Nextcure, Inc. · NASDAQ:NXTC
Nextcure — Corporate Update (November 2021)
45 slides from Nextcure's corporate update, Nov 15, 2021
Slide 1: Investor Update
Cure Investor Update November 15, 2021
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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. Words such as “may,” “will,” “expect,” “anticipate,” “est
Slide 3: Pipeline and platform overview
NC318 (S15): Phase 2 mono - SITC presentation NC410 (LAIR-2): Phase 1 mono - SITC posters NC762 (B7-H4): Phase 1 mono * New Product Candidate: NC525 - ASH poster NC318 (S15) Phase 2 NC410 (LAIR-2) Patient selection increasing probability of success Phase 1 PRODUCT Biomarkers for detecting early acti
Slide 4: Advancing Product Development Pipeline
is Advancing Product Development Pipeline PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 PRODUCT CANDIDATES Tumors and a == NC318 S15 macrophages NSCLC, BREAST, H&N NC318 sis Tumors and Anti-PD-1 Combo* macrophages Myeloid NC410 LAIR-2 and Teelis B7-H4 Tumors N C, BREAST, OVARIA
Slide 5: Agenda
2 i Agenda Update, patient selection, dosing, sS15 ay | Roy Herbst, MD, PhD Unmet need in lung cancer NC410 - Phi Safety, dose escalation, biomarkers nd c NC525 - PC New program; IND 4Q 2022 +a NC318 - Phi & Ph2 Next€ure
Slide 6: Agenda — NC318 Phase 1 & Phase 2
i Agenda — NC318 Phase 1 & Phase 2 + a NC318 - Phi & Ph2 Update, patient selection, dosing, sS15 ( } Unmet need in lung cancer ( J Safety, dose escalation, biomarkers New program; IND 4Q 2022 Next€ure
Slide 7: NC318 Clinical Trial History and Update
NC318 Clinical Trial History and Update SITC Data ( Amended Phase 2 7 Phase 1 * 343 design * S15+ selection (CLIA assay) * Dose escalation, 8 - 1600 mg * 800 mg Q1W: drug exposure - 15 tumor types * NSCLC, H&N and breast * 49 patients \ J fi \ Phase 2 Yale Phase 2 (Combo) * Simon 2-stage design * NS
Slide 8: NC318 Historical Clinical Outcomes
NC318 Historical Clinical Outcomes Phase 1 Phase 2 + 3+3 design + Simon 2-stage design + Dose escalation, 8 - 1600 mg + 400 mg Q2W + 15 tumor types + NSCLC, ovarian, H&N and breast + 49 patients + 47 patients * 1 CR (NSCLC); 1 PR (NSCLC); 18 SD + 2 PRs (H&N and TNBC); 10 SD 2. B Complete Response (C
Slide 9: Time to & Duration of Disease Control
EES Time to & Duration of Disease Control ( ———— * EE rag ©@ CRStart —SS_ @ PRstart —_—S— © SOStart SSS b> On Study OE ——————— Cc —————— Ties Oe) + To date, two subjects with i —<$$———————— NSCLC (1CR and 1PR) remain 7 on therapy for 2.8 and 2.3 - — —_ years, respectively. Other? = j — SEE eT ves§ 1
Slide 10: Analysis in All Patients
Analysis in All Patients
Slide 11: Early Evidence of Disease Control Without S15 Selection in Ph1 & Ph2
Early Evidence of Disease Control Without S15 Selection in Phi & Ph2 Disease Total mPFS in Responses Control Progressive . | Evaluable Disease Disease Cancer Types n=32 ( t+SD) (n=54) Subjects Control n=32 (37%) | (n=86)? (5.0 months) Lung 1CR, 1 PR, 13SD H&N 1PR 1 (20%) 4 5 N/A Breast 1 PR, 3 SD 4
Slide 12: Progression-free Survival in the Absence of S15 Selection
Progression-free Survival in the Absence of S15 Selection ( ie 2 ” —— CR#PR —- sp' — PD = 100 g 2 Median PFS across all tumor types in a Disease Control (DC; CR/PR/SD) is 5.0 3 50- months = — CR+PR: 18.3 months 2 - SD: 4.5 months 3 - PD: 1.7 months 8 a °? | 0 5 10 Time (months) +ASD subjects were lo
