Stifel Nicolaus 2013 Healthcare Conference. John Scarlett, M.D. Chief Executive Officer September 11, 2013

Transcription

1 Stifel Nicolaus 2013 Healthcare Conference John Scarlett, M.D. Chief Executive Officer September 11,

2 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 Investors are cautioned that without limitation, the following statements in this presentation regarding Geron's plans or expectations for or of: (a) timelines for any clinical trial data reporting in 2013, including investigator sponsored clinical trials (ISTs); (b) timelines for any clinical trial initiation in 2014 or, at all, including ISTs; (c) prospects for the clinical success of imetelstat, including imetelstat s clinical activity in the bone marrow and potential to be disease modifying; (d) U.S. patent protection through 2025 with patent extension expected beyond for imetelstat; and (e) having sufficient financial resources to develop imetelstat in hematologic myeloid malignancies, constitute forward-looking statements. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include without limitation, regarding: (a) dates to report clinical trial data safety issues, dependence on clinical trial investigators and collaborators for data, delays or stoppages caused by institutional review boards or regulatory agencies, shortage of supply, and delays in enrollment; (b) timelines/dates to initiate clinical trials safety issues, dependence on clinical trial investigators and collaborators for data, delays or stoppages caused by institutional review boards or regulatory agencies, shortage of supply, and delays in enrollment; (c) clinical success of imetelstat, imetelstat s clinical activity in the bone marrow and potential to be disease modifying those risks and uncertainties inherent in the development of potential therapeutic products such as successful clinical trial results, technical and scientific challenges, limitations on freedom to operate arising from intellectual property of others, and challenges or enforcement of Geron's intellectual property rights; (d) having U.S. patent protection through 2025 and patent extension beyond for imetelstat limitations on freedom to operate arising from intellectual property of others, challenges to or enforcement of Geron s intellectual property rights, the granting of patent term extension by the governmental patent offices, and access to third-party patents; and (e) having sufficient financial resources to develop imetelstat unanticipated expenses, such as those related to clinical trials, manufacturing, litigation and challenges to or enforcement of Geron's intellectual property rights and freedom to operate. More detailed additional information and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron's periodic reports filed with the Securities and Exchange Commission under the heading "Risk Factors," including the quarterly report on Form 10-Q for the quarter ended June 30, Undue reliance should not be placed on forward-looking statements, which speak only as of the date of this presentation, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. 2

3 geron imetelstat in hematologic myeloid malignancies Imetelstat: a novel and differentiated product in Phase 2 clinical development first telomerase inhibitor in clinical development discovered and developed by Geron; IP through 2025 with patent extension expected beyond may selectively inhibit telomerase-driven proliferation of malignant cells in bone marrow Proof-of-concept data from Phase 2 trial in essential thrombocythemia (ET) durable hematologic and molecular responses presented at EHA 2013 potential for disease modifying activity in multiple hematologic myeloid malignancies Focus on myelofibrosis (MF) with investigator-sponsored trial ongoing at Mayo Clinic enrollment completed for two cohorts administering imetelstat at different dosing intensities pre-specified safety and efficacy criteria met in both cohorts for expanded enrollment data expected at ASH 2013 if data are positive, expect to begin Geron-sponsored multi-center clinical trial Well-positioned to develop imetelstat in hematologic myeloid malignancies approximately $71 million in cash and investments at June 30,

4 imetelstat a novel first-in-class telomerase inhibitor chromosome imetelstat binds to RNA template preventing maintenance of telomeres RNA Template telomere Telomerase A U C C C A A U C U G U U T A G G G T T A G A C A A Telomerase enzyme adds nucleotide repeats for maintenance of telomeres (protective caps of chromosome for stability and integrity) transiently upregulated in normal hematopoietic progenitor cells to support controlled proliferation highly upregulated in malignant progenitor cells, enabling continued and uncontrolled proliferation Proprietary oligonucleotide chemistry 13-mer oligonucleotide with lipid tail competitive inhibitor of telomerase: oligo sequence complementary to the telomerase RNA template (active site) potent: IC50 = nm (cell-free) T T A G G G Telomere Imetelstat long half-life in bone marrow, spleen, liver and tumor (estimated human t½ = 41 hr with doses mg/kg) administered by intravenous infusion 4

