Phase 1 Data from ECHO-202. ESMO 2016, Copenhagen October 7 th, 2016

Transcription

1 Phase 1 Data from ECHO-202 ESMO 2016, Copenhagen October 7 th, 2016

2 Speakers Hervé Hoppenot Chief Executive Officer Steven Stein Chief Medical Officer Reid Huber Chief Scientific Officer 2

3 Forward-looking Statements Except for the historical information set forth herein, the matters set forth in this presentation contain predictions, estimates and other forward-looking statements, including without limitation statements regarding: plans and expectations regarding the Company s product pipeline and strategy - including timelines for advancing its drug candidates through clinical trials (including enrollment and commencement), timelines for regulatory submissions and timelines for releasing trial data, and whether any specific program will be successful or be best in class - including, without limitation, with respect to its IDO1 inhibitor (epacadostat) program; anticipated future investments and accomplishments in drug discovery and development; and the potential therapeutic and commercial value of our drug candidates. These forward-looking statements are based on the Company s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: the efficacy or safety of Jakafi; the acceptance of Jakafi in the marketplace; market competition; further research and development; sales, marketing and distribution requirements; clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; integrating the planned acquisition of ARIAD s European operations; other market, economic or strategic factors and technological advances; unanticipated delays; the ability of the Company to compete against parties with greater financial or other resources; the Company's dependence on its relationships with its collaboration partners; greater than expected expenses, including with regard to litigation or strategic activities; our ability to obtain additional capital when needed; obtaining and maintaining effective patent coverage for the Company s products; and other risks detailed from time to time in the Company s reports filed with the Securities and Exchange Commission, including its Form 10-Q for the period ended June 30, The Company disclaims any intent or obligation to update these forward-looking statements. 3

4 Incyte is Building a World-Class Biopharmaceutical Organization Global RA market 1 Jakafi Growth Baricitinib Opportunity Expanding Commercial Footprint 1. IMS data 2015; RA = rheumatoid arthritis 4

5 A Balanced and Diversified Development Portfolio of Large and Small Molecules 1. Jakafi marketed by Incyte in the US; ruxolitinib licensed to Novartis ex-us 2. Patients with intermediate or high-risk myelofibrosis; Patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea 3. European rights to Iclusig licensed from ARIAD 4. Registration program expected to begin in H Co-development with Agenus 6. Worldwide rights to baricitinib licensed to Lilly, SLE = Systemic lupus erythematosus 7. Worldwide rights to capmatinib licensed to Novartis, GBM = Glioblastoma multiforme 5

6 Incyte has an Extensive Drug Discovery and Development Portfolio in Immuno-Oncology Discovery and Development Clinical Combinations Pivotal Small Molecules Large Molecules 1 Epacadostat (IDO1) INCB39110 (JAK1) INCB50465 (PI3Kδ) INCSHR1210 (PD-1) INCAGN1876 (GITR) INCAGN1949 (OX40) 2 IDO1 + PD-1 PD-L1 JAK1 Vaccines JAK1 + PD-1 PI3Kδ PI3Kδ + PD-1 Phase 3 study evaluating treatment-naive patients with advanced melanoma Epacadostat + pembrolizumab 600 patients Pembrolizumab Dual-Primary Endpoints: Progression-free survival Overall survival 1. Includes alliance with Agenus and license and collaboration agreement with Hengrui 2. Clinical program expected to be initiated in the fourth quarter of

7 Initial Presentation of the Melanoma Patients within the Phase 1 Data from ECHO-202 was at SITC and SMR ,2 SITC / SMR 2015 ESMO 2016 Percent Change From Baseline in Target Lesions; treatment-naïve melanoma (n=16) Percent Change From Baseline in Target Lesions; treatment-naïve melanoma (n=19) 1. Gangadhar et al, Society for Immunotherapy of Cancer (SITC) Hamid et al, Society for Melanoma Research (SMR)

