Geron Corporation · NASDAQ:GERN
Geron — Investor Presentation (January 2017)
26 slides from Geron's investor presentation, Jan 9, 2017
Slide 1: Corporate Presentation January 2017
jaro Corporate Presentati January 2017
Slide 2: Forward-Looking Statements
geron ooking 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 statements in this presentation re
Slide 3: Overview
rview Imetelstat’s clinical activity suggests impact on underlying disease in hematologic myeloid malignancies * Inhibiting telomerase activity impedes production of malignant cells * First telomerase inhibitor in clinical development * Molecular responses seen in essential thrombocythemia (ET) and
Slide 4: Telomerase: a target in oncology
Se r target in oncology Telomerase enzyme RNA template (hTR) Catalytic subunit Telomeric DNA (hTERT) Comprised of an RNA template component (hTR) Binds to the 3’ strand of DNA and adds TTAGGG and a reverse transcriptase catalytic protein nucleotide repeats to offset the loss of telomeric subunit (hT
Slide 5: Telomerase in hematologic malignancies
matologic malignancies Normal hematopoietic progenitor cells mature blood cells hematopoietic progenitor calls @ ematopoietic normal ae O—| blood counts —e@ Le o- a @ oom i EEE ‘ote OO telomerase jaar - upregulated downregulated Telomerase transiently upregulated to support controlled proliferation;
Slide 6: Imetelstat: first-in-class telomerase inhibitor
t geron lass telomerase inhibitor * Proprietary: 13-mer thio-phosphoramidate \ {N oligonucleotide complementary to hTR, with imetelstat covalently-bound lipid tail to increase cell lipid tail permeability/tissue distribution * Long tissue residence time in bone marrow, spleen, liver (0.19 — 0.51 4M
Slide 7: Hematologic Myeloid Malignancies
ic Myeloid Malignancies alignant progenitor cells in the bone ESSENTIAL THROMBOCYTHEMIA (ET) platelets + ~12,000 cases diagnosed ey Pe wyevopyspiasTic —* Pe Pvearin the Us paneer et a + 60,000 people in the US living with MDS ° e + ~70% of patients have POLYCYTHEMIA VERA lower risk disease ACUTE MYE
Slide 8: A mechanism to address the underlying disease in MF and MDS
nd MDS :A mechanism to address the underlyi malignant megakaryocyte clone (growth factor phenotypic drivers: independent) JAK/STAT signaling pathway gain-of-function mutations JAK2V617F, CALR, MPL telomerase malignant malignant hematopoietic —_ progenitor cells stem cell driver mutations unknown mal
Slide 9: Clinical data suggest disease-modifying activity
linical data suggest disease-modifying act ion of Malignant Clones by Ime Proof-of-concept in essential thrombocythemia * Molecular responses and allele burden reductions in patients with JAK2V617F, CALR or MPL mutations, and others * Increases in average telomere length in patients’ granulocytes at
Slide 10: Myelofibrosis
sis cteristics + Malignant clonal proliferation and atypical megakaryocytic hyperplasia leads to bone marrow fibrosis and impaired hematopoiesis - Fibrosis thought to be induced by inflammatory cytokines produced by megakaryocytes originating from the malignant progenitor cell clone - Constitutional
Slide 11: Evolution of Therapy in High/Int-2 Risk MF
Evolution of Therapy in High/Int-2 Risk MF Treatment paradigm before ruxolitinib approval in Nov 2011 Conventional treatments * drug therapies: e.g., hydroxyurea, steroids, r immunomodulatory agents, androgens Median survival: * splenectomy, radiotherapy 1-3 years High or * allogeneic hematopoietic
Slide 12: Evolution of Therapy in High/Int-2 Risk MF: high unmet need remains
of Therapy in High/Int-2 Risk h unmet medical need remains Symptoms or splenomegaly * treatment with ruxolitinib * stay on drug as long as tolerated (conventional drugs viewed as ineffective, especially in advanced disease) 5-year discontinuation rate is ~75% (COMFORT I & I!) * major reasons: - subo
Slide 13: Patient populations in clinical trials
Therapy in High/Int-2 Risk ent populations in clinical trials Frontline Second line (JAK inhibitor naive) (JAK inhibitor exposed) + No prior treatment with a + Prior treatment with a JAK + Disease progression during JAK inhibitor inhibitor (e.g., for 228 days) or after treatment with a JAK inhibitor
