– 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, USA I February 20, 2025 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 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.
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.
SOURCE: Shattuck Labs
Post Views: 154
– 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, USA I February 20, 2025 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 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.
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.
SOURCE: Shattuck Labs
Post Views: 154
