Discovering Medicines. Hervé Hoppenot, Chief Executive Officer January 7, th Annual J.P. Morgan Healthcare Conference

Transcription

1 Discovering Medicines Hervé Hoppenot, Chief Executive Officer January 7, th Annual J.P. Morgan Healthcare Conference 1

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: whether we will successfully execute on our near-and long-term growth, product launch and product development plans and whether our strategies will lead to increased revenue or sustained profitability; Jakafi net revenue guidance; growth prospects for Jakafi; plans to consolidate our leadership in MPNs, including expected timing for receipt of data and regulatory submissions, expectations regarding targets and indications, and expectations regarding combinations with ; expectations regarding our projects to accelerate near-term growth, including potential indications; expectations regarding, cream, itacitinib, pemigatinib, parsaclisib, INCMGA0012 and INCB54707 trial results and timing thereof and of trial launches and NDA submissions; expectations by our collaborative partners regarding timing of trial results and NDA submission for capmatinib and baricitinib; expectations regarding our 2019 newsflow for key developments; expectations regarding our 2019 revenue and R&D expense growth and expected R&D expense breakdown allocations, and our plans and expectations for development of, and clinical trials involving, our other product candidates, including the potential timing for regulatory submissions. 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 unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of 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; determinations made by the FDA; Incyte's dependence on its relationships with its collaboration partners; the efficacy or safety of Incyte s products and the products of Incyte s collaboration partners; the acceptance of Incyte s products and the products of Incyte s collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; unanticipated variations in demand for products; greater than expected expenses; expenses relating to litigation or strategic activities; and other risks detailed from time to time in Incyte s reports filed with the Securities and Exchange Commission, including its Form 10-Q for the quarter ended September 30, Incyte disclaims any intent or obligation to update these forward-looking statements. 2

3 Royalties Net Sales Product-related revenue (US$m) Significant Top-line Momentum from Four Sources of Revenue Product-related revenue for first nine months of each year Total 4-year CAGR = 44% Jakavi 4-year CAGR = 42% Jakafi 4-year CAGR = 41% Long-term Jakafi net revenue guidance: $ billion Product-related revenue excludes milestone revenue Jakavi () 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 Increased Use of Jakafi in Both MPN Indications Over 12,500 patients taking Jakafi at end Q Myelofibrosis 9% YoY growth in total patients Polycythemia Vera 18% YoY growth in total patients Jakafi () 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. MPN = myeloproliferative neoplasm 4

5 Expanding and Consolidating Incyte s Leadership in MPNs Multiple strategies to improve patient outcomes Improved pharmacokinetics Ruxolitinib-based combinations Novel targets beyond JAK inhibition Preliminary data presented at ASH Potential for improved outcomes via lower peak-to-trough plasma concentrations 1 Initial data expected to be available in 2019 Multiple internal and collaborative discovery initiatives are already underway 1. Verstovsek et al (2018) Hematological Oncology 36: ; 2. Daver et al, ASH

6 Percent change from baseline PI3Kδ Inhibition has Potential to Improve Outcomes in MPNs Addition of parsaclisib (PI3Kδ) to suboptimal responders Definition of suboptimal response: - Treated with for 6 months - Stable dose for 8 weeks - Enlarged spleen; residual symptoms Spleen volume reduction at week 12 Data at ASH 2018 Daily dosing for 8 weeks Weekly dosing thereafter Ongoing cohorts Daily dosing for 8 weeks Daily dosing thereafter Data expected Daver et al, ASH

