PharmaTher repurposes drugs to treat neurological disorders
Psychedelic Pharmaceuticals
PharmaTher Holdings Ltd. -- a clinical-stage psychedelics biotech -- is currently conducting an FDA approved phase 2 clinical study with ketamine to treat Parkinson’s disease. The company, which focuses on the research, development and commercialization of novel uses, formulations and delivery methods of psychedelics to treat mental illness, neurological and pain disorders, is developing a novel microneedle patch for the intradermal delivery of psychedelics. Commencing trading in 2020, the Vancouver-based psychedelics company repurposes psychedelic pharmaceuticals for FDA approval to treat disorders of the brain and nervous system.
In June PharmaTher filed a pre-Investigational New Drug (“pre-IND”) meeting request and complete pre-IND briefing package with the U.S. Food and Drug Administration (“FDA”) to support the clinical development of KETABET™ and the proposed Phase 2 clinical study as a potential next-generation treatment for depression. The company and the agency also discussed the product development plan for the company’s patented hydrogel-forming microneedle patch delivery technology.
According to PharmaTher, KETABET™ has the potential to receive FDA approval under the 505(b)(2) regulatory pathway and Fast Track designation by the FDA for treatment in patients with major depressive disorder. The company said that the hydrogel-forming microneedle patch offers a novel way to deliver ketamine and other psychedelics such as psilocybin, DMT, MDMA and LSD, and has the potential to improve on the safety (i.e. fewer side effects), efficacy (i.e. bioavailability, optimized dosing regimen including continuous system delivery) and compliance (i.e. storage, distribution and self-administration) of these psychedelics that currently must be taken orally, inhaled, injected and intravenously.
As Fabio Chianelli, chief executive officer of PharmaTher, explained, “We have an insatiable focus on developing and commercializing novel uses, formulations and delivery forms of ketamine. We are committed to solving the ketamine puzzle and unlocking its true potential to treat depression by leveraging our robust intellectual property portfolio, clinical and regulatory experience, and our recently approved IND by the FDA to evaluate ketamine to treat Parkinson’s disease in a Phase 2 study. We are now in a position to lead the way in reviving ketamine and KETABET™ as a potential FDA-approved prescription-based therapy for mental health, neurological and pain disorders.”
More than 300 million people suffer from major depressive disorder, and 100 million people are resistant to available treatments worldwide. Ketamine is emerging as a viable treatment option for depression. Recent clinical studies have shown that low dose ketamine produces a rapid-acting and sustained antidepressant effect in major depressive disorder, bipolar depression, depression with suicidal ideation and post-traumatic stress disorder. Despite this, the potential for abuse and misuse of ketamine and the adverse mental effects of ketamine has resulted in its limited clinical use and discontinuation.
KETABET™, a patented combination formulation of FDA-approved ketamine and betaine anhydrous, has been shown in research to enhance the antidepressant effect while having the potential to reduce the known negative side effects of ketamine significantly. Side effects such as hallucinations, confusion, memory loss and abuse liability compromise the compliance and potential therapeutic value of ketamine. The combination of ketamine and betaine anhydrous produced more robust antidepressant-like responses than their individual effects and that the combination blocked the psychotomimetic effects of ketamine. This suggests that betaine anhydrous can be considered as an add-on therapy to ketamine or as a fixed-dose combination therapy for treatment-resistant depression, treatment-resistant bipolar disorder, post-traumatic stress disorder, obsessive-compulsive disorder and chronic pain.
Betaine anhydrous (CYSTADANE®) was approved by the FDA in 1996 to treat homocystinuria to decrease elevated homocysteine blood concentrations. There is growing evidence that betaine plays a critical role in regulating brain functions and has an antidepressant-like effect. Betaine has been reported to prevent seizures in rodents, to improve symptoms of Rett syndrome, and to delay the onset of neurologic impairment due to vitamin B12 deficiency10 clinically. Furthermore, betaine attenuates memory deficits induced by homocysteine.
The pre-IND briefing package included a discussion of the product development plan for the patented hydrogel-forming microneedle (“MN”) patch to deliver ketamine and KETABET™ for intradermal administration to treat various mental health, neurological and pain disorders. The MN patch consists of hydrogel-forming microneedle arrays and an accompanying reservoir that will overcome limitations by the quantity of drug loaded into the needles or onto the needle surfaces. As such, the MN patch can significantly increase the amount of drug that can permeate through the microneedle array and into the skin. The MN patch is specifically tailored for ketamine and KETABET™ because of the volume of drug that is required to maximize their therapeutic utility and increase potential market opportunities.
