10-K: Shattuck Labs Advances SL-325 to Phase 2, Narrows 2025 Net Loss

Shattuck Labs, a clinical-stage biotech, is advancing its lead DR3 blocking antibody, SL-325, into Phase 2 for Crohn's Disease while reporting a reduced net loss for fiscal year 2025.

Summary

• Shattuck Labs is a clinical-stage biotechnology company focused on developing first-in-class monoclonal and bispecific Death Receptor 3 (DR3) blocking antibodies for inflammatory and immune-mediated diseases.
• The lead program, SL-325, is a high-affinity DR3 blocking monoclonal antibody designed to achieve a more complete and durable blockade of the DR3/TL1A pathway than existing TL1A blocking antibodies.
• SL-325 is currently undergoing a Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial in healthy volunteers, expected to complete in the second quarter of 2026.
• A randomized, placebo-controlled Phase 2 clinical trial evaluating SL-325 in patients with Crohn's Disease (CD) is expected to initiate in the third quarter of 2026.
• Preclinical studies for SL-325 suggest a favorable safety profile, durable receptor occupancy, and potential for extended dosing intervals.
• The company reported a net loss of $48.8 million for the year ended December 31, 2025, an improvement from a net loss of $75.4 million in 2024.
• As of December 31, 2025, the accumulated deficit was $430.5 million, with cash, cash equivalents, and short-term investments totaling $78.1 million, projected to fund operations into 2029 assuming full exercise of outstanding common stock warrants.
• The SL-172154 program was discontinued in October 2024, leading to workforce reductions and a decrease in research and development expenses.
• Shattuck Labs is also developing SL-425, a half-life extended version of SL-325, and multiple preclinical DR3-based bispecific antibodies.

Sentiment

Score: 7

Explanation: StockSavvy.ai views this as a positive update due to the significant reduction in net loss, extended cash runway, and clear progression of the lead asset SL-325 into Phase 2 with promising preclinical data, despite ongoing capital needs and the inherent risks of early-stage biotech development.

Positives

• Net loss significantly reduced to $48.8 million in 2025 from $75.4 million in 2024.
• Existing cash, cash equivalents, and short-term investments of $78.1 million as of December 31, 2025, are estimated to fund operations into 2029, assuming full exercise of outstanding common stock warrants.
• SL-325 preclinical data indicates a favorable safety profile, durable receptor occupancy, and potential for prolonged dosing intervals, de-risking future clinical development.
• SL-325 is engineered to avoid immune complex formation, which is a primary source of immunogenicity for TL1A blocking antibodies, potentially leading to single-digit anti-drug antibody (ADA) rates in humans and improved efficacy.
• A Phase 2 clinical trial for SL-325 in Crohn's Disease is expected to initiate in Q3 2026, demonstrating clear pipeline progression.
• Successful completion of an IND-enabling GLP acute toxicology study for SL-325 in non-human primates (NHPs) showed no observed adverse effects at the highest dose of 100 mg/kg.
• SL-425, a half-life extended version of SL-325, demonstrated the expected half-life extension in an ongoing chronic GLP toxicology study.
• Received $1.0 million in related party license revenue in 2025 from Kayak Therapeutics, Inc. for the oncology-focused TRIM7 program.

Negatives

• The company has incurred significant operating losses since inception, with an accumulated deficit of $430.5 million as of December 31, 2025.
• No products have been approved for commercial sale, and no revenue has been generated from product sales to date.
• Additional funding will be required to complete development and commercialize products, and such funding may not be available on acceptable terms or at all.
• The SL-172154 program was discontinued in October 2024 due to overall survival data readouts not translating into improved outcomes, resulting in workforce reductions.
• The company relies on a single third-party contract manufacturer (Kemwell Biopharma Private Limited) for the supply of bulk drug substance for SL-325, posing a supply chain risk.
• Reliance on third parties for preclinical studies, nonclinical studies, and clinical trials means less direct control over these activities.
• The market value of voting and non-voting common equity held by non-affiliates was approximately $22,826,702 as of June 30, 2025, indicating a relatively small market capitalization.
• Cash and cash equivalents decreased from $57.387 million in 2024 to $54.192 million in 2025.
• Other income decreased from $5.157 million in 2024 to $2.699 million in 2025.

