Genta Incorporated A Multiproduct Late-Stage Oncology Company
This presentation may contain forward-looking statements with respect to business conducted by Genta Incorporated. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. Forward-looking statements include, without limitation, statements about: the Company s ability to obtain necessary regulatory approval for its products from the U.S. Food and Drug Administration ( FDA ) or other regulatory authorities; the safety and efficacy of the company s products or product candidates; the Company s assessment of its clinical trials; timing of the commencement and completion of clinical trials; the Company s ability to develop, manufacture, license and sell its products or product candidates; the Company s ability to enter into and successfully execute license and collaborative agreements, if any; the adequacy of the Company s capital resources and cash flow projections, and the Company s ability to obtain sufficient financing to maintain the Company s planned operations; the adequacy of the Company s patents and proprietary rights; and the other risks described under Certain Risks and Uncertainties Related to the Company s Business, as contained in the Company s Annual Report on Form 10-K and Quarterly Report on Form 10-Q. The Company does not undertake to update any forwardlooking statements. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the Company's most recent Annual Report on Form 10-K and its most recent quarterly report on Form 10-Q.
Genta Incorporated Oncology focus on novel small molecules De-risked pipeline: oral analogs of highly active agents Objective: direct marketer in U.S. Experienced senior management Berkeley Heights, NJ USA
Oncology Focused Pipeline Small Molecules PIPELINE Preclinical Phase 1 Phase 2 Phase 3 Market Tesetaxel PLANNED Ganite (gallium nitrate injection) Oral Gallium
Tesetaxel Phase 3 Oncology Opportunity New Chemical Entity (NCE) Indications: Gastric, Breast, Prostate First-to-Market Oral Taxane
Tesetaxel A leading anti-tubulin agent Taxanes: established market O Tubulin: highly validated target Current products: marked limitations O N N H F H O O O O O N Tesetaxel features: H O O H O O Convenient oral dosing O O No infusion reactions or premeds Reduced nerve damage Active in taxane-resistant disease Established Phase 2 activity Projected launch: 2015
Tesetaxel: Phase 1 Studies Summary of 5 completed/ongoing trials Dose range: 1.5 40 mg/m 2 Every 3 week schedule: Maximally tolerated dose (MTD): 27 mg/m 2 Dose-limiting: neutropenia Weekly schedule: Weekly x 3 weeks, one week off MTD: defined Dose-limiting: constitutional symptoms (fatigue, anorexia) Two dose-ranging studies with capecitabine (Xeloda ): Full doses of each drug can be co-administered DLTs: neutropenia vs. thrombocytopenia/hand-foot (capecitabine)
Clinical Development Program Broad Phase 2; pending Phase 3 Confidential Tesetaxel Preclinical Phase 1 Phase 2 Phase 3 Market Gastric Cancer (2 nd Line) Open (Confirmatory) (Pending) Gastric Cancer (1 st Line) Open Breast Cancer (1 st Line) Open (Confirmatory) Prostate Cancer (1 st Line) Open Bladder Cancer (2 nd Line) Open
Confidential Gastric Cancer Program Completed Phase 2 2 nd line Ongoing Confirmatory Phase 2 2 nd -line Ongoing Initial Phase 2 1 st line combination Planned Phase 3 Trial -- 2 nd -line
Phase 2a Trial (completed) 2 nd Line gastric cancer efficacy* Response n Percent Partial 7 20% Stable 13 37% Progression/non-evaluable 15 40% * Efficacy population: n = 35
Ongoing Phase 2b Trial (confirmatory) 2 nd Line gastric cancer Trial design Phase 2, open-label, multi-center Progression on 1 chemotherapy regimen: 5-FU or platinum, or both Taxane-naive Three cohorts: Cohort A 40 mg flat dose (complete; n=13) Cohort B 50 mg flat dose (complete; n=13) Cohort C 27 mg/m 2 BSA (ongoing; n=15+)* Dose/schedule: once every 3 weeks Primary endpoint: Overall response rate (RECIST) *November 2011
Ongoing Phase 2b Trial (confirmatory) 2 nd Line gastric cancer overall response rate Response Cohort A (40 mg) n=13 Cohort B (50 mg) n=13 Cohort C (27 mg/m 2 ) n=15* Partial 1 (8%) 2 (15%) 3 (20%)* Stable 2 4 2 Progression 6 6 4 Not evaluable 4 1 1 Too early - - 4 *Pending update ASCO GI, January 2012
Gastric Cancer -- Single-Agent Comparative 2 nd -line therapies Event Tesetaxel Docetaxel 1-4 Everolimus 5.6 Response rate 20% 5% 14% 18% 19% 0% Time-toprogression (median, mos) 3.6 1.4 2.6 n/a 4.2 2.7 (95% CI: 50-91d) Neutropenia Gr 3-4: 37% Gr 3-4: 10-60% N/A Plts: 21% 1 Graziano F et al.: Ann Oncol. 11:1263, 2000; 2 Jo J-L et al.: Jpn J Clin Oncol 37:936, 2007; 3 Vanhoefer U, et al.: Proc ASCO 18:303a, 1999; 4 Lee J-L et al.: Cancer Res Treat. 37:201, 2005; 5 Doi et al., J Clin Oncol. 28:1904, 2010; 6 Currently in multinational Phase 3 trials as 2 nd -line therapy.