5 hematologic myeloid malignancies represent a spectrum of diseases with unmet needs platelets (abnormal) essential thrombocythemia (ET) malignant myeloid progenitor collagen and reticulin fibers (fibrosis) myelofibrosis (MF) ~2,300 cases/year (US) ~16,000 prevalence myeloproliferative neoplasms (MPNs) polycythemia vera (PV) malignant clone red blood cells (abnormal) acute myelogenous leukemia (AML) ~13,000 cases/year (US) myelodysplastic syndromes (MDS) ~12,000 cases/year (US) 5

6 imetelstat in myeloproliferative neoplasms essential thrombocythemia (ET): proof-of concept Rationale for proof-of-concept in ET: Representative of the myeloproliferative neoplasms (MPNs), which include myelofibrosis High levels of telomerase in malignant megakaryocytes in the bone marrow Imetelstat selectively inhibits proliferation of malignant megakaryoctes (ex vivo) Molecular mutations (e.g., JAK2 V617F) acquired in malignant progenitor cells are transmitted through progeny (malignant clones) and may be used as molecular markers of disease Decrease in JAK2 V617F indicates selective inhibition of malignant clone and disease modifying activity in ET Positive results suggest potential for disease modifying activity in multiple hematologic myeloid malignancies, including myelofibrosis 6

7 imetelstat in ET proof-of-concept phase 2 study design Patients (n=18): refractory to or intolerant of prior therapies Imetelstat dosing: single agent administered by intravenous infusion Induction: weekly until complete hematologic response (CR; normalization of platelet count 4 weeks) Maintenance: as needed to maintain CR (titrated to platelet count) Efficacy endpoints 1 : Hematologic response rate: reduction in platelet counts Molecular response rate: reduction in JAK2 mutation allelic burden Principal investigators: US: David Snyder, MD, City of Hope Europe: Gabriela Baerlocher, MD, University of Bern 1 Barosi et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 2009, 113:

8 JAK2 V617F % Allelic Burden proof-of-concept: molecular responses suggest disease modifying activity in ET 100% hematologic response rate (89% CR, 11% PR) rapid: median time to CR is 6.1 weeks durable: median time on therapy is 14 months (range 3 months years) 88% molecular response rate (7/8 patients with mutation) durable: maintained in 6/7 patients (86%) Decreases in JAK2 V617F allele burden ET Patient 1 ET Patient 3 ET Patient 5 ET Patient 6 ET Patient 10 ET Patient 14 ET Patient 16 ET Patient Month Presented at the 2013 EHA Congress Abstract #4398 (Gabriela Baerlocher) 8

9 molecular responses are rare in myeloproliferative neoplasms Limited evidence of disease modifying activity with other agents minimal impact with hydroxyurea in ET low frequency reported with peg-infα 1 in ET JAK inhibitors in myelofibrosis (MF) ruxolitinib 2 : 21% of patients achieved 20% reduction in JAK2 V617F allele burden CYT387 3 : none reported SAR : minimal reduction in JAK2 V617F allele burden observed Based on data from ET: imetelstat may have disease modifying activity against malignant clones in the bone marrow 1 Quintas-Cardama et al, JCO 2009;27: Vannucchi et al, 2012 ASH Annual Meeting (Abstract #802) - 3 Pardanani et al, 2012 ASH Annual Meeting (Abstract #178) - 4 Lui et al, 2013 AACR Annual Meeting (Abstract #LB-294) 9

10 imetelstat s safety profile in ET generally well tolerated for up to 2.5 years * Toxicity is primarily hematologic three patients had Grade 4 neutropenia (no cases of febrile neutropenia) no thromboembolic events or bleeding events associated with thrombocytopenia reported Non-hematologic adverse events (AEs) most frequent assessed as imetelstat related by investigators were gastrointestinal events and fatigue majority mild-to-moderate (Grade 1-2) no drug-related Grade 4 AEs *13 of the 16 patients (81.3%) with a hematologic CR remain on treatment *median time on therapy: 14 months (range 3 months years) Presented at the 2013 EHA Congress Abstract #4398 (Gabriela Baerlocher) 10

