Slide 1: Incyte at ESMO 2024
Incyte at ESMO 2024 September 14, 2024
Slide 2: Welcome & Introduction
Welcome & Introduction Pablo Cagnoni President, Head of Research & Development
Slide 3: Forward Looking Statements
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 any discussion of the following: opportunities for near-term and future product and portfolio g
Slide 4: Incyte at ESMO 2024 Agenda
Incyte at ESMO 2024 Agenda Pablo J. Cagnoni, MD Welcome & introduction President, Head of Research & Development Sheela Rao, MBBS FRCP MD Phase 3 retifanlimab (Zynyz®) results in squamous Medical Oncologist, Royal Marsden Hospital cell carcinoma of the anal canal (SCAC) Rebecca Kristeleit, BSc MBChB
Slide 5: Near-Term Product Growth Opportunities and Differentiated Pipeline
Near-Term Product Growth Opportunities and Differentiated Pipeline with First-in-Class and/or Best-in-Class Potential Near-Term Launches IAI / Dermatology Oncology MPN / GVHD and Filings Axatilimab (anti-CSF1R) Povorcitinib (JAK1i) CDK2i Ruxolitinib XR (QD) Approved on August 14, Pivotal trial data
Slide 6: Niktimvo (Axatilimab-csfr) Approved for Chronic GVHD
Niktimvo (Axatilimab-csfr) Approved for Chronic GVHD Differentiated Mechanism of Action Responses in Fibrosis-Dominant Organs: by targeting CSF-1R esophagus, joints/fascia, lung and skin The Phase 2 study (AGAVE-201) met the primary 100 Esophagus Joints/Fascia Lungs Skin Response Rate, % efficacy en
Slide 7: Positive Pivotal Phase 3 Trial for Tafasitamab in FL/MZL
Positive Pivotal Phase 3 Trial for Tafasitamab for Patients with Follicular Lymphoma (FL)/Marginal Zone Lymphoma (MZL) Disease Characteristics Current SOC Future • FL most common indolent form • Treatment goal is to maintain Statistically significant and clinically meaningful improvement of B-cell N
Slide 8: Retifanlimab: A Practice-Changing Treatment for SCAC
Retifanlimab: A Practice-Changing Treatment for SCAC Featured during the Presidential Symposium at ESMO 2024 Squamous Cell Carcinoma of the Anal Canal First potential approved Statistically significant and clinically meaningful improvement in progression free survival (PFS) anti PD-1/PD-L1 inhibitor
Slide 9: CDK2 Inhibitor in Ovarian Cancer
CDK2 Inhibitor in Ovarian Cancer Opportunity to be first-in-class Potential to enhance outcomes and establish CCNE1 amplification and cyclin E overexpression INCB123667 as foundational treatment for in cancer cells is predictive of CDK2 dependency ovarian cancer • Meaningful tumor shrinkage observed
Slide 10: Sheela Rao, MBBS FRCP MD
Sheela Rao, MBBS FRCP MD Medical Oncologist specializing in gastrointestinal cancers and cancers of unknown primary within the Gastrointestinal Unit at the Royal Marsden Hospital, London, UK Reader at The Institute of Cancer Research Member of The International Rare Cancers Initiative - Anal Cancer
Slide 11: Rebecca Kristeleit, BSc MBChB PhD FRCP FRSB
Rebecca Kristeleit, BSc MBChB PhD FRCP FRSB Dr. Rebecca Kristeleit is Clinical Senior Lecturer and Consultant Medical Oncologist at University College London and University College London Hospitals NHS Foundation Trust Dr. Kristeleit specializes in the treatment of gynaecological cancers, including
Slide 12: Squamous Cell Carcinoma of the Anal Canal (SCAC)
Squamous Cell Carcinoma of the Anal Canal (SCAC) Sheela Rao, MBBS, FRCP, MD Medical Oncologist, Royal Marsden Hospital
Slide 13: Background
Background • SCAC is a neglected orphan disease; incidence is increasing ~3% per year mainly due to endemic HPV, the causative agent for most anogenital cancers1-4 – HIV is an important amplifier of SCAC; people with HIV are 25- to 35-fold more likely to develop SCAC5,6 • Relapse after primary thera
Slide 14: Epidemiology of Anal Cancer
Epidemiology of Anal Cancer Incidence Deaths U.S.1 EU2 U.S.1 EU2 Estimated new cases per year, n Estimated deaths per year, n 10,540 9,901 2,190 2,968 Annual growth rate for incidencea Annual growth rate for mortality +2.2% +5.1% Squamous Cell Anal Cancer (SCAC) accounts for ~ 85-90% of anal cancers
Slide 15: Current Treatment Landscape- U.S.
