Enveric Biosciences Inc(NASDAQ: ENVB) is an early-development-stage biosciences company developing next-generation mental health and oncology treatments using its clinical discovery platform to help leverage psychedelic-derived molecules for the mind and synthetic cannabinoids for the body. The Company seeks to improve the lives of patients suffering from cancer, initially by developing palliative and supportive care products for people suffering from certain side effects of cancer and cancer treatment such as anxiety, depression, pain, and skin damage from radiation treatment. Enveric currently intends to offer such palliative and supportive care products in the United States, following approval through established regulatory pathways.

Enveric acquired MagicMed; a Company that develops and commercializes psychedelic-derived pharmaceutical candidates.MagicMed’s psychedelic derivatives library, the Psybrary™, is an essential building block from which industry can develop new patented products. The initial focus of the Psybrary™ is on psilocybin and DMT derivatives, and it is then expected to be expanded to other psychedelics.

Following the MagicMed acquisition the Company continued to pursue the development of MagicMed’s proprietary psychedelic derivatives library, the Psybrary™ which the Company believes will help it identify and develop the right drug candidates needed to address mental health challenges, including cancer-related distress. Enveric synthesize novel versions of classic psychedelics, such as psilocybin, N-dimethyltryptamine (DMT), mescaline and MDMA, using a mixture of chemistry and synthetic biology, resulting in the expansion of the Psybrary™, which includes 15 patent families with over a million potential variations and hundreds of synthesized molecules. Within the Psybrary™ there are three different types of molecules, Generation 1 (classic psychedelics), Generation 2 (pro-drugs), and Generation 3 (new chemical entities). The Company is working to add novel psychedelic molecular compounds and derivatives (“Psychedelic Derivatives”) on a regular basis through its work at Enveric Labs in Calgary, Alberta, Canada, where it has a team of PhD scientists with expertise in synthetic biology and chemistry. To date Enveric has created over 500 molecules that are housed in the Psybrary.

Enveric screens newly synthesized molecules in the Psybrary™ through PsyAI™, a proprietary artificial intelligence (AI) tool. Leveraging AI systems is expected to reduce the time and cost of pre-clinical, clinical, and commercial development. Management believes it streamlines pharmaceutical design by predicting ideal binding structures of molecules, manufacturing capabilities, and pharmacological effects to help determine ideal drug candidates, tailored to each indication. Each of these molecules that ENVB believes are patentable can then be further screened to see how changes to its makeup alter its effects in order to synthesize additional new molecules.New compounds of sufficient purity are undergoing pharmacological screening, including non-clinical (receptors/cell lines), preclinical (animal), and ultimately clinical (human) evaluations. ENVB intends to utilize its Psybrary™ and the AI tool to categorize and characterize the Psybrary™ substituents to focus on bringing more psychedelics-inspired molecules from discovery to the clinical phase.

ENVB is looking to help solve cancer related distress for millions of patients.

Enveric is working with the University of Calgary’s Hotchkiss Brain Institute (“HBI”) to establish a groundbreaking clinical trial of EVM-101 for the treatment of Cancer Related Distress (“CRD”). Better still, Enveric is discovering and developing more effective treatments for cancer patients living with psychological distress and is currently working on three classes of new medicines: EVM-101, a first-generation oral psi-lo-cybin; EVM-201, a second-generation pro-dr-ug; and EVM-301, a third-generation psych-e-delic-inspired and optimized new molecule. ⁽¹⁸⁾

Enveric is also aiming to advance a pipeline of novel cannabinoid combination therapies for the side effects of cancer treatments, such as chemotherapy and radiotherapy. The Company intends to bring together leading oncology clinicians, researchers, academic and industry partners to develop both external proprietary products and a robust internal pipeline of product candidates aimed at improving quality of life and outcomes for cancer patients.

Enveric owns full rights to 16 patent applications related to psychedelics. Of those, 10 patent applications relate to psilocybin derivatives, methods of making psilocybin derivatives, and methods for treatment of mental disorders, such as cancer-related distress, PTSD, and other psychiatric conditions; 1 patent application relates to prodrugs of psilocin; and 5 patent applications related to mescaline derivatives and methods of using mescaline derivatives. 

