrosis
Investigator-Sponsored Single Center Study in Myelofibrosi Principal Investigator & Study Sponsor: Ayalew Tefferi, MD ~ Mayo Clinic, Rochester Single Agent Imetelstat 1 Endpoint: High risk or 2hr infusion + Overall response rate intermediate-2 (CR, PR or Cl) per IWG-MRT 11) (DIPSS Plus) ‘ered lt cri
Slide 12: Analysis Performed by Geron
Analysis P ‘med by Geron © Obtained and reviewed updated data available as of October from Mayo Clinic, including summary tables, patient listings, and pathology reports * Patients: first 22 (11 in Arm A and 11 in Arm B) = Data cutoff: 18 October 2013 * Onsite review of the patient charts and clinic
Slide 13: Primary Outcome Criteria for Response in Myelofibrosis
ary Outcome Criteria for Response in Myelofibrosis* © normal cellularity and reversal of bone marrow fibrosis and CUI o normal peripheral blood counts and smears and © complete resolution of symptoms and splenomegaly ‘© as CR with bone marrow response but pai without full recovery of peripheral bloo
Slide 14: Patient Demographics
Patient Demographics Total (n=22) ‘Median Age (range; years) 68.0(54.0-76.0) 69.0 (53.0-79.0) 68.0 (53.0-79.0) Male 7 (63.6%) 9 (81.8%) 16 (72.7%) Previously Treated 8 (72.7%) 40 (90.9%) 18 (81.8%) Myelofibrosis Subtype Primary Myelofibrosis 4 (36.4%) 5 (45.5%) 9 (40.9%) Post-ET Myelofibrosis 1 (9.1
Slide 15: Clinical Disease Characteristics at Baseline: Organomegaly & Symptoms
Clinical Disease acteristics at Baseline: Organomegaly & Symptoms Total (n= 22) Palpable Splenomegaly 5to< 10cm 0 (0.0%) 1(9.1%) 1 (4.5%) 2 10cm 7 (63.6%) 5 (45.5%) 12 (54.5%) Median (Range in cm) 19.0 (13.0-25.0) 11.0 (8.0-23.0) 16.0 (8.0-25.0) Palpable Hepatomegaly 5to< 10cm 1(9.1%) 1(9.1%) 2 (9.1
Slide 16: Previous Treatment for Myeloproliferative Neoplasms
Pre us Treatment for Myeloproliferative Neoplasms Prior Regimen. [Arma (n=11) | ‘Arm B (n = 11) Total (n = 22) ‘Any Prior Treatment 8 (72.7%) 10 (90.9%) 18 (81.8%) Median # of Treatments (range) 2 (1-4) 2 (1-4) 2(1-4) Hydroxyurea 4 (36.4%) 6 (54.5%) 10 (45.5%) JAK2 Inhibitor 5 (45.5%) 4 (36.4%) 9 (4
Slide 17: Efficacy Assessment
Efficacy Assessment ° Original protocol (October 2012) used the 2006 IWG-MRT criteria? 2013 IWG-MRT criteria? were adopted after their publication in June ¢ Enrollment of all 22 patients was complete by May 2013, therefore some procedures were not in place at baseline and precluded full adoption of
Slide 18: Median Duration of Follow-up and Patient Status
¢ As of October 2013, the median duration of follow-up*: = Arm A: 7.6 months (range 1.3-10.4) * Arm B: 4.8 months (range 1.6-5.6) = Overall: 5.3 months (range 1.3~10.4) * Defined as time between date of first dose and date of last contact Inthe clinical database as ofthe data cutoff date. Patient St
Slide 19: Overall Response by IWG-MRT
it (Overall Response by IWG-MR Best Response by 2013 IWG-MRT N(%) N(%) N(%) Overall Response (CR+PR+C!) 3 (27.3%) 6 (54.5%) 9 (40.9%) Remission (CR+PR) 2 (18.2%) 3 (27.3%) 5 (22.7%) Complete Remission (CR) 2 (18.29%) 1(9.1%) 3 (13.6%) Partial Remission (PR) 2 (18.2%) 2 (9.1%) Clinical Improvement (C
Slide 20: Response Parameters for Patients Who Achieved CR or PR
Response Parameters for Patients Who Achieved CR or PR (IWG-MRT] + Median onset time to CR or PR of 2.8 months (range 1.4 - 3.0) Patient Be ‘Anemia or | Leukocytosis | Thrombo- Marrow | Transfusion oytosis Requirement Response: transfusion Independence Response 2 A CR transfusion a independence Comp
