Establishing cGMP supply for IND-enabling and up to Phase 2 clinical studies for PD-001 oral formulation for esophageal cancer and mild to moderate COVID-19
Toronto, Ontario–January 26, 2022- PharmaDrug Inc. (CSE: PHRX) (OTCQB: LMLLF) (“PharmaDrug” or the “Company“), 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 the Company has initiated the manufacturing of PD-001, a patented enteric-coated oral formulation of cepharanthine, for non-clinical and clinical studies in cancer and infectious diseases. This follows the Company’s recent announcements of the successful completion of its pre-IND meeting with the U.S. Food and Drug Administration (the “FDA“) regarding the proposed development of PD-001 for the treatment of mild to moderate COVID-19 and positive preclinical study results with PD-001 for esophageal cancer and other undisclosed cancers. The current scale of manufacturing activities should fully support development of PD-001 through IND-enabling studies and potential future FDA Phase 1 and 2a clinical studies.
Consistent with FDA requirements, a core battery of drug development activities need to be completed prior to initiation of human testing regardless of the disease indication under development. As such, parallel development of PD-001 for oncology and infectious disease indications will provide valuable time and cost efficiencies to the Company by way of eliminating the need to duplicate multiple standard activities. One such place relates to drug manufacturing control and the need to reproducibly generate a sufficient quantity and quality of drug material to support all non-clinical and clinical testing. To that end, PharmaDrug has purchased a significant quantity of bulk cepharanthine material and has engaged Southwest Research Institute (SwRI) to initiate cGMP manufacturing activities in Q1, 2022. SwRI has a previous track record for producing the Company’s drug substance and drug product according to required specifications. Following receipt of feedback from the FDA in November 2021 on its pre-IND application to treat COVID-19, the Company is confident of its ability to simultaneously execute on both its PD-001 programs (COVID-19 and esophageal cancer) and that the drug product manufactured using existing methodology will yield material that complies with the rigorous standards set forth by the regulator.
Daniel Cohen, CEO and Chairman of PharmaDrug commented, “We are extremely excited to be moving forward with the manufacturing of a cGMP lot of PD-001. We believe cepharanthine has tremendous potential to treat several indications. Following the completion of a successful pre-IND meeting with the FDA and ongoing studies in both rare cancers and COVID-19, we are confident we have a clear path to the clinic on a number of fronts.”
About PD-001 (Enteric-coated Oral 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 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 rare cancers and COVID-19. 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.
PD-001 for Cancer
PharmaDrug’s cancer program is based on cepharanthine’s known anti-cancer activities. Cepharanthine has been shown in multiple preclinical efficacy models 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 drugs3-6. Collectively the two studies already completed by the Company, and those currently underway aim to identify and provide focus to novel opportunities in oncology by revealing optimal cancer cell types as a monotherapy and/or drug combinations and situations where PD-001 can prevent, lessen, or reverse chemoresistance, and provide additive or synergistic benefit to existing standard of care treatments (for reference please see previous press releases Nov 18, Oct 15 and July 28, 2021). The Company’s ongoing animal efficacy studies are designed to experimentally examine the role of cepharanthine in restoring chemosensitivity. Based on compelling preclinical data in esophageal cancer and a streamlined path to approval which comes by way of a recently granted FDA Orphan Drug Designation, the Company continues its plans to pursue cepharanthine for this indication.
PD-001 for COVID-19
The global significance of coronavirus infection has been rising following the emergence and identification of the virus that causes severe acute respiratory syndrome (SARS) was first documented in Guandong, China in 2002. Since then, a related virus causing middle east respiratory syndrome (MERS) in 2012 and currently SARS-CoV-2, first identified in 2019, have revealed obvious vulnerabilities related to containing and treating novel coronavirus outbreaks. To date, several third party validated library screens of approved and investigational drugs have identified cepharanthine as a forerunner candidate molecule in the treatment SARS-CoV-2, the virus that causes COVID-197-9. In fact, cepharanthine has now been shown to be highly effective at blocking cell death following exposure to multiple different coronaviruses, including COVID-19, lab-attenuated SARS-CoV (original SARS) and the virus that causes Middle East respiratory syndrome (MERS)7-9. In November 2021 an independent research group examined the potential of cepharanthine to limit the cytopathic effects of the South African COVID-19 variant, B.1.3514. It was found that cepharanthine was at least 6-times more active against the South African variant strain than original SARS-CoV-2, and that cepharanthine was the most effective of all the drugs used in the in vitro screen that was perfomed10. Although the recent Omicron variant discovered in South African nations shares several features in common with the previous South African variant, B.1.351, it remains to be determined how well cepharanthine will perform at treating this ongoing threat. Despite the promising findings for cepharanthine noted above, translation into clinical application has thus far been hampered by the need for the generic formulation of the drug to be delivered by intravenous due to its intrinsically poor oral bioavailability. As such, it is believed that the Company’s novel oral formulation of cepharanthine, PD-001 would be an ideal candidate to evaluate as a potential treatment for mild to moderate COVID-19. By leveraging its exclusive rights to U.S. Patent: 10,576,077, titled “Pharmaceutical Salt forms of Cepharanthine and Tetrandrine”, PharmaDrug intends to develop and commercialize PD-001 as an oral antiviral treatment for patients with mild to moderate SARS-CoV-2 infection and variants thereof.
How Cepharanthine May Work to Block Coronavirus Entry
In a recent peer reviewed manuscript cepharanthine was shown to display greater antiviral potency against SARS-CoV-2 than existing clinical development candidates remdesivir, lopinavir, favipiravir, nelfinavir and chloroquine7. Researchers identified a putative binding site on the surface of SARS-CoV-2 spike protein known to facilitate viral docking with the human ACE2 receptor. Consistent with this mechanism of action, application of cepharanthine to cells exposed to SARS-CoV-2 fully blocked viral internalization and subsequent production of viral particles 24 hours post infection7.
Ongoing Need for a Deep Arsenal of Oral Antiviral Medications
The magnitude of the current pandemic has brought into sharp focus how susceptible the world remains to known and novel coronaviruses and has underlined the extreme and urgent need for additional research aimed at pre-emptively developing broad classes of oral antiviral agents that can be stockpiled for rapid distribution. With increasing population density, shifts in agricultural practice, international trade and expanded travel all contributing to elevated health and financial burden related to infectious disease, continued focus on development of oral antivirals to treat existing and emerging viral strains is expected to remain a worldwide priority for the foreseeable future.
The Company is not making any express or implied claims that its product has the ability to eliminate, cure or contain the Covid-19 (or SARS-2 Coronavirus) at this time.
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 COVID-19 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.