Cybin on Converting Psychedelic Molecules


Cybin is conducting clinical trials with a number of tryptamines to treat a plethora of disorders. Today it was awarded a patent for its proprietary DMT analogue CYB004, which it hopes will treat anxiety disorders. PSYCH sat down with Cybin’s CEO Doug Drysdale to discuss the organisation’s drug development pipeline and plans for 2022.

‘We are currently looking at 50 or 60 molecules, from which we are selecting the ones we believe have the greatest potential,’ said Drysdale. ‘We want to be able to offer healthcare providers a range of different psychedelic medicines.

‘There is a lot of overlap and comorbidities in mental health; patients with anxiety often develop depression and those with depression often turn to substance misuse for support. There aren’t hard lines between these conditions and sometimes they coexist. By providing a range of options for providers, it gives them the opportunity to match the best treatment to each particular patient.’

Cybin recently released data from studies with CYB003, its proprietary psilocybin derivative, which demonstrated a reduced onset time and 50% reduction in variability compared with psilocybin. PSYCH asked Drysdale to expand on the importance of the results.

‘Accessibility is really the core of everything we’re trying to do. Part of the challenge in converting these classical psychedelic molecules into prescribable therapeutics is to overcome some of those limitations that impact accessibility. 

‘The first of those is duration and psilocybin is very long-acting. Patients can be in the clinical setting for a whole day, eight hours or so. When we speak to our partners who run depression clinics and addiction clinics, they really struggle with that, as many only have a handful of treatment rooms. 

‘To take up a whole room for a whole day with a single patient is inefficient and probably not practical. This resource requirement limits accessibility for patients, so we’ve managed to increase the speed of onset by two times and cut duration in half.

‘This means a patient will spend less than half of the time in the clinic than they would with traditional psilocybin. This frees up the resources and makes the treatments more accessible.

‘On the variability front, it’s been well understood for a long time that outcomes with psilocybin, or the responses of patients, are quite unpredictable. That is because psilocybin is a pro-drug and not active in itself; it is converted to psilocin in the body which is active, and that conversion or metabolism varies from one individual to another. 

‘This means one patient might have quite a mild response to a dose that has a very profound response in another. This unpredictability is exactly what the FDA and healthcare providers do not want, particularly with psychiatric patients. 

‘Overall, CYB003 is about half as variable as traditional psilocybin. In fact, at peak plasma levels it is about 80% less variable, and we hope that that will lead to far more predictable responses for patients.’

PSYCH asked Drysdale why the company was focused on reducing the duration of experiences with psilocybin, when other tryptamines such as DMT are faster acting.

‘It is largely because the greatest body of evidence is around psilocybin, so it’s a great place to start. With metabolic stabilisations we are able to remove variability, but, you’re right, there are faster-acting tryptamines. DMT has a very short plasma spike, a bit like a 10-minute rocket ride and that can be unpleasant. It can create anxiety in patients and is also just not therapeutically particularly useful.

‘With deuteration we can slow the breakdown of DMT in the body, reducing the spike and keeping the patient in the therapeutic window for a more optimal period. It can also generate a smoother, more pleasant experience and help with brain penetration. With DMT analogues, Cybin can deliver tryptamines into the brain more efficiently and maybe get the same effects as slightly lower doses. We think CYB003 might be twice as effective as traditional DMT.’

Cybin is using Kernel’s quantitative neuroimaging technology, Kernel Flow, to measure ketamine’s effect on cerebral cortex activity. PSYCH asked if this will be implemented into its studies going forward.

‘Kernel Flow technology works really well in parallel with what we’re doing with CYB003 and CYB004 at the moment. This first study will help us understand what kind of data we can generate during a psychedelic experience. We might be able to see certain areas of the brain light to detect areas of neuroplasticity and see how long that lasts. 

‘What will be most valuable is the quantity of data, as this is a wearable device rather than a big MRI machine. We should be able to collect much more data, and larger data sets are useful in helping us potentially find more targeted treatments in the future.’ 

The company has a meeting with the MHRA to discuss hosting its study into Major Depressive Disorder in the UK. PSYCH probed Drysdale for further information and Cybin’s hoped-for outcome.

‘It’s taking place later this month and the team has done an awful lot of preparation to make sure we have a solid briefing for the MHRA. We are hoping to get valuable feedback on our study design and development programme to ensure we are on the right track. Following the study, we hope to file a clinical trial application in the UK and an IND with the FDA, to start around mid-year.

‘The first study will hopefully demonstrate CYB003 is safe and effective. Then we’ll move to a larger study to test in broader, more diverse populations, but, as we move forward, we will learn about duration of effect, onset of action, level of variability and required integration session.

‘There is room to continue to improve and optimise the treatment as we get closer to market, to minimise the burden on the healthcare system, and make these treatments as accessible as possible.’

Investors have been watching the sector closely, but the stock market has not performed as many had hoped. PSYCH asked Drysdale for his perspective on the fall of share prices across the board.

‘When I look at what is happening across the biotech space, it is all macro driven. There seems to be a lot of economic uncertainty between COVID-19, interest rates and inflation. There is now political uncertainty in Ukraine and the biotech index is down 30% since early November when COMPASS’s topline study data was released.

‘The Psychedelic ETF is down 47% since then, whereas the S&P is only down 6.5%. This says to me that in these uncertain times people cycle out of more speculative stocks, like psychedelics, but this creates an opportunity. Fundamentally, nothing has changed about the sector or about Cybin.

‘We continue to make great progress and are one of the few companies that is still above its public price, but we have seen a few of our peers really take a beating.’

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