'We're ripe': Cygnal draws the curtain on Flagship's latest bet on exoneural biology — and $65M in cash
No matter how many times one’s heard Flagship Pioneering’s ideation process described, there always seems to be an element of evolutionary wonder: bold, new concepts that are “several standard deviations away from what is known,” put through a rigorous vetting process first aimed at trying to kill the idea, and only the fittest survive.
That’s perhaps why Pearl Huang found its latest creation, Cygnal Therapeutics, and its focus on the peripheral nervous system “irresistibly attractive.” While Huang’s appointment as CEO back in January was well-publicized, Cygnal is just spelling out the details on its platform today, with $65 million — mostly from Flagship — to boast.
Before she decided to jump from Roche to take on the role, Huang did her homework on the field that Flagship is calling exoneural biology.
“When you look back through the literature, for example, in cancer biology, the peripheral nerves were described to be a part of tumors in the late 1800s,” she said. “So the knowledge was already out there.”
But the general preoccupation with the central nervous system and the brain, as well as a lack of methods to illuminate the roles at peripheral nerves play in diseases, relegated the PNS to a wiring diagram in charge of executing orders in many scientists minds. It wasn’t until better imaging techniques came around in recent years that they could see just how extensive that system is in the body and in multiple disease states. And it’s also what attracted Flagship’s Noubar Afeyan, Avak Kahvejian and Jordi Mata Fink to launch the venture.
“We see that the peripheral nervous system it branches and goes as deeply into tissue as your vascular system,” she said. And through Cygnal’s work, “we can see that non-neural cells and tissues in the disease state are actually coopting the language of the neurons. They are now expressing neural genes and activating neural pathways but they are non-neural in origin themselves.”
There are six components in Cygnal’s effort to decode the role the PNS plays in diseases and how drug hunters can use it to their advantage:
- Culture technologies to test reductionist neurobiology ideas where “we grow disease tissue / cell types in the presence of primary neurons to dissect the signaling”
- Chemical genetics
- Identify causality for a group of 2,000 genetic targets dubbed the “neurome,” via CRISPR-Cas9
- Bioinformatics platform focused on neural signals and neural pathways
- A neuropharmacopia with 1,000 molecules designed to treat CNS disorders
“Right now in this place in time, we’re the only people — the only commercial organization on the planet that can take those six technologies, put them together, throw one question into that platform, get six different answers and then connect the dots between those answers to get novel insights into biology,” Huang said.
That will, in turn, lead to the discovery of new small and large molecules — admittedly traditional modalities that Cygnal believes will do the job. With 41 staffers on hand (and a plan to expand the office to accommodate 80), the goal is to nominate two programs for development this year, most likely for cancer and inflammation. But down the line, Huang can see plugging in any disease from fibrosis and endometriosis to wound healing and obesity into their platform and yielding new drugs.
So why come out of stealth mode now?
“It’s kind of overdue, don’t you think?” Huang said. “It’s just time. We’re ripe.”