Discovering Medicines - static.seekingalpha.com

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Discovering Medicines

Hervé Hoppenot, Chief Executive OfficerJanuary 7, 2019

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37th Annual J.P. Morgan Healthcare Conference

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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 ruxolitinib; expectations regarding our projects to accelerate near-term growth, including potential indications; expectations regarding ruxolitinib, ruxolitinib 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, 2018. Incyte disclaims any intent or obligation to update these forward-looking statements.

Forward-looking Statements

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Significant Top-line Momentum from Four Sources of Revenue

Pro

du

ct-r

elat

ed r

even

ue

(US$

m)

Jakafi 4-year CAGR = 41%

Jakavi 4-year CAGR = 42%

Product-related revenue excludes milestone revenue

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

Total 4-year CAGR = 44%

Long-term Jakafi net revenue guidance:

$2.5-3.0 billion

Product-related revenue for first nine months of each year

Net

Sal

es

Ro

yalt

ies

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Increased Use of Jakafi® in Both MPN IndicationsOver 12,500 patients taking Jakafi at end Q3 2018

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. MPN = myeloproliferative neoplasm

Myelofibrosis

9% YoY growth in total patients

Polycythemia Vera

18% YoY growth in total patients

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Expanding and Consolidating Incyte’s Leadership in MPNsMultiple strategies to improve patient outcomes

Improved pharmacokinetics

Ruxolitinib-based combinations

Novel targets beyond JAK inhibition

Initial data expected to be available in 2019

Preliminary data presented at ASH 20182

Potential for improved outcomes via lower peak-to-trough plasma concentrations1

Multiple internal and collaborative discovery initiatives are already underway

1. Verstovsek et al (2018) Hematological Oncology 36:701–708; 2. Daver et al, ASH 2018

• Daily dosing for 8 weeks

• Daily dosing thereafter

Ongoing cohorts

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• Definition of suboptimal response:- Treated with ruxolitinib for ≥6 months

- Stable dose for ≥8 weeks

- Enlarged spleen; residual symptoms

PI3Kδ Inhibition has Potential to Improve Outcomes in MPNsAddition of parsaclisib (PI3Kδ) to ruxolitinib (JAK1/JAK2) suboptimal responders

• Daily dosing for 8 weeks

• Weekly dosing thereafter

Data at ASH 2018

Data expected 2019

-5 0

-2 5

0

2 5

5 0

Spleen volume reduction at week 12

Daver et al, ASH 2018

Per

cen

t ch

ange

fro

m b

asel

ine

Steroid-refractory acute and chronic GVHD

3,000 new patients per year in US

Phase 3 data in both indications expected

in 2019

Steroid-naïveacute and chronic GVHD

15,000 new patients per year

Phase 3 data in acute GVHD expected

in 2019

Cholangiocarcinoma,bladder cancer, 8p11 MPN and solid tumors


Cholangiocarcinoma NDA expected in 2019

Follicular, mantle cell and marginal zone

lymphoma

22,000 new patients per year (2L+)

Initial data expected in 2020

MSI-high endometrial, anal and merkel cell

carcinoma



Atopic dermatitis and vitiligo

~12 million potential patients in the US

Phase 2 data in vitiligo expected in 2019

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Six Projects in 16 Indications Aim to Accelerate Near-Term Growth

ruxolitinib cream

(JAK1/JAK2)

itacitinib (JAK1)

INCMGA0012 (PD-1)

ruxolitinib1

(JAK1/JAK2)pemigatinib(FGFR1/2/3)

parsaclisib(PI3Kδ)

Graft-versus Host Disease Targeted Therapies Immuno-Oncology IAI

1. Development of ruxolitinib 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 ruxolitinib cream.

References in subsequent slides or upon request.

