SL-325 / Shattuck - LARVOL DELTA

DEVELOPMENT AND CHARACTERIZATION OF SL-846: A HALF-LIFE EXTENDED, DUAL-RECEPTOR (DR3 X IL23RA) TARGETING BISPECIFIC ANTIBODY (UEGW 2026) - "However, TL1A blocking monoclonal antibodies cause high rates of anti-drug antibody formation, and this propensity was compounded in a bispecific format, leading to >95% ADA, nearly all neutralizing, in the case of AMG966 (TL1A x TNFα) and RG6730 (TL1A x IL-23p40)...In healthy donor and IBD patient PBMC assays, SL-846 blocked combined TL1A- and IL-23–induced IFNγ, IL-17A/F and IL-22 production with efficacy equivalent to individual monotherapy agents or combined SL-325 (anti-DR3 mAb) plus Risankizumab or icotrokinra treatment controls... Together, these data demonstrate that SL-846 is a potent, dual-specific antagonist of TL1A and IL-23 signaling. Its dual-receptor targeting and durable antagonism support its potential as a first-in-class bispecific therapeutic with superior efficacy prospects for the treatment of IL-23 and TL1A-driven inflammatory diseases."

Bispecific • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • CD123 • IFNG • IL17A • IL22 • IL23A • TNFA

Shattuck Labs Announces Phase 2 Clinical Trial of SL-325 in Hidradenitis Suppurativa and Appointment of Shoba Ravichandran, M.D., as Senior Vice President, Clinical Development (Investing News Network (INN)) - "The RECEPTIVE-HS1 study is designed as a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the efficacy and safety of two dose levels of SL-325 versus placebo in patients with moderate to severe HS. The trial will include a 16-week placebo-controlled treatment period followed by an extension period with SL-325 through Week 52...IND submission is expected in October 2026; Week 16 data for the primary and secondary endpoints are expected to be disclosed in the first half of 2028."

IND • New P2 trial • Hidradenitis Suppurativa

Targeting the TL1A pathway in inflammatory bowel disease: mechanistic insights and emerging therapeutic pipeline. (PubMed, Inflamm Bowel Dis) - "Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn's disease, alongside favorable safety profiles...The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class."

Journal • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD40LG • IL23A • TNFA • TNFRSF25 • TNFSF15

RECEPTIVE-CD1 Phase 2b clinical trial of SL-325 in patients with moderately-to-severely active Crohn's disease is expected to initiate in the third quarter of 2026. (GlobeNewswire) - "Designed as a randomized, double-blind, placebo-controlled Phase 2b clinical trial; Will evaluate three dose levels of SL-325 compared with placebo in approximately 232 patients, randomized 1:1:1:1; Primary endpoint is endoscopic response at 12 weeks. These data are expected in the first half of 2028."

New P2b trial • P2b data • Crohn's disease • Immunology

Preclinical development of SL-325, a novel high-affinity DR3-blocking antibody for durable inhibition of the DR3/TL1A axis in inflammatory bowel disease. (PubMed, Inflamm Bowel Dis) - "These data demonstrate that SL-325 is a novel DR3-blocking antibody with the potential to provide durable inhibition of the TL1A/DR3 axis and support the clinical development of SL-325 to treat IBD."

Journal • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD40 • TNFA • TNFRSF25

Shattuck Labs Announces Phase 1 Results for SL-325 (GlobeNewswire) - "The ADA assay used to detect ADA to SL-325 has a sensitivity of 5.0 ng/ml and drug tolerance of up to SL-325 concentrations of 160.0 µg/ml in the serum. For each participant in this Phase 1 trial, samples were analyzed over a time course, ensuring that samples from each participant fell within the dynamic range of the assay across the full dose range, and thus limiting the possibility of false negative results...Complete DR3 occupancy, as measured by blockade of TL1A binding, was observed at doses of 0.1 mg/kg and higher in all participants; Complete inhibition of TL1A binding was durable for more than 10 weeks, and extended PK modeling suggests that complete inhibition of TL1A binding may be sustained for greater than 3 months at doses of greater than1 mg/kg of SL-325...No evidence of DR3 agonism was observed."

