Rising High: Exclusive talk with biotech company Enveric Biosciences

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

NEUROACTIVE MOLECULES: Enveric, based in Florida, 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.

“We look at this as a very new and exciting sector that was really borne out of academic work and a lot of history of the use of the molecules that came from psychedelics,” Tucker said. “These are very potent, profound, neuroactive molecules, which need to be regulated by the likes of the FDA, Health Canada and EMA and which are most likely to be commercialized by big pharma.” Enveric’s lead program, the EVM201 Series, comprises next generation synthetic prodrugs of psilocin and the program’s first product, EB-373, is being developed for the treatment of anxiety disorders. The company is also advancing a second program, the EVM301 series, to develop treatments promoting neuroplasticity without the inducement of hallucinations in patients.

“We started by saying, ‘Where are the opportunities to improve upon what nature has already provided us?’,” the CEO said. “The first is what our lead program is all about, the molecule called EB-373. The premise of that program is to improve on psilocybin to make it have less side effects and be more acceptable to the patients as well as all the different parties of the healthcare system.” The program seeks to make a “better” psilocybin without changing the treatment paradigm, he said, which includes psychological support and the induction of hallucinations as a therapeutic modality.

“The second program asks, ‘How can we really turn this world upside down and how can we radically improve upon what nature has provided us?’,” Tucker said. “That’s where we get into the category of neuroplastogens. It is essentially the idea of inducing neuroplasticity in patients causing a reversal of neuronal atrophy that is typical of people suffering from psychiatric conditions like anxiety or depression.” He added Enveric recognizes the need for novel compounds with composition of matter intellectual property, as the company expects the molecules to ultimately become pharmaceutical products. “Everything needs to be significantly improved over what nature has provided us,” the CEO said. “We need to go through all the rigorous testing for clinical trials to prove that these molecules are in fact not just better than the ones currently out there, but better than any of the other neuropsychiatric medicines being developed today.”

INTELLECTUAL PROPERTY: As competition continues to increase in the psychedelic biotechnology space, Tucker pointed to Enveric’s intellectual property portfolio as a key differentiator for the company. “There are not so many other companies in the space that have strong composition of matter intellectual property surrounding the molecules that they are moving forward,” he said. “Many of the companies are working with generation one molecules that are straight from nature in many cases. You don’t get composition of matter intellectual property for a molecule or a drug that you did not create.”

The CEO noted quite a few companies have accelerated quickly into clinical trials but with historically-used molecules. “That is going to become a problem in our opinion,” he said. “Once you become approved by the regulatory agencies, you have very little in the way of protection to stop others from competing with you and making your molecules.”

Enveric’s development of neuroplastogens also serves as a differentiator for the company, Tucker said. “These are really very different from the initial wave of molecules,” he said. “Our neuroplastogens are designed to be very minimal in the way of detectable hallucinations or disassociation. It allows you to have a drug, that instead of having to go through this very onerous psychotherapy-associated approach, it is much more classic pharma. Take a pill and get the benefit you’re looking for without having to go through this big hallucinatory experience.” The CEO said the molecules will offer patients much greater accessibility. “There are very few companies that have the capability to design such molecules,” he said. “A requirement to even be able to consider that is to have the ability to create a large number of novel molecules and screen them.” Enveric does just that with its proprietary Psybrary, a collection of new chemical entities created through a combination of synthetic biology and chemistry, Tucker said. “We have been able to screen through that portfolio,” he said. “You learn a heck of a lot when you take molecules that have never existed before and test them against the target receptors. And because we have been able to create such a large portfolio that’s enabled us to find very good drug candidates.”

EB-373: In July, Enveric announced results from pharmacokinetic animal studies demonstrating oral bioavailability, rapid onset of action and systemic clearance, and a more favorable side effect profile for the company’s lead product candidate, EB-373. PK measurements that were consistent in both dogs and rats confirmed that oral administration of EB-373 resulted in dose-dependent increase in psilocin blood concentration, correlating to levels expected to be effective in humans. “We are looking at Q4 or possibly 1Q24 as the start of a first-in-human clinical trial of EB-373 in anxiety disorder,” the CEO said. “Our intention is to complete all of our preclinical studies this year and we may or may not start the Phase I immediately.” He noted Enveric is excited about the Phase I trial as it will not only test the safety of the molecule, but also the efficacy.

