afimkibart (RG6631) / Roche - LARVOL DELTA

Afimkibart: Data from P3 AMETRINE-1 trial (NCT06589986) for moderately to severely active ulcerative colitis in 2027 (Roche) - Pharma Day 2026: Data from P3 AMETRINE-2 trial (NCT06588855) for moderately to severely active ulcerative colitis in 2027

P3 data • Inflammatory Bowel Disease • Ulcerative Colitis

AMETRINE-SC: A Study to Assess the Efficacy and Safety of Afimkibart for Induction Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=350 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Novel Agents on the Therapeutic Horizon For Paediatric Inflammatory Bowel Diseases: An Analysis of Clinical Trials Registries. (PubMed, Paediatr Drugs) - "Efforts to expedite approval of new agents in pIBD are warranted to ensure timely access to effective medications. Consideration for novel trial designs alongside continued engagement with regulatory bodies, sponsors, and the academic pIBD community is essential to advance drug approvals for pIBD."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics

Tumor necrosis factor-like cytokine 1 A antagonists for inflammatory bowel disease: A systematic review and meta-analysis. (PubMed, Indian J Gastroenterol) - "Anti-TL1A agents appear to be a promising therapeutic option in patients with IBD. Overall, anti-TL1A demonstrated an acceptable short-term safety profile, although mild adverse events were reported in almost half of treated patients."

Journal • Retrospective data • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • TNFA

INDIRECT COMPARISON OF AFIMKIBART AND ADALIMUMAB TREATMENT EFFECTS USING DATA FROM TUSCANY-2 AND HIBISCUS IN PATIENTS WITH ULCERATIVE COLITIS (UEGW 2026) - P2, P3 | "This is the first comparison of the efficacy of afimkibart with another biologic using UC clinical trial data and PS methods. In the absence of head-to-head trials, PS adjustment methods generated robust comparisons of therapeutic effects, accounting for baseline covariate differences between trials. Due to limited availability, histological and laboratory data were not included in PS modelling, and residual confounding by those and other unmeasured factors cannot be ruled out."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

DEVELOPMENT AND PRECLINICAL TESTING OF A NOVEL BISPECIFIC ANTIBODY TARGETING P40 AND TL1A FOR THE TREATMENT OF IBD (UEGW 2026) - P1, P2 | "A Quantitative Systems Pharmacology model for IBD was calibrated to UC Ph IIa anti-TL1A afimkibart and UC Ph III ustekinumab data and then used to project biomarker and efficacy outcomes of the combined target blockade. PF-07261271 is a bispecific antibody that potently blocks p40-containing cytokines IL-12/IL-23 and TL1A. Dual blockade of p40 and TL1A reveals superior suppression of IFN-γ in human T cell and whole blood assays. QSP modeling projects better clinical outcomes when combining anti-TL1A and anti-p40 treatments compared to the respective monotherapies."

Bispecific • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Ulcerative Colitis • CD4 • IFNG • IL12A • IL23A • STAT3 • STAT4

SYMPTOMATIC REMISSION AND HEALTH-RELATED QUALITY OF LIFE WITH AFIMKIBART TREATMENT FOR MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS IN THE PHASE IIB TUSCANY-2 TRIAL (UEGW 2026) - "Afimkibart-treated patients reported early and rapid symptomatic remission from as early as week 2 compared with placebo. Improvements from baseline were seen in IBDQ across the induction period, with improvements in fatigue, abdominal bloating and pain at week 14. Safety data for afimkibart has been previously reported."

Clinical • HEOR • P2b data • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA • TNFRSF25

A Patient-Centric Evolution: Impact of Trial Design on Inflammatory Bowel Disease Clinical Trials (ACG 2026) - P3 | "IBD trials often use re-randomization (RR) designs that re-assign treatment responders to either placebo or active drug for the maintenance period following induction. A treat-through (TT) study design was chosen for the ongoing 52-week afimkibart trials in adult (NCT06589986, NCT06819878) and pediatric (NCT07158242, NCT07298421) populations. This TT design, in which patients remain on their initially randomized treatment throughout the study, mirrors real-world management of IBD, supports evaluation of durable results over time, eliminates the selection bias of enriched responder populations inherent to RR designs, and ensures treatment continuity for patients."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

