telazorlimab (ISB 830) / Glenmark, Astria Therap - LARVOL DELTA

Safety and Efficacy of Anti-OX40 Therapies in Atopic Dermatitis: A Systematic Review and Meta-Analysis. (PubMed, Dermatitis) - "We aimed to systematically evaluate the efficacy and safety of anti-OX40 therapies (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. In conclusion, anti-OX40 therapies demonstrate clinically meaningful efficacy and an acceptable safety profile for moderate-to-severe AD, offering a potential alternative for patients with inadequate responses to current treatments. Further research is warranted to confirm these results and to refine optimal dosing strategies."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Preclinical data supporting the differentiated profile of STAR-0310, a novel OX40 antagonistic monoclonal antibody (AAAAI-WAO 2025) - "Results STAR-0310 demonstrated an approximately 8-fold increase in binding affinity to human OX40 compared to telazorlimab...STAR-0310 induced significantly lower ADCC on activated T-cells and regulatory T-cells, compared to an in-house analogue of rocatinlimab (AMG451)...Conclusions These preclinical data support further development of STAR-0310 for the treatment of moderate-to-severe atopic dermatitis and other immunologic diseases. The extended half-life suggests potential for sustainable efficacy and prolonged suppression of disease symptoms."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Development and characterization of STAR-0310: a novel OX40 antagonistic monoclonal antibody (EAACI 2024) - "STAR-0310 is being compared to telazorlimab, rocatinlimab, and amlitelimab in detailed preclinical pharmacology studies including in vitro potency of T cell proliferation inhibition, cytotoxicity effects on activated T cells and regulatory T cells. Conclusion STAR-0310, an anti-OX40 antibody, demonstrates the potential for increased half-life, high-potency T cell inhibition, and reduced toxicities with minimized effector (ADCC) functions. These promising preclinical findings support the potential use of STAR-0310 in moderate-to-severe AD and other immunologic diseases."

Atopic Dermatitis • Dermatitis • Immunology • TNFSF4

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target. (PubMed, Am J Clin Dermatol) - "As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD."

IO biomarker • Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Pain • Pruritus • TNFA • TNFRSF4 • TNFSF4

Phase 2b randomized trial of OX40 inhibitor telazorlimab for moderate-to-severe atopic dermatitis. (PubMed, J Allergy Clin Immunol Glob) - P2b | "Telazorlimab was well tolerated, with similar distribution of adverse events between telazorlimab- and placebo-treated subjects in both part 1 and part 2. Telazorlimab, administered subcutaneously at 300 mg every 2 weeks or 600 mg every 2 weeks following a loading dose, was well tolerated and induced significant and progressive clinical improvement in adults with moderate-to-severe atopic dermatitis."

Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

An overview of new and emerging antibody therapies for moderate-severe atopic dermatitis in adults. (PubMed, Expert Rev Clin Pharmacol) - "Some monoclonal antibodies, such as dupilumab (anti-IL-4 Rα) and tralokinumab (anti-IL13) are already approved for the treatment of moderate-to-severe atopic dermatitis, and numerous articles in the literature have demonstrated their efficacy and safety...Data from phase 2b and phase III clinical trials in moderate-to-severe atopic dermatitis in adults indicate that these drugs have a promising efficacy and safety profile. Monoclonal antibodies currently under investigation will be available in the coming years to enrich the therapeutic choice of new alternatives that are valid both in terms of efficacy and safety."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL13 • IL4

ICHNOS SCIENCES ENTERS LICENSING AGREEMENT FOR OX40 ANTAGONIST MONOCLONAL ANTIBODY PORTFOLIO WITH ASTRIA THERAPEUTICS (PRNewswire) - "Ichnos Sciences...announced that the company has entered into an exclusive worldwide licensing agreement for its OX40 antagonist monoclonal antibody portfolio with Astria Therapeutics....With the execution of this agreement, Ichnos has successfully licensed its two assets for inflammatory and immunological diseases....Astria Therapeutics is granted global rights to develop and commercialize OX40 portfolio, comprised of Telazorlimab and its follow-on molecules, for use in inflammatory and immune diseases....In exchange, Ichnos will receive up to $320 million in upfront, development, regulatory and sales milestone payments in addition to up to low double-digit royalties....Astria plans to develop an affinity-matured version of telazorlimab and apply YTE half-life extension technology to create a product that aims to address the need for a safe, effective, and infrequently administered AD treatment."

