At the start of 2022, the FDA cleared MindMed’s Investigational New Drug (IND) application for MM-120, paving the way for the largest commercial study of LSD ever conducted.
Topline data from a landmark Phase IIa trial will be presented at May’s PSYCH Symposium, with the CEO of MindMed, Robert Barrow, joining a panel to discuss the company’s approach to dynamic drug development.
Ahead of the seminal event, PSYCH spoke with Barrow about studies of the proprietary compound and its potential applications.
‘At MindMed we have built a world-class pharmaceutical organisation to deliver on the therapeutic potential of the psychedelic drug class,’ said Barrow.
‘We have done this by bringing in highly experienced pharmacologists and drug developers. I believe we have the best team, not only in psychedelics but in the whole of CNS, and can continue to be successful as a mid-size company and maximise every opportunity that arises.
‘As everyone in our organisation comes from pharma, we know the importance of lifecycle management and how market protection needs to be done ethically, but also in a way that drives quality, value and patient outcomes.
‘Often regulatory approval is thought of as the end, when, in fact, it’s actually the starting point. If you get a drug approved, but there is no market for it, you actually haven’t done the world a service and haven’t done your stakeholders any service as you’re not helping patients in need.
‘We think about the opportunity and how we can have the biggest impact for patients. My firm belief is that the only way to do this efficiently, at scale and with quality, is by approaching the opportunity as an innovative CNS pharmaceutical organisation.
‘We are thinking about near-term opportunities and long-term opportunities, so we are already investing in subsequent generations of products that will enable us to iterate and improve as time progresses.’
As the first study of its kind, MindMed’s Phase IIb trial with MM-120 could have wide-reaching implications for the rest of the industry. PSYCH was eager to learn about the trial and the differences between MM-120 and LSD-25.
‘When we talk about it being pharmaceutically optimised, it’s driven by both the physicochemical and pharmaceutical development aspects,’ explained Barrow.
‘The active molecule that is getting to the target is LSD. Now, the LSD that has been used historically has a very different pharmaceutical product profile.
‘For the Phase II programme with MM-120 for generalised anxiety disorder (GAD), we had our IND application cleared at the beginning of this year and anticipate dosing patients in the summer.
‘We have a number of sites that have previously run studies of psychedelics and that are great for our organisational set-up. We are doing what I believe to be the most comprehensive dose-response study ever undertaken with these molecules in a disease population, with four treatment arms and a placebo.
‘These have been well categorised in terms of pharmacology and pharmacodynamics, through our collaborators at the University Hospital Basel. In one study, we believe we will be able to answer many questions that will be critically important to design our pivotal development programme in Phase III.
‘For many years, the FDA has emphasised the need to spend adequate time in Phase II, to generate the data that justifies the dosing regimen in Phase III.
‘It is convenient to just pick a dose and justify that dose because it produces the intended effect. However, no one knows if the magnitude of the psychedelic effect is directly causative for improvements in clinical outcomes. It may be highly correlated and may even be inseparable, but we just don’t know the answer to that yet.
‘If people rate the psychedelic experience as being similar at both 100- and 200-microgram doses, but they experience different changes in anxiety symptoms or durations of activity, then that could have significant implications on how treatments are actually delivered in the real world.
Dr Holze and Professor Liechti, MindMed’s collaborators from University Hospital Basel, will present results from their Phase IIa study at PSYCH Symposium. PSYCH asked Barrow about the importance of academic partnerships.
‘Collaborations with academic institutions are essential for any drug company, as these are the organisations conducting the research with access to hard data,’ responded Barrow.
‘The level of experience we are able to tap into through our collaborations and connections has been hugely valuable to us and to the entire field.
‘Not all drugs are going to work for every patient, which is a fact of any medical treatment, so I think as the field progresses, we’ll see an increase in non-competitive collaborations.
‘Everyone benefits by looking at common themes that don’t have competitive dynamics with a unified multi-stakeholder view. Set, setting and research method controls are also big questions that need to be answered and we’ve seen positive growth through the sharing of insights between academic and commercial organisations. Ultimately, everyone wins in that situation.’
