Shattuck Labs, Inc. · NASDAQ:STTK
Shattuck Labs — Investor Presentation (November 2025)
30 slides from Shattuck Labs's investor presentation, Nov 6, 2025
Slide 1: Corporate Overview
Corporate Overview Shattuck Labs, Inc. NASDAQ: STTK November 6, 2025 1
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: We Are Focused on Improving the Lives of Patients
We Are Focused on Improving the Lives of Patients OUR PURPOSE Develop novel biologics for inflammatory and immune-mediated diseases OUR VALUES Bold, respectful, honest, balanced, grateful OUR MISSION Work with a sense of urgency, focused on scientific excellence and thoughtful stewardship of resourc
Slide 4: Shattuck Labs Overview
Shattuck Labs Overview Clinical-stage biotechnology company pioneering the development of novel Shattuck Labs therapeutics targeting tumor necrosis factor (TNF) superfamily receptors for the (NASDAQ: STTK) treatment of patients with inflammatory and immune-mediated diseases • Potential first-in-clas
Slide 5: Highly Experienced Management and Board
Highly Experienced Management and Board Management Team Taylor Schreiber, MD, PhD Lini Pandite, MD, MBA Casi DeYoung, MBA Andrew R. Neill, MBA Abhinav Shukla, PhD Suresh de Silva, PhD Stephen Stout, PhD Chief Executive Officer Chief Medical Officer Chief Business Officer Chief Financial Officer Chie
Slide 6: Shattuck's Pipeline Targeting the TL1A/DR3 Pathway
Shattuck’s Pipeline Targeting the TL1A/DR3 Pathway Programs Stage of Development Lead Target(s) Indications Preclinical IND-Enabling Phase 1 SL-325 DR3 IBD SL-425 DR3 IBD Extended Half-Life Bispecifics DR3 x Undisclosed Autoimmune Developing potential first-in-class DR3 monospecific and bispecific
Slide 7: TL1A / DR3 Biology
TL1A / DR3 Biology Rationale for Targeting the Receptor In a Clinically-Validated Axis 7
Slide 8: TL1A Is the Sole Activating Ligand for DR3 and DR3 Activation Leads to Inflammation
TL1A Is the Sole Activating Ligand for DR3 and DR3 Activation Leads to Inflammation TL1A/DR3 Axis Biology Increased Inflammation Tissue Resident Lymphoid Cells TL1A is expressed primarily on tissue- APCs In Blood and Tissue Caused by T Helper (Th) Cell 1 Driven Cytokine Production resident antigen p
Slide 9: Clinical Validation of Blocking TL1A/DR3 Axis and Rationale for DR3 Targeting
Clinical Validation of Blocking TL1A/DR3 Axis and Rationale for DR3 Targeting Anti-TL1A Antibodies Potential First-in-Class DR3 Antibody: SL-325 Validated Biology: Multiple third-party anti-TL1A antibodies have demonstrated clinical activity in Phase 2 trials in IBD; Phase 3 Potential for Greater Ef
Slide 10: Inflammatory Bowel Disease Is a Large and Growing Market
Inflammatory Bowel Disease Is a Large and Growing Market Worldwide IBD Sales ($B)1 $23.0 B $33.3 B $20.1 B $15.2 B $7.8 B $13.2 B 2023 2030 ■ UC ■ CD Worldwide inflammatory bowel disease sales and prevalence expected to grow steadily to 2030 UC = Ulcerative Colitis; CD= Crohn's Disease 1. Evaluate
Slide 11: DR3 Inhibition Is Potentially More Potent Than TL1A Inhibition
DR3 Inhibition Is Potentially More Potent Than TL1A Inhibition Butto L. Inflamm Bowel Dis. 2019 Jan; 25(1): 14–26 11
Slide 12: SL-325 Is a High-Affinity DR3-Specific Blocking Antibody
SL-325 Is a High-Affinity DR3-Specific Blocking Antibody Crohn’s Disease is TL1A is less abundant than DR3 in characterized by actively inflamed areas Tissue Lymphoid Cells discontinuous and Resident APCs In Blood and Tissue migratory inflammation 8.4% TL1A 17.4% DR3 Expression Expression TL1A DR3 S
Slide 13: RNA Sequencing Data From UC and CD Patient Biopsies Confirm Constitutive and Higher Expression of DR3
RNA Sequencing Data From UC and CD Patient Biopsies Confirm Constitutive and Higher Expression of DR3 GI Tissue Blood Aggregated transcriptomic data (>2000 patients) confirms higher expression of DR3 than TL1A in the GI tract of UC and CD patients DR3 is also highly expressed in peripheral blood
Slide 14: TL1A Is Transiently Expressed, Primarily in Tissues
TL1A Is Transiently Expressed, Primarily in Tissues TL1A is the monogamous ligand to DR3/TNFRSF25 TL1A is rapidly inducible in dendritic cells, macrophages and certain non-hematopoietic cells by TLR or FcγR ligation TL1A is turned on and off quickly Migone et al. Immunity. 2002;16:479-92 Meyla
Slide 15: Targeting DR3 May Enable More Effective Treatment of Inflammation
