Apogee Therapeutics, Inc. announced positive interim Phase 1 data from its first-in-human study of APG777, one of its lead product candidates being developed as a frontline treatment for moderate-to-severe AD and other inflammatory diseases. Pharmacokinetic (PK) data showed a half-life of approximately 75 days across doses tested and Pharmacodynamic (PD) data showed deep and sustained inhibition of key AD biomarkers pSTAT6 and TARC for ~3 months (longest follow-up available, with inhibition still ongoing at time of the data cut). Results from the trial exceeded the Company?s trial objectives and support the potential for APG777, a novel anti-IL-13 antibody, to optimize exposure levels in 16-week induction and be dosed once every three or six months in maintenance.

These findings represent the potential for improved clinical responses from greater exposures in induction and significantly less frequent dosing in maintenance compared to currently approved biologic therapies, which are dosed at every two to four weeks, a potential major advancement for patients with AD and other inflammatory diseases. APG777, in single doses up to 1,200mg and multiple doses of 300mg, was well tolerated and showed a favorable safety profile, in line with the existing body of third-party evidence for the safety of the anti-IL-13 class. Based on these data, the company plans to initiate a randomized, placebo-controlled, Phase 2 clinical trial in patients with moderate-to-severe AD in the first half of 2024 ahead of schedule.

APG777 is a novel, subcutaneous extended half-life monoclonal antibody targeting IL-13 ? a critical cytokine in inflammation and a primary driver of AD. In head-to-head preclinical studies, APG777 demonstrated equivalent or better potency to lebrikizumab in the inhibition of IL-13 signaling.

Based on its potentially best-in-class PK profile, APG777 has the potential for improved clinical responses from greater exposures of drug in induction and dosing as infrequently as once every three or six months. AD is a chronic inflammatory skin disorder which can lead to sleep disturbance, psychological distress, elevated infection risk and chronic pain, all of which significantly impact quality of life. Today?s treatments are associated with many challenges, including frequent injection regimens that can lead to poor patient compliance.

APG777 represents the first clinical-stage product candidate from the company?s strategic collaboration with Paragon Therapeutics, Inc., an innovative discovery engine for biologics. Key Phase 1 Interim Findings: The Phase 1 trial is a first-in-human, randomized, double-blind, placebo-controlled study designed to evaluate safety and PK of APG777 in healthy volunteers. The study enrolled 40 healthy adult participants into three single-ascending dose (SAD) and two multiple-ascending dose (MAD) cohorts.

Doses of subcutaneous APG777 evaluated in the study included 300mg, 600mg and 1,200mg. Detailed findings from the SAD portion and interim results from MAD portion of the Phase 1 trial are as follows: PK differentiation supports further development of APG777 as a treatment for moderate-to-severe AD and other inflammatory diseases: Potentially best-in-class PK profile, including a half-life of approximately 75 days, supporting: Testing higher exposures of drug in induction to potentially achieve improved clinical responses, Testing of maintenance dosing of every 3- or 6-months, representing 2-4 injections per year compared to the current treatment paradigm of 13-26 injections per year, Dose-proportional increases in serum concentrations and key parameters (e.g., Cmax, AUC) were observed in the Phase 1 trial, PK was consistent across subjects with low variability. Single doses of APG777 demonstrated a deep and sustained effect on PD markers for approximately 3 months (longest follow-up available with inhibition still ongoing at time of data cut): Single doses of APG777 suppressed pSTAT6, one of the first downstream markers of IL-13 pathway inhibition, with near-complete inhibition for approximately 3 months, Single doses of APG777 suppressed TARC, an inflammatory mediator and the most strongly correlated biomarker to AD severity, with deep and sustained inhibition for approximately 3 months.

Well tolerated across all dose groups. Single doses of APG777 up to 1,200mg and multiple doses of 300 mg were well tolerated with a favorable safety profile consistent with the existing third-party data supporting the safety of the anti-IL-13 class. The most common treatment-emergent adverse events (TEAEs) were vascular access site pain, vessel puncture site bruise, headache, and vascular access bruising: 60% of participants observed at least one TEAE; 15% of participants observed at least one drug-related AE.

There were no Grade 3 TEAEs or severe adverse events (SAEs). No AEs led to study discontinuation. Apogee plans to advance APG777 into a randomized, placebo-controlled, 16-week Phase 2 clinical trial in patients with moderate-to-severe AD.