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SHATTUCK SHATTUCK LABS , INC . NASDAQ : STTK LABS Corporate Overview August 11 , 2026
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2 Disclaimer and 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 historical facts included in this presentation, are forward-looking statements, including statements, express or implied, concerning: our plans, objectives, goals, strategies or intentions relating to products and markets; the potential purity, potency, safety, and clinical benefits of our product candidates, including SL- 325; the anticipated timing and design of our planned and ongoing preclinical studies and clinical trials, including timing of enrollment; the anticipated timing for data and the association of preclinical data with potential clinical benefit; the timing of anticipated milestones, plans and objectives of management for future operations; the anticipated development of additional preclinical pipeline programs; potential addressable market size; and our expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “plan,” “develop” or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the forward-looking statements expressed or implied in this presentation, in addition to those risks and uncertainties, such as global macroeconomic conditions and related volatility; expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; our expectations regarding the overall benefit of the strategic prioritization of our pipeline; liquidity and capital resources; and other risks and uncertainties described in “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K (File No. 001-39593) for the fiscal year ended December 31, 2025 and elsewhere in such filing and in our other periodic reports and subsequent disclosure documents filed with the U.S. Securities and Exchange Commission. We cannot assure you that we will realize the results, benefits or developments that we expect or anticipate or, even if substantially realized, that they will result in the consequences or affect us or our business in the way expected. Forward-looking statements are not historical facts, and reflect our current views with respect to future events. Given the significant uncertainties, you should evaluate all forward-looking statements made in this presentation in the context of these risks and uncertainties and not place undue reliance on these forward-looking statements as predictions of future events. All forward-looking statements in this presentation apply only as of the date made and are expressly qualified intheir entirety by the cautionary statements included in this presentation. We have no intention to publicly update or revise any forward-looking statements to reflect subsequent events or circumstances, except as required by law. We obtained the data used throughout this presentation from our own internal estimates and research, as well as from research, surveys and studies conducted by third parties. Internal estimates are derived from publicly available information released and our own internal research and experience, and are based on assumptions made by us based on such data and our knowledge, which we believe to be reasonable. In addition, while we believe the data included in this presentation is reliable and based on reasonable assumptions, we have not independently verified any third- party information, and all such data involve risks and uncertainties and are subject to change based on various factors. This presentation concerns a discussion of investigational drugs that are under preclinical and/or clinical investigation andwhich have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated.
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3 Milestones and Cash Preclinical Pipeline Lead Program: SL-325 Shattuck Labs (NASDAQ: STTK) DR3 = Death Receptor 3 (TNFRSF25) Shattuck Labs Overview 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 ● Potentially first-in-class blocking antibody targeting DR3, the receptor for TL1A ● Potentially best-in-mechanism immunogenicity profile ● Durable inhibition of TL1A may enable quarterly maintenance dosing ● Potential for superior efficacy in comparison to TL1A blocking antibodies ● RECEPTIVE-CD1 Phase 2B clinical trial in Crohn’s disease expected to initiate in Q3 2026 ● May explore additional indications beyond inflammatory bowel disease ● SL-846, a potentially first-in-class, half-life-extended, DR3 x IL-23 receptor blocking antibody ● SL-425, a half-life extended DR3 blocking antibody ● SL-325 Phase 2b initiation in Crohn's Disease Q3 2026, induction data expected 1H 2028 ● SL-846 Phase 1 initiation and initial data expected in 2027 ● As of June 30, 2026: $208.3 million in cash and cash equivalents and short terminvestments, expected to fund planned operations into 2029
