Pro-Patient Psychedelic Treatments Are Finally Moving Forward In A 'New Paradigm Shift'

Last week, Benzinga’s Psychedelics Capital Conference brought a premier gathering of the biggest publicly traded psychedelics companies in North America with forward-thinking investors to Miami, where the hottest topic seemed to revolve around LSD and derivative molecules.

Having spent the majority of my life dealing with severe anxiety disorder, I have only recently shifted my thinking away from “what pills” can I take to push it down to conversations about what forms of treatment and studies have been done that could help me navigate the almost defeating waters of my own mind I experience everyday, from the moment I wake up each morning.

At the Capital Conference, Shark Tank’s Kevin O’Leary (Mr. Wonderful) sat down on a panel with Benzinga’s founder and CEO Jason Raznick to explain the market opportunities for legal psychedelics in the space, which O’Leary says is in the “hundreds of billions of dollars.”

“This sector is medicine: FDA-approved, non-recreational use,” referring to psychedelics usage as a form of mental health treatment. “It’s a once-in-a-lifetime opportunity.”

A few weeks prior to Benzinga’s inaugural conference, I had just begun my own research into psychedelics, looking for ways to finally address my own anxiety head-on.

And that’s where I came across MindMed MNMD, a clinical stage biopharmaceutical company developing novel products to treat brain health disorders, with a particular focus on psychiatry, addiction, pain, and neurology.

Currently, the company focuses on compounds linked to LSD, ibogaine, and MDMA as it continues assembling a compelling and innovative drug development pipeline. Its Phase 2b clinical trial for LSD is the most advanced program in the company’s pipeline and is the first commercial study of LSD in over 40 years.

The objective is to determine the reduction in anxiety symptoms for up to twelve weeks after a single administration of MindMed’s proprietary drug candidate, MM-120, a pharmacologically optimized form of LSD being developed for GAD and other brain-based disorders.

O’Leary, who entered the space just three years ago, also has a stake in MindMed, serving as an early financial and media supporter of the company. He has since become a strong advocate for the entire psychedelics space.

In an interview with MindMed CEO Robert Barrow, I spoke with him about where the industry currently stands, debunking the myths and misnomers held by consumers and investors. Barrow also sits on Benzinga's Psychedelics Advisory Council.

Parsing Through Myth

When you think about the history of psychedelics it’s hard not to think of the bias, preconceived notions, and of course, political backdrop that was the counterculture movement and government responses in the 1950s and 1960s.

Historically, LSD has been studied as part of a rigorous, drug discovery process. But the compound’s reputation has been muddied by disinformation and misinformation.

Barrow referenced a conference he attended where the FDA was presenting a particular narrative around the genotoxic effects LSD had upon birth defects:

“...and that data has been debunked entirely. The FDA speaker went on to say that they no longer view that as a concern with LSD. While we have our own studies that support that conclusion, that’s just a small example of the many ways in which the narrative around the opportunity here, historically, has been distorted.”

At the end of the day, Barrow believes that the critical importance of organizations such as MindMed is to “build out a pharma company that can deliver on the therapeutic opportunity of the psychedelic drug class, and any other novel CNS mechanisms that will improve patient outcomes.”

Where Do We Fall On the Spectrum?

In 2022, LSD is now being examined appropriately by regulators for bringing a positive, medical treatment option to consumers, specifically by targeting unmet medical needs.

For companies like MindMed, bringing a rigorous, pharmaceutical approach to drug development is critical for getting these types of products out to every patient who is in need - regardless of their age, demographic characteristics, or where they live.

So, where do we as an industry fall on the psychedelics spectrum? Barrow distinguished three generations of psychedelics in answering this question.

“We think of the first generation as just the classic psychedelics, with the second generation being some sort of optimized form that has enhanced pharmaceutical properties. And then the third being new chemical entities and drugs that have never necessarily been in humans before.”

He mentioned that MindMed, for example, is not working on the same LSD that has been around forever in its precise form. “We’ve been able to enhance its stability and improve its profiles as a pharmaceutical product, which gives us a better path towards getting it to market and solve some of those challenges inherent in the historical, illicit use of LSD.”

Pointing to the opportunities with LSD, psilocybin, and MDMA, Barrow says this is a pathway for further innovation that will give companies like MindMed a direct path to take it through an approval and development process.

The DEA, by and through The Controlled Substances Act (CSA), divides controlled substances into categories known as Schedules I through V, based on their medical utility and their potential for abuse and dependence. The lower the schedule number, the greater the restrictions and controls.

At its core, MindMed is focused on conducting high quality drug development clinical research programs, to demonstrate the safety and effectiveness of a drug to take to the regulators and get the approval.

Pointing to the FDA and DEA, Barrow says we should be applauding how this space has been approached thus far. “We see a willingness to look at the opportunity objectively, to take this as science and research…and not overlay the cultural or political backdrop on top of that.”

A New Treatment Paradigm?

One of the biggest challenges current trials face, according to Barrow, is how these products can ultimately be delivered to patients.