Slide 13: Retrospective Analysis in S15+ Patients
Retrospective Analysis in S15+ Patients
Slide 14: Disease Control Rate Increased in S15+ Patient Population
Disease Control Rate Increased in S15+ Patient Population ( ie Complete Response (CR) Subjects treated All Subjects : with NC318 B Partial Response (PR) & Stable Disease (SD) Not Evaluable (10) THC available & Complete responsei(2) Hi Progressive Disease (PD) evaluable ee 3 (Fai Not Evaluable (NE) S
Slide 15: Soluble S15 Changes Associated with NC318 Dosing
Soluble S15 Changes Associated with NC318 Dosing (- 7 *) ~@PR @SD -@ PD + After infusion, soluble S15 (sS15) increased several fold compared to baseline - PD was observed with a higher fold increase post-infusion (24 hours) (pg/ml) + PD may also correlate with a higher baseline sS15 level Soluble $1
Slide 16: NC318 at 800mg Weekly Provides Increased Drug Exposure
NC318 at 800mg Weekly Provides Increased Drug Exposure ‘a >) NC318 Area Under the Curve (AUC) by Dosing Schedule oO") modeled 0@ 400mg am O®@ 800mg \ Observed PK/PD modeling showed 800mg Q1W would result in ~10-fold increase in drug exposure than achieved with AUC Cumulative Exposure to NC318 (ug*hi
Slide 17: NC318 Phase 1 and Phase 2 Learnings & Current Trials
a NC318 Phase 1 and Phase 2 Learnings & Current Trials Phase 1 & Phase 2 Learnings Current Trials r Y Evidence of disease control at 400 mg Q2W -Lung: 45% Disease control; mPFS 5.2 months -All tumors: 37% Disease control; mPFS 5.0 months G Enhanced outcomes in S15+ patients 4 PK/PD modeling shows 80
Slide 18: Agenda - Dr. Roy Herbst
a i Agenda - Dr. Roy Herbst ( ) Update, patient selection, dosing, sS15 ay | Roy Herbst, MD, PhD Unmet need in lung cancer ( ) Safety, dose escalation, biomarkers ( J New program; IND 4Q 2022 © Next@ure
Slide 19: What are we waiting for?
What are we waiting for? Time for more targeted immunotherapy! YaleNewHaven CANCER Yale eset Yale SCHOOL OF MEDICINE
Slide 20: Siglec15 as a new target for lung cancer immunotherapy
Siglec15 as a new target for lung cancer immunotherapy | aa Siglec-15 as an immune suppressor and potential Lieping Chen, MD PhD target for normalization cancer immunotherapy a b . Membrane genes aAPC Jurkat-NF-xB/NFAT ie ~6,500 al reporter 5 OK © @e ce o F s > ¢ i E Roy Herbst, MD PhD Asaglere & sé
Slide 21: Why Did We Select S15?
WHY DID WE SELECT S15? EXPRESSION STRUCTURE FUNCTION Expressed by Both Tumor Similar Potently Suppresses Cells and Macrophages to PD-UI T Cell Activities YaleNewHavenHealth ‘Smilow Cancer Hospital Yale stuses —="" 6 Yale sCHOOL OF MEDICINE
Slide 22: Time to & Duration of Disease Control In Lung Cancer
Time to & Duration of Disease Control In Lung Cancer @ CR Start @ PR Start @ SD Start On Study —" ne * n=15 * To date, two subjects with NSCLC (1CR and 1PR) remain on therapy for 2.8 and 2.3 years. respectively. YaleNewHavenHealth Smilow Cancer Hospital | Yale CANCER CENTER 9 Yale scHOOL OF MEDICINE
Slide 23: S15 mAb for use as a companion diagnostic test
S15 mAb for use as a companion diagnostic test * Tested extra-cellular domain antibodies * Tested 2 batches (about 6 per batch) of NextCure produced intra-cellular domain mAbs * Successfully identified IF-7 (below) for use in S15 CLIA validated diagnostic assays $15 H Score? PD sp‘ YaleNewHavenHealt
Slide 24: Confirmed Partial Response and Conclusions
