When Roche veteran Pearl Huang landed at Cygnal Therapeutics in January, the company painted a broad picture of its exoneural approach to cancer treatment. Now, as Flagship Pioneering officially launches Cygnal, the startup is filling in some details including how its drug discovery platform works, where it wants to go beyond cancer and its funding.
Founded in 2017, Cygnal spent two years in the Flagship Labs foundry before the VC firm tapped Huang to take it forward. The Cambridge, Massachusetts-based biotech is zeroing in on the peripheral nervous system as an active player in human health and disease rather than as a conduit of the central nervous system, namely the brain and the spine. It calls its approach exoneural because it’s working on drugs that target pathways and signals outside—or exo—the usual suspects.
“When Flagship incubated this idea, it really was just an idea. They were truly exploring—it was not clear this idea would work,” Huang told FierceBiotech.
“The peripheral nervous system started appearing in medical textbooks as an entity in the 1830s and, in the case of cancer biology, peripheral nerves were described as components of tumor tissue in the late 1800s,” Huang said. “The main reason they have been ignored for such a long time is that it’s difficult to see them.”
Recent advances in imaging 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,” she said.
For example, when cancer 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.
“When we look into why and how this is happening, what we find is in diseased tissue, cancer cells started to coopt neural signals that we previously thought were only active in neurons,” Huang said.
So, what is Cygnal doing with this new understanding? Armed with $65 million in funding and its Exoneural Medicines Platform, the company is pinpointing the kind of neurons, and how many there are, in diseased tissue. A co-culture system can grow a diseased cell next to a neuron and see what it does: “We can recapitulate that signaling, observe it in whole animals and then start to manipulate it to see what the molecular drivers are for that biology,” Huang said.
From there, Cygnal can look at how small molecules and turning gene expression on and off in neurons might affect preclinical disease models. It has a “neuro-pharmacopeia,” or a collection of about 1,000 molecules that have been described as having some activity in the brain and spinal cord.
“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. Looking at how these drugs work in the peripheral nervous system is a starting point for Cygnal’s drug development.
In January, Cygnal highlighted cancer as its primary focus. It’s pursuing inflammatory diseases in tandem and believes its approach could be applied to metabolic diseases, neurology, wound healing and regeneration as well as what it calls diseases of proliferation such as autoimmune diseases, fibrosis and endometriosis, Huang said.
But the best way to show its approach can be successful is to make progress with cancer and inflammation first.
“We’re advancing drug discovery programs as aggressively as we can. We chose oncology and inflammation because, No. 1, the role of neurons in the tumor microenvironment is extremely compelling. Second, we feel that showing clinical proof of concept with the knowledge we have can be done very quickly,” Huang said.