Shattuck Labs, Inc. · NASDAQ:STTK
Shattuck Labs — SITC 2021 Annual Meeting Investor Conference Call & Webcast
44 slides from Shattuck Labs's conference presentation, Nov 12, 2021
Slide 1: SITC 2021 Investor Conference Call & Webcast
SITC 2021 Investor Conference Call & Webcast NASDAQ: STTK November 12, 2021
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties and are based on our estimates and assumptions. All statements, other than statements of historica
Slide 3: SITC 2021 Investor Conference Call and Webcast Agenda
SITC 2021 Investor Conference Call and Webcast Agenda Introduction Conor Richardson – Sr. Director, Finance & Investor Relations ARC Platform Overview Taylor Schreiber, M.D., Ph.D. – Chief Executive Officer Review of SL-172154 Clinical Data Lini Pandite, MBChB, M.B.A. – Chief Medical Officer Review
Slide 4: Taylor Schreiber, M.D., Ph.D. Chief Executive Officer
Taylor Schreiber, M.D., Ph.D. Chief Executive Officer 4
Slide 5: ARC Platform Technology
ARC Platform Technology Designed to Simultaneously Block Immune Checkpoints and Activate TNF Receptors 6 Checkpoint Binding Domains ARC Platform Structure and Advantages ✓ Checkpoint Inhibition Removes the “brakes" from the immune system Proprietary Engineered Fc Domain ✓ TNF Superfamily Agonism Tri
Slide 6: Current Antibody Therapy Approaches Have Limitations
Current Antibody Therapy Approaches Have Limitations Bivalent Antibodies Cannot Efficiently Activate Trimeric Receptors A. B. C. ARC COMPOUND ANTIBODY (BIVALENT BINDING) TNF RECEPTORS TNF RECEPTOR 2 SETS OF TRIMERS (TRIMER) (DIMER) T CELL TNF receptors require Bivalent antibodies cannot bring ARCs c
Slide 7: Shattuck's Development Pipeline
Shattuck’s Development Pipeline Deep Pipeline of Scientifically Validated and Novel Targets DOMAINS STAGE OF DEVELOPMENT PLATFORM PROGRAM DOMAIN 1 DOMAIN 2 INDICATIONS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 CLINICAL-STAGE PIPELINE Ovarian Cancer (1) SL-172154 SIRPα CD40L CSCC and HNSCC ARC AM
Slide 8: SITC Clinical Data Overview
SITC Clinical Data Overview Key Highlights SL-172154 SL-279252 ARC Platform (SIRPα-Fc-CD40L) (PD1-Fc-OX40L) Validation Active Clinical Compounds High Target Engagement Anti-Tumor Activity Initial anti-tumor activity and unique High CD47 target occupancy and Response rate consistent with PD1 pharmaco
Slide 9: Lini Pandite, MBChB, M.B.A. Chief Medical Officer
Lini Pandite, MBChB, M.B.A. Chief Medical Officer 9
Slide 10: SL-172154 (SIRPα-Fc-CD40L)
ABSTRACT #459 SL-172154 (SIRPα-Fc-CD40L) Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint SL-172154 (SIRPα-Fc-CD40L) in Subjects with Platinum-Resistant Ovarian Cancer 10
Slide 11: SL-172154: Novel CD47 Inhibitor + CD40 Agonist
SL-172154: Novel CD47 Inhibitor + CD40 Agonist Rationally Designed to Maximize the Benefits of CD47 Blockade SL-172154 (SIRPα-Fc-CD40L) Highly Differentiated 6 SIRPα Binding Domains CD47 Inhibitor Blocks “Don’t Eat Me” CD47 Macrophage Checkpoint Dual Mechanism of Action Inert IgG4 Fc Unique Activato
Slide 12: SL-172154: Phase 1A in Ovarian Cancer
SL-172154: Phase 1A in Ovarian Cancer Trial Design and Objectives Dose Escalation per Modified Toxicity Probability Interval (mTPI-2) Design (N=15) Study Objectives: Evaluate the safety, identify a dose and schedule, and characterize the PK, immunogenicity, 10.0 mg/kg PD, and anti-tumor activity of
Slide 13: SL-172154: Baseline Characteristics and Disposition
