Cygnal Therapeutics to Develop Drugs Based on Exoneural Biology

Flagship Pioneering has unveiled Cambridge-based Cygnal Therapeutics which was founded in 2017 in Flagship Labs. Cygnal is the first company to develop drugs in the field of exoneural biology, a new understanding of how nerves and neural signaling drive human health and disease. The company has discovered biologically relevant pathways and advanced starting points for drug targets based on exoneural biology, and its initial areas of focus are cancer and inflammatory disease. Cygnal is led by CEO Pearl Huang, Ph.D.

“For decades, scientists have known that the human body is interconnected by peripheral nerves that communicate with the central nervous system. Yet the traditional neurobiological view relegated these nerves to an auxiliary status,” said Noubar Afeyan, Ph.D., founder and CEO of Flagship Pioneering and co-founder of Cygnal Therapeutics. “Flagship conducted explorations into the role of nerves in health and disease, finding far-reaching and powerful connections. We created Cygnal to develop drugs based on these insights, and we believe the company will bring relief to patients in need with unprecedented exoneural medicines.”

Cygnal’s story began several years ago, when Flagship became interested in the role of the peripheral nervous system (PNS) in health and disease. This network of neurons conveys the body’s sense of touch and pain, transmits movement and mood, and connects distant parts of the body. Although there have been indicators in research that the PNS is active in human health and disease, this important system has been overlooked in favor of the brain and spine, which are the traditional focus of neurobiology.

Flagship asked: What if, instead of being mere conduits of the central nervous system’s commands, peripheral nerves are independent biological actors and even decision makers? What if the most important neural signals in disease come not from the brain, but from the PNS?

Led by Flagship Pioneering Partner Avak Kahvejian, Ph.D. (Cygnal’s co-founder and founding CEO until Dr. Huang’s appointment in early 2019) and Principal Jordi Mata-Fink, Ph.D., a team of entrepreneurial scientists leveraged new, advanced tools to examine peripheral innervation in tumor tissue, observing new interactions between neurons, tumors, and other cells in the tumor microenvironment. It turns out that from tumors to gut inflammation and other areas of disease, nerves are functioning in ways far beyond canonical contexts and mechanisms—the tissues they permeate make use of biochemical neural pathways and signals. This is a novel way of thinking about neural signaling as outside—or exo—traditional neurobiology, giving rise to the term exoneural biology to describe the field.

Cygnal Therapeutics was founded to build the first platform to develop drugs in this new field of exoneural biology. Cygnal’s Exoneural Medicines Platform enables the company to rapidly identify key exoneural pathways implicated in numerous disease settings and to create drugs. Using advanced starting points generated by its platform, Cygnal has initiated drug development programs in cancer and inflammation and has filed more than 40 patents.