ABCL575
OX40 Ligand (OX40L)
Atopic Dermatitis (AD)
Immunology & Inflammation
ABCL575 is an investigative monoclonal antibody for the treatment of moderate-to-severe atopic dermatitis (AD), with potential applications to other inflammatory and autoimmune conditions.
ABCL575 binds OX40L to disrupt OX40/OX40L signaling, a regulator of inflammatory pathways in AD. It has been engineered with a modified Fc domain to support Fc-silencing and half-life extension. In preclinical studies, ABCL575 shows potent inhibition of T cell-mediated inflammatory pathways, favorable tolerability, and an in vivo half-life that is expected to support less frequent dosing than current clinical-stage molecules. ABCL575 is projected to enter Phase 1 clinical trials in Q3 of 2025.
Treatment options remain limited for one of the most common chronic skin conditions.
AD, more widely known as eczema, is one of the most common chronic diseases worldwide, affecting 15-20% of children and up to 10% of adults.1 Individuals with moderate-to-severe AD experience recurrent flare ups of inflamed, itchy skin that can be painful and negatively impact quality of life, including sleep and mental wellbeing.2
Despite its high prevalence, moderate-to-severe AD remains challenging to treat, with more than half of all patients having inadequate control of symptoms with existing treatments.3 Recent insights into the underlying source of skin inflammation have led to the development of more targeted treatments, such as biologics. However, a significant number of patients show limited response or discontinuation of these therapies,4 warranting a need for alternative treatment options.
- Ständer S. N Engl J Med. 2021 Mar 25;384(12):1136-1143. doi: 10.1056/NEJMra2023911.
- Weidinger S, et al. Nat Rev Dis Primers. 2018 Jun 21;4(1):1. doi: 10.1038/s41572-018-0001-z.
- Wei W, et al. J Dermatol. 2018 Feb;45(2):150-157. doi: 10.1111/1346-8138.14116.
- Lé AM, Torres T. Pharmaceutics. 2022 Dec 8;14(12):2753. doi: 10.3390/pharmaceutics14122753.
ABCL575 targets multiple immune pathways.
Immune cells found in the middle layer of the skin (dermis) function to combat invading pathogens. In people with AD, these cells become over-stimulated, leading to persistent skin inflammation, dryness, and itch.
OX40 and OX40L are proteins found on the surface of immune cells that help regulate the immune response. In AD, increased OX40/OX40L expression leads to the over-activation of inflammatory pathways, inducing production of inflammatory signals and formation of memory T cells.1
ABCL575 is an antibody that binds to OX40L to prevent interaction with OX40. Blocking the OX40/OX40L interaction has been shown to reduce the inflammatory response and help to address symptoms associated with AD.1,2
Proposed mechanism of action for ABCL575 based on AbCellera nonclinical data and published literature.
- Guttman-Yassky E, et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2023 Jan 21;401(10372):204-214. doi: 10.1016/S0140-6736(22)02037-2.
- Weidinger S, et al. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2024 Nov 8:S0091-6749(24)01175-8.