An Open-Label, Phase 1b Study of SL-172154 (SIRPα-Fc-CD40L) Administered With Either Pegylated Liposomal Doxorubicin or Mirvetuximab Soravtansine in Subjects With Platinum-Resistant Ovarian Cancers

SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate SL-172154 administered in combination with pegylated liposomal doxorubicin (PLD) or mirvetuximab soravtansine (MIRV) in patients with platinum resistant ovarian cancer. Approximately 102 patients will be enrolled in this study.

Start Date18 Aug 2022

Sponsor / Collaborator

Shattuck Labs, Inc.

NCT05275439

/ TerminatedPhase 1

An Open-Label Phase 1a/1b Dose Escalation and Expansion Cohort Study of SL-172154 (SIRPα-Fc-CD40L) in Combination With Azacitidine or With Azacitidine and Venetoclax for the Treatment of Subjects With Higher-Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)

SL03-Old Hundred(OHD)-104 is designed as a Phase 1a/1b open label, trial to evaluate the safety, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary efficacy of SL-172154 monotherapy as well as in combination with azacitidine or in combination with Azacitidine and Venetoclax.

Start Date17 Mar 2022

Sponsor / Collaborator

Shattuck Labs, Inc.

NCT04502888

/ TerminatedPhase 1

Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L), Administered Intratumorally in Subjects With Cutaneous Squamous Cell Carcinoma or Squamous Cell Carcinoma of the Head and Neck

This is a Phase 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell carcinoma of the head and neck (SCCHN).

Start Date17 Sep 2020

Sponsor / Collaborator

Shattuck Labs, Inc.

100 Clinical Results associated with SL-172154

100 Translational Medicine associated with SL-172154

100 Patents (Medical) associated with SL-172154

Literatures (Medical) associated with SL-172154

20 Jun 2026·BRITISH JOURNAL OF CANCER

Phase Ib trial of SL-172154, a bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, in combination with mirvetuximab soravtansine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer

Article

Author: Martinez Bueno, Alejandro ; Gaba Garcia, Lydia ; Lakhani, Nehal ; Matei, Daniela ; Franke, Amy ; Miller, Rowan ; Galvez, Elisa ; Moreno, Victor ; Martínez García, Jerónimo ; Richardson, Debra L ; Miriyala, Jayalakshmi ; Barretina-Ginesta, Maria-Pilar ; Kristeleit, Rebecca S ; Yiannakis, Dennis ; Pandite, Lini ; Banerjee, Susana ; Jayson, Gordon C ; Wang, Guanfang ; Oza, Amit ; Drew, Yvette ; Gilbert, Lucy ; Oaknin, Ana

BACKGROUND:

Platinum resistant ovarian cancer (PROC) is associated with poor survival. This clinical trial sought to determine whether the bispecific CD47 inhibitor and CD40 agonist, SL-172154, could be combined safely and improve the efficacy of mirvetuximab (MIRV) or pegylated liposomal doxorubicin (PLD) through enhanced tumor cell phagocytosis and antigen presentation to T cells.

METHODS:

Patients with PROC received MIRV (21-day cycle) or PLD (28-day cycle) on day 1 and SL-172154 (3 mg/kg) on days 8 and 15 of each cycle. Objectives included safety, anti-tumor activity, PK, and immunogenicity.

RESULTS:

65 patients (60% folate receptor alpha (FRα) high and 40% medium/low) were enrolled in the MIRV cohort and 21 patients in the PLD cohort. Most common TEAEs ( > 40%) in the MIRV cohort were blurred vision, nausea, infusion related reaction, transaminase increase, diarrhea, and in the PLD cohort, nausea, constipation, neutropenia and fatigue. The objective response rate in the MIRV cohort was 33% (95% CI, 19%, 50%) for FRα high subgroup, and 15% (95% CI, 4%, 35%) for FRα medium/low subgroup, and in the PLD cohort was 20% (95% CI, 6%, 44%).

CONCLUSIONS:

Combination of SL172154 with MIRV did not improve upon the previously reported ORR for MIRV, while the combination with PLD resulted in a higher ORR than reported for PLD, albeit in a small number of patients. Limited tumor penetration of SL-172154, lack of durable CD47 blockade, inability to overcome T cell exhaustion and other mechanisms of resistance may explain these findings. Trial register number: NCT05483933.