Current Treatment Landscape- U.S. Locoregional Diseaseb Metastatic Disease • 5-FU/mitomycin + RT Preferred regimen Re-evaluate and Treatmenta • Capecitabine/mitomycin + RT • Carboplatin + paclitaxel consider Primary • 5-FU/cisplatin + RT (category 2B) Other recommended regimens chemo/RT to the prima
Slide 16: Current Treatment Landscape- E.U.
Current Treatment Landscape- E.U. Stage I-III Cancer of the Anal Canal Stage IV Anal Cancerb • Mitomycin C + 5-FU [I, A] + RTa [III, B] First line: • Capecitabine replacing 5-FU [III, B] • Carboplatin/paclitaxel [I, B] Residual tumor: Complete response: Second line: • Surgery • Follow-up • Cisplatin
Slide 17: No Immunotherapy Approved
No Immunotherapy Approved 1L • No immunotherapy approved or recommended • NCCN Guidelines® recommend the use of three PD-1–directed mAbs (pembrolizumab, nivolumab, or retifanlimab-dlwr) for patients with 2L metastatic anal cancer who have progressed on 1L chemotherapy, if no prior immunotherapy was
Slide 18: HPV-Driven Cancers are Ideal Indications for PD-1 Targeted Therapy
HPV-Driven Cancers are Ideal Indications for PD-1 Targeted Therapy HPV shapes the tumor PD-1 therapy leads to HPV is tumor initiating immune microenvironment durable tumor control 18
Slide 19: POD1UM-303/InterAACT 2: Phase 3 Study of Retifanlimab
POD1UM-303/InterAACT 2: Phase 3 Study of Retifanlimab With Carboplatin-Paclitaxel in Patients With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal (SCAC) Not Previously Treated With Systemic Chemotherapy
Slide 20: POD1UM-303/InterAACT 2 Study Design
POD1UM-303/InterAACT 2 Study Design Patients with locally recurrent or metastatic SCAC Retifanlimab (iv, 500 mg q4w) • No prior chemotherapy except as radiosensitising (12 months) + standard-dose treatment or (neo) adjuvant therapy ≥6 months prior carboplatin–paclitaxel to study entry (6 months) • P
Slide 21: Patient Flow
Patient Flow Assessed for eligibility (N=376) Screening not completed due to other reasons (n=8) Enrolment Screen failures (n=60) Randomised 1:1 to intervention (full analysis set) (N=308) Retifanlimab + Chemotherapy (n=154) Placebo + Chemotherapy (n=154) Treated (n=154) Treated (n=152) Completed tr
Slide 22: Patient Demographics and Characteristics (ITT Population)
Patient Demographics and Characteristics (ITT Population) Placebo + Retifanlimab + Carboplatin–Paclitaxel Carboplatin–Paclitaxel Characteristic (n=154) (n=154) Median age, years 61 62 Female, % 77 68 White, % 89 86 Prior RT, % 73 68 Metastatic disease, %* 83 82 Liver, % 36 36 ECOG PS 0, % 56 53 HIV+
Slide 23: PFS by BICR (Primary Endpoint)
PFS by BICR (Primary Endpoint) 1.0 Placebo + Retifanlimab + Carboplatin–Paclitaxel Carboplatin–Paclitaxel 0.9 (n=154) (n=154) Median PFS 0.8 7.4 (7.1, 7.7) 9.3 (7.5, 11.3) (95% CI), months 0.7 HR (95% CI) 0.63 (0.47, 0.84) Probability of PFS P value* 0.0006 0.6 0.5 0.4 0.3 Treatment group 0.2 Retifa
Slide 24: OS (Interim Analysis)
