Slide 1: NC318, a Siglec-15 antibody, shows early evidence of disease control
NC318, a Siglec-15 antibody, shows early evidence of disease control in subjects with Siglec-15 positive advanced or metastatic solid tumors in Phase 1 & 2 studies Elaine Shum1, Han Myint2, Jahangheer S. Shaik2, Qinjie Zhou2, Emilia A. Barbu2, Aaron Morawski2, Hasan Abukharma2, Linda N. Liu2, Megan
Slide 2: Disclosure
DISCLOSURE • Elaine Shum o Consulting: AstraZeneca, Boehringer Ingelheim, Genentech (Roche) • Omid Hamid o Consulting/Advisory Boards: Aduro, Akeso, Amgen, Beigene, Bioatla, BMS, Genentech (Roche), GSK, Immunocore, Idera, Incyte, Janssen, Merck, NextCure, Novartis, Pfizer, Sanofi/Regeneron, Seattle
Slide 3: Introduction
INTRODUCTION • Siglec-15 (S15) is a member of the Siglec family (Sialic acid binding Immunoglobulin Lectins), a distinct subgroup of immunoglobulin (Ig) superfamily proteins involved in the discrimination of self and non-self immune regulation1. • S15 is an immune suppressor upregulated on various c
Slide 4: NC318: Mechanism of Action
NC318: MECHANISM OF ACTION S15 is Immunosuppressive in the Tumor Microenvironment NC318 Blocks Immunosuppressive Activity Induced by S15 S15 S15 S15 S15 Tumor M2 M2 macrophage Tumor Dead cell cell macrophage NC318 NC318 tumor cell OR Inactive OR T cell Myeloid Myeloid Tumor cell Increase in cell Pro
Slide 5: NC318 Phase 1 & 2 Study Design
NC318 PHASE 1 & 2 STUDY DESIGN Key Inclusion Criteria Phase 1 Dose Escalation Study Design • Men and women aged 18 or older • Phase 1: 3 + 3 Design 8 mg (n=4) o Subjects dosed every 2 weeks • ECOG performance status 0 to 1 o 28-day DLT period 24 mg (n=4) o Safety expansion enrolled additional subjec
Slide 6: NC318 Phase 1 & 2 Demographics
NC318 PHASE 1 & 2 DEMOGRAPHICS Demographic Information Phase 1 (n=49) Phase 2 (n=47) Age • Median 62 65 • Range (32 – 78) (36 – 86) Gender, n (%) • Female 28 (57%) 30 (64%) • Male 21 (43%) 17 (36%) Number of subjects with 32 (65%) 33 (70%) prior immunotherapy, n (%) Tumor Diagnoses • Lung (NSCLC; SC
Slide 7: Incidence of Treatment-Related Adverse Events ≥ 5%
INCIDENCE OF TREATMENT-RELATED ADVERSE EVENTS ≥ 5% Phase 1 (n=49) Phase 2 (n=47) Adverse Event1,2, n (%) Any Grade Grade 3-4 Any Grade Grade 3-4 Amylase Increased 4 (8.2) 1 0 0 Diarrhea 8 (16.3) 0 N/A N/A Fatigue 4 (8.2) 0 4 (8.5) 0 Headache 3 (6.1) 0 0 0 Infusion Related Reaction 5 (10.2) 0 9 (19.1
Slide 8: NC318 Showed Early Evidence of Disease Control in the Absence of S15 Selection
NC318 SHOWED EARLY EVIDENCE OF DISEASE CONTROL IN THE ABSENCE OF S15 SELECTION Complete Partial Stable Disease Progressive Total Efficacy mPFS4 in Tumor Response Response Disease Control Disease Evaluable Disease Diagnoses1 (CR) (PR) (SD) (DC) (PD) Subjects Control (n=1) (n=3) (n=28) (n=32; 37%) (n=
Slide 9: Progression-Free Survival in Subjects with Previously Treated Advanced Solid Tumors
PROGRESSION-FREE SURVIVAL (PFS) IN SUBJECTS WITH PREVIOUSLY TREATED ADVANCED SOLID TUMORS Progression-free Survival (%) CR+PR SD1 PD 100 • Median PFS of subjects across all tumor types in Disease Control (DC; CR+PR+SD) was 5.0 months. 50 • Median PFS of subjects from each group is as follows: o CR+P
Slide 10: Time to & Duration of Disease Control in Subjects with Previously Treated Advanced Solid Tumors
TIME TO & DURATION OF DISEASE CONTROL IN SUBJECTS WITH PREVIOUSLY TREATED ADVANCED SOLID TUMORS Lung CR Start PR Start SD Start On Study H&N Breast • To date, two subjects with Ovarian NSCLC (1CR and 1PR) remain on therapy for 2.8 and 2.3 years, respectively. Other1 Weeks 0 25 50 100 150 1SD subject
Slide 11: Retrospective Analysis of Biopsies: Selecting S15+ Subjects Might Have Predicted Better Disease Control
RETROSPECTIVE ANALYSIS OF BIOPSIES: SELECTING S15+ SUBJECTS MIGHT HAVE PREDICTED BETTER DISEASE CONTROL SD PD P = 0.0141 100 n=6 S15 n=9 (40%) S15 H Score3 Positive2 (60%) 50 n=3 (12%) S15 Negative 0 n=21 (88%) PD SD4 • 40% of S15+ subjects (H score ≥ 1) achieved stable disease (SD), whereas 12% of
Slide 12: Soluble S15 Level May Serve as a Marker for NC318 Activity
SOLUBLE S15 LEVEL MAY SERVE AS A MARKER FOR NC318 ACTIVITY PR SD PD • Patients treated with NC318 had soluble Soluble S15 Concentration1 (pg/ml) form of Siglec-15 (sS15) present in their serum. o After NC318 infusion, sS15 increased several fold compared to the baseline. • Progressive disease was se
Slide 13: Increasing the Dose of NC318 May Increase Drug Exposure ~10-Fold
INCREASING THE DOSE OF NC318 TO 800 mg Q1W MAY INCREASE DRUG EXPOSURE ~ 10-FOLD COMPARED TO 400 mg Q2W NC318 Area Under the Curve (AUC) by Dosing Schedule AUC Cumulative Exposure to NC318 6×10 6 400mg Modeled1 800mg 4×10 6 (ug*hr/ml) Observed 2×10 6 0 Q1W Q2W 1Modeled AUC was estimated based on a 75
Slide 14: Conclusion & Discussion
CONCLUSION & DISCUSSION • NC318 showed early evidence of clinical benefit in subjects with advanced or metastatic solid tumors in Phase 1 (with escalating dose) & Phase 2 studies (at 400 mg Q2W). o To date, 2 subjects with NSCLC remain on therapy for 2.8 and 2.3 years, respectively. o 13 out of 33 s
Slide 15: Acknowledgment
ACKNOWLEDGMENT • We would like to dedicate this presentation to all the brave patients. Without whom, this study and the data we have generated would not have been possible.