PharmaTher’s proposed MN patch was successfully validated in a proof-of-concept study in delivering esketamine, the S(+) enantiomer of ketamine, which may overcome the drawbacks of ketamine administration in an intravenous or nasal spray format. The KETABET™ MN patch attempts to empower patients to dose their medication remotely, safely and conveniently rather than being supervised by a healthcare provider at a certified medical office. KETABET™ MN patch has the potential for enabling continuous delivery of KETABET™ (without pain) with minimal formulation manipulation into systemic circulation while maintaining constant plasma levels for more than 24 hours that will improve efficacy and compliance for patients.12-13 Also, PharmaTher's KETABET™ MN patch will incorporate anti-tampering and anti-abuse features that parallel the approach used by commercially available tamper-resistant transdermal fentanyl patches.
Ketamine was approved by the FDA in 1970 and is clinically used for analgesia, sedation, and anesthetic induction. The FDA granted Fast Track and Breakthrough Therapy designations for SPRAVATO® (esketamine) nasal spray and in March 2019 approved SPRAVATO®, in conjunction with an oral antidepressant, for treatment-resistant depression to Janssen Pharmaceuticals, Inc. SPRAVATO® requires numerous administration sessions in a certified medical office under medical supervision by a health care provider.14 An equity analyst predicted that SPRAVATO® could generate $3 billion in peak sales.15
According to Chianelli, “We are well-positioned, both financially and operationally, to execute on our remaining milestones for 2021, which includes completing a Phase 2 study with ketamine to treat Parkinson’s disease, a Phase 2 study with KETABET™ for treatment-resistant depression, and the development of our novel microneedle patches for delivering psychedelics such as ketamine, psilocybin, DMT, MDMA and LSD. The recent FDA acceptance of our IND to proceed to a Phase 2 study in Parkinson’s disease will pave the way for us to confidently submit future IND’s and advance clinical studies evaluating novel uses, formulations and delivery forms of psychedelics to treat various mental health, neurological and pain disorders.”
Following the FDA acceptance of the company’s investigational new drug application to proceed with a Phase 2 clinical trial to evaluate the safety, efficacy and pharmacokinetics of ketamine in the treatment of levodopa-induced dyskinesia in patients with Parkinson’s disease, PharmaTher has begun clinical trial start-up activities to begin enrolling patients in Q3-2021 and to announce clinical results in Q4-2021. Assuming that the Phase 2 clinical trial is positive, the company will request a meeting with the FDA to discuss its plan and obtain an agreement to move to a Phase 3 clinical study under the 505(b)2 regulatory pathway in 2022.
Following PharmaTher’s recent submission to receive orphan drug designation for ketamine to treat ALS, the company is working with its clinical advisors in finalizing a proposed Phase 2 study design. The objective is to request a pre-IND meeting with the FDA in Q3-2021 and submit the IND in Q4-2021. PharmaTher has an exclusive license agreement with the University of Kansas for the intellectual property protecting the potential use of ketamine to treat ALS, which was discovered by Dr. Richard J. Barohn, M.D., John A. Stanford, Ph.D., and Dr. Matthew Macaluso, D.O. Preclinical research has shown that the administration of ketamine preserves muscle function in advancing ALS and increases life expectancy when given in the early stages of muscle decline.
For the second half of 2021, PharmaTher will focus on working with its research and development partners to advance next generation microneedle patches for the delivery of psychedelics. The company is working with Professor Ryan Donnelly under a research agreement with The Queen’s University of Belfast to finalize the patented hydrogel-forming microneedle patch development to deliver ketamine and KETABET™. The research leverages the successful proof of concept achieved in delivering esketamine, the S(+) enantiomer of ketamine, via the microneedle patch, which may overcome the drawbacks associated with ketamine administration in an intravenous or nasal spray format. Validation and tech transfer to support clinical studies will be completed in Q4-2021.
The company is working with the Terasaki Institute, led by Dr. Ali Khademhosseini, under a research agreement to finalize the development of a proprietary microneedle delivery system comprised of a biocompatible and biodegradable gelatin methacryloy (“GelMA”) composite for use with psychedelics such as psilocybin, DMT, MDMA and LSD. The GelMA patch delivery system is the driving force of the Company’s psychedelics microdosing program. It is expected that validation results in delivering these psychedelics will be completed in Q4-2021.
In the last month, PharmaTher stock has rocketed from $0.19 CAD to $0.81 CAD, a 326 percent increase. The price jump may or may not be sustainable, but it has piqued interest.