Psychedelic: Exclusive talk with biopharma company MindMed

In this edition of “Psychedelic”, The Fly conducted an exclusive interview with Daniel Karlin, Chief Medical Officer at Mind Medicine (MNMD), a late-stage clinical biopharmaceutical company developing novel product candidates to treat brain health disorders. Here are some highlights:

PSYCHEDELIC DRUG DEVELOPMENT: Mind Medicine’s mission is to be a global leader in the development and delivery of treatments that unlock new opportunities to improve patient outcome. The company uses rigorous science to develop its evidence-based pipeline of product candidates, striving to deliver on the therapeutic potential of psychedelics and other novel compounds to address unmet needs in Generalized Anxiety Disorder, Major Depressive Disorder and Autism Spectrum Disorder.

“MindMed is focused on opportunities to treat psychiatric illness and the lead candidate we are developing is MM120, a proprietary formulation of LSD that has really nice clinical characteristics,” Karlin said. “Effectively what we are doing is taking some drugs that have shown historical promise for our lead candidates and developing them using as rigorous and established scientific methods as possible.”

He noted these drugs, which have a complicated sociopolitical and sociocultural history, have been attracting a lot of attention for many stakeholders.

“We are applying the best possible modern drug development techniques to bring them forward for potential regulatory approval and ultimately to try to get them to the widest group of folks with unmet need today,” the CMO said.

MindMed’s commitment to applying well established and methodologically sound drug development techniques serves as a differentiator that sets the company apart from others in the field, he said.

“In some cases, you have seen less than that across this base where there have been studies, techniques and historical precedence brought forward without investigation,” Karlin said. “I also think our lead molecule differentiates us. LSD historically showed the greatest promise in the psychedelic space for treating a variety of illnesses and in our study, we were able to continue to show that this promise is sustained in modern, clinical research techniques. The durability and the robustness of the effect are both best in the category. Applying the rigor that we do to a molecule with such historical promise, and now modern evidence, is a differentiator.”

PHASE 2B MM120 STUDY: MindMed announced in September that JAMA had published full results from the company’s Phase 2b study of MM120 in 198 adults with moderate-to-severe GAD. The randomized, placebo-controlled trial evaluated a single treatment across four dose levels as a monotherapy and did not include any form of study-related psychotherapeutic intervention. The study met its primary and key secondary endpoints, with MM120 demonstrating a dose-response relationship and significant symptom improvement versus placebo on the Hamilton Anxiety Rating Scale.

“The study was designed to assess the safety and efficacy of MM120 in particular with regard to a dose-response relationship and the treatment of GAD,” the CMO said. “We set out to assess whether we could figure out the optimal dose to treat GAD. We used a single dose at five different potential dose levels – a placebo, 25 micrograms, 50 micrograms, 100 micrograms and 200 micrograms – in patients with moderate to severe GAD.”

He said the primary endpoint of the study was the dose-response relationship and change from baseline in anxiety measured using the HAM-A.

“For the primary outcome, we looked at the change from baseline to Week 4,” Karlin said, “We also looked at the change from baseline to Week 8 and Week 12. Ultimately what we were able to demonstrate is that there is a dose-response relationship in the treatment of GAD with MM120 and we were able to establish that the optimal dose to bring forward was 100 micrograms. We also showed a statistically and clinically significant differentiation for 100 micrograms of MM120 out to Week 12, a substantial benefit that clinically and statistically significantly exceeded placebo with 12 weeks duration after a single treatment.”

He added that when looking at anxiety and depression, MindMed chose to focus on the indication of GAD after realizing the area has had many fewer treatment options than MDD for the past thirty years.

“While there are a tremendous number of people who suffer from GAD and have potentially disabling anxiety, the majority of focus on drug development has been on MDD,” the CMO said. “We saw this opportunity in a drug that has shown promise in anxiety to develop it for a massive unaddressed and unmet need. “

PHASE 3 STUDIES: MindMed is currently conducting the Phase 3 Voyage study of MM120 for the treatment of GAD, the Phase 3 Panorama study of MM120 in GAD and the Phase 3 Emerge study of MM120 in MDD. The company expects topline data for Voyage in 1H26 and for Panorama and Emerge in 2H26.