ENVB Exclusive Supply Agreement

Enveric entered into an exclusive supply agreement with PureForm Global, Inc., a biotechnology company focused on the research, development, and commercialization of synthesized CBD and other cannabinoids not derived from hemp or cannabis, for use in development and commercialization of products for cancer supportive/palliative care associated with radiodermatitis, chemotherapy induced peripheral neuropathy, and glioblastoma. Pursuant to the Development and Clinical Supply Agreement, PureForm will be the exclusive provider of synthetic Cannabidiol for Enveric’s development plans for cancer treatment and supportive care. Under the terms of the Development and Clinical Supply Agreement, PureForm has granted Enveric the exclusive right to purchase Synthetic Cannabidiol and related products for cancer treatment and supporting care.

Enveric current academic and industry partners include Tikun Olam Ltd.,  St. George’s University of London, The Soroka Medical Cancer Center, and the University of Calgary.

Enveric is currently working to advance a pipeline of novel cannabinoid combination therapies for hard-to-treat cancers, including glioblastoma multiforme (GBM) and several other indications. For the treatment of Glioblastoma Multiforme (GBM), ENVB believes only one drug product (Epidiolex, developed by GW Pharmaceuticals) is a potential late-stage competitor to its GBM product candidate, EV101: Cannabinoid + Chemotherapy Combination Therapy. Other than Epidiolex, the Company is aware of exploratory research into the effects of cannabinoid drug formulations. Enveric is also aware of discovery research within the pharmaceutical industry into synthetic agonists and antagonists of CB1 and CB2 receptors, as well as companies that supply synthetic cannabinoids and cannabis extracts to researchers for pre-clinical and clinical investigation, and various companies that cultivate cannabis plants with a view to supplying herbal cannabis or non-pharmaceutical cannabis-based formulations to patients. These therapies have not been approved by the FDA.

Patients suffering from GBM in the U.S. are treated with a variety of FDA-approved products, including, but not limited to, Bevacizumab, Carmustine Implant, Lomustine, and Temozolomide. Enveric potential competitors regarding the GBM product candidate include pharmaceutical and biopharmaceutical companies such as Pfizer, Genentech, Arbor Pharmaceuticals, Next Source Pharmaceuticals, and Merck, among others, depending on when the candidate is approved for commercialization.

Enveric radiation dermatitis (also referred to as radiodermatitis) product candidate, EV102: Cannabinoid Cream for Topical skin Application, faces competition from Lutric Pharma, which has a topical B-Raf Inhibitor in Phase 1/2 studies that is intended to treat radiation dermatitis.

ENVB Released news today:

Enveric Biosciences Advances Drug Development for Mental Health Indications and Intellectual Property Portfolio 

— Advancing to IND-enabling studies with multiple drug candidates — 

— Enveric’s Growing Patent Portfolio Validated — 

CAMBRIDGE, Mass., July 13, 2022–(BUSINESS WIRE)–Enveric Biosciences, Inc. (NASDAQ: ENVB) (“Enveric” or the “Company”), a neuroscience-focused biotechnology company developing next-generation, psychedelic-inspired mental health medicines, today revealed drug discovery and development progress targeting mental health indications and intellectual property (IP) advances achieved during the first half of 2022. 

“The first half of 2022 was foundationally successful for Enveric. We validated and executed on the corporate premise that we can deploy PsyAITM, our proprietary artificial intelligence tool, and PsybraryTM, our expanding proprietary portfolio of new chemical entities and drug candidates, to design and improve upon new drug molecules inspired by legacy psychedelic drugs,” said Dr. Joseph Tucker, PhD, Enveric’s Chief Executive Officer. 

“Enveric is pleased to advise that our predictions have materialized, and our platforms have successfully generated a large number of promising new molecules that have successfully passed primary screening and moved on to lead optimization, providing us with a strong slate of drug candidates. Our leading program, EVM-201, includes a number of new molecules currently in lead optimization that are geared towards providing improved characteristics and drug-like properties compared with psilocybin. The successful outcomes from our testing efforts completed in the first half of 2022 have positioned the company very well to advance our drug candidates towards the clinic,” continued Dr. Tucker. 

Clinical-Need Driven 

Based on extensive direct clinical understanding of the current unmet needs in anxiety, depression, PTSD, and other mental health indications, coupled with in-depth knowledge of the current treatment landscape, Enveric’s Clinical Team is well positioned to tackle the challenges ahead, while aiming to shepherd novel new treatments for a host of mental health indications. 

