Expert Interview: George Goldsmith

George Goldsmith is a co-founder and director of COMPASS Pathways, a non-profit medical research organisation dedicated to accelerating access to evidence-led innovation in mental health and well-being. A serial entrepreneur, he has developed pioneering businesses in collaboration software and professional services. He has served as the Managing Director of the Lotus Institute and as CEO of TomorrowLab at McKinsey & Company.


Tell me about yourself, about COMPASS Pathways and how the idea for the company came about?

I’m a serial entrepreneur, particularly in healthcare, and Ekaterina, my wife and co-founder, is a medical doctor. A few years ago, we experienced first-hand the frustration of trying to find help for a loved one suffering with mental health challenges. We tried so many things – and nothing worked. We met many other families in the same position and realised that mental healthcare is not good enough for so many people; we need a new approach – and a transformation in patient experience. COMPASS is a mental healthcare company. Our mission is to accelerate patient access to evidence-based innovation in mental health.

Why psychedelics and why psilocybin in particular?

There has been lots of innovation in psychedelics over the past couple of decades, with early signals from a number of academic studies showing that psychedelic substances, coupled with psychological support, could have an impact on mental health conditions such as anxiety and depression. Depression affects more than 300 million people around the world and a third of these are ‘treatment-resistant’ and don’t respond to existing traditional medicines. Our first programme is psilocybin therapy for treatment-resistant depression (TRD), which is a huge unmet need.  Psilocybin has shown signs that it can have a rapid-acting, sustained positive impact after a single session. It also fits into a clinical setting more easily and carries less ‘baggage’ than other psychedelics.

Tell me briefly about your journey to FDA Breakthrough Therapy status and about the clinical trials involved.

The FDA gave us Breakthrough Therapy Designation in October 2018 for our programme in psilocybin therapy for TRD; this is recognition of the huge unmet need and the potential of psilocybin therapy. Our submission was based on preliminary clinical evidence generated by institutions, including Imperial College London, showing that psilocybin therapy may demonstrate substantial improvement over available therapy.

Numbers of patients involved in each phase? Outcomes? Any adverse side effects?

We are currently running a phase IIb, dose-ranging clinical study, recruiting 216 patients in Europe and North America. The study is expected to finish recruitment later this year, with a report out in 2021. We completed a phase I study in 89 healthy volunteers in 2019, which showed our synthesised psilocybin formulation (COMP360) was well tolerated, with no serious adverse events and no negative effects on cognitive and emotional functioning. The study also demonstrated the feasibility of administering COMP360 in a controlled setting to healthy participants with 1:1 therapist support, with up to six sessions running simultaneously.

When do you hope your psychedelic therapy will become commercially available?

Depending on the clinical trials (phase II and phase III), this psilocybin therapy could be available within five years.

Do you expect psychedelic therapy will displace other conventional medications for depression?

We are developing psilocybin therapy for TRD patients who are not helped by existing medications, e.g. SSRIs. About 100 million people suffer with TRD.

Are there challenges inherent in synthesising psilocybin to produce consistent and uniform effects?

We have developed a method for synthesising our psilocybin at scale to GMP (Good Manufacturing Practice) standard, demonstrating the highest quality and consistency. We also work to GCP (Good Clinical Practice).

When we are talking about public health, and making this available to large numbers of people, we have to do things properly. Psilocybin therapy combines a dose of the psilocybin substance with psychological support – the psilocybin on its own does not produce the result, the therapy is equally important. This is very different from taking a medicine at home; the results of psychedelic therapy are dependent on the whole protocol – which includes preparation sessions with a therapist; the dosing session with the right ‘set and setting’ and therapist support throughout; and integration sessions afterwards.

Is COMPASS Pathways in a position to begin production immediately once FDA approval has been secured? 

Yes

Do you have distribution networks in both Europe and North America? What are the challenges associated with each market?

For our clinical trial, we have a secure global supply chain in place to ensure our psilocybin is available at our trial sites. This requires a huge logistical and operational effort. We are also always working on continuous iteration and improvement of our manufacturing – a process that is as rigorous as the clinical trial itself. We look at how we can keep improving the quality and supply of our medicine, and how we can create greater efficiencies. Generating evidence for the use of the medicine runs in tandem with development of the drug supply.

If psilocybin therapy is approved, we need to ensure that patients have access to it. The unmet need is huge across both Europe and North America, although the access systems are different. We are already talking to regulators and payers to understand the best way to get this therapy (if approved) reimbursed and integrated into health systems – in a way that makes it accessible to all patients who might benefit, regardless of their ability to pay. Our medicine is a tool within a therapeutic process and patient safety is at the centre of this. Psilocybin should never be separated from the care model within which it is administered – similar to chemotherapy.

