Slide 1: Next Generation Immunomedicines March 2022
Next Generation Immunomedicines March 2022
Slide 2: Forward-Looking Statements
PROPRIETARY AND CONFIDENTIAL 2 2 Forward - Looking Statements This presentation contains forward - looking statements, including statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . These statements are based on current expectations, forecasts,
Slide 3: NextCure Highlights
PROPRIETARY AND CONFIDENTIAL 3 3 3 • NC318 (S15): Phase 2 monotherapy & combo therapy • NC410 (LAIR - 2): Phase 1 monotherapy • NC762 (B7 - H4): Phase 1 monotherapy • NC525 (LAIR - 1): IND Q4 2022 PIPELINE Progress • Patient selection increasing probability of success • Biomarkers for detecting earl
Slide 4: Significant Momentum & Milestones in 2022
PROPRIETARY AND CONFIDENTIAL 4 4 NC318, NC410, NC762 On Track BUILDING PIPELINE Momentum RUNWAY Q1 2024 EXPERIENCED Team Significant Momentum & Milestones in 2022
Slide 5: Advancing Product Development Pipeline
PROPRIETARY AND CONFIDENTIAL 5 5 Advancing Product Development Pipeline PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT MILESTONE PRODUCT CANDIDATES NC318 S15 Tumors and macrophages Phase 2 update Q4 2022 NC318 Anti - PD - 1 Combo* S15 Tumors and macrophages Initial Data 2H
Slide 6: Product Development: Getting it Right
PROPRIETARY AND CONFIDENTIAL 6 6 Product Development: Getting it Right Patient Selection Biomarkers Combos Triangulation Strategy Unmet Needs of Cancer Patients • Non - Responders • Rapid Progression • Limited Treatments We Need New Solutions
Slide 7: NC318 Humanized Siglec-15 (S15) Monoclonal Antibody
PROPRIETARY AND CONFIDENTIAL 7 7 NC318 Humanized Siglec - 15 (S15) Monoclonal Antibody Phase 2 CLINICAL TRIALS BIOLOGY MOA HIGHLIGHTS • NSCLC, Breast, H&N • Evidence of disease control • Evidence of enhanced outcomes in S15+ patients Suppressed T Cell • Decreases suppressive myeloid cells & pro - tu
Slide 8: NC318 Mechanism of Action
PROPRIETARY AND CONFIDENTIAL 8 8 NC318 Mechanism of Action Tumor cell Inactive T cell Distinct S15 - induced myeloid cells M2 macrophage Myeloid cell Immunosuppression and tumor growth Increase in inflammatory cytokines Differentiation and survival OR S15 S15 Tumor cell M2 macrophage Myeloid cell OR
Slide 9: Time to & Duration of Disease Control
PROPRIETARY AND CONFIDENTIAL 9 9 Time to & Duration of Disease Control 1 SD subjects in other types of cancer include Esophageal cancer (n=1), Endometrial cancer (n=1), Hepatocellular carcinoma (n=1), Melanoma (n=3), Merkel cell carcinoma (n=1), and SCC/Basaloid (n=1). 0 150 25 50 100 Weeks H&N Brea
Slide 10: Analysis in All Patients: Early Evidence of Disease Control
PROPRIETARY AND CONFIDENTIAL 10 10 Analysis in All Patients: Early Evidence of Disease Control Without S15 Selection in Ph1 & Ph2 Cancer Types Responses n=32 Disease Control ( CR+PR+SD ) n=32 (37%) Progressive Disease (n=54) Total Evaluable Subjects (n=86) 2 mPFS in Disease Control (5.0 months) Lung
Slide 11: Retrospective Analysis: Disease Control Rate Increased in S15+ Patients
PROPRIETARY AND CONFIDENTIAL 11 11 Retrospective Analysis: Disease Control Rate Increased in S15+ Patients Subjects treated with NC318 (n=96) IHC available & evaluable (n=39) n=9 n=30 S15 Positive 1 (n=15) S15 Negative (n=24) n=3 n=21 n=6 n=9 • Lung = 5 • Other = 3 • Breast = 1 • Lung = 3 • Other =
Slide 12: NC318 Restores Immune Function in a Highly Suppressive TME
PROPRIETARY AND CONFIDENTIAL 12 12 NC318 Restores Immune Function in a Highly Suppressive TME UPCOMING MILESTONES Amended Phase 2 • S15+ selection (CLIA assay) • 800 mg Q1W: drug exposure • NSCLC, H&N and breast • Update 4Q 2022 Yale Phase 2 (Combo) NSCLC • Mono therapy: PD - 1 refractory • Pembro c
Slide 13: NC410 LAIR-2 Collagen-Binding Fusion Protein Decoy
PROPRIETARY AND CONFIDENTIAL 13 13 NC410 LAIR - 2 (Collagen - Binding) Fusion Protein Decoy BIOLOGY MOA HIGHLIGHTS Phase 1/2 CLINICAL TRIAL • Targets LAIR - 1/LAIR - 2 pathway • Enhances T cell infiltration and tumor killing • Patient selection assay • Evidence of immune activation • Synergistic com
Slide 14: Scientific Advancement in Understanding Collagen Biology
PROPRIETARY AND CONFIDENTIAL 14 14 Scientific Advancement in Understanding Collagen Biology Elevated collagen correlates with PD - 1/ PD - L1 resistance Changes in collagen expression correlate with worse prognosis LAIR - 2 & NC410 sensitizes tumors 2020 2019 2019 2021 collagen collagen Collagen col