01 Jan 2025·Journal for ImmunoTherapy of Cancer

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer

Article

Author: Lakhani, Nehal J ; Hamilton, Erika ; Ma, Bo ; Pandite, Lini ; Metenou, Simon ; Call, Justin ; Wang, Guanfang ; Richardson, Debra L ; Huguet, Jade ; Rangwala, Fatima ; Van Le, Linda ; Offman, Elliot ; Stewart, Daphne ; Dockery, Lauren E

Background:

SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG4-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

Methods:

SL-172154 was administered intravenously at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg. Dose escalation followed a modified toxicity probability interval-2 design. Objectives included evaluation of safety, dose-limiting toxicity, recommended phase II dose, pharmacokinetic (PK) and pharmacodynamic (PD) parameters, and antitumor activity.

Results:

27 patients (median age 66 years (range, 33–85); median of 4 prior systemic therapies (range, 2–9)) with ovarian (70%), fallopian tube (15%), or primary peritoneal (15%) cancer received SL-172154. Treatment-emergent adverse events (TEAEs) were reported for 27 patients (100%), with 24 (88.9%) having a drug-related TEAE and infusion-related reactions being the most common. 12 patients (44.4%) had grade 3/4 TEAEs, and half of these patients (22.2%) had a drug-related grade 3/4 TEAE. There were no fatal adverse events, and no TEAEs led to drug discontinuation. SL-172154 Cmax and area under the curve increased with dose with greater than proportional exposure noted at 3.0 and 10.0 mg/kg. CD47 and CD40 target engagement on CD4+ T cells and B cells, respectively, approached 100% by 3.0 mg/kg. Dose-dependent responses in multiple cytokines (eg, interleukin 12 (IL-12), IP-10) approached a plateau at ≥3.0 mg/kg. Paired tumor biopsies demonstrated a shift in macrophages from an M2- to an M1-dominant phenotype and increased infiltration of CD8 T cells. PK/PD modeling showed near maximal margination of B cells and a dose-dependent production of IL-12 nearing a plateau at >3.0 mg/kg. The best response was stable disease in 6/27 (22%) patients.

Conclusions:

SL-172154 was tolerable as monotherapy and induced, dose-dependent, and cyclical immune cell activation, increases in multiple serum cytokines, and trafficking of CD40-positive B cells and monocytes following each infusion. The safety, PK, and PD activity support 3.0 mg/kg as a safe and pharmacologically active dose.

Trial registration number:

NCT04406623.

News (Medical) associated with SL-172154

05 Mar 2026

·www.biospace.com

Shattuck Labs Reports Fourth Quarter and Full-Year 2025 Financial Results and Recent Business Highlights

