Shattuck Labs : May 7, 2025 Shattuck Labs (STTK) Corporate Presentation

Published: 2026-05-07 11:48:14 ET STTK

Published on 05/07/2026 at 11:48 am EDT

Shattuck Labs, Inc. NASDAQ: STTK May 7, 2026

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 resources, to translate innovative ideas into medicines that improve the lives of patients with serious diseases

OUR VISION

3

Build incredible therapeutics off the beaten path by challenging ourselves to think differently

Shattuck Labs Overview

Shattuck Labs

(NASDAQ: STTK)

Clinical-stage biotechnology company pioneering the development of potentially first-in-class monoclonal and bispecific DR3 blocking antibodies for the treatment of patients with inflammatory and immune-mediated diseases

Lead Program: SL-325

Potentially first-in-class blocking antibody targeting DR3, the receptor for TL1A

Picomolar binding affinity to DR3 and overlapping epitope with TL1A

Potential for superior efficacy in comparison to TL1A blocking antibodies

Initial Phase 2 clinical development planned in Crohn's disease

Enrollment completed in Phase 1 clinical trial in healthy volunteers, data expected in the second quarter of 2026

Preclinical Pipeline

SL-425, a half-life extended DR3 blocking antibody

Bispecific antibodies targeting DR3 and other clinically validated targets in IBD

Experienced Team and Strong Cash Position

Highly experienced management team, board of directors, and scientific advisory board

$90.4 million in cash and cash equivalents as of March 31, 2026

Cash runway expected to fund planned operations and clinical development into 20291

DR3 = Death Receptor 3 (TNFRSF25)

1. Based on cash and cash equivalents as of March 31, 2026, and assuming the receipt of $51.5 million upon the full exercise of the outstanding common

Highly Experienced Management and Board

Board of Directors

Mona Ashiya, PhD

Member, OrbiMed Advisors

Dan Baker, MD

Helen M. Boudreau

CEO of KiRa Biotech, Interim CFO of Proteostasis, CDO of Cue Biopharma, VP, FORMA, Novartis US Immunology, R&D at

Johnson & Johnson (Janssen/Centocor)

Neil Gibson, PhD George Golumbeski, PhD Taylor Schreiber MD, Clay Siegall, PhD

Chief Scientific Officer, COI Chairman of the Board; EVP PhD President, CEO and Chairman Pharma; Chief Scientific of Business Development, Chief Executive Officer, of the Board of Immunome; Officer, Pfizer Oncology Celgene Shattuck CEO & Founder of Seagen

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

Chief Technical Officer

Chief Scientific Officer

General Counsel, Corporate Secretary and Chief Ethics and Compliance Officer

Shattuck's Pipeline Targeting the TL1A/DR3 Pathway

Programs Stage of Development

Developing potential first-in-class DR3 monospecific and bispecific antibodies

Blocking DR3 may provide more potent inhibition of the TL1A/DR3 axis than TL1A blockade

Blocking DR3 may prove to be less immunogenic than TL1A blockade

Lead Target(s) Indications IND-Enabling Phase 1 Phase 2

SL-325

DR3

IBD

SL-425

Extended Half-Life

DR3

IBD

Bispecifics

DR3 x Undisclosed

Autoimmune

TL1A / DR3 Biology

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Rationale for Targeting the Receptor In a Clinically-Validated Axis

TL1A Is the Sole Activating Ligand for DR3 and DR3 Activation Leads to Inflammation

TL1A/DR3 Axis Biology

Tissue Resident APCs

Lymphoid Cells In Blood and Tissue

Increased Inflammation Caused by T Helper (Th) Cell Driven Cytokine Production

TL1A

protease

cleavage

DR3

Th1 (IFNγ & TNFα)

Th2 (IL-13) Th9 (IL-9) Th17 (IL-17)

soluble TL1A

1

TL1A is expressed primarily on tissue-

resident antigen presenting cells (APCs), signals solely via DR3, and is neutralized by the soluble decoy receptor (DcR3)

2

DR3 is expressed by circulating and

tissue-resident lymphoid cells and binds only to TL1A

3

Aberrant TL1A/DR3 pathway activation

leads to inflammation, contributing to IBD and other autoimmune and inflammatory diseases

DcR3

binds to soluble TL1A

Clinical Validation of Blocking TL1A/DR3 Axis and Rationale for DR3 Targeting

Anti-TL1A Antibodies

Validated Biology: Multiple third-party anti-TL1A antibodies have demonstrated clinical activity in Phase 2 trials in IBD; Phase 3 trials ongoing in IBD

Clinical Efficacy: Encouraging clinical remission rates vs. other IBD drug classes

Safety and Tolerability: Anti-TL1A therapies have been generally well tolerated

Immunogenicity: High rates of immunogenicity (ADA) due to formation of immune complexes, as anti-TL1A antibodies bind to free, circulating TL1A. ADA have been shown to reduce efficacy for TL1A blocking antibodies.

Potential First-in-Class DR3 Antibody: SL-325

Potential for Greater Efficacy: Blocking DR3 receptor may provide more potent and durable blockade of the TL1A/DR3 axis, due to the stable expression of DR3. This may allow SL-325 to be more efficacious than TL1A blocking antibodies.