P1 data • PK/PD data • Immunology

RECEPTIVE-CD1 Phase 2b Trial of SL-325 in Crohn’s Disease (GlobeNewswire) - "RECEPTIVE-CD1 is expected to enroll approximately 174 patients, randomized 1:1:1, with patients receiving either low dose SL-325, high dose SL-325, or placebo. RECEPTIVE-CD1 will enroll patients at clinical sites in the United States, Canada, and Europe; RECEPTIVE-CD1 is expected to enroll patients with moderate-to-severe Crohn’s disease, as defined with a Crohn’s Disease Activity Index ('CDAI') score of between 220 and 450; The primary endpoint is expected to be endoscopic response at Week 12, and the key secondary endpoint will be clinical remission at Week 12; Patients randomized to the placebo arm will be eligible to receive SL-325 after the 12-week induction period; The primary endpoint, endoscopic response at 12 weeks, is expected to be disclosed in the first half of 2028....SL-325 is expected to be evaluated in a Phase 2b clinical trial in Crohn’s Disease patients initiating in the third quarter of 2026."

New P2b trial • P2b data • Crohn's disease

Shattuck Labs Reports First Quarter 2026 Financial Results and Recent Business Highlights (Investing News Network (INN)) - "Enrollment of all six single-ascending dose cohorts and all three multiple-ascending dose cohorts of the trial is now complete, with participant follow-up, data collection, and data analysis ongoing; Shattuck plans to present safety and tolerability, PK, receptor occupancy, duration of receptor occupancy, pharmacodynamics, 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....S1hattuck plans to disclose the targets of its lead bispecific product candidate, supporting preclinical data, and expected development timelines in the second quarter of 2026."

New P2 trial • P1 data • Pipeline update • Trial status • Crohn's disease • Ulcerative Colitis

DR3 Program Development in 2025 (The Manila Times) - "...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 plans to disclose the targets of its lead bispecific product candidate, supporting preclinical data, and expected development timelines in the first half of 2026."

New P2 trial • Pipeline update • Crohn's disease • Immunology • Inflammation

Shattuck’s lead product candidate, SL-325, is a potentially first-in-class DR3 antagonist antibody for the treatment of IBD and other inflammatory and immune-mediated diseases (Shattuck Labs Press Release) - "First participants dosed in the single-ascending dose (SAD) portion of the Phase 1 clinical trial in the third quarter of 2025; Enrollment of SAD and multiple-ascending dose (MAD) portions is expected to be completed in the second quarter of 2026; Safety, tolerability, DR3 occupancy, immunogenicity, and PK data will be evaluated in this open-label study, and Shattuck expects to disclose initial results by the second quarter of 2026."

P1 data • Trial status • Immunology

Shattuck Labs Announces Closing of up to $103 Million Private Placement… (GlobeNewswire) - "Aggregate net proceeds from private placement expected to fund SL-325 through multiple Phase 2 clinical trials, including in Inflammatory Bowel Disease (IBD) and potentially another autoimmune disease."

Financing • Inflammatory Bowel Disease

Shattuck Labs Announces IND for SL-325 Is in Effect for the Treatment of Inflammatory Bowel Disease (The Manila Times) - "Dosing of the first participant is expected this quarter, and enrollment of the Phase 1 clinical trial is expected to be completed in the second quarter of 2026."

IND • New P1 trial • Inflammatory Bowel Disease

Shattuck’s lead product candidate, SL-325, is a potentially first-in-class DR3 blocking antibody for the treatment of IBD and other inflammatory and immune-mediated diseases (GlobeNewswire) - "An IND was submitted to the FDA for SL-325 in July 2025; clearance expected in the third quarter of 2025...Phase 1 clinical trial will evaluate safety, tolerability, immunogenicity and pharmacokinetics in healthy volunteers, and determine the recommended Phase 2 dose and dosing schedule of SL-325. Subject to regulatory alignment, dosing of the first participant in the single-ascending dose (SAD) portion of the trial is expected in the third quarter of 2025, and the multiple-ascending dose (MAD) portion of the trial is expected to commence in the fourth quarter of 2025; Phase 1 enrollment of the SAD and MAD portions of the clinical trial is expected to be completed in the second quarter of 2026."

