Shattuck Labs, Inc. · NASDAQ:STTK
Shattuck Labs — Corporate Update (June 2026)
25 slides from Shattuck Labs's corporate update, Jun 9, 2026
Slide 1: Phase 1 Clinical Data of SL-325, a Potentially First-In-Class DR3 Blocking Antibody & Pipeline Update
Phase 1 Clinical Data of SL-325, a Potentially First-In-Class DR3 Blocking Antibody & Pipeline Update SHATTUCK LABS, INC. NASDAQ: STTK Exhibit 99.3
Slide 2: Disclaimer
Disclaimer 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 historical facts included
Slide 3: Call Agenda and Participants
Call Agenda and Participants SL-325 Phase 2b Study in Crohn’s Disease RECEPTIVE-CD1 Taylor Schreiber, MD, PhD Chief Executive Officer Lini Pandite, MD, MBA Chief Medical Officer Suresh De Silva, PhD Chief Scientific Officer Michael Choi, MD VP Clinical Development Andrew Neill, MBA Chief Financial O
Slide 4: Introduction
Introduction SL-325 DR3 SL-325 is a fully human, Fc-silenced, IgG1 monoclonal antibody (mAb) that selectively binds to DR3 and blocks its interaction with TL1A* DR3 blockade has the potential to provide superior efficacy in comparison to TL1A blockade because: DR3 is a more abundant and stable targe
Slide 5: SL-325 Is a High-Affinity, Highly Specific, DR3 Blocking Antibody
Bamias G. Gut 2025;74:652-668 Hussain M et al. IBD Journal 2026. In Press SL-325 Is a High-Affinity, Highly Specific, DR3 Blocking Antibody TL1A Is Primarily Expressed by Tissue-Resident APCs TL1A is the sole known signaling ligand for DR3 and does not signal through any other receptors SL-325 poten
Slide 6: Potentially First-in-Class Pipeline Targeting DR3
Potentially First-in-Class Pipeline Targeting DR3 IBD = Inflammatory Bowel Disease; RA = rheumatoid arthritis; PsA = psoriatic arthritis; HS = hidradenitis suppurativa, I&I = inflammatory and immune-mediated diseases Developing potentially first-in-class DR3 monospecific and bispecific antibodies LE
Slide 7: Immune Complex Mediated Immunogenicity Limits Efficacy of TL1A Blocking Antibodies
*Danese S et al. Lancet Gastroenterol and Hepatol. 2025;10:882-895; SYRE Corp Update 6/17/2025; Balyan R et al. J Crohn‘s and Colitis 2024;18:1206-1207; RXDX Corp Update 12/7/2021; XNCR Corp Update 5/4/2026. **Emery P et al. Scand J Rheumatol 2020;49:361-370 Created in https://BioRender.com Immune C
Slide 8: High ADA May Limit Durability of Clinical Benefit in IBD
*Combined 450 mg and 900 mg dose levels **50à50, 150à150 and 450à450 mg dose levels combined ***AT-IR patients Data in the figure are presented as a proportion of the total number of patients in remission at the maintenance timepoint relative to the induction timepoint. Example for upadacitinib: 90
Slide 9: Immune Complexes Between TL1A and Anti-TL1A Antibodies Directly Increase TL1A Expression
Immune Complexes Between TL1A and Anti-TL1A Antibodies Directly Increase TL1A Expression *Meylan et al. Immunity 2008; 29:79-89 **Data demonstrate fold increase in TL1A mRNA expression from human monocytes following exposure to the indicated test articles in vitro. Study conducted by Shattuck. Study
Slide 10: Phase 1 Clinical Trial of SL-325 in Healthy Participants
Phase 1 Clinical Trial of SL-325 in Healthy Participants 0.1 mg/kg 1 mg/kg 0.3 mg/kg 3 mg/kg 1 mg/kg 10 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg Single Ascending Dose PART B Multiple Ascending Dose (3 doses, q2w) Single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy participants Dosi
Slide 11: SL-325 Was Safe and Well Tolerated Across a Wide Dosing Range
TEAE = treatment emergent adverse events; TRAE = treatment related or possibly related adverse events; IRR = infusion-related reaction *The participant experienced a mild IRR during the second infusion. The symptoms resolved without therapeutic intervention and within 10 minutes. ADA remained negati
Slide 12: No Evidence of Residual DR3 Agonism in Phase 1 in Healthy Human Participants
*Cytokine panel evaluated: IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 and IL-13 No Evidence of Residual DR3 Agonism in Phase 1 in Healthy Human Participants The risk of agonism must be discharged for receptor targeted antibodies No SL-325 mediated changes in serum cytokines were observe
