Shattuck Labs Announces Positive Data from the Preclinical GLP Toxicology Study of SL-325 at the 20th Congress of European Crohn’s and Colitis Organization (ECCO) in Inflammatory Bowel Diseases 2025
Shattuck Labs (NASDAQ: STTK) announced positive preclinical data from an IND-enabling GLP toxicology study of SL-325, their DR3 blocking antibody for inflammatory bowel disease (IBD) treatment. The study, presented at the 20th Congress of ECCO, demonstrated that SL-325 was well-tolerated in non-human primates with no evidence of toxicity or residual agonism.
The study evaluated safety, pharmacokinetics, pharmacodynamics, and immunogenicity over a 4-week dosing period followed by a 4-week recovery period. Three doses (1, 10, and 100 mg/kg) were administered intravenously, showing full and durable DR3 receptor occupancy at all dose levels. No adverse effects, infusion-related reactions, or organ dysfunction were observed, even at the highest dose of 100 mg/kg.
The company expects to file an IND in Q3 2025, with projected human dosing at 1 mg/kg Q2W through Q4W maintenance and 3 mg/kg Q2W through Q8W maintenance.
Shattuck Labs (NASDAQ: STTK) ha annunciato dati preclinici positivi da uno studio di tossicologia GLP abilitante per l'IND relativo a SL-325, il loro anticorpo bloccante DR3 per il trattamento della malattia infiammatoria intestinale (IBD). Lo studio, presentato al 20° Congresso dell'ECCO, ha dimostrato che SL-325 è stato ben tollerato nei primati non umani, senza evidenze di tossicità o agonismo residuo.
Lo studio ha valutato la sicurezza, la farmacocinetica, la farmacodinamica e l'immunogenicità durante un periodo di dosaggio di 4 settimane seguito da un periodo di recupero di 4 settimane. Sono state somministrate tre dosi (1, 10 e 100 mg/kg) per via endovenosa, mostrando un'occupazione completa e duratura del recettore DR3 a tutti i livelli di dose. Non sono stati osservati effetti avversi, reazioni correlate all'infusione o disfunzione d'organo, nemmeno alla dose più alta di 100 mg/kg.
La società prevede di presentare un'IND nel terzo trimestre del 2025, con dosaggi umani previsti di 1 mg/kg ogni due settimane fino a quattro settimane di mantenimento e 3 mg/kg ogni due settimane fino a otto settimane di mantenimento.
Shattuck Labs (NASDAQ: STTK) anunció datos preclínicos positivos de un estudio de toxicología GLP habilitante para el IND de SL-325, su anticuerpo bloqueador de DR3 para el tratamiento de la enfermedad inflamatoria intestinal (IBD). El estudio, presentado en el 20° Congreso de ECCO, demostró que SL-325 fue bien tolerado en primates no humanos sin evidencia de toxicidad o agonismo residual.
El estudio evaluó la seguridad, farmacocinética, farmacodinamia e inmunogenicidad durante un período de dosificación de 4 semanas seguido de un período de recuperación de 4 semanas. Se administraron tres dosis (1, 10 y 100 mg/kg) por vía intravenosa, mostrando una ocupación completa y duradera del receptor DR3 en todos los niveles de dosis. No se observaron efectos adversos, reacciones relacionadas con la infusión ni disfunción orgánica, incluso a la dosis más alta de 100 mg/kg.
La empresa espera presentar un IND en el tercer trimestre de 2025, con dosificación humana proyectada de 1 mg/kg cada dos semanas hasta el mantenimiento de 4 semanas y 3 mg/kg cada dos semanas hasta el mantenimiento de 8 semanas.
샤턱랩스 (NASDAQ: STTK)는 염증성 장질환 (IBD) 치료를 위한 DR3 차단 항체 SL-325의 IND 승인 가능성을 위한 GLP 독성학 연구에서 긍정적인 전임상 데이터를 발표했습니다. 20회 ECCO 총회에서 발표된 이 연구는 SL-325가 비인간 영장류에서 잘 견뎌졌으며 독성이나 잔여 작용 증거가 없음을 보여주었습니다.
이 연구는 4주 투여 기간 동안 안전성, 약리학적 동태, 약리학적 작용 및 면역원성을 평가했으며, 이후 4주 회복 기간이 있었습니다. 세 가지 용량 (1, 10 및 100 mg/kg)이 정맥 주사로 투여되었으며, 모든 용량 수준에서 DR3 수용체의 완전하고 지속적인 점유가 나타났습니다. 100 mg/kg의 가장 높은 용량에서도 부작용, 주입 관련 반응 또는 장기 기능 장애가 관찰되지 않았습니다.
