2008 Bank of America Health Care Conference May 2008

Transcription

1 2008 Bank of America Health Care Conference May 2008 NASDAQ: ALTH -1-

2 Safe Harbor Statement This presentation contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of Generally, you can identify these statements by the use of terms such as may, will, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, potential, continue, and other similar terms or the negative of these terms, but their absence does not mean that a particular statement is not forwardlooking. Forward-looking statements may include statements concerning: time lines for completing clinical trials; time lines for releasing data from clinical trials; time lines for initiating new clinical trials; our collaboration efforts; future licensing and acquisition activity; future product development activities; the expected safety and effectiveness of our product candidates in treating diseases; our competitive position; plans for regulatory filings; receipt of future regulatory approvals; our expected cash resources and requirements; plans for sales and marketing; implementation of corporate strategy; and other statements that are other than statements of historical facts. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. Additional information concerning the risks and uncertainties that may cause such differences is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2007, and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this presentation. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law. Note: The Allos logo is a trademark of Allos Therapeutics, Inc. -2-

3 Company Highlights Oncology-focused biopharmaceutical company Prioritized, high-potential R&D pipeline with 2 proprietary candidates in development PDX unique antifolate with potential in hematologic malignancies and solid tumors o 6 ongoing studies evaluating PDX in multiple indications o SPA-approved pivotal Phase 2 trial in PTCL RH1 targeted chemotherapeutic prodrug o Phase 1 study in advanced solid tumors & NHL ongoing Business model focused on opportunities that can be addressed with a targeted sales and marketing organization Experienced management team with proven results Worldwide exclusive rights to both PDX and RH1-3-

4 Product Development Pipeline PDX HEMATOLOGIC MALIGNANCIES Preclinical Phase 1 Phase 2 Phase 3 NDA Market Peripheral T-cell Lymphoma B-cell Non-Hodgkin s Lymphoma Non-Hodgkin s Lymphoma Cutaneous T-cell Lymphoma SOLID TUMORS Non-small Cell Lung Cancer Non-small Cell Lung Cancer Additional Indication RH1 Solid Tumors/NHL (Phase 2) (Phase 1/2) (Phase 1/2a) (Phase 1) (Phase 2b) (Phase 1) (Phase 2) (Phase 1) PROPEL: SPA approved, registration trial PDX + Gemcitabine PDX vs. Erlotinib ongoing planned -4-

5 PDX (pralatrexate): Unique Antifolate Small molecule inhibitor of dihydrofolate reductase (DHFR), a key enzyme in folate metabolism and well-validated oncology target Rationally designed for improved cancer cell uptake and retention Superior preclinical profile compared to other folate analogs targeting DHFR Clinical evidence of activity in T-cell malignancies and NSCLC SPA-approved pivotal Phase 2 trial on-going in patients with relapsed or refractory PTCL FDA Orphan Drug and Fast Track designation in patients with T- cell lymphoma Mechanistic rationale for development in other oncology indications based on broad use of folate antagonists -5-

6 PDX: Mechanism of Action Selectively Targets Folate Metabolism Methylene FH 4 FH 4 PDX (Glu n ) PDX dump FPGS DHFR Thymidylate Synthase FH 2 Folate dtmp DHFR Thymine PDX is: More potent than other DHFR inhibitors due to greater cell entry and retention Efficient permeant RFC-1 (transport) Effective substrate FPGS (polyglutamation) Primarily targets DHFR (pm affinity) Alimta, 5-FU, Tomudex target TS PDX RFC-1 Folate Cell membrane Differential Activity And Potential Mechanism of Action of PDX, MTX, and Alimta in Human Cancer Models In Vivo and in Vitro 2007 AACR-NCI-EORTC: -6-

