Changing the Practice of Cancer Treatment. 36 th Annual J.P. Morgan Healthcare Conference Hervé Hoppenot, Chief Executive Officer January 8, 2018

Transcription

1 Changing the Practice of Cancer Treatment 36 th Annual J.P. Morgan Healthcare Conference Hervé Hoppenot, Chief Executive Officer January 8, 2018

2 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: Incyte s financial guidance for 2017 and its long-term revenue guidance for Jakafi (ruxolitinib); Incyte s vision over the next several years (including without limitation whether any or all current late stage clinical candidates will be developed successfully, approved for use in humans or produce revenue, and including without limitation whether current early stage clinical candidates will be developed successfully or progress into later-stage development); plans for continued development of Jakafi (ruxolitinib) in essential thrombocythemia and GVHD as well as additional indications and life cycle management plans for Jakafi (ruxolitinib) and myeloproliferative neoplasm research; whether the pivotal trials of epacadostat in combination with pembrolizumab and in combination with nivolumab will be successful, including without limitation the ECHO-301 study in advanced or metastatic melanoma, and the expected timing of developments relating to those studies, including without limitation the expected timing of progression-free survival data from the ECHO-301 study; plans for studying epacadostat in other potential combination therapies, including without limitation the planned timing and design of such studies; whether epacadostat combination therapies with pembrolizumab and with nivolumab will continue to demonstrate similar efficacy and safety in current or future pivotal trials in any or all of the selected tumor types as has been demonstrated in the Phase 2 studies presented herein and presented previously; whether and when epacadostat will be submitted for approval in any indication to the U.S. FDA or any other regulatory authority outside the U.S., whether any such approvals will be granted and whether Incyte will ever launch epacadostat as a commercial product in the U.S. or in any markets outside the U.S.; plans and expectations regarding our product pipeline and strategy - including without limitation timelines and strategies for advancing our drug candidates (including without limitation epacadostat, ruxolitinib, itacitinib, MGA012, INCB54828, and INCB50465) through clinical trials (including without limitation enrollment and commencement), whether certain trials will serve as the basis for registration, timelines for regulatory submissions and timelines for releasing trial data, and whether any specific program will be successful - and plans and expectations regarding development activities of our collaboration partners (including without limitation baricitinib by Lilly and capmatinib by Novartis); whether the FDA will take action on the resubmitted NDA for baricitinib in 2018 and what that action might be; whether Incyte will launch any new products over the next several years; and whether Incyte s plans will lead to transformational growth.. These forward-looking statements are based on our current expectations and are subject to risks and uncertainties that may cause actual results to differ materially, including without limitation unanticipated developments in and risks related to: the efficacy or safety of our products and the products of our collaboration partners; the acceptance of our products and the products of our collaboration partners in the marketplace; market competition; further research and development; sales, marketing and distribution requirements; our or our collaboration partners clinical trials, including without limitation pivotal trials, possibly being unsuccessful or insufficient to meet applicable regulatory standards for clinical advancement or approval or warrant continued development; the ability to enroll sufficient numbers of subjects in any such clinical trials; other market, economic or strategic factors and technological advances; unanticipated delays; our ability to compete against parties with greater financial or other resources; our dependence on our relationships with our collaboration partners; greater than expected expenses; expenses relating to litigation or strategic activities; our ability to obtain additional capital when needed; obtaining and maintaining effective patent coverage for our products and our product candidates; and other risks detailed from time to time in our reports filed with the Securities and Exchange Commission, including our Form 10-Q for the quarter ended September 30, 2017, as amended. We disclaim any intent or obligation to update these forward looking statements. 2

3 Five Years of Building our Capabilities, Expanding the Portfolio and Growing Revenue Sources of Revenue ,106 Development Discovery Locations Team 6 compounds Small molecules US compounds Small molecules US compounds Small molecules Large molecules US compounds Small molecules Large molecules US Europe compounds Small molecules Large molecules Bispecifics US Europe Japan 1, Figure represents Incyte total revenue for (US$ millions, 2017 based on current guidance) Jakavi (ruxolitinib) licensed to Novartis ex-us, Olumiant (baricitinib) licensed to Lilly worldwide; these brands are trademarks of Novartis (Jakavi) and Lilly (Olumiant) and are not trademarks of Incyte 3

