ASCO Oncology Roundtable June 3, 2007 ASCO 2007 Oncology Roundtable
Overview of PDL’s oncology pipeline – Update on volociximab development program – Summary of early stage programs focused on novel new targets Roundtable discussion/Q&A with PDL oncology experts Biogen Idec presence demonstrates commitment to volociximab collaboration A solid oncology team in place
Mark McCamish, MD, PhD Senior Vice President & Chief Medical Officer
Isagani (Gani) Chico, MD Therapeutic Area Head, Oncology
Lamia Mounedji-Boudiaf, MD Head, European Clinical Development
Vanitha Ramakrishnan, PhD Senior Director, Translational Research Focused mAb discovery efforts
Tracking to 1 new mAb IND per year in oncology or AID Created 4 oncology mAb candidates since April 2003 – Outlicensed 1 to Genentech in ’05 – Two currently in clinical development – 4th expected to file IND in late ‘07 Building our oncology franchise with PDL192 – Our newest novel humanized oncology mAb, targeting Q4’07 IND Creating a flow of oncology programs
PDL192 program 2007 IND candidate
DiscoveryDiscovery eefffortsforts toto createcreate averageaverage 11 INDIND perper yearyear
HuLuc63 – phase 1 In multiple myeloma
Volociximab – multiple phase 2 studies Volociximab: preclinical summary
Potent activity in preclinical models of angiogenesis Development of a surrogate antibody targeting murine α5β1 permits biological and therapeutic profiling: – Dissecting mechanisms of tumorigenesis vs angiogenesis – Dose, schedule, pharmacodynamic characterization – Comparisons, synergies and contrast with various combo therapies Application of findings to therapeutic development strategies: – Simultaneous demonstration of safety with dose ranging trials – Enabling studies for registration trials – Confirmation of proof-of-concept in early patient trials Strong translational research collaboration with Biogen-Idec A novel axis for angiogenesis inhibition
RTKs (e.g., PDGFR; VEGFR) α5β1 Integrin
VEGF Fibronectin
Avastin Volociximab
Sutent SHP-1 SHP-2 Shc PLCγ Grb2 PKA Sos FAK p53 PIP2 Nexavar Ras PI-3K Caspases Bcl-2 IP3 DAG Raf Bax Ca2+/NOS PKC MAPK AKT
VASOPERMEABILITYVASOPERMEABILITY PROLIFERATIONPROLIFERATION SURVIVALSURVIVAL APOPTOSISAPOPTOSIS Volociximab: a unique anti-angiogenic agent
50-50 partnership with Biogen Idec
Novel mAb that targets alpha5-beta1 integrin – a novel angiogenesis pathway Discovered and developed in-house Potential treatment for numerous solid tumor cancers Multiple P1 or P1/2 studies being explored Volociximab inhibits endothelial tube formation
Control Volociximab
Volociximab blocks endothelial tube formation in vitro (compared to control) This effect is independent of the growth factor stimulus α5β1 in Xenograft Models: Tools to dissect contributions
XenograftXenograft
Anti-angiogenic Anti-Tumor 339.1 M200 Mouse vasculature Human tumor
Volociximab will target both human vasculature and tumor Volociximab and surrogate (339.1) demonstrate combinational efficacy
LOX (melanoma)
800 Vehicle
) 339.1 3
m 600 M200 m 339.1 + M200 ( me
u 61%
l 400
o p = 0.03 v r
mo 200 u t
0 5 10 15 20 time (days) Volociximab: clinical program strategy
Our clinical development approach:
Preclinical studies help determine the best tumor types and path for clinical trials Phase 1 single agent studies and multiple combinations studies to evaluate safety in different tumor types Subsequent study designs driven by existing and emerging data Clinical strategy adapt to the competitive landscape and evolving standard of care Volociximab: current clinical program
Phase 1 single agent studies completed to explore safety and optimal dosing Ongoing Phase 1/2 studies in renal cell carcinoma, pancreatic cancer, and melanoma ASCO 2007 data for ongoing open-label P2 studies in renal cell carcinoma and pancreatic cancer: – Continued follow up from ongoing cohorts – Safety profile is reassuring – Data support further evaluation in combination Volociximab: clinical program plan
Next steps: Complete phase 2 single agent studies Phase 2 trials in 2nd line combination and 3rd line monotherapy ovarian cancer planned for H2’07 Phase 1/2 combination trials in NSCLC to start by year-end ’07 – P1/2: volociximab + paclitaxel/carboplatin – P1/2: volociximab + paclitaxel/carboplatin + bevacizumab – Other combinations for first and second-line being evaluated Other combination trials in RCC planned HuLuc63
A humanized monoclonal IgG1 antibody directed to CS1 (CD2-subset 1, CRACC, SLAMF7, CD319) CS1 – A cell surface glycoprotein uniformly and highly expressed on multiple myeloma cells and normal plasma cells – Expressed at lower levels on NK and CD8+ T cells – No expression on stem cells or in other normal tissues HuLuc63 eliminates or reduces xenograft tumors in MM mouse models in vivo Proposed MOA is NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) HuLuc63 exhibits dose-dependent anti-tumor activity towards MM xenografts in vivo
OPM2 model
Dosing Days Control Antibody 10mg/kg
Tumor Volumes HuLuc63 1mg/kg
HuLuc63 10mg/kg
Study Day HuLuc63: current clinical program
Phase 1 open-label, dose-finding trial underway – 0.5 to 20 mg/kg doses; traditional dose escalation design Additional combination dose ranging studies planned Pipeline driving future growth product TX area indication status*
Nuvion® autoimmune IV steroid-refractory UC (IVSR-UC) P3 daclizumab autoimmune Multiple sclerosis (MS) P2
Cardene® cardio Acute HTN in pediatrics (LCM) P2 ularitide cardio Acute heart failure (ADHF) P1 (US) volociximab oncology Solid tumors P2
HuLuc63 oncology Multiple myeloma (MM) P1
PDL192 oncology Solid tumors Pre-IND
* See www.pdl.com for more information. Key Takeaways from ASCO 2007
PDL has an emerging oncology pipeline focused on novel oncology antibodies Volociximab has potent anti-angiogenic and anti-tumor effects based on novel MOA and preclinical data Early clinical results support safety as single agent and in combination with chemotherapy Comprehensive clinical approach: – Three phase 2 open label trials ongoing: renal cell carcinoma & pancreatic data updates at ASCO – Combination trials being initiated to allow data driven guidance for pivotal trials – Additional studies in ovarian cancer and NSCLC planned for H2 07 Strong team in place in collaboration with Biogen Idec