“We’re currently enrolling in all three of them,” Karlin said. “Voyage is a 200-person, two-arm study, testing MM120 100 micrograms against placebo. Panorama, which is a very similar study, has a slightly higher total in 250 people and is testing 100 micrograms versus placebo with an additional 50 microgram control arm. Each of those studies is assessing the efficacy of 100 micrograms of MM120 versus placebo to treat GAD. The third Phase 3 study called Emerge, which is a very similar study, is testing 100 micrograms of MM120 versus placebo in the treatment of MDD.”

Along with seeing very meaningful change in the HAM-A score for GAD in the Phase 2b study, the CMO said MindMed saw these patients improving overlapping symptomologies of depressive disorder using the Montgomery-Asperg Depression Rating Scale.

“What we saw in 2b was that we were also able to clinically and statistically improve the MADRS versus placebo with the 100 microgram and 200 microgram doses,” he said. “Given that evidence from the Phase 2b and the preponderance of the historical evidence, we decided that we could go directly into a Phase 3 for MDD with high confidence.”

PHASE 1 MM402 STUDY: The company also completed a Phase 1 study of MM402, a single-ascending dose study in adult healthy volunteers. The study characterized the tolerability, pharmacokinetics and pharmacodynamics of MM402. The company expects to initiate further studies of MM402 to assess its potential efficacy for the treatment of ASD.

“MM402 is the right enantiomer of MDMA,” Karlin said. “Folks who are following the space may be familiar with MDMA as a drug to augment psychotherapy and that is what we saw in another company’s study in Post Traumatic Stress Disorder that led to a Complete Response Letter from the FDA. With our MDMA, this is the right enantiometer, which seems to be the more serotonin-affecting one, while the left enantiometer of MDMA seems to be dopamine-affecting. We saw the opportunity to use this molecule that has the characteristics of enhancing communication, empathy and emotional awareness. Rather than bringing that forward as a psychotherapy adjuvant, we decided to bring it forward as a potential drug for ASD.”

The company hopes that the drug creates enhanced social communication and social awareness for patients that take it, he said, adding when the drug wears off, there are no persistent or lasting effects.

“It’s a tool that people can use to enable those particular characteristics in themselves, if and when they felt that that was something that would benefit them,” the CMO said. “The analogy is psychostimulants in Attention Deficit Hyperactivity Disorder, where folks who have attentional deficits are able to take a drug that enhances their attention for work or school. Then when it wears off, it wears off and they go about their lives. In the case of MM120, we are talking about where a single administration creates lasting change, while with MM402, we are testing its ability to enhance certain skills while it’s in the system.”

DRUG ADMINISTRATION: MindMed has developed MM120 as an oral disintegrating tablet formulation which enables more rapid absorption and creates a more controlled, less adverse event-prone experience for the patient, Karlin said.

“It is a very thoughtful formulation that also offers intellectual property protection,” he said. “The main difference with the way we give MM120 from others in the category is that we are not providing psychedelic-assisted therapy. We in our Phase 2b study and our Phase 3 studies have not provided a secondary psychotherapy component, rather we are attempting to assess the drug only efficacy of the compound. That is a pretty major differentiator from others in the field who have been engaging in the study of psychedelic-assisted therapy that involves interpersonal interaction with a therapist.”

The CMO said there is little doubt that additional therapy alongside a drug creates additional benefit, but MindMed felt it was critical to test their drug in the absence of additional therapy, opening up a wider range of possibilities for subsequent use if the drug is approved.

“This makes the path to approvability far more streamlined and straightforward because it looks a lot more like a traditional drug approval, where there is no secondary intervention being tested alongside the drug,” he said.

MM402 is also different from others in the category, Karlin said, as it’s a daily drug and can be thought of as an intermittent intervention.

“In each case, we’ve taken the more traditional thinking of a psychedelic and tried to bring it more in line with certain modern scientific rigor,” he said.

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act including LSD, MDMA and psilocybin, but the CMO noted scheduling just signifies a drug has no established medical use so this will change for FDA-approved drugs.