4 Our Vision: Incyte in 2018 Revenue Clinical Discovery Jakafi (JAK1/JAK2) Iclusig (BCR-ABL) --- Jakavi (JAK1/JAK2) Olumiant (JAK1/JAK2) epacadostat (IDO1) itacitinib (JAK1) INCB54828 (FGFR) TIM-3 LAG-3 ARG AXL/MER MGA012 (PD-1) INCB50465 (PI3Kδ) ruxolitinib (JAK1/JAK2) PIM LSD1 FGFR4 GITR OX40 BRD Small molecules, large molecules, bispecifics Jakavi (ruxolitinib) licensed to Novartis ex-us, Olumiant (baricitinib) licensed to Lilly worldwide 4

5 Our Vision: Incyte in 2022 Jakafi (JAK1/JAK2) Iclusig (BCR-ABL) --- Jakavi (JAK1/JAK2) Olumiant (JAK1/JAK2) Revenue Jakafi (JAK1/JAK2) Iclusig (BCR-ABL) --- Jakavi (JAK1/JAK2) Olumiant (JAK1/JAK2) epacadostat (IDO1) MGA012 (PD-1) itacitinib (JAK1) INCB54828 (FGFR1/2/3) INCB50465 (PI3Kδ) Topical ruxolitinib (JAK1/JAK2) --- capmatinib (c-met) Clinical Discovery epacadostat (IDO1) itacitinib (JAK1) INCB54828 (FGFR) TIM-3 LAG-3 ARG AXL/MER MGA012 (PD-1) INCB50465 (PI3Kδ) ruxolitinib (JAK1/JAK2) PIM LSD1 FGFR4 GITR OX40 BRD Small molecules, large molecules, bispecifics TIM-3 LAG-3 ARG AXL/MER Small molecules Large molecules Bispecifics PIM LSD1 FGFR4 GITR OX40 BRD Small molecules, large molecules, bispecifics Jakavi (ruxolitinib) licensed to Novartis ex-us, capmatinib licensed to Novartis globally, Olumiant (baricitinib) licensed to Lilly worldwide Figure represents illustrative intent for the potential evolution of Incyte s development, regulatory and commercial activities from 2018 to 2022 Clinical development of candidates might not be successful, and regulatory approval of clinical candidates may never be achieved 5

6 Discovery Development Revenue Small molecules Large molecules Bispecifics AXL/MER TIM-3 LAG-3 FGFR4 ARG OX40 BRD PIM LSD1 Proof-of-concept INCB50465 (PI3Kδ) itacitinib (JAK1) MGA012 (PD-1) INCB54828 (FGFR1/2/3) epacadostat (IDO1) ruxolitinib (JAK1/JAK2) Small molecu les Small molecu les Small molecu les Revenue Royalties GITR Small molecu les Jakavi (ruxolitinib) licensed to Novartis ex-us, Olumiant (baricitinib) licensed to Lilly worldwide 6

7 Jakafi net product revenue (US$m) Jakafi has Transformed Treatment of Myelofibrosis & Polycythemia Vera Myelofibrosis (COMFORT, pooled 5 year data, ASH 2016) 70% of BAT/placebo patients switched to Jakafi 30% reduction in risk of death for Jakafi patients Myelofibrosis Small molecules Polycythemia vera Polycythemia vera (RESPONSE, 4 year data, ASH 2017) 88% of BAT patients switched to Jakafi 73% remain Jakafi responders at 4 years Jakafi (ruxolitinib) is approved by the FDA for treatment of people with intermediate or high-risk myelofibrosis and for treatment of people with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. 7