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4 Blocking the TL1A Receptor, Known as DR3, Is Potentially Superior to Blocking TL1A Itself Clinically validated TL1A-DR3 axis Multiple Phase 2 trials with anti-TL1A antibodies have shown that TL1A-DR3 blockade potentially provides best-in-disease placebo adjusted clinical remission rates with well-tolerated safety profiles. Targets the receptor, not the ligand Blocks DR3 rather than binding soluble TL1A circulating in the blood. Stable target for better efficacy Targeting the constitutively expressed DR3, across inflamed and adjacent tissue may enable more complete inhibition of the axis. This may translate to higher response rates in comparison to blocking a transiently expressed ligand like TL1A. Avoids immunogenicity that may limit efficacy TL1A blocking antibodies create immune complexes with soluble TL1A, leading to high rates of anti-drug antibodies. SL-325 has a potentially best-in-mechanism immunogenicity profile, which may improve efficacy and response durability. May enable extended dosing and patient convenience Highly durable inhibition of TL1A binding to DR3 may enable quarterly maintenance dosing with a subcutaneous autoinjector-compatible format. 1 2 3 4 5
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5 IBD = Inflammatory Bowel Disease; RA = rheumatoid arthritis; PsA = psoriatic arthritis; HS = hidradenitis suppurativa, I&I = inflammatory and immune-mediated diseases Potentially First-in-Class Pipeline Targeting DR3 ● Developing potentially first-in-class DR3 monospecific and bispecific antibodies LEAD TARGET(S) INDICATIONS IND-ENABLING PHASE 1 PHASE 2 EXPECTED MILESTONES SL-325 DR3 IBD Potentially RA, PsA, HS, other I&I • RECEPTIVE-CD1 Phase 2b in Crohn’s disease initiation in Q3 2026 • RECEPTIVE-CD1 Phase 2b in CD 12W induction data in 1H 2028 SL-425 EXTENDED HALF-LIFE DR3 Potentially RA, PsA, HS, other I&I SL-846 EXTENDED HALF-LIFE DR3 X IL-23R Potentially IBD, PsA, other I&I • Phase 1 Initiation in 1H 2027 ● DR3 blockade with SL-325 provides potentially best- in-mechanism immunogenicity compared to TL1A blocking antibodies ● Blocking DR3 may provide more potent inhibition of the TL1A/DR3 axis than TL1A blockade due to more durable inhibition of TL1A signaling
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TL1A / DR3 Biology Rationale for Targeting the TL1A Receptor in a Clinically-Validated Axis
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7 TL1A/DR3 Signaling Promotes Inflammation in IBD and a Potentially Broad Range of Diseases TL1A/DR3 Axis Biology TL1A is expressed primarily on tissue-resident antigen presenting cells (APCs), signals solely via DR3, and is neutralized by the soluble decoy receptor (DcR3) DR3 is expressed by circulating and tissue-resident lymphoid cells and binds only to TL1A TL1A is the only ligand for DR3, and contributes to inflammation in IBD and other autoimmune and inflammatory diseases 1 2 3 PROTEASE CLEAVAGE TL1A DR3 SOLUBLE TL1A DCR3 BINDS TO SOLUBLE TL1A Tissue Resident APCs Lymphoid Cells In Blood and Tissue Increased Inflammation Mediated by T Helper (Th) Cell Driven Cytokine Production ● TH1 (IFNγ & TNFα) ● TH2 (IL-13) ● TH9 (IL-9) ● TH17 (IL-17)
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8 Sands B. et al. NEJM 2024; 391:1119-1129. 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. 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. TL1A/DR3 Blockade Is Clinically Validated and May Become the Backbone of IBD Therapy Induction Efficacy at 12 weeks in Ulcerative Colitis, Placebo-adjusted clinical remission, % Well Tolerated to Date Less Well Tolerated Safest TL1A α4β7 IL-23s TNFas S1P1s JAKs UPADACITINIB TOFACITINIB ETRASIMOD OZANIMOD GOLIMUMAB INFLIXIMAB ADALIMUMAB RISANKIZUMAB MIRIKIZUMAB USTEKINUMAB VEDOLIZUMAB OBEFAZIMOD AFIMKIBART TULISOKIBART DUVAKITUG 27% 25% 20% 16% 12% 12% 11% 14% 8% 23% 12% 12% 15% 12% 25% miRNA