“EB-373 is designed based around the anticipated efficacy mechanism of action of psilocybin,” Tucker said. “We are designing our molecule to improve upon the side effects of what are noted for psilocybin in human trials right now. What that means is in our Phase I, where normally all you’re able to see is side effects or lack thereof, you’ll actually see the efficacy.” The company is looking to discover if EB-373 has less side effects for patients as well as a faster onset and completion time compared to psilocybin, he said. “The study will give us good indications as to whether or not this is going to be a successful drug compared to the psilocybins of the world that are already being clinically investigated,” the CEO said. He added that the company will conduct the first-in-human trial in Australia and may possibly run the Phase IIa portion in the county as well.

“We took a look at multiple jurisdictions around the world and what we discovered is that Australia has built for themselves a robust, early clinical stage infrastructure,” Tucker said. “The regulatory hurdles to start a Phase I trial in Australia are less than in jurisdictions such as the United States or Canada. That saves significant time and significant capital. The second big benefit is Australia also recognizes that they have become a destination for numerous companies to do these Phase I clinical trials.”

Australia has created a tax rebate program that pays a company back 43.5% on the dollar for clinical trials and preclinical studies, he said. “That is a significant cost savings for a little company such as Enveric and makes a very compelling reason to go there,” the CEO said.

EVM301 SERIES: The EVM301 Series, Enveric’s third generation of therapeutics, are intended to offer a holistic approach for treating central nervous system disorders. The program is progressing through early discovery and characterization efforts to define additional neuroactive drug candidates. “These molecules called neuroplastogens induce neuroplasticity,” Tucker said. “People that suffer from anxiety, depression, PTSD or similar neuropsychiatric conditions experience what is called neuronal atrophy, a reduction in neurons or a reduction in interneuron productivity. If you can stimulate neuroplasticity, you can actually get the brain to cause more connections between the neurons and restore the brain back to its normal state.”

He said the company has created a significant number of test molecules and identified several that are very promising. “They look to indeed fall into the category of neuroplastogens, to have this beneficial effect and yet to be dosable at levels that don’t appear to cause hallucinations,” the CEO said. “Those molecules we think are going to be of great interest to the pharmaceutical industry as well as to patients because they’re much more amenable to dosing by patients and coverage through healthcare.”

Enveric’s goal is to pick a lead candidate from the program at the end of the year and embark on preclinical studies. “We think that this program has a very good potential for partnering with big biotech or innovative pharma,” he said.

FDA DRAFT GUIDANCE: The FDA recently published its first draft guidance on clinical trials with psychedelic drugs highlighting fundamental considerations for researchers investigating the use of these drugs for potential treatment of medical conditions, including psychiatric or substance use disorders. “I have been very happy with honestly all the interactions that we have had with regulatory agencies,” Tucker said. “They recognize that these molecules are very potent and that they have been showing some very positive effects in the early work. They have actually been very forward-thinking.”

The guidance represents a very good sign for the industry, he said, as it shows regulatory agencies are trying to help it become streamlined and get rigorous. “It’s going to be positive for the industry to really move things forward and get the most out of this class of molecules,” the CEO said.

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act, including MDMA and psilocybin, however Tucker said these molecules will inevitably be rescheduled following regulatory approvals. “It’s well known that the rationale that makes something a Schedule I is high-abuse potential and no benefits,” he said. “Meanwhile, we have many clinical trials going that appear to be demonstrating the benefits. Post-approval of these molecules, both MDMA and psilocybin seem to be coming within the next few years, it’ll be inescapable that those would likely be rescheduled out of Schedule I into a different class.”

