Late Breaking Abstract - The safety and PK of an inhaled pan JAK inhibitor (KN-002) in subjects with COPD

<bold>Background:</bold> Multiple pro-inflammatory mediators implicated in the pathogenesis of COPD signal via the JAK/STAT pathway. KN-002, a potent pan-JAK inhibitor (inhaled via as a dry powder), has been administered to patients with asthma without safety concern, resulting in clinically relevant reductions in FeNO levels. We now report a Phase 1b, randomized, double-blind, placebo-controlled study (<ext-link>NCT05006521</ext-link>) evaluating the safety and pharmacokinetics (PK) of 4 mg BID KN-002 in subjects with COPD. <bold>Methods:</bold> COPD patients had mMRC ≥2 or CAT score ≥ 10 at screening and were using ICS, and/or LABA, and/or LAMA mono- or combination therapy. Treatment was administered over 10 days followed by a 2-day no treatment period and a follow-up 7 days later. Adverse Events (AEs) were recorded at each visit with hematology/chemistry and PK blood samples collected on multiple occasions during the 17-day period. <bold>Results:</bold> 13 subjects (9 KN-002:4 placebo) received treatment. No serious AEs were reported and no subject withdrew due to an AE. 11 subjects (53.8%) experienced AEs; 5 (55.6%) KN-002 and 2 (50.0%) placebo. The most common AE was headache; 2 subjects [22.2%] KN-002 and 1 subject [25.0%] placebo. Safety lab assessments did not reveal findings of clinical concern. Steady state PK was achieved by Day 3 with minimal accumulation upon repeat dosing. Plasma levels were below pharmacologically active concentrations. The KN-002 safety/PK profile was consistent with that reported in subjects with mild and moderate to severe asthma. <bold>Conclusions:</bold> Inhaled KN-002 was well tolerated by subjects with COPD on background therapy. Outcomes support further evaluation to determine the clinical efficacy of KN-002 in subjects with COPD.