Rising High: Exclusive talk with biopharma company HMNC Brain Health

In this edition of “Rising High,” The Fly conducted an exclusive interview with Hans Eriksson, Chief Medical Officer of HMNC Brain Health, a global precision psychiatry biopharma company headquartered in Munich, Germany. Here are some highlights:

PERSONALIZED THERAPIES: HMNC Brain Health is focused on the development of personalized therapies for mental health disorders powered by predictive companion diagnostics. The company is paving the way for the targeted use of antidepressants through co-developing novel compounds with matching companion diagnostics, powered by its AI platform. “Our chairman, Dr. Franz Humer, was previously the CEO and chairman of Roche (RHHBY) for a long period time,” Eriksson said. “Roche had substantial success with precision medicine in the oncology space, where mainly genetic tests are applied to patients to determine whether they would benefit from a treatment. He brought that concept with him to HMNC Brain Health, being a strong advocate of using this approach in neuroscience.”

The approach allows HMNC Brain Health to move away from the current standard in psychiatry, he said. “There may be two patients who are accurately diagnosed with depression, who do not share a single symptom, highlighting the fact that there is huge heterogeneity in the broad psychiatric diagnosis,” the CMO said. “Up until now it has essentially been a trial-and-error approach for clinicians, where they just start with a standard antidepressant. If that works, it’s fine. If it doesn’t work, they open up another path and these paths are sometimes different from clinician to clinician. We want to get away from that. We want to, before the start of treatment, have a better understanding of which intervention is going to benefit that particular patient.”

He noted that the company currently has three clinical programs underway, with two precision psychiatry programs aimed at addressing a disturbance in the stress hormone imbalance in the body. The Nelivabon program comprises the Phase-II-ready compound nelivaptan and the matching molecular diagnostic test, targeting 30% of Major Depressive Disorder patients, and the Cortibon program comprises Spruce Bioscience’s (SPRB) tildacerfont, a second-generation CRHR1 antagonist, and HMNC Brain Health’s companion diagnostic, the Cortibon genetic selection tool. “The hypothalamus-pituitary adrenal axis is the way the brain drives the adrenals to produce the stress hormone cortisol,” Eriksson said. “The brain needs to send signals to those glands before they can release the human stress hormone. It does so using small hormones in the brain with the two most important ones being vasopressin and corticotropin-releasing hormone.”

A substantial proportion of depressed individuals have a disturbance in the HPA axis, with hyperactivity of either vasopressin or CRH, he said. “There have been attempts to develop inhibitors for both vasopressin and CRH and they have showed some signals of efficacy but have never made it all the way to market,” the CMO said. “We believe the reason that they have not made it to market is that they have generally been tested in a non-selective population, where only a subset of patients has the disturbance these medications are presumed to correct. What we are doing right now is we have the genetic test that can identify individuals that have this disturbance and then we can develop the medicine only for them.”

The company’s third clinical program is Ketabon, a joint venture with Develco Pharma, comprising an oral prolonged release formulation of ketamine that could significantly advance the medication of treatment-resistant depression. “The medicine is released very slowly after taking a tablet and this leads to a very different result to when you take ketamine as an intravenous infusion or nasal spray,” Eriksson said. “We have been able to get rid of practically all these traditional side effects of ketamine, which is dissociation, a psychosis-like experience, and cardiovascular effects. We can take away the side effects, but we still have a separation versus placebo in clinical trials that is similar to other ketamine-based treatments for depression. We are now building a precision medicine and companion diagnostic, but we are not completely there yet.”

He added he believes HMNC Brain Health’s more focused approach and vastly improved benefit-risk ratio for its ketamine serve as key differentiators for the company. “We’re looking for a specific biological disturbance and when we find these patients, we have a treatment for that disturbance,” the CMO said. “This is a much tighter relationship than some of the other companies and academic groups that are looking more broadly. When it comes to ketamine, one of the two mirror images of ketamine, called esketamine, was approved by the FDA in 2019. It is quite efficacious, but because of the side effects, the FDA has determined that this medication should be given under medical supervision. There are lots of practical obstacles to the use of this medication, which has limited its accessibility. With our new medication, we have been able to administer it at home safely without supervision. The main differentiator here is that we have a much better tolerated medication that has the potential to get used by a large group of patients in need of relief from their depressive symptoms.”

