It’s a familiar story—you need a cavity filled, so the dentist gives you a local anesthetic before she starts drilling. Hours later, you’re biting into your cheek or drooling on yourself because your mouth is still numb. But that’s just part of the deal, right?
What if there were an anesthetic that relieved pain without causing numbness or paralysis? A drug that specifically targeted neurons involved in signaling pain, but left other neurons—the ones that respond to touch or the ones responsible for movement—alone?
Enter Nocion Therapeutics, a biotech developing drugs that silence nociceptors, the neurons that send pain or itch signals when they are inflamed. The Cambridge, Massachusetts-based biotech is starting out with $27 million in series A funding from F-Prime Capital Partners, Canaan, Partners Innovation Fund and Bio-Innovation Capital. The capital will bankroll the company from discovery through proof of concept.
Its platform and pipeline are based on the work of Bruce Bean, Ph.D., and Dr. Clifford Woolf of Harvard University and Boston Children’s Hospital. Bean and Woolf discovered that drugs could be modified to selectively target inflamed nociceptors by giving them a positive charge. This is possible because nociceptors have specific ion channels that open up only when they are inflamed—that is, only when an “external insult” is causing them to send a pain signal.
Instead of trying to create drugs that are very selective for a certain receptor, Bean and Woolf took advantage of something neurons already do.
“We can use the large-pore channels opened by painful stimuli or inflammatory mediators as Trojan horses to deliver drug molecules into the cells and stop their electrical activity,” Bean said in a statement. “The large-pore channels instigate the firing of the cells, but they can also be used to quench it.”
Nocion’s first target is chronic cough and postviral cough, or cough that lingers after a viral infection. After all, cough is nothing but an itch of the airways, Nocion CEO Richard Batycky told FierceBiotech.
"There isn’t an underlying insult to be treated in patients with these types of cough,” he said. “There’s really nothing for them. ... And another tidbit is that the No. 1 prescribed medicine for cough is opiates. They are known to get rid of cough as well, [but] we want to treat it locally with something that’s not addictive.”
A local anesthetic such as lidocaine can also be used to treat cough, but it can have undesirable side effects like suppressing the gag reflex. And that’s not all—despite having the word “local” in their name, high doses of these short-acting anesthetics can permeate to other parts of the body such as the heart, and cause problems there.
In addition to specifically targeting nociceptors, Nocion’s charged molecules are designed to act locally and have a longer half-life. They stay put to the extent that they must be administered locally: “If you ingest a charged molecule, you get pretty much nothing in the blood,” Batycky said.
If Nocion can prove its approach works in cough, it will have its pick of other potential applications. A big one is postsurgical pain.
“Physicians may leave some local anesthetic in the wound, but it only lasts 30 minutes or an hour,” Batycky said. “If we can get [a local anesthetic] to last two to three days, we might actually skip the place where opiates get prescribed.”
Beyond that, the platform could be used to develop topical treatments for skin diseases or drugs for eye pain, “where you’d want a molecule that stays local and doesn’t hit off target—you wouldn’t want to numb the blink reflex while treating pain,” Batycky said.
Nocion launched with a team of five and operates on a mixed model, outsourcing some work and doing the rest in-house. It’s cough program is underway, but the company is still figuring out how it wants to grow and use its platform for the myriad diseases it could be useful in. It could expand into new indications via partnerships, strategic investments or further fundraising, Batycky said, but Nocion hasn’t decided which route it wants to take.