Phase 1 clinical trial of SL-325 ongoing, with data expected in the second quarter of 2026 – Phase 2 clinical trial of SL-325 in patients with Crohn’s disease expected to initiate in the third quarter of 2026 – AUSTIN, Texas and DURHAM, N.C., March 05, 2026 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck or the Company) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of potential first-in-class monoclonal and bispecific DR3 blocking antibodies for the treatment of patients with inflammatory and immune-mediated diseases, today reported financial results for the fourth quarter and full year ended December 31, 2025 and provided recent business highlights. “SL-325 is now the first DR3 blocking antibody to generate human clinical data, and we are very pleased with the progress we have made in our Phase 1 clinical trial, which is nearly complete. We look forward to sharing the data from this trial in the second quarter, and anticipate initiating our Phase 2 clinical trial in Crohn’s disease in the third quarter,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. DR3 Program Development in 2025 Shattuck’s lead product candidate, SL-325, is a potentially first-in-class and best-in-mechanism DR3 blocking antibody for the treatment of Crohn’s disease, ulcerative colitis, and other inflammatory and immune-mediated diseases. Recent updates and anticipated upcoming milestones for SL-325, and Shattuck’s other DR3 blocking antibodies, include: The Phase 1 trial evaluating the safety, tolerability, immunogenicity, and pharmacokinetics (PK) of SL-325 in healthy volunteers is ongoing and progressing as planned, and will determine the recommended Phase 2 dose and dosing schedule. Enrollment of all six single-ascending dose (SAD) cohorts is now complete, and full enrollment in the final multiple-ascending dose (MAD) cohort of the trial is expected to be completed in the second quarter of 2026. Shattuck expects to disclose safety and tolerability, PK, receptor occupancy, duration of receptor occupancy, and immunogenicity data from this trial in the second quarter of 2026. Subject to positive Phase 1 data and regulatory alignment, Shattuck expects to initiate a Phase 2 clinical trial of SL-325 in patients with Crohn’s disease in the third quarter of 2026. Shattuck continues to develop multiple DR3-based bispecific antibodies. Shattuck’s lead bispecific antibody has entered IND-enabling activities. This bispecific antibody was designed to inhibit both the DR3/TL1A axis and another biologically relevant target for the treatment of patients with inflammatory and immune-mediated diseases. Shattuck plans to disclose the targets of its lead bispecific product candidate, supporting preclinical data, and expected development timelines in the first half of 2026. Appointment to Management Team Michael Choi, M.D., joined Shattuck Labs as Vice President of Clinical Development in November 2025. Dr. Choi brings extensive experience advancing inflammatory bowel disease programs, including as clinical lead at Morphic Therapeutic, where he led the development of MORF-057, its oral α4β7 antagonist. Earlier in his career, Dr. Choi served as Assistant Professor of Medicine at Harvard Medical School and Affiliated Faculty at the Harvard Stem Cell Institute. Dr. Choi received his medical degree from Cornell University, trained in Internal Medicine at UCSF, and completed his Gastroenterology Fellowship at Massachusetts General Hospital. Recent Events Shattuck participated in the Piper Sandler 37 th Annual Healthcare Conference on December 2, 2025. Dr. Schreiber presented at the conference and management participated in one-on-one meetings. Shattuck participated in the Evercore ISI 8 th Annual HealthCONx Conference on December 3-4, 2025. Dr. Schreiber participated in a fireside chat and management participated in one-on-one meetings. Shattuck participated in the Piper Sandler Virtual Novel Targets in Immunology Symposium on February 12-13, 2026. Dr. Schreiber, Andrew R. Neill, Chief Financial Officer, and Michael Choi, M.D., Vice President of Clinical Development participated