회사는 2025년 3분기에 IND를 제출할 예정이며, 인간 투여는 2주마다 1 mg/kg의 유지 요법과 2주마다 3 mg/kg의 유지 요법으로 예상하고 있습니다.
Shattuck Labs (NASDAQ: STTK) a annoncé des données précliniques positives d'une étude de toxicologie GLP habilitante pour l'IND de SL-325, leur anticorps bloquant DR3 pour le traitement de la maladie inflammatoire de l'intestin (IBD). L'étude, présentée au 20e Congrès de l'ECCO, a démontré que SL-325 était bien toléré chez les primates non humains sans preuve de toxicité ou d'agonisme résiduel.
L'étude a évalué la sécurité, la pharmacocinétique, la pharmacodynamie et l'immunogénicité sur une période de dosage de 4 semaines suivie d'une période de récupération de 4 semaines. Trois doses (1, 10 et 100 mg/kg) ont été administrées par voie intraveineuse, montrant une occupation complète et durable du récepteur DR3 à tous les niveaux de dose. Aucun effet indésirable, réaction liée à l'infusion ou dysfonctionnement organique n'a été observé, même à la dose la plus élevée de 100 mg/kg.
L'entreprise prévoit de déposer une demande d'IND au troisième trimestre 2025, avec un dosage humain projeté de 1 mg/kg toutes les deux semaines jusqu'à l'entretien de 4 semaines et 3 mg/kg toutes les deux semaines jusqu'à l'entretien de 8 semaines.
Shattuck Labs (NASDAQ: STTK) gab positive präklinische Daten aus einer IND-fähigen GLP-Toxizitätsstudie zu SL-325, ihrem DR3-blockierenden Antikörper zur Behandlung von entzündlichen Darmerkrankungen (IBD), bekannt. Die Studie, die auf dem 20. Kongress der ECCO präsentiert wurde, zeigte, dass SL-325 bei nichtmenschlichen Primaten gut vertragen wurde, ohne Hinweise auf Toxizität oder verbleibenden Agonismus.
Die Studie bewertete Sicherheit, Pharmakokinetik, Pharmakodynamik und Immunogenität über einen 4-wöchigen Dosierungszeitraum, gefolgt von einem 4-wöchigen Erholungszeitraum. Es wurden drei Dosen (1, 10 und 100 mg/kg) intravenös verabreicht, wobei eine vollständige und dauerhafte Besetzung des DR3-Rezeptors auf allen Dosenebenen festgestellt wurde. Es traten keine unerwünschten Wirkungen, infusionsbedingte Reaktionen oder Organfunktionsstörungen auf, selbst bei der höchsten Dosis von 100 mg/kg.
Das Unternehmen plant, im dritten Quartal 2025 einen IND-Antrag einzureichen, mit einer geplanten menschlichen Dosierung von 1 mg/kg alle zwei Wochen bis zur Erhaltung über 4 Wochen und 3 mg/kg alle zwei Wochen bis zur Erhaltung über 8 Wochen.
- Successful preclinical toxicology study showing no adverse effects
- Full and durable DR3 receptor occupancy achieved at all dose levels
- Extended dosing intervals possible, improving potential treatment convenience
- No-observed-adverse effect level at highest tested dose (100 mg/kg)
- None.
Insights
The preclinical toxicology results for SL-325 represent a significant milestone for Shattuck Labs, demonstrating three important advantages that position the company favorably in the competitive IBD therapeutic landscape:
First, the clean toxicology profile - with no adverse effects even at doses up to 100 mg/kg - substantially de-risks the upcoming clinical development program. This is particularly noteworthy for antibody therapeutics targeting novel pathways, where safety concerns can often derail development.
Second, the demonstrated pharmacokinetic profile enabling extended dosing intervals (potentially up to 8 weeks during maintenance) could provide a meaningful competitive advantage. Current IBD biologics typically require dosing every 4-8 weeks, and matching this convenience while targeting a novel pathway could aid market adoption. The ability to achieve full receptor occupancy at relatively low doses (1-3 mg/kg) also suggests favorable manufacturing economics.
Third, and perhaps most strategically important, is the company's focus on DR3 rather than TL1A blockade. The constitutive expression pattern of DR3 in IBD patients suggests potential for more complete pathway inhibition compared to targeting TL1A. This mechanistic advantage, combined with remission rates that "match or exceed" current standards of care (IL-23 and α4β7 inhibitors), positions SL-325 as a potentially best-in-class therapeutic.