2025 PREDICTIONS: In 2025, Eriksson said he expects ketamine and other psychedelics to see significant adoption. “There is a need for novel mechanisms of action,” he said. “Psychiatrists for 70 years have been using medications that mainly modulate serotonin and noradrenaline neurotransmission to treat depression. These medications are efficacious, but they still do not treat all patients and even after a couple of cycles with different antidepressants, as many as 40% of depressed patients felt they did not help. We have seen with psychedelics like psilocybin for instance that there really seems to be a potential to get substantial efficacy very quickly. With ketamine you often see an improvement within a day or so in contrast to standard antidepressants that take four to six weeks to have full efficacy. The psychiatric and clinician community have been looking for something that could provide relief for patients faster and in a more predictable way.”

The CMO added as more clinical data comes out around these formulations, awareness and acceptance will increase. “If we’re talking about our ketamine formulation, we will be progressing and running additional trials,” he said. “We will start Phase 3 trials during 2025 and there is quite a lot of new data coming within the broader field. We are on the brink of being able to use these medications in a proper way after FDA regulatory approval.”

Eriksson said he also expects hyper-personalized treatments, driven by genetic, biometric, and AI-powered tools, to redefine depression care. “If you are a treating physician and a patient comes to you with any disorder, you would like to be able to have a tool that helps you to suggest to the patient which treatment is better,” he said. “Within the interaction with the patient, a clinician should be able to select the treatment that is most attractive. I do believe that we will within five years end up with such a paradigm and AI will be helpful here. At the recent ACNP conference, there were numerous presentations where investigators are collecting lots of background variables. It could be more basic ones like age, sex, duration of depression and number of previous episodes, but it also could be measures of how severe the current depression is. They are using different types of rating scales and feeding that into a computerized tool that uses AI and machine learning to suggest which path is probably most beneficial for the patient. There will never be a clear-cut path, but it could be very good guidance.”

The CMO also said he sees key hurdles like functional unblinding and ongoing debates over psychedelic decriminalization determining which companies thrive. “Functional unblinding is quite an issue for those medications that have profound psychological effects,” he said. “We can take psilocybin as an example which is now being developed for treatment-resistant depression. It is very likely that an individual participating in such a study will be able to say whether he or she is on the active drug. It’s a problem. On the other hand, we cannot say that we should not develop powerful and beneficial treatments because of that issue. I think we probably need to use as many outcome measures as possible to really demonstrate the benefit over time.”

In terms of abuse potential, Eriksson noted that ketamine is a controlled substance in the U.S. and most other countries. “There are people who are using it inappropriately to achieve some sort of dissociative high and we take this very seriously,” he said. “It is very important when we are developing this new medication for depression that it will not backfire so that it becomes a source for abuse. With our formulation there is no dissociative experience and if there had been one, it would have come at the time for peak concentration, which comes about seven hours after intake. People who are using drugs inappropriately typically want to have an early kick. We think that the problem is smaller for our medication, but we are also aware that people may try to find ways to use the medication inappropriately. We are planning a very ambitious program to evaluate the abuse liability and different approaches to minimize abuse.”

He added he also sees the demand for at-home treatments accelerating innovation in non-invasive therapeutic options. “Roughly speaking about 5% of the population has major depressive disorder,” the CMO said. “One in 20 people you meet on the street is depressed, so it’s very common. It’s important to make sure that efficacious and safe medicines can be made available to these patients on a broad scale. If it was possible to take ketamine at home, I believe that more people would use it.”

HMNC Brain Health is conducting clinical trials in Europe and has now dosed over 130 patients with its at-home ketamine formulation, he said. “We have not seen any issues with it and we see no signs of the diversion of the medicine to be used inappropriately,” Eriksson said. “We have seen no reports of the typical side effects like dissociation or cardiovascular effects, so what we are doing right now is building our experience and creating a larger and larger database supporting the use of ketamine taken at home. We are planning for the Phase 3 program to start during 2025, and when that program has read out, we hope to be able to submit applications to regulatory authorities to be able to have an approval for treatment of depression.”