in a fireside chat. Shattuck participated in the TD Cowen 46 th Annual Health Care Conference on March 2-4, 2026. Dr. Schreiber presented at the conference and management participated in one-on-one meetings. Upcoming Events Shattuck plans to attend the following investor conference. Details will be included on the Events & Presentations section of the Company’s website. Leerink Global Healthcare Conference 2026 (Miami, FL), March 8-11, 2026. Dr. Schreiber will present at the conference and participate in one-on-one meetings. Capital Markets Update In the first quarter of 2026, Shattuck sold shares of its common stock under its at-the-market offering facility for aggregate gross proceeds of $21.4 million. As a result of these sales, accounts advised by T. Rowe Price Investment Management, Inc. reported beneficial ownership of more than 10% of the Company’s outstanding common stock. As of February 28, 2026, cash and cash equivalents and short-term investments were approximately $94.5 million (unaudited), which includes the gross proceeds of $21.4 million from sales of Shattuck’s common stock under its at-the-market offering facility, as described above. This amount is preliminary, has not been audited or reviewed by the Company’s independent registered public accounting firm, and is subject to change upon completion of the Company’s financial closing procedures. Fourth Quarter and Full-Year 2025 Financial Results Cash and Cash Equivalents and Investments: As of December 31, 2025, cash and cash equivalents and short-term investments were approximately $78.1 million, as compared to $73.0 million as of December 31, 2024. Research and Development (R&D) Expenses: R&D expenses were $9.1 million for the quarter ended December 31, 2025, as compared to $15.4 million for the quarter ended December 31, 2024. R&D expenses for the year ended December 31, 2025 were $35.3 million, as compared to $67.2 million for the year ended December 31, 2024. This full year decrease was a result of the discontinuation of the SL-172154 program and related workforce reductions and other pipeline compound costs, partially offset by an increase in SL-325 expenses primarily as a result of moving SL-325 into clinical development in 2025. General and Administrative (G&A) Expenses: G&A expenses were $4.3 million for the quarter ended December 31, 2025, as compared to $4.2 million for the quarter ended December 31, 2024. General and administrative expenses for the year ended December 31, 2025 were $17.2 million, as compared to $19.1 million for the year ended December 31, 2024. This full year decrease was primarily the result of a decrease in compensation and related benefit expenses as a result of workforce reductions in 2024 as well as a decrease in legal fees. Net Loss: Net loss was $12.6 million for the quarter ended December 31, 2025, or $0.12 per basic and diluted share, as compared to a net loss of $18.7 million for the quarter ended December 31, 2024, or $0.37 per basic and diluted share. Net loss for the year ended December 31, 2025 was $48.8 million, or $0.70 per basic and diluted share, as compared to $75.4 million, or $1.49 per basic and diluted share, for the year ended December 31, 2024. Financial Guidance As of December 31, 2025, cash and cash equivalents and short-term investments were approximately $78.1 million. Shattuck’s current cash and cash equivalents and short-term investments, including the gross proceeds from its sale of common stock under its at-the-market offering facility of $21.4 million in the first quarter of 2026, and assuming the full exercise of the outstanding common stock warrants, are expected to fund operations into 2029. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken. About SL-325 SL-325 is a potential first-in-class Death Receptor 3 (DR3) blocking antibody designed to achieve a complete and durable blockade of the clinically validated DR3/TL1A pathway. Shattuck’s preclinical studies demonstrate high affinity binding and superior activity over TL1A antibodies, and offer a data-driven rationale for targeting the TNF receptor, DR3, versus its ligand, TL1A. SL-325 is a fully Fc-silenced, humanized immunoglobulin G monoclonal antibody with a favorable safety pro non-human primates, currently being evaluated in a Phase 1 clinical trial. About Shattuck Labs, Inc. Shattuck Labs, Inc. is a 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. Shattuck’s expertise in protein engineering and the development of novel TNF receptor therapeutics come together in its lead program, SL-325, a potentially first-in-class DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated DR3/TL1A pathway. The Company has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit:  Forward-Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations regarding: plans for our preclinical studies, clinical trials and research and development programs, particularly with respect to SL-325; the anticipated timing of release of data from our ongoing Phase 1 clinical trial of SL-325; the expected timing of enrollment in the MAD cohort of our Phase 1 clinical trial of SL-325; the anticipated timing of initiation of a Phase 2 clinical trial of SL-325 in patients with Crohn’s disease; the clinical benefit, safety and tolerability of SL-325; anticipated development of additional preclinical pipeline candidates the timing of nomination, release of preclinical data and development timelines of a lead bispecific antibody candidate; and expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While we believe these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in our filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: 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 preclinical studies and 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 identified in our Annual Report on Form 10-K for the year ended December 31, 2024, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. The Company intends to use the investor relations portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD. Investor & Media Contact: Andrew Neill Chief Financial Officer Shattuck Labs, Inc. InvestorRelations@shattucklabs.com FINANCIAL INFORMATION SHATTUCK LABS, INC. BALANCE SHEETS (In thousands) December 31, 2025 2024 Assets Current assets: Cash and cash equivalents $ 54,192 $ 57,387 Investments 23,873 15,600 Prepaid expenses and other current assets 4,410 6,228 Total current assets 82,475 79,215 Property and equipment, net 6,114 9,812 Investment in related party 1,000 — Other assets 1,437 2,022 Total assets $ 91,026 $ 91,049 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 2,101 $ 2,419 Accrued expenses and other current liabilities 4,951 6,498 Total current liabilities 7,052 8,917 Non-current operating lease liabilities 1,584 2,506 Total liabilities 8,636 11,423 Stockholders’ equity: Common stock 7 5 Additional paid-in capital 512,906 461,339 Accumulated other comprehensive income 6 2 Accumulated deficit (430,529 ) (381,720 ) Total stockholders’ equity 82,390 79,626 Total liabilities and stockholders’ equity $ 91,026 $ 91,049 SHATTUCK LABS, INC. STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (In thousands, except share and per share amounts) Three Months Ended December 31, (Unaudited) Year Ended December 31, 2025 2024 2025 2024 Related party license revenue $ — $ — $ 1,000 $ — Collaboration revenue — — — 5,721 Total revenue — — 1,000 5,721 Operating expenses: Research and development 9,057 15,395 35,273 67,211 General and administrative 4,316 4,246 17,235 19,077 Expense from operations 13,373 19,641 52,508 86,288 Loss from operations (13,373 ) (19,641 ) (51,508 ) (80,567 ) Other income (expense): Interest income 804 959 2,703 5,174 Other income (expense) (24 ) 3 (4 ) (17 ) Total other income 780 962 2,699 5,157 Net loss $ (12,593 ) $ (18,679 ) $ (48,809 ) $ (75,410 ) Unrealized gain (loss) on investments 6 (50 ) 4 (2 ) Comprehensive loss $ (12,587 ) $ (18,729 ) $ (48,805 ) $ (75,412 ) Basic and Diluted Per Common Share Data: Net loss per share - basic and diluted $ (0.12 ) $ (0.37 ) $ (0.70 ) $ (1.49 ) Weighted-average shares outstanding - basic and diluted 103,782,503 50,840,259 69,584,937 50,758,290

