A year after its official debut, Cygnal Therapeutics is signing a chief medical officer to translate its exoneural approach into treatments for cancer and other diseases. John Wagner, M.D., Ph.D., joins from Foresite Capital, where he was a venture partner, bringing experience in early development and translational medicine from his time at Merck and Takeda.
Over his career, Wagner has brought more than 150 prospects into human testing, working on clinical development, clinical pharmacology and regulatory filings for various drugs, including Merck’s diabetes med Januvia and lymphoma drug Zolinza. At Takeda, he led translational research and early clinical development before jumping over to Foresite in 2019.
"When I first heard of Cygnal's approach, I was highly intrigued. Exoneural biology is an exciting and foundational way to understand the connection between nerves and cells—and the impact on human health and disease," Wagner said in a statement.
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Cygnal calls its approach exoneural because it is targeting pathways and signals in the peripheral nervous system, outside—or exo—traditional targets in the central nervous system, namely the brain and the spine.
Recent advances in technology have allowed Cygnal to understand the role exoneural biology plays in various disease models: “What we learned is that architecture of nerves in disease settings are quite myriad. We have identified many non-overlapping mechanisms and signals that are sent from neurons to the tissue in the diseased state,” Cygnal CEO Pearl Huang, Ph.D., said in a previous interview.
In cancer, when tumor cells grow near neurons, they can recruit the outgrowth of neurites—little projections that come out of nerve cells—and travel along them in a form of metastasis. They co-opt neural signals that scientists previously thought were only active in neurons, Huang said.
The company launched with $65 million and its Exoneural Medicines Platform to identify what kinds of neurons appear in diseased tissue and how many there are. By studying what diseased cells do when they grown next to neurons, Cygnal hopes to pinpoint the molecular drivers of disease.
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From there, the company can look at how small molecules or toggling gene expression might affect preclinical disease models.
“There has been quite a bit of effort in the pharma industry to create molecules against many of the targets we’re interested in, but they were originally intended for diseases of the brain,” Huang said. Cygnal wants to look at these targets as starting points for the treatment of cancer and inflammatory diseases. The approach could also be useful in various other areas including metabolic diseases, neurology, fibrosis, autoimmune disease, wound healing and regenerative medicine.
"John brings a tremendous amount of experience in developing drugs and ushering therapeutics to market, and his extensive knowledge across multiple disease areas complements our broad, multi-disciplinary Exoneural Medicine Platform. With his seasoned clinical and scientific perspective, John will be an important part of driving both our strategy and our science forward,” Huang said in the statement.