With an IND filing expected in Q3 2025, investors should monitor the transition into clinical trials, particularly early safety data and biomarker results that could validate the preclinical findings. The clean toxicology profile significantly increases the probability of successful clinical development, while the potential for extended dosing intervals could translate into meaningful market differentiation.
– SL-325 is a high-affinity DR3 blocking antibody being developed for the treatment of inflammatory bowel disease (IBD); No evidence of toxicity or residual agonism observed in non-human primate toxicology study –
– SL-325 receptor occupancy (RO) and pharmacokinetic (PK) profile observed suggestive of extended dosing intervals; IND filing expected in the third quarter of 2025 –
AUSTIN, TX & DURHAM, NC, Feb. 20, 2025 (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 inflammatory and immune-related diseases, today announced positive preclinical data from an IND-enabling GLP toxicology study of SL-325 in non-human primates (NHP). These data were featured in a digital oral presentation on February 20, 2025, during the 20th Congress of ECCO in Inflammatory Bowel Diseases 2025 in Berlin, Germany.
“Clinical data has continued to demonstrate that inhibition of the TL1A/DR3 signaling axis provides monotherapy complete remission rates that match or exceed those observed with IL-23 or α4β7 blocking antibodies. While DR3 blocking antibodies are technically more challenging to develop than TL1A blocking antibodies, the constitutive expression pattern and greater abundance of DR3 in IBD patients as compared to TL1A, suggests DR3 blockade may more completely neutralize the axis than TL1A blockade,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “The preclinical data shared today at ECCO from our NHP toxicology studies showed that SL-325 was very well tolerated, achieved full and durable DR3 receptor occupancy at low doses, and confirmed the absence of DR3 agonism at any dose level. Population PK modeling indicates that extended dosing intervals are likely in humans. We are excited for SL-325 to enter Phase 1 clinical trials later this year.”
A copy of the ECCO digital oral presentation, titled “Pre-Clinical Development of SL-325, a High Affinity DR3 Blocking Antibody, for Durable Blockade of the DR3/TL1A Axis in Inflammatory Bowel Disease,” will be made available under the Events and Presentations section of Shattuck’s website.
Key Takeaways from Preclinical Testing of SL-325 in Non-Human Primates:
- Safety, PK, pharmacodynamics, and immunogenicity of SL-325 were evaluated in a GLP toxicology study in cynomolgus macaques over a 4-week dosing period followed by a 4-week recovery period to support a Phase 1 single ascending and multi-ascending dose trial in healthy volunteer subjects.
- Naïve cynomolgus macaques received three doses of intravenous SL-325 (vehicle, 1 mg/kg, 10 mg/kg or 100 mg/kg dose groups), each given two weeks apart, and no evidence of toxicity or organ dysfunction was observed.
- No-observed-adverse effect level is the top dose of 100 mg/kg.
- No infusion-related reactions were observed in any groups.
- No significant SL-325-related variations were noted in any clinical pathology parameter in any group, nor in the gross pathology or histopathology analysis.
- Full and durable DR3 RO was observed in peripheral blood lymphocytes at each of the three doses.
- Peripheral blood flow cytometry confirmed that there was no evidence of CD4 or CD8 T cells activation or Treg proliferation in any treated animal during the course of the study.
- Results from this preclinical study indicate that SL-325 is a high-affinity DR3 blocking antibody with no evidence of toxicity or residual agonism in cynomolgus macaques, and with an RO/PK profile suggestive of extended dosing intervals that will be studied in an upcoming Phase 1 clinical trial.
- Projected dose and schedule in human subjects are 1 mg/kg at Q2W induction through Q4W maintenance and 3 mg/kg Q2W induction through Q8W maintenance.
- Projected dose and schedule in human subjects are 1 mg/kg at Q2W induction through Q4W maintenance and 3 mg/kg Q2W induction through Q8W maintenance.
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 has completed 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. The Company is developing a potentially first-in-class antibody for the treatment of inflammatory bowel disease (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 potential 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: 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; the anticipated timing of any regulatory filings for SL-325; the anticipated timing of our preclinical studies and Phase 1 clinical trial for SL-325; the clinical benefit, safety and tolerability of SL-325; and the anticipated trial design for our Phase 1 clinical trial of SL-325. 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 Richardson
Vice President of Investor Relations
Shattuck Labs, Inc.
InvestorRelations@shattucklabs.com
FAQ
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