Health

Seattle startup with fresh approach to Parkinson’s and Alzheimer’s disease raises $96M

Cajal Neuroscience, a Seattle startup taking a unique approach to developing treatments for neurodegenerative diseases like Alzheimer’s and Parkinson’s, revealed more details about its strategy and announced $96 million in funding Tuesday.

Biopharma companies have spent billions of dollars over decades on failed trials for Alzheimer’s directed at just one target, amyloid-beta. The one drug available against that target, Biogen’s Aduhelm, was approved in the U.S. based on limited data and has not been commercially successful.

There are numerous potential unexplored drug targets for neurodegenerative diseases, said Cajal CEO Ignacio Muñoz-Sanjuán in an interview with GeekWire. Large-scale human genetic studies have identified hundreds of genetic variants that affect the risk of developing such conditions. But how the genes involved affect cellular processes and disease is not fully known.

Cajal was founded in 2020 to systematically collect such data to reveal key molecules involved in neurodegeneration, with an intitial focus on Alzheimer’s and Parkinson’s disease.

By exploring a large range of potential drug targets, “the field is going back to the basics in some ways,” said Muñoz-Sanjuán.

Other companies exploring fresh approaches to neurodegenerative disease include Seattle startup Athira Pharma. Athira’s compound to affect neuronal growth, however, has proven disappointing so far in phase 2 trials for Alzheimer’s disease, prompting a change in the design of the ongoing study.

On Tuesday researchers are expecting full data from a phase 3 study of lecanemab, another Biogen and Esai experimental drug targeting amyloid-beta. The companies released preliminary data in September suggesting that lecanemab could ease cognitive decline, but more recently the agent has been linked to two deaths, according to reports in Science and STAT.

Yet another amyloid-beta targeting experimental drug, developed by Roche, failed to show benefit in two large trials this month. Late stage trials of experimental drugs for Parkinson’s disease have similarly failed to yield new treatment options.

Muñoz-Sanjuán was previously vice president of translational biology at the Cure Huntington’s Disease Initiative (CHDI) Foundation and took the helm of Cajal earlier this month.

Earlier, two co-founders helped construct the company: chief operating officer Andrew Dervan, who previously led cell therapy business development at Bristol Myers Squibb, and chief scientific officer Ian Peikon, previously director of platform biology and technology at Kallyope, a New York City biotech startup. Cajal board chair and co-founder Robert Hershberg, a venture partner at Frazier Life Sciences and former Celgene executive, also contributed along with other board members.

Cajal now has 56 employees.

Building the company in Seattle

When Peikon left Kallyope in 2019 he was tapped to become an entrepreneur-in-residence at New York City-based Lux Capital, which led the new Series A funding round for Cajal, along with The Column Group. Lux Capital and The Column Group were also both investors in Kallyope.

Peikon helped pull together three scientific co-founders to form Cajal: Cold Spring Harbor Laboratory professor Anthony Zador; Baylor College of Medicine professor Huda Zoghbi, a science partner at The Column Group; and Columbia professor Charles Zuker, a Kalyope co-founder who is also a science partner at The Column Group.

Together, they conceived of an approach to identify and systematically assess new drug targets. “The three of them put their heads together,” said Peikon.

Cajal pinpoints genes involved in neurodegeneration and interrogates how they affect the biology of disease using cell-based screens and animal models. Methods of interrogation include sequencing active genes in cells and imaging techniques such as 3D microscopy of mouse brains.

Zoghbi’s lab provides expertise in large-scale screens and animal studies. Zador’s lab licensed tech to Cajal that maps how neurons connect to each other using a sequencing-based method that labels and analyzes their projections.

In addition to exploring molecules that affect neurons, the company also focuses on support cells often ignored by other researchers.

The company spent its first years developing computational expertise to ingest and analyze data from human genomic and clinical studies, and building tools for its target discovery system.  

More recently, its researchers have identified molecular processes that “we are really excited about,” said Peikon. Cajal is now developing its drug discovery arm, focused on finding compounds that interact with their identified targets and affect their activity.

The team tapped into a talented pool of employees in Seattle, including experts in functional genomics and neuroscience. Dervan pointed to the deep biotech talent pool in the region, home to the University of Washington and the Allen Institute for Brain Science.

“That was the nucleating force, the gravitational pull that brought us to Seattle,” said Dervan.

The company spent its early days at Alexandria Launch Labs, an incubator space in Seattle’s Eastlake neighborhood, and is now growing in a larger space in the same Alexandria-owned building. The company will move into a nearby new Alexandria building at 1150 Eastlake in 2023.

Alexandria Venture Investments participated in the funding round, along with Two Sigma Ventures, Evotec, Dolby Family Ventures and others.

The startup is named after Santiago Ramón y Cajal, a Spanish scientist and artist who drew the first maps showing the cellular content and connectivity of the brain in the late 1800’s.

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