Cybin Uses Psychedelic Mushroom Derivative To Tackle Depression With Improved Safety
Executive Summary
Emerging Company Profile: Cybin’s novel approach to psilocybin therapeutics aims for better safety, shorter duration and less variability through the process of deuteration.
Fresh from a CAN$32.3m ($25.9m) public offering in July, Cybin Inc. is focused on getting its lead candidate, CYB003, into the clinic for major depressive disorder (MDD) next year. However, the firm had quite a journey in its development of psilocybin drugs, a hotly anticipated class that has piqued investor interest.
Headquartered in Toronto, Canada, Cybin kicked off with a CAN$3.5m seed funding round. It was founded in 2019 by three people who shared personal experiences with friends and family suffering mental health disorders, CEO Doug Drysdale told Scrip. The company has grown to encompass 55 employees across four countries over the past year.
“Rather than simply working with psilocybin, we wanted to create a treatment that has greater opportunity for reimbursement due to reduced timelines and side effects, and therefore provide greater accessibility to patients,” Drysdale said. The company’s previous lead candidates, CYB001 and CYB002, were psilocybin formulations whereas CYB003 is a deuterated psilocybin analog, he explained.
Deuteration is the process of substituting hydrogen atoms on a molecule with a heavy version of the element called deuterium. It is expected to reduce the metabolic variability associated with oral psilocybin candidates, which could lead to more predictable responses and a safer drug profile. Indeed, preclinical data show that CYB003’s plasma variability, time to onset and duration are half that of psilocybin.
The Canadian firm is requesting a pre-IND meeting with the US Food and Drug Administration and scientific advice from the UK Medicines and Healthcare products Regulatory Agency, Drysdale said. It plans to file an IND in the second quarter of 2022 to begin a Phase I dosing trial in MDD by the middle of the year, with a proof-of-concept study expected to follow at the end of 2022, he added. CYB003 is also in preclinical studies for alcohol use disorder.
Finance-wise, the company reported CAN$75.2m in cash and cash equivalents as of 30 September. The cash provides a 24-month runway to support the Phase I study and two other milestones: a feasibility study of Cybin’s novel Kernel Flow neuroimaging device and a Phase II trial of psilocybin for burnout and depression in frontline healthcare workers at the University of Washington, Seattle.
Psilocybin Opportunities Expanding
Criminal prohibitions on psilocybin, which is derived from hallucinogenic liberty cap mushrooms, have hindered its clinical study for the last few decades. Now, “it’s only getting better and easier to study these molecules,” Drysdale said, adding that Cybin has run 74 preclinical studies in the last twelve months alone.
Government action has further mitigated former hurdles. The FDA granted psilocybin breakthrough therapy designation (BTD) for MDD in 2019 based on research from non-profit Usona Institute, just one year after it granted the active ingredient BTD for the narrower indication of treatment-resistant depression based on research from rival firm COMPASS Pathways. (Also see "Keeping Track: Oxbryta Approval Headlines Pre-Thanksgiving Week Of News " - Pink Sheet, 1 Dec, 2019.)
Sure enough, Compass’s Phase IIb study of its sole asset COMP360 in TRD met its primary endpoint of difference in MADRS score, although some adverse events raised concerns. (Also see "COMPASS Psilocybin Depression Data Excite Despite Safety Issues" - Scrip, 10 Nov, 2021.) By contrast, Cybin hopes the deuterated approach will curb similar safety worries for CYB003. The expected shorter duration of CYB003 could also remove the need for a six-to-eight hour session supervised by two trained therapists, which was the prescribed regimen in the COMP360 trial.
Drysdale said Compass’ efficacy data were “great” but suggested that clinicians could struggle with the idea of an eight hour treatment day. “If they can see three or four patients a day, that makes the system less expensive and more scalable for everyone,” he added.
EU Partnerships On The Cards
Looking to the future, Drysdale said that Cybin was focused on North American and European territories, but may take a different approach to each.
The relative homogeneity of the US and Canadian markets mean the firm could well commercialize independently there.
However, the diversity and complexity of European markets could necessitate late-stage development or commercialization partnerships in this region, Drysdale explained. The ideal partner would have a deep experience of CNS psychiatry and good commercial infrastructure and reach in all the major European markets, he added.