Upload
vuliem
View
214
Download
1
Embed Size (px)
Citation preview
-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 1995. 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 forward-looking. 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.
-3-
Company HighlightsOncology-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
-4-
Product Development Pipeline
Preclinical Phase 1 Phase 2 Phase 3 NDA MarketPDX
Peripheral T-cell Lymphoma
Additional Indication
Non-Hodgkin’s Lymphoma
B-cell Non-Hodgkin’s Lymphoma
PDX + Gemcitabine
Cutaneous T-cell Lymphoma
RH1
ongoing planned
Non-small Cell Lung Cancer
HEMATOLOGIC MALIGNANCIES
SOLID TUMORS
PROPEL: SPA approved, registration trial
Solid Tumors/NHL
(Phase 2)
(Phase 1/2)
(Phase 1/2a)
(Phase 1)
(Phase 2b)
(Phase 2)
(Phase 1)
PDX vs. Erlotinib
Non-small Cell Lung Cancer(Phase 1)
-5-
PDX (pralatrexate): Unique AntifolateSmall 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
-6-
PDX: Mechanism of ActionSelectively Targets Folate Metabolism
FolateRFC-1
Folate
FH2FH4
DHFR
Methylene FH4
dUMP dTMP
ThymineThymidylate Synthase
DHFR
PDX
PDX
FPGS
PDX (Glun)
PDX is:
More potent than other DHFRinhibitors 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
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:
-7-
Disease Overview: NHL & PTCL
PTCL is an aggressive NHL subgroup with poor clinical prognosis
Peripheral T-Cell Lymphoma (PTCL)Non-Hodgkin’s Lymphoma (NHL)
2nd + line treatment
1st line treatment
Prognosis
Grade
Common Subtypes
Cell Origin
Definition
No labeled product or regimenNo standard 2nd line treatment
- Aggressive (+/-Rituxan)- ESHAP, ICE, DHAP (RR 30%-70%)
-Indolent- Rituxan, Zevalin (RR 47%-80%)
No labeled product or regimen- CHOP: 50-70% 1st line TRx response
rate, high relapse, short duration 4
CHOP + Rituxan- DLBCL (Aggressive): 2.9 yrs EFS3
- Follicular (Indolent): 2.4 yrs median PFS 3
- Worse than aggressive B-cell NHL - PTCL 5 yr OS = 25%2
- Better if NHL is of B-cell origin- DLBCL (intermed. risk) 5 yr OS = 49%1
AggressiveIndolent or aggressive
PTCL NOS (not otherwise specified) Angioimmunoblastic, Anaplastic large cell
Diffuse large B-cell, Follicular, Mantle, Burkitt
Mature T-cells (post-thymic)B-cell (85 - 90%) T-cell (10 -15%)
Aggressive subgroup of NHL (10 -15%)Diverse group of cancers originating in lymphatic system
1 Lossos et al., NEJM, 2004.; 2 Blood. 1997 Jun 1;89(11):3909-18; 3- Rituxan package insert; 4 Angelopoulou, M. et al., HAEMA, 2004
-8-
Non-Hodgkin’s Lymphoma63,200
Precursor T-Cell1,600
Peripheral T-Cell6,300
Cutaneous TCL (Indolent)
1,000
Non-Cutaneous TCL(Aggressive)
5,000
T-Acute Lymphoblasticleukemia
T-Lymphoblastic Lymphoma
Peripheral TCL - Not otherwise specified
Anaplastic Large Cell Lymphoma (cutaneous)
Angioimmunoblastic TCL
NK/TCL Nasal
Mycosis Fungoides/Sezary Syndrome
Adult T-cell Leuk/Lymphoma (HTLV+)
T-cell granular Lymphocytic (indolent)**
Predominantly Leukemic300
Subcutaneous paniculitis-like TCL
Enteropathy typeIntestinal TCL
Hepatosplenic gamma-delta TCL
Anaplastic Large Cell Lymphoma (systemic) NK T-cell Leukemia
T-Cell Prolymphocytic Leukemia**
T-cell Lymphoma*7,900
B-Cell Lymphoma49,290
Transformed Mycosis Fungoides
Arranon: 3rd line T-ALL and T-LBL
Ontak, Zolinza, Targretin: 2nd line CTCL
PDX: 2nd line Aggressive PTCL
Source: “Aggressive Peripheral T-Cell Lymphomas” Hematology 2005, Savage, K. *12.5% (10 -15%) of NHL is T-cell ** Excluded from PROPEL
NHL Patient Population: T-Cell Subtypes
No approved agents or treatments for peripheral T- cell lymphoma
-9-
0
5
10
15
20
25
30
Evaluable T-cell Lymphoma Patients
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
• 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 6
Source: O’Connor et al. AACR-NCI-EORTC 2007 Conference
Did not achieve
CR or PR(n=12)
Complete response
(n=9)
Partial response
(n=5)
(N=26)
54% RR
Achieved durable responses in pre-treated PTCL patients
-10-
Duration of responseProgression-free survivalOverall survival
Secondary Endpoints
Response RatePrimary Endpoint
30 mg/m2 of PDX weekly x 6 then 1 week rest1 mg vitamin B12 intramuscular every 8 – 10 weeks; 1 mg folic acid by mouth once a day
Treatment
At least 100 evaluable patientsNumber of Patients
Adult patients with relapsed or refractory PTCLTarget Population
Single arm, open label, multi-centerTrial Design
PROPEL: Pivotal Phase 2 Trial in PTCL
Trial Conducted Under FDA SPA; PDX Granted Fast Track Designation
-11-
02468
101214161820
PROPEL: Pivotal Phase 2 Study in PTCL65-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%
Source: Allos Press Release – May 15, 2008
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.