SL-172154: Baseline Characteristics and Disposition Heavily Pre-Treated Patient Population Tumor Characteristics (All Treated) Total number of subjects N = 15 Tumor characteristics (all treated) n (%) Cancer type Ovarian cancer 9 (60) Primary peritoneal cancer 4 (27) • Age: 67 (median), 33-79 (range
Slide 14: SL-172154: Summary of Safety in All Treated Subjects
SL-172154: Summary of Safety in All Treated Subjects Favorable Safety Profile Treatment-Related AEs in ≥ 2 Subjects Total number of subjects N = 15 Infusion Related Reactions (IRR) Treatment-related AEs (any grade) n (%) Any 14 (93%) 17 IRR events in 8 subjects (53%) IRR 8 (53%) • 14 IRRs were G2 in
Slide 15: Distinct Profile of TNFα and IL-6 Relative to CD40 mAbs
Distinct Profile of TNFα and Interleukin-6 (IL-6) Relative to CD40 mAbs TNFα IL-6 A. CP-870,893 † SL-172154 B. CP-870,893† SL-172154 (CD40 mAb) Median TNF-α (pg/mL) at C1D1 Predose and 2Hr (CD40 mAb) Median IL-6 (pg/mL) at C1D1 Predose and 2Hr 800 800 - 300 Baseline 300 - Baseline Predose Predose 1
Slide 16: High CD47 Target Occupancy of SL-172154
High CD47 Target Occupancy of SL-172154 Preferentially Binds CD47 on Leukocytes Compared to RBCs SL-172154 WBC Binding (%) on C1D1 SL-172154 RBC Binding (%) on C1D1 Median Subject 0.1 0.3 1.0 3.0 0.1 0.3 1.0 3.0 Dose (mg/kg) Dose (mg/kg) ➔SL-172154 approaches near full occupancy on leukocytes with i
Slide 17: Evidence of CD40 Activation
Evidence of CD40 Activation SL-172154 Stimulates Dose-Dependent B Cell Margination and Activation A. CD40 Margination (%) B. Median B Cells (%) by Dose Level C. Median Fold Change on C1D1 100 4.0 3.5 80 3.0 60 2.5 2.0 40 1.5 20 1.0 0 0.5 0.1 0.3 1.0 3.0 C1D1 C1D1 C1D1 C1D15 C1D15 C1D15 C2D1 C2D1 C2D
Slide 18: SL-172154 Stimulates Dose-Dependent Increases in Serum IL-12
SL-172154 Stimulates Dose-Dependent and Reproducible Increases in Serum Interleukin-12 (IL-12) A. IL-12 Level (pg/mL) Upon Repeat Dosing B. IL-12 Fold Change From Predose to 2 Hours on C1D1 4500 Dose level 1 – 0.1 mg/kg Dose level 3 – 1.0 mg/kg Median Dose level 2 – 0.3 mg/kg Dose level 4 – 3.0 mg/k
Slide 19: SL-172154 Induces Innate Immune Response in TME
SL-172154 Induces Innate Immune Response in TME Individual Case Study: Patient A CD68+ 350 Pre-treatment 300 10 250 % CD40+ Immune Cells 8 H-Score 200 6 Pre-treatment 150 On-treatment 4 100 50 2 Post-treatment 0 0 MHCI MHCII CD40 ➔SL-172154 increases CD68+ macrophages and upregulates activation mark
Slide 20: SL-172154 Induces Adaptive Immune Response in TME
SL-172154 Induces Adaptive Immune Response in TME Individual Case Study: Patient A 5 CD8+ GZMB CD68+ Ki67 4 Pre-treatment PD-L1 (%) 3 Pre-treatment On-treatment 2 1 0 TPS CPS Post-treatment ➔SL-172154 increases cytotoxic CD8+ T cells in TME ➔ Induction of PD-L1 on immune cells is a consequence of CD
Slide 21: SL-172154: Best Overall Response
SL-172154: Best Overall Response Dose Escalation Continues ➔ Best response among 14 subjects with post-baseline scan • SD, n=4 Sch 1:Dose level 1 – 0.1 mg/kg All Treated Sch 1:Dose level 2 – 0.3 mg/kg • PD, n=9 Subjects Sch 2:Dose level 2 – 0.3 mg/kg • NE, n=1 Sch 2:Dose level 3 – 1.0 mg/kg Sch 2:Do
Slide 22: SL-172154: Ovarian Dose Escalation
SL-172154: Ovarian Dose Escalation CD47 Inhibition Combined with Potential Best-In-Class CD40 Agonist Key Takeaways High Target Engagement ✓ High target occupancy on CD47; preferential binding to leukocytes ✓ High target engagement on CD40+ leukocytes Active PD Profile ✓ Binding to CD40+ B cells and
