Pharmadrug Announces Positive Research Results of Cepharanthine to Treat Multiple Cancers

  • Validates Cepharanthine’s potential in treating various cancers with unsatisfactory treatment options
  • Positions Cepharanthine’s ‘pipeline in a pill’ strategy focusing on esophageal, colorectal, liver and skin cancers
  • Advance to FDA IND-enabling studies to support human clinical studies

PharmaDrug Inc. (CNSX: BUZZ) (OTCMKTS: 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 the completion of their preclinical cancer study which evaluated cepharanthine-2HCl, the active pharmaceutical ingredient in PD-001, the Company’s patented oral formulation of cepharanthine. The results from the study validate cepharanthine’s potential in treating different types of cancer including esophageal, colorectal, liver and skin. The results also provide confidence in the Company’s plan to dedicate resources to advance PD-001 through FDA IND-enabling studies to support Phase 1 and 2 clinical studies. The study was conducted by a respected contract research organization with deep expertise in preclinical oncology model development and drug testing and data corresponding to all studied cancer cell lines have now been reported to the Company.

PharmaDrug was pleased to find that twenty of the sixty cancer cells lines screened showed growth inhibition of at least fifty percent when exposed to cepharanthine levels previously determined to be well tolerated in a human clinical population. Additionally, there were several instances in which cepharanthine displayed growth inhibition which was comparable or superior to current gold standard treatments, including colorectal, liver and skin cancers. More notably, results of the current study demonstrated that esophageal cancer was the most highly responsive of all sixty cancers examined; with cepharanthine showing 99.96% growth inhibition at the top concentration tested and displayed approximately 5-times greater potency (at IC50) than cisplatin, a chemotherapy commonly used to treat esophageal cancer despite the fact that development of chemoresistance to this family of agents is common. Previously the Company announced that it had secured FDA Orphan Drug Designation for cepharanthine in the treatment of esophageal cancer. However, prior to committing to a substantial clinical program for that indication, PharmaDrug looked to further expand on the body of existing supportive data for esophageal cancer, while also potentially revealing new, promising cancer indications. Based on these promising findings, PharmaDrug reiterates that it remains committed to the clinical development of PD-001 for the treatment of patients suffering from esophageal cancer.

The Study

The Company’s study examined potential anti-cancer properties of cepharanthine (monotherapy) in a panel of sixty solid and liquid cancer cell types and does so by comparing cell growth inhibition following exposure to cepharanthine as well as current standard of care agents. Cepharanthine has been an approved drug in Japan for approximately 70 years. Generic cepharanthine has been safely and effectively delivered to patients via an intravenous route of administration, however oral administration has not received broad adoption owing to its poor bioavailability. Borrowing from what is already known about safe circulating levels in patients for generic cepharanthine, the Company’s current 60 cancer screen was designed to investigate the impact of their patented cepharanthine formulation at concentrations that are predicted to be safe to patients1. Using these criteria, PharmaDrug was pleased to find that twenty of the sixty cancer cells lines screened showed growth inhibition of at least 50 percent when exposed to cepharanthine levels previously determined to be well tolerated in a human clinical population. Additionally, there were several instances in which cepharanthine displayed growth inhibition which was comparable or superior to current gold standard treatments examined.

With these highly encouraging results, PharmaDrug is advancing its cancer program with the initiation of IND-enabling studies to support human clinical studies, such as an in vitro efficacy study to assess the potential of cepharanthine to provide additive and/or synergistic benefits in combination (combo-therapy) with current standard of care agents and in vivo efficacy studies designed to further validate cancer indication selection with a view to de-risking downstream clinical programs. The outcome of these IND-enabling studies is anticipated to strengthen and broaden the foundation of the Company’s intellectual property portfolio, as well as validate the proposed clinical development plans to be put forward to the FDA in future IND applications to conduct both Phase 1 and 2 clinical studies.  These efforts will provide PharmaDrug with additional intellectual property, downstream licensing opportunities in the oncology space, but most importantly, a clear path for electing a lead cancer indication for their internal development program.

We are extremely excited with the results of this study demonstrating the potential of cepharanthine in treating multiple forms of cancer known to commonly escape response through the development of chemoresistance. Although cepharanthine is described in scientific literature as a potential cancer therapeutic, we did not expect to see the noted significant growth inhibition in difficult to treat cancers. Cepharanthine is on its way to establishing itself as a once per day, oral anti-cancer therapeutic with a well-established safety profile which will pave the way for an expedited clinical development pathway and future partnering opportunities with pharmaceutical companies. We look forward to providing continued updates on our intellectual property, research, clinical, regulatory and manufacturing activities for PD-001; our novel oral formulation of cepharanthine, with the aim of working towards a first-in-human, proof-of-concept clinical trial under an FDA IND approval.

Daniel Cohen, CEO of PharmaDrug

Next Steps

Based on the de-risked and positive results from the study, the Company has initiated the following activities:

  • Broadening intellectual property strategy with planned filing of provisional patents on cepharanthine for specific cancers. These findings will be made public after being filed with the patent office;
  • Expanding orphan drug designations in the U.S. and Europe for certain cancers based on the Company’s proprietary results;
  • Completing a second, drug combination preclinical study in September which may generate additional discoveries and facilitation a broadening of the Company’s intellectual property portfolio;
  • Pursuing FDA IND-enabling animal studies in the fall to evaluate the benefit of cepharanthine alone (monotherapy) or when combined with relevant first and second-line chemotherapy drugs to support future human clinical studies; and
  • Initiating the scale-up processes and Good Manufacturing Practice (GMP) production of PD-001 (novel oral formulation of cepharanthine) in preparation for the first-in-human proof-of-concept clinical trial.

Cepharanthine’s Rationale in Cancer

PharmaDrug’s cancer program is based on cepharanthine’s known anti-cancer activities. Cepharanthine has been shown in preclinical efficacy models to 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 drugs25. Collectively the studies currently being undertaken by the Company aim to identify and provide focus to novel opportunities in oncology by revealing optimal drug combinations and situations where PD-001 can prevent, lessen, or reverse chemoresistance, and/or provide additive/synergistic benefit to existing treatments.

About PD-001 (Enteric-Coated Cepharanthine)

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 properties5. 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 oral formulation of Cepharanthine (PD-001) to treat rare cancers and infectious diseases. Compared to generic Cepharanthine, PD-001 has been shown in rodent and non-rodent models to possess markedly superior 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.

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