8 Jakafi net product revenue (US$m) Jakafi is also being Evaluated in Essential Thrombocythemia & GVHD Myelofibrosis (COMFORT, pooled 5 year data, ASH 2016) 70% of BAT/placebo patients switched to Jakafi 30% reduction in risk of death for Jakafi patients Myelofibrosis Polycythemia vera Polycythemia vera (RESPONSE, 4 year data, ASH 2017) 88% of BAT patients switched to Jakafi 73% remain Jakafi responders at 4 years Small molecules Graft vs host disease Essential thrombocythemia Graft vs host disease (REACH, three pivotal trials ongoing) Essential thrombocythemia (RESET, pivotal trial ongoing) 120 patients, 2 nd -line (post hydroxyurea) Head-to-head versus anagrelide Steroid-refractory patients; first pivotal result expected in H Jakafi (ruxolitinib) is approved by the FDA for treatment of people with intermediate or high-risk myelofibrosis and for treatment of people with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Development of ruxolitinib in GVHD in collaboration with Novartis. 8

9 Increased Long-term Revenue Guidance for Jakafi Driven by robust demand & increased persistency in MPNs, and potential in GVHD and ET New guidance for long-term US revenue from Jakafi: Raised to $ billion 2017 Jakafi net product revenue guidance: $1,125-1,135 million Jakafi (ruxolitinib) is approved by the FDA for treatment of people with intermediate or high-risk myelofibrosis and for treatment of people with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Previous guidance for long-term US revenue from Jakafi was $2 billion. 9

10 Increased Long-term Revenue Guidance for Jakafi Driven by robust demand & increased persistency in MPNs, and potential in GVHD and ET 1 Revlimid 2 Imbruvica 3 Ibrance 4 Xtandi 5 Jakafi/Jakavi New guidance for long-term US revenue from Jakafi: Raised to $ billion 2022 global oncology sales; small molecules Consensus estimates (Evaluate Pharma) 2017 Jakafi net product revenue guidance: $1,125-1,135 million Jakafi (ruxolitinib) is approved by the FDA for treatment of people with intermediate or high-risk myelofibrosis and for treatment of people with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Previous guidance for long-term US revenue from Jakafi was $2 billion. 10

11 Pioneering Progress in Myeloproliferative Neoplasm Research Ruxolitinib combinations 1 MPN target discovery Collaboration with Syros New target discovery and validation collaboration Centered on expression of diseasedriving genes Drug discovery and development executed by Incyte Collaboration with Moffitt Cancer Center Combination clinical trials JAK plus PI3Kδ and JAK plus PIM studies already underway Incyte has worldwide rights for development and commercialization 1. Samples from an essential thrombocythemia patient (JAK2-V617F-positive; currently on hydroxyurea) 11

12 JAK Inhibition has Potential to Treat Graft versus Host Disease Development plan designed to leverage both ruxolitinib and itacitinib programs ruxolitinib, acute GVHD ruxolitinib, chronic GVHD Steroid-refractory: 2 nd + line Data expected in H Pivotal REACH1 (n=70) Single arm Primary Endpoint: ORR day 28 Pivotal REACH2 (n=300) Randomized vs BAT Primary Endpoint: ORR day 28 Pivotal REACH3 (n=300) Randomized vs BAT Primary Endpoint: ORR month 6 Development of ruxolitinib in GVHD in collaboration with Novartis. 12

13 JAK Inhibition has Potential to Treat Graft versus Host Disease Development plan designed to leverage both ruxolitinib and itacitinib programs ruxolitinib, acute GVHD ruxolitinib, chronic GVHD Steroid-refractory: 2 nd + line Data expected in H Pivotal REACH1 (n=70) Single arm Primary Endpoint: ORR day 28 Pivotal REACH2 (n=300) Randomized vs BAT Primary Endpoint: ORR day 28 Pivotal REACH3 (n=300) Randomized vs BAT Primary Endpoint: ORR month 6 itacitinib, acute GVHD Steroid-naïve: 1st line Data expected in 2019 Pivotal (n=400) Randomized vs placebo, + steroids Primary Endpoint: ORR Day 28 Global trial Development of ruxolitinib in GVHD in collaboration with Novartis. 13

14 epacadostat (IDO1) Epacadostat plus PD-1 Blockade has Promising Profile in Melanoma Evolution of responses to epacadostat plus pembrolizumab (melanoma patients) SITC 2015 ESMO 2016 ESMO 2017 epacadostat plus pembrolizumab, Gangadhar et al epacadostat plus pembrolizumab, Gangadhar et al epacadostat plus pembrolizumab, Hamid et al 14