Phase 1Financial StatementExecutive Change

14 Nov 2024

·www.globenewswire.com

Shattuck Labs Reports Third Quarter 2024 Financial Results and Recent Business Highlights

– Announced development of SL-325, a first-in-class antagonist antibody to DR3, the receptor for TL1A; IND filing expected in Q3'2025 – – Cash balance of approximately $90M as of September 30, 2024; expected to fund operations into 2027 – AUSTIN, TX and DURHAM, NC, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a biotechnology company pioneering the development of novel therapeutics targeting tumor necrosis factor (TNF) superfamily receptors for the treatment of patients with cancer and chronic immune-related diseases, today reported financial results for the quarter ended September 30, 2024 and provided recent business highlights. “Last month we announced a strategic shift to focus on the development of SL-325, a first-in-class DR3 blocking antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 signaling pathway. We are underway with IND-enabling, non-human primate studies to evaluate the safety, pharmacokinetic and pharmacodynamic profile of SL-325,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “As of this month, we have substantively completed our restructuring plans to focus on the development of SL-325 and are well-positioned to fund our planned operations into 2027.” Upcoming Events Shattuck plans to attend the following investor conferences. Details will be included on the Events & Presentations section of the Company’s website. Piper Sandler & Co. 36th Annual Healthcare Conference (New York City, NY), December 3–5, 2024. Taylor Schreiber, M.D., Ph.D., CEO of Shattuck Labs will participate in a presentation on December 3, 2024.Evercore ISI 7th Annual HealthCONx Conference (Miami, FL), December 3–5, 2024. The Company’s management will participate in a fireside chat on December 4, 2024. Third Quarter 2024 Financial Results Cash and Cash Equivalents and Investments: As of September 30, 2024, cash and cash equivalents and investments were approximately $90.1 million, as compared to $101.1 million as of September 30, 2023.Research and Development (R&D) Expenses: R&D expenses were $16.3 million for the quarter ended September 30, 2024, as compared to $24.2 million for the quarter ended September 30, 2023.General and Administrative (G&A) Expenses: G&A expenses were $4.6 million for the quarter ended September 30, 2024, as compared to $5.1 million for the quarter ended September 30, 2023.Net Loss: Net loss was $16.7 million for the quarter ended September 30, 2024, or $0.33 per basic and diluted share, as compared to a net loss of $27.5 million for the quarter ended September 30, 2023, or $0.65 per basic and diluted share. Financial Guidance Shattuck has effectuated its restructuring plan to prioritize the development of the DR3 program and align the Company’s cost and workforce structure with the its current goals and clinical development strategy. The Company has substantially completed the reduction in force associated with the discontinuation of SL-172154. Shattuck believes its cash and cash equivalents and investments will be sufficient to fund its planned operations into 2027, beyond results from its Phase 1 clinical trial of SL-325. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from potential business development transactions, and/or additional costs associated with additional development activities that may be undertaken. About SL-325 SL-325 is a first-in-class Death Receptor 3 (DR3) antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 pathway. Shattuck’s preclinical studies demonstrate high affinity binding, superior efficacy over TL1A antibodies, and offer a data-driven rationale for targeting the TNF receptor, DR3, versus its ligand, TL1A. SL-325 is currently being evaluated in a GLP toxicology study in non-human primates, with an IND filing expected in the third quarter of 2025. About Shattuck Labs, Inc. Shattuck Labs, Inc. (Nasdaq: STTK) is a biotechnology company specializing in the development of potential treatments for autoimmune/inflammatory diseases and cancer. The Company is developing a potentially first-in-class antibody for the treatment of IBD and other inflammatory autoimmune diseases. Shattuck's expertise in protein engineering and the development of novel TNF receptor agonist and antagonist therapeutics come together in its lead program, SL-325, a first-in-class DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 pathway. The Company has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com. Forward-Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations regarding: plans for our preclinical studies, clinical trials and research and development programs, particularly with respect to SL-325; plans for the realignment of our strategic pipeline and discontinuation of clinical development of SL-172154; the anticipated timing of any regulatory filings for SL-325; the anticipated timing of our preclinical studies and clinical trials for SL-325; the clinical benefit, safety and tolerability of SL-325; the effects of the proposed restructuring and reduction in force on the Company’s results of operations and financial condition; and expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While we believe these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in our filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: 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 identified in our Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. The Company intends to use the investor relations portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD. Investor & Media Contact: Conor RichardsonVice President of Investor RelationsShattuck Labs, Inc.InvestorRelations@ShattuckLabs.com SHATTUCK LABS, INC. CONDENSED BALANCE SHEETS(In thousands) September 30, 2024 December 31,2023 (unaudited) Assets Current assets: Cash and cash equivalents$43,829 $125,626 Investments 46,229 4,999 Prepaid expenses and other current assets 8,682 12,595 Total current assets 98,740 143,220 Property and equipment, net 10,827 13,804 Other assets 2,153 2,540 Total assets$111,720 $159,564 Liabilities and Stockholders’ Equity Current Liabilities: Accounts payable$2,927 1,587 Accrued expenses 9,474 9,866 Total current liabilities 12,401 11,453 Non-current operating lease liabilities 2,742 3,406 Total liabilities$15,143 $14,859 Stockholders’ equity: Common stock 5 5 Additional paid in capital 459,561 451,006 Accumulated other comprehensive income 52 4 Accumulated deficit (363,041) (306,310)Total stockholders' equity 96,577 144,705 Total liabilities and stockholders' equity$111,720 $159,564 SHATTUCK LABS, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Unaudited) (In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Collaboration revenue$2,997 $686 $5,721 $943 Operating expenses: Research and development 16,313 24,211 51,816 59,083 General and administrative 4,604 5,073 14,831 14,866 Expense from operations 20,917 29,284 66,647 73,949 Loss from operations (17,920) (28,598) (60,926) (73,006)Other income 1,245 1,057 4,195 3,395 Net loss$(16,675) $(27,541) $(56,731) $(69,611)Unrealized gain on investments 57 81 48 884 Comprehensive loss$(16,618) $(27,460) $(56,683) $(68,727) Net loss per share – basic and diluted$(0.33) $(0.65) $(1.12) $(1.64)Weighted-average shares outstanding – basic and diluted 50,833,538 42,477,642 50,730,767 42,461,644