OS (Interim Analysis) 1.0 Placebo + Retifanlimab + Carboplatin–Paclitaxel Carboplatin–Paclitaxel 0.9 (n=154) (n=154) Median OS 0.8 23.0 (15.1, 27.9) 29.2 (24.2, NE) (95% CI), months 0.7 HR (95% CI) 0.70 (0.49, 1.01) P value* 0.0273 Probability of OS 0.6 0.5 0.4 0.3 Treatment group 0.2 Retifanlimab P
Slide 25: OS Adjusted for Crossover
OS Adjusted for Crossover 1.0 Placebo + Retifanlimab + Carboplatin–Paclitaxel Carboplatin–Paclitaxel 0.9 (Adjusted; n=154) (n=154) Median OS 0.8 19.1 (13.4, 27.9) 29.2 (24.2, NE) (95% CI), months 0.7 HR (95% CI) 0.63 (0.44, 0.90) P value* 0.0055* Probability of OS 0.6 0.5 0.4 0.3 Treatment group 0.2
Slide 26: Secondary Endpoints by BICR
Secondary Endpoints by BICR* Placebo + Retifanlimab + Carboplatin–Paclitaxel Carboplatin–Paclitaxel (n=154) (n=154) ORR (95% CI), % 44 (36, 52) 56 (48, 64) CR, % 14 22 P=0.0129† Median DOR (95% CI), months 7.2 (5.6, 9.3) 14.0 (8.6, 22.2) DCR (95% CI), % 80 (73, 86) 87 (81, 92) *Results by BICR. †Nom
Slide 27: InterAACT vs POD1UM-303/InterAACT 2
InterAACT vs POD1UM-303/InterAACT 2 InterAACT 1 (Rao, 2020) POD1UM-303/InterAACT 2 Placebo + Retifanlimab + Treatment Carboplatin–Paclitaxel Carboplatin–Paclitaxel Carboplatin–Paclitaxel n 91 154 154 Participating countries UK, AU, Norway, US EU, AU, JPN, US, PR Demographics and disease characterist
Slide 28: Safety Summary
Safety Summary Placebo + Carboplatin–Paclitaxel Retifanlimab + Carboplatin–Paclitaxel Total Variable (n=152) (n=154) (N=306) Median treatment duration, months 6.8 7.4 7.2 Patients with any TEAEs, n (%) 152 (100) 154 (100) 306 (100) Patients with ≥ grade 3 TEAEs, n (%) 114 (75.0) 128 (83.1) 242 (79.1
Slide 29: TEAEs by Preferred Term
TEAEs by Preferred Term Most common (≥3%) grade 3 or higher TEAE Most common (≥2%) immune-related TEAE Placebo + Retifanlimab + Placebo + Retifanlimab + Carboplatin– Carboplatin– Carboplatin– Carboplatin– MedRA Preferred Paclitaxel Paclitaxel Total MedRA Preferred Paclitaxel Paclitaxel Total Term (n
Slide 30: Conclusions
Conclusions • This first and largest known phase 3 trial of a checkpoint inhibitor in SCAC, a disease with high unmet medical need, demonstrated benefit of addition of retifanlimab to standard of care chemotherapy • The study met its PFS primary endpoint: • 9.3 months with retifanlimab vs 7.4 months
Slide 31: Gynecologic Cancers
Gynecologic Cancers Rebecca Kristeleit, BSc MBChB PhD FRCP FRSB Consultant Medical Oncologist GSTT and Adjunct Reader (Associate Professor) KCL, London
Slide 32: Global Ovarian Cancer Epidemiology
Global Ovarian Cancer Epidemiology Ovarian Cancer is often diagnosed late/in advanced stages which shows poor survival outcomes Estimated Estimated Early stages have high 5-year survival rates compared to advanced stages number of number of 2022 new cases death cases 100% 90% (Incidence) (Mortalit
Slide 33: Clinical Course of Advanced Ovarian Cancer
Clinical Course of Advanced Ovarian Cancer • Treatment goal: Prevention of disease recurrence • Median Overall Survival ~5 years 1L 2L 3L 4L 5L 6L Surgery Chemotherapy mPFS ~18m mPFS ~10m mPFS ~6.5m mPFS ~5.5m mPFS ~4.5m mPFS ~4m Predictive Factors: Recurrence Recurrence Recurrence Recurrence Recurr