15 Responses in Combination with both Pembrolizumab and Nivolumab ECHO-202 (epacadostat plus pembrolizumab, ESMO 2017) ECHO-202 (epacadostat plus pembrolizumab, ESMO 2017) ECHO-204 (epacadostat plus nivolumab, ASCO 2017) Combination with PD-1 is well tolerated 20% Grade 3/4 TRAEs (w/ pembrolizumab); 25% Grade 3/4 TRAEs (w/ nivolumab) 15

16 Improved Response Rates Compared to PD-1 Monotherapy In multiple tumor types and in combination with both pembrolizumab and nivolumab ECHO-204 ECHO-202 Checkmate-025 ECHO-202 Keynote -055 ECHO-204 ECHO-202 Keynote-045 ECHO-202 Keynote -010 ECHO-202 Keynote-006 Melanoma NSCLC Bladder SCCHN Renal Comparative anti-pd-1 monotherapy data are provided for illustrative purposes only; head-to-head comparative trials were not conducted. Epa = epacadostat, Pembro = pembrolizumab, Nivo = nivolumab; CR = complete response, PR = partial response; Treatment-naïve melanoma, all other tumor types in second-line setting ECHO-202 data for melanoma from ESMO 2017 (E100mg tx-naïve); all other ECHO-202 and ECHO-204 data from ASCO Keynote-006; Robert et al, NEJM Keynote-010; Herbst et al, Lancet Keynote-045; Bellmunt et al, NEJM Keynote-055; Bauml et al, JCO Checkmate-025; Motzer et al, NEJM 2015

17 In Addition to Melanoma, Multiple Hypotheses for IDO1 Inhibition Proof-of-concept combination trials 1 Epigenetic therapies + azacitadine Immune agonists + GITR, OX40 Myeloid directed + arginase Vaccines + survivin antigen Intra-tumoral adjuvants + TLR9 agonists Cell therapies + CAR-T Translational sciences Pivotal trials in combination with PD-(L)1 Metastatic therapy - Melanoma - Bladder, x2 - Kidney - Head and neck, x2 - Lung, x3 Consolidation therapy - Lung PFS result expected in H Including PD-L1, IDO1, tumor mutation burden and gene expression profiling 1. Ongoing or planned 17

18 MGA012 (PD-1) Why License the N th -to-market PD-1 Antagonist? MGA012 (PD-1) monotherapy (Lakhani et al, SITC 2017) Humanized IgG4 anti-pd-1 MAb No DLTs at completion of dose escalation Evidence of complete receptor occupancy Monotherapy dose expansion Multiple solid tumors, incl. niche opportunities Expected to be initiated in 2018 Proprietary combinations Expected to be initiated in 2018 IDO1 JAK1 BRD PI3Kδ FGFR1/2/3 Arginase GITR OX40 18

19 INCB54828 (FGFR1/2/3) Cholangiocarcinoma Data Accelerating; Now Expected in 2018 INCB54828 (FGFR1/2/3) monotherapy (Saleh et al, AACR 2017) Activity observed in cholangiocarcinoma tumors with FGFR2 pathway activation As expected, serum phosphate level correlated with steady-state exposure Cholangiocarcinoma (n=160) Primary endpoint: - ORR in patients with FGFR2 translocations Epidemiology: % of patients have FGFR2 translocations Data expected in 2018 Cholangiocarcinoma Bladder cancer (n=140) Primary endpoint: - ORR (all patients must have known FGF/FGFR alteration) Epidemiology: - ~15% of patients have activating FGFR3 mutations - ~5% of patients have activating FGFR3 translocations 19

20 INCB50465 (PI3Kδ) Daily Induction Therapy for Efficacy, Weekly Maintenance Dosing INCB50465 (PI3Kδ) monotherapy (Forero-Torres et al, ASH 2017) Rapid, deep, and durable responses Supports daily induction regimen Switch to weekly maintenance dosing No QW discontinuations due to AEs DLBCL MZL Evaluation in four NHLs: DLBCL, follicular, marginal zone and mantle cell lymphomas Follicular MCL 20