Steroid-refractory acute and chronic GVHD

3,000 new patients per year in US

Phase 3 data in both indications expected

in 2019

Steroid-naïveacute and chronic GVHD


Phase 3 data in acute GVHD expected

in 2019

Cholangiocarcinoma,bladder cancer, 8p11 MPN and solid tumors


Cholangiocarcinoma NDA expected in 2019

Follicular, mantle cell and marginal zone

lymphoma

22,000 new patients per year (2L+)


MSI-high endometrial, anal and merkel cell

carcinoma



Atopic dermatitis and vitiligo

~12 million potential patients in the US

Phase 2 data in vitiligo expected in 2019

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Six Projects in 16 Indications Aim to Accelerate Near-Term Growth

ruxolitinib cream

(JAK1/JAK2)

itacitinib (JAK1)

INCMGA0012 (PD-1)

ruxolitinib1

(JAK1/JAK2)pemigatinib(FGFR1/2/3)

parsaclisib(PI3Kδ)

Graft-versus Host Disease Targeted Therapies Immuno-Oncology IAI


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 ruxolitinib cream.

References in subsequent slides or upon request.

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GVHD is a Major Cause of Morbidity & Mortality in Transplant PatientsDonor T-cells recognize the recipient’s tissues as foreign, and attack the tissues

Corticosteroids are currently standard-of-care in first-line treatment

Steroid-naïve acute GVHD

Steroid-naïve chronic GVHD

Steroid-refractory acute GVHD

Steroid-refractory chronic GVHD

Up to 50% of acute GVHD patients do not achieve sustained responses

with corticosteroid therapy

First-line Second-line

Acu

teC

hro

nic

Prognosis is dismal, especially among patients with severe GVHD

Acute Grade (% of total)1

Survival at Year 12,3

Grade II (60%) 75%

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 less4

1. 1L 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, 855-864;

3. Khoury et al Hematologica (2017) 102 (5):958-966 4. MacMillan et al Biology of Blood and Marrow Transplantation (2002); 8:387-394

Sarmiento Maldonado et al. Exp Hematol Oncol (2017) 6:32

Acute GVHD

Before ruxolitinib After ruxolitinib

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

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Ruxolitinib Under FDA Priority Review for GVHDRapid and durable responses in patients with steroid-refractory acute disease

ruxolitinib1

(JAK1/JAK2)

~3,000 annually new steroid-refractory GVHD patients in U.S.

ruxolitinibsteroid-refractory

chronic GVHD

Best overall response rate: 73% Median duration of response: 345 days


acute GVHD


acute GVHD

Phase 3data expected in 2019

Jagasia et al, ASH 2018


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.

~15,000 new patients in US, EU and Japan

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Itacitinib Represents a Significant Revenue OpportunityApproximately 15,000 new treatment-naïve GVHD patients annually

Acute GVHD

Chronic GVHD

Incidence: 12,000 new patients in US, EU and Japan

Incidence: 9,000 new patients in US, EU and Japan

3,000 de novo

itacitinib (JAK1)

Acute GVHDFirst-line therapy: ORR 83%

Itacitinib(200mg and 300mg dose groups)

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)

Partial response 2 (16.7) 7 (41.2)

Overall response 10 (83.3) 11 (64.7)

Schroeder et al. ASH 2016

Phase 3data expected 2019

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):113 – 8

Prevalence: 25,000 patients in US, EU and Japan

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Pemigatinib is a Potent and Selective Oral FGFR InhibitorDevelopment program across multiple indications

• 2nd-line recruitment completed

• 1st-line program recruiting (vs. gem/cis)

Cholangiocarcinoma NDA expected 2019

• 1st-line program in preparation (vs. chemo / PD-1)

• 2nd-line (continuous dosing) recruiting

Bladder cancer sNDA expected 2020

• Ultra-rare indication

• No approved therapies for aggressive disease

8p11 MPN

• Tumor-agnostic development plan

• Leverage increased availability of genetic testing

Solid tumors

2nd line cholangiocarcinomaIntermittent dosing: ORR 40%, DCR 85%

pemigatinib(FGFR1/2/3)

Hollebecque et al, ESMO 2018

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Targeted Development in Genetically-defined PopulationsSubstantial potential in patients with driver activations of FGF/FGFR