Confirmed Partial Response Conclusions 74 y/o NSCLC dosed 400 mg every 2 weeks Diagnostic biopsy: NC318 has been well tolerated across Prior therapies: S15 PD-L1 (TPS) multiple dose levels : ; * Immunotherapy: “LAG3/PD-1” (best N/A +086 Adverse event profile consistent with other approved immunother
Slide 25: Investigator Initiated SPORE Trial
PROJECT 1 — Investigator Initiated SPORE Trial PD-I Axis Inhibitor Naive TRIAL SCHEMA | Pretreatment Tumor Biopsy and Blood Collection | 7 = K A ¥ Came Arm 1b Arm 2 NC318 Monotherapy NC318 q2w+ NC318 q2w+ 800mg (a1) Pembrolizumab q 3w Pembrolizumab q 3w Stage 1 With Stage 1 With Stage 1 Safety Run-I
Slide 26: Agenda - NC410
i's Agenda - NC410 ( ) Update, patient selection, dosing, sS15 ( J Unmet need in lung cancer NC410 - Phi Safety, dose escalation, biomarkers ( J New program; IND 4Q 2022 © a Next@ure
Slide 27: LAIR Biology
LAIR Biology LAIR-1 IS LAIR-2 ALLEVIATES NC410 REMODELS COLLAGEN & IMMUNOSUPPRESSIVE IMMUNOSUPPRESSION NORMALIZES IMMUNE SYSTEM SS =~. -Binds collagen and Ciq - Differs from LAIR-1 *NC410, fusion protein of LAIR-2 -Collagen density is a barrier to T cell ~ Soluble i ‘ion and ‘ivatic - Greater affini
Slide 28: NC410 Safety & Early Efficacy Data from Cohorts 1-5
NC410 Safety & Early Efficacy Data from Cohorts 1-5 (Phase 1a Dose Escalation NC _——————— TT, ») ; 130mg + 3+3 design enone at + Dosing every 2 weeks cone nero Reaiiene * Solid tumors Ovarian | EEE Bio + No DLTs through cohort 5 ; Bro + Two subjects reported with Prostate | ET BB so worsening Grade
Slide 29: NC410 Biomarkers
NC410 Biomarkers cb4/cb8 a T Cells NG Pit of COLLAGEN LAIR LIGANDS REMODELING *Soluble LAIR-1 “Collagen *Collagen derived -CD4 / CD8 T cells *LAIR-2 “Clq products (CDPs) _ © > Next@ure
Slide 30: Transient Reduction of Soluble C1q: Evidence of NC410 Binding
Transient Reduction of Soluble Ciq: Evidence of NC410 Binding C1Q Levels Pre- & Post-Dosing Pre-Dose C1iQ Levels ‘a 125 ‘NF 425 ) ° ° ° ° e : ° ° = 100 o 8 = 100 A e 0° = 0% E 4 ; o0 8 © © : B [2B oo og 488 08 BS 54 — .0o 63 =, 15 9 2000 090 ey Po — e°o ts} ° eo” 68 6 . eer ° ° io” a of oT ° ° U 8 S
Slide 31: ECM Remodeling
is ECM Remodeling ( Pro-C3 & Pro-C6 7 4 c4G 7 + Generated by collagen deposition + Produced by cleavage from Granzyme B + ECM becomes dense and thick which is produced by activated T cells + Excludes T cells + ECM becomes less dense + Promotes T cell infiltration and activation
Slide 32: Collagen Derived Products - Early Evidence of Collagen Remodeling
Collagen Derived Products - Early Evidence of Collagen Remodeling “ Remodeling of Collagen in Clinical Samples )(/— Remodeling of Collagen in Non-clinical Model c4G PRO-C3 PRO-C6 Control NC410 Concentration (ng/mL) & 8 ° ° > s . > ro ‘ > ‘ '° Concentration (ng/mL) > “ ’ s > tes ‘ ‘ ’ ’ s id . Concen
Slide 33: LAIR-2 Levels in Peripheral Blood Increase in a Dose-Dependent Fashion
LAIR-2 Levels in Peripheral Blood Increase in a Dose-Dependent Fashion (— Total detectable LAIR-2 Y\) i i. Dose = Cohort 1(3mg) = Cohort 2(6mg) — Cohort 3(15mg) — Cohort 4 (30mg) — Cohort 5 (60 mg) 800004 © Cohort 1&2 © Cohort 3 60000 @ Cohort4&5 500000 250000] 0 ° C1iD1 C1iD1 C2D1 C2D1 C3D1 C3D1 C5
Slide 34: Soluble LAIR-1 in Peripheral Blood Over Time
