Touting new way of mining neuro targets, Takeda spinout draws $45M from GV, Bill Gates, Foresite
More than three years after Takeda spun out its top neuroscience team in Cambridge, UK into a transatlantic biotech, GV, Bill Gates and Foresite Capital are chipping in $45 million to power the discovery engine it was founded on.
Cerevance has moved one program — for Parkinson’s — into the clinic; the proceeds should fund others, including several designed to address neuroinflammation in Alzheimer’s disease. With an expected second close of the Series B that should roughly double their take, the biotech should have four more drugs in human trials before they need to raise another round, CEO Brad Margus said.
But perhaps more importantly, the syndicate is interested in finding more targets on Cerevance’s NETSseq platform. Pioneered by Nathaniel Heintz at the Rockefeller University, the technology profiles post-mortem human brain tissue samples, mapping out transcriptional and epigenetic properties of neurons and glial cells.
The company works with 14 brain banks around the world to assemble its brain tissue collection — which now stands at 7,000 samples in total, including healthy controls. A look at their existing samples could offer a hint on their next steps: Parkinson’s (with or without dementia), Alzheimer’s, Huntington’s, amyotrophic lateral sclerosis and essential tremor. Additional donor samples are planned for a range of CNS disorders from major depression to progressive supranuclear palsy, according to Cerevance’s website.
It goes one step further than the mouse-based work at Envoy, the last biotech founded by Heintz and Margus. Envoy was sold to Takeda in 2012, and from its pipeline Cerevance picked out a preclinical lead asset that it has since ushered into Phase II.
“Knowing that target, we [turned to] the Cerevance platform and looked at human tissue and confirmed that the target was really selectively expressed in this one cell type in the striatum in the brain that’s important for Parkinson’s,” Margus told Endpoints News.
Just what precise protein CVN424 acts on, Cerevance isn’t disclosing, except to emphasize that it is present in dopamine receptor D2-expressing medium spiny neurons — meaning the compound modulates the inhibitory D2-dependent indirect pathway but not the excitatory D1-dependent direct pathway.
Similarly, its other (very early) Parkinson’s and Alzheimer’s candidates hit targets selectively expressed on a particular cell type.
“The platform is really playing out where we had hoped,” Margus said. “It’s revealing targets that changed in disease or that are selectively expressed in diseased cell types.”
All but one of its six preclinical programs should address a target that’s present in the overall patient population — and not a subset identified by a biomarker. In neurodegenerative diseases, he added, certain cell types appear more vulnerable than others: With Alzheimer’s, for instance, the hippocampus and the memory cortex lose cells much earlier in the disease.
While Cerevance has only small molecule discovery expertise internally, it’s open to partnering for targets where antibodies, antisense oligonucleotides or even protein degraders would make more sense. The same goes for disease areas the 34-person team doesn’t have the time or energy for — including one PhI drug that they licensed from Takeda.
“We absolutely are about finding great targets, not about limiting to one modality,” Margus said.
Takeda is both a partner and an investor, having signed on for a research alliance applying the tech in gastrointestinal disorders (a project overseen by Mark Carlton, a veteran of the Japanese pharma and now Cerevance’s CSO). It returned for the Series B alongside Lightstone Ventures and the Dementia Discovery Fund.
“A few months ago we thought we were gonna have to not be able to do anything in China and do everything in the US or UK,” he said. “Now it’s the other way around, where we’re pushing more of our work to China.”