Ensysce Biosciences is developing solutions that make opioids safer, and virtually impossible to abuse. BioSpace spoke with CEO Lynn Kirkpatrick about the company’s novel technology.
Against the backdrop of a global opioid crisis, Ensysce Biosciences is developing solutions that make opioids safer, and virtually impossible to abuse.
Rather than reformulate opioids, Ensysce is modifying the chemical structure of the opioid so it only takes effect when swallowed and shuts down when more than a few pills are taken. Its candidate, PF614, is a prodrug of oxycodone and is currently in Phase II clinical trials. Its analgesic profile is equivalent to that of oxycodone except that it has a 12-hour half-life once ingested – longer than other marketed opioids.
“Opioids are wonderful products to eliminate pain, but they also create – in some individuals – a sense of euphoria,” Lynn Kirkpatrick, Ph.D., CEO of Ensysce Biosciences told BioSpace. “Therefore, people take them when they aren’t needed to control pain, which leads to abuse and the current opioid crisis.” To put numbers to that, nearly 50,000 people die of opioid overdoses each year in the United States, and more than 10 million people misuse opioids, according to DrugAbuseStatistics.org.
“When some want to achieve that euphoria faster and for it to be more intense, they start chewing it, snorting it or injecting it,” Kirkpatrick continued. “Our chemistry reduces one’s ability to abuse PF614 by any of those means.”
To that end, Ensysce has two technology platforms.
For the first, “We use the body’s own enzymes to start the activation process,” she said. “Trypsin, which everybody has in their body to digest meat, breaks off part of the PF614 molecule to start activation. The rest of the chemistry releases the opioid over time. In the body, trypsin is only found in the small intestine, so you can’t abuse PF614 by injecting it into your arm or chewing it to activate it any faster, or snorting it. Those methods won’t deliver the effects any faster than swallowing it, so we could possibly deliver PF614 in a glass of water for people who have problems swallowing.” This platform is called TAAP – trypsin abuse protection.
Many people who truly need opioid pain medication currently refuse them because of fears of becoming addicted. Physicians then prescribe non-steroidal anti-inflammatory drugs or other pain products, which are less effective and may come with dangerous toxicities if taken for a period of time. PF614 with TAAP™ offers a safer alternative that is difficult to be abused.
“We also have another layer of safety, MPAR – the multi-pill abuse resistance platform – which nobody else delivering opioids has,” she said. This is a combination product that includes a small amount of a trypsin inhibitor. Therefore, if a patient takes another dose, either by accident or on purpose, there’s more trypsin inhibitor to block activation of the pills, thus preventing overdose and reducing the possibility of respiratory depression (cessation of breathing). This failsafe platform protects forgetful patients and children who get into the medicine cabinet, as well as those who want to abuse the drug.
“The inhibitor starts to work immediately,” Kirkpatrick said. Ensysce is determining the proper dosage now, but if, for example, the prescription called for two pills twice per day, “if you take three or four, it diminishes what you would receive without its protection.” If the patient needs a larger dose, the physician would prescribe a higher-dose product.
PF614’s safety profile is similar to that of traditional opioids and can be abused less easily. This puts it in a prime position, assuming it gains regulatory approval, to be used in cases of severe pain in which people need to take opioids for a period of time, such as for acute pain after surgery or to treat chronic indications such as osteoarthritis lower back pain when non-steroidal anti-inflammatory drugs (NSAIDs) and similar medications aren’t potent enough.
The U.S. Food and Drug Administration has granted Fast Track designation to PF614 because of the large unmet need in combatting the opioid crisis. There are applications beyond the opioid crisis, too. TAAP and MPAR can be applied to approximately half of all prescription drugs, Kirkpatrick hypothesized. Ensysce is exploring their development for therapeutic molecules it is creating to treat ADHD and opioid use disorder.
“We’re moving our first product to commercialization as quickly as we can,” she said. “For opioids, you have to conduct human abuse liability studies (sometimes called liking trials) to determine how well a drug abuser would like your product. We are starting those initial studies in May. We believe our product won’t be liked as much as equivalent doses of conventional opioids, because we know there’s no trypsin in the blood or the nose. This is the only kind of pharmaceutical study where companies hope the study participant hates the drug.”
