PharmaDrug Advances Product and Clinical Development of Cepharanthine to Treat Infectious Diseases Including COVID-19
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 that the Company has initiated preparation of a Pre-Investigational New Drug Application (pre-IND) for its patented enteric-coated formulation of cepharanthine (PD-001), an oral antiviral pill to treat mild-moderate COVID-19.
Vaccination programs aimed at controlling the impact of COVID-19 have proceeded at an unprecedented pace; the positive impact of which is clear when examining case counts in jurisdictions that have seen an efficient immunization rollout. However, there remains an urgent need for additional antiviral therapies for COVID-19 and future coronavirus outbreaks.
On June 17, 2021 the U.S. government announced a ‘Whole-of-Government Effort’ to spend more than $3 billion on developing next generation COVID-19 treatments in preparation to respond to future virus threats. A major focus for the spend is earmarked to develop oral antiviral drugs for home use, following onset of disease symptoms and to treat people who are vulnerable to the virus such as those who are immunosuppressed or unvaccinated.
According to Dr. David Kessler, Chief Science Officer for the Biden Administration’s COVID-19 Response, “An easily administered oral antiviral drug would be an important part of our therapeutic arsenal that would complement the great success of our vaccine efforts.”
Approved for more than 70 years in Japan, cepharanthine has been used to successfully treat a variety of acute and chronic diseases. Extensive mechanism of action studies have shown cepharanthine to exhibit potent antiviral properties as well as other pharmacological traits that are of benefit in treating infectious diseases including anti-oxidative, anti-inflammatory, immuno-regulatory, and anti-parasitic properties. To date, several third party validated library screens of approved and investigational drugs have identified cepharanthine as a forerunner candidate based on the superior antiviral properties it displays against SARS-CoV-2, the virus that causes Covid-191,2,3.
In fact, cepharanthine has now been shown to be highly effective at blocking cell death following exposure to multiple different coronaviruses, including COVID-191,2,3. As such, it is believed that the Company’s novel formulation of cepharanthine, PD-001 would be an ideal candidate to evaluate as a potential treatment for mild to moderate COVID-19. The U.S. FDA commitment in supporting novel therapies for mild to moderate COVID-19 is apparent with the issuance of Emergency Use Authorization (“EUA”) for bamlanivimab (manufacturer Eli Lilly) and the combination of casirivimab and imdevimab (manufacturer Regeneron) for the treatment of mild to moderate COVID-19.
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. On June 9th, 2021, the U.S. Government announced that it has committed to purchase $1.2 billion worth of 5-day treatment courses of molnupiravir only if FDA grants EUA or approval. Molnupiravir aims to reduce the replication of the SAR-CoV-2 virus and is being evaluated in an ongoing Phase 3 trial for its potential to reduce the risk of hospitalization or death in non-hospitalized patients who have symptoms for five days or less and are at high risk for severe illness.
Cepharanthine was found to block viral cell entry of lab-attenuated SARS-CoV (original SARS), the virus that causes Middle East respiratory syndrome (MERS)2. However, optimism thus far for translating these findings into an improved treatment for COVID-19 has been limited based on the need to deliver generic cepharanthine by intravenous due to its intrinsically poor oral bioavailability. 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.
The Company will capitalize on the known potential of cepharanthine by evaluating the benefit of their novel oral formulation of PD-001 as a potential oral antiviral therapeutic agent to treat mild-moderate COVID-19. The Company has already initiated a fair amount of preparation and expects to be in a position to proceed with filing a Pre-IND with the FDA before the end of July to determine the appropriate next steps to advance to human clinical studies that would position PD-001 as a potential first-in-class therapeutic against coronaviruses and future pandemics.
We are committed to advance the development of our patented and novel formulated version of cepharanthine, designated as PD-001, for infectious diseases, with a particular focus on developing it as a potential first-in-class oral antiviral pill to complement vaccines in the treatment of COVID-19 and future coronaviruses globallyDaniel Cohen, Chairman and CEO of PharmaDrug
The Company would like to make it clear that is not making any express or implied claims that its product (cepharanthine) has the ability to treat, eliminate or cure COVID-19 (SARS-CoV-2) and/or other infectious diseases at this time.