Risks

• As an early clinical-stage biotechnology company, significant losses have been incurred since inception, and profitability may never be achieved or maintained.
• Substantial additional funding will be required to complete product development and commercialization, and this funding may not be available on acceptable terms or at all, potentially forcing delays or elimination of programs.
• Raising additional capital may dilute existing stockholders, restrict operations, or require relinquishing rights to technologies or product candidates.
• The company is substantially dependent on the success of its lead product candidate, SL-325, and its clinical trials may not be successful.
• Product candidates are in preclinical and early clinical stages of development and may fail or suffer delays, as preclinical and clinical development is a lengthy, expensive, and uncertain process.
• Clinical trials may fail to demonstrate substantial evidence of safety and efficacy, preventing or delaying regulatory approval and commercialization.
• The company may not be successful in identifying or discovering additional product candidates.
• Intense competition from entities with significantly greater financial resources and expertise in the pharmaceutical and biotechnology industries.
• Product candidates may have serious adverse, undesirable, or unacceptable side effects, delaying or preventing marketing approval.
• Delays or difficulties in initiating clinical trial sites or enrolling patients in planned clinical trials could materially and adversely affect research and development efforts.
• The development and commercialization of biopharmaceutical products are subject to extensive, lengthy, time-consuming, and inherently unpredictable regulatory approval processes by the FDA and comparable foreign authorities.
• Product candidates intended for approval as biologics may face biosimilar competition sooner than anticipated due to regulatory pathways like the Biologics Price Competition and Innovation Act (BPCIA).
• The company may not be able to meet chemistry, manufacturing, and control requirements for its programs.
• Disruptions at the FDA and other government agencies (e.g., government shutdowns, policy changes, public health crises) could negatively affect the review of regulatory submissions.
• Research and development activities could be affected or delayed by possible restrictions on animal testing.
• Current and future laws and regulations, such as the Inflation Reduction Act of 2022 (IRA), may increase the difficulty and cost of obtaining marketing approval and affect product pricing and reimbursement.
• Business operations and relationships with healthcare professionals are subject to applicable healthcare fraud and abuse laws, which could expose the company to penalties.
• Reliance on third parties to supply raw materials and manufacture product candidates, with potential for production difficulties or supply interruptions.
• Reliance on third parties to conduct preclinical studies, nonclinical studies, and clinical trials, with limited direct control over their contractual duties and compliance.
• The company may not realize the benefits of any future collaboration or licensing arrangement, and failure to enter into new strategic relationships could adversely affect the business.
• Success depends on the ability to obtain and maintain patents and other intellectual property rights, which is challenging, costly, and uncertain, and third parties may challenge or infringe these rights.
• Economic downturns, inflation, fluctuating interest rates, changes in trade policies, natural disasters, public health crises, political crises, or geopolitical events could materially and adversely affect business operations and financial condition.
• Adverse developments affecting the financial services industry, including liquidity concerns or bank failures, could adversely affect the business, as cash held exceeds FDIC insurance limits.
• If securities or industry analysts do not publish research or publish inaccurate/unfavorable research, the trading price or volume of common stock could decline.
• The requirements of being a public company, especially ceasing to be an emerging growth company, may strain resources, result in litigation, and divert management's attention.
• Litigation filed against the company could harm the business, and insurance coverage may not be sufficient to cover all related costs and damages.
• Exposure to costly and damaging product liability claims, with insurance potentially insufficient to cover all liabilities.
• Failure to maintain proper and effective internal controls over financial reporting could impair the ability to produce accurate and timely financial statements.
• Provisions in the company's amended and restated certificate of incorporation and bylaws, and Delaware law, might discourage, delay, or prevent a change in control or management.
• The ability to use net operating loss carryforwards and other tax attributes may be limited by Section 382 of the Internal Revenue Code following an ownership change.