Enveric’s Clinical Team is led by a past Board-certified psychiatrist and clinical trialist Chief Medical Officer, Dr. Bob Dagher, MD. Dr. Dagher joined Enveric in December 2021, bringing a wealth of clinical trial management and new CNS-drug development experience from his past roles, including at WCG, Cadent, Covance, Sanofi and GSK, in addition to his first-hand experience in treating patients from his previous clinical practice in psychiatric medicine. 

Next-Generation Drug Discovery 

Enveric’s Discovery Team, spearheaded by Chief Innovation Officer Dr. Peter Facchini, PhD, an international leader in natural product biochemistry and biotechnology, completed the rational design of more than 300 Generation-2 (“Gen-2”) psilocin prodrug candidates using well-established design strategies, but adapted to the unique structure of psilocin. 

The 300 Gen-2 original concept designs, now housed within the PsybraryTM, were screened using PsyAITM. The assessment helped predict chemical structures with appropriate receptor binding, toxicology, and pharmacokinetic profiles that would trigger the desired mechanisms of action while reducing undesirable side effects, and the initial candidate evaluation included, among other metrics, prodrug-likeness, toxicity, ease of chemical synthesis and degree of IP-white space surrounding the molecule. 

Ranked scoring of these and other AI assessments, as well as commercial considerations (e.g., ease of procuring synthetic starting materials), prioritized 31 novel Gen-2 molecules that have been synthesized in sufficient quantities (~10 mg, 95% purity) for preliminary pharmacological screening. Enveric’s Chemistry Group, led by Dr. Kaveh Matinkhoo, PhD, completed these syntheses, 29 of which were deemed stable enough to advance. 

Deep-dive chemical structure searches, patentability, and freedom-to-operate reviews were performed on all 29 candidates, under the leadership of Lead Internal Counsel C. Michael Gegenheimer. All the patentability analyses indicated potential patentability results, and 25 of the 29 molecules presented minimal concern with freedom to operate. 

To strengthen the IP protection for the overall Gen-2 prodrug program, three provisional patent applications, covering 7 structurally diverse clinical classes and thousands of additional potential new drug candidates, have been filed so far in 2022, and additional provisional and PCT filings are expected to continue throughout the year. 

In other IP developments, an additional three of Enveric’s international patent applications protecting tryptamine derivatives have been published by the World Intellectual Property Organization, bringing the total published so far to seven. 

EVM-201 Drug Candidate Testing 

Following the initial Gen-2 ideation, patent filing, synthesis, and screening efforts, more extensive assays were performed on the advancing drug candidates. Numerous internal assays were performed under the leadership of Dr. Jill Hagel, PhD, Vice-President of Innovation and Dr. Sheetal Raithatha, PhD, Director of Research and Development. The internal results were then confirmed and validated using leading independent, third-party Contract Research Organizations (CROs), covering 122 Toxicology tests, 72 receptor-binding and potency tests, 31 pharmacokinetic tests and 24 animal-model tests to provide ample information to support candidate nomination. 

The synthesis and analysis of these comprehensive pharmacology and toxicology datasets, both internal and external, was led by Dr. Kevin Leach, PhD DABT, Vice President of Preclinical and Translational Research. Enveric is now moving towards lead-candidate nomination and, in preparation for IND filing, has initiated numerous IND-enabling studies on several of the leading candidates at third-party CROs. 

Recognizing the need for stable drugs with robust, reproducible, and cost-effective manufacturing, several Contract Development & Manufacturing Organizations (CDMOs) are currently engaged with Enveric’s Chemistry Team to determine how best to manufacture our molecules. Enveric has plans in place to produce material at commercial facilities and the CDMO personnel have worked with our chemists to validate that our processes will work at their facilities. This is another necessary step prior to filing the IND. Finally, preliminary formulation work is underway, with a particular focus on enabling improved routes of administration. 

“The first half of the year has indeed been busy and productive for the dedicated team here at Enveric. We are all very excited at how those efforts have begun to bear fruit. We look forward to advising our shareholders of further key developments, which we anticipate will continue to unfold during the remainder of 2022,” concluded Dr. Tucker. 

