Nextcure, Inc. · NASDAQ:NXTC
Nextcure — Investor Presentation (March 2024)
38 slides from Nextcure's investor presentation, Mar 21, 2024
Slide 1: Corporate Presentation
Corporate Presentation NASDAQ: NXTC MARCH 2024
Slide 2: Forward-Looking Statement
Forward-Looking Statement 2 To the extent that statements contained in this presentation are not descriptions of historical facts, they may be deemed to be forward-looking statements under the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations, forec
Slide 3: Focus on Two Promising Programs
3 Focus on Two Promising Programs • Early Clinical Responses in Ovarian & CRC • Additional Clinical Data Expected 2024 NC410 COMBO LNCB74 • Differentiated B7-H4 ADC • Collaboration with LegoChem Biosciences • IND 2024 $108 M - RUNWAY THROUGH 2H 2026
Slide 4: Advancing Our Prioritized Programs
Advancing Our Prioritized Programs 4 PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT MILESTONE NC410 COMBO (Pembro) LAIR-2 Extracellular Matrix Ph1b Data 2H 2024 Ph1b Data 2Q 2024 LNCB74 (ADC) B7-H4 Tumor Cells IND 4Q 2024 Colorectal (CRC) Ovarian Co-development with Breast,
Slide 5: NC410 Combo
5 NC410 COMBO BUILDING ON CLINICAL RESPONSES & BIOMARKER OBSERVATIONS PH1B DATA 2H 2024 Ovarian CANCER Colorectal CANCER PH1B DATA 2Q 2024
Slide 6: Addressing Unmet Needs for Non-Responders
6 POTENTIALLY FIRST-IN-CLASS Improved safety profile Addresses tumor resistance LARGE UNMET NEEDS Ovarian cancer Colorectal cancer DEEP EXPERTISE Extracellular matrix collagen drives tumor resistance DIFFERENTIATED APPROACH Remodeling tumor architecture removing physical barrier and allowing T cells
Slide 7: Leader in Understanding LAIR & Extracellular Matrix (ECM) Biology
Leader in Understanding LAIR & Extracellular Matrix (ECM) Biology 7 Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix An Emerging Area of Interest for New Therapies Collagen Fragments Produced in Cancer Mediate T Cell Suppression Through Leukocyte-Associated I
Slide 8: NC410 Combo
NC410 Combo Overcoming tumor resistance by remodeling ECM to remove physical barrier and enhance T cell tumor killing 8 ✓ Safe & well tolerated ✓ No dose limiting toxicities ✓ Evidence of clinical activity in ovarian & colorectal • Expansion of ovarian & colorectal cohorts • 2024 anticipated data (o
Slide 9: NC410 Combo: A Synergistic Approach to Breaking the Collagen Barrier
NC410 Combo: A Synergistic Approach to Breaking the Collagen Barrier and Enhancing Anti-Tumor Activity 9 Inhibited T cell Tumor cells Excluded from the tumor COLLAGEN BUILDUP AND DENSITY LEAD TO RESISTANCE Collagen Efficacy Tumor cells proliferate and become resistant T cells kill the tumor ECM REMO
Slide 10: Ovarian Cancer: NC410 Combo Phase 1b Findings
NEXT STEPS POPULATION 10 NC410 Combo Phase 1 Study PD-(L)1 Naïve DOSE & REGIMEN FINDINGS TO DATE Additional ~18 patients being added to confirm clinical activity DATA EXPECTED 2H 2024 Ovarian CANCER 100 mg NC410 Q2W 400 mg pembro Q6W 200 mg NC410 Q2W 400 mg pembro Q6W ORR 42.8% (3/7) DCR 42.8% (3/7)
Slide 11: Evidence of Peripheral Immune Modulation and TME Infiltration in Responders
Evidence of Peripheral Immune Modulation and TME Infiltration in Responders from Ovarian Cohort 11 • Remodels ECM allowing effector immune cell infiltration into TME from periphery Decrease Granzyme B-expressing CD8+ T cells Decrease suppressive MDSCs Decrease CCR7+ CD4+ T cells • Reduces suppressiv
Slide 12: Colorectal Cancer: NC410 Combo Phase 1b Findings
NEXT STEPS POPULATION NC410 Combo Phase 1 Study 12 PD-(L)1 Naïve, MSS/MSI-L*, without Liver Metastasis Colorectal CANCER DOSE & REGIMEN 100 mg NC410 Q2W 400 mg pembro Q6W FINDINGS TO DATE Follow additional ~20 patients to confirm clinical activity DATA EXPECTED 2Q 2024 ORR 10.5% (2/19) DCR 47.3% (9/
