Slide 1: IPH4102-101 First-in-Human Phase I Study in Relapsed/Refractory CTCL
IPH4102-101 FIH, OPEN LABEL, MULTICENTER PHASE I STUDY OF IPH4102, FIRST-IN-CLASS HUMANIZED ANTI-KIR3DL2 MAB, IN RELAPSED/REFRACTORY CTCL: PRELIMINARY SAFETY AND CLINICAL ACTIVITY RESULTS M. BAGOT, P. PORCU, C. RAM-WOLFF, M. VERMEER, M. KHODADOUST, M. DUVIC, S. WHITTAKER, S. MATHIEU, M. BATTISTELLA,
Slide 2: IPH4102-101 Study Design: Dose-Escalation & Schedule of Administration
IPH4102-101 STUDY DESIGN DOSE-ESCALATION & SCHEDULE OF ADMINISTRATION 3-6 pts Dose-escalation 3-6 pts Cohort expansion: (doses in mg/kg) 3-6 pts in subtypes of 3 pts CTCL patients. 4 pts RPh2D 3 pts for 3 pts Dataset cohorts 1 pt for this presentation 1 pt 1 pt 1st patient treated in Nov 2015; curre
Slide 3: Study Objectives
STUDY OBJECTIVES • Primary objective: to assess safety & tolerability of increasing IV doses of single agent IPH4102 by: > Characterizing the dose-limiting toxicities (DLT) and (S)AEs > Identifying the MTD or Recommended Phase 2 Dose (RP2D) • Secondary objectives: > To explore antitumor activity (re
Slide 4: Key Eligibility Criteria (Dose-Escalation Portion)
KEY ELIGIBILITY CRITERIA (DOSE-ESCALATION PORTION) • Key inclusion criteria > Patients with relapsed/refractory primary CTCL who have received at least 2 previous systemic antineoplastic therapies > For MF/SS patients: clinical stage ≥ IB > Centrally assessed KIR3DL2 expression (>5%) on malignant ce
Slide 5: Patient Disposition & Demographics
PATIENT DISPOSITION & DEMOGRAPHICS • Cut-off date September 10, 2016 • Dose cohorts 1-7 (0.0001 – 1.5 mg/kg) enrolled completely • Patients who received at least 1 dose are evaluable for safety • Patients who had a baseline and at least 1 disease assessment (W5) are evaluable for efficacy (Doses in
Slide 6: Baseline Disease Characteristics
BASELINE DISEASE CHARACTERISTICS 0.0001 0.001 0.01 0.05 0.2 0.75 1.5 All mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg Dose cohorts Patients (N) N=1 N=1 N=1 N=3 N=3 N=4 N=3 N = 16 CTCL Subtype MF 0 0 1 1 0 0 0 2 SS 1 1 0 2 2 4 3 13 CD4+ T Cell Lymphoma, NOS 0 0 0 0 1 0 0 1 Stage at screening IB 0 0 1 0
Slide 7: IPH4102-101 Preliminary Safety Results
IPH4102-101 PRELIMINARY SAFETY RESULTS 3RD WCCL, NY OCTOBER 28, 2016
Slide 8: Patient Exposure up to Sept 10th, 2016
PATIENT EXPOSURE UP TO SEPT 10TH, 2016 Number of administrations per level 0.0001 0.001 0.01 0.05 0.2 0.75 1.5 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg Pat ID (N=1) (N=2) (N=3) (N=6) (N=8) (N=11) (N=12) Total 01-001 5 2 3 3 3 1 1 18 01-003 5 3 3 1 12 01-004 7 3 4 2 1 17 11-005 9 4 2 1 16 11-006 7 7
Slide 9: Summary of Adverse Events (AE) as of September 10th 2016
SUMMARY OF ADVERSE EVENTS (AE) AS OF SEPTEMBER, 10TH 2016 • 88% of patients have experienced an AE over the TOTAL Patients AEs Related AEs duration of treatment N = 16 Patient # (%)-Event # Patient # (%)-Event # Any 14 (88%) – 87 6 (38%) – 20 • No related AE of grade 3 or higher were seen Grade 1 12
Slide 10: SAE Details
SAE DETAILS CTCAE Patient ID AE verbatim Grade Related Study day 01-001 SEPSIS STAPH. AUREUS 4 No 27 DYSPNEA 2 No 270 01-003 FEVER 1 No 92 SEPSIS STAPH. AUREUS 5 No 138 01-008 ATRIAL FLUTTER 2 Yes 1 PULMONARY ODEMA 2 No 15 ASTHMA DECOMPENSATION 2 No 174 11-015 HIP FRACTURE 3 No 6 Pt 01-008: • 88 y o
Slide 11: Related Adverse Events by SOC and Grade
RELATED ADVERSE EVENTS BY SOC AND GRADE (IN >1 PATIENT (6%)) All Patients N=16 Related Adverse Events • No related AE of All grades Grade 1 Grade 2 grade 3 or higher System Organ Class n (%) - event # n (%) - event # n (%) - event # All 6 (38%) - 20 6 (38%) - 13 3 (19%) - 7 • 1 patient experienced G
Slide 12: Preliminary Safety Conclusions
PRELIMINARY SAFETY CONCLUSIONS In this first in human study of IPH4102: • 16 patients were enrolled, treated at 7 dose levels (ranging from 0.0001 to 1.5 mg/kg) • All were evaluable for safety (range of administrations: 5 – 18) • 12 patients escalated IPH4102 dose at least once • 15 patients receive
Slide 13: IPH4102-101 Preliminary Clinical Activity Results
IPH4102-101 PRELIMINARY CLINICAL ACTIVITY RESULTS 3RD WCCL, NY OCTOBER 28, 2016
Slide 14: Preliminary Clinical Response Results (as of Sept 10th, 2016)
PRELIMINARY CLINICAL RESPONSE RESULTS (AS OF SEPT 10TH, 2016) All Patients Sézary Syndrome patients Best Global Best Global Best Best Best Response Response Response Response Response in Skin in Blood in LN N=16 n=13 n=13 n=13 n=9 Best Response (n) CR 0 0 2 3 0 PR 6 5 4 5 1 SD 10 8 7 5 5 PD 0 0 0 0
Slide 15: Timeline Plot for Individual Responses in Skin & Blood
TIMELINE PLOT FOR INDIVIDUAL RESPONSES IN SKIN & BLOOD Responses in skin Responses in blood There is a trend for dose-response relationship: • At lower dose-levels, responses seem to appear earlier in blood than responses in skin • All responses are still ongoing and some responses need to be confir
Slide 16: Representative Pictures
REPRESENTATIVE PICTURES Patient 01-001: • 80-year old female • Sézary Syndrome diagnosed in DEC 2013 • 2 lines of previous therapies (methotrexate and bexarotene) • T4NxM0B2 at study entry • Started at 0.0001 mg/kg on 18NOV15 progressively dose-escalated to all doses • Response in skin: PR at W22 (0
Slide 17: Representative Pharmacology Results
REPRESENTATIVE PHARMACOLOGY RESULTS Patient 11-017: Patient 11-005: • 69-year old male • 77-year old female • Sézary Syndrome diagnosed in APR 2012 • Sézary Syndrome diagnosed in NOV 2008 • 4 lines of previous therapies (incl. ECP + • 6 lines of previous therapies (incl. ECP + bexarotene + INFα, mog
Slide 18: Preliminary Clinical Pharmacokinetics
PRELIMINARY CLINICAL PHARMACOKINETICS IPH4102 concentration ( g/ml) So far, preliminary PK results fit the predictions (>Lower Limit Of Quantification, up to dose-level 1.5 mg/kg). 3rd WCCL - NY, October 28 2016 Page 18
Slide 19: Conclusion on Preliminary Safety and Clinical Activity
CONCLUSION ON PRELIMINARY SAFETY AND CLINICAL ACTIVITY • Sixteen patients were evaluable for safety and efficacy, including 13 SS, 2 MF and 1 CD4+ TCL NOS • IPH4102 is well tolerated with a good safety profile in an elderly and heavily pretreated patient population • The majority of AE is typical fo
Slide 20: Acknowledgements
AKNOWLEDGEMENTS Dpts of Dermatology & Pathology Stanford Cancer Institute (CA, USA) St Louis Hospital (Paris, France) Youn Kim Martine Bagot Michael Khodadoust Caroline Ram-Wolff Steve Mathieu Maxime Battistella Ohio State University (OH, USA) Pierluigi Porcu INSERM Unit 976 (Paris, France) Anne Mar