PharmaDrug Inc. announced that the Company has now completed cGMP manufacturing of a multi-kilogram lot of cepharanthine-2HCl for use in the final drug product production of PD-001, its patented, orally bioavailable version of cepharanthine. The Company's capital investment directed at drug synthesis optimization over the last two quarters have resulted in a product yield increase of approximately 30% compared to historical values. Completion of this lot significantly advances the Company's efforts to support pre-clinical and clinical development, including commencement of Phase 2 clinical studies, for parallel indications in oncology and infectious disease.

On behalf of the Company, and pending satisfaction of all release testing criteria, Genvion Corporation is scheduled to take receipt of the cGMP drug substance in early November. As the Company's contract development and manufacturing organization, Genvion Corporation has been engaged to complete necessary ICH-compliant stability testing and forced degradation studies in support of future IND filing to the FDA (See press release dated August 19,2022). All downstream manufacturing efforts necessary to produce the orally bioavailable clinical drug product, PD-001 will also be completed by Genvion Corporation.

Following submission of its Type B pre-IND meeting request and briefing package to the U.S. Food and Drug Administration (FDA), the Company received a written response regarding its clinical development plan for PD-001, as a potential oral antiviral pill for COVID-19 and variants of concern. PharmaDrug has executed on feedback, specifically as it related to necessary chemistry and manufacturing controls set forth by the regulator, to meaningfully advance its preclinical development programs for PD-001 as a potential treatment for infectious disease and oncology indications including prostate and esophageal cancers. Cepharanthine is a natural product and an approved drug used for more than 70 years in Japan to successfully treat a variety of acute and chronic diseases.

In clinical research, Cepharanthine has been shown to exhibit multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno- regulatory, anti-cancer, anti-viral and anti-parasitic effects1,2. However, historically cepharanthine's low oral bioavailability has represented a major obstacle to realizing its full clinical potential. The Company is focused on advancing the clinical development of an improved and patented enteric- coated oral formulation of cepharanthine (PD-001) to treat responsive cancers and COVID-19. Compared to generic cepharanthine, PD-001 has been shown in rodent and non-rodent models to possess markedly improved oral bioavailability (more easily absorbed).

These findings support the development of an orally administered formulation, and in so doing, removes the undesirable requirement for frequent intravenous dosing to maintain therapeutic levels of drug in circulation. The Company endeavours to develop an efficacious oral therapeutic to potentially improve outcomes for infectious disease and oncology applications. PharmaDrug's oncology program is based on cepharanthine's known anti-cancer activities.

Cepharanthine has been shown in over 160 peer-reviewed publications to inhibit cancer cell proliferation, induce cancer cell apoptosis (death) and restore cancer cell sensitivity to multiple unrelated classes of chemotherapy. Multidrug resistance continues to represent a considerable clinical challenge. As such, preclinical cancer studies aimed at elucidating the mechanisms that underly chemoresistance; including the critical role drug efflux pumps play in this phenomenon by reducing the intracellular concentration of chemotherapeutic drugs, are of particular interest to PharmaDrug.

Cepharanthine has been shown in preclinical studies to potently reverse chemoresistance by downregulating expression of ABCB1, the transcript of which codes for multidrug resistance protein 1, (MDR1, aka P- glycoprotein). Importantly, several prior in vitro and in vivo studies have shown that cepharanthine-mediated reductions in ABCB1 expression restores cancer cell sensitivity to a range of chemotherapeutics including taxanes, vinca alkaloids and platinum-based drugs.