Slide 13: NC410 Combo Timeline and Potential Catalysts
2024 2025 2026 2027 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 NC410 Combo Timeline and Potential Catalysts 13 *Ph3 *Randomized Ph2 N = 150 Ph1b Data Ph2 Initiation Ph1b N=~40 CRC (ICI Naïve, MSS/MSI/L, without Liver Metastasis) Ph2 Initial Data Ph2 Full Data Set *Ph3 *Randomized Ph2 N = 150 Ph
Slide 14: Opportunity to Treat Large Unmet Needs
Opportunity to Treat Large Unmet Needs 14 EARLY CLINICAL ACTIVITY PLANNING FOR PH2 EXPANDING OVARIAN & CRC ADDITIONAL CLINICAL DATA 2024 VALUE CREATION
Slide 15: LNCB74
15 LNCB74 LEVERAGING OUR DEEP EXPERTISE IN B7-H4 AND COLLABORATION WITH LCB TO DEVELOP A DIFFERENTIATED THERAPEUTIC IND 4Q 2024 Breast CANCER Ovarian CANCER Endometrial CANCER
Slide 16: LNCB74 Differentiated ADC Positioning
16 THERAPEUTIC POSITIONING Improved safety and efficacy PATIENT SELECTION STRATEGY CLIA validated IHC biomarker assays NOVEL APPROACH Unique antibody linker strategy Co-development partnership with LCB DEEP EXPERTISE Significant B7-H4 experience LCB’s substantial ADC know-how Differentiated ADC LNCB
Slide 17: B7-H4 is the Next Target of Interest in Women's Cancer
B7-H4 is the Next Target of Interest in Women’s Cancer 17 In 2nd big deal of the day, GSK inks $1.4B pacy for Hansoh gynecology cancer asset NextCure, LegoChem join big-league rivals in antibody-drug conjugate race
Slide 18: Third Party Validation of B7-H4 as an ADC Target
Third Party Validation of B7-H4 as an ADC Target 18 Key Features SGN-B7H4V HS-20089 ADC Design • Val-Cit cleavable linker • MMAE • DAR 4 • Linker • Exatecan (TOPO1 inhibitor) • DAR 6 DLT 1.25 mg/kg (N=1) or 1.5 mg/kg (N=2) 7.2 mg/kg (N=2) Common AEs Neutropenia, peripheral sensory neuropathy, nausea
Slide 19: Deep Expertise in B7-H4
Deep Expertise in B7-H4 19 • Extensive publications • Expertise in expression • Repertoire of models • Top-tier KOL collaborative network • Validated patient selection assay • Co-development partner since 2022 • Significant success advancing ADCs • Differentiated linker technology Option to Develop
Slide 20: LNCB74 On Track for an IND Year-End 2024
LNCB74 On Track for an IND Year-End 2024 20 ✓ Potent pre-clinical activity in vitro and in vivo ✓ Pilot tox study – safe and tolerable ✓ Favorable pre-IND feedback from FDA • Tox studies • GMP manufacturing • Planning for Ph1 COMPLETED ONGOING
Slide 21: LNCB74 Is an Anti-B7-H4 MMAE ADC
LNCB74 Is an Anti-B7-H4 MMAE ADC Fc Modification Protects immune cells Tumor Selectivity Glucuronidase cleavable linker provides greater selectivity and specificity 21 MMAE DAR 4 Improves safety and control over how the payload is dispersed Antibody Linker Payload STRUCTURAL DIFFERENTIATION
Slide 22: Differentiating Glucuronidase & Other Linkers
Differentiating Glucuronidase & Other Linkers 22 Bloodstream Tissues Cancer Cell •Efficient release of toxin •Higer concentration Stable No Toxicity + + Transfer to albumin Released by platelets & neutrophils Unstable Toxicity •Inefficient release of toxin •Lower concentration Potent Less potent Bys
Slide 23: Key Differentiating Features of Glucuronidase Linkers
Key Differentiating Features of Glucuronidase Linkers 23 Time (Hours) Relative Toxin Concentration per Cancer Cell 100% Val-cit Linker Glucuronidase Linker Control ADC Glucuronidase Linker Val-Cit Linker Site specific attachment to mAb □ Non-specific attachment to mAb Highly stable linkage □ Uns
Slide 24: LNCB74 Shows Potent Anti-Tumor Activity in CDX and PDX Models
24 LNCB74 Shows Potent Anti-Tumor Activity in CDX and PDX Models OVARIAN (OVCAR-3-B7-H4-OE) Days from Treatment Initiation Mean Volume (mm3) +/- SEM TNBC (CTG-0012) Mean Volume (mm3) +/- SEM Days from Treatment Initiation BREAST (ZR-75-1) Days from Treatment Initiation Mean Tumor Volume (mm3) +/- SE
