Flagship unveils Cygnal, a nervy take on cancer, inflammation

Flagship’s Cygnal is deploying $65M to drug neurological drivers of cancer, inflammation

Cygnal Therapeutics Inc. believes overlooked corners of neurobiology could unlock therapeutic strategies in cancer, inflammation and beyond. With $65 million from Flagship Pioneering and other undisclosed investors, the company launched Tuesday to advance two candidates discovered via its “exoneural biology” platform.

The company’s founding thesis is that the nervous system, particularly the peripheral nervous system (PNS), contributes to the pathology of a much wider range of diseases than those traditionally thought to be neurological.

CEO Pearl Huang told BioCentury Cygnal defines exoneural biology in two ways: how the PNS affects non-neural diseased tissues, and how those tissues in turn co-opt neural pathways. At the forefront are programs targeting interactions between cancer cells and nerve cells in the tumor microenvironment, tumor expression of neural regulators, and nerve cell modulation of immune function.

Huang is the former SVP and global head of therapeutic modalities at Roche (SIX:ROG; OTCQX:RHHBY), and prior to that she was VP and global head of discovery academic partnerships at GlaxoSmithKline plc (LSE:GSK; NYSE:GSK). She also co-founded BeiGene Ltd. (NASDAQ:BGNE; HKEX:6160), where she served as CSO.

To uncover targets, the company has developed a six-part discovery engine dubbed the Exoneural Medicines Platform, which has yielded over 40 patent applications.

The platform’s neurobiology-specific tools include imaging methods to map PNS architecture in patient biopsies, co-cultures to identify molecular interactions between primary neurons and cells from diseased tissues, and a pharmacologically controlled gene delivery system to study the in vivo consequences of turning on specific genes in mouse neurons.

The other components of Cygnal’s platform are standard biological tools with a neurobiology lens.

The company conducts bioinformatic analyses and CRISPR screens for a defined set of genes expressed in nerve cells. “Rather than probe the entire genome, we’re focused on these 2,000 genes,” Huang said.

Cygnal has tested the effect of individually knocking out each of those genes in tumor cell lines that are then transplanted into mouse models. “There are multiple tumor types that have taken on expression of neural pathways that are essential for tumorigenesis,” said Huang.

The company also uses a library of more than 1,000 compounds “known to have activity against our neurome targets” to dissect the targets’ roles in disease and serve as starting points for therapeutics, she said.

Although Cygnal has not disclosed the molecular targets or indications of its programs, it has said that it is focusing on four target classes: those that regulate axon growth, synapse formation, neurotransmission or membrane potential. The company has developed assays to track how cancer cells promote axon sprouting or use neurites to metastasize, and how neurons drive cancer proliferation or modulate immune function.

Beyond its first programs in cancer and inflammation, Cygnal sees opportunities for its targets in metabolic syndromes, endometriosis, fibrosis and wound healing.

Huang said the company has experts in both small molecule and biologics development, and believes those two modalities are enough to take on its targets. She declined to disclose a timeline to clinic, how much runway the company’s funding will provide, or whether the funding came from a single or multiple venture rounds.

Other companies targeting the PNS’s role in broad sets of diseases are developing bioelectric stimulation therapies, including implantable devices.

A major player in this space is GSK, which launched its own bioelectronics R&D unit in 2012 and co-founded Galvani Bioelectronics Ltd. with Verily Life Sciences LLC in 2016 (see “Galvanizing Bioelectronics”).

The pharma has also invested in seven bioelectronics companies via its $50 million Action Potential Venture Capital fund. Among these is SetPoint Medical Inc., which is developing an implantable vagus nerve stimulation device to treat inflammatory diseases and has presented clinical proof-of-concept data in rheumatoid arthritis and Crohn’s disease.

Cygnal thinks its programs will be complementary to bioelectronic devices. “We are looking at similar but not identical biology,” Huang said.

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