Opportunities in tumor-defined trials(all trials already ongoing)

FGFR alterationPatient incidence1

Alteration type Prevalence (%)

Intrahepatic cholangiocarcinoma FGFR2 translocation 13-20 2,000-3,000

Bladder cancer FGFR3 mutation or fusion 15-20 15,000-20,000

8p11 MPN FGFR1 translocation 100 ~100

Example opportunities within tumor-agnostic pivotal trial (expected to start in 2019)

FGFR alterationPatient incidence1

Alteration type Prevalence (%)

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. 2018 Mar 1;17(2):274-285; Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1461-1467; J Natl Compr Canc Netw. 2018 Apr;16(4):370-376; Clin Cancer Res. 2018 Sep

1;24(17):4154-4161; Clin Cancer Res. 2016 Jan 15;22(2):291-300. Bladder: Epidemiology, Decision Resources Group, Bladder: 7/2017; Nature Vol 507 20 March 2014, TCGA; Gust KM, et al. Mol

Cancer Ther. 2013;12(7):1245-1254 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323288/ Japan National Cancer Registry; NIH/American Cancer Society for US death rate; SEER 2018. GBM:

Ostrum QT, et al. Neuro Oncol. 2018 Oct 1;20(suppl_4):iv1-iv86; Surveillance of Rare Cancers in Europe (1995-2002), RARECARE [Projected] Other three tumors: Epidemiology, Decision Resources

Group: NSCLC: 7/2017; Rectal: 1/2018; H&N: 12/2015.

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Multiple New Opportunities in Inflammation and Auto-immunity Capitalizing on our discovery and development expertise

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)

Baricitinib (JAK1/JAK2)1

• Ulcerative colitis (PoC trial)

Itacitinib (JAK1)2

• Hidradenitis suppurativa(PoC trial)

INCB54707 (JAK1)

• Pemphigus vulgaris

• Autoimmune hemolytic anemia

• Sjögren’s syndrome

(all PoC trials)

Parsaclisib (PI3Kδ)

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)

Partnered Proprietary

• Atopic dermatitis (Phase 3)

• Vitiligo (Phase 2)

Ruxolitinib cream (JAK1/JAK2)

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Ruxolitinib Cream has Significant Potential in Atopic DermatitisRapid and durable responses seen in randomized Phase 2 trial

ruxolitinib cream

(JAK1/JAK2)

Mild/moderate atopic dermatitisSignificant improvement of IGA response

Phase 3 now underway Data expected 2020

MILD/MODERATE~10 million

SEVERE1 million

US prevalence and treatment landscape1

The treatment of mild to moderate atopic dermatitis has seen little effective innovation since topical steroids

1. 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), 283-289. Silverberg J, Simpson E. Associations of Childhood Eczema Severity.

Dermatitis. 2014;25(3):107-114 Epidemiology of atopic dermatitis in adults: Results from an international survey Allergy. 2018 Jan 10. doi: 10.1111/all.13401. 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 2018. US Census Data 2016

Kim et al, EADV 2018

Uncontrolled AD

Opportunity for ruxolitinib cream

Biologics

Oral JAK inhibitorsTCS/TCI/PDE4 or systemic therapies

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Vitiligo is an Auto-immune Disease with No Approved TherapiesInitial proof-of-concept data illustrate potential of ruxolitinib cream

ruxolitinib cream

(JAK1/JAK2)

VitiligoSignificant improvement in facial vitiligo1

Phase 2 underway Data expected 2019

US prevalence2

More than 2 million US patients suffer from vitiligo; fewer than 1% currently seek therapy as no treatments are approved

2-3 million vitiligo patients in the US

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)

Phase 3 program expected to start in 2019

Baseline

Week 8

Week 20

Opportunity for ruxolitinib cream

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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 20181

2011-2017 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.

1. 2019 expectations for R&D expense do not include impact of any business development transactions.