Slide 21: Patient 1 - CR
Patient 1-CR Hematology, Dosing and Baseline Characteristics ‘Aim AMT3PUTastton Dependent ‘avin ere arene Fons Grade, Celaiy86%, arto cent [Sistine Spm: Nene Bistn Pate Sen Se em ip ‘eT | ich Pa RD ro Only Beslne and Day 1b results ofeach cyte ae presented: Onna onset of responses noted if geron
Slide 22: Baseline vs 7-months post-imetelstat therapy
Baseline _______,_7-months post-imetelstat therapy geron
Slide 23: Patient - CR: seven-months post-imetelstat therapy, megakaryocytes
Patient 1 - CR: seven-months post-imetelstat therapy, megakaryocytes quantitatively and morphologically became unremarkable with only rare abnormalities
Slide 24: Hematology, Dosing and Baseline Characteristics
Hematology, Dosing and Baseline Characteristics ‘em Ana Ptrranstaion Dependent ‘tte Bone arow ion rae, Cluay-S0%, tenet nresed ‘tocine Symp: ran eghttons ‘issn Pe Sen Siem tp e - Ls ein? Ey rte tp Reston WSL ee _ Weert Only Beslne and Day 1a result ofeach cyl ae presented: Online onset of responses
Slide 25: Patient - CR
Patient 2 - CR Baseline _________, 5.5-months post-imetelstat therapy geron
Slide 26: Hematology, Dosing and Baseline Characteristics
Hematology, Dosing and Baseline Characteristics + Nee i & Pott wo: i i i (2 Foon mesmo Only Baseline and Day 1 lab results of each cycle are presented; Only inital onset of responses noted a Qeron
Slide 27: Patient: Baseline vs 3 months post-imetelstat therapy
Patient Baseline > 3.months post-imetelstat therapy _— geron
Slide 28: Patient - CR: six-months post-imetelstat therapy
Patient 3 - CR: six-months post-imetelstat therapy: “Normocellular bone marrow with normal trlineage hematopoiesis. No bone marrow fibrosis" A&E 400K
Slide 29: Patient - PR (with Bone Marrow CR)
Patient 4 R (with Bone Marrow CR) Hematology, Dosing and Baseline Characteristics Ammer uetanusonInscenent {ive Son tarow: Faron Grader, Clary 80%, Bate nreated Shscie Symons None SiscinePapuic Speen Seem 0 Only Baseline and Day 1 lab results of each cycle are presented; Only inital onset of respons
Slide 30: Patient - PR (Bone Marrow CR)
Patient 4 - PR (Bone Marrow CR) Hematology, Dosing and Baseline Characteristics Ammer uetanusonInscenent ince Sore tone nese roe, carne 80, Bastsotnreased SERRE Ace temso challenge to have ll peripheral counts meet CR criteria atthe same time te ad Only Baseline and Day 1 lab results of each cycle a
Slide 31: Hematology, Dosing and Baseline Characteristics
Hematology, Dosing and Baseline Characteristics ‘dum eave ation independent : se — i Seas Sse Only Baseline and Day 1 lab results of each cycle are presented; Only inital onset of responses noted a Qeron
Slide 32: Efficacy Results: Spleen, Anemia and Symptoms Responses
acy Results: Spleen, Anem and Symptoms Responses Spleen Response (by palpation) 2/7 (28.6%) 3/6(50%) 5/13 (38.5%) ‘Anemia Response 3/5 (60%) 1/7 (14.3%) 4/12 (33.3%) * Symptoms response was observed in 10/13 (77%) of patients Spleen response: defined as either 2 50% decrease if baseline 2 10 cm or b
Slide 33: Exploratory Endpoints: Impact on Blasts, Leukocytosis & Thrombocytosis
Exploratory Endpoints: Impact on Blasts, Leukocytosis & Thrombocytosis © Benefit not just limited to the patients achieving CR, PR or Cl Circulating Blasts (21% at baseline) Complete Resolution Partial Resolution** Leukocytosis (counts >ULN at baseline) Complete Resolution Partial Resolution Marked
Slide 34: Patient Response Status & Dosing: Arm A