In few indications is there a greater global patient need than GAD, which affects 6.8 million adults in the US alone. Barrow explained why MindMed is investigating MM-120’s efficacy to treat the mental illness.
‘We think that anxiety offers a great target because it is comorbid with depression, substance-use disorders and pain conditions. It has such significant symptom overlap, and typically highly correlated outcomes, that we believe anxiety is actually a key underlying cause of many of these illnesses.
‘One of the most exciting things is that in more advanced/treatment resistant populations, anxiety is one of the remaining core clusters of symptoms.
‘This means even in that population we think we would see a pretty significant improvement in patient outcomes. As we progress through development, we will hopefully gain positive evidence that shows improvements in anxiety symptoms – whether solely in GAD and/or associated with depression.’
Historically, LSD was one of the most intensively studied psychedelic medicines, with 1,000 scientific papers authored prior to prohibition. However, best practices governing clinical trials have shifted since then, with the introduction of control groups and rigorous regulations.
PSYCH was keen to learn how beneficial historical data was in spite of changes in study methodology.
‘That is a great question. We think about the historical data as de-risking our decision-making and informing how we can be most efficient in our development programmes.
‘Some historical data, particularly if it comes from academic institutions or investigation initiated studies, can be quite useful for regulatory discussions. This jump-started conversations in the US and allowed us to progress through Phase I and on to Phase II studies much faster.
‘Even more valuable than that, in some ways, is knowing what we know about pharmacokinetics and pharmacodynamics. We don’t have all the answers definitively but we do know where to look for opportunities from a safety and efficacy standpoint.
‘As a drug developer, you couldn’t ask for a better level of confidence, with the data to inform what to do next and where to expand your pipeline.
‘We are thinking about the magnitude of the opportunity beyond anxiety and depression. There is an enormous set of evidence to support our decision-making and it allows us to be very efficient, and ultimately drive a huge commercial value.’
Building on this data, MindMed is developing experiential therapies for a number of health conditions. PSYCH asked Barrow if recent innovation in psychiatry was solely down to regulatory reform.
‘It is multifactorial,’ stated Barrow. ‘Certainly, the backdrop against which these innovations are happening cannot be overlooked.’
‘We have double-digit rates of growth for psychiatric disorders. Here in the US, children as young as eight are now being recommended for paediatric anxiety screening. The number of deaths from overdoses across the world has been growing, and so the entire backdrop has set us up for a worsening mental health crisis.’
‘Now we have a drug class that has never been taken forward to regulatory approval, with direct agonist activity on the serotonin system. When you think about developing innovative CNS products, often they are highly speculative until you get late in development as you don’t actually know whether these products work.
‘In the case of psychedelic medicines, we have 80 years of data on these compounds. So, we have this large database supporting patient safety and preliminary evidence on efficacy, which gives us enormous confidence in taking these molecules and applying them to the mental health crisis.’
To explore solutions to the mental health crisis and accelerate the adoption of psychedelic healthcare in Europe, PSYCH Symposium: London 2022 is taking place at the prestigious National Gallery on Wednesday, 11 May.
From MindMed, Chief Medical Officer Daniel Karlin will be at the event alongside Barrow. Barrow commented on the importance of the upcoming event.
‘It creates an opportunity for idea-sharing and a cross-pollination of concepts, as no one has a monopoly on the right answer. Many opportunities exist – many could work and many might not.
‘I’ve had wonderful conversations at conferences with regulators, our peers and also those from the pharmaceutical industry without a close connection to psychedelics.
‘Events like this, where the industry can come together, are highly valuable assets and we look forward to being in London in a few weeks’ time.’
Tickets to the seminal PSYCH Symposium are selling fast. To secure your attendance at Europe’s premier psychedelic healthcare conference and connect with industry influencers, please visit the website: https://www.psychsymposium.com/
To secure your ticket to Europe’s premier psychedelic healthcare conference and connect with industry influencers, please visit the website: https://www.psychsymposium.com/