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 chloroquine1. The authors 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 hypothesis, application of cepharanthine to cells simultaneously exposed to SARS-CoV-2 fully blocked viral internalization and subsequent production of viral particles 24 hours post infection1. Cepharanthine-mediated inhibition of SARS-CoV-2 viral entry is further supported by the work of Chen CZ, et al2. Using a panel of 2678 approved drugs, the authors identified 6 promising SARS-CoV-2 viral entry inhibitors. Among the six, cepharanthine was favorably non-toxic and displayed the greatest capacity to reduce viral entry and block virus-induced cell death. Of additional note, cepharanthine was also found to block viral cell entry of lab-attenuated SARS-CoV (original SARS) as well as to the virus that causes Middle East respiratory syndrome (MERS), suggesting that cepharanthine might have considerable utility as an ‘off the shelf’ pan-coronavirus antiviral2. Finally, using a two libraries of 2406 clinically approved drugs, a third research group used a SARS-CoV-2-related corona virus isolated from pangolin to identify potential repurposing candidates. Like SARS-CoV-2, the related virus (called 2019-nCoV-related) was found to use ACE2 as the cell docking receptor. The pangolin coronavirus model was used to identify drugs capable of inhibiting virus-induced cell death3. The spike protein of coronavirus 2019-nCoV shares 92.2% amino acid identity with that of SARS-CoV-2. Of all compounds screened, cepharanthine provided the most potent inhibition of 2019-nCoV-related infection.
How Cepharanthine May Work to Lessen the Effects of Coronavirus Infection
Cell, animal, and human studies have long reported the immunomodulatory and anti-inflammatory properties of cepharanthine4. Agents capable of targeting host response are conceptually attractive because they minimize the potential loss of therapeutic drug effects that are sometimes noted as mRNA viruses undergo genetic mutation. Cepharanthine has previously been shown to suppress cytokine production and the expression of cyclooxygenase; both of which are crucial to viral replication and inflammatory response5,6. A 2019 study examined the effects of cepharanthine on human lung cells infected with the coronavirus HCoV-OC437. Following pre-treatment with cepharanthine lung cells showed no virus-induced death. These findings were attributed to the ability of cepharanthine to inhibit viral RNA replication, block expression of viral proteins, and suppress production of proinflammatory molecules, thus preventing a deleterious exacerbation of cytokine response to the viral infection.
Cepharanthine for Cancer
The Company is focused on advancing the clinical development of its improved highly bioavailable, patented enteric-coated formulation of cepharanthine, ‘PD-001’ to treat rare, serious, high unmet medical needs including cancer and infectious disease. PharmaDrug remains fully committed to its cancer strategy and sees it as a parallel path for the development of PD-001. As a reminder, The Company was granted Orphan Drug Designation (ODD) by the FDA for Cepharanthine in the treatment of esophageal cancer in January of 2021 and subsequently added some world class experts to its scientific advisory team. Before requesting an IND meeting with the FDA, management made the decision to conduct some pre-clinical work to more fully evaluate the mechanism of action for cepharanthine given that the drug displays potential as a direct anti-cancer agent as well a prospect for reducing resistance to common chemotherapies. Furthermore, there is ample literature that speaks to cepharanthine’s potential with other cancers and PharmaDrug believes it makes sense to explore other potential avenues as well.
As previously announced in a press release dated May 06, 2021, PharmaDrug has signed a service agreement with a contract research organization to evaluate Cepharanthine in a broad panel of human cancers. The first phase of the study will compare Cepharanthine to the current standard of care in 60 human cancers. The company has already seen preliminary results from approximately 25% of the planned cell lines and several cancers were shown to be impacted by cepharanthine. The company expects final results from all 60 cell lines by mid to late July and will inform the market of all its findings. The following phase of the program will compare cepharanthine in conjunction with 3 types of chemo to assess the drug’s potential in reducing chemo resistance in cancer cells. The company will then move to initiate an animal study in the fall for Esophageal Cancer as well as any other cancer type that shows comparable potential.
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