7 Disease Overview: NHL & PTCL Non-Hodgkin s Lymphoma (NHL) Peripheral T-Cell Lymphoma (PTCL) Definition Cell Origin Common Subtypes Diverse group of cancers originating in lymphatic system B-cell (85-90%) T-cell (10-15%) Diffuse large B-cell, Follicular, Mantle, Burkitt Aggressive subgroup of NHL (10-15%) Mature T-cells (post-thymic) PTCL NOS (not otherwise specified) Angioimmunoblastic, Anaplastic large cell Grade Indolent or aggressive Aggressive Prognosis 1 st line treatment 2 nd + line treatment - Better if NHL is of B-cell origin - DLBCL (intermed. risk) 5 yr OS = 49% 1 CHOP + Rituxan - DLBCL (Aggressive): 2.9 yrs EFS 3 - Follicular (Indolent): 2.4 yrs median PFS 3 - Aggressive (+/-Rituxan) - ESHAP, ICE, DHAP (RR 30%-70%) -Indolent - Rituxan, Zevalin (RR 47%-80%) - Worse than aggressive B-cell NHL - PTCL 5 yr OS = 25% 2 No labeled product or regimen - CHOP: 50-70% 1 st line TRx response rate, high relapse, short duration 4 No labeled product or regimen No standard 2 nd line treatment PTCL is an aggressive NHL subgroup with poor clinical prognosis 1 Lossos et al., NEJM, 2004.; 2 Blood Jun 1;89(11): ; 3 - Rituxan package insert; 4 Angelopoulou, M. et al., HAEMA,

8 NHL Patient Population: T-Cell Subtypes Non-Hodgkin s Lymphoma 63,200 B-Cell Lymphoma 49,290 T-cell Lymphoma* 7,900 Precursor T-Cell 1,600 Peripheral T-Cell 6,300 T-Lymphoblastic Lymphoma Cutaneous TCL (Indolent) 1,000 Non-Cutaneous TCL (Aggressive) 5,000 Predominantly Leukemic 300 T-Acute Lymphoblastic leukemia Mycosis Fungoides/ Sezary Syndrome Peripheral TCL - Not otherwise specified Adult T-cell Leuk/ Lymphoma (HTLV+) Anaplastic Large Cell Lymphoma (cutaneous) Anaplastic Large Cell Lymphoma (systemic) NK T-cell Leukemia Transformed Mycosis Fungoides Angioimmunoblastic TCL T-Cell Prolymphocytic Leukemia** Arranon: 3rd line T-ALL and T-LBL NK/TCL Nasal T-cell granular Lymphocytic (indolent)** Ontak, Zolinza, Targretin: 2 nd line CTCL Subcutaneous paniculitis-like TCL PDX: 2 nd line Aggressive PTCL Hepatosplenic gamma-delta TCL Enteropathy type Intestinal TCL No approved agents or treatments for peripheral T- cell lymphoma Source: Aggressive Peripheral T-Cell Lymphomas Hematology 2005, Savage, K. *12.5% (10-15%) of NHL is T-cell ** Excluded from PROPEL -8-

9 PDX: Phase 1/2 PTCL Clinical Results 2007 AACR-NCI-EORTC Conference Summary Interim Phase 1/2 Results Favorable activity observed in heavily pre-treated PTCL patients 54% of evaluable patients (14 of 26) achieved response Duration of response typically exceeded that of prior line of chemotherapy Complete response (n=9) Partial response (n=5) 54% RR Mucositis mitigated by vitamins and correlated with MMA, Hcy levels and AUC of PDX exposure Other major toxicities were thrombocytopenia and leukopenia Recommended Phase 2 dose is 30 mg/m2 weekly x Did not achieve CR or PR (n=12) Evaluable T-cell Lymphoma Patients (N=26) Achieved durable responses in pre-treated PTCL patients Source: O Connor et al. AACR-NCI-EORTC 2007 Conference -9-

10 PROPEL: Pivotal Phase 2 Trial in PTCL Trial Design Target Population Single arm, open label, multi-center Adult patients with relapsed or refractory PTCL Number of Patients Treatment Primary Endpoint At least 100 evaluable patients 30 mg/m 2 of PDX weekly x 6 then 1 week rest 1 mg vitamin B 12 intramuscular every 8 10 weeks; 1 mg folic acid by mouth once a day Response Rate Secondary Endpoints Duration of response Progression-free survival Overall survival Trial Conducted Under FDA SPA; PDX Granted Fast Track Designation -10-

