afimkibart (RG6631) / Roche - LARVOL DELTA

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

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 completion date: Nov 2026 ➔ Apr 2027

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

Indirect Comparison of Afimkibart and Adalimumab Treatment Effects in Patients with Ulcerative Colitis Using Data from TUSCANY-2 and HIBISCUS (ECCO-IBD 2026) - P2, P3 | "It is worth noting that histological and lab data were not included in the PS modeling due to limited availability, and residual confounding by them and other unmeasured factors cannot be entirely ruled out. Overall, afimkibart showed greater improvement across clinical and endoscopic endpoints compared to adalimumab in biologic-naïve patients."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Understanding the clinical trial experience of people living with Inflammatory Bowel Disease (IBD), and identifying unmet needs and key challenges that impact trial participation (ECCO-IBD 2026) - P3 | "More convenient study visits and improving access to open-label extension programmes could make IBD trials more participant-inclusive, reduce trial burden and improve recruitment and retention. The results of this study have informed the trial design for four ongoing phase 3 clinical trials of afimkibart for people with UC (AMETRINE-1 [NCT06589986], AMETRINE-2 [NCT06588855]) and CD (SIBERITE-1 [NCT06819878] and SIBERITE-2 [NCT06819891])."

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

Afimkibart downregulates Th17, myeloid, and fibrotic pathways in ulcerative colitis: serum proteomics from the phase 2b TUSCANY-2 trial (ECCO-IBD 2026) - "Conclusion This large-scale, placebo-controlled proteomic analysis from TUSCANY-2 confirms and extends mechanistic insights from TUSCANY, showing that afimkibart consistently downregulates proteins associated with Th17, Th9, myeloid, and fibrotic signaling pathways in UC, including markers of TNF non-response. Collectively, these findings show that afimkibart goes beyond inflammation by modulating both immunological and fibrotic pathways, provide preliminary evidence of TL1A differentiation from TNF as a therapeutic target, and underscore afimkibart’s potential as a novel disease-modifying therapy in IBD."

P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL17A • IL6 • MMP8 • TNFRSF25

Afimkibart Fully Neutralizes TL1A Activity, Rendering DcR3-TL1A Blockade Biologically Inconsequential (ECCO-IBD 2026) - "The lower cellular potency and circulating levels of DcR3, together with the absence of a clear association for DcR3 with clinical remission, suggest that afimkibart may be sufficient for blockade of TL1A signaling. However, given that these findings are based on a single-arm study of 50 patients, they should be confirmed in larger, placebo-controlled studies."

Inflammatory Bowel Disease • Ulcerative Colitis • FASLG • TNFA • TNFRSF25

Functional Advantage of Afimkibart’s Preference for Trimeric TL1A in Blocking Active TL1A Signaling (ECCO-IBD 2026) - "The inability of afimkibart to bind monomeric TL1A may represent a distinct pharmacologic advantage by ensuring selective targeting of the signaling-competent TL1A form for optimal pharmacokinetic and pharmacodynamic properties. This functional specificity underpins the therapeutic potential of afimkibart in TL1A-driven diseases such as IBD."

Inflammatory Bowel Disease • IFNG • IL12A • IL18 • TNFA • TNFRSF25

Satellite Symposium: Is TNF-Like Ligand 1A (TL1A) Inhibition the Answer to Improving Disease Remission in Inflammatory Bowel Disease? (CCCongress 2026) - "Early studies of investigational anti-TL1A agents—including tulisokibart, afimkibart, and duvakitug—demonstrate encouraging outcomes in patients with moderate-to-severe IBD, showing improvements in symptoms as well as reductions in chronic intestinal inflammation and fibrosis. Through case-based discussions and interactive polling, participants will gain practical, up-to-date strategies to enhance IBD management and remain at the forefront of therapeutic innovation. To Register: https://www.gotoper.com/courses/is-tnf-like-ligand-1a-tl1a-inhibition-the-answer-to-improving-disease-remission-in-inflammatory-bowel-disease"

Clinical • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Ametrine-1: A Study to Assess the Efficacy and Safety of Afimkibart (Also Known as RO7790121) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=400 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

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

RG6631: Regulatory submissions in US/EU for ulcerative colitis in 2027 (Roche) - FY 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

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

Japan filing • Inflammatory Bowel Disease • Ulcerative Colitis

SIBERITE-PEDS: A Study to Assess the Pharmacokinetics, Effectiveness and Safety of Afimkibart for Induction and Maintenance Therapy in Children With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=100 | Not yet recruiting | Sponsor: Hoffmann-La Roche

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

Velarite-LTE: A Long Term Extension Study to Evaluate the Safety and Efficacy of Afimkibart (RO7790121) in Participants With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

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

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 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Velarite-LTE: A Long Term Extension Study to Evaluate the Safety and Efficacy of Afimkibart (RO7790121) in Participants With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

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