Targeting DR3 May Enable More Effective Treatment of Inflammation DR3 Is Constitutively Expressed - TL1A Is Not • TL1A is expressed transiently at sites of inflammation in Inflamed Inflamed High the gut but not by adjacent non-inflamed tissue1 • DR3 is expressed constitutively both at sites of TL1A
Slide 16: SL-325 Program
SL-325 Program Potential First-In-Class DR3 Blocking Antibody 16
Slide 17: SL-325 Designed for Potent DR3 Blockade
SL-325 Designed for Potent DR3 Blockade DR3 binding domains Picomolar binding affinity (1.3 pM) to DR3 and overlapping epitope with TL1A binding site Does not bind to DcR3 (decoy receptor) Potent blockade of monomeric and trimeric TL1A Silent Fc domain to DR3 in preclinical models Receptor blockade
Slide 18: Phase 1 Clinical Trial of SL-325 is Currently Enrolling
Phase 1 Clinical Trial of SL-325 is Currently Enrolling • Phase 1 Clinical Trial Design • Single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy volunteers • Planned enrollment of ~70 participants • Objectives of Phase 1 Study • Safety and Tolerability • PK Profile • Immunoge
Slide 19: SL-325 Preclinical Data
SL-325 Preclinical Data In vitro and GLP NHP Data 19
Slide 20: SL-325 Blocks TL1A Binding at Lower Concentrations Than Benchmark Anti-TL1As
SL-325 Blocks TL1A Binding at Lower Concentrations Than Benchmark Anti-TL1As SL-325 potently blocks TL1A binding to DR3 in vitro ~10-fold greater potency than benchmark anti-TL1A antibodies No head-to-head clinical trials of SL-325 and Tulisokibart or RO7790121 have been conducted. Note: Studies
Slide 21: SL-325 Blocks TL1A-Induced IFNγ Secretion From IBD Patient PBMCs
SL-325 Blocks TL1A-Induced IFNγ Secretion From IBD Patient PBMCs SL-325 efficiently blocked IFNγ across all tested IBD patient samples PBMCs = Peripheral blood mononuclear cells 21
Slide 22: SL-325 NHP Study Design and Safety Overview
SL-325 NHP Study Design and Safety Overview Compound Dose Level Treatment Period Recovery Period 1 mg/kg (3 Male, 3 Female) 10 mg/kg (3 Male, 3 Female) 100 mg/kg SL-325 (5 Male, 5 Female) Day 1 15 29 4 weeks No infusion-related reactions were observed in any group No-observed-adverse effect leve
Slide 23: SL-325 Achieved Full and Durable Receptor Occupancy
SL-325 Achieved Full and Durable Receptor Occupancy (RO) Day 29 on study Receptor Occupancy (%) 125 Full RO 100 1 mg/kg 106 1 mg/kg SL-325 Conc. (ng/mL) 10 mg/kg 75 105 10 mg/kg 100 mg/kg 50 104 100 mg/kg 1mg/ml 25 103 0 102 101 <50% RO 100 se 1 D 7 D 5 D 2 D 3 57 1 2 4 ay ay do ay ay ay ay 0.5 1 2
Slide 24: SL-325 Showed No Signs of DR3 Agonism
SL-325 Showed No Signs of DR3 Agonism %Tregs (CD4+ T Cells) %Ki67+ (CD4+ T Cells) 8 10 Vehicle CD25+FoxP3+ (%) 8 1 mg 6 10 mg Ki67+ (%) 4 6 100 mg/kg 4 2 2 0 0 15 1 22 se 7 15 22 7 e 1 os ay ay ay ay do ay ay ay ay d D D D D e- e- D D D D Pr Pr Peripheral blood flow cytometry confirmed that there
Slide 25: Predicted Human SL-325 PK Profiles Full RO at All Doses and High Trough Concentrations
Predicted Human SL-325 PK Profiles Full RO at All Doses and High Trough Concentrations with Repeat Dosing Predicted Human SL-325 PK Profiles in Serum Following Single IV Dose Predicted Human SL-325 PK Profiles in Serum Following Q2W*3 IV Dose Last RO Timepoint: Day 76 (1824h) Full RO at 0.3 ug/mL
Slide 26: Corporate Development Opportunities and Milestones
Corporate Development Opportunities and Milestones 26
Slide 27: TL1A/DR3 Axis Development Landscape
TL1A/DR3 Axis Development Landscape TL1A Blocking mAbs DR3 Blocking mAbs Potential for more durable blockade of the TL1A/DR3 axis Humanized Human IgG1 Fully human Fully human IgG1 Potential for higher rates of mAb mAb mAb mAb endoscopic remission Tulisokibart Duvakitug Afimkibart SPY002 No ris
Slide 28: Shattuck Labs Expected Milestones
Shattuck Labs Expected Milestones First-in-Class DR3 Pursuing Established Executing on Antagonist Program Clinical Market Upcoming Milestones SL-325 demonstrated superior SL-325 positioned in established Enrollment ongoing in Phase 1 TL1A/DR3 blockade in head-to- clinically-validated IBD patie
Slide 29: Cash and Shares Outstanding
Cash and Shares Outstanding $86.1 million cash as of September 30, 2025(1) Expected cash runway into 2029(2) Shares Outstanding Number of Shares (M) Common Stock Shares Outstanding 63.1 Common Stock Pre-Funded Warrants 40.5 Equivalents Warrants Common Stock Warrants 52.6 Outstanding ($1.0846 Exercis
Slide 30: Thank You
Thank You Investor Relations InvestorRelations@ShattuckLabs.com 30
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