11 PROPEL: Pivotal Phase 2 Study in PTCL 65-Patient Interim Data Heavily pre-treated patients Median of 3 prior treatment regimens 29% response rate in first 65 evaluable patients as assessed by central independent review 45% response rate in first 65 evaluable patients as assessed by PROPEL investigators Median duration of response cannot be estimated due to current length of follow up Most common drug-related grade 3/4 adverse events: Mucositis 14% Thrombocytopenia 23% # Patient Responses (CR+PR) % Response Rate 19 Responders First 65 Evaluable Patients *A patient is considered evaluable if the patient received at least one dose of PDX and their diagnosis of PTCL has been confirmed by independent review. Source: Allos Press Release May 15,

12 PROPEL: Key Clinical & Regulatory Milestones Reached agreement under FDA s SPA process Jul 2006 Initiated patient enrollment Aug 2006 Received FDA s fast track designation Oct 2006 Positive outcome of 10-patient safety assessment Jan 2007 Positive outcome of 35-patient safety & response assessment Sep 2007 Positive outcome of 65-patient safety assessment Dec 2007 Completed patient enrollment Apr 2008 Reported 65-patient interim response data May 2008 Expected to report top line results YE 2008 File NDA as Expeditiously as Possible -12-

13 PDX: Expanded Lymphoma Development Phase 1/2a study: PDX + gemcitabine in NHL Phase 1 study: PDX in CTCL Study Design Single-arm, open-label, multi-center Study Design Single-arm, open-label, multi-center Target Population Adult patients with relapsed or refractory NHL or Hodgkin s disease Target Population Adult patients with relapsed or refractory CTCL Number of Patients Up to 54 patients in Phase 1 Up to 30 PTCL patients - Phase 2 Number of Patients Up to 56 patients Treatment PDX followed the next day by gemcitabine weekly x 2 or 3 with 1 week rest 1 mg vitamin B12 intramuscular every 8 10 weeks and 1 mg folic acid by mouth once a day Treatment PDX weekly x 2 or 3 with 1 week rest 1 mg vitamin B12 intramuscular every 8 10 weeks and 1 mg folic acid by mouth once a day Objectives Determine MTD Evaluate safety and tolerability Determine PK profile Assess preliminary efficacy in PTCL patients Objectives Determine optimal dose & schedule Evaluate safety and tolerability Interim Study Updates Expected by Year End -13-

14 PDX: Compelling Solid Tumor Opportunity Tumor type Under Development NSCLC: Stage IIIB/IV 2007 U.S. Incidence 98,950 Clinical and Commercial Rationale PDX activity in relapsed NSCLC comparable to approved agents: 11% RR w/o vitamins, TTP: 3 mos. High unmet medical need: 5-yr survival rate for Stage IIIB/IV approximately 15% Under Evaluation Head & Neck: Stage III/IV Breast: Stage III/IV Bladder: Stage III/IV 25,125 31,730 8,900 Demonstrated antifolate clinical activity; no investigational agent superior to MTX head-to-head High unmet medical need; MST for Stage III/IV approximately 6 mos. MTX well established in adjuvant setting Cytotoxics utilized up to 4 th 5 th lines of therapy 10-deaza-aminopterin demonstrated activity: 21% RR MTX actively used 1 st and 2 nd line No approved treatments/no SOC/unmet medical need Potential for expanded development of PDX in solid tumors Incidence source: Decision Resources

15 PDX: Prior Advanced NSCLC Clinical Results Phase 2 study of PDX in relapsed/refractory stage IIIB/IV NSCLC without vitamin supplementation; MTD 135 mg/m2 11% response rate 13.5 months median survival 3 months median time to progression Grade 3/4 stomatitis 21% of patients Subsequent Phase 1 study- PDX w/ vitamin supplementation; MTD 270 mg/m2 Data presented at AACR-NCI-EORTC 2007 Conference Previously treated Stage IIIB/IV NSCLC patients Clinically significant radiologic responses observed Recommended Phase 2 starting dose 190 mg/m2 Addition of vitamins to PDX treatment regimen enabled higher dosing, which may lead to greater therapeutic benefit Krug LM, Azzoli CG, Kris MG, et al. 10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer. Clin Cancer Res 2003;9(6):