Symptomatic Remission and Health-Related Quality of Life in the Phase 2b TUSCANY-2 Trial of Afimkibart in Ulcerative Colitis (ACG 2026) - P2 | "Overall, 245 patients were randomized to afimkibart (n=200; pooled data) or placebo (n=45). Afimkibart-treated patients showed greater rates of symptomatic remission versus placebo starting at week 2 and continuing through week 14 (Figure). Increased symptomatic improvements in RB and SF were observed in patients receiving afimkibart versus placebo from week 2, with increasing and sustained improvement through week 14."

Clinical • HEOR • P2b data • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA • TNFRSF25

Functional Advantage of the Preference of Afimkibart for Trimeric Tumor Necrosis Factor-Like Ligand 1A in Blocking Active TL1A Signaling (ACG 2026) - "In contrast to monomeric rhTL1A, trimeric rhTL1A robustly induced NF-κB activation in peripheral T lymphocytes and peripheral blood mononuclear cells (PBMCs). Afimkibart potently inhibited this NF-κB signaling, with PRA023 inhibiting to a lesser extent. With IL-12 and IL-18 co-stimulation, trimeric rhTL1A also significantly enhanced IFN-γ production in human PBMCs; monomeric rhTL1A elicited only a marginal response, even at high concentrations."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • IFNG • IL12A • IL18 • TNFA • TNFRSF25

Indirect Comparison of Treatment Effects of Afimkibart and Adalimumab Using Data From the TUSCANY-2 and HIBISCUS Trials in Ulcerative Colitis (ACG 2026) - P2, P3 | "Patients who met the inclusion criteria for both studies and received either afimkibart (n=101) or adalimumab (n=273) were included in the analysis. Before matching, clinical remission rates were 26.0% for adalimumab vs 10.8% for placebo in HIBISCUS I/II, and 41.6% for afimkibart vs 16.7% for placebo in TUSCANY-2. One hundred fifty-two biologic-naïve patients were included in the comparison after PS matching."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

FUNCTIONAL DIFFERENTIATION OF AFIMKIBART'S PREFERENCE FOR TRIMERIC TL1A IN BLOCKING ACTIVE TL1A SIGNALING (UEGW 2026) - "Afimkibart is a potent and selective antagonist of the functionally active, trimeric TL1A, efficiently blocking TL1A-induced NF-κB signaling and IFN-γ production. The selective binding of afimkibart to trimeric TL1A may represent a mechanistically distinct profile compared to antibodies that bind both monomeric and trimeric forms, such as PRA-023, by ensuring selective targeting of the signalling-competent TL1A form for optimal pharmacokinetic/pharmacodynamic properties. These data suggest that afimkibart may be differentiated within the anti-TL1A class by its selective binding to the active trimeric form of TL1A, a class-unique feature; the clinical impact of this selectivity is currently under investigation in TL1A-driven diseases such as IBD."

Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • IFNG • IL12A • IL18 • TNFA • TNFRSF25

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE (UEGW 2026) - "This TL1A receptor-selective profile was not observed with tulisokibart or afimkibart analogues and was more pronounced than that of a duvakitug analogue...In the TNBS-induced mouse colitis model, BBT003 outperformed single-targeting mAbs including guselkumab and tulisokibart analogues, and demonstrated dose-dependent, statistically significant efficacy in reducing disease activity index, colon histopathology, inflammation and fibrosis while restoring body weights... Dual blockade of the IL-23 and TL1A pathways by BBT003 demonstrates the potential to achieve better efficacy over single-targeting mAbs in IBD, with enhanced inhibition of in vitro biological functions and superior in vivo anti-inflammatory/anti-fibrotic and disease-modifying effects in preclinical models. Tolerability at the highest tested dose in cynomolgus monkeys suggests potentially a wide therapeutic window in humans. Its half-life extension technology further supports the potential for more convenient..."