11 hematologic myeloid malignancies represent a spectrum of diseases with unmet needs platelets (abnormal) essential thrombocythemia (ET) malignant myeloid progenitor collagen and reticulin fibers (fibrosis) myelofibrosis (MF) ~2,300 cases/year (US) ~16,000 prevalence myeloproliferative neoplasms (MPNs) polycythemia vera (PV) malignant clone red blood cells (abnormal) acute myelogenous leukemia (AML) ~13,000 cases/year (US) myelodysplastic syndromes (MDS) ~12,000 cases/year (US) 11

12 understanding myelofibrosis (MF) Clonal myeloproliferation leads to bone marrow fibrosis Impaired bone marrow hematopoiesis shifts blood production to spleen and liver (extramedullary hematopoiesis) Constitutional symptoms (e.g., fatigue, fever, night sweats, pruritis) thought to be due to abnormal cytokine expression Compromised quality of life: severe anemia (requiring blood transfusions) hepatosplenomegaly debilitating symptom burden cachexia Shortened survival leukemic transformation to AML thrombohemorrhagic complications associated with dysfunctional hematopoiesis malignant myeloid progenitor malignant clone normal bone marrow multiple myeloid precursors collagen and reticulin fibers (fibrosis) advanced fibro-osteosclerosis 12

13 patients with myelofibrosis have a poor prognosis Dynamic International Prognostic Scoring System (DIPSS) Plus Prognostic category Number of risk factors Median survival Patients High risk years 24 % Intermediate-2 risk years 46 % Intermediate-1 risk years 22 % Low risk years 8 % Data from cohort of 793 consecutive patients treated at Mayo Clinic between 1970 and % of patients Eight risk factors for inferior survival: Red blood cell transfusion need Anemia Thrombocytopenia Leukocytosis Circulating blasts 1% Constitutional symptoms Unfavorable karyotype Age >65 years optimal therapies would address prognostic disease characteristics 1 Gangat et al. DIPSS Plus: A Refined Dynamic International Prognostic Scoring System for Primary Myelofibrosis That Incorporates Prognostic Information From Karyotype, Platelet Count, and Transfusion Status. JCO 2011, 29:

14 JAK inhibitors primarily address splenomegaly and symptoms Ruxolitinib (Jakafi ) is currently the only approved JAK inhibitor for patients with MF Phase 3 trials spleen response reduction 35% by MRI/CT symptom response patient assessed molecular response 20% red. in JAK2V617F allele burden overall survival median survival not reached Phase 1/2 trial COMFORT-I v. placebo by 24 weeks 41.9% ruxolitinib 1 0.7% placebo 45.6% ruxolitinib 1 5.3% placebo (>50% reduction Total Symptom Score) HR = 0.58 (log rank test P=0.028) 2 median follow up: 102 weeks v. database controls (BAT) at 48 months COMFORT-II v. BAT by 48 weeks 28.5% ruxolitinib 3 0% BAT (best available therapy) ruxolitinib: improvement in QoL measures and symptoms BAT: worsening of symptoms 21% ruxolitinib 4 0% BAT other JAK inhibitors currently in clinical development with similar activity HR = 0.48 (log rank test P=0.009) 5 median follow-up: 151 weeks bone marrow fibrosis 22% ruxolitinib show improvement (by WHO scoring system) 6 2% controls show improvement 1 Verstovsek et al, 2012 NEJM 2012;366: Verstovsek et al, 2012 ASH Annual Meeting (Abstract #800) 3 Harrison et al, 2012 NEJM 366: Vannucchi et al, 2012 ASH Annual Meeting (Abstract #802) - 5 Vannucchi et al, 2013 EHA Annual Meeting - 6 Kvasnicka et al, 2013 EHA Annual Meeting 14

15 the unmet medical need in MF address the underlying malignant process Revised IWG/ELN criteria for response in myelofibrosis 1 JAK inhibitors CR: complete remission normal cellularity and reversal of bone marrow fibrosis normal peripheral blood counts and smears complete resolution of symptoms and splenomegaly none reported PR: partial remission as CR without bone marrow response or as CR with bone marrow response but without full recovery of peripheral blood counts none reported CI: clinical improvement anemia, spleen or symptoms response no progressive disease or increase in severity of anemia, thrombocytopenia or neutropenia spleen response anemia response symptoms response improvements in splenomegaly, anemia or symptoms stabilization of the other criteria not required Duration must be 12 weeks to qualify as a response under any category 1 Tefferi, A et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood 122: ,