Proportion Surviving Ongoing Phase 2b Trial (confirmatory) 2 nd Line gastric cancer overall survival* 100 Confidential Cohort A Cohort B Cohort C 80 Median (mos) Events (N) 7.8 12/13 7.5 10/13 1/13 Percent (92%) (77%) 60 40 20 0 0 2 4 6 8 10 12 14 Overall Survival (Months) *K-M estimate, November 2011 N = 39 patients accrued Pending update: ASCO GI, January 2012
Gastric Cancer Proposed pivotal study Phase 3, randomized, double-blind trial Stratification/ Randomization Active + Tesetaxel Active + Placebo Population: 2 nd -line; progression on 1 st -line platinum/fp regimen Multinational: U.S., Western Europe, East Asia; 580 patients Primary endpoint: OS; target HR: 0.75; 90% power: a =0.05 Secondary Endpoints: TTP; ORR; DCR; PE analyses; safety Stratifications: Geography (Asia/Other); Liver mets (Y/N); Gastrectomy (Y/N); progression on 1 st line 4 mos
Confidential Breast Cancer Program Completed Phase 2 Confirmatory Phase 2 (ongoing)
Phase 2 Trial (completed) 2 nd Line breast cancer efficacy (n = 32) Response N Percent Partial 13 38% Stable 10 29% Progression 9 28% Not Evaluable 2
Ongoing Phase 2 Trial (confirmatory) 1 st Line breast cancer design Phase 2 open label, single arm, multicenter study N = 45+ (New cohort planned for weekly schedule) Chemotherapy naive; adjuvant taxane permitted if 12 months prior to study No limitation on prior hormonal regimens HER2+ excluded Dose/schedule: 27 mg/m 2 every 3 weeks 15 mg/m 2 weekly x 3 (amendment pending) Primary endpoint: Overall response rate (RECIST)
Percent Change From Baseline Ongoing Phase 2 Trial (confirmatory) 1 st Line breast cancer efficacy in 24 evaluable pts* 100 80 60 49 = CR/PR = SD 40 20 33 27 20 10 8 = PD 0-20 0-1 -8-17 -23-25 -40-32 -43-60 -56-57 -65-67 -80-76 -100-88 -95-97 -98-100 SABCS 12/9/11 Major response rate: 50% (12/24) Disease control rate: 79% (19/24)
Hematological Toxicity -- Phase 2 Comparative safety with other taxanes Confidential Event Tesetaxel 1 N = 159 Paclitaxel 2 N = 812 Docetaxel 3 N = 2045 Neutropenia (Grade 4) Febrile Neutropenia 23% 52% 75% 3% 2-15% 11% Anemia (Gr 3-4) 11% 16% 9% 1 Aggregated results of tesetaxel Phase 2 studies for patients who initiated treatment at 27 mg/m 2 (MTD); 2 Taxol 2000 package insert; 3 Taxotere 2006 package insert
Non-Hematological Toxicity -- Phase 2 Comparative safety with other taxanes Confidential Event Tesetaxel 1 N = 159 Paclitaxel 2 N = 812 Docetaxel 3 N = 2045 Diarrhea 4% 2%-4% 5% Nausea 4% 10%-29% 3%-10% Vomiting 3% 10%-29% 2%-8% Neurosensory 2% 30-45% 4 -- Hypersensitivity 0% > 50% > 50% 1 Aggregated results of tesetaxel Phase 2 studies for patients who initiated treatment at 27 mg/m 2 (MTD); 2 Taxol 2000 package insert; 3 Taxotere 2006 package insert 4 Conlin et al., J Clin Oncol (Suppl.) 2009 (data for nab-paclitaxel [Abraxane ] in 200 patients)
Regulatory Status Global activity reflects broad program interest Activities Status* Orphan Drug designations: Gastric cancer (US and EU) Fast Track designation (U.S.: Gastric) EMA Scientific Advice (Phase 3 Gastric) FDA End-of-Phase 2 (Phase 3 Gastric) Japan PMDA submissions/mtg: trial open Korea KFDA submissions: 2 trials open Taiwan Phase 3 Gastric China IMPD/SFDA Granted Granted Completed Completed Completed Completed Approved Submitted *Q1 2012
Tesetaxel: Market Opportunity Large population -- validated markets Treatable Patients 800000 700000 600000 500000 400000 300000 200000 100000 0 US EU JAPAN CHINA Large global population in multiple tumor types Gastric Cancer Breast Cancer Prostate Cancer Market Opportunity Product 2010 Sales VALIDATED CLASS Microtubule Inhibitors VALIDATED STRATEGY Oral Alternatives Taxotere $2.440M Taxol $ 460M Abraxane $ 350M Ixempra $ 419M Total Projected $3.669M Xeloda $1.005M S-1 $ 357M Total Projected $1.362M Sources: Oncology Inc/Synovate; Foster IIBD; Datamonitor Cytotoxic Therapy Cancer Brands ; ACS/ IARC databases.
Tesetaxel Value proposition First-to-market oral taxane Large well-validated markets Abraxane : validated taxane market for reduced side-effects No oral taxane competitor in clinical trials Phase 3 opportunities in gastric and breast cancer Established clinical activity No hypersensitivity; no pre-medications; reduced neuropathy Lack of taxane cross-resistance increases market potential Potential approval(s) within 3 years; clear paths to registration Convenience enables novel combinations All oral combinations with new targeted therapies Strong pharmaco-economic arguments
Financials Cash/short-term investments $5.9 MM* Completed (conditional) financing $8.5 MM Projected cash burn/month ~ $1.0 MM *EOQ3 2011 September 2011
Genta Milestones Multiple products drive value: 2012 Milestones Tesetaxel: Phase 2b gastric: updated response/survival Q1 11 Phase 2a gastric: initial data -- 1 st -line Q2 11 Phase 2b breast: updated response/pfs Q2 11 Phase 2a prostate: initial data 1 st -line Q2 11 Weekly dosing schedule: final data Q2 11 Phase 3 gastric cancer: initiation Co-development /commercial partnership(s) TBD TBD All events /dates are forward-looking estimates and subject to FDA approval, funding, and other factors