“Scheduling represents knowledge available at the time the drug was scheduled and when LSD was made Schedule I many years ago, it did not have an established clinical use,” he said. “We were able to do research on Schedule I drugs through a process with the DEA and FDA, where we had our investigators acquire Schedule I licenses that allowed them to work with the drugs. This introduces some administrative complexity, but we haven’t really viewed that as a hindrance to our ability to do the studies. If and when the drug receives FDA approval, the DEA engages in a process of rescheduling the approved drug for prescription use.”

Karlin said he doesn’t think scheduling creates a barrier to public acceptance of these drugs as he doesn’t believe it is something that the general public necessarily thinks of.

“It does represent that there is this sociopolitical history around the drug that cuts in both directions,” he said. “There are people who are aware of the rich scientific history of LSD and that makes them have hope and expect something positive from the drug. Then there are the people who associate it with things that they are not supportive of. Whatever side of the historical political spectrum you fall on, there are certainly positives and negatives in the history of the drug. It represents something for us to overcome and to work on in repositioning our drug, if approved, as representing what we demonstrated in terms of safety and efficacy rather than its history.”

TRUMP ADMINISTRATION: In the 2024 election, Donald Trump was elected president and in subsequent months, several of his administration’s appointees have made positive remarks regarding psychedelics.

“We are very aware of what folks in the administration and in the federal government have to say and think about the category as a whole,” the CMO said. “We are encouraged when folks see the promise of the category and certainly of our compound as well. We have had very positive interactions with the FDA over the time that preceded the previous election and have very much continued post the election. While it’s encouraging to see support from appointees and politicians, we are staying the course. We are just continuing to engage in the best science, following established regulatory policies and procedures and continuing to have a productive and aligned dialogue with our regulators at the FDA.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic biopharma space, Karlin said the category saw a lot of entrants early on amid a cycle of tremendous enthusiasm from the general public.

“We’ve seen many of those companies fall off over time,” he said. “It has left us with a few leading companies who are engaging in better science, have better development programs and are well-funded to move forward. In my view, the ongoing good science and good regulatory interactions will continue to drive these companies and our company forward in a positive way. In many ways, a rising tide lifts all boats in this space.”

The CMO added MindMed is hopeful that it continues to see companies that are doing the best science and drug development continue to progress.

“The public perception of these drugs is certainly changing over time,” he said. “Maybe five years ago, we would have said that that represents a bigger hurdle than it does today, similarly with regulatory interactions. The fact that we have been able to move forward in our conversations with the regulators represents the progress of the science.”

OPPORTUNITIES: As the psychedelic biopharma industry develops and matures, Karlin said the biggest opportunities lie in treating patients with unmet needs who are currently suffering.

“We could actually bring relief to more than 60M people, just in the U.S. alone, who are suffering from MDD and GAD,” he said. “We saw a 50% remission rate at four weeks after a single administration of MM120 and that was nearly 48.5% twelve weeks after single administration. That kind of change, the ability to drive full remission from these illnesses, could mean a real change for millions and millions of people.”

The CMO added that amid all the interest surrounding these drugs, one thing that can get lost is that these treatments are being developed to help the most people as possible.

“That means we need to have widespread access and we need to have payor coverage, particularly for folks who have limited means and are on publicly-supported insurance options,” he said. “Everything we do in our development program is aimed toward ensuring that there can be access, even for folks who don’t have the means to access the highest quality care to date. That’s an obligation we all feel here at MindMed.”

OTHER PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Algernon Pharmaceuticals (AGNPF), Allied Corp. (ALID), atai Life Sciences (ATAI), BetterLife (BETRF), Bright Minds Biosciences (DRUG), Clearmind (CMND), Compass Pathways (CMPS), Cybin (CYBN), Enveric Biosciences (ENVB), Filament Health (FLHLF), GH Research (GHRS), Incannex (IXHL), MIRA Pharmaceuticals (MIRA), NRx Pharmaceuticals (NRXP), Numinus Wellness (NUMIF), Pasithea Therapeutics (KTTA), PharmAla Biotech (MDXXF), PharmaTher (PHRRF), Psyence Biomedical (PBM), Psyence Group (PSYGF), Relmada Therapeutics (RLMD), Revive Therapeutics (RVVTF), SciSparc (SPRC), Seelos Therapeutics (SEEL) and Silo Pharma (SILO).