Phase 1Financial StatementPROTACs

02 Oct 2024

·pipelinereview.com

Shattuck Labs Provides Company Update and Announces SL-325, a First-In-Class Death Receptor 3 (DR3) Antagonist Targeting the TL1A/DR3 Signaling Pathway

– Interim clinical data for SL-172154 in combination with azacitidine in TP53 mutant (TP53m) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) showed only modest improvement in median overall survival compared to azacitidine monotherapy benchmarks; further development of SL-172154 discontinued – – Prioritization to focus on SL-325, a first-in-class antagonist antibody to DR3, the receptor for TL1A, intended for clinical development in inflammatory bowel disease (IBD); IND filing expected in Q3 2025 – – SL-172154 associated restructuring expected to extend cash runway into 2027 – AUSTIN, TX and DURHAM, NC, USA I October 01, 2024 I Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a biotechnology company pioneering the development of novel therapeutics targeting tumor necrosis factor (TNF) superfamily receptors for the treatment of patients with cancer and chronic immune-related diseases, today announced a strategic pipeline prioritization to include the discontinuation of its clinical program, SL-172154. The Company will turn its focus to SL-325, its DR3 antagonist antibody, and plans initial clinical development in patients with IBD, where TL1A/DR3 blocking antibodies have demonstrated compelling monotherapy efficacy. “We are disappointed that the promising complete remission rates we previously shared from our Phase 1 clinical trial did not translate to clinically meaningful improvements in median overall survival for TP53m AML and HR-MDS patients treated with SL-172154 in combination with azacitidine. We thank our clinical team and investigators for conducting an excellent clinical study, yet we must accept this result as it stands and move on to other opportunities with a higher probability of success,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. Dr. Schreiber continued, “We are announcing a strategic shift to focus on SL-325, a DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 signaling pathway. We believe SL-325 could be a first-in-class DR3 receptor blocking antibody, and that this approach will prove more potent than blocking TL1A, for many of the same reasons that blocking PD-1 has proven more potent than blocking PD-L1. This strategic shift in our clinical development plans and subsequent realignment of our organization with an approximate 40% reduction in workforce will allow us to use our resources most efficiently to position Shattuck for long-term success. I would like to express my gratitude to the patients who participated in our clinical trials to date as well as to the Shattuck team members who were impacted by this realignment.” Top-line Phase 1B SL-172154 Clinical Trial Results HR-MDS TP53m AML Corporate Updates Financial Guidance Update As of June 30, 2024, cash and cash equivalents and investments were $105.3 million. Shattuck has implemented a restructuring plan to prioritize the development of the Company’s DR3 program. The plan is intended to optimize the Company’s cost structure by aligning the size and structure of its workforce with the Company’s current goals and strategy, following the discontinuation of SL-172154. Approximately 40% of Shattuck’s workforce will be impacted by the changes. The Company expects to complete the reduction in force in the fourth quarter of 2024. Given the changes to Shattuck’s operations and cost structure, the Company believes its cash and cash equivalents and investments will be sufficient to fund its planned operations into 2027, beyond results from its planned Phase 1 clinical trial of SL-325. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from potential business development transactions, and/or additional costs associated with additional development activities that may be undertaken. Shattuck Labs Investor Call and Webcast Shattuck will host a conference call and webcast at 8:00 a.m. ET on Tuesday, October 1, 2024, to discuss clinical data from SL-172154 and outline a strategic pipeline prioritization to focus on SL-325, a first-in-class DR3 antagonist targeting the TL1A/DR3 signaling pathway. Participants are invited to listen by dialing (800) 715-9871 (domestic) or +1 (646) 307-1963 (international) five minutes prior to the start of the call and providing the passcode 6989140. A live webcast presentation will be available here or on the company’s website at www.ShattuckLabs.com under Events & Presentations . A replay of the webcast will be archived on the company’s website following the presentation. About Shattuck Labs, Inc. Shattuck Labs, Inc. (Nasdaq: STTK) is a biotechnology company specializing in the development of potential treatments for autoimmune/inflammatory diseases and cancer. Shattuck is developing a potentially first-in-class antibody for the treatment of IBD and other inflammatory autoimmune diseases. Shattuck’s expertise in protein engineering and the development of novel TNF receptor agonist and antagonist therapeutics come together in its lead program, SL-325, a first-in-class DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 pathway. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com . SOURCE: Shattuck Labs