Slide 34: ESMO Treatment Algorithm: Newly Diagnosed & Recurrent Ovarian Cancer
ESMO Treatment Algorithm: Newly Diagnosed & Recurrent Ovarian Cancer Newly diagnosed EOC (FIGO stage III-IV) Recurrent EOC Low Likelihood of complete High Assessment of the following factors [I-II,A]: Unfit or not Cytoreduction [III,A] • Histotype • TFIp willing to • BRCA1/2 status • Potential for s
Slide 35: Cyclin E in Different Segments of Ovarian Cancer
Cyclin E in Different Segments of Ovarian Cancer • Approximately 50% of ovarian cancer patients have high Cyclin E protein expression 1 HRD FOLR+ • FOLR+ is 36% of PROC2 – 18.5% FOLR+ overlaps Cyclin E+ high3 – 32.5% of ovarian cancer is FOLR-negative HRD- and Cyclin E high3 CyclinE+ • HRD- is 52% o
Slide 36: Development Opportunity in HRD- Ovarian Cancer
Development Opportunity in HRD- Ovarian Cancer • In the 1L setting, most patients receive bevacizumab maintenance therapy • HRD- patients represent ~52% of 1L maintenance patient population1 • PFS in 1L maintenance for HRD- patients is significantly lower than for BRCA+ or HRD+ patients • Cyclin E p
Slide 37: Classes of Agents in Development in Ovarian Cancer
Classes of Agents in Development in Ovarian Cancer • Multiple targets: HER2, FR-alpha (luveltamab, mirv, FZEC), TROP2, CDH6, Napi2B Antibody Drug Conjugates • GLORIOSA Phase III mirv+bev vs bev maintenance in 2L PSOC DNA Damage • Next generation selective PARPi, ATRi, ATMi, Pol theta inhibition, Wee
Slide 38: Late-Stage Endometrial Cancer
Late-Stage Endometrial Cancer First-line Therapy1 Second-line Systemic Therapy Third-line Systemic Therapy Systemic therapy alone Receive 2L Systemic Therapy Receive 3L Systemic Therapy (40.8%) MSI-Low/ (40.2%) (33.2%) MSS/Untested Progress, untreated (15.5%) Progress, untreated (19.9%) Deceased (18
Slide 39: Opportunities for Development of CDK2 Inhibitor in Cyclin E Overexpressed Gynecologic Cancers
Opportunities for Development of CDK2 Inhibitor in Cyclin E Overexpressed Gynecologic Cancers Ovarian Cancer Endometrial Cancer Platinum Sensitive Platinum Resistant • 1st line maintenance • Monotherapy • 3rd line + • 2nd line maintenance • Future combinations • 1L/2L in combination with CPI/chemoth
Slide 40: INCB123667 – A Novel CDK2 Inhibitor
INCB123667 – A Novel CDK2 Inhibitor Ekaterine Asatiani Group Vice President & Head of Early Development
Slide 41: Role of CDK2/Cyclin E Complex in Normal and Cancer Cells
Role of CDK2/Cyclin E Complex in Normal and Cancer Cells • CDK2/cyclin E is crucial for cell cycle progression and DNA replication CDK4/6 P • Cancer cells with CCNE1 amplification/cyclin E1 Cyclin D P G0 phase RB P overexpression are dependent on CDK21 (resting) E2F P CDK2 RB • CCNE1 amplification a
Slide 42: INCB123667 has the Potential to be First-in-Class and Best-in-Class
INCB123667 has the Potential to be First-in-Class and Best-in-Class • Incyte's CDK2i has a competitive profile of on-target potency and selectivity • Incyte has first-in-class opportunity for CDK2i approval in Ovarian Cancer CDK2 Potency (IC50) Biochemical Selectivity CDK2i Asset Company Clinical St