7 Six Projects in 16 Indications Aim to Accelerate Near-Term Growth Graft-versus Host Disease Targeted Therapies Immuno-Oncology IAI 1 itacitinib (JAK1) pemigatinib (FGFR1/2/3) parsaclisib (PI3Kδ) INCMGA0012 (PD-1) cream Steroid-refractory acute and chronic GVHD Steroid-naïve acute and chronic GVHD Cholangiocarcinoma, bladder cancer, 8p11 MPN and solid tumors Follicular, mantle cell and marginal zone lymphoma MSI-high endometrial, anal and merkel cell carcinoma Atopic dermatitis and vitiligo 3,000 new patients per year in US 15,000 new patients per year 35,000 new patients per year 22,000 new patients per year (2L+) 15,000 new patients per year ~12 million potential patients in the US Phase 3 data in both indications expected in 2019 Phase 3 data in acute GVHD expected in 2019 Cholangiocarcinoma NDA expected in 2019 Initial data expected in 2020 Initial data expected in 2020 Phase 2 data in vitiligo expected in Development of in GVHD in collaboration with Novartis. All epidemiology data for US, Europe and Japan except where noted for US only; all incidence data for unresectable or metastatic disease, except prevalence data for cream. References in subsequent slides or upon request. 7

8 Six Projects in 16 Indications Aim to Accelerate Near-Term Growth Graft-versus Host Disease Targeted Therapies Immuno-Oncology IAI 1 itacitinib (JAK1) pemigatinib (FGFR1/2/3) parsaclisib (PI3Kδ) INCMGA0012 (PD-1) cream Steroid-refractory acute and chronic GVHD Steroid-naïve acute and chronic GVHD Cholangiocarcinoma, bladder cancer, 8p11 MPN and solid tumors Follicular, mantle cell and marginal zone lymphoma MSI-high endometrial, anal and merkel cell carcinoma Atopic dermatitis and vitiligo 3,000 new patients per year in US 15,000 new patients per year 35,000 new patients per year 22,000 new patients per year (2L+) 15,000 new patients per year ~12 million potential patients in the US Phase 3 data in both indications expected in 2019 Phase 3 data in acute GVHD expected in 2019 Cholangiocarcinoma NDA expected in 2019 Initial data expected in 2020 Initial data expected in 2020 Phase 2 data in vitiligo expected in Development of in GVHD in collaboration with Novartis. All epidemiology data for US, Europe and Japan except where noted for US only; all incidence data for unresectable or metastatic disease, except prevalence data for cream. References in subsequent slides or upon request. 8

9 Chronic Acute GVHD is a Major Cause of Morbidity & Mortality in Transplant Patients Donor T-cells recognize the recipient s tissues as foreign, and attack the tissues Corticosteroids are currently standard-of-care in first-line treatment Prognosis is dismal, especially among patients with severe GVHD Before Acute GVHD After Steroid-naïve acute GVHD Steroid-refractory acute GVHD Acute Grade Survival (% of total) 1 at Year 1 2,3 Grade II (60%) 75% Steroid-naïve chronic GVHD First-line Steroid-refractory chronic GVHD Second-line Up to 50% of acute GVHD patients do not achieve sustained responses with corticosteroid therapy Grade III (25%) 51% Grade IV (15%) 24% Up to 40% of acute GVHD patients have initial Grade of III-IV disease, and therefore 12 month survival of 50% of less 4 Severe duodenal GVHD No clinical improvement on corticosteroids; progressive malnutrition detected Ruxolitinib initiated at 10 mg QD After 3 weeks treatment diarrhea was controlled and all nutritional parameters were improved After 12 months treatment patient had normal nutritional parameters and no signs of GVHD Sarmiento Maldonado et al. Exp Hematol Oncol (2017) 6: L acute GVHD defined as Grade II-IV; Grade I acute GVHD is either untreated or treated with oral steroids, no systemic treatment 2. Rowlings et al, British Journal of Haematology, 1997, 97, ; 3. Khoury et al Hematologica (2017) 102 (5): MacMillan et al Biology of Blood and Marrow Transplantation (2002); 8:

10 Ruxolitinib Under FDA Priority Review for GVHD Rapid and durable responses in patients with steroid-refractory acute disease 1 Best overall response rate: 73% Median duration of response: 345 days Phase 3 data expected in 2019 steroid-refractory acute GVHD steroid-refractory acute GVHD steroid-refractory chronic GVHD ~3,000 annually new steroid-refractory GVHD patients in U.S. Jagasia et al, ASH Development of in GVHD in collaboration with Novartis. Incidence estimates based on Allo HSCT from CIBMTR data. Estimates of US agvhd and cgvhd incidence based on market analysis and research (Data on file. Incyte Corporation. Wilmington, DE). Patients with GVHD can have both agvhd and cgvhd, numbers of estimated cases may not represent agvhd- or cgvhd-unique patients. 10