Slide 23: Overall Clinical Development Strategy for SL-172154
Overall Clinical Development Strategy for SL-172154 Rapidly Expanding Strategy in 2022 PHASE 1A Development Programs Monotherapy Ovarian Trial in 2022 and Beyond SL-172154 IV Dose Level (DL) DL5 – 10.0 mg/kg Ovarian cancer [+ liposomal doxorubicin] DL4 – 3.0 mg/kg AML [+ azacitidine + venetoclax] DL
Slide 24: SL-279252 (PD1-Fc-OX40L)
ABSTRACT #494 SL-279252 (PD1-Fc-OX40L) Phase 1 Dose Escalation and Dose Expansion Study of an Agonist Redirected Checkpoint (ARC) Fusion Protein, SL-279252 (PD1-Fc-OX40L), in Subjects with Advanced Solid Tumors or Lymphomas 24
Slide 25: SL-279252: Novel PD-1 Inhibitor + OX40 Agonist
SL-279252: Novel PD-1 Inhibitor + OX40 Agonist Rationally Designed to Increase Clinical Responses to PD-1 Blockade SL-279252 (PD1-Fc-OX40L) Shattuck’s First 6 PD-1 Receptor Domains Product Candidate Blocks PD-1/PD-L1 Pathway Significant Platform Risks Inert IgG4 Fc Discharged 2 OX40L Trimers Dual Me
Slide 26: SL-279252: Study Design and Objectives
SL-279252: Study Design and Objectives Dose Escalation per Keyboard Design (N=43) 12.0 mg/kg DL11 enrolling 6.0 mg/kg Study Objectives: Evaluate the safety, identify a dose and DL10 n=4 schedule, and characterize the PK, immunogenicity, PD, and 3.0 mg/kg DL9 n=6 3.0 mg/kg n=3 anti-tumor activity of
Slide 27: SL-279252: Study Population and Tumor Characteristics
SL-279252: Study Population and Tumor Characteristics Tumor Characteristics (All Treated Subjects) Total (N = 43) Cancer Type, n (%) Ocular Melanoma 7 (16) Adeno NSCLC 6 (14) Gastric Adenocarcinoma 5 (12) Renal Cell Cancer 4 (9) • Age: 64 (median), 31-82 (range) SCC of Head and Neck 4 (9) • 56% male
Slide 28: SL-279252: Summary of Safety in All Treated Subjects
SL-279252: Summary of Safety in All Treated Subjects All Causality AEs in >10% of Subjects Total number of subjects N = 43 ➔ No dose-limiting toxicities All causality AEs (any grade) n (%) Any AE 40 (93) ➔ Most common TRAEs were maculo-papular rash Constipation 11 (26) (n =4; 9%), infusion-related r
Slide 29: SL-279252: Pharmacokinetics
SL-279252: Pharmacokinetics Cycle 1 Day 1 Cycle 1 Day 15 ➔ Cmax and AUC increase withlimit LLOQ = Lower increasing of quantitation dose up to 6 mg/kg ➔ A trend towards non-linear increase in exposure is apparent for AUC and reflected by a decrease in CL with increasing dose ➔ Preliminary observation
Slide 30: SL-279252: Maximal OX40 Receptor Engagement by Dose
SL-279252: Maximal OX40 Receptor Engagement by Dose 1 1 8 8 Dose evel Maximal margination on Day 1 Maximal margination on Day 2 1 mg/kg 1 mg/kg 3 mg/kg 1 mg/kg 3 mg/kg 4 4 1 mg/kg 3 mg/kg 2 1 mg/kg 2 3 mg/kg mg/kg 1 1 2 3 4 5 1 1 1 1 1 1 2 1 3 1 4 1 5 1 1 1 1 1 1 1 1 1 ce t t S 2 2 2 ce t t S 2 2 2
Slide 31: SL-279252: Dose Dependent Increases in CD8+ T cells
SL-279252: Dose Dependent Increases in CD8+ T cells Proliferating CD8+ Proliferating CD8+ e t Central e t Memory Te Cellsce s e t Effector ect Memory e Cells T ce s 15 Dose mg/kg 0.0001 1 1000 0.001 Ki67 CD8 CM cells Dose mg/kg %△ from baseline Dose mg/kg Ki67 CD8 EM cells 1 1000 0.003 %△ from basel
Slide 32: SL-279252: Increases CD8+/GZMB/Nkp46 in MSI-H CRC
SL-279252: Increases CD8+/GZMB/Nkp46 in MSI-H CRC Individual Case Study: Patient B CD8+ CD8+GZMB NK cell Baseline • SL-279252 causes local changes within the TME • Increases in proliferating and granzyme-B expressing On Treatment lymphocytes • Similar increases observed in multiple treated subjects
