To evaluate the safety, PK, and PD of NVG-2089 following single and multiple ascending doses in healthy volunteers.

NVG-2089 is a recombinant human IgG1 Fc molecule bearing a single F241A substitution that induces the same conformational change in the Fc domain as is observed on sialylated IVIg.  This enables activation of Type II FcγRs (DC-SIGN and CD23) which play a key role in promoting immune tolerance by upregulating the inhibitory immune checkpoint FcγRIIB and expanding Tregs, critical for controlling autoimmune responses. Unlike IVIg (standard of care for CIDP), which relies on a small fraction (5-10%) of sialylated IgG for its therapeutic effect, NVG-2089 specifically targets these immune-tolerizing receptors, potentially offering a more potent/targeted therapeutic.

This was a randomized, blinded, placebo-controlled SAD/MAD study in healthy volunteers. In the SAD, 40 subjects were randomized to placebo or single i.v. infusion of 9, 30, 100, 250, or 500mg/kg NVG-2089.  In the MAD, 16 subjects were randomized to placebo or 3 bi-weekly doses of 150 or 300mg/kg NVG-2089.  Overall, 42 subjects were randomized to NVG-2089 and 14 to placebo.

NVG-2089 caused no SAEs, AEs leading to early termination, or severe AEs. Five NVG-2089 treated subjects and 3 placebo treated subjects reported at least 1 AE. Exposure was dose-proportional, with an observed half-life of 11-12 days.  FcγRIIB upregulation and expansion of functionally activated Tregs was observed in circulating immune cells at all dose levels examined. 

NVG-2089 was well tolerated in healthy subjects with exposures that may enable therapeutic dosing intervals of up to 4 weeks.  PD responses following treatment with NVG-2089 were similar to that observed in humans following treatment with 1-2g/kg IVIg.  These data support further development of NVG-2089 in patients with CIDP and other autoimmune diseases.  A phase 2 study of NVG-2089 in CIDP is currently underway.