11 Itacitinib Represents a Significant Revenue Opportunity Approximately 15,000 new treatment-naïve GVHD patients annually itacitinib (JAK1) Acute GVHD First-line therapy: ORR 83% Phase 3 data expected 2019 Itacitinib (200mg and 300mg dose groups) Acute GVHD Incidence: 12,000 new patients in US, EU and Japan Response, n (%) First-line (n = 12) Steroid-refractory (n = 17) Complete response 8 (66.7) 3 (17.6) Very good partial response 0 1 (5.9) ~15,000 new patients in US, EU and Japan Partial response 2 (16.7) 7 (41.2) Overall response 10 (83.3) 11 (64.7) Schroeder et al. ASH 2016 Chronic GVHD Incidence: 9,000 new patients in US, EU and Japan 3,000 de novo Prevalence: 25,000 patients in US, EU and Japan Incidence estimates represent US, Europe and Japan based on data from CIBMTR, EBMT, JDCHCT Survey reports. Limited to Adult Population estimation only (>18 or 20 years of age). Total GVHD incidence exceeds number of total allogeneic transplants because multiple incidences can be attributed to a single patient as disease progresses rapidly within 12 months. Incidence of acute GVHD is Grades II-IV only; Grade I acute GVHD is either untreated or treated with oral steroids, no systemic treatment. Approximately 30% of patients with chronic GVHD are diagnosed with de novo chronic GVHD. Prevalence estimates from Jones C et al, Journal of Health Economics and Outcomes Research, 2016; 4(2):

12 Pemigatinib is a Potent and Selective Oral FGFR Inhibitor Development program across multiple indications pemigatinib (FGFR1/2/3) Cholangiocarcinoma NDA expected nd -line recruitment completed 1 st -line program recruiting (vs. gem/cis) 2 nd line cholangiocarcinoma Intermittent dosing: ORR 40%, DCR 85% Bladder cancer snda expected st -line program in preparation (vs. chemo / PD-1) 2 nd -line (continuous dosing) recruiting 8p11 MPN Ultra-rare indication No approved therapies for aggressive disease Hollebecque et al, ESMO 2018 Solid tumors Tumor-agnostic development plan Leverage increased availability of genetic testing 12

13 Targeted Development in Genetically-defined Populations Substantial potential in patients with driver activations of FGF/FGFR pemigatinib (FGFR1/2/3) Opportunities in tumor-defined trials (all trials already ongoing) FGFR alteration Alteration type Prevalence (%) Patient incidence 1 Intrahepatic cholangiocarcinoma FGFR2 translocation ,000-3,000 Bladder cancer FGFR3 mutation or fusion ,000-20,000 8p11 MPN FGFR1 translocation 100 ~100 Example opportunities within tumor-agnostic pivotal trial (expected to start in 2019) FGFR alteration Alteration type Prevalence (%) Patient incidence 1 Endometrial carcinoma FGFR2 mutation or fusion 10% 3,000 Glioblastoma FGFR3 mutation or fusion 10% 4,000 Squamous NSCLC FGFR1, 2 or 3 mutation or fusion 5% 4,000 Rectal cancer FGFR2 mutation 2% 2,000 SCCHN FGFR3 mutation or fusion 2% 2,000 Note: There are 12 additional solid tumor types where 1% of patients have FGFR1, 2 or 3 mutations or fusions 1. Patient incidence = estimated number of patients with unresectable / metastatic disease with specific FGFR alteration(s) in US, Europe and Japan. CCA: Ann Hepatol Mar 1;17(2): ; Biochim Biophys Acta Mol Basis Dis Apr;1864(4 Pt B): ; J Natl Compr Canc Netw Apr;16(4): ; Clin Cancer Res Sep 1;24(17): ; Clin Cancer Res Jan 15;22(2): Bladder: Epidemiology, Decision Resources Group, Bladder: 7/2017; Nature Vol March 2014, TCGA; Gust KM, et al. Mol Cancer Ther. 2013;12(7): Tumor agnostic: Endometrial American Cancer Society, NCI; Cancer Research; SEER 2018; EU DRG 2018; IARC, 2017 for France, Italy and Spain; ZfKD, 2016 for Germany and ONS, 2016 for UK; Japan Japan National Cancer Registry; NIH/American Cancer Society for US death rate; SEER GBM: Ostrum QT, et al. Neuro Oncol Oct 1;20(suppl_4):iv1-iv86; Surveillance of Rare Cancers in Europe ( ), RARECARE [Projected] Other three tumors: Epidemiology, Decision Resources Group: NSCLC: 7/2017; Rectal: 1/2018; H&N: 12/