Licensing / partnership • Atopic Dermatitis

Mitigation and evaluation of agonistic risk of an OX40 antagonistic mab (WCD 2023) - " We showed that OX40 signaling was not activated in any condition where we tested on IMG-007, while Fc-wildtype variant of IMG-007 and another clinical stage Fc-wildtype anti-OX40 antagonistic mab, GBR830, induced OX40 activation when cocultured with increasing density of Raji cells, which imitate cells with high level of FcγR. Our data reported that IMG-007 which possessed excellent binding affinity significantly reduced the agonistic risk of pharmacologically targeting OX40. This study provides a strategy to mitigate agonistic risk of antagonistic anti-OX40 antibody through Fc engineering"

Atopic Dermatitis • Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation

OXFORAD TM: Phase 2b Study to Evaluate the Efficacy and Safety of ISB 830 in Adults With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2b | N=462 | Completed | Sponsor: Ichnos Sciences SA | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

[VIRTUAL] A computational model suggested potential therapies for dupilumab poor responders in atopic dermatitis (ESDR 2021) - "To investigate promising therapies in dupilumab poor responders, we developed a computational model that describes systemslevel AD pathogenesis and effects of nine biologics (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma). The model will serve as a computational platform for model-informed drug development for precision medicine, as it allows to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients. Similar mathematical models and simulation can be also applicable for other diseases and therapies when there are reported clinical efficacies of multiple drugs."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

Telazorlimab: "The primary endpoint-statistically significant improvement in EASI, % change from baseline to week 16- was met both in part 1 and part 2 for the highest doses of telazorlimab tested (300mg q2w and 600mg q2w) vs placebo"; Atopic dermatitis (Ichnos Sciences) - SID 2021

P2b data • Atopic Dermatitis • Dermatology

Novel Targeted Biological Agents for the Treatment of Atopic Dermatitis. (PubMed, BioDrugs) - "If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered...Dupilumab is the first biological agent approved for the treatment of AD in patients aged 6 years and older in the United States. Tralokinumab, lebrikizumab, and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials. Also, fezakinumab was effective in severe AD patients in a phase IIa trial. However, phase II trials of ustekinumab, tezepelumab, etokimab, secukinumab, and omalizumab have failed to meet their primary endpoints. Phase II trials of GBR 830 and KHK 4083 are ongoing. In general, further studies are needed to explore new therapeutic targets and improve the efficacy of biological agents."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation • IL13 • IL17A • IL33 • TSLP

Ichnos Sciences Presents Positive Data From Ongoing Phase 2b Study Of Telazorlimab In Atopic Dermatitis At The 2021 SID Virtual Meeting (PRNewswire) - P2b, N=462; "Ichnos Sciences...today presented positive data from a Phase 2b study of telazorlimab in atopic dermatitis (AD) at the 2021 Society for Investigative Dermatology (SID) Virtual Meeting....At the end of the double-blind portion of the study, for the primary efficacy endpoint of % change in Eczema Area and Severity Index (EASI) score from baseline to Week 16, the two highest doses of telazorlimab, 300 mg and 600 mg administered every two weeks, were statistically superior to placebo (p < 0.05)."

