Slide 1: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab
COM701 DEMONSTRATES ANTITUMOR ACTIVITY AS MONOTHERAPY AND IN COMBINATION WITH NIVOLUMAB IN PATIENTS WITH ADVANCED MALIGNANCIES Ryan J Sullivan, MD Assistant Professor, Medicine, Harvard Medical School and Assistant Professor, Hematology/Oncology, Massachusetts General Hospital. Boston, MA Ryan Sulli
Slide 2: Disclosures
DISCLOSURES • Consulting/Advisor for Bristol Myers Squibb, Merck, Novartis, Replimune • Research funding from Merck, Amgen 2 2 Ryan J Sullivan, MD et al: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies, AACR 2020
Slide 3: Introduction
INTRODUCTION • There is a high unmet medical need for the treatment of patients who are refractory to or relapse following treatment with checkpoint inhibitors • Inhibition of poliovirus receptor related immunoglobulin domain containing (PVRIG) leads to enhanced activation of T and NK cells, and res
Slide 4: PVRIG Pathway in the DNAM Axis
PVRIG PATHWAY IN THE DNAM AXIS Potential Molecular Interactions Between PVRIG/TIGIT and PD-1 Pathways Support Combination Approach to Overcome Immunotherapy Resistance COM701 PVRIG TUMOR CELL T CELL TUMOR CELL or APC PVRL2 - or APC PD-1 + - DNAM PD-L1 - PVR TIGIT COM902 Biomarker and Biology - Drive
Slide 5: PVRIG Knockout or Inhibition Reduces Tumor Growth in Combination with PD-L1 or TIGIT in Mouse Models
PVRIG KNOCKOUT OR INHIBITION REDUCES TUMOR GROWTH IN COMBINATION WITH PD-L1 OR TIGIT IN MOUSE MODELS PVRIG KO MICE (MC38) anti-PVRIG + anti-PD-L1 (CT26) PVRIG + TIGIT Double KO (B16) Control IgG Wild-type Mean Tumor Volume (mm3 ) 2500 WT a PD-L1 PVRIG -/- KO WT + αPD-L1 a PD-L1+ a-mPVRIG TIGIT -/- 2
Slide 6: Study Design
STUDY DESIGN PHASE 1 (Identifier: NCT03667716) PHASE 1/2 (in development) Study Objectives Arm A • Safety & Tolerability Monotherapy Monotherapy • PK/PD Triple Combination Dose Escalation Dose Escalation Cohort Expansion • Clinical activity – COM701 Escalating doses of COM701 with fixed doses of (20
Slide 7: Patient Baseline Characteristics
PATIENT BASELINE CHARACTERSTICS Parameter Arm A (COM701 monotherapy) Arm B (COM701 + nivolumab) N=16 N=12 Sex, F (n) 9 9 Age ≤ 65 yrs (n) 13 7 Median prior therapies (range) 6 (2, 15) 4 (2, 12) ECOG (0, 1) 0 8 3 CRC (6), PDAC (2), ovarian/PPSC (2), Endometrial (3), CRC (2), NSCLC (2), NSCLC (1), ade
Slide 8: Patient Disposition Summary
PATIENT DISPOSITION SUMMARY Arm A (COM701 Parameter Arm B (COM701 + nivolumab) monotherapy) N=12 N=16 Number of DLTs 0 0 Number of patients continuing on study treatment 2 6 Number of patients treated at IV Q4 wks schedule (dose) 3 (20 mg/kg) 3 (10 mg/kg + nivolumab 480 mg) Number of patients contin
Slide 9: Dose Escalation Schema
DOSE ESCALATION SCHEMA Arm A: COM701 monotherapy 20** 10*/** 3* 1* 0.3* 0.1* Arm B: COM701 + nivolumab 0.03* IV Q3 wks*, (for Arm B Nivolumab 360mg) 0.01* IV Q4 wks**, (for Arm B Nivolumab 480mg) DLTs – within 21 or 28 days window in 1st cycle based on dosing schedule of study drugs www.cgen.com I 9
Slide 10: Summary of Adverse Events – Safety Analysis Set
SUMMARY OF ADVERSE EVENTS – SAFETY ANALYSIS SET Parameter Arm A Arm B Dose escalation (All patients) N= 18 N=13 n (%) n (%) Any TEAE (n, %) 17 (95) 13 (100) ≤G2 10 (56) 7 (54) G3 6 (33) 5 (38) G4 - - Grade 5 1* (6) 1** (8) AE leading to study treatment discontinuation 5 (28) - Any SAE (n, %) 7 (39)
Slide 11: Summary of Serious Adverse Events Leading to Study Treatment Discontinuation
SUMMARY OF SERIOUS ADVERSE EVENTS LEADING TO STUDY TREATMENT DISCONTINUATION Subject ID (Arm) Tumor type Adverse event Relatedness (per investigator assessment) 801 (A) Pancreatic cancer Cardiac arrest (G5) Related to disease 4 (A) Pancreatic cancer Vomiting (G3) Related to disease 13 (A) CRC Pulmon
Slide 12: Incidence of Treatment Emergent Adverse Events in ≥3 Patients - Monotherapy