14 Multiple New Opportunities in Inflammation and Auto-immunity Capitalizing on our discovery and development expertise Partnered Proprietary Baricitinib 1 Rheumatoid arthritis Atopic dermatitis (Phase 3) Systemic lupus erythematosus (Phase 3) Alopecia areata (Phase 2/3) Psoriatic arthritis (Phase 3 planned) Axial spondyloarthritis (Phase 3 planned) Ruxolitinib cream Atopic dermatitis (Phase 3) Vitiligo (Phase 2) Itacitinib (JAK1) 2 Ulcerative colitis (PoC trial) INCB54707 (JAK1) Hidradenitis suppurativa (PoC trial) Parsaclisib (PI3Kδ) Pemphigus vulgaris Autoimmune hemolytic anemia Sjögren s syndrome (all PoC trials) 1. Worldwide rights to baricitinib licensed to Lilly: approved as Olumiant in multiple territories globally for certain patients with moderate to severe rheumatoid arthritis. 2. Using a sustained-release formulation of itacitinib (INCB39110) 14

15 Ruxolitinib Cream has Significant Potential in Atopic Dermatitis Rapid and durable responses seen in randomized Phase 2 trial cream Mild/moderate atopic dermatitis Significant improvement of IGA response US prevalence and treatment landscape 1 The treatment of mild to moderate atopic dermatitis has seen little effective innovation since topical steroids MILD/MODERATE ~10 million SEVERE 1 million Opportunity for cream Uncontrolled AD Kim et al, EADV 2018 TCS/TCI/PDE4 or systemic therapies Oral JAK inhibitors Biologics Phase 3 now underway Data expected Diagnosed and treated adults and adolescents (aged 12 years) with atopic dermatitis in the US. Epidemiology estimates: Silverberg, J. I. (2017). Public Health Burden and Epidemiology of Atopic Dermatitis. Dermatologic Clinics, 35 (3), Silverberg J, Simpson E. Associations of Childhood Eczema Severity. Dermatitis. 2014;25(3): Epidemiology of atopic dermatitis in adults: Results from an international survey Allergy Jan 10. doi: /all and Fuxench et al Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population BJD US Census Data

16 Vitiligo is an Auto-immune Disease with No Approved Therapies Initial proof-of-concept data illustrate potential of cream cream Vitiligo Significant improvement in facial vitiligo 1 US prevalence 2 More than 2 million US patients suffer from vitiligo; fewer than 1% currently seek therapy as no treatments are approved Week million vitiligo patients in the US Week 8 Baseline Opportunity for cream Phase 2 underway Data expected 2019 Phase 3 program expected to start in 2019 Only 150,000 currently seek treatment 1. Rothstein et al (2017) J AmAcad Dermatol. 2. US Vitiligo Foundation data and Vitiligo by the Numbers (AAD 2017) 16

17 Revenue to R&D Expense Ratio Projected to Improve in 2019 Product-related revenue expected to grow in 2019 vs 2018 Non-GAAP R&D in 2019 expected to be comparable to product-related revenue and Non-GAAP R&D expense; 2018 product-related revenue based on consensus, 2018 Non-GAAP R&D based on company guidance expectations for R&D expense do not include impact of any business development transactions. 17