Slide 14: Additional JAK inhibitors with Phase 3 results reported
Evolution of Therapy in High/Int-2 Risk MF Additional JAK inhibitors with Phase 3 results reported Frontline Second line (JAK inhibitor naive) (JAK inhibitor exposed) momelotinib SLi (vs. ruxolitinib) JAKA/JAK2 SVR: 26.5% vs. 29.0! reap. TsS: non-inferiority ~s not achieved pacritinib PERSIST 1* JAK
Slide 15: Additional JAK inhibitors with Phase 3 results reported
Evolution of Therapy in High/Int-2 Risk MF Additional JAK inhibitors with Phase 3 results reported Frontline Second line (JAK inhibitor naive) (JAK inhibitor exposed) momelotinib Cie (vs. ruxolitinib) JAKA/JAK2 SVR: 26.5% vs. 29.0! aisles TSS: non-inferiority = not achieved pacritinib PERSIST 1 JAK2
Slide 16: Focusing imetelstat on relapsed or refractory patients
Evolution of Therapy in High/Int-2 Risk MF Focusing imetelstat on relapsed or refractory patients Frontline Second line (JAK inhibitor naive) (JAK inhibitor exposed) imetelstat telomerase inhibitor (intravenous) IMbark Phase 2 clinical trial ae being conducted by + Unprecedented complete and partial
Slide 17: IMbark original study design
IMbark Original study design A multi-center, open label study being conducted by Janssen + Objectives: - Define proper dosing by evaluating potential therapeutic range of the drug 4.7 mg/kg q3w: lowest dose where telomerase inhibition is predicted 9.4 mg/kg q3w: max dosing regimen derived from the M
Slide 18: Status of IMbark
atus of IMbark ng to evaluate more mature MF data First planned internal data review completed by Janssen in September 2016 * 20 patients from each dosing arm who had been followed for at least 12 weeks Safety profile was consistent with previous imetelstat clinical trials in hematologic myeloid mal
Slide 19: Myelodysplastic Syndromes
lastic Syndromes cteristics Diverse group of clonal hematologic malignancies with disordered and ineffective production of the myeloid lineage in the bone marrow characterized by abnormal cell morphology and counts (anemia and other cytopenias) Median age at diagnosis is ~70 years Up to 30% of patie
Slide 20: No new drugs approved for >10 years
's approved for >10 years Approved or conventional treatments Del 5q Lenalidomide cytogenetic *+ 55% to 65% RBC-TI (28 wk) i abnormality + median duration: 2-2.5 years Lower Risk (5-20% Mps patients) Median survival: Erythropoiesis 3.5-5.7 years stimulating agents (ESAs) Non-del 5q + improvement in
Slide 21: Clinical Development in Lower Risk MDS
Clinical Development in Lower Risk MDS Chronic anemia remains an unmet need luspatercept ligand trap inhibiting TGF-B superfamily imetelstat telomerase inhibitor Mayo Pilot Study: IPSS int-1/int-2 RARS Ringed sideroblast 3/8 (37.5%) transfusion PACE Phase 2: positive dependent patients IPSS low/int-
Slide 22: IMerge: multi-center, two part study being conducted by Janssen
A multi-center, two part study being conducted by Janssen * Objectives: - Part 1 (Phase 2) to evaluate safety and efficacy of imetelstat to advance to Part 2 based on positive assessment of benefit-risk profile in significant unmet medical need population - Part 2 (Phase 3) to compare imetelstat to
Slide 23: Status of IMerge
status of IMerge ig to evaluate more mature data geron First internal data review completed by Janssen in September 2016 * Subset of patients in Part 1 * Emerging safety and efficacy consistent with data reported from Mayo Clinic Pilot Study MDS-RARS cohort * Part 1 of the trial continues unmodified
Slide 24: Key Milestones for IMbark and IMerge
Key Milestones for IMbark and IMerge Expectations for 2017 1H 2017 2H 2017 Internal data review Possible outcomes: © to include patients from ‘© enrollment is resumed at 9.4 mg/kg to reach a IMbart 9.4 mg/kg arm with at total of ~100 patients for primary analysis, or myelofibrosis least 24 weeks fol
Slide 25: Partnership with Janssen
ership with Janssen worldwide collaboration for imetelstat 1 First Stage Continuation Stage IMbark (Phase 2 MF study) IMerge (Phase 2/3 MDS study) * Janssen conducting IMbark and IMerge * Janssen to provide Continuation Decision following primary analysis of IMbark™” First Stage Economics Upfront $3
Slide 26: Thank you