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Safety, Pharmacokinetic, and Pharmacodynamic Evaluations of PI‐2301, a Potent Immunomodulator, in a First‐in‐Human, Single‐Ascending‐Dose Study in Healthy Volunteers

PI‐2301 is an amino acid copolymer acting as an immunomodulator for the treatment of autoimmune diseases. The present study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics of PI‐2301 in a single ascending dose, first‐in‐human study involving healthy, male adult volunteers. A total of 56 subjects were given a subcutaneous injection of PI‐2301 ranging from 0.035 to 60 mg. The only consistent side effect was transient injection site reactions. We describe, for the first time, a pharmacokinetic assay to monitor amino acid copolymer concentration in human serum. PI‐2301 was detected in the serum of subjects in the 10‐, 30‐, and 60‐mg cohorts. Maximum serum concentration was achieved between 10 and 30 minutes postdosing with some compound detected 4 hours after dosing. PI‐2301's lasting immunological properties were evident by an ex vivo recall assay showing T‐cell proliferation and IL‐13 production in subjects dosed with 1, 3, or 10 mg of PI‐2301, up to 6 months after dosing. A transient increase in chemokine CXCL9 and CXCL10 plasma levels was seen in subjects dosed with 30 or 60 mg of PI‐2301. These results are highly consistent with our preclinical findings and suggest that PI‐2301 could facilitate the expansion of a favorable immune posture in patients with autoimmune disorders.