resTORbio has reported positive interim findings from three cohorts in the Phase Ib/II clinical trial of RTB101 in patients with Parkinson’s disease.
RTB101 is an oral, selective TORC1 inhibitor that blocks the phosphorylation of various targets downstream of TORC1, which is known to be associated with a decline in the function of various organ systems, including the neurologic system.
The multi-centre, randomised, double-blind, placebo-controlled Phase Ib/IIa trial is being conducted to investigate the safety and tolerability of once-weekly RTB101 alone or along with sirolimus.
Participants have been enrolled in three cohorts to date and were treated with 300mg RTB101 alone, 2mg of sirolimus alone, or 300mg of RTB101 plus 2mg of sirolimus.
Data showed that the three dosing regimens were well-tolerated, while the 300mg once-weekly dose was observed to cross the blood-brain barrier.
RTB101 concentrations in cerebrospinal fluid (CSF) in patients on 300mg dose were higher compared to preclinical models. These concentrations are believed to have the potential to trigger autophagy in the brain.
Meanwhile, 2mg sirolimus, alone or in combination with RTB101, was not detected in the CSF. Enrolment for the combination cohort is ongoing.
resTORbio co-founder and chief medical officer Dr Joan Mannick said: “We are pleased to have observed that RTB101 is well-tolerated and crosses the blood-brain barrier in Parkinson’s disease patients at concentrations that have the potential to induce autophagy, the process by which cells break down toxic misfolded protein aggregates.
“Preclinical data suggest that induction of autophagy has the potential to slow the progression not only of Parkinson’s disease but also of multiple other neurodegenerative diseases that are characterised by the accumulation of toxic protein aggregates in cells such as Huntington’s and Alzheimer’s disease.”
In November last year, the company stopped the clinical development of RTB101 in the prevention of clinically symptomatic respiratory illness (CSRI) after its Phase III PROTECTOR 1 trial failed to meet the primary goal.