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9 *Prehn J et al. J Clin Immunol 2004; Bamias G et al. Gut 2024 Multiple Independent Opportunities for Best-in-Mechanism Profile for SL-325 DR3 Expression and Stability ● TL1A is expressed transiently at sites of inflammation in the gut but not by adjacent non-inflamed tissue ● DR3 is expressed constitutively both as sites of inflammation and adjacent non-inflamed tissue* ● Blockade of DR3 may allow for more complete and durable inhibition of the TL1A/DR3 pathway ● DR3 is potentially a “more druggable” target, and our QSP modelling suggests higher signal inhibition than TL1A targeting antibodies ● ADA rate of 3.7% in Phase 1, a potentially best-in- mechanism immunogenicity profile. Anti-TL1A antibodies have reported 48-82% ADA in similar Phase 1 trials ● DR3 targeted antibodies avoid immune complex formation ● ADA negatively impacts efficacy in patients with inflammatory bowel disease ● SL-325’s immunogenicity profile may improve efficacy at both induction and maintenance time points, compared to TL1A antibodies Immunogenicity Profile Patient Convenience ● Phase 1 data demonstrated highly durable inhibition of TL1A binding to DR3 at low doses (0.1 mg/kg and higher) ● Data indicate the potential for quarterly maintenance dosing at doses of 1 mg/kg and higher ● A subcutaneous formulation of SL-325 has been developed, enabling administration of up to ~4 mg/kg doses at a volume compatible with a self-administered autoinjector pen device Expectation for Increased Efficacy
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10 Prehn J. J Clinical Immunol 2004. DR3 Is a More Abundant and Stable Target Than TL1A Crohn's Disease is characterized by discontinuous and migratory inflammation DR3 is expressed throughout the gut in IBD patients, TL1A is not TL1A is less abundant than DR3 in actively inflamed areas DR3 is evenly upregulated in both inflamed and adjacent uninflamed tissue 8.4% TL1A Expressing Cells 42.4 TL1A/DR3 Expression at Inflamed Sites TL1A/DR3 Expression at Adjacent Sites 17.4% DR3 Expressing Cells 52.6 18.8% DR3 Expressing Cells 38.6 3.4% TL1A Expressing Cells 49.9 mb-TL1A CD4 CD4 DR3 mb-TL1A CD4 CD4 DR3
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11 Migone et al. Immunity. 2002;16:479-92. Meylan et al. Immunity 2008; 29:79-89. Schreiber et al. J Immunol 2012;189(7);3311-8. TL1A Is Transiently Expressed, Primarily in Tissues ● TL1A is the sole ligand to DR3/TNFRSF25 ● TL1A is rapidly inducible in dendritic cells, macrophages and certain non-hematopoietic cells by Toll Like Receptor or FcγR ligation 0 100 200 300 Relative TL1A Expression Time (hours) 0 5 10 15 1 hr 6 hr 24 hr Relative TL1A Expression ● TL1A is turned on and off quickly primarily by tissue-resident antigen presenting cells ● TL1A is not expressed in the absence of stimulation by innate factors NT TNF IL-1α PMA bFGF IFNγ NT TNF IL-1α PMA bFGF IFNγ NT TNF IL-1α PMA bFGF IFNγ 0 10 20 ● UNSTIMULATED ● LPS ● IMMUNE COMPLEX
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12 *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 BioRender.com Maximal Efficacy of TL1A Blocking Antibodies Is Limited by Immunogenicity ● Anti-TL1A antibody binding to soluble TL1A in blood is an undesired site of action that causes immune complex formation ● This leads to anti-drug antibody (ADA) rates for anti-TL1A antibodies of 48-100% in Phase 1 trials* ● Both total ADA and neutralizing ADA cause similar reduction in efficacy** ● ADA can accelerate clearance of TL1A blocking antibodies, which correlates with reduced efficacy*
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13 *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 utilized a sequence-equivalent of tulisokibart. Created in BioRender.com Immune Complexes Between TL1A and Anti-TL1A Antibodies Directly Increase TL1A Expression Tulisokibart/TL1A immune complex (IC) triggers >75-fold increase in TL1A production by human monocytes in vitro** A feedback loop of TL1A immune complexes increasing TL1A expression may: ● Further increase immunogenicity risk ● Increase the amount of antibody needed to neutralize free TL1A, potentially contributing to high dose requirements for TL1A antibodies
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14 *Combined 450 mg and 900 mg dose levels. **50🡪50, 150🡪150 and 450🡪450 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 patients in remission in maintenance divided by 55 patients in remission at induction equates to an increase in the number of patients in remission from induction to maintenance of 38% High ADA May Limit Durability of Clinical Benefit in IBD ● The mechanism of immune complex formation is similar for anti-TL1A and anti- TNF antibodies, leading to high rates of ADA to both classes ● ADA rates to IL-23 inhibitors are significantly lower than TL1A or TNF inhibitors ● The number of patients in clinical remission improves over time for IBD drugs with low rates of ADA Placebo Adjusted Clinical Remission at Induction No. Patients in Remission Induction Maintenance Infliximab UC FDA Label 19.5% 161 160 Adalimumab UC Sandborn Gastro 2012, FDA Label 8.25% 41 43 Tulisokibart UC Ma C UEGW 2024 25% 18 19 Duvakitug UC* Teva Corp Updates 2/24/2025 & 2/19/2026 27% 39 37 Afimkibart UC Danese S, Lancet Gastro 2025** 20% 33 33 Upadacitinib UC Danese, Lancet 2022 29% 58 80 Tofacitinib UC Sandborn, NEJM 2017, FDA Label 13% 55 90 Ustekinumab UC Sands, NEJM 2019, FDA Label 12% 41 79 Risankizumab UC Panaccione, J Crohn’s & Colitis 2025***, FDA Label 16% 38 90