8 Epacadostat Plus Pembrolizumab in Patients With Advanced Melanoma and Select Solid Tumors: Updated Phase 1 Results From ECHO-202/KEYNOTE-037 T. C. Gangadhar, 1 O. Hamid, 2 D. C. Smith, 3 T. M. Bauer, 4 J. S. Wasser, 5 A. J. Olszanski, 6 J. J. Luke, 7 A. S. Balmanoukian, 2 D. R. Kaufman, 8 Y. Zhao, 9 J. Maleski, 9 M. J. Jones, 9 L. Leopold, 9 T. F. Gajewski 7 1 Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2 The Angeles Clinic and Research Institute, Los Angeles, CA, USA; 3 University of Michigan, Ann Arbor, MI, USA; 4 Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA; 5 University of Connecticut Health Center, Farmington, CT, USA; 6 Fox Chase Cancer Center, Philadelphia, PA, USA; 7 University of Chicago, Chicago, IL, USA; 8 Merck & Co., Inc., Kenilworth, NJ, USA; 9 Incyte Corporation, Wilmington, DE, USA

9 Patients, Study Design, and Treatment ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; CRC, colorectal cancer; DLBCL, diffuse large B-cell lymphoma; EA, endometrial adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; IV, intravenous; MSI, microsatellite instability; MTD, maximum tolerated dose; NSCLC, non small cell lung cancer; Q3W, every 3 weeks; RCC, renal cell carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; SCCHN, squamous cell carcinoma of head and neck; TCC, transitional cell carcinoma of the genitourinary tract; TNBC, triple-negative breast cancer; ULN, upper limit of normal. * Includes: melanoma, NSCLC, RCC, EA, TCC, TNBC, and SCCHN. 1. Eisenhauer EA, et al. Eur J Cancer. 2009;45(2):

10 Patient Characteristics Phase 1 has completed patient enrollment with a total of 62 patients receiving epacadostat Doses of 25 mg BID (n=4), 50 mg BID (n=20), 100 mg BID (n=18), and 300 mg BID (n=20) Variable Total (n=62) Variable Total (n=62) Biomarker evaluation for the expression of PD-L1 Men, n (%) 35 (56) Race, n (%) White 56 (90) Black/A-A 3 (5) Asian 2 (3) NH/PI 1 (2) ECOG PS, n (%) 0 35 (56) 1 27 (44) Tumor type, n (%) Melanoma 22 (35) NSCLC 12 (19) RCC 11 (18) EA 7 (11) TCC 5 (8) TNBC 3 (5) SCCHN 2 (3) Median age, y (range) 59 (30 88) PD-L1 IHC 22C3 pharmdx Kit; cutoffs for positivity at baseline Melanoma or RCC, 1% staining on tumor cells and immuneinfiltrating cells NSCLC, 50% staining on tumor cells A-A, African American; BID, twice daily; EA, endometrial adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; NH, Native Hawaiian; NSCLC, non small cell lung cancer; PI, Pacific Islander; RCC, renal cell carcinoma; SCCHN, head and neck squamous cell carcinoma; TCC, transitional cell carcinoma of the genitourinary tract; TNBC, triple-negative breast cancer 10

11 Phase 1: Treatment-Related AEs 5 patients (8%) experienced treatment-related AEs that led to discontinuation - Including grade 3 arthralgia, grade 3 AST increased/grade 2 ALT increased, grade 3 lipase increased, grade 3 aseptic meningitis, and grade 2 nervous system disorder There were no treatment-related deaths MTD of epacadostat was not reached Treatment-Related AEs,* n (%) All Grades (n=62) Grade 3/4 (n=62) Treatment-Related AEs, n (%) (cont d) All Grades (n=62) Grade 3/4 (n=62) Total 50 (81) 12 (19) Fatigue 18 (29) 0 (0) Rash 18 (29) 5 (8) Pruritus 14 (23) 0 (0) Arthralgia 12 (19) 1 (2) Diarrhea 11 (18) 0 (0) Nausea 10 (16) 1 (2) Pyrexia 7 (11) 0 (0) Vomiting 7 (11) 1 (2) AST increased 5 (8) 1 (2) Chills 5 (8) 0 (0) Dizziness 5 (8) 0 (0) Myalgia 5 (8) 0 (0) Constipation 4 (6) 0 (0) Headache 4 (6) 1 (2) Lipase increased 3 (5) 3 (5) Amylase increased 2 (3) 2 (3) Anxiety 2 (3) 1 (2) Mucosal inflammation 2 (3) 1 (2) Meningitis aseptic 1 (2) 1 (2) AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities. * All-grade AEs 5% or grade 3/4 AEs in 1 patient in total phase 1 population. Rash includes the following MedDRA preferred terms: rash, rash erythematous, rash generalized, rash maculo-papular, rash pruritic, and rash follicular. Pruritus includes the following MedDRA preferred terms: pruritus and pruritus generalized. 11