18 Majority of 2019 Clinical Development Expense on Late-Stage Programs Late-stage development Clinical development Estimated 2019 R&D expense allocation Targeted therapy Immunotherapy Dermatology Partnered 18

19 2019 Newsflow for Key Development Projects itacitinib (JAK1) Report Phase 3 data in SN-aGVHD FDA decision in SR-aGVHD Report Phase 3 data in both SR-aGVHD and SR-cGVHD Submit NDA for cholangiocarcinoma pemigatinib (FGFR1/2/3) Initiate first-line Phase 3 trials in bladder and cholangiocarcinoma Initiate tumor-agnostic solid tumor trial Recruit 3 key monotherapy trials and continue combination strategy INCMGA0012 (PD-1) cream Report Phase 2 data in vitiligo, initiate Phase 3 program Recruit 3 key monotherapy trials and continue combination strategy parsaclisib (PI3Kδ) baricitinib 2 Lilly expected to report Phase 3 data in atopic dermatitis Novartis expected to submit NDA in NSCLC capmatinib 1 (MET) 1. Worldwide rights to capmatinib licensed to Novartis 2. Worldwide rights to baricitinib licensed to Lilly 19

20 Proof-of-concept Late-stage development itacitinib (JAK1) Steroid-naïve agvhd Steroid-naïve cgvhd Small molecules AXL/MER, IDO1, ARG, PD-L1 FGFR4, PIM, LSD1 Steroid-refractory agvhd Steroid-refractory cgvhd Cholangiocarcinoma Monoclonal antibodies pemigatinib (FGFR1/2/3) Bladder cancer 8p11 MPN TIM-3, LAG-3, OX40, GITR Bispecific antibodies MSI-H endometrial cancer Merkel cell carcinoma Anal cancer INCMGA0012 (PD-1) Solid tumors PD-L1 x CD137 cream Atopic dermatitis Vitiligo Follicular lymphoma Marginal zone lymphoma Mantle cell lymphoma parsaclisib (PI3Kδ) baricitinib 2 Atopic dermatitis Systemic lupus erythematosus Alopecia areata MET mutated NSCLC capmatinib 1 (MET) 1. Worldwide rights to capmatinib licensed to Novartis 2. Worldwide rights to baricitinib licensed to Lilly 20

21 Proof-of-concept Late-stage development itacitinib (JAK1) Steroid-naïve agvhd Steroid-naïve cgvhd Small molecules AXL/MER, IDO1, ARG, PD-L1 FGFR4, PIM, LSD1 Steroid-refractory agvhd Steroid-refractory cgvhd Cholangiocarcinoma Monoclonal antibodies pemigatinib (FGFR1/2/3) Bladder cancer 8p11 MPN TIM-3, LAG-3, OX40, GITR Bispecific antibodies MSI-H endometrial cancer Merkel cell carcinoma Anal cancer INCMGA0012 (PD-1) Solid tumors PD-L1 x CD137 cream Atopic dermatitis Vitiligo Follicular lymphoma Marginal zone lymphoma Mantle cell lymphoma parsaclisib (PI3Kδ) baricitinib 2 Atopic dermatitis Systemic lupus erythematosus Alopecia areata MET mutated NSCLC capmatinib 1 (MET) 1. Worldwide rights to capmatinib licensed to Novartis 2. Worldwide rights to baricitinib licensed to Lilly 21

22 INCB86550 is an Oral, Small Molecule PD-L1 Inhibitor An opportunity to transform cancer immunotherapy Preclinical profile comparable to anti-pd-l1 mab Unique mechanism of action: Internalizes PD-L1 on cancer and immune cells Functionally inhibits PD-1/PD-L1 axis signaling First-in-human study initiated 0 min 135 min 180 min 285 min Confocal imaging of cells treated with INCB86550 shows time-dependent internalization of PD-L1 (green) over ~5 hours Why is this important? Potential for differential clinical profile Benefits of oral administration Rapid dose titration Potential for all-oral combinations 22

23 Discovering Medicines Breakout Q&A session in Georgian Room Connect with 23