Slide 25: Preclinical Development of LNCB74 is on Track
TOX STUDY GMP MANUFACTURING 25 Preclinical Development of LNCB74 is on Track Species Cynomolgus Dose Range 4, 7 & 10 mg/kg Q3W, i.v. Evaluation Toxicology profiling, pathology, hematology, immunotoxicology Goal Define starting dose Master cell bank generated Process development complete Antibody bei
Slide 26: LNCB74 Ph1 Monotherapy Study Plans
DOSE ESCALATION DOSE EXPANSION 26 LNCB74 Ph1 Monotherapy Study Plans • 5 dose cohorts • Regimen Q3W • N=15-45 subjects • 2 dose cohorts • 2 tumor types • N=80 subjects • Pre-treatment & on study biopsies Breast CANCER Ovarian CANCER Endometrial CANCER Readouts: Scans every 6 weeks Endpoints: Safety
Slide 27: LNCB74 Timeline and Potential Catalysts
2024 2025 2026 2027 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 LNCB74 Timeline and Potential Catalysts 27 Ph1 Dose Expansion N = 80 Ph1 Dose Escalation N = 15-45 Tox Readout Initial Ph1 Data IND Enabling Studies IND
Slide 28: Opportunity to Develop Differentiated B7-H4 ADC Therapeutic
IND Opportunity to Develop Differentiated B7-H4 ADC Therapeutic 28 B7-H4 ADC PH1 INITIATION VALUE CREATION
Slide 29: Programs Available for Partnering
Programs Available for Partnering 29 PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT MILESTONE NC525 LAIR-1 Leukemia Ph1a Data 4Q 2024 NC605 S15 Osteoclasts Tox Studies NC181 APOE4 Microglia & Neurons Master Cell Bank FIND-ADC New Targets Tumor Cells Lead Selection Oncology
Slide 30: Anticipated 2024 Milestones
Anticipated 2024 Milestones 30 Q1 Q2 Q3 Q4 Ovarian CRC LNCB74 IND Filing Ph1b Data Ph1b Data NC410 Combo
Slide 31: Advancing Innovative Medicines for Cancer
P R O P R I E T A R Y A N D C O N F I D E N T I A L Advancing Innovative Medicines for Cancer 31 ADCs Treatments for Non-Responders Differentiated Programs
Slide 32: Appendix
@ure APPENDIX
Slide 33: 1087-001 CRC: Partial Response
1087-001 CRC: Partial Response 71% Reduction in Sum of Target Lesions 33 Right Axillary lymph node TARGET LESION 1 3.0 cm 1.4 cm 2.2 cm 1.2 cm BASELINE – 9.15.2023 WEEK 9 – 11.20.2023 0.7 cm 0.8 cm Right Pelvic lymph node TARGET LESION 2 WEEK 18 – 1.19.2024
Slide 34: 1110-003 CRC: Partial Response
BASELINE – 4.8.2023 WEEK 9 – 6.20.2023 Paraaortic lymph node Gastrohepatic lymph node 1.9 cm 1.0 cm TARGET LESION 1 TARGET LESION 2 1110-003 CRC: Partial Response 59% Reduction in Sum of Target Lesions 34 1.8 cm 0.5 cm
Slide 35: NC525 LAIR-1 MAB
NC525 LAIR-1 MAB 35 • Ph1 dose escalation study ongoing • Phase 1a data 4Q 2024 • Currently seeking partner • Leukemia (AML) • High-risk myelodyplastic syndrome • Chronic myelomonocytic leukemia • LAIR-1 is essential for AML development and cell survival • Data defining MOA recently published (Lovew
Slide 36: NC605 Siglec-15 MAB
NC605 Siglec-15 Disease Healthy TRAP+ osteoclast Precursor cells PDGF-BB NC605 SIGLEC-15 MAB 36 • Master cell bank available • Initiating tox studies • Currently seeking partner • Osteogenesis imperfecta • Osteoporosis • Non-union fracture • Prevents bone loss • Promotes bone formation • Decreases f
Slide 37: NC181 APOE4 MAB
NC181 APOE4 MAB 37 • Master cell bank being generated • Currently seeking partner • Alzheimer’s disease • Cerebral amyloid angiopathy (CAA) • Parkinson’s disease • Reduces amyloid plaques • Suppresses neuroinflammation • Improves cerebrovascular function
Slide 38: FIND-ADC Technology Uniquely Unlocks New Targets for ADCs
38 FIND-ADCTM Technology Uniquely Unlocks New Targets for ADCs Incremental payload and linker improvements to the same pool of existing targets (HER2, EGFR, FRα, TROP-2,CLDN18.2, BCMA, CD19) Identifying new targets for ADCs that unlock novel products and value TRADITIONAL DISCOVERY FIND-ADC