Spotlight: Cerevance Raises $45 Million to Advance Therapeutics Against Novel CNS Targets

by Marie Daghlian

Cerevance has raised $45 million in a series B financing to continue deploying its platform to identify novel therapeutic targets for central nervous system diseases, and advance a pipeline of therapies for Parkinson’s disease, Alzheimer’s disease, and neuroinflammation.

New investors GV, Bill Gates, and Foresite Capital joined previous investors Takeda Ventures, the Dementia Discovery Fund, and Lightstone Ventures, providing enough capital to take the company through its first mid-stage trial, and advance four programs into the clinic.

CEO Brad Margus, Chief Scientific Advisor Nathaniel Heintz, and others founded Cerevance three years ago to take a different approach to identifying and tracking novel targets in intractable CNS diseases. Licensed from the Rockefeller University where it was developed by Heintz and Xiao Xu,  Cerevance’s NETSseq technology sorts nuclei by cell type in post-mortem brain tissue.

CEO Brad Margus

“It’s a more thorough approach to identifying new targets than currently used methods such as animal models, neurons developed from stem cells, and single cell analysis,” says Margus. Cerevance’s NETSseq can probe cells much more deeply to get a better picture of all the genes that are selectively expressed in a specific cell type.

“For identifying new targets, genes that change with disease, genes that change with age or genes that are very selectively expressed in one cell type that are druggable, you need to be able to see all the genes that are expressed in that cell type. That’s what NETSseq allows you to do. You get very rich, deep data that allow you to see everything.”

At the same time that Cerevance was industrializing the NETSseq platform, it began collecting human brain tissue samples. Working with 14 biobanks mostly in the European Union and the United States, it has collected more than 7,000 human brain tissue samples from both healthy and diseased donors ranging in age from 8 to 97.

The diversity of samples allows the company to see changes that occur even in healthy people as they age.

“We have been able to look at how the gene expression patterns change with disease from cell type to cell type,” Margus said. “One of the things we are really interested in is why, in diseases often caused by some genetic mutation that should affect all cell types, for some reason only certain cell types are vulnerable. In Alzheimer’s disease several cell types in the hippocampus and entorhinal cortex die much earlier than other cell types. Regardless of the cause, the biology and pathways in specific cell types makes them more vulnerable or more resilient. This can offer us places where we can intervene.”

Cerevance has so far identified and selected six new targets to which it is applying small molecule drug discovery. They are in preclinical development for Parkinson’s disease, AD, and neuroinflammation, which plays a role in many CNS diseases.

Cerevance licensed its lead program, CVN424, from Takeda—a preclinical compound discovered by Envoy Therapeutics, Margus’ previous company that he sold to Takeda. The molecule acts on a target very selectively expressed only in one cell type that is relevant to Parkinson’s both in a mouse model in and human tissue samples.

In December, Cerevance began enrolling Parkinson’s patients in a phase 2 trial of CVN424 as a treatment for Parkinson’s patients. The compound selectively targets the dopamine D2 receptor-dependent, indirect pathway associated with Parkinson’s disease. It is intended to generate the positive effects of L-dopa and deep brain stimulation without the adverse effects. Data readout from the trial is expected in December, Margus says.

Cerevance also signed its first major deal in December—a collaboration with Takeda in gastrointestinal diseases in which Cerevance will use its platform to profile two cell types in the CNS that Takeda has identified as critical in mediating these diseases. Cerevance will identify targets that are selectively expressed only in those cell types to select and take forward.

It’s a chance to apply NETSseq to another area we would not have thought of and where it could prove powerful, said Margus, who also mentioned that the company will be announcing at least one or two more such research collaborations in the near future.

Despite the workarounds right now in dealing with the COVID-19 pandemic, there’s a lot to look forward to at Cerevance. “The new investors that came in seem to really appreciate our datasets and you can’t think of better people who might be evaluating large data sets than Google and Gates,” said Margus. “We think they will be helpful in giving us guidance and strategy – all we can do with mining our data sets for targets of interest.”