INCIDENCE OF TREATMENT EMERGENT ADVERSE EVENTS (TEAE) IN ≥3 PATIENTS - MONOTHERAPY Preferred Term Grade 1/2 Grade 3/4/5* All Grades N (%) N (%) N (%) Any TEAE 10 (56) 7 (39) 17 (95) Fatigue 7 (39) - 7 (39) Nausea 5 (28) - 5 (28) Anxiety 4 (22) - 4 (22) Diarrhea 3 (17) 1 (5) 4 (22) Dyspnea 3 (17) 1 (
Slide 13: Incidence of TEAEs in ≥3 Patients – Combination Therapy
INCIDENCE OF TEAEs IN ≥3 PATIENTS – COMBINATION THERAPY Preferred Term Grade 1/2 Grade 3/4/5* All Grades N (%) N (%) N (%) Any TEAE 7 (54) 6 (46) 13 (100) Fatigue 5 (39) - 5 (39) Anemia 3 (23) 1 (7) 4 (31) Constipation 3 (23) - 3 (23) Nausea 2 (15) 1 (8) 3 (23) Oedema peripheral 3 (23) - 3 (23) Safe
Slide 14: Incidence of Serious TEAEs in All Patients - Monotherapy
INCIDENCE OF SERIOUS TEAEs IN ALL PATIENTS - MONOTHERAPY (N = 18) Preferred Term Grade 1/2 Grade 3/4/5# All Grades N (%) N (%) N (%) Any serious TEAE 1 (6) 6 (33) 7 (39) Ascites* - 1 (11) 1 (11) Abdominal pain* - 1 (6) 1 (6) Atrial fibrillation* - 1 (6) 1 (6) Blood bilirubin increased* 1 (6) - 1 (6)
Slide 15: Incidence of Serious TEAEs in All Patients - Combination
INCIDENCE OF SERIOUS TEAEs IN ALL PATIENTS - COMBINATION (N = 13) Preferred Term Grade 1/2 Grade 3/4/5* All Grades N (%) N (%) N (%) Any serious TEAE 1 (8) 4 (31) 5 (39) Pulmonary embolism* - 2 2 (15) Hypokalaemia* - 1 (8) 1 (8) Malignant neoplasm - 1 (8) 1 (8) progression* Pyrexia* 1 (8) - 1 (8) Sa
Slide 16: COM701 PK Profile Following IV Infusion at Cycle 1 Day 1 - Arms A and B
COM701 PK PROFILE FOLLOWING IV INFUSION AT CYCLE 1 DAY 1 - ARMS A and B www.cgen.com I 16 Ryan J Sullivan, MD et al: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies, AACR 2020 16
Slide 17: Summary of Investigator-Assessed Response (per RECIST v1.1)
SUMMARY OF INVESTIGATOR-ASSESSED RESPONSE (per RECIST v1.1 DLT-EVALUABLE POPULATION) Arm A (N = 16) Arm B (N = 12) N (%) N (%) ORR (CR+PR) 1 (6) 1 (8) Disease control rate (CR+PR+SD) 11 (69) 9 (75) Durable SD (SD ≥ 6 months) 2 (13) 4 (33) Best response CR 0 0 PR 1 (6) 1 (8) SD 10 (63( 8 (67) PD 4 (2
Slide 18: Swimmer Plot – Arm A
SWIMMER PLOT – ARM A Data cut www.cgen.com I 18 Ryan J Sullivan, MD et al: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies, AACR 2020 18
Slide 19: Swimmer Plot – Arm B
SWIMMER PLOT – ARM B www.cgen.com I 19 Ryan J Sullivan, MD et al: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies, AACR 2020 19
Slide 20: Waterfall Plot
WATERFALL PLOT www.cgen.com I 20 Ryan J Sullivan, MD et al: COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies, AACR 2020 20
Slide 21: COM701 + Nivolumab – Confirmed PR in a Patient with MSS Colorectal Cancer
COM701 + NIVOLUMAB – CONFIRMED PR IN A PATIENT WITH MSS COLORECTAL CANCER (ONGOING STUDY TREATMENT 44 WKS) 66 year old male with metastatic CRC (MS Stable), with KRAS mutation 4 prior lines of chemotherapy; Best response of PD to anticancer therapy prior to study enrollment Study Treatment: COM701 0
Slide 22: COM701 Monotherapy – Confirmed PR in a Patient with MSS Platinum Resistant Primary Peritoneal Cancer
COM701 MONOTHERAPY – CONFIRMED PR IN A PATIENT WITH MSS PLATINUM RESISTANT PRIMARY PERITONEAL CANCER ONGOING STUDY TREATMENT 25 WKS 63 year old female with microsatellite stable platinum resistant primary peritoneal cancer. PDL1 negative, MRE11 mutation; 3 prior lines of chemotherapy Study Treatment
Slide 23: Conclusion
CONCLUSION • COM701 well tolerated and with a manageable safety profile as monotherapy and in combination with nivolumab - No increase in toxicity in combination with nivolumab - No subjects discontinued study treatment due to toxicity of any study drug • Single-agent MTD COM701 20 mg/kg IV Q4 wks;
Slide 24: Acknowledgment
ACKNOWLEDGMENT • We thank the patients for participating in this clinical trial and their families • The investigators and their staff at the clinical trial sites • Study Sponsor – Compugen Ltd in collaboration with Bristol-Myers Squibb www.cgen.com I 24 Ryan J Sullivan, MD et al: COM701 Demonstrate