Roche may have been exploring ways to shuttle drugs to the brain for well over a decade, but that’s not stopping the pharma from handing $55 million to Manifold Bio for a fresh route through the blood-brain barrier.
The pact will allow Roche to use Manifold’s tissue-targeting shuttle portfolio and its in vivo discovery engine, dubbed mDesign, to create “multiple next-generation BBB shuttles” for the treatment of neurological and neurodegenerative diseases.
Manifold is going to lead on the R&D activities required to identify and develop new BBB shuttles that can transport Roche therapies to the brain. Roche will then take the baton for preclinical work and beyond.
In addition to the $55 million upfront fee, Manifold could end up receiving development and sales milestones totaling $2 billion as well as tiered royalties should a resulting therapy make it to market.
The nonexclusive agreement also leaves open the option for Manifold to co-fund development of one program in exchange for enhanced royalties.
Manifold was born out of the Harvard lab of biotech entrepreneur and famed geneticist George Church, Ph.D. The company touts its mDesign platform as being able to “systematically measures thousands of prospective BBB shuttles that transit medicines to the brain through multiple ‘portals’ (receptors) directly in vivo.”
Once these shuttles have been identified, the biotech fuses them with antibodies or conjugates them with other therapeutic molecules like siRNAs or antisense oligonucleotides.
“Manifold’s mission is to unlock the full potential of AI-guided drug design with drastically increased experimental throughput in living systems to overcome the translational barrier holding back the creation of critical new medicines,” Manifold CEO Gleb Kuznetsov, Ph.D., said in the release.
“Engineering molecules to safely cross the blood-brain barrier has been a grand challenge for decades, and it’s exactly the kind of problem where Manifold’s direct-to-vivo approach provides a decisive edge,” Kuznetsov added. “We look forward to working with Roche, already a world-leader in technology to enable medicines to cross the BBB, to bring our approach and novel shuttle technologies to expand the breadth of brain-shuttled medicines.”
Roche started working on its own BBB shuttle tech way back in 2008. These efforts have led to trontinemab, a brain shuttle bispecific 2+1 amyloid-beta-targeting monoclonal antibody that entered phase 3 development this year.
“Roche has worked in the field of BBB shuttles for over 15 years and has demonstrated the significant impact BBB shuttles can have on improving antibody pharmacology,” Boris Zaïtra, head of corporate business development at Roche, said in the release.
“We are excited about our partnership with Manifold to identify the next generation of highly specific BBB shuttles, applicable across multiple therapeutic modalities, to tackle some of the most important neurological and neurodegenerative diseases,” Zaïtra added.