Apogee Therapeutics (APGE) Study Update summary

Introduction and Context

• Apogee Therapeutics is advancing therapies for atopic dermatitis, targeting a projected $50B market with multiple candidates, including APG279, a combination of APG777 and APG990, designed for best-in-class efficacy and extended dosing intervals.

• APG990 targets OX40L, enabling broader inhibition across Type 1, 2, and 3 inflammation, and both APG279 and APG990 are formulated for high-concentration, long-acting subcutaneous injections.

• Multiple clinical readouts are planned before the end of 2026, including head-to-head trials against DUPIXENT.

Interim Phase I Results for APG990

• APG990 demonstrated a favorable safety profile with all tested doses up to 1,200 mg well tolerated, no serious adverse events, and no dose-dependent trends in adverse events observed.

• Pharmacokinetic data showed an approximately 60-day half-life for APG990, 2.5 to 3 times longer than amlitelimab, supporting every three or six-month dosing.

• Dose proportionality and low variability were observed, with modeled exposures at three and six-month intervals comparable to amlitelimab at relatively low doses.

• No anti-drug antibody impact was observed on PK curves in the interim analysis.

• Most common adverse events were mild and infrequent, such as headache and mild injection site reactions, with no drug-related serious adverse events or discontinuations.

Combination Strategy and Scientific Rationale

• APG279, a co-formulation of APG777 and APG990, targets IL-13 and OX40L, aiming for best-in-class efficacy in atopic dermatitis by inhibiting Type 1, 2, and 3 inflammation.

• Both antibodies are Fc-engineered for extended half-life, with APG777 showing a 77-day half-life and APG990 a 60-day half-life.

• Preclinical proof of concept demonstrated broader inhibition of inflammatory pathways compared to monotherapy, approaching JAK-like efficacy without associated safety liabilities.

• GLP toxicology studies in non-human primates showed APG279 was well tolerated at high doses, with no toxicity observed.

• Co-formulation is stable at high concentrations, enabling a single 2 mL injection every three or six months.