Slide 13: PK Profile of SL-325 from Phase 1 in Healthy Human Participants
PK Profile of SL-325 from Phase 1 in Healthy Human Participants Dose proportional increase in Cmax and AUClast across all dose levels from 0.1 to 30 mg/kg Clearance consistent across all dose levels Estimated half-life of 16 days Figure shows participant-level PK profiles from all SAD cohorts Accumu
Slide 14: A Single Dose of SL-325 Blocked TL1A Binding in a Dose-Dependent Manner for Months
A Single Dose of SL-325 Blocked TL1A Binding in a Dose-Dependent Manner for Months DR3 occupancy was measured by inhibition of TL1A binding Full DR3 occupancy was achieved even at the lowest dose of 0.1 mg/kg Dose-dependent extension in the duration of TL1A blockade was observed, lasting months at ≥
Slide 15: Anti-Drug Antibody (ADA) Assay Performance and Data Interpretability
*Wang Y et al. Pharm Res 2012;29:3384-3392, Wang Y ASCPT 2017 Anti-Drug Antibody (ADA) Assay Performance and Data Interpretability Inadequate assay tolerance contributes to a commonly held belief that higher doses of drug lead to lower incidence of ADA Sponsors commonly report ADA qualitatively, or
Slide 16: SL-325 Demonstrated a Potentially Best-In-Mechanism Immunogenicity Profile with 3.7% ADA
*ADA rates are provided as they were reported in the referenced publications/reports. These data were not generated in head-to-head clinical trials. Comparisons across trials have inherent limitations and caution should be exercised when comparing data from unrelated studies. **Data as of June 8, 20
Slide 17: Key Questions Answered in Phase 1 for SL-325
Key Questions Answered in Phase 1 for SL-325 Is SL-325 as well-tolerated as anti-TL1A antibodies? Yes, SL-325 was well tolerated across a wide dosing range. Does human data confirm that SL-325 is a pure DR3 blocking antibody? Yes, SL-325 is a pure blocking antibody with no evidence of residual agoni
Slide 18: A Multi-Dose, Placebo-Controlled Planned Phase 2b Study of SL-325 in Crohn's Disease
*Study design as currently contemplated, subject to change Study Design Elements Double-blind, placebo-controlled IV induction and maintenance Dose selection informed by Phase 1 PK/RO based QSP modeling with >95% TL1A signal inhibition throughout the dosing interval Population Moderate to severe CD
Slide 19: SL-846 A Potentially First-in-Class DR3 x IL-23R Bispecific Antibody
SL-846 A Potentially First-in-Class DR3 x IL-23R Bispecific Antibody
Slide 20: Strategies to Block TL1A/DR3 in Future Combination Therapy
Strategies to Block TL1A/DR3 in Future Combination Therapy Created in https://BioRender.com
Slide 21: TL1A-Directed Bispecific Antibodies Are Hyper-Immunogenic
TL1A-Directed Bispecific Antibodies Are Hyper-Immunogenic Kroenke M et al. Frontiers Immunol 2021; Neelakantan S et al. Br J Clin Pharmacol 2026 Genovese M et al. Arth & Rheumatol 2018; Kroenke M et al. AAPS Journal 2021 Created in https://BioRender.com
Slide 22: SL-846 – A Potentially First-In-Class DR3 x IL-23R Half-Life Extended Bispecific Antibody
SL-846 – A Potentially First-In-Class DR3 x IL-23R Half-Life Extended Bispecific Antibody DR3 Binding Arm IL-23R Binding Arm Same binding epitope as SL-325 Avoids risk of immune complex formation Enables binding in cis to IL-23R expressing cells Validated mechanism of action (icotrokinra) Similar in
Slide 23: SL-846 Demonstrated Competitive In Vitro Potency to Icotrokinra and Risankizumab
*Sequence equivalents of tulisokibart, risankizumab, and icotrokinra SL-846 Demonstrated Competitive In Vitro Potency to Icotrokinra and Risankizumab SL-846 was tested head-to-head against tulisokibart, risankizumab and icotrokinra* in a variety of in vitro binding and potency assays SL-846 performe
Slide 24: Conclusions
Conclusions SL-325 Has the Profile of a Winning Antibody Phase 2 Initiation in CD Expected in Q3 2026 12W Induction Data Expected in 1H 2028 SL-846 is a Potentially First-In-Class DR3 x IL-23R Bispecific Antibody NHP Tox/Immunogenicity Data Expected in 2H 2026 Phase 1 Initiation Expected in 1H 2027
Slide 25: Thank You
Thank You SHATTUCK LABS, INC. NASDAQ: STTK INVESTORRELATIONS@SHATTUCKLABS.COM