Psychedelic therapy company Cybin (NEO:CYBN/NYSE American:CYBN) hosted a virtual R&D Day on February 28, 2023. In the event, the company’s leadership team provided an update on its development pipeline of deuterated psychedelic-based therapeutics, including CYB003 and CYB004.
CYB003 is synthetic psilocybin analog, for the potential treatment of major depressive disorder. Cybin provided an interim readout from the ongoing Phase 1/2a study of CYB003.
Additionally, Cybin offered an update from the ongoing Phase 1 exploratory CYB004-E trial evaluating IV N,N-dimethyltryptamine (DMT). The company is also evaluating CYB004, a deuterated form of DMT that has a longer duration of action than traditional DMT that holds potential for generalized anxiety disorder.
Phase 2a study of CYB003
Cybin’s ongoing Phase 1/2a clinical trial of CYB003 demonstrated positive interim findings, including rapid and short-acting psychedelic responses in participants.
To date, CYB003 has met the company’s expectations for providing fast onset of action, short duration of effect, good tolerability and low plasma variability. “It was gratifying that we’re seeing what we expected to see,” said Cybin CEO Doug Drysdale.
The company has tested four different CYB003 doses to date: 1, 2, 8 and 10 mg. Some patients in the latest cohort will receive a 12 mg dose. “We saw psychedelic effects fairly early on,” Drysdale said. The company observed psychedelic effects starting at a dose of 3 mg, and robust psychedelic effects at doses of 8 and 10 mg.
By contrast, researchers at Johns Hopkins University have reported psychedelic effects of 30 mg/70 kg of traditional psilocybin.
CYB003’s optimized lipophilicity appears to assist it in crossing the blood-brain barrier. Still, it’s difficult to draw direct comparisons between Cybin’s deuterated psilocybin analog and traditional psilocybin. “But broadly speaking, it looks like, with 8 mg, we’re getting the same kind of psychedelic effects you might expect for 25 mg of psilocybin,” Drysdale said.
Some of the clinical trial volunteers who received 8 or 10 mg doses of CYB004 reported their experiences were among the most profound experiences of their lives.
Adverse events in the trial to date have been mild, including headache, nausea and transient increased blood pressure. “All of these side effects cleared up within the duration of the treatment session,” Drysdale said.
The company expects top-line data from the Phase 2a portion of the trial in the late third-quarter of 2023.
CYB004, another deuterated psychedelic
The Phase 1 CYB004-E study showed promising results indicating good tolerability of IV DMT, which led to an expansion of the study design to accelerate the first-in-human dosing of CYB004, a deuterated DMT molecule. The company aims to use CYB004 to treat generalized anxiety disorder.
The Phase 1 CYB004-E study focused on dosing dynamics of traditional DMT is designed to provide a bridge to study CYB004, a deuterated version of the compound.
The company acquired Part A of that trial, which dosed 40 healthy volunteers using a slow infusion of DMT at escalating doses. “That’s been useful in identifying the dose and the infusion rate,” Drysdale said.
Based on early data, Cybin decided to increase the rate of infusion in the future. “Part B is using DMT as a bolus plus infusion,” Drysdale said. It will explore a variety of dose levels.
The duration of action of DMT can vary depending on the route of administration and dose, but generally it ranges from 30 minutes to an hour when administered intravenously, and up to 4 to 6 hours when taken orally with an MAOI. However, the deuterated form of DMT being developed by Cybin, CYB004, has a longer half-life and improved bioavailability. Those properties could lead to a longer duration of action compared to traditional DMT.
Plans for CYB004
Ultimately, the company plans on moving away from IV infusions to administer CYB004.
“Psychiatrists are generally not going around putting needles in people or relying on a nurse or technician to operate an infusion pump in their office,” Drysdale said.
“So the beauty of the deuteration as well as extending the half life is that it improves bioavailability and brain penetration,” Drysdale said.
Cybin thus expects that it could offer CYB004 via intramuscular injection or subcutaneous injection.
Cybin is targeting generalized anxiety disorder (gAD) in part because of the unmet need. There is good data indicating that DMT works on depression, which is present in about 60-70% of GAD patients, according to Drysdale.
Potential advantages over traditional therapies
Assuming regulators approve psychedelic treatments in the coming years, demand could be considerable owing to their rapid-acting effects and potential to treat mood disorders. Unlike SSRIs, which can have many side effects, psychedelics can quickly transform a patient from being somnolent and lacking energy to being talkative, expressive and having a light in their eyes, Drysdale said
Burgeoning interest in ketamine as an off-label treatment for mood disorders demonstrate the demand for interventional treatments for mental health disorders, Drysdale said. But the inconvenience, cost and needle fears tied to IV ketamine limit their adoption.
Similarly, promising data from Phase 3 MDMA studies in PTSD help show the potential of psychedelics for mental health disorders. “Our goal from the outset has been to try to optimize the treatment so they can be more patient friendly, and more scalable.”
Filed Under: Psychiatric/psychotropic drugs