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SL-325 Program Potential First-In-Class DR3 Blocking Antibody
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16Bamias G. Gut 2025;74:652-668 Hussain M et al. IBD Journal 2026. In Press SL-325 Is a High-Affinity DR3-Specific Blocking Antibody ● TL1A is the sole known signaling ligand for DR3 and does not signal through any other receptors ● SL-325 potently inhibits TL1A binding to DR3 ● SL-325 does not bind DcR3, allowing TL1A clearance by DcR3 to remain intact ● SL-325 binds DR3 with very high affinity (1.3 pM) ● Highly durable DR3 occupancy is expected to extend dosing intervals ● By targeting membrane-bound DR3 rather than soluble TL1A, SL-325 was designed to avoid circulating TL1A immune complex formation which leads to high ADA rates TL1A Is Primarily Expressed by Tissue-Resident APCs DR3 Is Primarily Expressed by Lymphoid Cells In Blood and Tissue TL1A DR3 SOLUBLE TL1A DCR3 BINDS TO SOLUBLE TL1A PROTEASE CLEAVAGE SL-325
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17 Completed 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 ● Dosing is complete for all 72 participants Phase 1 Clinical Trial Design Key Questions Evaluated in Phase 1 ● Is SL-325 as well tolerated as anti-TL1A antibodies? ● Does human data confirm that SL-325 is a pure DR3 blocking antibody? ● How durable is DR3 occupancy, and what does that translate to with regard to expected maintenance dosing intervals? ● Is SL-325 less immunogenic than TL1A blocking antibodies? INCREASING DOSE PART A 6 SL-325 : 2 Placebo Participants Per Cohort 6 SL-325 : 2 Placebo Participants Per Cohort Placebo SL-325 N 18 54 Median Age (years, range) 31 (21, 53) 35 (22, 54) Sex, % Female 56 69 Participant Demographics
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18TEAE = 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 negative. The participant was diagnosed with severe Strep throat the following day. The underlying medical condition may have contributed to the reaction. The third dose was not given. SL-325 Was Safe and Well Tolerated Across a Wide Dosing Range SL-325 DOSE LEVEL (mg/kg) Placebo 0.1 0.3 1.0 3.0 10 30 N 18 6 6 12 12 12 6 ≥ 1 TEAE 5 2 2 6 7 4 2 ≥ 1 TRAE Mild (SAD) 1 0 0 1 2 0 1 Mild (MAD) 0 - - 2 3 3 - Moderate 0 0 0 0 0 0 0 Severe 0 0 0 0 0 0 0 Serious AE 0 0 0 0 0 0 0 Discontinued Due to TRAE 0 0 0 0 0 1* 0 ● Data are inclusive of all participants in all SAD and MAD cohorts ● TEAE observed in ≥2 participants included: headache, nasal congestion, nausea, venipuncture site pain, cough, diarrhea, feeling hot, hyperhidrosis, dizziness, urinary tract infection, arthropod bite, and elective termination of pregnancy ● Mild TRAE (all Grade 1) observed in ≥2 participants included: headache (n=8), hyperhidrosis (n=2), dizziness (n=2), feeling hot (n=2) ● SL-325 was discontinued in one participant who experienced a mild IRR (Grade 1)*
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19 *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 targeting antibodies ● No SL-325 mediated changes in serum cytokines were observed (IFNγ shown as example below)* ● No change from baseline in the serum concentration of TL1A was observed ● These data corroborate our preclinical findings that SL-325 is a pure DR3 blocking antibody Dose LevelNo changes from pre-dose in proportions of cells (upper panels), nor the proportion of proliferating cells (lower panels) at any dose level
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20 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 ● Accumulation ratio of between 1.64-1.75 with repeated dosing
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21 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 ≥1 mg/kg ● Durable inhibition of TL1A binding could enable quarterly dosing intervals in the maintenance phase of therapy for SL-325 ● Shattuck has developed a subcutaneous formulation of SL-325, and these data also potentially indicate feasibility of administration with an autoinjector pen
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22 *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 simply report an ADA percentage ● ADA assay results are only valid if the serum concentration of the therapeutic antibody is below the assay’s drug tolerance threshold (Assay Tolerance) at the time of sample analysis ● FDA has reported that only 25% of antibodies have sufficient drug tolerance in the ADA assay at the time of BLA submission* ● This may be a source of high rates of false- negative results in reported ADA percentages, especially in high-dose cohorts.