Phase 1Financial Statement

100 Deals associated with SL-172154

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Platinum-Resistant Fallopian Tube Carcinoma	Phase 1	United States	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Fallopian Tube Carcinoma	Phase 1	Canada	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Fallopian Tube Carcinoma	Phase 1	Spain	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Fallopian Tube Carcinoma	Phase 1	United Kingdom	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Ovarian Carcinoma	Phase 1	United States	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Ovarian Carcinoma	Phase 1	Canada	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Ovarian Carcinoma	Phase 1	Spain	Shattuck Labs, Inc.	18 Aug 2022
Platinum-Resistant Ovarian Carcinoma	Phase 1	United Kingdom	Shattuck Labs, Inc.	18 Aug 2022
Acute Myeloid Leukemia	Phase 1	United States	Shattuck Labs, Inc.	17 Mar 2022
Acute Myeloid Leukemia	Phase 1	Canada	Shattuck Labs, Inc.	17 Mar 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05483933 (CTgov)	Phase 1	Platinum-Resistant Fallopian Tube Carcinoma \| Platinum-Resistant Primary Peritoneal Carcinoma \| Ovarian Epithelial Carcinoma ... View more	86	SL-172154+Pegylated Liposomal Doxorubicin (Pegylated Liposomal Doxorubicin + SL-172154)	ymtrjkibcu = nmakhrxizk zqijwktiqx (nesinfsrup, zmyroknqhc - dtyeotyyke) View more	-	23 Dec 2025
				Mirvetixumab+SL-172154 (Mirvetixumab + SL-172154)	ymtrjkibcu = valfxiwmmb zqijwktiqx (nesinfsrup, ttiotsbunq - jkaxbmosrt)
NCT04502888 (CTgov)	Phase 1	Cutaneous Squamous Cell Carcinoma of the Head and Neck	5	SL-172154	cocodojmdr = qrtrowivmv trswqdruem (cqoxebhvhk, pprvlgozcz - yepbepmgpc)	-	24 Feb 2025
NCT04406623 (First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154, CTgov)	Phase 1	Primary peritoneal carcinoma \| Ovarian Cancer \| Platinum-Resistant Primary Peritoneal Carcinoma ... View more	27	SL-172154	rbsqniowcl = mflzcpjsvw iakaotnzdt (orczfjkptf, ddtoydmsnh - awplzvgbrs)	-	30 Jan 2025
NCT04406623 (First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154, Pubmed \| J Immunother Cancer)	Phase 1	Platinum-Resistant Ovarian Carcinoma CD47- \| CD40-positive	27	SL-172154 0.1 mg/kg	infnwxyifp(lhicmykvhv) = infusion-related reactions being the most common bjjqodzedr (dfrfqiskxq )	Positive	01 Jan 2025
				SL-172154 0.3 mg/kg
NEWS Manual	Not Applicable	Acute Myeloid Leukemia	-	SL-172154	fdaxkuekpb(kzuoepbzrq) = idhthdzlri pylxwjjkag (soloxguaiq )	Negative	01 Oct 2024
				azacitidine	fdaxkuekpb(kzuoepbzrq) = wbmytnlfwy pylxwjjkag (soloxguaiq )
NCT05275439 (GlobeNewswire) Manual	Phase 1	Acute Myeloid Leukemia \| Myelodysplastic Syndromes TP53 Mutation	45	SL-172154+ Azacitidine (HR-MDS)	jttiqyzgjg(ajexuvnkwl) = mkqdsjlcil wotypyhkzj (xnbwtjutte ) View more	Positive	14 Jun 2024
				SL-172154+ Azacitidine (TP53m AML)	jttiqyzgjg(ajexuvnkwl) = jwmojdwcyh wotypyhkzj (xnbwtjutte ) View more
NCT05483933 (Biospace) Manual	Phase 1	Platinum-Resistant Ovarian Carcinoma	21	SL-172154 + PLD	utklfeoama(hecppbjotp) = rudlutiwfn rlmwbgnvcp (kdfxgebtnc )	Positive	14 Jun 2024
				SL-172154 + Mirvetuximab	-
EHA2024 Manual	Phase 1	Acute Myeloid Leukemia \| High Risk Myelodysplastic Syndrome TP53 Mutation	39	SL-172154 (Azacitidine40L, 154) + Azacitidine	eiknvcbttf(iupyzhmksk) = hetebgtczn hgoytwcdbc (iyhaalslbl ) View more	Positive	14 May 2024
ASH2023 Manual	Phase 1	Acute Myeloid Leukemia \| Myelodysplastic Syndromes TP53 Mutation	37	SL-172154	kwucnjrizt(bobenfhitw) = movjulchlx bxajdvqyba (vujadoojcp ) View more	Positive	11 Dec 2023
				SL-172154+Azacitidine	kwucnjrizt(bobenfhitw) = kjtcjdiopa bxajdvqyba (vujadoojcp ) View more
NCT04406623 (ASCO 12023 \| ASCO 22023) Manual	Phase 1	Platinum-Resistant Ovarian Carcinoma	27	SL-172154	bfzptixbnp(yfxzpnddoz) = Treatment-emergent AEs (>15%) regardless of grade (G) included infusion related reaction (IRR) (67%), fatigue (44%), nausea (33%), back pain (26%), constipation, diarrhea (both 22%), decreased appetite and pruritus (both 19%). bdgasbbbhn (xvditigtbn ) View more	Positive	31 May 2023

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