IND • New P1 trial • Immunology • Inflammation

Shattuck Labs Reports First Quarter 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "Phase 1 clinical trial will evaluate safety, tolerability, and pharmacokinetics, and determine the recommended Phase 2 dose and dosing schedule of SL-325. First patient in for the SAD portion of the trial expected in the third quarter of 2025. Phase 1 enrollment completion expected in the second quarter of 2026....Shattuck Labs to present at the PEGS Boston Summit on May 12, 2025...will present on SL-325 in the Advances in Immunotherapy section of the conference....Research and Development (R&D) Expenses: R&D expenses were $9.9 million for the quarter ended March 31, 2025, as compared to $16.3 million for the quarter ended March 31, 2024."

Clinical • Commercial • Enrollment status • New P1 trial • Inflammatory Bowel Disease

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 (GlobeNewswire) - "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....We are excited for SL-325 to enter Phase 1 clinical trials later this year."

IND • New P1 trial • Preclinical • Inflammatory Bowel Disease

Pre-Clinical Development of SL-325, a High Affinity DR3 Blocking Antibody, for Durable Blockade of the DR3/TL1A Axis in Inflammatory Bowel Disease (ECCO-IBD 2025) - "Sequence equivalents of tulisokibart and RO7790121 were produced by transient transfection and affinity purification. No evidence of residual DR3 agonist activity was observed. Conclusion These results indicate 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."

Preclinical • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Shattuck Labs Announces Oral Presentation at Upcoming 20th Congress of European Crohn’s and Colitis Organization (ECCO) in Inflammatory Bowel Diseases 2025 (GlobeNewswire) - "Shattuck Labs...announced an upcoming oral presentation at the 20th Congress of ECCO in Inflammatory Bowel Diseases 2025 being held in Berlin, Germany from February 19–22, 2025. This presentation will feature results from the IND-enabling toxicology studies of SL-325, a first-in-class DR3 blocking antibody, in non-human primates."

Preclinical • Inflammatory Bowel Disease

DEVELOPMENT AND CHARACTERIZATION OF SL-325, A DR3-TARGETED, ANTAGONISTIC ANTIBODY FOR THE TREATMENT OF IBD (CCCongress 2025) - "Affinity of SL-325 to recombinant DR3 was determined to be 1.36 pM by SPR, while no binding was observed to DcR3, TNFR1 or TNFR2 by MSD. SL-325 bound to native cynomolgus DR3 with an EC50 that was comparable to human DR3 and no detectable binding was observed to other members of the TNF receptor family. SL-325 blocked recombinant TL1A binding to DR3 with an IC50 of 0.06 nM and 0.80 nM by MSD and FACS, respectively, which was equal to or better than the benchmark anti-TL1A mAbs."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • CD40 • IFNG • TNFA • TNFRSF1A • TNFRSF25

Shattuck Labs Announces Poster Presentation at Upcoming 2025 Crohn’s and Colitis Congress (GlobeNewswire) - "Shattuck Labs, Inc...today announced an upcoming poster presentation at the 2025 Crohn’s and Colitis Congress being held in San Francisco, California from February 6–8, 2025."

Clinical data • Inflammatory Bowel Disease

Shattuck Labs Provides Corporate Update and Highlights Upcoming Key Milestones in 2025 (GlobeNewswire) - "DR3 Program Milestones Expected in 2025: i) Preclinical SL-325 data readout from GLP toxicology study in NHPs expected in the first quarter of 2025. ii) IND filing for SL-325 expected in the third quarter of 2025. iii) SL-325 Phase 1 clinical trial initiation expected in the third quarter of 2025. iv) Nomination of lead DR3 bispecific development candidate(s) anticipated in the second half of 2025."

IND • New P1 trial • Pipeline update • Preclinical • Immunology • Inflammation

Shattuck Labs Reports Third Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Announced development of SL-325, a first-in-class antagonist antibody to DR3, the receptor for TL1A; IND filing expected in Q3'2025..."

IND • Inflammatory Bowel Disease

Shattuck Labs Provides Company Update and Announces SL-325, a First-In-Class Death Receptor 3 (DR3) Antagonist Targeting the TL1A/DR3 Signaling Pathway (GlobeNewswire) - "Shattuck Labs, Inc...today announced a strategic pipeline prioritization....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."

Pipeline update • Immunology • Inflammatory Bowel Disease