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23 *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. **As of August 11, 2026, all follow-up has been completed, confirming the data shared on June 8th, 2026 SL-325 Demonstrated a Potentially Best-In-Mechanism Immunogenicity Profile with 3.7% ADA ● SL-325 ADA assay has a sensitivity of 5 ng/mL and assay tolerance up to SL-325 concentrations of 160 µg/mL in serum ● Data includes all participants from all SAD and MAD cohorts in all dose levels in the study** ● ADA were observed in 2/54 participants who received SL-325. ● In the two participants who developed ADA, titers remained low (8 and 16), without any impact on PK or RO ● Longitudinal sampling was performed to ensure that SL-325 concentrations fell within the dynamic range of the ADA assay for all study participants Reported Aggregate ADA Rates from Phase 1 Trials* Afimkibart ADA titer of ≤60 was reported as ADA negative: Danese S et al. Lancet Gastroenterol and Hepatol. 2025;10:882-895. SL-325 ADA rate is 0% when analyzed using this cutoff.
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24 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 agonism How durable is DR3 occupancy, and what does that translate to for expected maintenance dosing intervals? A single dose of SL-325 inhibits TL1A binding to DR3 for months, potentially enabling quarterly dosing intervals Is SL-325 less immunogenic than TL1A blocking antibodies? Potentially best-in-mechanism immunogenicity profile with ADA rate of 3.7%
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26 *Lewis JD et al. Gastroenterol 2023 Unmet Need With Existing Therapies for a Majority of Crohn’s Disease Patients ● Approximately 1 million US citizens, and 3-4 million people worldwide, are living with Crohn’s disease* ● Approved therapies for Crohn’s disease provide placebo-adjusted clinical remission rates following induction therapy at a ‘ceiling’ of approximately 20% ● Improving clinical remission rates for Crohn’s disease patients with safe and well-tolerated therapies could improve the lives of millions of people 0 20 40 60 80 100 Upadacitinib Risankizumab Ustekinumab Vedolizumab Mirikizumab Placebo Adjusted Remission Rate
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27 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 (CDAI 220-450) ● All patients have opportunity to receive SL-325 ● N = 232, randomized 1:1:1:1 Key Endpoints ● Primary: Endoscopic response at 12 weeks ● Secondary: Clinical remission at 12 weeks *Study design as currently contemplated, subject to change HD = high dose; MD = middle dose; LD = low dose; LTE = long term extension Blinded 12 Week Induction 38 Week Maintenance A Multi-Dose, Placebo-Controlled Phase 2b Study of SL-325 in Crohn’s Disease SL-325 HD SL-325 MD SL-325 LD SL-325 HD SL-325 HD (n=58) SL-325 MD (n=58) SL-325 LD (n=58) Placebo (n=58) LTE
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SL-846 A Potentially First-in-Class DR3 x IL-23R Bispecific Antibody
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29 Created in BioRender.com Strategies to Block TL1A/DR3 in Future Combination Therapy DR3 Targeted Bispecific Antibody Multi-Antibody Coformulation TL1A Targeted Bispecific Antibody Low Medium/High High Low High Low Excess to Target Saturation Excess to Target Saturation Excess to Target Saturation SC Autoinjector Possible IV or High-Volume On-Body Device Likely IV or High-Volume On-Body Device Likely Immunogenicity Risk Clinical Trial Complexity Dose Selection Delivery Format IL23RDR3 × IL23 p19+ IL23 p19, IL23 p40×TL1A TL1A
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30 Kroenke M et al. Frontiers Immunol 2021; Neelakantan S et al. ECCO 2026 Genovese M et al. Arth & Rheumatol 2018; Kroenke M et al. AAPS Journal 2021 Created in BioRender.com Strategies to Block TL1A/DR3 in Future Combination Therapy AMG966 RG6730/R07837195 JNJ-61178104/ ABT-122/COVA322 98.1% 100% 56-100% 100% 83% Not Reported Resulted in increased drug clearance ISRs common with repeated dosing TNFα directed bsAb terminated in early development due to ADA Reporter ADA Rate Reporter Neutralizing ADA Rate Other TNFαTL1A × IL23 p40× ×TL1A TNFαIL23 p40
