It’s notoriously difficult to develop drugs for pain, in part because the results from animal tests rarely hold up in human studies. Still, a new startup from Atlas Venture called Quartet Medicine will to try to navigate the minefield, buoyed by new insights it believes can help connect the dots between animals and humans.
Cambridge, MA-based Quartet has closed a $17 million Series A round from Atlas, the venture arms of two Big Pharmas (Pfizer and Novartis), and Partners Innovation Fund. Quartet, which is developing small molecule drugs for chronic pain conditions, expects the cash will propel it to identify its first lead program by mid-2015, with a first clinical trial in 2017, according to CEO and Atlas venture partner Kevin Pojasek.
Novartis’s Henry Skinner has joined Quartet’s board as part of the funding. Atlas partner Bruce Booth is Quartet’s chairman. Aside from Pojasek, the company has two other employees at this point: head of biology Annika Malmberg (formerly of Amgen) and head of chemistry Mark Tebbe (previously the head of chemistry at Forma Therapeutics).
Quartet’s plan is no small feat. It’s attempting to prove the clinical relevance of new scientific insights into a well-known biological pathway—tetrahydrobioprotein (BH4)—that’s implicated in the onset of nerve pain.
It also faces competition from several companies, including GlaxoSmithKline spinout Convergence Pharmaceuticals and Spinifex Pharmaceuticals, that are trying to develop treatments for various forms of chronic pain.
What’s more, clinical trials for pain drugs are hard to properly design, enroll, and distinguish the signal from the noise—particularly early on, before the trials get larger and the costs get ratcheted up.
“Quite frankly, chronic pain is tough,” Pojasek says. “And the reason it’s tough is the animal models aren’t predictive, and the clinical endpoints in people are subjective.”
Despite the obstacles, companies have tried again and again to treat pain because of the huge financial upside if they succeed. Pregabalin (Lyrica), Pfizer’s drug for neuropathic pain, generated close to $4.6 billion in 2013. But it doesn’t work for everyone, and has its share of side effects, like dizziness and weight gain. Opioids can be effective, but carry significant addiction risks.
There’s clearly room for improvement, and Pojasek believes that even if his competitors are successful, there’ll be plenty of room in the market for a number of drugs, perhaps working in tandem with one another.
“It’ll really be more of a poly-pharmacy type approach that’s likely to lead to better pain relief,” Pojasek says.
Quartet was founded in late 2013 based on the insights of Clifford Woolf of Harvard Medical School and Boston Children’s Hospital and Kai Johnsson of the Ecole Polytechnique Federale de Lausanne, in Switzerland. The duo have studied the connection between BH4 levels and chronic pain. BH4 is a co-factor—a chemical that enzymes rely on to kickstart chemical reactions. Pojasek says a variety of enzymes use BH4 in pain signaling, and Quartet believes it can ameliorate pain by lowering BH4 levels when they’re too high.
The firm aims to use small molecule drugs to block one of two enzymes in the BH4 pathway: GTP cyclohydrolase 1 or sepiapterin reductase.
“It’s kind of like you’re restoring homeostasis to a system that’s been upregulated, [but] without turning it off—that’s the key,” Pojasek says. “We’ve been able to show [in preclinical studies] that with these two targets that we’re interested in, we can selectively go in and turn [BH4] back down to a normal level.”
That selectivity is critical, because BH4 is involved in a lot of different processes. Throwing normal BH4 levels out of whack might lead to some safety issues. What the company hopes to show is that bringing BH4 back into equilibrium can lead to greater efficacy in more people than the current pain drugs can, Pojasek says.
Now that the firm has figured out how to measure BH4, it may be able to use those levels as a biomarker to see if the drug is hitting its target, and in turn whether that activity actually reduces people’s pain.
Turning BH4 into a biomarker will also help Quartet determine which patient populations—those with, say, diabetic neuropathy or postherpetic neuralgia—might respond better than others, and that will let the company plan a clinical strategy accordingly.
“I’m confident that if we deliver on the promise on the Series A and our research plan, that we will have that optionality to consider a deal, or to raise additional capital,” Pojasek says.
