A small Cambridge, Massachusetts-based company is hoping its bet on CNS drugs using a well established pharmaceutical approach — allosteric modulators — will cement its place as a biotech powerhouse in the years to come. Cadent Therapeutics — currently a 9-person team — has already found a partner in Novartis $NVS.
The company is working on treatments for movement and cognitive disorders using allosteric modulators, from which some of the biggest neuroscience products, such as Xanax and Ambien, have been developed. On Thursday, Cadent said it had emerged “out of stealth mode” by announcing a $40 million Series B round of funding, led by Cowen Healthcare Investments and Atlas Venture. Investors such as Qiming Venture Partners and Novartis Institutes for Biomedical Research also participated in the round, which will be used to shepherd two of the company’s experimental drugs into three Phase II trials.
Cadent is using allosteric modulators – which function somewhat like dimmer switches – to target ion channels that are essential to neuronal activity. The biotech’s movement disorders program is focused on the SK channel – which regulates the amount of potassium that enters a cell – for the treatment of essential tremor (ET) and spinocerebellar ataxia (SCA). Meanwhile, Cadent’s second program is centered on cognitive disorders. It employs the use of allosteric modulators to regulate the the NMDA receptor, which has been shown to play a critical role in cognition and depression.
“We have both flavors of the NMDA receptor, we can turn it up in the case of cognitive impairment, and we can turn it down, in the case of depression,” chief Michael Curtis told Endpoints News.
Cadent’s depression program is partnered with Novartis $NVS, so the Swiss drugmaker is tasked with competing with Sage $SAGE, Allergan $AGN, Johnson & Johnson $JNJ and others in the depression space, he added. Without delving into specifics, Curtis said the Novartis deal generates non-dilutive funding for Cadent.
In the case of positive allosteric modulators for the NMDA receptor, Cadent is targeting cognitive impairment associated with schizophrenia. What sets the company apart, according to Curtis, is the use of an EEG (electroencephalogram) — that measures brain electrical activity — as a biomarker. An EEG deficit is believed to be directly related to NMDA receptor hypo-activity, but using this measure as a biomarker was previously not a practical proposition because scientists required the use of a specialized facility to conduct the test in a clinical trial setting. Cadent has solved this problem by partnering with a company called Cognision that has developed a portable EEG system, Curtis said.
“The theory is that if we can turn up the NMDA receptor using allosteric modulators — we can restore the EEG signature, which is considered to be a precursor in improving cognition. That gives us a rapid way in a Phase II to look at target engagement in the patient population that we’re going after before we ever have to ask the cognition question.”
“We have several shots on goal in indications that don’t require huge capital investments – we’re talking about a 2-week phase II in ET, a 12-week phase II in SCA. Maybe a hundred patients tops in these trials, so for relatively small capital we can get the value inflective points,” Curtis said.
Depending on the results of these mid-stage studies, which the company expects to readout over the next 12-18 months, Cadent is open to all possibilities, such as further capital raises, an IPO, a partnership and a takeover, he added.
Cadent also announced it had hired industry veteran Bob Dhager, who has worked with Covance, Sanofi $SNY and GlaxoSmithKline $GSK, as their chief medical officer and that Cowen’s Tim Anderson, among others, had joined the company’s board.
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