16 focusing imetelstat in myelofibrosis (MF) Rationale for pilot study in MF: Compelling activity in ET; molecular responses indicate selective inhibition of a malignant clone in the bone marrow and disease modifying activity A myeloproliferative neoplasm (MPN), as ET, which can evolve into MF No approved drug therapy that addresses underlying bone marrow malignancy Established regulatory path through approval of ruxolitinib Commercial opportunity ruxolitinib only approved therapy imetelstat provides novel mechanism of action 16

17 imetelstat myelofibrosis IST study design high risk or intermediate-2 (DIPSS_plus) primary or secondary (post-pv or post-et) MF patients single agent imetelstat (prior therapy with JAK inhibitors allowed) 1 Endpoint: overall response rate (CR, PR or CI) per IWG-MRT criteria 2 Endpoints: reduction of spleen size transfusion independence safety/tolerability Simon Two- Stage Design: 2/11 responders (CR,PR or CI) expand enrollment Principal Investigator & Study Sponsor: Ayelew Tefferi, MD Mayo Clinic, Rochester 17

18 imetelstat myelofibrosis IST recent status report by investigator (August 2013) high risk or intermediate-2 (DIPSS_plus) primary or secondary (post-pv or post-et) MF patients Cohort A: imetelstat every three weeks Cohort B: imetelstat induction weekly x4 then every three weeks Enrollment (n=11) completed March 2/11 responders (CR, PR or CI) per IWG criteria; expanded enrollment enabled Enrollment (n=11) completed May 2/11 responders (CR, PR or CI) per IWG criteria; expanded enrollment enabled blast phase-mf patients imetelstat weekly IRB approval to initiate enrollment (n=11) 18

19 imetelstat development in 2013 and beyond upcoming events Data from myelofibrosis IST expected at ASH in December 2013 If positive data from myelofibrosis IST, expect to initiate Geron-sponsored multi-center clinical trial in 1H14 Pilot studies expected in other hematologic myeloid malignancies, such as MDS 19

20 geron imetelstat in hematologic malignancies Imetelstat: a novel and differentiated product in Phase 2 clinical development first telomerase inhibitor in clinical development discovered and developed by Geron; IP through 2025 with patent extension expected beyond may selectively inhibit telomerase-driven proliferation of malignant cells in bone marrow Proof-of-concept data from Phase 2 trial in essential thrombocythemia (ET) durable hematologic and molecular responses presented at EHA 2013 potential for disease modifying activity in multiple hematologic myeloid malignancies Focus on myelofibrosis (MF) with investigator-sponsored trial ongoing at Mayo Clinic enrollment completed for two cohorts administering imetelstat at different dosing intensities pre-specified safety and efficacy criteria met in both cohorts for expanded enrollment data expected at ASH 2013 if data are positive, expect to begin Geron-sponsored multi-center clinical trial Well-positioned to develop imetelstat in hematologic myeloid malignancies approximately $71 million in cash and investments at June 30,

21 For further information, please contact: Anna Krassowska, Ph.D., Investor Relations or 21

22 revised (2013) IWG response criteria for MF: Complete Remission (CR) Partial Remission (PR) bone marrow: age-adjusted normocellularity; <5% blasts; grade 1 MF peripheral blood: hemoglobin 100g/L, neutrophil count 1x10 9 /L, platelet count 100x10 9 /L, all <ULN; <2% immature myeloid cells clinical: resolution of symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis peripheral blood: as CR above clinical: as CR above bone marrow: as CR above peripheral blood: hemoglobin 85<100g/L, neutrophil count 1x10 9 /L, platelet count 50<100x10 9 /L, all <ULN; <2% immature myeloid cells clinical: as CR above Clinical Improvement (CI) Anemia Response Spleen Response Symptoms Response anemia, spleen or symptoms response no progressive disease or increase in severity of anemia, thrombocytopenia or neutropenia transfusion-independent patients: 20g/L increase in hemoglobin transfusion-dependent patients: becoming transfusion independent baseline splenomegaly palpable at 5-10cm below LCM: not palpable baseline splenomegaly palpable at >10cm below LCM: decrease by 50% (confirmation by MRI showing 35% reduction in volume) patient assessed 50% reduction in symptoms (fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, fevers) Duration must be 12 weeks to qualify as a response under any category Tefferi, A et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood 122: ,