Patient Response Status & Dosing: Arm A Imetelstat Dosing by Week ‘Ana 8 Weeks © 75maKg M94 moo Initial Response: © PR_O Liver Response BestResponse: #2 CR O PR C Ciby Anemia C Ciby wer CG Clby Spleen O Spleen Response “Indicates patient had discontinued treatment, Died on study (GI bleed unvelated
Slide 35: Patient Response Status & Dosing: Arm B
Patient Response Status & Dosing: Arm B Imetelstat Dosing by Week weslediaysBeen ' eee Terme | i 7) 8 6 © 2 Weeks © 75maKg m 94 moo Initial Response: © PR_O Lier Response Best Response: # CR O PR Cl CbyAnemia CO Ciby ver C Clby Spleen © Spleen Response “Indicates patient had discontinued treatment,
Slide 36: Efficacy Conclusions
acy Conclu: ns © Geron’s independent review of the data from the first 22 patients in the Mayo Clinic IST suggests that imetelstat has disease-modifying activity in MF Unprecedented remissions (CR+PR) by IWG-MRT criteria observed in 5/22 patients — Bone marrow reversal in 4/5 CRKPR patients ~ Resolu
Slide 37: Preliminary safety results from Mayo Clinic investigator-sponsored trial
Preliminary safety results from Mayo Clinic investigator- sponsored trial of imetelstat in myelofibrosis Mayo Clinic analysis of the first 33 MF patients enrolled in the study 7 geron
Slide 38: Original Plan
ginal Plai Principal Investigator & Study Sponsor: Ayalew Tefferi, MD ~ Mayo Clinic, Rochester Cohort A (n=11): 9.4 mg/kg q3 weeks Cohort B (n=11): 9.4 me/ke weekly cycle 4, then q3 weeks Cohort C (n=11): 9.4 mg/kg Weekly geron
Slide 39: Additional Patients Distributed to Arm A & B
Additional 11 Patients Distributed to Arm A & B (' Principal Investigator & Study Sponsor: Ayalew Tefferi, MD ~ Mayo Clinic, Rochester Cohort A (n=19): 9.4 mg/kg 3 weeks Cohort B (n=: 9.4 me/ke weekly cycle 1, then q3 weeks geron
Slide 40: Patient Disposition
Patient Disposi Current disposition All patients (n=33) Follow-up in months; median (range) Currently still on treatment ‘Treatment clecontinvation Son - aT Dose-reduced Lack of response ‘Transformation into CMML Death: unrelated Death: related Teer, etal 2013 st abstract 8662 s geron
Slide 41: Safety Results (n=33)
Safety Results (n=33) All grade 3/4 extramedullary adverse events not related to myelosuppression (Includes all events regardless of attribution) Fatigue 3 (9%) Acfib 2.(6%) ALP 2 (6%) Heart failure 1 (3%) Hyponatremia 1 (3%) Gl bleed 1 (3%) Hyperkalemia 1 (3%) Pruritus 1 (3%) Intestinal obstruction
Slide 42: Safety Results (n=33)
Safety Results (n=33) Treatment-related toxicity of imetelstat among 33 patients with high/int-2 risk myelofibrosis Grade-1 nausea 5 (15%) Grade-1 vomiting 1 (3%), Grade-1/2 fatigue 4 (12%) Grade-2 hyperbilirubinemia 2(6%) Grade-2 APTT increase 13%) Grade-3/4 neutropenia T(21%) 211%) 5 (36%) Grade-3
Slide 43: Safety Observations
Safety Observations * Myelosuppression is the principal dose-l ing toxicity * Believed to be an on-target toxicity due to effects on progenitor cells = Manageable through dose hold rules and dose modifications + To mitigate against risk of severe, persistent cytopenias, Mayo Clinic protocol amended
Slide 44: Imetelstat for Treating Myelofibrosis — Key Conclusions
etelstat for Treating Myelofibrosis — Key Conclusions * Geron’s independent review of the data from the first 22 patients in the Mayo Clinic IST suggests that imetelstat has disease-modifying activity in MF + Unprecedented remissions (CR+PR) by IWG-MRT criteria observed in 5/22 patients ~ fone marro
Slide 45: Q&A
Q&A geron