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Majority of 2019 Clinical Development Expense on Late-Stage Programs

Clinical development

Late-stage development

Estimated 2019 R&D expense allocation

Targeted therapy

Immunotherapy

Dermatology

Partnered

Recruit 3 key monotherapy trialsand continue combination strategy

Recruit 3 key monotherapy trialsand continue combination strategy

Novartis expected to submit NDA in NSCLC

FDA decision in SR-aGVHD

Report Phase 3 data in both SR-aGVHD and SR-cGVHD

Submit NDA for cholangiocarcinoma

Initiate first-line Phase 3 trials in bladder and cholangiocarcinoma

Initiate tumor-agnostic solid tumor trial

Report Phase 2 data in vitiligo, initiate Phase 3 program

Lilly expected to report Phase 3 data in atopic dermatitis

Report Phase 3 data in SN-aGVHD

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ruxolitinib cream

(JAK1/JAK2)

ruxolitinib(JAK1/JAK2)

INCMGA0012 (PD-1)

itacitinib (JAK1)


parsaclisib(PI3Kδ)

baricitinib2

(JAK1/JAK2)

1. Worldwide rights to capmatinib licensed to Novartis

2. Worldwide rights to baricitinib licensed to Lilly

capmatinib1

(MET)

2019 Newsflow for Key Development Projects

MSI-H endometrial cancer

Merkel cell carcinoma

Anal cancer

Follicular lymphoma

Marginal zone lymphoma

Mantle cell lymphoma

MET mutated NSCLC

Steroid-refractory aGVHD

Steroid-refractory cGVHDCholangiocarcinoma

Bladder cancer

8p11 MPN

Solid tumors

Atopic dermatitis

Vitiligo

Atopic dermatitis

Systemic lupus erythematosus

Alopecia areata

Steroid-naïve aGVHD

Steroid-naïve cGVHD

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ruxolitinib cream

(JAK1/JAK2)


INCMGA0012 (PD-1)

itacitinib (JAK1)


parsaclisib(PI3Kδ)

baricitinib2

(JAK1/JAK2)



capmatinib1

(MET)

Small molecules

AXL/MER, IDO1, ARG, PD-L1FGFR4, PIM, LSD1

Monoclonal antibodies

TIM-3, LAG-3, OX40, GITR

Bispecific antibodies

PD-L1 x CD137

Proof-of-concept Late-stage development

MSI-H endometrial cancer

Merkel cell carcinoma

Anal cancer

Follicular lymphoma

Marginal zone lymphoma

Mantle cell lymphoma

MET mutated NSCLC

Steroid-refractory aGVHD

Steroid-refractory cGVHDCholangiocarcinoma

Bladder cancer

8p11 MPN

Solid tumors

Atopic dermatitis

Vitiligo

Atopic dermatitis

Systemic lupus erythematosus

Alopecia areata

Steroid-naïve aGVHD

Steroid-naïve cGVHD

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ruxolitinib cream

(JAK1/JAK2)


INCMGA0012 (PD-1)

itacitinib (JAK1)


parsaclisib(PI3Kδ)

baricitinib2

(JAK1/JAK2)



capmatinib1

(MET)

Small molecules

AXL/MER, IDO1, ARG, PD-L1FGFR4, PIM, LSD1

Monoclonal antibodies

TIM-3, LAG-3, OX40, GITR

Bispecific antibodies

PD-L1 x CD137

Proof-of-concept Late-stage development

Preclinical profile comparable to anti-PD-L1 mAb

Unique mechanism of action:Internalizes PD-L1 on cancer and immune cellsFunctionally inhibits PD-1/PD-L1 axis signaling

First-in-human study initiated

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INCB86550 is an Oral, Small Molecule PD-L1 InhibitorAn opportunity to transform cancer immunotherapy

• Potential for differential clinical profile

• Benefits of oral administration

• Rapid dose titration

• Potential for all-oral combinations

Why is this important?

Confocal imaging of cells treated with INCB86550 shows time-dependent internalization of PD-L1 (green) over ~5 hours

0 min 285 min180 min135 min

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Connect with us:

[email protected]@Incyte

Discovering Medicines

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