Bispecific • Preclinical • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IFNG • IL17A • IL23A • TNFA • TNFRSF25

EVALUATION OF CHANGES IN GENE EXPRESSION IN COLONIC BIOPSY SAMPLES FROM PATIENTS TREATED WITH AFIMKIBART IN THE TUSCANY-2 TRIAL (UEGW 2026) - P2 | "This is the first interventional trial in this class to assess TL1A blockade at single-cell resolution in colonic tissue. Afimkibart induced complete target inhibition in the tissue and broad transcriptional changes across immune and tissue-resident mucosal populations, including cell types without prominent DR3 expression. These findings support a mode of action that extends beyond suppression of inflammation to modulation of dysregulated epithelial and stromal/fibrotic tissue programmes after TL1A blockade."

Biopsy • Clinical • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Ulcerative Colitis • CD4 • TNFRSF25

TL1A-Targeted Therapy in Ulcerative Colitis: A Meta-Analysis of Randomized Placebo-Controlled Induction Trial (ACG 2026) - "Three induction trials met inclusion criteria; ARTEMIS-UC evaluating Tulisokibart (Sands et al., 2024), TUSCANY-2 evaluating Afimkibart (Danese et al., 2025), and RELIEVE UCCD-UC evaluating Duvakitug (Reinisch et al., 2025). Three randomized controlled trials were included. For clinical remission, Sands et al., 2024 (ARTEMIS-UC) contributed 18/68 TL1A-treated versus 1/67 placebo-treated patients, Danese et al., 2025 (TUSCANY-2) contributed 63/195 versus 5/43, and Reinisch et al., 2025 (RELIEVE UCCD-UC) contributed 39/93 versus 9/44. The pooled analysis showed significantly higher clinical remission with TL1A inhibition versus placebo (RR 3.09, 95% CI 1.36-6.99; I²=52%)."

Retrospective data • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

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

TL1A-DR3 Signaling in Inflammatory Bowel Disease: From Pathogenesis to Therapeutic Targeting. (PubMed, Kurume Med J) - "Recent clinical trials of TL1A-neutralizing antibodies, including afimkibart, tulisokibart, and duvakitug, have demonstrated encouraging efficacy and safety in moderate-to-severe IBD, with emerging biomarker strategies suggesting potential for personalized treatment. Collectively, current evidence highlights TL1A blockade as a promising dual-pathway therapeutic approach targeting inflammation and fibrotic remodeling, with ongoing studies expected to define its long-term impact on disease modification."

Journal • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CD40LG • TNFSF15

Afimkibart: Regulatory submission in Japan for ulcerative colitis in 2027 (Chugai) - Q2 FY2026 Results

Japan filing • Inflammatory Bowel Disease • Ulcerative Colitis

RG6631: Regulatory submissions in US/EU for ulcerative colitis in 2027 (Roche) - Q2 2026 Results: Regulatory submissions in US/EU for Crohn's disease in 2029 and beyond

EMA filing • FDA filing • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

SIBERITE-2: A Study to Assess the Efficacy and Safety of Induction Therapy With Afimkibart (RO7790121) in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=425 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2029 ➔ Apr 2033

Trial completion date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

SIBERITE-2: A Study to Assess the Efficacy and Safety of Induction Therapy With Afimkibart (RO7790121) in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=425 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Apr 2029

Trial completion date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

SIBERITE-2: A Study to Assess the Efficacy and Safety of Induction Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=425 | Not yet recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2033 ➔ Dec 2028

Trial completion date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

SIBERITE-2: A Study to Assess the Efficacy and Safety of Induction Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=425 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

SIBERITE-2: A Study to Assess the Efficacy and Safety of Induction Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=425 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

Indirect Comparison of Afimkibart and Adalimumab Treatment Effects Using Data from TUSCANY-2 and HIBISCUS in Patients with Ulcerative Colitis (AOCC-IMKASID 2026) - "This is the first comparison of the efficacy of afimkibart with another biologic using UC clinical trial data and PS methods. In the absence of head-to-head trials, PS adjustment methods generated robust comparisons of therapeutic effects, accounting for baseline covariate differences between trials. Due to limited availability, histological and laboratory data were not included in PS modeling, and residual confounding by those and other unmeasured factors cannot be ruled out."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis