Psychedelic: Exclusive talk with biotech company Enveric Biosciences

In this edition of “Psychedelic”, The Fly conducted an exclusive interview with Joseph Tucker, Chief Executive Officer and Director of Enveric Biosciences (ENVB), a company focused on the development of novel neuroplastogenic small-molecule therapeutics for the treatment of neuropsychiatric disorders. Here are some highlights:

NEUROPLASTOGENS: Enveric, based in Naples, FL, with offices in Cambridge, MA and Calgary, AB Canada, aims to develop novel treatments to transform the lives of patients living with mental illness. Through its proprietary discovery and development platform, The Psybrary, the company has created a robust intellectual property portfolio of new chemical entities for mental health indications.

“At Enveric, we are focused right now on where I believe the entire future of psychedelics is going, which is the non-hallucinogenic neuroplastogens,” Tucker said. “This whole space was inspired by psychedelics but with the goal of solving for the drawbacks and the risks of psychedelics. This is a very hot space right now and big pharma is very interested.”

Enveric is concentrating on the coming wave of novel neuroplastogenic therapeutics, he said, and has shown the ability of its discovery engine in the last few years to create interesting candidates.

“We have demonstrated our ability to outlicense those to others,” the CEO said. “Having survived this down market for the last three or four years, we have arrived at a very lean and very nimble team, and yet we managed to maintain a Nasdaq listing and the access to capital that comes with that, which we think is essential for innovative drug development.”

THE PSYBRARY: Enveric boasts a rich repository of patented and patent-pending synthetic derivatives of classic psychedelics N,N-dimethyltryptamine, psilocybin, and 3,4-methylenedioxymethamphetamine through its discovery platform the Psybrary.

“One of the many interesting idiosyncrasies of the psychedelic space is it was formed around a finite, small number of known molecules that have been used, more recreationally for the last 50 years, but in many cases for thousands of years,” Tucker said. “What we now have is this new sector created, all focused on a few known molecules, which is the opposite of what you generally want to do with drug development.”

Enveric looked at the space through a big pharma lens, he said, taking one molecule for inspiration and creating a thousand variants, which are developed to improve upon the molecule with less side effects and stronger benefits.

“On top of that because they are new, you can get composition of matter patent protection,” the CEO said. “You protect this major investment you are about to make, so that’s what we did. Our Psybrary is very, very rare in this sector and we actually have about 20 issued patents that cover composition of matter for many possible drugs, as well as the specific drug that we are trying to develop. It gives us a great deal of flexibility to work with molecules to find the very best drug candidate and it gives our future big pharma partners confidence that somebody else isn’t going to be able to come along and quickly copy the good work that we have done.”

EB-003: Enveric’s lead molecule, EB-003, is a neuroplastogen designed to promote neuroplasticity, without inducing hallucinations, in patients suffering from difficult-to-address mental health disorders. The company is focused on advancing EB-003 towards clinical trials for the treatment of neuropsychiatric disorders while out-licensing all other novel, patented Psybrary drug candidates to third-party licensees.

“EB-003 is our lead and most important program, the non-hallucinogenic neuroplastogen,” Tucker said. “To solve for the shortcomings of psychedelics at large, what you want is a drug that you can administer every day to a patient that has no hallucinatory side effects, a drug that you can imagine taking regularly. You want it to be orally available, you want to know that it gets to the brain because that is the site of action, and you want to know that it doesn’t cause any hallucinations.”

In November, the company announced the completion of preclinical pharmacokinetic studies in rats and dogs further supporting the oral bioavailability and targeted non-hallucinogenic profile of EB-003. The PK studies demonstrated oral bioavailability in rat and dog studies that was dose-proportional and no clinical safety signals, including those associated with hallucination, were observed in either study.

“What we are doing right now is the formal Investigational New Drug-enabling studies that are required in order to have a pre-IND and make an IND submission to the FDA to start testing in humans,” he said.

LICENSING DEALS: Enveric announced in February that its subsidiary, Akos Biosciences, entered into two licensing agreements with Restoration Biologics, a biotech focused on the treatment of joint disease. The companies executed two licenses for Akos’ cannabinoid-COX-2 conjugate compounds, for pharmaceutical and potential non-pharmaceutical applications.

“As a company, we have such a large repository of really exciting drug candidates that all are worth advancing,” the CEO said. “We decided that we wanted to focus all of our energy on the 003 non-hallucinogenic neuroplastogen and we looked at our portfolio and we saw this great molecule, the cannabinoid-COX-2 conjugate.”

The conjugate is a molecule that has potential in anti-inflammatory treatments, initially in topical administration but also in joint disease, he said.

“We found this interesting, young company with a lot of experts in joint disease working there and we realized that the best thing that we could do was license this molecule to them,” Tucker said. “They are totally focused on joint disease and it’s kind of a perfect hand-off. They are now able to move this molecule forward, they will expend the resources, and they have the experts to give us the greatest possible chance of success. If it succeeds, there will be royalty payments and milestone payments coming back to us as the original innovators of this molecule.”

The company also announced in November that it had executed a licensing agreement with MycoMedica Life Sciences, out-licensing the EVM201 program, including drug candidate EB-002. MycoMedica will seek to develop EB-002, a synthetic prodrug of the active metabolite psilocin, in treatment of neuropsychiatric disorders such as depression.

“The primary driver for us was again that we have innovated a very exciting drug candidate with a lot of potential, but want to focus on our non-hallucinogenic neuroplastogen,” the CEO said. “The 201 series of molecules were designed specifically to compete with companies that have created hallucinogenic neuroplastogens, which we think could face a number of development challenges, including around intellectual property protection.”

Intellectual property for classic psychedelics might protect the molecules for four or five years, he said, but not necessarily for twenty years, so the 201 program was designed for when those molecules get approved but start to come under intellectual property attack.

“When that happens you look at what’s a better drug, an improved drug, which works on the same mechanism, but has stronger intellectual property and better efficacy to side effect profile,” Tucker said. “That program is absolutely worth pursuing but we wanted someone else to do it. We found MycoMedica, which is a well-funded private company that is interested in that space. They have experts, they’re well-funded so they can make the investments into that program and again if successful, there will be milestone payments and royalty payments coming back to Enveric.”

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act, including MDMA, psilocybin and DMT, however the CEO said the scheduling only creates a barrier to street drug usage.

“Using MDMA, DMT or psilocybin in an unapproved, un-watched over, unconfirmed way, absolutely the scheduling creates quite a barrier to that type of usage as it should,” he said. “These are very powerful molecules and whether or not the benefit of MDMA or psilocybin outweighs the risks has not yet been proven.”

Once a molecule has been confirmed by the FDA to have a benefit, which hasn’t happened yet, the DEA is likely to reschedule the molecule, Tucker said.

“In terms of widespread acceptance of street drugs, yes it’s a barrier,” he said. “In terms of widespread acceptance of an FDA approved drug, it is not. Once the FDA approves something, you’ve proven the benefits outweigh the risks, then you will be able to reschedule that molecule. It ends up becoming not an issue if you have proven that the drug is valuable to society.”

ELECTION RESULTS: In this year’s U.S. election, Massachusetts voters rejected a ballot measure that proposed decriminalization of psychedelic use for people older than 21, which the CEO said he felt was very encouraging.

“It’s pretty clear that society at large is unconvinced that we as a society should have unfettered access to these molecules,” he said. “They have been scheduled for a long time for a pretty good reason. They definitely have activities that cause a lot of concern. I thought that was quite encouraging honestly. Voters, despite all you read about in the media and the very vocal minority that are proponents of unrestricted access, are able to say no, these are powerful and potentially dangerous, and we should wait until somebody gets a drug approved by the FDA.”

