PharmAla Biotech: Bringing MDMA To A Clinic Near You

More Than A Party Drug

MDMA

MDMA (3,4-methylenedioxymethamphetamine, also known as "Ecstasy" and "Molly") is a psychoactive stimulant that is notorious for its recreational use at concerts and "raves". Acting as a potent releaser and reuptake inhibitor of serotonin (5-HT), dopamine, and norepinephrine, MDMA promotes nervous system stimulation and gives the user increased energy, but also has distinct effects unrelated to other substances within the same class. These unique effects include a profound sense of "closeness" to others, which can facilitate the development of interpersonal relationships, increased empathy, and intense euphoria. While the clinical benefits for treating mental disorders (such as PTSD, the most well studied disease indication for MDMA thus far) are becoming more well defined, MDMA is also associated with dangerous side effects such as hyperthermia, hyperreflexia, muscle rigidity, and increased blood pressure and heart rate. Clearly, MDMA has the potential to be a powerful treatment for depressed, anxious, and trauma-ridden patients, but empirical clinical trial evidence that establishes a safe and effective dose range must first be attained (see section below).

Learn more about the field of medical psychedelics.

Research and development

MDMA was first synthesized by a Dr. Anton Köllisch, who worked for the German pharmaceutical company Merck, in 1912. Interestingly, the MDMA was produced a by-product while trying to synthesize hydrastinin for blood clotting. Merck quickly filed a method of preparation patent which was granted in 1914, but no follow up work was done and MDMA never entered clinical studies.

Originally known as methylsafylaminc, MDMA gained interest among psychiatrists in the 1970s and early 1980s (despite lack of regulatory approval) due to its ability to enhance communication and allow patients to achieve insights into their traumas (likely due to the overall sense of well-being and decreased fear response that MDMA facilitates, allowing for confrontation of anxiety-inducing issues). The DEA banned MDMA in 1985, placing it on the Schedule 1 list of narcotics, where it has stayed ever since.

MDMA research picked back up in the late 1990s and has been primarily explored as a treatment for PTSD. Recently, the Multidisciplinary Association For Psychedelic Studies (MAPS) completed a Phase 3 study of MDMA in PTSD patients. The results were astounding, confirming the positive results of MAPS' pilot Phase 3 in which 88% of participants responded to the treatment and robust attenuation of CAPS-5 score (Clinician-Administered PTSD Scale for DSM-5) was observed with MDMA (P < 0.0001, d = 0.91) and significant decrease in SDS (Sheehan Disability Scale) total score (P = 0.0116, d = 0.43).

Market Forecast

Indications of interest

MDMA has been granted breakthrough designation by the FDA, and the Phase 3 data from MAPS' PTSD study will be released later this year. MDMA is also under evaluation as a treatment for couples therapy, eating disorders, alcohol addiction, anxiety, and depression. This represents a multi-billion dollar opportunity in North America alone.

Regulatory catalysts

• FDA approval of MDMA for the treatment of PTSD (MAPS study) later this year will serve as a major industry catalyst.
• On July 1, 2023, The Australian Therapeutic Goods Agency (TGA) will allow MDMA and psilocybin to be prescribed to patients suffering from PTSD and treatment-resistant depression, respectively, under the Authorized Prescriber Scheme.
• Health Canada is currently reviewing MDMA clinical trial procedures to ensure patient safety.

Solving the supply crisis

There is a growing need for GMP-grade MDMA for clinical research and patient care. PharmAla is positioned to capture the commercial MDMA manufacturing market by leveraging its pre-existing infrastructure and relationships formed as the largest supplier MDMA to clinical trial sites in AU. Its materials have already been approved by Human Research Ethics Committees (HRECs) in several major universities within Australia, allowing it to be used in human clinical studies.

MDMA-assisted psychotherapy is expected to cost USD $10,000-$15,000 per 3-month course, with the drug representing $1,500 of the total cost. While the therapy is likely to be covered by insurance, the MDMA drug product will remain an out-of-pocket expense for the foreseeable future. PharmAla expects the North American, Caribbean, and European markets to add to their revenues in exponential fashion over the next three years (see figure below). The company estimates USD$350,000 in clinical trial supply revenues for 2023, and the European and Caribbean markets to add an additional USD $1-2M to their top line. PharmAla is also the exclusive global broker for MindSet’s GMP psilocybin drug product, offering potential revenues of up to CAD $250K in 2023.

More Than A Manufacturer

PharmAla's innovation

PharmAla has two families of new chemical entities (NCEs), the ALA and ABA Families of proprietary, MDMA analogs. The ALA family consists of three NCEs that have an MDMA-like efficacy profile but improved toxicology and reduced adverse events compared to the base (generic) MDMA molecule. These patented MDMA analogs are expected to enter clinical trials in late 2023.

PharmAla’s second family of NCEs, the ABA family, also have shown significant toxicology benefits and are not considered controlled substances in many jurisdictions. These patent-protected, novel compounds are in the preclinical proof-of-concept stage, and appear to have an improved neurotoxicity profile. Additionally, the company leveraged their expertise in computational chemistry to design “PharmAla-1”, which is anticipated to trigger neuronal growth through exceptional target binding.

MDMA and autism

The company’s lead drug candidate, ALA-002, has demonstrated significantly improved cardio- and neuro-toxicity profiles compared to MDMA in animal model of autism. These improvements, in addition to a significant reduction in hyperthermia, solve the three major adverse events associated with MDMA. PharmAla expects to move directly into a Phase 2 as an Investigational New Drug (IND) opening study (i.e., first-in-human clinical trial) based on the improved safety profile of ALA-002.

ALA-002 has also shown to be exceptionally effective in improving sociability in autism mouse models. PharmAla intends to pursue social anxiety in an autistic sub-population, as the efficacy of racemic MDMA has already been proven for this indication in a Phase 2 clinical study.

A Stock On The Rise

MDMA (Daily)

MDMA shares staged a meteoric rise from the end of December 2022 until the first week of May. A correction back to important support near $.30 has been completed, and price remains in a longer term uptrend above a rising 50-day moving average. A consolidation on lighter trading volume could be expected over the next 1-2 weeks.

Upcoming catalysts

3Q23

• Patent review for ALA and ABA new chemical entity families
• First AU treatments in the clinic with PharmAla manufactured MDMA
• Meeting with international regulators to present preclinical research on ABA001-003.
• Submission of patents for 2nd generation drug candidates

4Q23

• Launch of ALA clinical study of ALA-002 as a treatment for social anxiety in autism sub-population
• Publication of 2nd generation drug candidate patents
• Initiation of drug delivery workstream
• Preprint publication of relative toxicology of ALA001-003
• Drug product encapsulation completed

Financials

The company had CAD $731,000 in cash in its treasury as of the end of February, this makes a financing likely at some point in the next couple months.

Led By Industry Veterans

Executive management

Board of directors

Scientific advisory board

Disclosure

MedicalGold has no relationship with PharmAla Biotech and the author has no position in MDMA shares at the time of publishing. The article is presented for informational and entertainment purposes only and is not a recommendation to buy or sell any security