Future Outlook

Shattuck Labs expects to complete enrollment in its Phase 1 clinical trial for SL-325 in healthy volunteers in Q2 2026 and initiate a Phase 2 clinical trial in Crohn's Disease patients in Q3 2026. The company also plans to evaluate SL-325 in other inflammatory and immune-mediated diseases and will disclose targets and timelines for lead bispecific product candidates in H1 2026. An increase in research and development expenses is anticipated for 2026 as programs advance.

Management Comments

• "We believe that the underlying biological differences in the expression of DR3 and TL1A, and the design characteristics of SL-325, may allow SL-325 to achieve best-in-class clinical remission rates in patients with IBD due to a more complete and durable blockade of the clinically validated DR3/TL1A pathway."
• "We expect that SL-325 has the potential to demonstrate a superior immunogenicity profile in comparison to TL1A blocking antibodies."
• "By targeting DR3 instead of TL1A, we expect to avoid the formation of immune complexes, which we believe are the primary source of immunogenicity for all TL1A blocking antibodies, and lead to high rates of anti-drug antibody (ADA) formation toward TL1A targeting antibodies."
• "We believe that SL-325 may allow for improved efficacy in combination with other agents, compared to TL1A targeting antibodies."
• "Our goal is to select a dose and dosing schedule that maintains SL-325 concentrations in human peripheral blood which exceeds the threshold required to maintain full DR3 receptor occupancy both in peripheral blood and within affected tissues. We believe that SL-325 can achieve Q4W dosing during induction, and maintenance dosing no more frequently than once monthly."
• "We expect that our DR3-directed bispecific antibodies to be less immunogenic than TL1A-directed bispecifics."
• "We believe our management team has the experience necessary to effectively execute our strategy and advance our product and technology leadership."

Industry Context

StockSavvy.ai notes that Shattuck Labs is positioning SL-325 as a potentially differentiated therapy in the competitive inflammatory bowel disease (IBD) market, projected to grow from $23 billion in 2023 to $34 billion in 2030. The company's strategy to target DR3 rather than TL1A aims to overcome immunogenicity issues observed with existing TL1A blocking antibodies (e.g., afimkibart, tulisokibart, duvakitug) and TL1A-directed bispecifics (e.g., AMG966, RO7837195), which have shown high rates of anti-drug antibody formation. This approach, if successful, could offer a "best-in-mechanism" profile, potentially leading to improved efficacy and better combination therapy options compared to current and developing TL1A-targeting agents.

Comparison to Industry Standards

• SL-325 aims for "best-in-class clinical remission rates" in IBD, potentially surpassing the 23-28% placebo-adjusted clinical remission rates observed with third-party TL1A blocking antibodies (tulisokibart, duvakitug, afimkibart) in Phase 2 trials for ulcerative colitis (UC) and Crohn's Disease (CD).
• SL-325 is expected to demonstrate a "superior immunogenicity profile" compared to TL1A blocking antibodies, which have shown anti-drug antibody (ADA) formation in more than 64% of subjects treated with afimkibart, tulisokibart, or duvakitug in third-party clinical trials.
• SL-325's preclinical data suggests "single digit ADA rates in humans," which contrasts sharply with the nearly 100% ADA formation observed with TL1A-directed bispecific antibodies like AMG966 and RO7837195 following a single dose in Phase 1 clinical trials.
• The company's DR3-directed bispecific antibodies are expected to be "less immunogenic than TL1A-directed bispecifics," addressing a known challenge where soluble trimeric proteins like TNF and TL1A cause large immune complex formation and high ADA rates for bispecific antibodies targeting them.

