BBrm02: BioBlast Pharma’s Novel Approach To Combat SMA

In a recent press release BioBlast Pharma Ltd., a clinical-stage orphan disease-focused biotechnology company, announced positive results of its preclinical proof-of-concept studies, conducted both in vitro and in vivo, for the company’s premier drug candidate BBrm02 to treat patients with Spinal Muscular Atrophy (SMA).

BBrm02 belongs to a family of small molecule non-glycoside, repurposed drugs which specifically treat genetic disorders caused as a consequence of nonsense mutations arising from the presence of premature stop codons. These drugs prevent the synthesis of such stop codons, hampering protein synthesis and leading to conditions like SMA.

BBrm02 is an intrathecal formulation of the antibiotic azithromycin, which is produced with BioBlast Pharma’s proprietary technique. The drug works by increasing the amount of Survival Motor Neurone 2 (SMN2) protein, reducing disease burden and rescuing motor neuron damage, the main cause behind SMA.

In a series of cellular and murine-based studies, the drug significantly increased the level of SMN2 protein synthesis, with positive results in different cell lines with different levels of severity. These cell lines were obtained from human patients and upon testing for biological activity demonstrated highly functional SMN2 proteins.

Two different sets of murine models of SMA showed that the drug was successful to prevent weight loss, increasing animal survival and normalising a range of neurological functions which otherwise were hampered due to motor neurone damage, such as the ability of the mouse to return to four feet from a supine position (“time-to-right” test) and to walk on a narrow tube (“tube-test”), both of which need muscular strength and balance.

Colin Foster, BioBlast’s President and CEO commented, “We are excited to share this comprehensive proof-of-concept as it establishes the efficacy of our lead drug candidate in our Read-through Platform for Spinal Muscular Atrophy. Importantly, given that BBrm02 is a repurposed drug (azithromycin), we believe there is a reasonable possibility for a shorter developmental process. We plan to start a Phase 2a study with BBrm02 at year-end, 2015.”