afimkibart (RG6631) / Roche - LARVOL DELTA

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

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

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

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

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

submit phase I and phase II data for Crohn's disease: CDSCO Panel tells Roche Products India on RO7790121 study (Medical Dialogues) - "Reviewing Phase III clinical study protocol of the monoclonal antibody RO7790121, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the pharmaceutical major Roche Products (India) to submit the phase I and phase II data for Crohn’s disease for further review by the committee. This came after the firm presented phase 3 clinical study protocol no. GA45332 version 1.0 dated 22 August 2024."

Clinical protocol • Crohn's disease

Japanese Phase 1 Study for Global Development of Anti-TL1A Antibody PF-06480605: A Randomized, Placebo-Controlled, Single-Ascending Dose Study. (PubMed, Clin Transl Sci) - P1 | "This study satisfied the Japan regulatory requirements, while the favorable tolerability and PK of 450 mg SC in Japanese contributed to a waiver of the 150 mg SC cohort in the China local phase 1 study. NCT04269538."

Clinical • Journal • P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • TNFA

SIBERITE-1: A Study to Assess the Efficacy and Safety of Induction and Maintenance Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • 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 Atopic Dermatitis (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Hoffmann-La Roche

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

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

Treatment with RO7790121 induces and maintains histologic and histologic-endoscopic improvement and remission in moderately to severely active ulcerative colitis – Results from TUSCANY-2 (ECCO-IBD 2025) - P2, P3 | "Similarly, a higher proportion of pts treated with RO7790121 achieved histologic-endoscopic mucosal improvement and remission, sustained through Week 56. RO7790121 is currently being investigated in phase III studies (NCT06589986 and NCT06588855)."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

Development and characterization of LQ080, a novel extended half-life bispecific TL1A/IL-23 p19 single domain antibody for the treatment of IBD (ECCO-IBD 2025) - "The TL1A/IL-23 p19 biparatropic sdAb, LQ080, showed better IFNγ secretion inhibition than RVT-3101 and PRA023, and better inhibition of mouse IL-17 induction than Risankizumab and Guselkumab. No large immune complex formation when mixed with TL1A and IL-23 would make LQ080 safer when administrated by SC route. Overall, LQ080 is a promising TL1A/IL-23 p19 sdAb for IBD treatment."

Inflammatory Bowel Disease • IFNG • IL17A • IL23A

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 (ECCO-IBD 2025) - P3 | "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 • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

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

SIBERITE-1: A Study to Assess the Efficacy and Safety of Induction and Maintenance Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Hoffmann-La Roche

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

TREATMENT OF MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS WITH RO7790121 DEMONSTRATES EARLY CLINICAL RESPONSE AND SYMPTOM IMPROVEMENT – RESULTS FROM THE PHASE 2B TUSCANY-2 TRIAL (Posters of Distinction) (CCCongress 2025) - P3 | "These data indicate a favorable benefit/risk profile for RO7790121 including early symptom improvements. Phase 3 studies (NCT06589986, NCT06588855) are ongoing to confirm these findings."

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

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

RG6631: Regulatory submissions in US/EU for ulcerative colitis in 2027 and beyond (Roche) - FY 2024 Results: Regulatory submissions in US/EU for Crohn’s disease in 2027 and beyond

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

AI-guided generation and development of HXN-1001, a highly potent and half-life extended anti-TL1A antibody (ECCO-IBD 2025) - "In a DSS-induced colitis model in transgenic mice, HXN-1001 demonstrated superior anti-inflammatory effects compared to RVT-3101, MK-7240, and the α4β7 antibody Vedolizumab. In an IMQ-induced psoriasis model, HXN-1001 exhibited better therapeutic effects than the marketed anti-IL-23 monoclonal antibody Risankizumab...It has strong potential to enhance clinical efficacy and dosing convenience. HXN-1001 is anticipated to enter clinical development in Q2 2025."

Immunology • Inflammatory Bowel Disease • IFNG • IL23A

Engineering and Development of a Novel Bispecific Antibody Targeting IL-23 and TL1A (ECCO-IBD 2025) - "Results HXN-1003 features a tetravalent structure, with the anti-IL23 arm specifically binds to the p19 subunit of IL23, demonstrating superior affinity and blocking activity compared to benchmark Risankizumab. For TL1A, HXN-1003 binds to both the TL1A trimer and monomer with sub-nanomolar affinity, exhibiting similar blocking activity to its parent antibody HXN-1001 and RVT-3101...Conclusion HXN-1003 simultaneously blocks IL23 and TL1A, with each arm exhibiting activity comparable to the parent monoclonal antibodies. It has demonstrated synergistic/additive therapeutic effects in both in vitro and in vivo experiments, highlighting its potential to enhance clinical efficacy and benefit autoimmune patients in multiple clinical settings."

Immunology • Inflammatory Bowel Disease • IL22 • IL23A

Engineering and Development of a Novel Bispecific Antibody Targeting both TL1A and α4β7 for the Treatment of IBD (ECCO-IBD 2025) - "For TL1A, HXN-1002 binds to both TL1A trimer and monomer with sub-nanomolar affinity, with similar blocking activity to its parental antibody HXN-1001 and RVT-3101. The bsAb has great potential to significantly enhance efficacy and overcome resistance to Vedolizumab in clinics. Preclinical and IND-enabling studies of the bsAb are currently underway."

Immunology • Inflammatory Bowel Disease