16 PDX: Phase 2b Advanced NSCLC Study Study Design Randomized, multi-center study comparing PDX to Tarceva Target Population Stage IIIB/IV non-small cell lung cancer (NSCLC) who are, or have been, cigarette smokers who have failed treatment with at least one prior platinum-based chemotherapy regimen Number of Patients Treatment Primary Endpoint Secondary Endpoints A minimum of 160 evaluable patients PDX arm: mg/m 2 which may be increased to 230 mg/m 2 or reduced in 40 mg/m 2 decrements - IV push on days 1 and 15 of a 4-week/28 day cycle Tarceva arm: mg/day orally daily for a 4-week/28 day cycle Concurrent vitamin supplementation: - B12 (1mg intramuscular every 8-10 weeks) - Folic acid ( mg by mouth once a day) Overall survival Response rate Progression-free survival Safety and tolerability -16-

17 Product Development Pipeline PDX HEMATOLOGIC MALIGNANCIES Peripheral T-cell Lymphoma B-cell Non-Hodgkin s Lymphoma Non-Hodgkin s Lymphoma Cutaneous T-cell Lymphoma SOLID TUMORS Preclinical Phase 1 Phase 2 Phase 3 NDA Market (Phase 2) (Phase 1/2) (Phase 1/2a) (Phase 1) PROPEL: SPA approved, registration trial PDX + Gemcitabine RH1 Non-small Cell Lung Cancer Non-small Cell Lung Cancer Additional Indication Solid Tumors/NHL (Phase 2b) (Phase 1) (Phase 2) (Phase 1) PDX vs. Erlotinib ongoing planned -17-

18 RH1: Targeted Cytotoxic Prodrug Targeted cytotoxic prodrug bioactivated by enzyme DT-diaphorase (DTD) Over-expressed predominantly in lung, colon, liver and breast Cytotoxicity caused by DNA cross-linking Cancer Research UK completed Phase 1 dose escalation study in patients with solid tumors refractory to other chemotherapy regimens* Company sponsored Phase 1 dose escalation study in patients with advanced solid tumors and NHL initiated in November 2007 Determine maximum tolerated dose (MTD) Determine recommended Phase 2 dose Assess safety profile *Source Final results of a phase I clinical trial of the bioreductive drug RH1, S. Danson 2007 ASCO Annual Conference -18-

19 Commercial Considerations Exclusive worldwide commercial rights to PDX & RH1 for all indications Oncology market is attractive due to its: Size Unmet demand for safer and more effective treatments Relatively small physician population Potential for expedited regulatory review Moderate-sized oncology focused sales & marketing organization may effectively reach targeted physicians and medical institutions that treat the majority of patients with PTCL Potential for co-promotion or out-licensing to reach ex-us markets -19-

20 Financial Summary in millions and unaudited Cash at March 31, 2008 $ 50.5 Net cash used in operating activities for quarter ended 3/31/08 $ (9.3) Shares outstanding at May 1,

21 Key Achievements & Upcoming Milestones Positive outcome of PROPEL10-patient interim safety assessment EMEA Orphan Medicinal Product designation for PDX in PTCL Jan Apr Initiated Phase 2b study of PDX in NSCLC Jan Completed PROPEL patient enrollment Apr Reported PROPEL 65-patient interim data May Initiated Phase 1/2 study of PDX plus Gemcitabine in NHL May Expect to report CTCL interim data Jun Initiated Phase 1 study of PDX in CTCL Aug Expect to initiate Phase 2 study of PDX Q2 in additional solid tumor indication Positive outcome of PROPEL 35-patient response & safety assessment Sep Expect to initiate additional PDX studies YE Reported results from Phase 1 study of PDX in NSCLC Initiated Phase 1 study of RH1 in solid tumors/nhl Oct Nov Expect to report B-cell interim data YE Expect to report additional CTCL data YE Expect to report PROPEL top line results YE Positive outcome of PROPEL 65-patient interim safety assessment Dec -21-

22 Investor Presentation May 2008 NASDAQ: ALTH -22-

23 Management team Paul Berns President and CEO Dr. Pablo Cagnoni Chief Medical Officer James Caruso Chief Commercial Officer Marc Graboyes General Counsel Bruce Bennett Vice President, Manufacturing David Clark Vice President, Finance -23-