*Purpose: Execute a phase 1 study of AT-1501 to assess safety, pharmacokinetics, and functional activity.

*Methods: The study employed a placebo-controlled, sequential, dose-escalation design. 28 healthy subjects and 4 adults with ALS were enrolled. Five sequential ascending doses of AT‑1501 (0.5, 1, 2, 4, or 8 mg/kg) or placebo were administered by IV infusion. The primary endpoint was the safety and tolerability of AT-1501. The secondary endpoint was to determine plasma pharmacokinetics (PK) and anti-drug antibody (ADA) responses to AT-1501. An exploratory endpoint was to examine the ability of AT-1501 to block an immune challenge in subjects who received a Keyhole Limpet Hemocyanin (KLH) challenge.

*Results: Dose proportionality was achieved over the AT-1501 dose range of 0.5 to 8 mg/kg for C_max and AUC_0-t. AT-1501 plasma concentrations decreased over time at all dose levels and were measurable out to 42 days post dose. The mean AT-1501 t_1/2 in healthy volunteers was 18 to 26 days. The PK parameters in ALS were consistent with those from healthy volunteers at the 1 mg/kg dose level.AT-1501 had a safety profile comparable to placebo and was well tolerated in healthy subjects and subjects with ALS. 54% of subjects treated with AT-1501 had at least 1 TEAE and 62% of subjects treated with placebo had at least 1 TEAE. TEAEs ranged from 33% to 66.7% across groups and did not appear to be dose proportional. No subject had a Grade 2 or higher TEAE. The most commonly reported TEAEs overall were headache, somnolence, and upper respiratory tract infection. There were no meaningful laboratory abnormalities, vital sign assessments, ECG assessments, or physical examination findings.Positive ADA responses to AT-1501 were observed in 6 of 30 subjects in the study. There was no dose dependence with respect to the incidence of positive ADA titers. ADA did not appear to affect AT-1501 plasma PK profiles or parameters suggesting they were not neutralizing.8 mg/kg AT-1501 successfully blocked an immune response to KLH challenge in 2 of the 3 subjects tested.

*Conclusions: Our results support further clinical development of AT-1501 for transplantation and autoimmune indications.

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