21 Significant Progress in Early-Stage Portfolio INCB57643 (BRD) INCB62079 (FGFR4) 250x selectivity vs FGFR1/2/3 Development in hepatocellular carcinoma INCB01158 (ARG) Novel mechanism targeting myeloid cells IDO1 / PD-1 / chemo combinations INCAGN1949 (OX40) Dose escalation completed PD-1 +/- CTLA-4 combinations FGFR4 ARG OX40 BRD PIM LSD1 GITR First-in-man data at ASH 2017 Optimized PK profile for combination therapy INCB53914 (PIM) First-in-man data at ASH 2017 JAK / PI3Kδ combinations in hematological malignancies INCB59872 (LSD1) Epigenetic mechanism targeting cell differentiation Evaluating both oncology indications and sickle-cell disease INCAGN1876 (GITR) Dose escalation completed IDO1 / PD-1 +/- CTLA-4 combinations 21

22 Three New Clinical Candidates Expected in 2018 AXL/MER INCB81776 (AXL/MER) Tyro3 sparing, designed to mitigate toxicity Potential as both I-O and tumor-directed therapy Single-agent activity in preclinical models Additive efficacy in combination with anti-pd-l1 Preclinical tumor growth control in combination with PD-1 axis blockade TIM-3 LAG-3 INCAGN2390 (TIM-3), INCAGN2385 (LAG-3) Cell surface receptors that negatively regulate antigen-specific T cell responses Anti-TIM-3 restores immune responses by restimulating myeloid, NK and T cell activity Anti-LAG-3 relieves inhibition of activated T eff cells and promotes anti-tumoral immunity 22

23 Pharmacy sales, cash Partnership Progress adds Strength to Financial Profile Jakavi (ruxolitinib, JAK1/JAK2) Olumiant (baricitinib, JAK1/JAK2) capmatinib (cmet) Licensed to Novartis ex-us Co-development with Lilly Licensed to Novartis globally 39% royalty growth in Q Pivotal ongoing trials for GVHD 20-29% royalties on global sales NDA for RA resubmitted to FDA Phase 3 atopic dermatitis underway FDA action expected mid % royalties Trial ongoing in NSCLC with high cmet expression Potential for NDA in 2018 Launch-date adjusted comparison for RA therapies in Germany In NSCLC patients with high cmet expression (GCN 6), confirmed partial responses were seen in 7/15 patients (ORR 47%) 0 Months post launch Schuler et al, ASCO Year-on-year growth in royalty revenue as reported for Jakavi (ruxolitinib) sales by Novartis; development of ruxolitinib in steroid-refractory acute and steroid-refractory chronic GVHD 23

24 Incyte: The Value of Transformational Growth Potential Incyte Vision for 2022 Operations in North America, Europe and Japan Jakavi (ruxolitinib) licensed to Novartis ex-us, capmatinib licensed to Novartis globally, Olumiant (baricitinib) licensed to Lilly worldwide Figure represents illustrative intent for the potential evolution of Incyte s development, regulatory and commercial activities from 2018 to 2022 Clinical development of candidates might not be successful, and regulatory approval of clinical candidates may never be achieved 24

25 Incyte: The Value of Transformational Growth Potential Rapid revenue growth 38% YoY growth in product-related revenues, Q Increased long-term Jakafi net revenue guidance Substantial royalty potential from Jakavi and Olumiant Incyte Vision for 2022 Key newsflow expected in 2018 Ruxolitinib REACH1 result (steroid-refractory acute GVHD) Epacadostat ECHO-301 result (melanoma) Baricitinib FDA action (rheumatoid arthritis) INCB54828 data (FGFR, cholangiocarcinoma) Rich portfolio of late-stage candidates Potential for multiple product launches R&D drive to maintain development momentum Jakavi (ruxolitinib) licensed to Novartis ex-us, capmatinib licensed to Novartis globally, Olumiant (baricitinib) licensed to Lilly worldwide Figure represents illustrative intent for the potential evolution of Incyte s development, regulatory and commercial activities from 2018 to 2022 Clinical development of candidates might not be successful, and regulatory approval of clinical candidates may never be achieved 25

26 Thank