Enveric Biosciences Reports Full-Year 2021 Financial Results and Provides Business Update 

NAPLES, Fla., March 31, 2022 /PRNewswire/ – Enveric Biosciences Inc. (NASDAQ: ENVB) (“Enveric” or the “Company”), a neuroscience-focused biotechnology company developing next-generation, psychedelic-inspired mental health medicines, today reported its financial results for the full year ended December 31, 2021, and provided a business update. 

“2021 was a foundational year that set the stage for Enveric to execute on its strategy in the future,” said Dr. Joseph Tucker, Enveric’s Chief Executive Officer. “With the acquisition of MagicMed in September 2021, we immediately began moving forward with the clinical development strategy of our next-generation treatments and therapies for mental health. We find ourselves strategically positioned with an experienced team of industry professionals, collaborative partners including the University of Calgary, a growing intellectual property portfolio, and a robust Central Nervous System pipeline of promising drug candidates. As we build upon the three core pillars of our success, Drug Development, Drug Discovery, and Intellectual Property, we are focused on creating effective mental health medicines.” 

Corporate Updates During and Subsequent to the Fourth Quarter 2021: 

Clinical Trials 

Announced collaboration with the University of Calgary on a groundbreaking clinical trial for EVM-201 in cancer-related distress. A clinical trial, expected to launch in 2023, of EVM-201, a second-generation psychedelic treatment, for Cancer Related Distress will be led by HBI researcher, Dr. Valerie Taylor, Head of the Department of Psychiatry, in Calgary, Canada. 

Announced positive preclinical data for EV102 radiodermatitis drug candidate. EV102 has demonstrated a significant and meaningful reduction in dermatitis severity, skin redness, and duration in a preclinical rodent model. 

PsyAITM, an artificial intelligence platform, successfully identified viable psychedelic molecules for further drug discovery from Enveric’s initial list of 500 psychedelic molecular compounds within its “Psybrary.” We believe it is a first of its kind to employ this machine-learning technology against an extensive psychedelic molecule library to evaluate higher-likelihood molecules that treat conditions that include cancer-related distress, PTSD, and other central nervous system (CNS) indications. 

IP Portfolio 

Filed and published four patent applications for psychedelic-inspired drug candidates by the World Intellectual Property Organization (WIPO). The four patent applications are focused on the tryptamine family of novel molecules. 

Filed its 10th Patent Cooperation Treaty (PCT) patent application directed to tryptamine-based derivative molecules, completing the Company’s broad series of PCT applications covering this family of compounds. 

Successfully synthesized and filed a provisional patent for EV104, the Company’s cannabinoid, and celecoxib conjugate. EV104a and EV104b are the Company’s new molecular conjugates for Osteoarthritis (“OA”) and other pain indications. 

Filed an additional provisional patent application based on new discoveries by the company. The patent application and claimed drug candidates fall into the Company’s EVM201 second-generation, psychedelic-derived drug development program. 

Leadership Team 

Appointed Bob Dagher, MD, as Chief Medical Officer. Dr. Dagher is a Board-certified neurology and psychiatry physician, bringing over 15 years of clinical experience and extensive therapeutic knowledge in the neuroscience space. 

Capital Markets 

Closed a $10 million public offering. The Company intends to use the net proceeds from this offering for working capital and to fund other general corporate purposes. 

Included in the new AdvisorShares Psychedelics ETF, trading under the ticker symbol “PSIL” on the NYSE Arca exchange. PSIL is an ETF that focuses on investments in biotechnology, pharmaceutical, and life sciences companies that are leading the nascent but advancing psychedelic industry. 

Financial Results for the Full Year Ended December 31, 2021: 

Comprehensive net loss was $48.8 million for the year ended December 31, 2021, including $36.3 million in net non-cash expenses, with basic and diluted loss per share of $2.07, as compared to a comprehensive net loss of $7.0 million with basic and diluted loss per share of $1.19 per share for the year ended December 31, 2020. 

Net cash used in operations for the year ended December 31, 2021, was $11.5 million consisting of the net loss, adjusted by a net of $36.3 million in non-cash expenses and changes in asset and liability balances of $1.2 million. 

As of December 31, 2021, the Company had cash and cash equivalents of $17.4 million and working capital of $15.3 million. Subsequent to December 31, 2021, the Company raised an additional $10 million and expects to use the funds to help advance its new drug discovery platform, robust IP portfolio, and a growing pipeline of promising drug candidates.