PharmaDrug Inc. (CSE: PHRX) (OTCQB: LMLLF), a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs, is pleased to announce that in collaboration with the Terasaki Institute for Biomedical Innovation (TIBI), it has successfully completed fabrication of a novel medical device capable of delivering sustained, low (sub-psychedelic) quantities of their undisclosed tryptamine-based pharmaceutical to the front of the eye; the intended purpose of which is to potentially lower intraocular pressure (IOP) in patients suffering from glaucoma. Additionally, a head-to-head drug elution study of the Company’s three undisclosed DMT-analogue candidates has now been completed and supportive cell-based biocompatibility has been examined for all three candidate molecules. Future in vivo efficacy testing in an accepted model of primary open angle glaucoma (POAG) is currently being planned with the goal of providing all necessary support to file an investigative new drug (IND) application with the United States Food and Drug Administration (the “FDA”) to conduct clinical studies.

“We are excited to announce that our recently fabricated proprietary medical device, designed to deliver controlled release of tryptamine-based pharmaceutical agents, has now progressed from the concept stage into a functioning prototype. Drug release rates were successfully characterized for each of the candidates under evaluation and as such, the current studies provide the Company with the critical data necessary to fine-tune fabrication efforts while also facilitating informed design for its future IND-enabling efficacy studies which will use a well accepted animal model of glaucoma”.

Paul Van Slyke, CSO of PharmaDrug

The aim of PharmaDrug’s DMT-analogue research program in ocular health is to develop suitable prototype medical devices capable of sustained ocular drug-delivery while also confirming efficacy, biocompatibility and stability of its candidate molecules in models of elevated IOP. Previous press releases (Feb 23, 2022, and Dec 13, Nov 5, Aug 5, 2021) have provided updates on in vitro potency, surrogate markers of efficacy and safety/toxicity. With today’s announcement the Company is pleased to deliver on several additional key objectives-namely, fabrication of its drug eluting medical device and in vitro biocompatibility test results. The research program scope currently underway includes full establishment and demonstration of candidate molecule loading capacity, release rate evaluations for conjugated materials as well as model organism testing to support an IND application with the FDA in the future.

The Company has now completed fabrication and initial testing of its novel medical device designed to deliver therapeutic quantities of its DMT-analogues to the front of the eye. Specifically, drug-loaded medical device prototypes were suspended in a biological solution meant to mimic the somewhat harsh environment of the eye. Samples, maintained at body temperature were removed at defined periods of time over sixteen days and were quantified to determine concentration and rate of drug elution for each of the Company’s three candidate molecules. The stability of one of the candidate molecules did not meet minimal necessary criteria and has now been eliminated from further consideration. The remaining two DMT-analogues displayed suitable 2-week provisional stability and elution characteristics that support further evaluation and optimization. One candidate molecule/medical device in particular, displayed a consistent drug elution profile from days 2-16 (end of study) suggesting that drug delivery of greater than two weeks may be possible. The biocompatibility of drug-loaded medical devices was examined by way of monitoring cell proliferation and live/dead staining on human ciliary muscle cells over time. Concentrations expected to be within the therapeutic range were found to not statistically impact cell viability for any of the drug-loaded medical devices.

Test article potency was previously evaluated using an in vitro calcium mobilization assay on trabecular meshwork cells; a cell type known to be critically important in the maintenance of healthy IOP. Calcium mobilization is understood to provoke cellular contraction, and specifically in the case of trabecular meshwork cells, is thought to contribute to the maintenance of healthy IOP by channeling aqueous humor away from the front of the eye. Test articles were found to activate calcium mobilization, to levels that were comparable or greater than the experimental positive control, ionomycin. The Company’s test articles were also examined for in vitro toxicity and were found to be non-toxic to trabecular meshwork cells at concentrations expected to be used in treatment for various eye diseases. Collectively the results of the above studies will be used to select a lead development candidate that will be taken forward into in vivo efficacy models for eye diseases, including glaucoma.

The Need for Improved Medications to Treat Primary Open Angle Glaucoma

Glaucoma is a disorder of the optic nerve that results in irreversible vision loss and is the second leading cause of blindness in the world, according to the World Health Organization. Glaucoma impacts more than 2.7 million people aged 40 or older in the United States and current treatments are known to have poor rates of compliance of up to 80% of patients. The global market for glaucoma was estimated by Market Scope at $4.8 billion in 2019 with the U.S. market representing $1.9 billion. Although the exact etiology of primary open angle glaucoma remains poorly understood, and may be variable across patient subsets, it is generally accepted that the observed increase in IOP correlates with progressive vision loss1. Current treatments for POAG primarily consist of eye drops that can be grouped into three main categories: prostaglandin analogues, carbonic anhydrous inhibitors, and alpha-2 agonists. While these approaches usually provide partial improvement, they often result in side effects such as redness and stinging and require multiple daily applications; all of which diminish patient compliance. Tryptamines, including DMT-analogues are thought to work in a completely distinct way to lower IOP and as such potentially embody a new class of glaucoma medications that may be used alone, or in combination with already approved medications. The Company’s streamlined focus on two highly promising, undisclosed tryptamines as a potential therapeutic solution in treating glaucoma represents a potential paradigm shift.

Modulating the serotonin receptor pathway to improve glaucoma outcomes

Key regions of the eye that regulate fluid dynamics, including maintenance of healthy IOP, are known to be richly decorated with various serotonin receptor family members. Previous research has highlighted the role of serotonin receptor signaling in the regulation of IOP2-5. Tryptamines, often hallucinogenic above certain threshold concentrations, constitute a large collection of molecules that selectively act on multiple different serotonin receptors including 5-HT1A and 5-HT2A. Topical application of several different tryptamines have shown early promise in preclinical models of elevated IOP, however formulation, delivery, the potential for undesirable hallucinogenic side effects, and the controlled substances act of 1970 have all contributed to a lack of development of tryptamines to treat this serious threat to vision.

About Terasaki Institute for Biomedical Innovation

The Terasaki Institute for Biomedical Innovation is a biotechnology institute which develops medical devices and cutting-edge protocols for a variety of diagnostic, monitoring and treatment applications. Their research platforms include work in biomaterials, cellular and tissue engineering, wearable biosensors and organs-on-a-chip, with specific expertise in novel polymer development.

About PharmaDrug Inc.

PharmaDrug is a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs. PharmaDrug owns 100% of Pharmadrug Production GmbH (“Pharmadrug Production”), a German medical cannabis distributor, with a Schedule I European Union narcotics license and German EuGMP certification allowing for the importation and distribution of medical cannabis to pharmacies in Germany and throughout the European Union. PharmaDrug owns 100% Sairiyo Therapeutics (“Sairiyo”), a biotech company that specializes in researching and reformulating established natural medicines with a goal of bringing them through clinical trials and the associated regulatory approval process in the US and Europe. Sairiyo is currently developing its patented reformulation of cepharanthine, a drug that has shown substantial third party validated potential for the treatment of infectious disease and rare cancers. Sairiyo is also conducting R&D in the psychedelics space for the treatment of non-neuropsychiatric conditions. The Company also owns 100% of Super Smart, a company building a vertically integrated retail business with the goal to elevate the use of functional mushrooms, and psilocybin mushrooms where federally legal, as natural based medicines.