51³Ô¹ÏÍø

For World Mental Health Day, we spoke to Dr Rob Conley, our Chief Scientific and Medical Officer, to learn more about the current treatment landscape for mental health conditions like depression and substance use disorders and hear his hopes for the next generation of mental health treatments. As Chief Scientific and Medical Officer at 51³Ô¹ÏÍø, Rob oversees all of our clinical research and development. Rob previously served as Senior Vice President at Eleusis and Chief Science Officer, Late Phase Neuroscience at Eli Lilly and Co. Prior to that, he had a long clinical and academic career, first at the University of Pittsburgh, where he completed a Psychiatry residency and was Chief Resident, and then at the University of Maryland School of Medicine, where he remains an Adjunct Professor of Psychiatry and Psychopharmacology at Maryland.

Thanks for sitting down with us, Rob! Can you start by giving us an overview of what treatments are currently available for people living with mental health conditions like depression and substance use disorders?

Sure. Depression is primarily managed today through a combination of lifestyle changes, talking therapies and medications, with Selective Serotonin Reuptake Inhibitors (or SSRIs) being the most common drugs prescribed by doctors or physicians for depression. These medications are effective for some, but there still remains a large proportion of patients who are only partially or poorly responsive and many others who are completely intolerant of current medications. Treatments such as Spravato, intravenous ketamine and rTMS, however, have shown that there is a place for effective intermittently dosed treatments. In the US, in particular, there now exists a treatment model and infrastructure for interventional psychiatric treatment clinics which I predict will grow with the introduction of more effective therapies.

Substance use disorders remain undertreated. In the case of alcohol use disorder, less than 20% of people with the condition get any treatment and there is an incredibly high relapse rate. There are also issues of compliance with, and abuse of, currently available pharmacological treatments which are often prescribed as a daily medication. I believe that effective therapies based in psychiatric interventional clinic settings could overcome some of these issues and there is promising work going on in that space.

You’ve touched on why these conditions are often cited as having high unmet needs, but can you dive a little more into what the issues are with the current treatments for these conditions?

For depression treatments like SSRIs and antipsychotic agents, undesirable side effects, a slow onset of action and a daily dosing regimen can limit treatment adherence. Indeed, it’s believed that around 60% of people who are prescribed medications for depression end up switching or discontinuing their treatment within 12 weeks due to side effects. Furthermore, approximately 30% of people diagnosed with depression simply do not respond to antidepressant monotherapies, meaning there is a real need for more effective and well-tolerated treatments.

In the case of substance use disorders, most of the currently available treatments require daily oral compliance and are based on aversion, which can limit adherence due to tolerance issues. Here too, an alternative is desperately needed.

Why is 51³Ô¹ÏÍø investigating next-generation psychedelic-based medicines as potential treatments for these conditions?

Since the millennium, there has been a growing base of clinical and academic evidence pointing to the potential of psychedelic compounds to address the limitations of current treatment opportunities for conditions like depression and substance use disorders. Whilst there still remains some debate as to exactly how psychedelics bring about their therapeutic effects, current research suggests that psychedelics produce a state of neuroplasticity - that is, the formation of new connections in the brain that allows the brain to function differently than it did before. We believe that, combined with the deep introspection psychedelic experiences typically produce, can enable people to shift ingrained patterns of thinking or behaviours, which is particularly helpful for conditions like depression and substance use disorders.

51³Ô¹ÏÍø is at the forefront of understanding the therapeutic use of these serotonergic agents for use in the clinic and I am proud to be overseeing the clinical development of our two lead compounds: BPL-003 (our synthetic, proprietary, intranasal formulation of 5-MeO-DMT benzoate) and ELE-101 (our synthetic, proprietary, intravenous formulation of psilocin benzoate).

What makes you excited about the work of 51³Ô¹ÏÍø?

I believe that we are leading the way in developing effective, rapid-acting and accessible medications that will transform the treatment and understanding of many common psychiatric diseases. Our lead compounds, BPL-003 and ELE-101, are in Phase II clinical studies and we already have some really promising data.

Findings from an open-label Phase IIa study investigating 10mg of BPL-003 in patients with difficult-to-treat depression found that a single administration of BPL-003 demonstrated a rapid antidepressant effect, with 55% of patients having a 50% or greater improvement in depression symptoms the day after dosing. Furthermore, this robust antidepressant effect lasted, with 55% of patients meeting the criteria for remission from symptoms of depression at day 29 and 45% in remission at day 85. Importantly, BPL-003 required a short time in clinic, with patients deemed dischargeable within an average time of less than 2 hours which suggests that, if approved, BPL-003 could fit within the existing interventional psychiatry treatment paradigm I mentioned earlier. We’re following a robust development pathway and I am looking forward to investigating these compounds more in our studies.

What do you think the barriers facing the development of psychedelic medicines are?

Even though there has been a lot of progress in destigmatising these compounds and developing credible evidence for their therapeutic potential, there are still a number of barriers to overcome before they can actually make their way to patients.

Firstly, in many countries, psychedelics are a controlled and scheduled substance, which means you need to go through some additional processes to research them and conduct clinical trials on them. Psychedelics carry a lot of historical baggage and, despite recent scientific breakthroughs, there continue to be misconceptions and biases that can stunt public acceptance and progress. I hope that by following the science and building evidence of best practice and efficacy, those beliefs can change over time.

Another challenge is that, because these compounds are relatively new in the medical sphere, there is a lack of standardised protocols for running clinical trials with them. However, it was promising to see the U.S. Food and Drug Administration publish draft guidance last year for sponsors developing psychedelic drugs for the treatment of medical conditions, including considerations for designing clinical trials. This was an early sign that work is being done to think about how these novel treatments may eventually integrate into existing healthcare systems. On that, intermittent clinic-based therapy like I mentioned above remains a novel treatment model in psychiatry. Treatments like Spravato have only been available to patients for a few years and the infrastructure is still in its infancy. I trust that, by the time these compounds move towards regulation and market access, we will have a good picture of what works best for patients and healthcare providers in terms of delivery.

If psychedelics are approved for medical use, how do you envision their integration into mainstream healthcare?

I can speak to the development pathway we’re following at 51³Ô¹ÏÍø specifically. We’re interested in investigating short-acting psychedelic-based treatments that can be administered in a short clinic visit, be well-tolerated and can deliver rapid, robust and lasting effects. We imagine that our treatments, if they get approved, will be able to fit into the existing interventional psychiatric treatment paradigm that already exists in countries like the US where patients can receive intermittent treatment in a clinic visit that lasts around 2 hours. This would significantly change the delivery of healthcare for these conditions, freeing many from the need for daily oral medications, or even the weekly dosing of newer treatments such as esketamine, and potentially changing our understanding of what ‘mental illness’ actually is.  

Let’s fast-forward five to ten years - what do you hope the treatment of mental health looks like?

I see a large network of interventional clinics integrated into the health care system. These clinics would accept people from, and return people to, their primary treatment settings, improved and in need of less chronic medication. I also see many workplace health models offering effective assessment and treatment of neuropsychiatric disorders, removed from the stigma, poor care and limited outcomes offered today. Ultimately, I guess I see a future where more mental health and substance use disorders are truly seen as treatable, time-limited conditions rather than intractable, chronic disorders. We see this transformation beginning to take place with metabolic disorders today and the growing body of research and evidence around novel treatments for mental health disorders is really helping to shift perceptions. This will not be an immediate transition, but is certainly an attainable and worthy goal - and I’m proud to be part of it!