Late Breaking Abstract - A Phase 1 trial to evaluate the safety, PK and target engagement of MTX-463, a monoclonal antibody inhibitor of WISP1

<bold>Introduction:</bold> WISP1, a matricellular protein induced in fibrosing diseases, is believed to play a key role in maintaining myofibroblast activation. Inhibition of WISP1 reduces fibrosis in the bleomycin lung model. MTX-463 is a mAb against WISP1 which is being developed as potential treatment for IPF. Aims & Objectives: To evaluate safety, PK, immunogenicity and target engagement of increasing doses of MTX-463. <bold>Methods:</bold> The safety, tolerability and PK of MTX-463 were assessed in a dose-escalating, randomized, double-blind, placebo-controlled single and multiple ascending dose study in healthy volunteers. Target engagement was assessed by measuring serum WISP1 levels. <bold>Results:</bold> In the SAD portion, AEs occurred in 5/24 MTX-463 treated participants vs 1/8 placebo. Related AEs occurred in 2/24 vs 1/8, respectively. No SAEs, no severe AEs and no AEs leading to discontinuation were reported. In the MAD portion, AEs occurred in 5/18 MTX-463 vs 2/6 Pbo, all deemed related. There were no SAEs, no severe AEs and 1 AE leading to withdrawal was reported. PK was dose proportional. T1/2 was 25 days, and 1/42 participants on MTX-463 developed ADA. 79% had detectable WISP1 prior to treatment, and levels dropped to undetectable in all MTX-463 participants. <bold>Conclusions:</bold> MTX-463 appears to be safe and well tolerated with linear PK, a long T1/2 and low ADA. It successfully engaged WISP1 at all doses evaluated. <fig><object-id>erj;66/suppl_69/PA1031/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>