Slide 33: SL-279252: Percentage Change in Target Tumor Size from Baseline
SL-279252: Percentage Change in Target Tumor Size from Baseline Best Response ➔ Best response was 1 confirmed iPR NE iPR (ocular melanoma, 4 prior systemic iSD iUPD regimens, CPI-experienced) in iCPD PD subject who remained on treatment for >1 year ➔ iSD in 12 subjects • 1 unconfirmed iPR in a CPI-
Slide 34: SL-279252: Dosing in Context with Traditional mAbs
SL-279252: Dosing in Context with Traditional mAbs Current Dose Level Supports Continued Dose Escalation 20.0 Dose Level (mg/kg) 18.0 16.0 14.0 SL-279252 SITC data at 6 mg/kg 12.0 10.0 SL-279252 enrolling at 12 mg/kg 8.0 6.0 Approved anti-PD-L1 mAbs 4.0 2.0 0.0 ➔ PD-L1 inhibitors historically dosed
Slide 35: SL-279252: Dose Escalation
SL-279252: Dose Escalation PD-L1 Inhibition Combined with OX40 Agonist Safety Profile ✓ Well tolerated in heavily pretreated subjects with refractory solid tumors with no MTD reached PK Profile ✓ Linear PK at doses up to 3.0 mg/kg, and a greater than proportional increase in AUC was observed at 6.0
Slide 36: Andrew Neill, M.B.A. Chief Financial Officer
Andrew Neill, M.B.A. Chief Financial Officer 36
Slide 37: SL-172154 Expansion Into Combination Studies
SL-172154 Expansion Into Combination Studies Deep Pipeline of Scientifically Validated and Novel Targets DOMAINS STAGE OF DEVELOPMENT ANTICIPATED MILESTONES / PLATFORM PROGRAM DOMAIN 1 DOMAIN 2 INDICATIONS COMBINATION(S) DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 STATUS CLINICAL-STAGE PIPELINE Li
Slide 38: Shattuck Labs Well Positioned for High Growth
Shattuck Labs Well Positioned for High Growth Validation of ARC Platform • Two-clinical stage, immunologically active product candidates • Evidence of CD40 and OX40-mediated immune activation • Well tolerated to-date, with no DLTs Expanding Clinical Development • Five clinical trials in 2022 • Indic
Slide 39: Taylor Schreiber, M.D., Ph.D. Chief Executive Officer
Taylor Schreiber, M.D., Ph.D. Chief Executive Officer 39
Slide 40: ARC Platform Proof of Concept
ARC Platform Proof of Concept Key Clinical Observations SL-172154 SL-279252 (SIRPα-Fc-CD40L) (PD1-Fc-Ox40L) ✓ Highly potent and best-tolerated ✓ Initial anti-tumor activity in CPI CD40 agonist to date experienced melanoma ✓ High occupancy of both CD47 and ✓ OX40-dependent PD effects not CD40 achieve
Slide 41: Clinical Data Support ARC Platform Thesis
Clinical Data Support ARC Platform Thesis TNF Activation Without Bell Shaped Dose Response Agonist Activation† SL-172154 (Generalized Model) (ARC Model) ~50% receptor ~100% receptor ~50% target ~100% target occupancy occupancy occupancy occupancy 100 100 Agonist Function Effect (%) Effect (%) SL-172
Slide 42: ARC Platform Positioned for Expansion
ARC Platform Positioned for Expansion Major Takeaways ARC Platform Validation Rapidly Expanding Clinical Development Discharging Safety Risk SL-172154 1 No DLTs observed to date while 1 CD47 inhibitor in solid tumors expanding into approaching nearly full target occupancy hematologic malignancies an
Slide 43: Q&A Attendees
Q&A Attendees: Dr. Taylor Schreiber, CEO Dr. Lini Pandite, CMO Andrew Neill, CFO 43
Slide 44: Thank you
Thank you Investor Relations Investorrelations@ShattuckLabs.com
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