19
Responders
29% Response Rate
# P
atie
nt R
espo
nses
(CR
+PR
)
-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
-13-
PDX: Expanded Lymphoma Development
Determine MTDEvaluate safety and tolerabilityDetermine PK profileAssess preliminary efficacy in PTCL patients
Objectives
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
Up to 54 patients in Phase 1Up to 30 PTCL patients - Phase 2
Number of Patients
Adult patients with relapsed or refractory NHL or Hodgkin’s disease
Target Population
Single-arm, open-label, multi-centerStudy Design
Determine optimal dose & scheduleEvaluate safety and tolerability
Objectives
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
Treatment
Up to 56 patientsNumber of Patients
Adult patients with relapsed or refractory CTCL
Target Population
Single-arm, open-label, multi-centerStudy Design
Phase 1/2a study: PDX + gemcitabine in NHL Phase 1 study: PDX in CTCL
Interim Study Updates Expected by Year End
-14-
PDX: Compelling Solid Tumor Opportunity
Under Evaluation
Under Development
Demonstrated antifolate clinical activity; no investigational agent superior to MTX head-to-headHigh unmet medical need; MST for Stage III/IV approximately 6 mos.
25,125Head & Neck: Stage III/IV
10-deaza-aminopterin demonstrated activity: 21% RRMTX actively used 1st and 2nd lineNo approved treatments/no SOC/unmet medical need
8,900Bladder: Stage III/IV
MTX well established in adjuvant settingCytotoxics utilized up to 4th – 5th lines of therapy
31,730Breast: Stage III/IV
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%
98,950NSCLC: Stage IIIB/IV
Clinical and Commercial Rationale2007 U.S. Incidence
Tumor type
Incidence source: Decision Resources 2006
Potential for expanded development of PDX in solid tumors
-15-
PDX: Prior Advanced NSCLC Clinical Results
Addition of vitamins to PDX treatment regimen enabled higher dosing, which may lead to greater therapeutic benefit
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
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):2072-8.
-16-
PDX: Phase 2b Advanced NSCLC Study
Response rateProgression-free survivalSafety and tolerability
Secondary Endpoints
Overall survivalPrimary Endpoint
PDX arm: - 190 mg/m2 which may be increased to 230 mg/m2 or reduced in 40 mg/m2 decrements- IV push on days 1 and 15 of a 4-week/28 day cycleTarceva arm: - 150 mg/day orally daily for a 4-week/28 day cycleConcurrent vitamin supplementation: - B12 (1mg intramuscular every 8-10 weeks)- Folic acid (1 – 1.25 mg by mouth once a day)
Treatment
A minimum of 160 evaluable patientsNumber of Patients
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
Target Population
Randomized, multi-center study comparing PDX to TarcevaStudy Design
-17-
Product Development Pipeline
Preclinical Phase 1 Phase 2 Phase 3 NDA MarketPDX
Peripheral T-cell Lymphoma
Additional Indication
Non-Hodgkin’s Lymphoma
B-cell Non-Hodgkin’s Lymphoma
PDX + Gemcitabine
Cutaneous T-cell Lymphoma
RH1
ongoing planned
Non-small Cell Lung Cancer
HEMATOLOGIC MALIGNANCIES
SOLID TUMORS
PROPEL: SPA approved, registration trial
Solid Tumors/NHL
(Phase 2)
(Phase 1/2)
(Phase 1/2a)
(Phase 1)
(Phase 2b)
(Phase 2)
(Phase 1)
PDX vs. Erlotinib
Non-small Cell Lung Cancer(Phase 1)
-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 withadvanced solid tumors and NHL initiated in November 2007
Determine maximum tolerated dose (MTD)Determine recommended Phase 2 doseAssess safety profile
*Source – “Final results of a phase I clinical trial of the bioreductive drug RH1”, S. Danson – 2007 ASCO Annual Conference
-19-
Commercial Considerations
Exclusive worldwide commercial rights to PDX & RH1 for all indications
Oncology market is attractive due to its:SizeUnmet demand for safer and more effective treatmentsRelatively small physician populationPotential 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
-20-
Financial Summaryin 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, 2008 68.1
-21-
Key Achievements & Upcoming Milestones
2008Initiated Phase 2b study of PDX in NSCLC Jan
Completed PROPEL patient enrollment Apr
Reported PROPEL 65-patient interim data May
Expect to report CTCL interim data Jun
Expect to initiate Phase 2 study of PDX Q2 in additional solid tumor indication
Expect to initiate additional PDX studies YE
Expect to report B-cell interim data YE
Expect to report additional CTCL data YE
Expect to report PROPEL top line results YE
2007Positive outcome of PROPEL10-patient interim safety assessment Jan
EMEA Orphan Medicinal Product designation for PDX in PTCL Apr
Initiated Phase 1/2 study of PDX plus Gemcitabine in NHL May
Initiated Phase 1 study of PDX in CTCL Aug
Positive outcome of PROPEL 35-patient response & safety assessment Sep
Reported results from Phase 1 study of PDX in NSCLC Oct
Initiated Phase 1 study of RH1 in solid tumors/NHL Nov
Positive outcome of PROPEL 65-patient interim safety assessment Dec