P2b data • Atopic Dermatitis • Dermatology • Immunology

A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis. (PubMed, Allergy) - "Our model identified IL-13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL-13 and IL-22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model-informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

A COMPUTATIONAL MODEL TO INVESTIGATE DRUG TARGETS IN AD PATIENTS WITH HETEROGENOUS RESPONSE TO BIOLOGIC DRUGS (ISAD 2021) - "To understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, we conducted model-based meta-analysis of clinical trials data and developed a mathematical model that describes systems-level AD pathogenesis and effects of nine biologic drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma). The mathematical model will serve as a computational platform for model-informed drug development for precision medicine, as it allows us to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients as well as the influence of pathophysiological backgrounds of patients on variability in drug response. Similar mathematical models can be developed for other diseases and drugs by conducting model-based meta-analysis on reported clinical efficacies of multiple drugs."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

[VIRTUAL] Telazorlimab in atopic dermatitis: Phase 2b study shows improvement at 16 weeks (SID 2021) - "In conclusion, telazorlimab improved clinical signs and symptoms of moderate-to-severe AD, with a favorable safety and tolerability profile. Further evaluation of telazorlimab in the treatment of autoimmune disease is warranted."

P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immune Modulation • Immunology • Infectious Disease • Pain • Respiratory Diseases

Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect. (PubMed, J Allergy Clin Immunol Pract) - "Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830)."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

ISB 830: Data from part 2 of P2b trial (NCT03568162) for moderate-to-severe atopic dermatitis in Q4 2020 (Ichnos Sciences) - Corporate Update

P2b data • Atopic Dermatitis • Dermatology

Phase 2b Study to Evaluate the Efficacy and Safety of ISB 830 in Adults With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2b; N=468; Active, not recruiting; Sponsor: Ichnos Sciences SA; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

Review and analysis of biologic therapies currently in phase II and phase III clinical trials for atopic dermatitis. (PubMed, J Dermatolog Treat) - "Further assessment of tezepelumab and etokimab are needed to assess their safety and efficacy in patients with moderate-to-severe AD. Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD."

Clinical • Journal • P2 data • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

[VIRTUAL] OX40L EXPRESSING NEUTROPHILS INDUCE CD4 T FOLLICULAR AND PERIPHERAL HELPER CELL DIFFERENTIATION IN SYSTEMIC LUPUS ERYTHEMATOSUS (EULAR 2020) - "Inhibition of OX40-OX40L interaction in vitro was achieved using ISB 830, a novel anti-OX40 mAb currently used in clinical trials... Our results disclose an unprecedented phenomenon where cross-talk between TLR7/8-activated neutrophils and CD4 lymphocytes operates through OX40L-OX40 costimulation, and neutrophils promote the differentiation of pro-inflammatory Tfh and Tph, as well as IL21 production. Therefore, OX40L/OX40 should be considered as a potentially therapeutic axis in SLE patients."

IO Biomarker • Complement-mediated Rare Disorders • Immune Modulation • Immunology • Inflammation • Lupus • Lupus Nephritis • Oncology • Systemic Lupus Erythematosus • PD-1

GBR 830, an anti-OX40, improves skin gene-signatures and clinical scores in atopic dermatitis. (PubMed, J Allergy Clin Immunol) - "Two doses of GBR 830, 4-weeks apart, were well-tolerated and induced significant, progressive tissue and clinical changes until Day 71 (42 days after last dose), highlighting the potential of OX40-targeting in AD."

Biomarker • Clinical • IO Biomarker • Journal

Glenmark’s consolidated revenue increases by 14.85% to Rs. 16,807.08 Mn in Q2 FY 14-15 (Moneycontrol) - "Phase I enabling toxicity studies for GBR 830 have been completed and Glenmark has initiated a Phase I study in the Netherlands, Europe."

Trial initiation date • Inflammation

To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adult Patients With Moderate-to-severe Atopic Dermatitis (AD) (clinicaltrials.gov) - P2a; N=40; Not yet recruiting; Sponsor: Glenmark Pharmaceuticals S.A.

New P2a trial • Biosimilar • Dermatitis • Eczema • Immunology

New drug receives approval to treat atopic dermatitis (The Global Health News) - “…Glenmark Pharmaceuticals…GBR 830…for treating atopic dermatitis…planning to conduct phase 2b study in 2018.”

New P2b trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation