Biogen has bolted on a couple of early-stage drug candidates for neuromuscular diseases via a $535 million deal with California startup AliveGen.
The deal was announced among Biogen’s second-quarter results update and includes two drugs that target myostatin, a regulator of muscle growth and function. Biogen says it plans to develop the two candidates for indications such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).
Blocking the activity of myostatin has been proposed as a way to treat muscle-wasting disorders for years, but lab experiments with inhibitors have suggested that while they can increase muscle mass, that may not translate to increased muscle strength.
AliveGen’s two muscle-enhancing candidates—ALG-801 in a phase 1a study and ALG-802 in preclinical development—are recombinant proteins that work in a different way to other myostatin blockers and “may result in greater efficacy and improved safety,” according to Biogen.
The acquisition includes an upfront payment of $27.5 million, with development and commercialization milestones “across both assets and multiple indications” raising the ceiling of the deal to the $535 million mark.
The proteins act as ligand traps for the activin receptor type IIB (ActRIIB), a receptor for the transforming growth factor-beta family of molecules, that includes myostatin. ALG-801 has now been renamed BIIB110.
There’s not much information available on the two candidates, but the mechanism seems similar to that pursued by Acceleron Pharma with ACE-083, a ligand trap for TGF-beta receptors which is being tested in a phase 2 trial involving patients with facioscapulohumeral muscular dystrophy (FSHD) and Charcot-Marie-Tooth disease. Acceleron says its drug has both improved muscle mass and strength when injected directly into muscles.
Other companies looking at myostatin inhibition as a treatment for neuromuscular diseases include Scholar Rock—due to start trials of its SRK-015 drug in SMA this year—but the category has had some high-profile failures. Those include Novartis/Morphosys’ bimagrumab, which failed a phase 2b/3 trial in sporadic inclusion body myositis in 2016, as well as drugs from Amgen spinout Atara and Shire.
Myostatin was also the target for the CRISPr/Cas9 drug that former NASA biochemist and self-styled biohacker Josiah Zayner self-injected last year, claiming it was both an experiment to see if it would build muscle mass, as well as a stunt to draw attention to the potential of do-it-yourself gene editing in humans.