Slide 43: Phase 1 Dose Escalation and Expansion Study (INCB123667-101)
Phase 1 Dose Escalation and Expansion Study (INCB123667-101) Part 1: INCB123667 Monotherapy Objectives 1a Dose Escalation 1b Dose Expansion Primary • Advanced/ Identification of • Documented CCNE1 amplification or centrally • Safety and ≥1 RDE(s) metastatic solid confirmed cyclin E1 overexpression (
Slide 44: Phase 1 Dose Escalation and Expansion Cohorts
Phase 1 Dose Escalation and Expansion Cohorts • 7 dose levels were explored using QD and BID schedules and total daily dose ranging from 50 to 150 mg • Currently 3 dose levels are expanded: • 50 mg BID, 100 mg QD, 125 mg QD in selected tumor types • Enrollment in combination cohorts has started Data
Slide 45: Treatment Related Adverse Events Reveal a Manageable Safety Profile
Treatment Related Adverse Events Reveal a Manageable Safety Profile • Only 3 patients (1.5%) discontinued INCB123667 due to TRAEs (asthenia, neutropenia and vomiting) • 11 patients (5.4%) had INCB123667 dose reductions due to TRAEs • 75 mg BID exceeded the MTD due to hematologic DLTs; QD dosing was
Slide 46: Strong Selective Inhibition of CDK2 Resulting in ctDNA Reduction
Strong Selective Inhibition of CDK2 Observed Resulting in ctDNA Reduction at All Dose Levels During Part 1a dose escalation, 30 out of 33 Cyclin E-positive patients by IHC had reductions in ctDNA 6000 CDK1 range between C1D1 and C2D1 CDK1 IC50 (mean±SD) (mean) Concentration (nmol/L) % Max Change ctD
Slide 47: Tumor Shrinkage Observed in Platinum-Resistant Ovarian Cancer Patients
Tumor Shrinkage Observed in Platinum-Resistant Ovarian Cancer Patients Dose Escalation and Dose Expansion, Ovarian Cancer Patients 100% (n=78)* 80% 60% 40% 20% Best % change in target lesion size 0% -20% -40% -60% -80% 50 mg BID 75 mg BID 75 mg QD 100 mg QD 125 mg QD 150 mg QD 150 mg QD intermittent
Slide 48: Efficacy in Dose Expansion - Ovarian Cancer Patients
Efficacy in Dose Expansion - Ovarian Cancer Patients • Three dose levels expanded in Dose Expansion: 50mg BID (n=16), 100mg QD (n=11) and 125mg QD (n=10) • Sixteen patients are still ongoing, 7 in each QD schedule and 2 patients ongoing in 50 mg BID • Median of 3 prior lines of therapy (range: 1-4)
Slide 49: Dose Expansion: Ovarian Cancer Efficacy Responders
Dose Expansion: Ovarian Cancer Efficacy Responders (CR+PR) at 50 mg BID, 100 mg QD, 125 mg QD Majority of ovarian cancer patients in expansion with either CR, PR or SD remain ongoing 2 patients with Complete Response (CR) - 1 patient ongoing * 7 patients with Partial Response (PR) - 5 patients ongoi
Slide 50: Tumor Shrinkage Observed in Endometrial Cancer Patients
Tumor Shrinkage Observed in Endometrial Cancer Patients Dose Escalation and Dose Expansion, Endometrial Cancer Patients 100% (n=11)* Best % change in target lesion size 80% 60% 40% SD 20% PD PD SD PD PDa PR PR PR SDb PR 0% -20% -40% -60% -80% -100% 50 mg BID 125 mg QD 150 mg QD Cyclin E1 expression
