afimkibart (RG6631) / Roche - LARVOL DELTA

Baseline Characteristics Associated With Probability of Remission and Greater Absolute Benefit of Treatment With Afimkibart (RO7790121/RG6631) (ACG 2025) - P2 | "Overall, 32.5% of pts achieved clinical remission by mMS at W14 in the afimkibart arm (65/200; 90% CI 27.3–38.1) vs 13.3% (6/45; 90% CI 7.1–23.8) with PBO (treatment Δ 19.2%; 90% CI 7.6–27.9). Based on calibrated predictions from the multivariate model, all pts (PBO and afimkibart arms) had a 2–76% probability of W14 remission at baseline. On the clinically meaningful absolute scale, the treatment Δ in the top 50% of pts with a higher baseline probability of remission (27–76%) was 28.5% (90% CI 8–42; 45.2% afimkibart vs 16.7% PBO), versus a treatment Δ of 7.6% (90% CI –7–18; 18.8% afimkibart vs 11.1% PBO) in pts with a lower baseline probability of remission (2–27%; Figure)."

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

A Phase III, multicenter, double-blind, placebo-controlled study aimed at evaluating the efficacy and safety of induction therapy with RO7790121 in patients suffering from moderately to severely active ulcerative colitis. (ChiCTR) - P3 | N=350 | Recruiting | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

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

LBL-053, A Novel Anti-TL1A/p40 Bispecific Antibody for the Treatment of Autoimmune Disorders. [WITHDRAWN] (ACR Convergence 2025) - "Ustekinumab, targeting p40 subunit, has demonstrated robust efficacy and approved for IBD...The effect of LBL-053 on inhibiting TL1A-DR3 downstream signaling pathway was comparabile to RVT-3101, but better than MK-7240 and PF-07261271.LBL-053 also significantly blocked IL-23/IL-12Rβ1 interaction... LBL-053 showed dual immunosuppressive functions, simultaneously inhibiting TL1A-DR3 and IL-23/IL-12Rβ1 signaling pathway, indicating promising clinical applications for the treatment of autoimmune diseases."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • CD4 • IFNG • IL12A • IL18 • IL23A • TNFA

Afimkibart: Regulatory submission in Japan for crohn's disease in 2028 and beyond (Chugai) - Q3 FY2025 Results

Japan filing • Crohn's disease • Inflammatory Bowel Disease

A Study to Assess the Safety, Pharmacokinetics, and Activity of RO7790121 in Participants With Advanced MASH Liver Fibrosis (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Fibrosis • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

AFIMKIBART (ANTI-TL1A) IS EFFECTIVE IN THE BLOCKADE OF CELLULAR SIGNALING INDUCED BY ACTIVE TL1A (UEGW 2025) - "Herein, we demonstrate that afimkibart blocks NF-kB signaling and IFNγ production induced by TL1A stimulation. While some signaling activity was observed at high concentrations of monomeric TL1A protein, we hypothesize that any signaling observed with monomeric form is likely due to the formation of trimers, which are efficiently blocked by afimkibart. Overall, any monomeric TL1A present should not be functionally active nor be available as a sink for afimkibart, thus preserving the optimal pharmacokinetic (PK) and pharmacodynamic (PD) properties needed for effective target inhibition."

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

BASELINE CHARACTERISTICS ASSOCIATED WITH PROBABILITY OF REMISSION AND GREATER ABSOLUTE BENEFIT OF TREATMENT WITH AFIMKIBART (RO7790121/RG6631) (UEGW 2025) - P2 | "Pts with inflammatory bowel disease (IBD) have diverse baseline characteristics that are associated with variability of treatment outcomes, yet clinicians rely on reported averages from clinical trials to make individual treatment decisions. This analysis demonstrates how precision medicine approaches, that account for diverse characteristics, may improve interpretation of positive IBD clinical trial results. Integrating genetic and novel biomarkers alongside clinical features could help to better predict individual outcomes for pts with IBD."

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

DEVELOPMENT AND CHARACTERIZATION OF SIM0709, A NOVEL HALF-LIFE EXTENDED BI-SPECIFIC ANTIBODY SIMULTANEOUSLY TARGETING TL1A AND IL-23P19 FOR THE TREATMENT OF IBD AND BEYOND (UEGW 2025) - " SIM0709 simultaneously bound to both TL1A and IL-23 proteins with sub-nanomolar affinity and demonstrated superior functional activities under various functional assays on both TL1A and IL-23 axes compared to that of benchmark anti-TL1A mAb RG6631 and Guselkumab or its combination, respectively. Taken together, these data support the further development of SIM0709 as a potential FIC and BIC therapeutic agent for the treatment of IBD with expected first-in-human study in H1 2026."

Inflammatory Bowel Disease • CD4 • IFNG • IL12A • IL17A • IL18 • IL23A • IL2RA

RATIONALE AND DESIGN OF THE FIBROLITE STUDY EVALUATING SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF AFIMKIBART IN PATIENTS WITH ADVANCED LIVER FIBROSIS (AASLD 2025) - P1 | "While resmetirom is approved for the treatment of MASH with moderate to advanced fibrosis (F2–F3), a significant unmet need remains for patients with compensated cirrhosis (F4) for reversal of cirrhosis, prevention of liver decompensation, HCC, and transplantation. If an acceptable safety and PK/PD profile for afimkibart is demonstrated, a larger, placebo-controlled follow-up study in people with MASH and advanced fibrosis may be undertaken. The data obtained from NITs could elucidate the anti-fibrotic potential of afimkibart as well as the potential for composite NIT assessments in MASH therapy development."

