RG6631 / Roche - LARVOL DELTA

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

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) - No abstract available

Clinical • P2b data • 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 | 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 (DDW 2025) - No abstract available

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

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

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 ulcerative colitis (ChiCTR) - P3 | N=400 | Recruiting | Sponsor: The First Affiliated Hospital,Sun Yat-sen University; The First Affiliated Hospital,Sun Yat-sen University

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

RG6631: First patient in of P3 trial for Crohn’s disease in Q1 2025 (43rd Annual J.P. Morgan Healthcare Conference, Roche)

Enrollment status • Crohn's disease • Immunology • Inflammatory Bowel Disease

RG6631: First patient in of P3 trial for Crohn’s disease in Q1 2025 (43rd Annual J.P. Morgan Healthcare Conference, Roche)

Enrollment status • Crohn's disease • Immunology • Inflammatory Bowel Disease

RO7790121 as Treatment for Moderately to Severely Active Ulcerative Colitis: Efficacy and Health-Related Quality of Life Improvements: Results from the Phase IIb TUSCANY-2 Trial (AIBD 2024) - P2 | "Data from the phase IIb TUSCANY-2 study suggest that RO7790121 leads to meaningful improvements in clinical and endoscopic endpoints, as well as in HRQoL of patients with moderately to severely active UC, with a favorable risk/benefit profile. A confirmatory phase III study is currently underway."

Clinical • HEOR • P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

TUSCANY-2: A Dose-Ranging Phase IIb Study Evaluating Efficacy and Safety of RO7790121, an Antibody Against Tumor Necrosis Factor-Like Ligand 1A (Anti-TL1A) in Adults With Moderately to Severely Active Ulcerative Colitis (ACG 2024) - P2 | "A total of 245 patients received ≥1 dose of RO7790121; 228 patients completed induction and 224 entered maintenance. At week 14, a greater proportion of patients across all treatment doses achieved remission vs PBO by both tMS (p >0.05) and mMS (nominal p < 0.05), sustained through week 56 (Table). Patients receiving any dose of RO7790121 showed greater endoscopic improvement vs PBO at weeks 14 and 56 (Table)."

Clinical • P2b data • Anemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Oncology • Pain • Respiratory Diseases • Ulcerative Colitis • TNFA

CHARACTERIZATION OF TWO NOVEL EXTENDED HALF-LIFE MONOCLONAL ANTIBODY DRUG CANDIDATES TARGETING TL1A FOR THE TREATMENT OF IBD (UEGW 2024) - "Aims & SPY002-091 and SPY002-072 were evaluated in multiple in vitro and ex vivo assays and compared to other anti-TL1A mAbs in clinical development (MK-7240, RG6631, and TEV-48574). We have characterized two anti-TL1A antibodies that exhibit high selectivity and affinity for TL1A, demonstrate effective blockade of the TL1A interaction with DR3, and potently inhibit downstream cellular signaling. With an extended half-life observed in NHP, both SPY002-091 and SPY002-072 demonstrate therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • FASLG • TNFA

DISCOVERY AND CHARACTERIZATION OF A NOVEL HIGH-AFFINITY ANTI-TL1A MONOCLONAL ANTIBODY WITH EXTENDED HALF-LIFE FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE (UEGW 2024) - "Select clinical candidate antibodies were further compared to clinical-stage anti-TL1A mAbs PRA023/MK-7240/tulisokibart, RVT-3101/RG6631, and TEV-48574. The clinical candidate antibodies bind with high affinity and specificity to TL1A and demonstrate potent blockade of TL1A-mediated DR3 receptor signaling. In human FcRn knock-in mice and in cynomolgus monkeys, these antibodies show an extended half-life consistent with FDA-approved antibodies using the XtendTM technology. These data demonstrate the therapeutic potential of the clinical candidate antibodies in the treatment of TL1A-mediated diseases such as ulcerative colitis and Crohn’s disease - with the advantage of infrequent subcutaneous dosing."

Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD4 • FASLG • IFNG • TNFA • TNFRSF25

EFFICACY AND SAFETY OF RO7790121, A FULLY HUMAN MONOCLONAL ANTIBODY BLOCKING TUMOUR NECROSIS FACTOR-LIKE LIGAND 1A IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING PHASE 2B TUSCANY-2 STUDY (UEGW 2024) - P2 | "Data from the phase 2b TUSCANY-2 dose-ranging study suggests that RO7790121 has a favourable benefit/risk profile with clinically meaningful improvements in pts with moderately to severely active UC. A phase 3 study will be conducted to confirm these results.Table. Summary of efficacy outcomes at week 14 and week 56Induction, week 14PBO(n=43)50mg (n=47)150mg (n=60)450mg(n=88)Clinical remission by tMS,* % (90% CI) 11.6 (5.8–22.9)25.5 (15.4–37.2)23.3(15.0–34.0)23.9(16.6–32.1)Clinical remission by mMS,† % (90% CI)11.6(5.8–22.9)29.8(19.9–42.3)35.0 (25.1–45.2)31.8 (23.7–40.8)Endoscopic improvement,‡ % (90% CI)18.6 (9.6–30.2)40.4 (28.3–53.5)38.3 (27.8–48.6)40.9 (32.1–50.0)Maintenance, week 56§N/A‖50mg(n=42)150mg(n=26)450mg(n=28)Clinical remission by tMS,* % (90% CI) 31.0 (19.4–43.3)34.6 (20.9–52.6)39.3 (23.8–56.5)Clinical remission by mMS,† % (90% CI) 31.0 (19.4–43.3)38.5 (23.3–56.4)35.7 (20.9–52.7)Endoscopic improvement,‡ % (90% CI)..."

Clinical • P2b data • Anemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Oncology • Pain • Respiratory Diseases • Ulcerative Colitis