Tal Medical Gets NIMH Backing for Fast-Acting Depression Therapy

1/10/14Follow @benthefidler

If you’re suffering from depression, then going to a doctor’s office, sticking your head into a magnetic coil and getting your brain electronically stimulated might not seem all that appetizing. But what if the antidepressants you’ve been prescribed haven’t helped—and that new procedure, in a half hour or less, just might?

That’s the kind of thing Tal Medical, a company being incubated by PureTech Ventures, is trying to prove. Today, Boston-based Tal is announcing that the National Institute of Mental Health will fund a 90-patient proof-of-concept trial for its anti-depression device, which uses a low-strength magnetic field to try to essentially reset the circuitry of the brain and quickly alleviate the symptoms of depression.

Tal’s device, which is unnamed as of yet, was the first technology or experimental drug selected over an unspecified group of competitors under the NIMH’s Rapid-Acting Treatments for Treatment Resistant Depression (or RAPID) program—an initiative set up by the agency to bankroll initial trials for depression treatments that act quickly, within 72 hours.

That means Tal—a small company housed within the Boston offices of PureTech and still without a full-time CEO—now has the juice to run a sizeable study without bringing in an institutional investor and diluting ownership stakes. Between seed funding Tal has raised from PureTech and unnamed private angel investors, and the outside dollars going towards the NIMH trial—as well as a small, separate biomarker study—the company has gotten access to about $6 million in funding, according to chief operating officer and PureTech principal Andrew Miller.

“It’s allowed us to push the technology towards what could be a very key value inflection point for the company,” he says.

Miller points out, however, that while the NIMH will fund the study, it’s not a direct grant to Tal—it’s essentially a contract between the agency and Massachusetts General Hospital, one of the six sites the proof-of-concept trial is taking place in. Maurizio Fava, the director of the depression clinical and research program at MGH, is the study’s principal investigator.

Miller wouldn’t say how many others were vying for the NIMH’s support, only saying a “number” of other competitors were considered and it “wasn’t one or two.” And other similar studies will likely follow under the RAPID program. But Tal’s device was the first to win such backing, and because of it, the startup has already begun enrolling patients in its study.

Tal is recruiting patients with major depressive disorder who haven’t responded to one to three antidepressant courses. They’ll be broken into two groups and treated either with Tal’s device, or a sham therapy, in a 20-minute session up to four times over the course of four days. Investigators will follow up with these patients for 28 days, and judge the device’s effectiveness and durability based on how these patients score—both before and after treatment—on the Hamilton Depression Rating Scale, a standard diagnostic test administered by mental health specialists. Tal wants to see a clinically meaningful separation between the two groups, according to Miller. The company said it expects to wrap up the trial later this year.

For those unfamiliar with the Tal story, PureTech formed the company in 2011 based on work at McLean Hospital in Belmont, MA. Researchers at McLean had seen in a prior study that the moods of patients with bipolar disorder improved after their brains were imaged in an MRI machine. So a team of McLean researchers tried to figure out what caused that effect, and determined it was the brain’s short-term exposure to low-field magnetic stimulation (LFMS). They went on to publish a few studies on animals and some patients with bipolar and major depressive disorder, and the results were encouraging enough to catch PureTech’s attention.

PureTech consulted with former Eli Lilly executive and Weill Cornell Medical College professor Steven Paul, and then decided to license the technology and turn it into a depression treatment. Paul became chairman and co-founder of Tal, and over the past two years, the company has been working behind the scenes completing a prototype of the product and pushing its clinical development.

What they’ve come up with is a cylindrical magnetic coil that’s about 15 inches in diameter. It’s placed on a patient’s head, above the eyes. The coil produces a specific, time-varying magnetic field that in turn, induces a time-varying electric field in the brain. Miller says the patient doesn’t feel any sensation associated with treatment—the only indication the device is running is a beep, or tone. That’s important, because it means patients won’t be able to tell the difference between Tal’s device and a sham treatment in a blinded trial, Miller says.

If this type of device sounds familiar, that’s because Tal isn’t the first to try this sort of approach. Depression patients who don’t respond to drugs already have the option to undergo another brain stimulation technique, called, repetitive transcranial magnetic stimulation (rTMS), which is delivered via devices marketed by Neuronetics and Brainsway. Both of those, similarly, involve a magnetic coil and a therapy session conducted in a clinician’s office. Then, of course, there’s electroconvulsive therapy (ECT), which is much more invasive and essentially induces a seizure in a patient under anesthesia.

Tal, however, is trying to show that its method is both safe and works much faster than these other options. Miller says rTMS takes several weeks of five treatments per week to achieve a clinical benefit, while ECT typically requires two or more weeks of two to three treatment sessions.

The very early data Tal is encouraged by have shown a treatment effect, by comparison, within 20 to 30 minutes, he says. Tal also hasn’t seen any side effects that it can directly attribute to the device as of yet, and there haven’t been any seizures reported—always a risk when trying to electrically stimulate the brain.

Those data came from three small studies researchers at McLean and the NIH had already either finished, or were underway, before Tal licensed the technology. Miller says two of those were “pilot-style efficacy studies” done at the hospital, while the other was a PET imaging study done by a researcher at the NIH that looked at the technology’s impact on the glucose metabolism of healthy volunteers—a trial done to try to begin to understand the physiological impact of magnetic stimulation.

That data, according to Miller, indicated that Tal’s technology might work, on a physiological level, in a completely different way than rTMS and ECT. While Tal’s device hyperpolarizes neurons, for instance, the other methods depolarize them. Though its unclear at this point whether Tal’s technology is better or worse for patients than rTMS or ECT, Miller nonetheless says that the differentiation is significant.

“It implies that the physiological impact of [low-field magnetic stimulation] is different, and thus provides a rationale as to why the efficacy and safety profile may also be different from [those other methods],” he says.

Of course this is something that Tal has a long way to go to prove. Neuronetics’ device has been FDA approved since 2008, and regulators cleared Brainsway’s a year ago. Tal, meanwhile, is running its proof-of-concept trial, as well as a second small, single-site biomarker study. The results of the former, however, will be critical. If Tal sees positive signs that it’s got a truly differentiated therapy, it’ll likely move from there to a larger, randomized trial—the kind that Neuronetics and Brainsway ran before getting the nod from regulators.

“Both [of their] regulatory paths provide us with what we believe will be a good benchmark for what would be our own regulatory path,” Miller says.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com Follow @benthefidler

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