Corporate Governance

Related Party Transactions

• In August 2025, Shattuck Labs granted Kayak Therapeutics, Inc. an exclusive license to its oncology-focused TRIM7 program, receiving preferred stock in Kayak with a fair market value of $1.0 million as upfront consideration.
• Shattuck Labs subleases certain lab space, office space, and lab equipment to Kayak for one year, with total consideration of $0.3 million, of which $0.1 million was received in 2025 and recorded as a reduction to research and development expenses.
• In November 2025, an officer of Shattuck Labs was elected to the board of directors of Kayak, resulting in Kayak becoming a related party.
• Two beneficial owners of 10% or more of Shattuck Labs' common stock participated in the August 2025 private placement offering, purchasing 8,963,785 pre-funded warrants and receiving accompanying common stock warrants to purchase an additional 8,963,785 shares of common stock, on the same terms as other participants.

Stakeholder Impact

• Shareholders: Face potential dilution from future equity raises (ATM facility, warrant exercises) and stock price volatility. No dividends are anticipated in the foreseeable future, making capital appreciation the sole source of gain. Principal stockholders and management retain significant control over matters requiring stockholder approval.
• Employees: Experienced workforce reductions in 2024 due to restructuring. The company competes for qualified personnel and offers a competitive total rewards package, including base salary, cash bonuses, equity compensation, and development plans.
• Customers (future): Potential for new, more efficacious treatments for inflammatory and immune-mediated diseases, particularly IBD, with potentially improved safety and immunogenicity profiles compared to existing therapies.
• Suppliers/Contractors: Continued reliance on third-party contract manufacturers (e.g., Kemwell Biopharma Private Limited) for bulk drug substance and Contract Research Organizations (CROs) for clinical trials, which introduces risks of supply shortages or production difficulties.
• Creditors: The company's ongoing net losses and accumulated deficit indicate a reliance on external financing. However, the current cash runway, extended by recent capital raises, is projected to fund operations into 2029, providing some financial stability in the near to medium term.

Next Steps

• Complete enrollment in the Phase 1 clinical trial for SL-325 in healthy volunteers in Q2 2026.
• Complete the six-month chronic GLP toxicology study of SL-325 (and SL-425) in NHPs in Q1 2026.
• Share data from the six-month chronic GLP toxicology study in Q2 2026.
• Initiate a randomized, placebo-controlled Phase 2 clinical trial evaluating SL-325 in patients with Crohn's Disease in Q3 2026.
• Disclose the targets of the lead bispecific product candidate, supporting preclinical data, and expected development timelines in H1 2026.
• Evaluate SL-325 in other inflammatory and immune-mediated diseases where the DR3/TL1A axis is implicated.
• Continue to augment internal research and technical operations capabilities.
• Deepen the intellectual property portfolio to protect platform technologies and product candidates.
• Potentially conduct clinical trials for SL-425 in the future, informed by SL-325 Phase 1 data.
• Continue to seek private or public equity and debt financing, and/or additional collaborations with third parties.

Key Dates

Recommendation

Shattuck Labs presents promising preclinical data for its lead asset, SL-325, targeting a large and growing market in IBD with a potentially differentiated mechanism to address immunogenicity challenges. The significant reduction in net loss and an extended cash runway into 2029 are positive indicators of improved financial management and operational efficiency. However, the company remains in early clinical stages with no approved products, faces intense competition, and will require substantial future funding to complete development and commercialization. A 'hold' recommendation reflects the balance between the potential upside of a novel therapeutic approach and the inherent high risks associated with early-stage biotechnology development and commercialization.

Keywords

Shattuck Labs, STTK, Biotechnology, Clinical-stage, DR3 blocking antibody, SL-325, Crohn's Disease, Inflammatory Bowel Disease, IBD, TL1A pathway, Immunogenicity, Phase 1 clinical trial, Phase 2 clinical trial, Drug development, Biologics, SEC filing, 10-K, Financial results, Pipeline, Preclinical, Orphan drug, Intellectual property, Corporate governance, Risk factors