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31 Strategies to Block TL1A/DR3 in Future Combination Therapy 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 vitro potency when compared to icotrokinra and risankizumab ● Enables binding in cis to DR3 expressing cells Effector-Null Human IgG1 Fc ● Mutations to remove Fc gamma receptor binding potential Knob-In-Hole Recombination ● Clinically validated bispecific antibody format Half-Life Extended ● Substitutions to increase exposure and allow for extended dosing intervals
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32 *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 performed similarly to, or slightly better than, each assay relative to the TL1A or IL-23 control ● Additional pre-clinical characterization of SL-846 versus controls will be provided at an upcoming medical meeting
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Corporate Development Opportunities and Milestones
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34 SL-325 offers a potentially first-in-class approach in the clinically validated TL1A/DR3 axis by blocking DR3 Clinically Validated Axis in IBD ● Potential for more durable blockade of the TL1A/DR3 axis ● Potential for higher rates of endoscopic remission ● No risk of soluble TL1A/mAb immune complex formation ● Low ADA potentially improves combinability with other mAbs ● Scaffold for co-targeting other inflammatory receptors, including IL-23 receptor TL1A/DR3 Axis Development Landscape TL1A Blocking Antibodies DR3 Blocking Antibodies Humanized mAb Tulisokibart Human IgG1 mAb Duvakitug Human IgG1 mAb Afimkibart Fully human IgG1 mAb SPY002 Fully human mAb ABBV-701 Human IgG1 mAb XmAb942 AI platform-designed mAb ABS-101 Humanized mAb SL-325 TARGETS LIGAND TARGETS RECEPTOR
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35 1.Evaluate Pharma 2. Based on $208.3 million in cash and cash equivalents and short-term investments as of June 30, 2026. Shattuck Labs Expected Milestones Industry Leading DR3 Blocking Antibody Pipeline Pursuing Established Clinical Market Executing on Upcoming Milestones ● Phase 1 results position SL-325 as potentially best-in-mechanism for the TL1A/DR3 axis ● Well tolerated ● Highly durable inhibition of TL1A binding may enable quarterly maintenance dosing ● No evidence of residual DR3 agonism ● Potentially best-in-mechanism immunogenicity profile with only 3.7% ADA rate ● SL-846 is a potentially first-in-class bispecific antibody which blocks both DR3 and the IL-23 receptor ● SL-325 positioned in established clinically-validated IBD patient population ● Large and growing market in IBD with $33.3 billion in worldwide sales by 20301 ● Despite approved therapies, continued high unmet need in IBD and other inflammatory autoimmune diseases ● Expect to initiate Phase 2b clinical trial for SL-325 in CD in Q3 2026, with 12-week induction data expected in 1H 2028 ● Initial SL-846 Phase 1 clinical trial data expected in 2027 ● Cash runway expected to fund planned operations and clinical development into 20292
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36 $208.3 million cash as of June 30, 20261 Expected cash runway into 20292 Shares Outstanding3 Number of Shares (M) Total Outstanding3 183.2 Common Stock Shares Outstanding 101.4 Common Stock Warrants4 0.0Warrants Outstanding Common Stock Equivalents Pre-Funded Warrants 81.8 1. Includes cash and cash equivalents and short-term investments as of June 30, 2026. 2. Based on cash and cash equivalents and short-term investments as of June 30, 2026. 3. As of August 10, 2026. Excludes shares issuable pursuant to issued and outstanding employee stock options and unvested restricted stock units. 4. As of July 2, 2026, all previously outstanding common stock warrants have been exercised. Cash and Shares Outstanding
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Thank You InvestorRelations@ShattuckLabs.com