Also in this year’s election, Donald Trump was elected president and Tucker noted Robert F. Kennedy Jr., newly appointed Department of Health & Human Services secretary, has been vocal about his support for psychedelics.

“I expect Trump and RFK to put pressure on the FDA to approve the drugs, but at the end of the day the reason the FDA exists is to protect the average citizen from companies that are going to try to sell them things that haven’t been proven to be more beneficial than risky,” he said. “I don’t think you are going to see Trump or RFK eliminate the FDA, I just don’t see it. Ultimately, I think there will be some noise and there will be some pressure, but I don’t really expect there to be significant changes to how psychedelics are viewed.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic space, the CEO pointed to the funding environment as well as the challenges around functional unblinding.

“The last three to four years have been one of the toughest times to raise money for innovative drug discovery companies, like ourselves, but also for the larger ones with late-stage molecules who usually have, in the eyes of the market, very high values,” he said. “Currently all of us are being deeply, deeply discounted, very undervalued in the market and that makes it a challenge to raise dollars that are absolutely essential to invest in the drug development.”

In regards to functional unblinding, Tucker said that many in the industry were excited last year when MDMA came to the FDA for approval, however it was not approved, in large part due to the inability to tell the difference between the patient getting better because of the drug or because they know they got the drug.

“They believe that if they got the drug they will feel better,” he said. “That is the placebo effect, which is a particular issue in psychiatry trials. If you’re depressed and you go into the drug trial, somebody gives you the drug and you know you got it. You feel less depressed automatically because you think, ‘I got the drug that is going to work for me’ and you become less depressed, which is the endpoint of the trial. That is a challenge that the FDA saw and that is apparently the main reason that MDMA did not get approved. That is a particular challenge for every hallucinogenic psychedelic and that’s a very big challenge for them. The non-hallucinogenic drugs, of which there are very few, Enveric being one of the leaders, don’t face that same challenge.”

OPPORTUNITIES: As the psychedelic industry develops and matures, Tucker said the biggest opportunities for the sector lie in the development of neuroplastogens.

“Psychedelics are being called neuroplastogens in two versions, hallucinogenic neuroplastogens or non-hallucinogenic neuroplastogens,” he said. “What the neuroplastogen part means is essentially a drug that stimulates rewiring of the brain and that is much bigger than psychiatry. It started in the field of psychiatry in attempting to treat anxiety or depression or PTSD, but the potential is much greater. When you think of things like Alzheimer’s, Parkinson’s, MS, there are all these diseases of the brain, which are currently very difficult to approach. If you could rewire the brain you might be able to really create a lot of additional benefits. It’s a much, much bigger world out there than psychiatry.”

The CEO added Enveric in particular is very excited about its big portfolio of molecules through the Psybrary.

“We may have some very interesting molecules in there that could be useful as neuroplastogens beyond psychiatry,” he said. “We are really excited about the future and everything that we’ll be able to continue to do moving forward.”

OTHER PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Algernon (AGNPF), Allied Corp. (ALID), atai Life Sciences (ATAI), BetterLife (BETRF), Bright Minds Biosciences (DRUG), Clearmind (CMND), Compass Pathways (CMPS), Cybin (CYBN), Entheon Biomedical (ENTBF), Filament Health (FLHLF), GH research (GHRS), Incannex Healthcare (IXHL), Mind Medicine (MNMD), MIRA Pharmaceuticals (MIRA), Mydecine Innovations (MYCOF), NRx Pharmaceuticals (NRXP), Numinus Wellness (NUMIF), Optimi Health (OPTHF), Pasithea Therapeutics (KTTA), PharmAla Biotech (MDXXF), PharmaTher (PHRRF), Psyence Biomedical (PBM), Psyence Group (PSYGF), Quantum BioPharma (QNTM), Relmada Therapeutics (RLMD), Revive Therapeutics (RVVTF), SciSparc (SPRC), Seelos Therapeutics (SEEL), Silo Pharma (SILO) and Synaptogenix (SNPX).