12 Phase 1 Melanoma: Best Overall Response Of the 19 treatment-naive patients, 11 (58%) achieved a CR or PR by RECIST All responses are confirmed and ongoing (median follow-up for responders [range], 56+ [46 to 90+] weeks) Responses were observed in all sites of target lesions, including liver, lung, and lymph nodes, and regardless of PD- L1 status Based on irrecist, 12/19 (63%) treatment-naive patients achieved a CR or PR 5 of 6 patients treated with epacadostat doses 100 mg BID were responders Patients, n (%) Treatment-Naive Melanoma (n=19) ORR (CR + PR) 11 (58) CR 5 (26) PR 6 (32) SD 3 (16) DCR (CR + PR + SD) 14 (74) PD 5 (26) Of the 3 patients who were previously treated for advanced melanoma, 1 patient each had a CR, SD, and PD by RECIST and irrecist BID, twice daily; CR, complete response; DCR, disease control rate; irrecist, immune-related RECIST; ORR, objective response rate; PD, progressive disease; PD-L1, programmed-death ligand 1; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. 12

13 Phase 1 Treatment-Naive Melanoma: Best Percentage Change From Baseline in Target Lesions Best Overall Response by RECIST: ORR=11/19 (58%); DCR=14/19 (74%) Best Overall Response by irrecist: ORR=12/19 (63%); DCR=15/19 (79%) BID, twice daily; CR, complete response; DCR, disease control rate; irrecist, immune-related RECIST; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. Horizontal dotted lines indicate the thresholds for PD and response according to RECIST (version 1.1) criteria. Of the 19 evaluable patients, data are shown for the 18 patients with postbaseline scans that included assessment of target lesions. One patient discontinued treatment for PD per new lesions (target lesions not assessed) and is not included in this figure. * Objective response is PD (SD for target lesions; PD per new lesions). No change from baseline. Objective response is PD (CR for target lesions; PD per new lesions). Objective response is PR (CR for target lesions; nontarget lesions still present). 13

14 Phase 1 Treatment-Naive Melanoma: Percentage Change From Baseline in Target Lesions AE, adverse event; BID, twice daily; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease. The blue shaded area represents a 100% change from baseline. The patients who reached a 100% reduction from baseline have been vertically offset to aid visibility. Of the 19 evaluable patients, data are shown for the 18 patients with postbaseline scans that included assessment of target lesions. 1 patient discontinued treatment for PD because of new lesions (target lesions not assessed) and is not shown in this figure. 1 patient with SD discontinued treatment for AE (arthralgia) but has not received other therapy and is being followed off study treatment. The 3 patients with response who discontinued treatment maintained their responses. Patient with PR discontinued study treatment for AE (lipase increased) and is being followed off study treatment. Patient receives pembrolizumab and has maintained PR. 2 patients with CR discontinued study treatment for CR (allowed per protocol) and are being followed on study. Patients have maintained CR. 14

15 Phase 1 Treatment-Naive Melanoma: Duration of Response AE, adverse event; BID, twice daily; CR, complete response; PR, partial response. * Patient discontinued study treatment for CR and is being followed on study. Patient has maintained CR. Patient discontinued study treatment for AE (lipase increased) and is being followed off study treatment. Patient receives pembrolizumab and has maintained PR. 15

16 Phase 1 Treatment-Naive Melanoma: Progression-Free Survival (PFS) RECIST, Response Evaluation Criteria in Solid Tumors. 16

