Development Programs

OX-1 (indole-3-propionic acid)

We are developing OX-1 for the treatment of Friedreich's Ataxia ("FA"). This drug candidate is a naturally occurring small molecular weight compound that prevents oxidative stress by a combination of hydroxyl radical scavenging activity and metal chelation.

Phase 1 studies in healthy adults were completed in 2010. The drug was found to be generally well tolerated. The pharmacokinetics revealed that the drug was rapidly absorbed and distributed in the body after oral administration.

A Phase 1b trial in 55 adults with FA was completed in 2015. The study was designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of OX-1 in patients suffering from FA. The drug was found to be generally safe and well tolerated when administered as single and multiple ascending doses. There were no severe treatment emergent adverse events ("TEAEs") or deaths reported in either the single or multiple dose groups, and the majority of TEAEs were of mild severity. The mean terminal elimination half-life ranged between 7.36 and 10.33 hours across all dose groups. Inter-subject variability appeared to be low to moderate.

Anti-TauC3 Monoclonal Antibody

In 2012, we obtained from Northwestern University an exclusive license to worldwide diagnostic and therapeutic applications of a novel monoclonal antibody targeted to caspase cleaved TauC3.

Scientific research and pre-clinical experiments have demonstrated that fragments of Tau protein are present in brains of patients suffering from various neurodegenerative diseases, commonly known as "tauopathies", and that the truncated form of Tau, known as TauC3, is especially toxic.

We have conducted experiments to demonstrate that caspase cleaved TauC3 is present in models of various tauopathies at a level detectable by our anti-TauC3 antibody and that our anti-TauC3 antibody shows sufficient binding specificity to the target TauC3 protein to indicate that the antibody may be a viable treatment agent.

In April 2016, we obtained positive data from an in-vitro study conducted on our behalf at Harvard Medical School and the MassGeneral Institute for Neurodegenerative Disease. The experiments demonstrated that our anti-TauC3 antibody significantly blocks TauC3 fragment seeding, aggregation and toxicity, demonstrating that caspase cleaved TauC3 is a potential target for treatment in Progressive Supranuclear Palsy, Traumatic Brain Injury and other tauopathies and that our antibody may be a viable treatment agent.

Presence of TauC3 in Tauopathies

Scientific evidence has proven that caspase cleaved TauC3 promotes formation of neurofibrillary tangles (NFTs), which are aggregates of hyper-phosphorylated tau found in numerous tauopathies.

Truncation of tau by caspases may occur relatively early in neurodegenerative disease, prior to the key folding steps that lead to the formation of phosphorylated pathological forms of tau. Also, it has been demonstrated that tau truncated at Asp421 (TauC3) aggregates more rapidly and to a greater degree than full-length tau.

Collectively, these studies suggest that the caspase cleavage of tau propagates the formation of NFTs and facilitates filament formation, which are disease- triggering events that are associated with various neurodegenerative conditions, such as Alzheimer's disease, PSP and TBI.

Illustrative Diagram of Presence of TauC3 in Pick's Disease, TBI and PSP