Slide 51: Favorable Safety Profile and Anti-Tumor Activity in Phase 1/2 Trial
Favorable Safety Profile and Anti-Tumor Activity in Phase 1/2 Trial Incyte’s CDK2i is generally well tolerated in patients with advanced/metastatic solid tumors up to a total daily 1 dose of 125 mg – low incidence of discontinuation was observed The most common treatment related AEs are nausea, thro
Slide 52: CDK2i Development Plan
CDK2i Development Plan Steven Stein Chief Medical Officer
Slide 53: PSOC Competitive Landscape: 1L Maintenance for HRD-
PSOC Competitive Landscape: 1L Maintenance for HRD- (BRCA WT) Consists Of Bevacizumab or Niraparib Utilization of Maintenance Therapy Following Bevacizumab-Based Induction, Stages II-IV, • HRD- represents ~52% of 1L maintenance1 Ovarian Cancer, U.S., 2023 (Table 18)* – ~22k patients in US, EU5, and
Slide 54: PROC Competitive Landscape
PROC Competitive Landscape: Various Single-agent Chemotherapies and Bevacizumab-Based Regimens Are Commonly Used Third-Line Systemic Therapy, Stages II-IV • Unmet need remains high in platinum resistant ovarian cancer with Ovarian Cancer, U.S., 2024 (Table 30)a an estimate survival of ~12 months • C
Slide 55: CDK2i: Potential Registration Scenarios Ovarian Cancer
CDK2i: Potential Registration Scenarios Ovarian Cancer – Study Designs (Regulatory Feedback Pending) Clinical Setting Line of Primary # Study Design Phase Treatment arms Data (Cyclin E1+ by IHC) Therapy Endpoint Expand current study or Platinum Resistant Ovarian Cancer 1 Single Arm Monotherapy 2 2-4
Slide 56: Summary and Outlook
Summary and Outlook Based on these encouraging Phase 1 results and pending regulatory feedback, Incyte plans to: Incyte’s CDK2i has shown clinical activity and ctDNA decreases, especially in ovarian cancer Initiate a pivotal study with CDK2i 1 monotherapy in Cyclin E1High PROC Incyte’s CDK2i indicat
Slide 57: Closing Remarks
Closing Remarks Pablo Cagnoni President, Head of Research & Development
Slide 58: Meaningful Upcoming Near-Term Catalysts
Meaningful Upcoming Near-Term Catalysts 2H 2024 1H 2025 2H 2025 Axatilimab 3L+ cGVHD PDUFA MPN / GVHD BETi P1 data & pivotal study plans ALK2i P1 data mCALR P1 PoC data JAK2V617Fi P1 MF data Retifanlimab P3 data (NSCLC & SCAC) SCAC/NSCLC approval Oncology Tafasitamab P3 data (FL/MZL) P3 data (1L DLB
Slide 59: New Molecular Entities Driving Portfolio Growth
New Molecular Entities Driving Portfolio Growth mCALR (MPN/GVHD) MRGPRX2 (Dermatology/IAI) MRGPRX4 (Dermatology/IAI) TGFßR2×PD-1 (Oncology) JAK2V617Fi (MPN/GVHD) Tafasitamab (FL/MZL) Jakafi XR KRASG12D (Oncology) (MPN/GVHD) (Oncology) Retifanlimab (SCAC) CDK2i BETi (Oncology) (Oncology) (MPN/GVHD) N
Slide 60: Potential High Impact Launches by 2030
>10 Potential High Impact Launches by 2030 Product Indication Status 2024 2025 2026 2027 2028 2029 2030+ Pediatric AD Phase 3 Prurigo Nodularis Phase 3 Ruxolitinib HS (mild/mod) Phase 3* Cream Dermatology/IAI Lichen Planus Phase 2 Lichen Sclerosis Phase 2 HS (mod/sev) Phase 3 Povorcitinib Vitiligo P
Slide 61: Q&A
Q&A
Slide 62: Solve On.
Solve On.