With a few tweaks, Synchroneuron believes it’s been able to turn an old, flawed drug for alcoholism into a new one for a completely different disorder. Now the Waltham, MA-based startup has just banked a big round of cash to go prove it in clinical trials.
Synchroneuron is announcing today that it’s raised a $20 million Series B round of equity financing, all from its sole backer, Hong Kong investment firm Morningside Technology Ventures. The cash will help Synchroneuron get to a key point in its development. SNC-102—the souped-up formulation of the alcoholism drug acamprosate calcium the company is developing to treat a debilitating movement disorder called tardive dyskinesia (TD)—is currently in a Phase 2 study.
By the time that study produces results in the first quarter of 2015, Synchroneuron will have a good read on whether or not it has a potential drug—and where it stands compared to San Diego-based Neurocrine Biosciences (NASDAQ: NBIX), which is developing a rival treatment for the disease and is further along in development.
“We think [there’s] going to be good news, but the question is how good,” says scientific founder Barry Fogel, of the mid-stage trial. “We’d be quite surprised if we see no benefit, and we’d be shocked if we saw adverse effects because the safety record for this drug is so impressive.”
The winner gets the first crack at an FDA-approved drug for TD, a debilitating disorder characterized by involuntary, repetitive movements—primarily of the lips, tongue, or jaw— tied to the chronic use of certain antipsychotic drugs that block dopamine. For most people, the disorder is irreversible. Around 300,000 people in the U.S. are affected with severe forms of TD, and they’re typically treated either with preventative measures—like lowering the doses of their antipsychotics—or with other drugs like calcium channel blockers or benzodiazepines that at times have worked to help certain patients.
“Nothing has emerged, though, as a standard of pharmacologic practice,” Fogel says. “[TD] is a disabling, stigmatizing thing.”
Synchroneuron is based on the work of Fogel, a neuropsychiatrist and professor of neurology at Harvard Medical School who began searching for a treatment for TD in the 1990s. Fogel determined that modulating the brain chemical glutamate could relieve the symptoms of TD, so he began using approved drugs that affect glutamate to treat his patients. That led him to acamprosate, a decades-old drug that works by essentially balancing out the glutamate and GABA neurotransmitters in the brain, as a potential treatment. Fogel found that certain patients responded particularly well to acamprosate, but the problem was the drug couldn’t be given chronically because its pharmacokinetic properties were poor—it doesn’t absorb into the blood particularly well. So while acamprosate has been approved for some 25 years to reduce the withdrawal symptoms alcoholics get when they stop drinking, it isn’t widely prescribed for alcoholism because it’s not very effective, according to Fogel; patients have to take a very high dose for it to work well (Fogel says upwards of nine pills per day), and if they take those doses, the drug often irritates the stomach and produces side effects like nausea, vomiting, and diarrhea.
The concept behind Synchroneuron is to essentially fix those flaws by making a version of acamprosate with better pharmacokinetic properties—as in, it can produce a bigger effect at a smaller dose, while limiting the GI side effects. Fogel co-founded the company in February 2012 with the help of drug development consulting firm Accellient Partners, and then raised $6 million in VC backing from Morningside to carry out that plan. Synchroneuron has since done the formulation work to create SNC-102 and test it in an early-stage clinical trial of healthy volunteers.
Chief executive William Kerns says that the company has seen positive signs so far: it’s been able to significantly reduce the daily dose of acamprosate through the formulation work, and is testing a regimen of one or two pills per day.
Ultimately, the company’s big plan is not just to target TD, but potentially other related diseases like Tourette’s syndrome and post-traumatic stress disorder. Synchroneuron will use some of the cash, for instance, to begin an exploratory study in Tourette’s patients later this year, according to Fogel.
All of these disorders “may have an underlying problem with the regulation of glutamate transmission,” he says.
The reality, however, is that Synchroneuron has much to prove in the clinic before it can succeed—like whether its drug, which would be taken chronically either once or twice a day, can really prove much more effective and tolerable than the approved acamprosate formulation. It’s also got some catching up to do, as its competitor Neurocrine has already finished a Phase 2 trial for its own candidate, a new chemical entity called NBI-98854.
For its part, Synchroneuron is pointing to the fact that SNC-102 is based on a well-studied, approved drug. That means safety wouldn’t be a primary study endpoint— the company could theoretically run shorter, smaller Phase 3 studies testing solely for efficacy, rather than waiting longer to guard for safety signals, according to Kerns. That also means Synchroneuron might have an opportunity to catch up to Neurocrine if things break right, since the San Diego company is testing a new chemical compound for TD.
The big test is now underway. Synchroneuron is enrolling 90 patients in a Phase 2 study in 12 sites across the U.S, which should give the company the chance to prove, in a placebo-controlled study, if SNC-102 can reduce the number of abnormal tics patients experience. By that point, it’ll have a better read on whether its formulation work is producing a meaningful clinical effect.
“The challenge is to determine whether our delivery system—our formulation—is delivering enough drug in a once-a-day or twice-a-day form,” Kerns says. “I think that’s an area of risk, and we’ll know soon.”