Safety and Tolerability: SL-325 is expected to have similar safety and tolerability as the TL1A blocking antibodies; SL-325 was well tolerated in acute toxicology study in non-human primates

Potential for Significantly Improved Immunogenicity Profile: SL-325 is expected to be less immunogenic than the anti-TL1A antibodies, because DR3 remains bound to the cell membrane and therefore immune complex formation is not expected. This may lead to greater and more durable efficacy and better use in combination strategies.

SL-325 is a potential first-in-class DR3 blocking antibody targeting a clinically-validated axis

Sands B. et al. NEJM 2024

Roche. TUSCANY-2: A Dose-Ranging Phase IIb Study Evaluating Efficacy and Safety of RO7790121, an Antibody Against Tumor Necrosis Factor-like Ligand 1A (Anti-TL1A) in Adults with Moderately to Severely Active Ulcerative Colitis. https://medically.roche.com/global/en/inflammatory-disease/acg-2024/medical-material/ACG-2024-presentation-danese-TUSCANY-2-a-dose-ranging-phase-pdf.html

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Teva. Teva and Sanofi Present New Positive Phase 2b Study Results at ECCO 2025 Reinforcing Best-in-Class Potential of Duvakitug (Anti-TL1A) in Ulcerative Colitis and Crohn's Disease. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Teva-and-Sanofi-Present-New-Positive-Phase-2b-Study-Results-at-ECCO-2025-ReinforcingBest-in-Class-Potential-of-Duvakitug-Anti-TL1A-in-Ulcerative-Colitis-and-Crohns-Disease/default.aspx

Inflammatory Bowel Disease Is a Large and Growing Market

$23.0 B

$33.3 B

$15.2 B

$20.1 B

$7.8 B

$13.2 B

2023

2030

UC ■ CD

Worldwide IBD Sales ($B)1

Worldwide inflammatory bowel disease sales and prevalence expected to grow steadily to 2030

UC = Ulcerative Colitis; CD= Crohn's Disease

1. Evaluate Pharma 10

DR3 Inhibition Is Potentially More Potent Than TL1A Inhibition

SL-325 Is a High-Affinity DR3-Specific Blocking Antibody

Tissue Resident APCs

Lymphoid Cells In Blood and Tissue

TL1A

DR3

SL-325

protease

cleavage

soluble

KD = 1.36pM IC50 = 0.8nM

TL1A

DcR3

binds to soluble TL1A

TL1A is less abundant than DR3 in

actively inflamed areas

8.4% TL1A

Expression

17.4% DR3

Expression

DR3 is evenly upregulated in both

inflamed and adjacent uninflamed tissue

3.4% TL1A

Expression

18.8% DR3

Expression

Crohn's Disease is characterized by discontinuous and migratory inflammation

DR3 is more abundant, constitutively expressed, and evenly upregulated in involved and adjacent uninvolved

GI tissue in UC and Crohn's Disease than TL1A, providing rationale as a better target for TL1A inhibition

DR3 is constitutively expressed by lymphocytes both at involved and uninvolved areas of the gut

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 cells, TL1A is not

GI Tissue

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 Meylan et al. Immunity 2008; 29:79-89

Targeting DR3 May Enable More Effective Treatment of Inflammation DR3 Is Constitutively Expressed - TL1A Is Not

Inflamed

Inflamed

Non-

inflamed

Inflammation in the GI Tract

High

TL1A is expressed transiently at sites of inflammation in

the gut but not by adjacent non-inflamed tissue1

DR3 Expression

Low

TL1A Expression

DR3 is expressed constitutively both at sites of inflammation and adjacent non-inflamed tissue

Inflammation in Crohn's disease and Ulcerative Colitis is not static, and can wax and wane at distinct areas of the gut over time

Constitutive expression of DR3 may enable durable receptor blockade to dampen the migration of inflammation from inflamed to adjacent non-inflamed areas of the bowel, contributing to endoscopic remission

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Potential First-In-Class DR3 Blocking Antibody

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)

Silent Fc domain

Potent blockade of monomeric and trimeric TL1A

to DR3 in preclinical models

Receptor blockade expected to provide more durable protection from inflammation than ligand blockade because DR3 is constitutively expressed

Phase 1 Clinical Trial of SL-325; Enrollment is Complete, Data expected in second quarter of 2026

Phase 1 Clinical Trial Design

Single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy volunteers

Planned enrollment of ~70 participants

Enrollment in the SAD portion of the trial, and two of three MAD cohorts, now complete

Objectives of Phase 1 Study

Safety and Tolerability

PK Profile

Immunogenicity Profile

Durability of DR3 Receptor Occupancy

Confirmation of Lack of Agonism

Outcomes from Phase 1 Study

Recommended Phase 2 Dose and Schedule

Acceptable profile for continued development

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In vitro and GLP NHP Data

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.

Disclaimer

Shattuck Labs Inc. published this content on May 07, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 07, 2026 at 15:45 UTC.