Slide 15: NC410 Mechanism of Action
PROPRIETARY AND CONFIDENTIAL 15 15 NC410 Mechanism of Action Tumor - specific Collagen NC410 Collagen is Immunosuppressive NC410 Normalizes Immune System Remodeled Collagen NC410 Infiltration Inhibited T Cell Activated T Cells • Physical barrier; excludes T cell from TME • Inhibits T cells Dead tumo
Slide 16: NC410: Key to Unlock TME and Normalize Immune Response
PROPRIETARY AND CONFIDENTIAL 16 16 NC410: Key to Unlock TME and Normalize Immune Response TME ACCESS LOCKED NC410 UNLOCKS ECM REMODELING & NORMALIZATION Inactive T cell Many “keys” but none fit lock Enhances T cell infiltration Activated T cell Activated T cells kill tumor
Slide 17: NC410 Safety & Early Efficacy Data from Cohorts 1-5
PROPRIETARY AND CONFIDENTIAL 17 17 NC410 Safety & Early Efficacy Data from Cohorts 1 - 5 • 5 SD subjects had time - on - study up to 42, 25+, 20, 16 and 16, respectively • 3 active subjects ongoing: one at 25+ and two at 5+ weeks • 3+3 design • Dosing every 2 weeks • Solid tumors • No DLTs through c
Slide 18: NC410 Demonstrates Synergistic Activity in Preclinical Models
PROPRIETARY AND CONFIDENTIAL 18 18 NC410 Demonstrates Synergistic Activity in Preclinical Models PD - L1 PD - L1 TGF - β TRAP 0 10 20 30 40 0 400 800 1200 1600 2000 Days Post Tumor Injection T u m o r V o l u m e ( m m 3 ) NC410 -PD-L1 Control Combination Horn et al., SITC 2020
Slide 19: NC410 Remodels ECM Enhancing Immune Infiltration & Tumor Killing
PROPRIETARY AND CONFIDENTIAL 19 19 NC410 Remodels ECM Enhancing Immune Infiltration & Tumor Killing Phase 1 monotherapy update 2H 2022 UPCOMING MILESTONE NC410 appears safe and well tolerated with no DLTs up to cohort 5; dose escalation continues Binding to C1q and collagen, modulates and restores i
Slide 20: NC762 Humanized B7-H4 Monoclonal Antibody
PROPRIETARY AND CONFIDENTIAL 20 20 NC762 Humanized B7 - H4 Monoclonal Antibody BIOLOGY MOA HIGHLIGHTS Phase 1/2 CLINICAL TRIAL • Initiated Phase 1 trial • IHC assay for patient selection • Biomarkers • AACR 2021 poster • Initial Phase 1 data 2H 2022 • Unique mechanism of action • Inhibits tumor cell
Slide 21: NC762 Inhibits Human Melanoma Tumor Growth In Vivo
PROPRIETARY AND CONFIDENTIAL 21 21 NC762 Inhibits Human Melanoma Tumor Growth In Vivo Activity Enhanced by Human PBMCs TUMOR INHIBITION 0 10 20 30 40 0 500 1000 1500 2000 2500 Days post inoculation T u m o r V o l u m e ( m m 3 ) PBS NC762 NC762.FES **** **** **** **** *** *** Control NC762 NC762.FE
Slide 22: NC762 Summary & Upcoming Milestones
PROPRIETARY AND CONFIDENTIAL 22 22 NC762 Summary & Upcoming Milestones Unique MOA • mAb inhibits tumor cell growth • Not dependent on immune cell infiltration into TME • NK cells enhance activity IND filed with FDA Initiated Phase 1 trial UPCOMING MILESTONE Initial Phase 1 data 2H 2022 SUMMARY
Slide 23: New Program - NC525 (LAIR-1 mAb)
PROPRIETARY AND CONFIDENTIAL 23 23 New Program - NC525 (LAIR - 1 mAb) BIOLOGY MOA UPDATE • LAIR - 1 expression ‒ High on AML blasts and leukemia stem cells (LSCs) ‒ Minimal on hematopoietic stem and progenitor cells ( HSPCs ) NC525 IND Q4 2022 • Inhibits colony formation of AML LSCs in vitro • Inhib
Slide 24: Finding Solutions with a Powerful Discovery Engine
PROPRIETARY AND CONFIDENTIAL 24 24 Finding Solutions with a Powerful Discovery Engine F unctional, I ntegrated, N extCure D iscovery in I mmuno - O ncology • T cell activation • Cytokine release • Proliferation • Apoptosis • Effector function • Pathway reporters FUNCTIONAL READOUTS • Primary • Cell
Slide 25: GMP Manufacturing Facility: Benefits of Added Capacity
PROPRIETARY AND CONFIDENTIAL 25 25 GMP Manufacturing Facility: Benefits of Added Capacity Operational and capital efficiency Speed Flexibility Quality Use of a CMO adds ~ 8 months to timelines Efficiency Prioritization and scheduling Controlling quality with experienced team 2,000L Capacity Utilized
Slide 26: Advancing Product Development Pipeline
PROPRIETARY AND CONFIDENTIAL 26 26 Advancing Product Development Pipeline PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT MILESTONE PRODUCT CANDIDATES NC318 S15 Tumors and macrophages Phase 2 update Q4 2022 NC318 Anti - PD - 1 Combo* S15 Tumors and macrophages Initial Data 2
Slide 27: Significant Momentum & Milestones in 2022
PROPRIETARY AND CONFIDENTIAL 27 27 Significant Momentum & Milestones in 2022 ON TRACK NC318, NC410, NC762 MOMENTUM Building Pipeline Q1 2024 Runway TEAM Experienced