Apogee Therapeutics plans to take combination approach to AD

Apogee plans to take a combination approach to AD by targeting Types 1-3 inflammation potentially offering JAK-like inhibition without their associated safety concerns. This approach offers the potential for improved clinical responses over monotherapies and best-in-class dosing. APG990 is a novel, SQ half-life extended mAb targeting OX40L, initially being developed for AD. OX40L is located further upstream in the inflammatory pathway than IL-13 and targeting it could have broader impact on the inflammatory cascade by inhibiting Type 1, Type 2 and Type 3 pathways. Apogee is evaluating APG990 in a Phase 1 healthy volunteer trial to establish safety, tolerability and PK profile, which would enable combination with APG777. The APG777 + APG990 coformulation has been shown to retain stability, injectability, and convenience of individual components. In preclinical studies it has demonstrated broad inhibition of Type 1, Type 2 and Type 3 inflammation with potential for better tolerability than JAK inhibitors. Pending APG990’s Phase 1 results expected in the first half of 2025, Apogee plans to initiate its first combination trial in 2025 – a Phase 1b trial designed to evaluate the safety, PK, PD and efficacy of the combination of APG777 and APG990 against DUPIXENT in ~50-75 patients with moderate-to-severe AD with readout expected in second half of 2026. Apogee plans to take a combination approach to the treatment of asthma and COPD, leveraging mechanisms that address both central and local drivers of respiratory diseases, potentially enabling enhanced efficacy and extended dosing regimens. APG333 is a novel, SQ extended half-life mAb targeting TSLP, a key driver of Type 2 and Type 3 inflammation in eosinophilic and non-eosinophilic conditions. A Phase 1 trial in healthy volunteers is planned to commence by the end of 2024, with data expected in the second half of 2025. In preclinical studies, the combination of APG777 + APG333 has been shown to drive broader and deeper inhibition of inflammation centrally with deeper impact on local airway responses compared to approved or in-development biologics, with the potential for a significantly less frequent dosing schedule. Apogee plans to evaluate APG777 and APG333 monotherapies in respective Phase 1b trials in patients with asthma in 2025 to support advancement into future combination trials in asthma and COPD.