Soluble LAIR-1 in Peripheral Blood Over Time ( \ £ © Cohort 1 & 2 4 8000 © Cohort 3 = @ Cohort 4&5 4 O° + Soluble LAIR-1 does not = 6000-7 ° change overtime a So eS we 5 = 40004 °° 80 * Continue to monitor at & >. © 20 higher doses to assess < os 5S 8, fo) mechanistic role in reducing 2004 © §5® 06
Slide 35: Early Evidence of Immune Activation in a Patient with Stable Disease
Early Evidence of Immune Activation in a Patient with Stable Disease Cycle 1 Day 1 Cycle 3 Day 1 % LAIR-1+ CD8 & CD4 Cells (5 as > ~ A ‘Count, 8 ~@ CD8+LAIR1+ -@ CD4+LAIR1+ T T T T T T T T C1D1 C1D2 C1D3 C1D8 C2D1 C3D1 C5D1 C1201 CD8+ % LAIR-1+ from Parent Population 80 ” ? Visit +> i be ie a . . e
Slide 36: NC410 Observations for Cohorts 1-5
NC410 Observations for Cohorts 1-5 19 [: Transient reduction is early peripheral pharmacodynamic marker + Implies no safety concern regarding complement activity in circulation [- Does not change overtime cp4 / cps + Time-dependent increase without increase in LAIR-1 expression + NC410 enhanced T ce
Slide 37: NC410: Key to Unlock TME and Normalize Immune Response
NC410: Key to Unlock TME and Normalize Immune Response REMODELING & TME ACCESS LOCKED NC410 UNLOCKS ECM NORMALIZATION leap Reavated { Many “keys” but none fit lock \. y, T cell Enhances T cell infiltration ae Activated T cells kill tumor Next@ure
Slide 38: Leveraging LAIR Biology and Distinct Candidate MOAs for Different Diseases
is Leveraging LAIR Biology and Distinct Candidate MOAs for Different Diseases a > fT rancer won anrearron NC410 ECM remodeling & LAIR-2 fusion Collagen & C1q normalizing Solid tumors immune response NC525 _ LAIR-1 mAb LAIR-1 Blast & LSC killing © Heme-onc XS A Next@ure
Slide 39: Agenda - NC525
Agenda - NC525 Y ese New program; IND 4Q 2022 Next€ure
Slide 40: New Program - NC525 (LAIR-1 mAb)
New Program - NC525 (LAIR-1 mAb) NC525 BIOLOGY MOA UPDATE ‘i *~ ) ae a + LAIR-1 expression Kills AML Blast Cells & LSCs + Inhibits colony formation of AML LSCs in vitro - High on AML blasts and Ss =f hibi hi leukemia stem cells (LSCs) ; P aninibits AME growty ini MMs: eee abe 11 derived xenografts (
Slide 41: Agenda - Closing Remarks
2 i Agenda - Closing Remarks +a NC318 - Phi & Ph2 Update, patient selection, dosing, sS15 ay | Roy Herbst, MD, PhD Unmet need in lung cancer NC410 - Phi Safety, dose escalation, biomarkers nd ' NC525 - PC New program; IND 4Q 2022 Next€ure
Slide 42: GMP Manufacturing Facility: Added Additional Capacity
GMP Manufacturing Facility: Added Additional Capacity Prioritization and scheduling Operational and capital efficiency Controlling quality with experienced team Utilized to Produce Clinical Material for All Lead Programs ® Next@ure
Slide 43: Product Development: Getting it Right
Product Development: Getting it Right —L———— Patient ¥Y NC318 Selection Phase 2 +f NC410 Phase 1 Triangulation ™ Strategy if NC762 . P Phase 1 all Combos Biomarkers nd NC525 Pre-Clinical Next@ure
Slide 44: Advancing Product Development Pipeline
es Advancing Product Development Pipeline NEXT PROGRAMS TARGET CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONE PRODUCT CANDIDATES Tumors and Phase 2 update NC318 $15 macrophages NSCL BREAST, H&N Q4 2022 NC318 “i Tumors and i Initial Data rashes ee macrophages ee Combo* ; Myeloid Phase
Slide 45: Significant Momentum & Milestones in 2022
Next©ure Significant Momentum & Milestones in 2022 NC318 BUILDING PIPELINE EXPERIENCED RUNWAY On Track Momentum Team 2H 2023 Oo + Next@ure