17 Phase 1 Treatment-Naive Melanoma: Progression-Free Survival (PFS) Median PFS not yet reached Comparator median PFS (per FDA-approved package inserts, melanoma) 1 Nivolumab + ipilimumab 11.5 months (CheckMate-067) Nivolumab 6.9 months (CheckMate-067) Pembrolizumab 5.5 months (Q2W) and 4.1 months (Q3W) (KEYNOTE-006) RECIST, Response Evaluation Criteria in Solid Tumors. 1. Cross-trial comparative data for illustrative purposes only; randomized comparison trials have not been conducted 17

18 Phase 1 NSCLC: Best Percentage Change From Baseline in Target Lesions Best Overall Response by RECIST and irrecist ORR=5/12; DCR=7/12 (5 PRs, 2 SDs); 4/5 PRs are ongoing BID, twice daily; CR, complete response; DCR, disease control rate; irrecist, immune-related RECIST; ORR, objective response rate; NSCLC, non small-cell lung cancer; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. Of the 12 evaluable patients, data are shown for the 8 patients with postbaseline scans that included assessment of target lesions. 4 patients are not shown on this figure: 2 patients discontinued treatment for PD per new lesions (target lesions not assessed) and 2 patients died prior to the first postbaseline scan. * Objective response is PD (SD for target lesions; PD per new lesions). Objective response is PR (CR for target lesions; nontarget lesions still present). 18

19 Phase 1 NSCLC: Percentage Change From Baseline in Target Lesions BID, twice daily; NSCLC, non small-cell lung cancer; PD, progressive disease. Of the 12 evaluable patients, data are shown for the 8 patients with postbaseline scans that included assessment of target lesions. 4 patients are not shown in this figure: 2 patients discontinued treatment for PD per new lesions (target lesions not assessed) and 2 patients died prior to the first postbaseline scan. 19

20 Phase 1 RCC: Best Percentage Change From Baseline in Target Lesions Best Overall Response by RECIST: ORR=2/11; DCR=7/11 (2 PRs, 5 SDs) Best Overall Response by irrecist: ORR=3/11; DCR=8/11 (3 PRs, 5 SDs); all PRs are ongoing BID, twice daily; DCR, disease control rate; irrecist, immune-related RECIST; ORR, objective response rate; PD, progressive disease; PR, partial response; RCC, renal cell carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. Of the 11 evaluable patients, data are shown for the 10 patients with postbaseline scans that included assessment of target lesions. 1 patient died prior to the first postbaseline scan and is not shown in this figure. 1 additional PR was reported in the abstract. However, based on serial on-study scans, a patient assessed as a PR on the basis of target lesion reductions was retrospectively identified to have a new lesion present at an earlier time point. By RECIST, this patient s response was reassessed as PD based on the presence of a new lesion. The patient s response is PR by irrecist and the patient remains on study after local treatment to the new lesion. * Objective response is PD based on occurrence of new lesions. 20

21 Phase 1 RCC: Percentage Change From Baseline in Target Lesions BID, twice daily; RCC, renal cell carcinoma. Of the 11 evaluable patients, data are shown for the 10 patients with postbaseline scans that included assessment of target lesions. 1 patient died prior to the first postbaseline scan and is not shown in this figure. 21

22 Phase 1 Data from ECHO-202 Reinforce our Confidence in Decision to Initiate the Pivotal Phase 3 Program in Melanoma Durable Clinical Activity 1 Favorable objective response rate (58%), CR rate (26%), and disease control rate (74%) All responses are confirmed and ongoing; median PFS not reached PFS rate was 74% at 6 months and 57% at 12 months Well Tolerated 12 patients (19%) experienced Grade 3/4 treatment-related AEs 5 patients (8%) experienced treatment-related AEs that led to discontinuation Maximum tolerated dose (MTD) not reached; there were no treatment-related deaths Strategic Considerations Recruitment ongoing into Phase 3 ECHO-301 (treatment-naïve, advanced melanoma) 2 Incyte has an expanding commercial footprint (US and EU already in place) Epacadostat is a wholly-owned asset for Incyte; no third-party royalties 1. Among treatment-naive patients with melanoma in phase 1 2. A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (NCT ) 22

23 Q&A