Mis-folded SOD1 can be detected in the majority of ALS patients suggesting that SOD1 is a common pathogenic driver across familial and sporadic forms of ALS. AP-101 is a fully human IgG1 antibody with high affinity and selective binding to misfolded SOD1 protein. In transgenic mouse models of ALS, a murine version of AP-101 was able to attenuate loss of spinal cord motor neurons and prolong overall survival.

Given the rapidly fatal nature ALS  an efficient accelerated dose escalation study was performed using an open label oncology style 3+3 design (ClinicalTrials.gov Identifier: NCT03981536). AP-101 was administered to patients via intravenous infusion over 1 hour at increasing dose levels of 100, 500 or 2500mg. A sentinel patient was observed before recruitment of additional patients into the cohort. After observation for 3 weeks and in the absence of any drug related toxicity the next dose cohort was opened for recruitment. If any safety signal had been observed in the first 3 patients, an additional 3 patients would have been recruited at the same dose level. Dose limiting toxicities in 2 or more patients at any dose level would result in a declaration of maximum tolerated dose. The overall goal was to assess safety, tolerability, and pharmacokinetics of AP-101 after intravenous administration. Cerebral spinal fluid was also collected from patients

To date, no dose-limiting toxicities effects or any safety and tolerability concerns related to AP-101 have been observed. The most common adverse events are related to the lumbar puncture associated with patient screening.