If the researchers, executives and investors behind Coda Biotherapeutics have their way, one day soon there really could be a cure for pain.
Co-founded by researchers Joseph Glorioso, from the University of Pittsburgh’s microbiology and molecular genetics department; and Dr. Nicholas Boulis, the founder of Emory’s Gene and Cell Therapy for Neurorestoration Laboratory; Coda uses gene therapies to treat neurological diseases starting with severe pain and epilepsy.
America is a country in pain. There are over 19 million Americans who live with chronic neuropathic pain, according to Coda’s own statistics. And over the past twenty years the doctors treating those Americans and the drug companies developing therapies for them have managed to turn their treatment into a new epidemic — opioid addiction.
In 2017, 47,600 Americans died from opioid-involved overdoses, according to the Centers for Disease Control. Of those deaths, about 60% involved synthetic opioids.
“The incentives were there for people to prescribe more and more, particularly when they had already been convinced it was the right thing to do — the compassionate thing to do,” Keith Humphreys, a psychiatrist at Stanford University and a former White House drug-policy adviser, told the journal Nature.
As the pain epidemic and attendant opioid crisis began to skyrocket several companies have been racing to find alternatives to the drug treatments that were now killing Americans by the thousands. Other approaches like electrical nerve stimulation can carry risks, and invasive surgeries are an unappealing last resort, according to Coda’s chief executive.
Coda’s experimental treatment is based on a science called chemogenetics, which uses a harmless virus to create new receptors in the sensory neurons that provide signals to the brain about physical stimuli. Those receptors can be unlocked by small molecule drugs, which would instruct the sensory neurons to stop firing, thereby cutting off the signals of pain to the brain.
Coda’s virus on a neural cell (Image courtesy of Coda Biotherapeutics)
The idea behind chemogenetics is to engineer a receptor that when you put it in with a… gene therapy… it does nothing. We’ve engineered it so that it is no longer responsive,” says Michael Narachi, the president and chief executive officer at Coda. “Most of these receptors are naturally opened or closed by acetylcholine… We’ve engineered these receptors so that they’re no longer responsive to acetylcholine, but they are responsive to a man-made drug.”
The company then draws from a portfolio of receptor small-molecule drug pairs that were developed and tested for their pharmacological and toxicological effects, but discarded because of a lack of efficacy, to create new therapies with receptors tailored to respond to those drugs.
“What we’ve done is flipped the whole paradigm on its head. We’re making the lock that can work with these keys,” says Narachi.
So far, the company has raised $34 million as investors including Versant Ventures, MPM Capital and Astellas Venture Management have doubled down on their initial $19 million commitment to the new drug developer.
“Since coming out of stealth mode last September, the CODA team has made tremendous progress in developing its gene therapy program that is tunable, durable and highly selective, which allows for better efficacy and safety with fewer off-target effects,” said Tom Woiwode, Ph.D., managing director at Versant Ventures and CODA Chairman, in a statement. “CODA’s platform holds great promise to significantly transform how we treat challenging conditions and disorders for which new therapeutic options are greatly needed.”
Pain isn’t the only condition that Coda hopes to treat. The company is also working on therapies that can reduce the severity of epilepsy for the nearly 3.4 million people in the U.S. who have the condition. While the company can’t treat all kinds of epilepsy, Coda says that it could address focal epilepsy, which represents 60% of all manifestations of the condition, and is linked to a specific region of the brain.
By engineering neurotransmitter receptors that are activated by medicines that can be taken orally, Coda thinks it can control the activity of neurons responsible for both chronic pain and focal epilepsy.
The next step for the company — and part of the use of proceeds from its new $15 million cash infusion — will . be to proceed with early animal trials. These clinical trials will be followed by human trials.
“This is a research platform,” says Narachi. “We have this portfolio of engineered receptors and we’re testing them in cells. The next step is to go into human clinical trials.”
