Martin Jefson, United States of America
Pinteon Therapeutics ClinicalAuthor Of 1 Presentation
A PHASE 1 SINGLE ASCENDING DOSE STUDY OF PNT001, A MONOCLONAL ANTIBODY RECOGNIZING CIS-PT231 TAU FOR TREATMENT OF TAUPATHIES
Abstract
Aims
Pinteon Therapeutics has generated a humanized monoclonal antibody, PNT001, that recognizes cis-pT231 tau with high affinity and selectivity and may reduce the spread of tau pathology and augment tau clearance in tauopathies. We performed a Phase 1, randomized, double-blind, placebo-controlled, single-ascending-dose trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of intravenous PNT001 in healthy volunteers.
Methods
The study was a single-dose, double-blind, placebo-controlled dose cohort escalation design with PNT001 at doses of 33mg, 100mg, 300 mg, 900 mg, 2700 mg, delivered as a single 30-minute intravenous infusion. Each dose cohort contained 6 active and 2 placebo subjects. Safety, tolerability, PK and biomarker data were collected over 16 weeks. CSF was collected at day 3 and day 28 to assess PNT001 CSF and biomarker concentrations. Dose escalation was determined by an external, independent data safety monitoring board based on review of adverse event data.
Results
Three non-serious adverse Grade 1 events were determined to be related to study drug/placebo and all resolved without sequelae. No maximum tolerated dose was identified and there were no premature discontinuations, dose reductions, or dose interruptions due to adverse events. Well-tolerated doses provided CSF concentrations of PNT001 several fold in excess of the Kd for PNT001-antigen binding.
Conclusions
PNT001 was well tolerated in human volunteers at doses that provide a potentially therapeutic CSF drug concentration. These results support further multiple ascending dose studies in patients with tauopathy.