“This is not a situation where we think it can be responsibly rolled out by just throwing drugs at patients,” Barrow clarifies. “In order for the opportunity to be seen through and done responsibly, there needs to be both a physical and human infrastructure that is going to be there to oversee the safety and give the level of psychosocial support and the therapy that is often accompanying these products.”

As someone who has been prescribed various types of SSRIs and told to just take the pill and come back in a month to provide feedback, I was relieved to finally hear the words Barrow uttered that no PCP or general practitioner I’ve presented with has told me:

“We have a new treatment paradigm coming to market potentially, or at least coming through clinical research that require a whole different dynamic that goes beyond ‘here’s an SSRI and take it every day, and come back and call me when you need a refill’ - this is different and it’s different in a very intentional, positive way that requires a lot of creativity.”

Barrow quickly walked me through MindMed’s three different treatment programs, beginning with its Phase 2b clinical trial for MM-120, an optimized form of LSD.

MM-120

This program revolves around MM-120, the company’s proprietary form of LSD, which MindMed is taking into Generalized Anxiety Disorder (GAD), which offers some treatments, including SSRIs and benzodiazepines.

However, according to Barrow, there’s an 80% overlap with depression in terms of what gets diagnosed as GAD versus depression.

“We think this will be the study that allows us to then move into pivotal phase three trials, and ultimately towards the drug approval.” Barrow says the Phase 2b trials will be a 200-patient study, launching in Q2 2022.

18-MC

MindMed’s second drug program is a molecule called 18-MC, a proprietary, non-hallucinogenic molecule that is based on ibogaine, which has been used to treat substance use disorders like opioid addiction.

Ibogaine, however, is extremely problematic due to its proarrhythmic effects, as it presents a pretty substantial cardiovascular risk in addition to it being hallucinogenic.

“The cardiovascular risk presents a real problem, because patients develop arrhythmias and there have been reports of sudden deaths that occur with the administration of Ibogaine; it’s not an acceptable profile for a drug to move forward to an approval stage and then be broadly uptaken.”

Barrow says 18-MC was designed to effectively do away with that cardiovascular risk, which is why early research on the compound received a $6.5 million dollar NIDA grant back in 2013.

“What we know is that it does not have the same sort of cardiotoxic risk,” Barrow explained. “It is not hallucinogenic, but it has the same sort of potency and every preclinical study we’ve done comparing it to Ibogaine, we see a similar potency in terms of reduction of administration of opioids, alcohol, nicotine, and stimulants. Across the board, every substance of abuse we’ve studied, we see this substantial dose responsive and equally potent response compared to Ibogaine.”

Towards the end of last year, MindMed finished its Phase I study of MC-18 for opioid withdrawal and will be launching its Phase II proof-of-concept study in the second quarter.

“That’s one of the really major unmet needs…and we’re looking at that first week when the patient is trying to get off the opioids and trying to facilitate the completion of withdrawing from those opioids and getting onto medication assisted therapy like suboxone.”

R(-)-MDMA

The third program MindMed has is R(-)-MDMA, which is a pharmacologically optimized enantiomer of MDMA.

MDMA, currently in development for the treatment of PTSD, has been extremely promising, according to Barrow, and is heading towards a pivotal Phase III trial run by MAPS.

“The R(-) enantiomer of MDMA seems to mitigate the potential toxicities of receiving MDMA, and those toxicities appear to be attributable to the S(-) enantiomer. The R(-) enantiomer also seems to maintain the pro-social effects of receiving MDMA. If we can use good drug optimization, good drug design and selection, we can mitigate some of the concerning or limiting side effects, while maintaining the pro-social effects that makes for a potentially better or more widely-usable uptake treatment model.”

Barrow says they’re also developing this product for ASD, or Autism Spectrum Disorder, as there are currently no approved therapies for the core symptoms of ASD. “The drugs that are available are largely there for behavioral control…and we want to create a new treatment paradigm that would enhance social functioning, reduce social anxiety, and at the end of the day, be pro-individual to help them function better - as opposed to just being treatments that are there, the antipsychotics that are used to just reduce agitation.”

Get the Treatment You Need With the Tools Available

With many of these anxiety disorders, Barrow says that we have seen a historical stigmatization of not just the drugs, but the conditions, which themselves go unspoken and fly below the radar in some respects.

“Don’t go so far down the road that you avoid interventions,” he advises those who struggle with GAD and other anxiety-related disorders.

“Even the interventions that are available today are there, and effective in some respects. We think there are many areas for improvement, which is why we are working on these new products, but it shouldn’t be lost on anyone - the SSRIs, the drugs that are available, psychotherapy - these are the tools that for many patients, do work; not for enough patients, but for some, they’re lifesavers.”

In setting expectations appropriately, Barrow explained that psychedelics are not a ‘cure all’, if and when they become approved:

 “We need to put that in context; we need to have realistic expectations that these are additional tools in the toolbox, but they aren’t going to cure everyone, and they shouldn’t be thought of that way. And patients shouldn’t wait on them. If someone is having depression, anxiety, or these disorders - get treatment, find what you need to find to get better. And at the end of the day, we hope to have additional tools that are going to be available to further enhance that healing and well-being.”

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