JP Morgan Healthcare Conference. January 8, 2007

Transcription

1 JP Morgan Healthcare Conference January 8, 2007

2 Safe Harbor Statement Except for the historical information set forth herein, the matters set forth in this presentation,including without limitation statements regarding our anticipated future success in drug discovery and development, growing product pipeline and strategy, strong cash position, plans and expected timelines for advancing our drug candidates through preclinical and clinical trials, potential therapeutic and commercial value, including attributes and indications of our drug candidates, the anticipated cash burn, intentions to commercialize drug candidates ourselves and intentions to enter into a strategic partnership, contain predictions, estimates and other forward-looking statements. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the risk that results of clinical trials may be unsuccessful or insufficient to meet applicable regulatory standards, the high degree of risk associated with drug development, the ability to enroll sufficient numbers of subjects in its clinical trials, the impact of competition and technological advances, the results of further scientific research, unanticipated delays, the ability of Incyte to compete against parties with greater financial or other resources, greater than expected expenses, economic factors, unanticipated or unpredictable expenses relating to litigation or strategic activities, our ability to obtain additional capital when needed, risks related to product candidates that are in-licensed, risks related to obtaining effective patent coverages for our products and other risks detailed from time to time in Incyte s reports filed with the Securities and Exchange Commission, including our Quarterly Report on Form 10-Q for the quarter ended September 30, 2006 and our filings with the SEC. Incyte disclaims any intent or obligation to update these forward-looking statements.

3 Incyte s Pipeline

4 CCR5 Antagonists: An Emerging New Class of Drugs to Treat HIV HIV enters T-cells by binding to CD4 and one of two obligate co-receptors: CCR5 or CXCR4 CCR5 antagonists block entry of HIV that bind to CCR5 (R5 tropic virus) but do not block entry of HIV that binds to CXCR4 (X4 tropic virus) About 85% of patients starting HIV therapy harbor HIV virus that only binds to CCR5 About 60% of highly treatment-experienced patients have R5 virus CCR5 antagonists may provide: Substantial benefit in patients with CCR5 (R5) tropic virus Immunologic benefit in all subjects based on increasing CD4 cell counts Less risk of developing drug resistance

5 Potential Profile of INCB9471 Better pharmacokinetic profile to allow for once daily use without ritonavir Use in first and second line regimens where most patients have only detectable R5 virus Avoidance of peak driven toxicities while maintaining very high anti-viral activity throughout the dosing interval Potential for better outcomes in treatment-experienced patients on ritonavir

6 INCB9471: Potential to be Preferred CCR5 Antagonist for Early Use Compound/Dose Cmax (nm) Cmin (nm) Peak/trough ratio Half-Life Maraviroc 300 mg once daily* hr Maraviroc 300 mg twice daily* INCB mg once daily hr hr Early use defined as first or second regimen, without ritonavir Maraviroc no longer being developed as a once daily regimen without ritonavir * company reports

7 Pharmacokinetic Comparison of INCB9471 and Maraviroc Concentration (nm) maraviroc 300 mg QD maraviroc 300 mg BID INCB mg QD Maraviroc concentrations simulated based on reported PK parameters Time (h)

8 INCB9471: Clinical Status Phase I Studies in Healthy Volunteers Completed Single doses of INCB9471 up to 300 mg Multiple doses up to 200 mg once daily for 10 days of dosing Phase I Safety Summary Very well tolerated No dose limiting toxicity identified Phase IIa Study Ongoing Treatment-naïve or treatment-experienced - not currently on HAART therapy R5 tropic HIV, naïve to CCR5 antagonists Viral load > 10,000 copies/ml Current cohort mg once daily for 14 days or placebo

9 INCB9471: Positive Top-Line Efficacy Data 200 mg INCB9471 given once daily for 14 days Change in Viral Load from Baseline Dosing Time in Days -1.7 logs -2.1 logs Placebo N=3 Actives N=7

10 INCB 9471: Potential to be Best in Class CCR5 Antagonist First once-daily CCR5 antagonist without ritonavir Impressive and sustained antiviral effect as once-daily monotherapy Provide forgiveness for noncompliance Potential for improved outcomes in treatment-experienced patients on ritonavir Excellent emerging safety profile

11 INCB9471: 2007 Clinical Plans Complete Phase IIa trial 1H/2007 Additional dosing cohorts Full data to be presented at a scientific meeting this year Complete required drug interaction studies mid-2007 Initiate Phase IIb clinical studies 2H/2007

12 11βHSD1 Inhibitors An emerging new class of drugs to treat type 2 diabetes and related cardiovascular risk factors

13 11βHSD1 Activity Underlies Adipose Tissue Dysfunction and Promotes Metabolic Disease Hypertension Angiotensinogen Adipose PAI-I TNFα Pro-thrombotic, Pro-inflammatory States Liver Free Fatty Acids Cortisol 11βHSD1 Free Fatty Acids Adiponectin Muscle Glucose production (Hyperglycemia) Lipid production (Dyslipidemia) Intracellular Cortisone Cortisol Glucose uptake (Hyperglycemia)

14 11βHSD1 Activity in Adipose Tissue Drives Metabolic Disease and CV Risk in Rodents Glucose Intolerance Metabolic Disease Blood Glucose (mg/dl) 3x 11βHSD1 Normal 11βHSD1 Time (min) Insulin resistance Hyperglycemia Triglycerides Body weight Visceral fat mass Blood pressure Elevated 11βHSD1 activity in mouse adipose tissue is sufficient to drive the complete T2D/Metabolic syndrome phenotype Equivalent hyper-activity of human 11βHSD1 is observed in obesity/t2d Basu et al. Diabetes 2004; Lindsay et al. JCEM 2003; Masuzaki et al. Science 2001; Masuzaki et al. JCI 2003