The CEO added he does think scheduling is necessary to prevent the molecules from becoming generally available recreationally. “The psychedelic agents are extremely potent molecules and have some significant impacts,” he said. “The potential harm that comes from the lack of ability to control your actions while under the influence probably means they should be scheduled.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic space, Tucker pointed to the hesitancy of the pharmaceutical industry to embrace the molecules. “The greatest barrier in my opinion is the pharma industry is still, as it should be, a very conservative industry,” he said. “The soonest to be approved molecules, the MDMAs and psilocybins of the world, are going to have the side effect of inducing hallucinations and potential loss of control of the patient, which requires all of the extra psychotherapy.”

This leads to added infrastructure and staffing costs as psychedelic experiences can last six to eight hours, the CEO said, causing big pharma to be less enthusiastic about supporting the space. “I think that we’re going to only see limited uptick, even once approved, for molecules that induce hallucinations as part of the treatment,” he said. “When things are going to completely change is once you get these new neuroplastogen molecules. I expect full embracing of that class by big pharma and then you’ll see a lot of patients really being able to benefit from it.”

OPPORTUNITIES: As the psychedelic industry develops and matures, Tucker said the biggest opportunities for the sector lie in the development of neuroplastogens. “The opportunity is in the ability to target a completely new mechanism, the idea of neuroplasticity reversing the loss of the neuronal atrophy,” he said. “It is super exciting to have a new way of coming at these big problems that still beleaguer society and we are really excited because that is an area that we are moving into with our second program. We’re seeing some very compelling evidence internally that should indeed be a really exciting new class. We want to do our part to move it forward to get patients much improved drugs relative to what is available to them now.”

CANNABIS/PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Aleafia Health (ALEAF), Acreage (ACRHF), Atai Life Science (ATAI), Audacious (AUSAF), Aurora Cannabis (ACB), Avant Brands (AVTBF), Awakn Life Sciences (AWKNF), Ayr Wellness (AYRWF), Body and Mind (BMMJ), BZAM (BZAMF), Cannara Biotech (LOVFF), Canopy Growth (CGC), Chicago Atlantic (REFI), Clearmind (CMND), Clever Leaves (CLVR), CordovaCann (LVRLF), Cresco Labs (CRLBF), Cronos Group (CRON), Columbia Care (CCHWF), Compass Pathways (COMP), Curaleaf (CURLF), CURE Pharmaceutical (CURR), CV Sciences (CVSI), Cybin (CYBN), Delic Holdings (DELCF), Delta 9 (DLTNF), Entourage Health (ETRGF), Fire & Flower (FFLWF), Flora Growth (FLGC), General Cannabis (CANN), Greenlane (GNLN), Green Thumb (GTBIF), GrowGeneration (GRWG), Goodness Growth (GDNSF), Hemp (HEMP), HEXO (HEXO), High Tide (HITI), India Globalization Capital (IGC), Indiva (NDVAF), Innovative Industrial Properties (IIPR), InterCure (INCR), IM Cannabis (IMCC), Wellbeing Digital (KONEF), Khiron Life Sciences (KHRNF), Lowell Farms (LOWLF), Lotus Ventures (LTTSF), MediPharm Labs (MEDIF), MedMen (MMNFF), MindMed (MNMD), NewLake Capital (NLCP), Numinus Wellness (NUMIF), Organigram (OGI), Planet 13 (PLNHF), Reunion Neuroscience (REUN), Revitalist (RVLWF), RIV Capital (CNPOF), Relmada (RLMD), RYAH Group (RYAHF), Safe Harbor (SHFS), Small Pharma (DMTTF), SNDL (SNDL), Sproutly (SRUTF), Skye Biosciences (SKYE), Stem Holdings (STMH), Sunniva (SNNVF), TerrAscend (TRSSF), Tetra Bio-Pharma (TBPMF), Tilray (TLRY), Trulieve (TCNNF), Tryp Therapeutics (TRYPF), Verano (VRNOF), Village Farms (VFF), Wesana Health (WSNAF), Zynerba (ZYNE) and 4Front Ventures (FFNTF).