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act, while ketamine is listed as a Schedule III and Eriksson said he believes the scheduling does create a barrier to public acceptance. “If you are not very much into newer psychiatric drugs and you see that there is, what you perceive as, a street labeling, you may very well think that these medications may not be appropriate for me,” he said. “It is a barrier, but there is a reason that these drugs are scheduled. These are medications that are so powerful that they need to be used with diligence and a good understanding of benefits and risks.”

The CMO said he expects public perception around psychedelics to shift as more data emerges. “There are indications that a single dose or a few doses may provide long-lasting changes, we’re talking about months of improvement,” he said. “To a patient I think that is very attractive, you can have one or a couple of treatments and then the benefit remains for a long period of time. When the general public starts to understand how these medications are different from the ones we have been using so far, I think the acceptance will be much higher.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic space, Eriksson pointed to the immense enthusiasm surrounding the industry. “Many of the banner holders for psychedelics come from some type of personal experience of using these drugs,” he said. “The experiences from using psychedelics are so powerful, so I can really understand that many of these people are absolutely convinced that these medications work. It is important to note the traditional steps we take when we develop medicines. I think there is a risk that some psychedelic enthusiasts are not really willing to go through all the rigorous methodology and steps that bring a new compound into becoming a new medicine. We need to follow all the rules that are set out by regulators as they are there to safeguard patients. We need to be careful that we are not letting the enthusiasm drive the uptake of the medicines.”

OPPORTUNITIES: As the psychedelic sector develops, the CMO said he sees the biggest opportunity in compounds under development that can achieve long-lasting effects with a short period of treatment. “That really has not happened before in psychiatry,” he said. “There is generally a huge potential there. The potential for HMNC is to be able to deliver the benefits of a compound like ketamine without the side effects that have become a safety issue and an obstacle to uptake. With our KET01 formulation, the prolonged release formulation of ketamine, we essentially have a non-psychedelic psychedelic, if you wish to place ketamine under the psychedelic “umbrella”. We are getting the best of both worlds and I really hope that this will be an attractive treatment that can help many patients to rapidly overcome the depression.”

CANNABIS/PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Acreage (ACRHF), Ascend Wellness (AAWH), Atai Life Sciences (ATAI), Aurora Cannabis (ACB), Avant Brands (AVTBF), Ayr Wellness (AYRWF), The Cannabist Company (CBSTF), Cannara Biotech (LOVFF), Canopy Growth (CGC), Cansortium (CNTMF), Chicago Atlantic (REFI), Clearmind (CMND), Clever Leaves (CLVR), Compass Pathways (CMPS), CordovaCann (LVRLF), Cresco Labs (CRLBF), Cronos Group (CRON), Curaleaf (CURLF), CV Sciences (CVSI), Cybin (CYBN), Entourage Health (ETRGF), Enveric Biosciences (ENVB), Flora Growth (FLGC), Trees Corporation (CANN), Greenlane (GNLN), Green Thumb (GTBIF), GrowGeneration (GRWG), Hemp (HEMP), Heritage Cannabis (HERTF), High Tide (HITI), IGC Pharma (IGC), IM Cannabis (IMCC), Innovative Industrial Properties (IIPR), InterCure (INCR), Ispire Technology (ISPR), Lowell Farms (LOWLF), Lucy Scientific Discovery (LSDI), MediPharm (MEDIF), MindMed (MNMD), NewLake Capital (NLCP), Numinus (NUMIF), Optimi Health (OPTHF), Organigram (OGI), PharmAla (MDXXF), Planet 13 (PLNHF), Psyence Biomedical (PBM), Red White & Bloom (RWBYF), Relmada Therapeutics (RLMD), Reunion Neuroscience (REUN), RIV Capital (CNPOF), Safe Harbor Financial (SHFS), SNDL (SNDL), Skye Bioscience (SKYE), Stem Holdings (STMH), TerrAscend (TRSSF), Tilray (TLRY), Trulieve (TCNNF), Tryp Therapeutics (TRYPF), Verano (VRNOF), Village Farms (VFF), Vireo Health (VREOF) and 4Front Ventures (FFNTF).