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Tarceva® (erlotinib) Tabletsin Combination with Gemcitabine as a 1st-line Treatment of Pancreatic Cancer

Presentation to theOncologic Drugs Advisory Committee

OSI Pharmaceuticals, Inc.

13 September 2005

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Introduction

Pablo J. Cagnoni, MD

Vice PresidentMedical Affairs & Translational Research

OSI Pharmaceuticals, Inc.

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Pancreatic Cancer Supplemental NDA

sNDA for pancreatic cancer indication was submitted29 April 2005

– Based on a 569 patient study that showed a statistically significant improvement in overall survival

Indication

– Tarceva, in combination with gemcitabine, for the1st-line treatment of patients with unresectable locally advanced, or metastatic pancreatic cancer

Dosage

– Tarceva: 100 mg PO once daily + gemcitabine(standard approved dose and schedule)

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Tarceva for Patients with Pancreatic Cancer Agenda

Introduction Pablo J. Cagnoni, MD

Background & PA.3Study Design Malcolm Moore, MD

Clinical Efficacy DataReview of Study PA.3 Gary M. Clark, PhD

Clinical Safety DataReview of Study PA.3 Karsten Witt, MD

Risk/Benefit Summary Mace Rothenberg, MD

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List of External Experts for Q & A

J. Randolph Hecht, MDClinical Professor of MedicineDirector, UCLA GI Oncology ProgramUniversity of CaliforniaLos Angeles School of Medicine

Wendy Parulekar, MDNCIC Clinical Trials GroupQueen’s University

Malcolm Moore, MDProfessor of Medicine and PharmacologyChair, NCIC Clinical Trials GroupGI CommitteePrincess Margaret HospitalUniversity of Toronto

Mace Rothenberg, MDProfessor of Medicine andDirector, Phase I Drug Development Vanderbilt Ingram Cancer Center

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OSI Pharmaceuticals Team for Q & A

Clinical Development– Pablo J. Cagnoni– Janna Christy-Bittel– Jennifer Culbertson– Karsten Witt

Biostatistics & Data Management– Gary M. Clark– Bret Wacker

Biopharmaceutics/Preclinical– Marta Hamilton– Ken Iwata– Frank Richardson

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Tarceva (erlotinib) Tablets

Orally available, small-molecule inhibitor of HER1/EGFR tyrosine kinase

Potent, selective EGFR-TK inhibitor (IC50 = 2 nM)

First clinical development candidate from OSI/Pfizer research collaboration in cancer

Collaboration with Genentech and Roche since January 2001

N

N

HN

O

O HCl

O

O

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Tarceva Regulatory History

Original NDA received full approval by FDA on18 November 2004

– Indication: monotherapy for the treatment of NSCLC after failure of at least 1 prior chemotherapy

– 731-patient study showed a statistically significant improvement in overall survival with Tarceva vs best supportive care

>18,000 patients have been treated since approval Over 100 clinical trials are currently ongoing

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Tarceva (n = 488)

Placebo (n = 243)

Single-Agent Tarceva in NSCLC Study BR.21—Overall Survival

† Two-sided log-rank test stratified by ECOG PS, number of prior regimens, prior platinum, best response to prior chemotherapy

HR = 0.7395% CI (0.61, 0.86)p-value < 0.001†

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Rationale for Targeting HER1/EGFRin Pancreatic Cancer

HER1/EGFR overexpression is common

Elevated HER1/EGFR and EGF are associated with more aggressive disease and poor patient prognosis

In preclinical models, HER1/EGFR inhibitors enhance gemcitabine-induced tumor apoptosis

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Objectives of Presentation

To review data supporting the need for new treatment options for patients with pancreatic cancer

To present evidence that Tarceva, when added to the current standard of care, gemcitabine, provides the first statistically significant and clinically meaningful increase in survival compared with gemcitabine alone

To demonstrate that the combination of Tarceva and gemcitabine offers an effective and tolerable new therapy for the management of pancreatic cancer