Cadent Therapeutics bags $40M for neuro pipeline, Bob Dagher as CMO

Cadent President and CEO Michael Curtis likens allosteric modulators to dimmer switches: they turn up or turn down the current in ion channels to treat movement disorders and cognitive impairment. (Cadent Therapeutics)

Cadent Therapeutics is coming out of stealth with a new chief medical officer and $40 million to move three of its programs into phase 2. The Cambridge, Massachusetts-based biotech is targeting ion channels to develop treatments for movement disorders and cognitive impairment.

Cadent will start testing its lead asset, an allosteric modulator of the SK ion channel, in patients with essential tremor by the end of this year and in spinocerebellar ataxia patients halfway through next year, said CEO Michael Curtis, Ph.D. The SK ion channel plays a key role in maintaining the regularity of the cerebellum, which is essential for the control of movement, he said. In movement disorders, this channel becomes “deranged and irregular.”

“When we think about [allosteric modulators], we equate them to dimmer switches,” Curtis said. Cadent’s lead asset, dubbed CAD-1883, is designed to “turn the lights up,” or increase the current, in the SK ion channel, thereby reducing neuronal irregularity.

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The company is looking to modulate ion channels because agonists and antagonists “just don’t work against these targets,” Curtis said. Such drugs are heavy-handed, he explained; they’re too potent, too active. Because ion channels work in networks, having one open—rather than tweaked with a modulator—would result in a harmful current that would cause adverse events and throw these networks out of whack.

Cadent is targeting a second ion channel, the NMDA (N-methyl-D-aspartate) receptor in psychiatric indications. This channel is underactive in patients with schizophrenia but overactive in those with depression. The company plans to start a phase 2 study of a positive NMDA receptor modulator as a treatment for cognitive impairment in schizophrenia patients by the end of 2019. It is partnering with Novartis on a negative modulator for depression, a treatment that will dial down the current in that ion channel rather than boosting it.

The company was founded at the beginning of 2017 through a merger of Luc Therapeutics, which worked on NMDA receptors, and Ataxion Therapeutics, which focused on the SK channel. Since then, the company has nominated development candidates across its programs, finished up a phase 1 in its lead program and secured the Novartis partnership.

“And that’s all been done with essentially four people, for the most part,” Curtis said.

As it moves toward phase 2, the company hired Bob Dagher, M.D., who brought extensive experience in both psychiatry and movement disorders. Cadent has grown from four to nine employees and could reach 15 by the end of the year, Curtis said. It’s looking to fill out its ranks in clinical operations and regulatory affairs as the new studies get under way and could hit 25 to 30 staffers by the end of 2019.

Cadent drew its financing from Cowen Healthcare Investments, Atlas Venture, Qiming Venture Partners, Access Industries, Clal Biotechnology Industries and Novartis Institutes for Biomedical Research.

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