15 INCB13739: Clinical Update First in human study initiated June 2006 Single-dose-escalation phase completed Multiple-dose-escalation phase nearing completion Phase IIa adipose and liver pharmacodynamic activity study in obese/insulin resistant subjects ongoing

16 INCB13739 Completely Inhibits Human Adipose Tissue 11βHSD1 Activity After a Single Oral Dose Relative 11 βhsd1 Activity hr 4 hr 24 hr 0 hr 4 hr 24 hr Placebo (n=4) INCB13739 (n=6)

17 INCB13739 Completely Inhibits Human Liver 11βHSD1 Activity After a Single Oral Dose Placebo Cortisol (ug/dl) n=4 INCB Time (hours) n=6

18 INCB13739: Clinical Development Plans Two-step insulin clamp study to be initiated in 1Q day study in Type 2 Diabetics Primary endpoints: hepatic glucose production and peripheral glucose uptake Three-month efficacy study in Type 2 diabetics to follow

19 Incyte s JAK Inhibitor Programs JAK (janus- associated kinases) enzymes mediate intracellular signals downstream of cytokines and growth factor receptors JAK-STAT pathways are clinically validated in both inflammatory and myeloproliferative diseases Incyte has discovered multiple classes of potent, selective, oral JAK inhibitors Several molecules expected to enter clinical trials beginning in 1Q/2007

20 JAK Signaling Pro-Inflammatory Factors Cell Proliferation Anti-Apoptosis

21 JAK Signaling P P Pro-Inflammatory Factors Cell Proliferation Anti-Apoptosis

22 JAK Signaling P P P P Pro-Inflammatory Factors Cell Proliferation Anti-Apoptosis

23 JAK2: Target For Inflammation Pfizer s moderately selective JAK3 inhibitor has demonstrated efficacy in RA and psoriasis at doses that should inhibit JAK2 Monoclonal antibodies that inhibit signaling through JAK2, but not JAK3, pathways are clinically effective in RA and psoriasis: IL-6R (Actemra) IL-12/IL23 (CNTO 1275) Inhibition of JAK3 is immunosuppressive JAK3 is predominantly involved in signaling that results in T-cell activation Clinical data suggests that T-cell directed immunosuppressive therapies are only modestly effective in RA Incyte compounds are 10 to 40-fold selective for JAK2 over JAK3

24 Clinical Data Validates JAK Pathway in Rheumatoid Arthritis Actemra (Anti-IL-6R) Weeks 4 mg/kg 8 mg/kg Placebo Nov., 06 at ACR % ACR20 Responses

25 Superior Clinical Efficacy in RA of a JAK Inhibitor vs. Anti-TNF Biologic, Humira CP (6 wk RA Results) Humira (6 wk RA Results) 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Placebo 5 mg bid 15 mg bid ACR 20 ACR 50 ACR 70 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Placebo 20 mg 40 mg 80 mg ACR20 ACR50 ACR70 Nov., 06 at ACR

26 Clinical Data Validates JAK Pathway in Psoriasis CP (2 wk Psoriasis Trial) Treatment Mean PASI Improvement Placebo 12% 5 mg bid 28% 10 mg bid 47% 20 mg bid 53% 30 mg bid 52%

27 Incyte s JAK2 Inhibitors Are Effective in Preclinical Models of Arthritis Rat Adjuvant Induced Arthritis Model Vehicle JAK2 Inhibitor Disease Score TREATMENT PERIOD (14 days)

28 JAK2 Inhibitors for Myeloproliferative Diseases A single amino acid mutation (V617F) in JAK2 was recently identified in MPDs: Polycythemia vera (>90%) Essential Thrombocythemia (50%) Myeloid Metaplasia (50%)

29 Clinical Results with VX-680 in MPD Supports Therapeutic Value of JAK2 Inhibition VX-680, the Merck/Vertex kinase inhibitor, which possesses activity against JAK-2, was tested in patients with MPD 6 of 8 evaluable patients had an objective response A patient with hepatosplenomegaly had complete resolution of hepatomegaly and 50% reduction in splenomegaly after a single 5 day I.V. infusion The authors concluded that the clinical benefit resulted from JAK2 inhibition VX-680 Must be administered intravenously ~300x less potent against JAK2 than Incyte s oral JAK2 inhibitors

30 Incyte JAK2 Inhibitors Block Growth of Cells Expressing V617F Mutant JAK2 Inhibition of V617F JAK2 Phosphorylation by JAK2 Inhibitor + CTRL JAK2 Inhibitor VEHICLE pjak2 Inhibition of V617F JAK2-Driven Cell Proliferation by JAK2 Inhibitor 100 % of Control JAK2 Inhibitor

31 Incyte JAK2 Inhibitors Suppress Clinical Manifestations of MPD in Mice Vehicle JAK2 Inhibitor Normal spleens Spleens from mice inoculated with V617F mutant JAK2 cells

32 Incyte s JAK2 Inhibitor Program Multiple potent, selective, orally bioavailable candidates currently in preclinical development >100x selectivity against a broad panel of kinases 10 40x selective over JAK3 enzyme GLP-safety studies successfully completed Multiple IND applications expected to be filed in 2007 Clinical studies in inflammatory diseases and hematological cancers planned in 2007

33 Third Quarter 2006 Key Financial Metrics Cash, Marketable Securities (Pro Forma) $ 352M Long-term Debt (Pro Forma) 3-1/2 % Convertible Sr. Notes (2011) $ 152M 3-1/2% Convertible Subordinated Notes (2011) $ 250M 0% Convertible Subordinated Note (2013) $ 10M 2006 Total Cash Use Guidance $85-90M

34 Incyte s Pipeline

35 Thank you