Slide 1: Initial Results from Dose Escalation Portion from the Phase 1 Trial of SIM0505
Initial Results from Dose Escalation Portion from the Phase 1 Trial of SIM0505, an Antibody Drug Conjugate (ADC) Cadherin-6 (CDH6) June 2, 2026
Slide 2: Forward Looking Statements
2 Forward Looking Statements This presentation and the accompanying slides (this “Presentation”) which have been prepared by NextCure are being delivered to a limited number of parties for discussion purposes only, and shall not form the basis for or be relied on in connection with any contract or b
Slide 3: Today's Speakers
3 Today’s Speakers Michael Richman Rakesh Dixit, Beryl Manning- Chief Executive PhD, DBAT Geist, MD, Officer, NextCure Scientific Advisory Assistant Professor, Board, NextCure Gynecology and Obstetrics, Emory Udayan Guha Ursula Matulonis, MD University MD, PhD Chief, Gynecologic Chief Medical Oncolo
Slide 4: Today's Agenda
4 Today’s Agenda Post-ASCO Investor Event Welcome Michael Richman, CEO SIM0505 Overview Rakesh Dixit, PhD, DBAT ASCO 2026 Data Ursula Matulonis, MD Unmet Need and Udayan Guha, MD, PhD, CMO, NextCure, Ursula Matulonis, MD, Clinical Perspective and Beryl Manning-Geist, MD Q&A NextCure Management and K
Slide 5: SIM0505 Demonstrated Best-in-Class Potential in Gynecologic Cancers
5 SIM0505 Demonstrated Best-in-Class Potential in Gynecologic Cancers • Positive SIM0505 Phase 1 dose escalation data at ASCO 2026 • 55% ORR response in gynecologic cancers at therapeutic doses* • 52.9% ORR in ovarian cancer, 66.7% ORR in uterine serous carcinoma (USC) • Favorable safety and tolerab
Slide 6: SIM0505 Differentiation
6 SIM0505 Differentiation Rakesh Dixit, PhD, DBAT ADC Specialist, NextCure Scientific Advisory Board
Slide 7: SIM0505 is a Differentiated CDH6 TOPOi ADC
7 SIM0505 is a Differentiated CDH6 TOPOi ADC VALIDATED TARGET WITH PROPRIETARY TOPOi PAYLOAD CDH6 mAb Linker Payload CPT116 (TOPO) DAR 8.0 Cysteine conjugation GGFG Linker Potent Cytotoxicity with Unique Binding Epitope Gly-Gly-Phe-Gly Provides High Systemic Clearance Anticipated Safety with Increas
Slide 8: SIM0505 Structural and Functional Differentiation by Design
8 SIM0505 Structural and Functional Differentiation by Design SIM0505 CPT116 (PAYLOAD) • Unique distal EC1 epitope on CDH6 • Designed for better tolerability & safety • Ovarian, uterine, RCC, NSCLC •Hydrophilic & high systemic clearance • High affinity & internalization •Good permeability & bystande
Slide 9: SIM0505 Phase 1 Dose Escalation Data
9 SIM0505 Phase 1 Dose Escalation Data Ursula Matulonis, MD Chief, Division of Gynecologic Oncology, Dana Faber Cancer Institute, and NextCure Scientific Advisory Board
Slide 10: SIM0505 Development Plan
SIM0505 Development Plan 10 COMPLETED INITIATED PLANNING DOSE ESCALATION DOSE OPTIMIZATION PIVOTAL TRIAL 2Q 2026 2Q 2026 Ovarian, USC, RCC, EC PROC & USC PROC Q3W Q3W Q3W Dose Escalation + Intermediate Doses 7.2 mg/kg (n = 20-40) SIM0505 9.6 mg/kg R (n = 215) (n = 4) 6.4 mg/kg (n = 20-40) 1:1 TPC* 8
Slide 11: SIM0505 Patient Demographics
SIM0505 Patient Demographics 11 Baseline US Patients China Patients All Patients Characteristic (n = 25) (n = 34) (n = 59) Age, years Median (range) 63 (49-78) 56 (42-72) 58 (42-78) Sex, n (%) Patient Population Male 0 (0.0) 2 (5.9) 2 (3.4) Female 25 (100) 32 (94.1) 57 (96.6) • Poor performance stat
Slide 12: SIM0505 Has Shown a Well Manageable Safety Profile
12 SIM0505 Has Shown a Well Manageable Safety Profile 1.6 – 9.6 mg/kg Overview of Adverse Events (n = 59) n (%) Treatment-emergent adverse events (TEAEs) (%) 59 (100) Grade ≥3 32 (54.2) Grade 5 a 2 (3.4) TEAEs related to study drug (TRAEs) (%) 57 (96.6) Grade ≥3 28 (47.5) Grade 5 0 Any Serious adver
Slide 13: Most Common TEAEs (≥10%)
13 Most Common TEAEs (≥10%) Anemia 13.6 62.8 Platelet count decreased 23.7 52.5 Vomiting 1.7 50.9 Neutrophil count decreased 23.7 50.8 White blood cell count decreased Nausea 1.7 16.9 47.4 47.5 •MTD not reached Hypokalaemia 6.8 37.3 Hyponatraemia Aspartate aminotransferase increased 0.0 1.7 35.6 33.
Slide 14: Swimmer Plot All Patients at All Doses
Swimmer Plot All Patients at All Doses 14 5101002 - USC - 2R 5101001 - HGSOC - 10R 5101003 - HGSOC - 6R 5101005 - HGSOC -12R 5104003 - HGSOC - 3R 5101006 - USC - 4R •6 dose cohorts + 2 intermediate 5103002 - HGSOC - 6R 5101007 - EC - 4R 5102002 - EC - 11R 5104002 - HGSOC - 4R 5102003 - RCC - 2R 5105
Slide 15: ORR at 4.8 – 8.0 mg/kg: ≥12 Weeks and Best Response
15 ORR at 4.8 – 8.0 mg/kg: ≥12 Weeks and Best Response Tumor type Evaluable (n) PRs (n) ORR Gynecologic Cancers (OC + USC) 20 11 55.0% (11/20) Ovarian Cancer (OC) 17 9 52.9% (9/17) Uterine Serous Carcinoma (USC) 3 2 66.7% (2/3)
Slide 16: Ovarian Cancer at Therapeutic Doses (4.8 – 8.0 mg/kg)
Ovarian Cancer at Therapeutics Doses (4.8 – 8.0 mg/kg) 16 5105005 - HGSOC - 9R 5101011 - HGSOC - 3R 5101009 - LGSOC - 2R 5101010 - HGSOC - 4R 5102009 - HGSOC - 5R 5206004 - HGSOC - 5R 5205001 - HGSOC - 9R 5205003 - HGSOC - 6R • n = 37 ovarian cancer patients 5208002 - HGSOC - 6R 5101020 - HGSOC - 7R
Slide 17: Tumor Percent Change from Baseline
Tumor Percent Change from Baseline -75 -60 -45 -30 -15 0 15 30 5103004 / HGSOC / 5R 17.4 5204001 / HGSOC-FT / 3R 2.6 5201002 / HGEOC / 4R 0.0 5203004 / HGSOC / 4R -9.1 5104007 / HGSOC / 4R -14.0 5102009 / HGSOC / 5R -14.9 5101009 / LGSOC / 3R -15.0 5104006 / HGSOC / 10R -27.2 5103003 / HGSOC / 3R -3
Slide 18: Tumor Percent Change from Baseline
18 Ovarian Cancer (4.8 – 8.0 mg/kg) 45 30 Dose Levels Tumor Percent Change from Baseline 4.8 mg/kg 15 5.6 mg/kg • Most patients (15/17) had 0 6.4 mg/kg tumor shrinkage 8.0 mg/kg -15 • Increasing tumor shrinkage with continued treatment -30 -45 • The greatest tumor shrinkage and durability occurred a
Slide 19: Uterine Serous Carcinoma (4.8 – 8.0 mg/kg)
19 Uterine Serous Carcinoma (4.8 – 8.0 mg/kg) • n = 6 USC patients enrolled Dose Levels 6.4 mg/kg • Patients with at least ≥12 5201001 - 5205006 - USC - 1R USC - 2R 7.2 mg/kg weeks follow-up Evaluable PR ORR 5206003 - USC - 3R 5201005 - USC- 2R 8.0 mg/kg 5201006 - USC - 3R 5203001 - USC - 4R n=3 2 6
Slide 20: Tumor Percent Change from Baseline
20 Uterine Serous Carcinoma 4.8 – 8.0 mg/kg 45 Dose Levels 6.4 mg/kg 30 7.2 mg/kg Tumor Percent Change from Baseline 8.0 mg/kg 15 0 -15 -30 -45 -60 -75 0 6 12 18 24 30 Weeks on Treatment Data cut 07Apr26
Slide 21: Clinical Perspective
21 Clinical Perspective Udayan Guha MD, PhD Beryl Manning-Geist, MD, Chief Medical Officer, Assistant Professor, Gynecology NextCure and Obstetrics, Emory University
Slide 22: Next Steps
22 Next Steps Michael Richman Chief Executive Officer NextCure
Slide 23: SIM0505 Development Plan
SIM0505 Development Plan 23 COMPLETED INITIATED PLANNING DOSE ESCALATION DOSE OPTIMIZATION PIVOTAL TRIAL 2Q 2026 2Q 2026 Ovarian, USC, RCC, EC PROC & USC PROC Q3W Q3W Q3W Dose Escalation + Intermediate Doses 7.2 mg/kg (n = 20-40) SIM0505 9.6 mg/kg R (n = 215) (n = 4) 6.4 mg/kg (n = 20-40) 1:1 TPC* 8
Slide 24: SIM0505 Demonstrated Best-in-Class Potential in Gynecologic Cancers
24 SIM0505 Demonstrated Best-in-Class Potential in Gynecologic Cancers • Positive SIM0505 Phase 1 dose escalation data at ASCO 2026 • 55% ORR response in gynecologic cancers at therapeutic doses* • 52.9% ORR in ovarian cancer, 66.7% ORR in uterine serous carcinoma (USC) • Favorable safety and tolera
Slide 25: Q&A
25 Q&A Michael Richman Rakesh Dixit, Beryl Manning- Chief Executive PhD, DBAT Geist, MD, Officer, NextCure Scientific Advisory Assistant Professor, Board, NextCure Gynecology and Obstetrics, Emory Udayan Guha Ursula Matulonis, MD University MD, PhD Chief, Gynecologic Chief Medical Oncology, Dana Far
Slide 26: Thank You!
4 eee? 0 bd od ie Thank You! Co I Os % ee . June 2, 2026 $e. ee, e * ead