The past year has seen several new biotech companies announce ambitious goals of tackling neurological disease, a vast, complex, and frustrating region of biomedicine.
The academic side of the field has had a shot in the arm, too, from National Institutes of Health funding, to scientific advances at the Allen Institute for Brain Research (now in its new Seattle headquarters), to the $650 million gift given to the Broad Institute of MIT and Harvard’s Stanley Center for Psychiatric Research a year ago.
One firm that has been percolating under the radar for more than a year, and likely to make its debut in 2016, is BlackThorn Therapeutics. It has quietly been building a business around neuroscience research spun out of the Scripps Research Institute.
Several top executives are in place. According to LinkedIn, the CEO is Alex Tkachenko, who previously worked at Genentech before co-founding the fuel company Siluria Technologies. Other team members include VP of corporate development Scott Forrest, who ran the licensing office at Scripps for three years, and head of R&D Bill Martin, who was a top scientist at Theravance for a decade.
The effort has been underway for some time. On its website, Scripps lists BlackThorn among its 2013 spinouts.
BlackThorn has at least one high profile venture backer in Arch Venture Partners, which has a track record launching ambitious biotech firms with massive rounds of startup funding. Arch was behind Seattle’s Juno Therapeutics (NASDAQ: JUNO), which licensed R&D programs from three nonprofit institutions to jumpstart a sprawling cancer immunotherapy pipeline. Earlier this year, Arch and others committed $217 million to a new neuroscience company, Denali Therapeutics, which is led by Genentech alumni.
Arch’s top life science partner in San Francisco is Kristina Burow, whose bio lists her as a BlackThorn director. On the website of California’s top biotech trade association, BlackThorn’s address and phone number are the same as that of Arch Venture’s San Francisco office.
Many details about the company have yet to emerge. I reached out to BlackThorn officials, and Forrest and Burow declined to comment. It’s not clear how much cash investors have put into BlackThorn, or if new funding is coming soon. The tag line on employees’ LinkedIn profiles and elsewhere says BlackThorn is developing “targeted medicines for neurodevelopmental disorders,” a phrase that generally refers to autism and other disorders that produce “impairments of personal, social, academic, or occupational functioning,” according to the Diagnostic and Statistical Manual of Mental Disorders.
The company is apparently working on preclinical programs. Forrest’s LinkedIn profile says he has “operational oversight of early stage discovery programs.”
While we don’t know which diseases or underlying molecular targets BlackThorn is pursuing, it joins the ranks of new companies buoyed by sophisticated new tools, techniques, and biological insights that have emboldened the drug industry to return to neuroscience, a field it had shied away from for a decade or more.
For example, advances in genetic screening and medical imaging have brought a burst of activity back to the Alzheimer’s disease field. A string of late-stage clinical failures forced researchers to look for ways to test people whose disease might still lie hidden. Only now, with more powerful genetic and imaging tools, are those kinds of tests underway. One of the most ambitious is a Phase 3 test of the monoclonal antibody aducanumab from Biogen (NASDAQ: BIIB).
One startup, Yumanity Therapeutics, is doing experiments in yeast, based on the work of National Medal of Science honoree Susan Lindquist, to find new ways to attack neurological disorders like Parkinson’s. Co-founders Tony Coles and Lindquist talked about their work at an Xconomy forum in May:
Meanwhile, certain neurological diseases, depression in particular, have confounded researchers because patients in clinical trials tend to get better even when they’re taking a placebo. With the so-called placebo effect, higher rates of improvement make it more difficult for researchers to pick up a meaningful signal from the people getting the real treatment.
More than a decade ago, Maurizio Fava and David Schoenfeld of Massachusetts General Hospital in Boston devised a new way to test these patients. With sequential parallel comparison design, or SPCD, patients are split randomly into a treatment arm and a placebo arm of the trial. The placebo patients who don’t show a response are then randomized a second time into either a placebo or treatment arm. It’s a way to “wash out” a lot of placebo responders—the “professional patients” who start feeling better simply by joining a trial.
In an interview earlier this year, Fava told Xconomy there have been about 25 psychiatric trials since 2003 using SPCD, a tiny number compared to more than 300 trials a year in indications where the placebo effect is significant, he says.
One of the most advanced SPCD trials is being run by Alkermes (NASDAQ: ALKS) to test its drug against major depression. The suite of Phase 3 tests, dubbed FORWARD, are slated to finish in early to mid 2016. Alkermes CEO Richard Pops told Xconomy earlier this year that SPCD is one way to blunt the placebo effect, “which has been a longstanding objective.”
“It’s not like you’re cutting corners, or you’re trying to embellish a signal that’s faint, it’s simply a way of minimizing placebo response,” Pops said.
Fava, who is or has been a consultant to Alkermes and a long list of other drug companies, said that better trial design is only part of the solution. Clinical sites, like hospitals, need to do a better job of patient selection—sometimes called quality assurance—instead of sending vans to homeless shelters to pick up people to participate, for example, or conducting interviews that “lead the witness,” Fava said.
Still, the Alkermes trial will be closely watched as part of the new wave of drugs that rely on deeper understanding of patients and biology.
Not all the new efforts focus on pharmaceuticals. As I wrote in March, mental health researchers and providers are moving toward digital therapies, used with or without drugs, to help patients with conditions that range from post-traumatic stress to autism to depression.
In this new rush of neurological intervention, money plays a big part, too. Denali Therapeutics has a ton of it, as well as at least five Genentech alumni in top positions. The South San Francisco, CA-based startup will deploy its initial $217 million commitment from Arch, Flagship Ventures, the State of Alaska Permanent Fund, and Fidelity to do basic research but also license work from the outside.
BlackThorn isn’t likely to pull down the same commitment as its Arch portfolio partner Denali. But one hallmark of the biotech boom is that early stage investors are not often shy about funding high risk startups with high risk capital. And even though neuroscience is somewhat back in fashion, there’s no argument that launching a new firm like BlackThorn is still high risk.
—Deputy Biotechnology Editor Ben Fidler contributed to this report.