What do you anticipate will be the duration of usage per ‘average’ patient and how might this differ between users and conditions?

We are doing the science and running the clinical trial to generate data and get more information on these issues. The goal will be to get patients into remission and to keep them there.

Do you see the integration of a psychedelic experience having any role in psychedelic therapies for patients? Why is/isn’t this important?

This is critically important, as mentioned above. Patients have described psilocybin therapy as one of the top five most meaningful experiences of their lives. It can be an empowering experience, one that allows them to change their relationship with their symptoms and make long-lasting changes to their lives.

How will the medication be consumed?

We use capsules.

In what dosages will the psychedelic therapy be available? Will a patient be ‘micro-dosing’ psilocybin?

Our current phase IIb trial is a dose-finding study involving three doses: 1mg, 10mg and 25mg. There is no ‘micro-dosing’ involved. There is no evidence at present to support the theory that there are any benefits to microdosing, and no evidence on its safety either. Macro-dosing psilocybin (full dose once or twice) has been shown in the available evidence to date to be safe, but chronic (repeated) microdosing over an extended period of time could cause issues. We just don’t know enough. Equally important is that focusing on taking a pill daily encourages a person to feel dependent. We want to change the narrative. We want to change the thought process by focusing on patient empowerment, not psychological dependence.

What will the cost be per treatment?

It’s too early to say. We are running the trial to generate data to see whether this works, and for whom, and in what dose. In the meantime, we are working with payers and regulators to look at how we would make this accessible to all patients who might benefit from it. We are committed to fair pricing, and to getting the right medicine to the right patient at the right time, at a cost society can afford. Our goal is patient access and that’s what we will be working to achieve.

You are working with psilocybin but do you have any plans to explore other psychedelic substances for the treatment of TRD or other conditions?

We are a mental healthcare company, not a psychedelic one. We want to transform the patient experience in mental healthcare and ensure more people are helped. Our vision is a world of mental well-being. We are developing an R&D programme to look at other indications for psilocybin therapy, as well as other substances (some psychedelic, some not) for a number of mental health conditions.

Are there any countries you will be watching with interest over the next number of years in the emerging psychedelic therapy field?

There is lots of interesting work going on all over the world! We work in collaboration with a number of academic centres on investigator-initiated studies (IISs), looking at many different indications. We are interested in projects that might develop into treatments that could positively impact patient outcomes.

What will the psychedelic therapies’ space look like for patients in five to ten years’ time?

We are aiming for a better system of mental healthcare – with patients having access to treatments that work, and innovation that has been tested and approved medically, and made available through health systems. We want these therapies, if shown to be safe and effective, to be a part of the toolkit that doctors can offer to patients.

Are ketamine infusion therapy clinics a potential model for the future for psilocybin treatment?

Therapy clinics are a potential model; we are working on the best way to make psilocybin therapy, if approved, affordable and accessible to all patients who might be helped. This means it will have to become integrated into health systems and a part of prescribing guidelines, not a treatment only available to those who can afford to pay for it. Ketamine is used ‘off label’ in clinics, which means it hasn’t had the same rigour in testing or research. At COMPASS, we believe we have a responsibility to do the trial and clinical work before we take this to the broader population. Esketamine followed a similar path, with clinical trials by Johnson & Johnson.

And finally…what are your thoughts on the commercialisation of psychedelics and its comparison with the green ‘rush’ for cannabis?

There are those who are seeking opportunity and chasing profits, and this can sometimes put people at risk. Vaping is a recent example of this. Regulation is important. It exists to manage profit-seeking and short-term thinking. We need to recognise and understand our responsibility towards our fellow human beings. The psychedelic ‘rush’ needs to be mitigated by responsibility, probity and transparency. We need to do the hard work of research and collecting evidence. We have to work carefully to set the right standards and to balance the rush for growth with the Hippocratic medical oath of ‘first do no harm.’ As a UK company, ‘duty of care’ is part of our governance structure, it’s core to what we do. Our responsibility to patients comes first. The rush towards the medicalisation of cannabis meant there were not enough studies done (GW Pharmaceuticals is the exception to this). There was no incentive to carry out research and so we don’t know enough about who will benefit and who won’t. The potential of psychedelics is huge – but we have a responsibility to do this properly with rigorous research.