Update: Entheon Acquires Genetic Testing Center and Discusses Upcoming Phase 1 Clinical Trial for DMT

Data-driven Approach to Treatment

Personalized genetic testing

Precision, personalized treatment is the future of medicine. Our ability to rapidly sequence the human genome is reducing the cost and time to identify abnormal genetic modifications (“polymorphisms”) that correlate with disease state and may influence treatment outcome. The Holy Grail of medicine is to develop treatments that are specific to a particular patient’s unique genetic make-up, reducing the occurrence and severity of side effects while maximizing the probability of treatment success. The goal is simple: identify a patient’s disease based on genetic and biomarker signatures and develop precise treatments that target their abnormalities. This is especially relevant in the field of psychiatry, where there is an extremely limited understanding of the physiology of mental illnesses, and treatment is as precise as throwing dirt on the wall and seeing what sticks.  

Entheon’s approach to delivering personalized psychedlic-assisted therapy involves screening patients for genetic markers that are known to play a role in mood regulation and may associate with an individual’s response to psychedelic-assisted therapy. The HaluGen genetic test kit (the “HaluGen Test”) was developed by Entheon’s wholly-owned subsidiary, HaluGen Life Sciences Inc, in collaboration with Lobo Genetics, a company that has engineered a genetic testing platform for THC and CBD. The HaluGen Test uses polymerase chain reaction (PCR) technology to identify specific genes known to correlate with emotional regulation and may play a role in mediating the effects of psychedelic compound. Relying on a non-invasive cheek swab, the test kit is returned to and processed by HaluGen's Toronto-based testing facility and a personalized genetic profile, with 5 sensitivity and risk reports, is sent directly to the patient. This genetic snapshot provides clinicians and patients insight into the sensitivity and risks associated with their individual psychedelic-assisted therapy plan.

“There's abundant evidence that characteristics such as levels of drug metabolism vary widely between individuals. There's also evidence that susceptibility to drug side-effects and perhaps even underlying responsiveness to drug therapy may also vary between patients. Bottom-line, we believe that one size does not fit all. Entheon believes that, by customizing or personalizing dosing, we can improve treatment success and contribute to helping more patients fight and overcome addiction. We are launching three new corporate programs focused on more effectively diagnosing, drugging, and monitoring mental health conditions implicated in addiction and substance use disorder: Entheon RX™, Entheon DNA™, and Entheon IQ™.”

~ David Mayoh, Entheon PR

Entheon’s triumvirate

Entheon’s approach to developing treatments and diagnostics for mental health diseases is unlike most pre-clinical, pre-revenue biopharmaceutical companies. The company is a hybrid between a direct-to-consumer laboratory testing company and a single-asset biopharmaceutical company pursuing clinical trials. What is very interesting about Entheon is that their approach to innovating the psychedelic treatment space creates a positive feedback loop. For example, the commercialization of their genetic test kit will provide the company with data that can be used to better predict a patient’s response to psychedelic compound treatment (like the company’s DMT compound), which in turn will enable Entheon to pre-screen candidates for their clinical trials. Once the safety of their DMT pharmaceutical is proven, then Entheon will be able to conduct a larger Phase 2 efficacy study to measure the dose-dependent effects of DMT on patients with addiction disorders. In theory, the design of this efficacy study could have multiple treatment arms, comparing “strong-responders” (i.e., patients that have genetic markers that suggest a positive response to psychedelic compounds) to “weak-responders”. Both treatment arms could then be compared to a placebo group to gauge the subjective response. The outcome of this study would not only provide strong, statistically significant efficacy data for DMT by excluding patients that are unlikely to respond at all, but also support the science behind their genetic test kit and be used to optimize future trials. Entheon’s data-driven approach involves collecting gene information from their HaluGen Test kit and measuring other related biomarkers, such as EEG scans, to better understand the link between an individual’s unique physiology and their response to psychedelic-assisted therapy.

3-pronged strategy:

1. Rapidly expand the market for their HaluGen Test, and make it the gold standard for pre-screening patients interested in psychedelic-assisted therapies (“Entheon DNA™" program)
2. Advance their synthetic DMT candidate as a treatment for addiction through the European Medicines Agency’s regulatory framework and get it approved for sale (“Entheon RX™" program)
3. Collect genetic and other biomarker data from patients undergoing treatment to create a predictive analytic model of the effects of psychedelic compounds in humans (“Entheon IQ™" program)

“Genetics can play an important role in how an individual responds to psychedelic-assisted psychotherapy. For example, the HTR2A gene mutation, carried by ~20% of the population, can impact how a person responds to serotonin, which is the primarily mechanism of action for serotonergic psychedelics such as psilocybin, LSD and DMT. Another gene, CYP2B6, can influence the metabolism of ketamine for the 10-20% of people that carry a specific CYP2B6 gene variant.”

~ Entheon press release, announcing commercialization of the HaluGen Test, on 4/6/2021

The HaluGen Test became available as a direct-to-consumer product on April 6 and June 10, 2021, in Canada and the US, respectively. Entheon’s genetic test is the 1st pre-screening genetic test for psychedlic-assisted therapies.

Spotlight on the HaluGen Test

Brand awareness through partnerships

Entheon’s commercialization strategy of the HaluGen Test involved partnerships with two industry leaders in the psychedlic-assisted therapy space. Earlier this year, Entheon entered into a referral agreement with Silo Wellness, a company offering psychedelic-assisted therapy retreats, to drive brand awareness to the HaluGen Test. Silo Wellness has retreats in Jamaica and Oregon that utilize a variety of psychedelic-assisted therapies to provide patients with an all-inclusive experience. The referral agreement will expand access and visibility for Entheon’s HaluGen Test.

On June 25, 2021, Entheon entered into a partnership with Maya Health, a company that has developed a measurement-based care platform designed to support psychedlic practitioners and patients. Maya’s platform brings together psychedlic practitioners, retreat facilitators, and ketamine clinicians to provide patients with “one-stop-shop” access to psychedelic-assisted therapies. Maya will promote the HaluGen Test kit to further their mutual goal of creating a data-based environment for clinicians and patients  to improve their treatment protocols and health outcomes.

"The commercial readiness of HaluGen's technology platform and genetic testing kit is an important achievement in executing our mission to developing tools that increase safety and outcome measures by screening patients for underlying psychiatric disorders prior to the administration of psychedelic molecules. We feel the widespread availability of this technology represents an important step forward, providing an additional layer of safety and confidence, widening the scope of patients and individuals who can feel confident accessing psychedelic medicines."  

~ Timothy Ko, CEO of Entheon

Stacking the bullpen

Entheon has attracted leading industry experts to their advisory board and management team; a good sign that the company is headed in the right direction and a vote of confidence for the existing management team. The company recently appointed 5 rockstars in the field to oversee their DMT clinical trial program, genetic/biomarker data acquisition and modeling, and the HalGuen Test kit commercialization strategy.

• Nancy Maher, previous executive and consultant for major pharma and IT companies (IBM, Gilead, Schering-Plough, Merck, Allergan, and Teva Pharmaceuticals), was appointed  as a Special Advisor of Data Science and Regulatory Affairs. Nancy will consult on development and implementation of Entheon's data management systems for collection and analysis of data from upcoming Phase 1 clinical trial.
• Dr. Brian Jahns was appointed  Chief Business Officer to develop a commercialization and post-market strategy for Entheon’s therapeutic protocols.
• Shimon Lecht, PhD (currently Chief R&D Officer at CannRX), was appointed as the preclinical project leader. Located in Israel, Dr. Lecht was the direct liaison with Science in Action, the Israeli-based CRO that conducted the 14-day in vivo toxicology study of DMT.
• Dr. Dinesh Bayana was appointed as a medical advisor for the company’s DMT clinical trial program. As a Board Member of MAPS Canada and with extended training and experience in the application of Ketamine-Assisted Psychotherapy, Dr. Bhayana is at the forefront of psychedelic medicine research and advancement. At Entheon, he will direct his expertise and medical background toward the future-medicalization of psychedelic-assisted psychotherapy with an emphasis on best practices, ethics, and accessibility.
• Dr. Andrew Greenshaw, Professor of Psychiatry and Neuroscience at the University of Alberta, was appointed as a scientific advisor. Dr. Greenshaw’s expertise in machine learning and data mining (in the context of computational psychiatry) will be leveraged to analyze the genetic and biomarker data that will soon become abundant as the HaluGen Test becomes mainstream and the company collects more human data in their clinical trials.

Lobos acquisition

On July 30, 2021, Entheon announced that it acquired Lobo Genetics in a stock deal. This purchase gives Entheon access to Lobo’s team of highly experienced experts in the fields of genetics, diagnostics, and analytics, as well as a fully operational 5,000 sq ft genetic research and testing facility in Mississauga, Ontario. Lobos also brings a network of distribution partnerships both domestically and internationally. A perfect strategic fit for Entheon’s market penetration and brand-awareness strategy.

"We are thrilled that the transaction with Lobo has successfully completed, and we very much look forward to working with the Lobo team toward our combined mission of researching a genetic-driven approach to developing personalized psychedelic-assisted psychotherapeutic (PAP) protocols to treat substance use disorders. With the acquisition of Lobo comes the addition of key staff members and enhanced expertise in the field of genetics. With increased capacity to screen patients, on a genetic basis, for underlying psychiatric disorders prior to undertaking PAP, Entheon is furthering its commitment toward safety and predictability in psychedelic therapies while aggregating data that can be used to determine which psychedelic molecules are best-suited for a particular patient."

~ Timothy Ko, Chief Executive Officer of Entheon

DMT as a Treatment for Addiction

Regulatory burden

Obtaining regulatory approval to begin a Phase 1 human clinical trial is a monumental achievement for a therapeutic class that is poorly studied. The regulatory agencies (FDA in the USA, EMA in the EU) pick apart the study design, pre-clinical data, and drug manufacturing documentation, looking for any reason to declare the company’s drug candidate unsatisfactory to be studied in humans. The design of the Phase 1 protocol itself is arduous; nothing can be left to chance, and consideration has to be given to the primary and secondary endpoints (typically safety and efficacy, respectively, in Phase 1 studies), the inclusion/exclusion criteria of the patient population, the number of patients (which has a significant impact on cost), the manufacturing and stability of the drug (which must be produced under Good Manufacturing Processes, a terribly costly and time-consuming effort), and the strength of the in vivo pre-clinical data to convince the regulatory body that your drug candidate has a good shot of working without side effects (and at the very least won’t kill anyone). Clinical-stage biopharma companies find themselves under immense pressure to accelerate their clinical trials and generate positive data, and investors often don’t realize the amount of preparation that goes into designing and conducting a single trial. Suffice to say, it is a big accomplishment when the nod is given to begin a Phase 1 clinical trial, and an indication that the company’s management is focused and capable of executing on a multi-year strategy. Entheon is on the verge of getting the thumbs-up from the European Medicines Agency, and has the GMP drug supply and key players needed to see proceed down the regulatory pathway to drug approval.

Entheon’s upcoming Phase 1 study

Entheon is well-positioned to begin a Phase 1 study in early 2022 as soon as their CTA is approved by the European Medicines Agency (EMA). Earlier this year, Entheon received ethics approval by Science in Action for their in vivo non-GLP toxicology study, which demonstrated that their DMT compound was safe in animals. The results of the study (acute toxicity of IV doses of DMT in a 14-day window) were used to design their upcoming Phase 1 study in humans, which is currently under review by the EMA.

• Entheon has acquired supply of GMP quality DMT from Laboratorium Ofichem BV, which will be used for all formulation, preclinical, clinical, and post-approval commercialization phases under the European medicines Agency’s regulatory process.
• The Phase 1 study will be conducted at Centre for Human Drug Research (CHDR) in the Netherlands.
• Entheon is preparing to submit the IMPD (Investigational Medicinal Product Dossier) + Investigator’s brochure in an EU Clinical Trial Application (CTA) to commence Phase 1 study at CHDR (Netherlands).
• They expect the Phase 1 clinical trial to begin in Q1 2022 once approval from the EMA is granted.
• The Phase 1 clinical trial will be used to evaluate the safety of a single dose of DMT administered continuously over 1 hour in healthy smokers, and to characterize the pharmacokinetics (absorption of the drug into the bloodstream, distribution of the drug throughout fluids and tissues, metabolism, and elimination of the drug from the body) after intravenous injection over that time period.
• The secondary endpoint of the Phase 1 study is to establish the minimum dose of DMT required to produce a moderate subjective psychedelic effect. The study will also be used to determine infusion rate of DMT required to maintain steady-stage psychedelic effects.

What to watch for:

• Acceptance of the Phase 1 Investigator Brochure by the EMA
• Initiation of the Phase 1 study in early Q1 2021 to determine the pharmacokinetics (PK) and safety of DMT injected intravenously
• Publication of Phase 1 result on clinicaltrials.gov
• Rapid expansion of HaluGen Test kit into the market
• Acquisition of genetic and biomarker data to develop a predictive analytic model of the effects of DMT on brain function/emotional regulation
• A Phase 2 efficacy study in 2023 to determine the dose-dependent effects of DMT on addiction

About Entheon Biomedical

Entheon Biomedical (CSE:ENBI) is a biotechnology research and development company that has developed a proprietary portfolio of N,N-dimethyltryptamine-based (DMT) psychedelic therapeutic products (“DMT Products“) for the treatment of addiction and substance use disorders. The company’s pre-clinical toxicology and pharmacokinetic studies showed promising safety results, and will be included in the Clinical Trial Application submitted to the European Medicines Agency prior to their Phase 1 study (Q1 2022). In addition to advancing their DMT Products through the regulatory process, the company has successfully commercialized a personalized, genetic screening approach to glean insights into optimal dosing and predicted efficacy of their psychedlic compounds (the “HaluGen Test”). Subject to obtaining all requisite regulatory approvals and permits, Entheon intends to generate revenue through the sale of its DMT Products and HaluGen Test to physicians, clinics, and licensed psychiatrists in the United States, the European Union, and throughout Canada.

About Lobo Genetics Inc.

Lobo Genetics is a Toronto-based arm's length private corporation incorporated on June 11, 2018 under the CBCA. Lobo is a personalized genetics company with a direct-to-consumer platform currently being used in both the psychedelics and cannabis space to provide personalized insights into an individual's response to hallucinogenic and psychoactive drugs. The company's core mission is to enable patients to better understand and predict their unique response to cannabis through genetics, data, and engagement. Through their proprietary genetic testing platform, the Lobo Cube, consumers can gain rapid genetic insights from a simple cheek swab, enabling both the patient and clinicians to optimize their treatment program.