A spinout of Flagship Pioneering has emerged from stealth mode to develop drugs based on pathways and targets the company has discovered in the peripheral nervous system, with an initial focus on cancer and inflammatory disease.
Cambridge, MA-based Cygnal Therapeutics says it is the first company focused on developing drugs in the field of exoneural biology, outside of traditional neurobiology focused on nerve-to-nerve interactions in the central nervous system.
Cygnal was created in 2017 as “Venture Labs 41,” an outgrowth of Flagship’s initial efforts to explore the role played in health and disease by the peripheral nervous system, the network of neurons that conveys the body’s sense of touch and pain, transmits movement and mood, and connects distant parts of the body.
Since then, Cygnal has identified specific interactions between neurons and non-neural and disease tissues—disease cells in the disease setting—and has also observed that cells of non-neural origin will co-opt or mimic the language of neurons in the disease state.
“For us, this makes perfect sense, because if a neuron is sending these signals, then it will evolve to send the signals back,” Cygnal CEO Pearl Huang, PhD, told GEN. “This is opening up a whole new area of biology, and fills the gaps in our understanding for multiple diseases. This is a really novel insight that allows us to look at a traditional oncology drug discovery, or traditional inflammation drug discovery in a completely new way.”
While researchers traditionally viewed the peripheral nervous system as merely executing biological decisions controlled by the brain and the spinal cord, “the evidence is, and the data that we generated ourselves, and the data that we’re exploiting, is that the peripheral nerves are actually very active in driving homeostasis independently,” Huang said. “We’re focused on biochemical signaling because that’s something that’s dominant in our system. But it’s also something that is very actionable.”
Cygnal has filed more than 40 patents related to its drug development programs. The company develops drugs through its Exoneural Medicine Platform™ for drug discovery. Its six core components are proprietary imaging, co-culture technology, neural cell control, neural functional genomics, neural pathway bioinformatics, and a custom neuropharmacopeia—a collection of molecules that the company uses to modify or to modulate targets in the brain.
“We actually have little subsets that we call MOA boxes—mechanism of action boxes—and that’s how we think about them. We group them in little clusters based on what they do, what they look like—we really see them as tools,” Huang said. “The way we describe our platform is, we ask one question, we answer it six different ways. Our ability to connect the dots between the answers is what gives us novel biological insight.”
Earlier this year, Cygnal advanced beyond discovery and target identification to begin development of two drug candidates—one in oncology, the other in immuno-oncology. Cancer is a therapeutic area where the company expects to rapidly demonstrate its hypothesis due to the rich exoneural signaling associated with the disease. So too, Cygnal reasons, is inflammation, where the company focuses on the enteric nervous system.
Other disease areas of interest to Cygnal include obesity/metabolism, where nerves are signaling to brown fat cells to regulate thermogenesis; wound healing; cell regeneration; and diseases caused by hyperproliferation, such as fibrosis, endometriosis, and autoimmune disease.
“The nerves are a part of the disease state. The nerves might even signal aberrantly in the disease state, and nobody has mapped out exactly how this is happening. That’s what our platform allows us to do,” Huang said. “By using CRISPR-Cas9 focused on neural genes, by using bioinformatics focused on and refined for nerve signaling pathways, we know where the biology is coming from, what signals are being sent, and how they are being received. The neuropharmacopeia is certainly is a tool that helps us decode a lot of what’s happening, and what the particular specifics are of targets and pathways, and its relevance to disease causality.”
The company examines both bulk tumor and single cell RNA sequencing to create novel neural signatures, including neural progenitors. The signatures are used for probing human tumor samples and model systems, with the aim of understanding interactions between neurons and the tumor microenvironment.
Since its launch, Cygnal has raised $65 million in total capital, but won’t disclose its investors or what stages of financing it has attained to date. The company will say, however, that its workforce has grown to 41 people, with plans to expand to 60 by year’s end.
“I don’t want to make any predictions, but I can tell you that things are moving quite well,” Huang said.