Clinical • Metastases • PK/PD data • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Solid Tumor • TNFA • TNFRSF25

Afimkibart: “Ph IIb (TUSCANY-2) in UC demonstrated strong efficacy and safety in a large group of pts (n=245)”; Ulcerative colitis (Roche) - Pharma Day 2025

P2b data • Inflammatory Bowel Disease • Ulcerative Colitis

AMETRINE-PEDS: A Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Afimkibart (RO7790121) in Children With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=100 | Not yet recruiting | Sponsor: Hoffmann-La Roche

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

A Study to Assess the Efficacy and Safety of RO7790121 in Participants With Moderate to Severe Rheumatoid Arthritis Who Have Not Responded to or Who Cannot Tolerate Tumor Necrosis Factor (TNF) and/or Janus Kinase (JAK Inhibitors) (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Anti-TL1A antibody, afimkibart, in moderately-to-severely active ulcerative colitis (TUSCANY-2): a multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b trial. (PubMed, Lancet Gastroenterol Hepatol) - P2 | "Differences in the primary endpoint of clinical remission by tMS were not significantly different for any dose of afimkibart compared with placebo. However, secondary endpoints suggest that afimkibart was associated with a favourable benefit-risk profile, with clinically meaningful improvements in clinical remission with the modified Mayo score for patients with moderately-to-severely active ulcerative colitis. These results support the continued development of afimkibart."

Journal • P2b data • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Nephrology • Novel Coronavirus Disease • Pain • Ulcerative Colitis

A Study to Assess the Efficacy and Safety of Afimkibart (RO7790121) in Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: May 2026 ➔ Aug 2026

Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Afimkibart: Regulatory submission in Japan for ulcerative colitis in 2027 (Chugai) - Q2 FY2025 Results

Japan filing • Inflammatory Bowel Disease • Ulcerative Colitis

RG6631: Regulatory submissions in US/EU for ulcerative colitis in 2027 (Roche) - H1 2025 Results: Regulatory submissions in US/EU for Crohn's disease in 2028 and beyond

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

Discovery and development of SIM0709 a novel bi-specific antibody targeting TL1A and IL23p19 for the treatment of IBD and beyond (IMMUNOLOGY 2025) - "In vitro, SIM0709 demonstrated superior functional activities under various functional assays on both TL1A and IL23 axes compared to that of benchmark anti-TL1A mAb RG6631 and Guselkumab, respectively. High solubility of SIM709 also supports patient-friendly formulation suitable for subcutaneous administration. Taken together, these data support the further development of SIM0709 as a potential FIC therapeutic agent for the treatment of IBD with expected first-in-human study in H1 2026.Keywords: Cells Monocytes/Macrophages T Cells; Diseases Autoimmunity; Molecules Antibodies; Tissues Mucosa"

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL23A

AI-GUIDED DESIGN AND DEVELOPMENT OF HXN-1001: A POTENT, HALF-LIFE-EXTENDED ANTI-TL1A ANTIBODY (DDW 2025) - "In a DSS-induced colitis model using hTL1A, hTL1A/hα4β7, or hTL1A/hIL23 transgenic mice, HXN-1001 provided enhanced anti-inflammatory effects compared to RVT-3101, MK-7240, and the α4β7 integrin-targeting antibody Vedolizumab. In addition, in an imiquimod (IMQ)-induced psoriasis model, HXN-1001 outperformed the marketed anti-IL23 monoclonal antibody Risankizumab in reducing psoriatic-like inflammation, suggesting its utility in broader immune-mediated conditions...The preclinical data collectively establish HXN-1001 as a promising therapeutic candidate with broad immunomodulatory capabilities, superior efficacy compared to current standards, and an extended dosing profile suited for chronic inflammatory and autoimmune diseases. HXN-1001 is anticipated to enter clinical development in Q2 2025."

Crohn's disease • Dermatology • Gastroenterology • Gastrointestinal Disorder • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis • Rheumatology • Ulcerative Colitis • CD40LG • IFNG • TNFSF15

RO7790121 SHOWS EARLY AND RAPID SYMPTOMATIC REMISSION IN THE TREATMENT OF MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS – FINDINGS FROM THE PHASE IIB TUSCANY-2 TRIAL (DDW 2025) - P3 | "Greater and earlier improvements in RB and SF were observed in pts receiving RO7790121 vs PBO. These results indicate early symptom relief and a favorable safety profile for pts treated with RO7790121, supporting its further clinical development. RO7790121 is currently being evaluated in phase III studies (NCT06589986 and NCT06588855)."

Clinical • P2b data • Anemia • Fatigue • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Nephrology • Oncology • Pain • Ulcerative Colitis • TNFA

TREATMENT WITH RO7790121 INDUCES AND MAINTAINS HISTOLOGIC AND HISTOLOGIC-ENDOSCOPIC IMPROVEMENT AND REMISSION IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS – RESULTS FROM TUSCANY-2 (DDW 2025) - P2, P3 | No abstract available

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

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

A Phase III, Multicenter, Double-Blind, Placebo-Controlled, Treat-Through Study To Assess The Efficacy And Safety Of Induction And Maintenance Therapy With RO7790121 In Patients With Moderately To Severely Active Crohn's Disease (ChiCTR) - P3 | N=600 | Not yet recruiting | Sponsor: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

New P3 trial • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • IL23A

RO7790121 as an induction therapy efficacy and safety study in subjects with moderately to severely active Crohn's disease (ChiCTR) - P3 | N=425 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital Chinese Academy of Medical Sciences; Peking Union Medical College Hospital Chinese Academy of Medical Sciences

New P3 trial • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • IL23A

A Study to Assess the Efficacy and Safety of RO7790121 in Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study to Assess the Safety, Pharmacokinetics, and Activity of RO7790121 in Participants With Advanced MASH Liver Fibrosis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Hoffmann-La Roche

New P1 trial • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis