Dr. David Kideckel reports

PHARMADRUG SAIRIYO THERAPEUTICS TO EXPLORE PD-001, ITS PATENTED REFORMULATED CEPHARANTHINE, FOR HANTAVIRUS

Sairiyo Therapeutics Inc., a company 51 per cent owned by Pharmadrug Inc. and 49 per cent owned by Pharmather Holdings Ltd., is pursuing its strategic plans to focus on the clinical development of its patented enteric-coated oral cepharanthine (PD-001) as a potential therapeutic candidate for hantavirus (HTNV).

Independent published research has identified cepharanthine as a potential hantavirus entry inhibitor. In the study titled "Screening and identification of HTNVpv entry inhibitors with high-throughput pseudovirus-based chemiluminescence," researchers developed a high-throughput screening method using Hantaan virus pseudovirus (HTNVpv) and evaluated a library of 1,813 approved drugs and 556 small-molecule compounds. The study identified six compounds with anti-HTNVpv activity in the low-micromolar range, including cepharanthine. Among the selected compounds, cepharanthine not only demonstrated in vitro anti-HTNVpv activity but also inhibited HTNVpv-fluc infection in Balb/c mice. In that mouse model, cepharanthine inhibited hantavirus pseudovirus infection five hours after infection by approximately 94 per cent at 180 milligrams per kilogram per day, 93 per cent at 90 mg/kg/day and 92 per cent at 45 mg/kg/day, with statistical significance reported at P less than 0.01. The researchers also reported that time-of-addition analysis suggested cepharanthine may act during the viral entry and membrane fusion phases, which are important early steps in the hantavirus infection cycle. The authors concluded that cepharanthine may represent a candidate for further evaluation in hantavirus-related diseases, including HFRS (hemorrhagic fever with renal syndrome) and HCPS (hantavirus cardiopulmonary syndrome).

The cepharanthine data described above are from independent third party preclinical studies and were not generated using Sairiyo's PD-001 formulation. While the company believes the findings support further evaluation of PD-001, pseudovirus, cell-based and animal-model results may not translate into clinical efficacy in humans, and no claim is being made that PD-001 can treat, prevent or cure hantavirus or any other infectious disease.

Hantavirus is an Old World hantavirus associated with hemorrhagic fever with renal syndrome (HFRS), a potentially severe disease affecting the kidneys and blood vessels. Hantaviruses remain a global public health concern because they are rodent-borne, can cause severe illness and death, and currently have limited treatment options. According to the World Health Organization, hantavirus infections can cause severe disease, HFRS occurs primarily in Europe and Asia, and there is no licensed specific anti-viral treatment for hantavirus infection, with care currently focused on supportive management of respiratory, cardiac and kidney complications.

"This independent research provides a reasonable scientific rationale to further evaluate Sairiyo's PD-001 as a potential anti-viral candidate for hantavirus and other hantavirus-related diseases," said Dr. David Kideckel, executive chairman of Pharmadrug. "The published findings suggest cepharanthine may interfere with early viral entry and membrane fusion, which are critical steps in the hantavirus infection cycle. PD-001 was specifically designed to address cepharanthine's historical limitation of poor oral bioavailability through a patented enteric-coated oral formulation."

Sairiyo has previously received approval from an Australian human research ethics committee to initiate a first-in-human phase 1 clinical study of PD-001 for viral infectious diseases. The planned phase 1 study is intended to evaluate the safety, tolerability, pharmacokinetics and bioavailability profile of PD-001 in healthy volunteers and is not designed to establish therapeutic efficacy or demonstrate that PD-001 can treat, prevent or cure any viral infectious disease, including hantavirus or related hantavirus indications. Any future advancement of PD-001 into further clinical studies or indication-specific development would be subject to successful completion of phase 1 activities, additional preclinical and/or clinical data, regulatory review, availability of financing, manufacturing readiness and other development risks. PD-001 was previously the subject of a $3.4-million (U.S.) contract from the Defense Threat Reduction Agency (DTRA) for ebola-virus-related research; however, this prior contract should not be interpreted as government endorsement or validation of PD-001, nor does it establish efficacy, regulatory approval, commercial viability or the likelihood of future development success in ebola virus, hantavirus or any other infectious disease indication.

The company would like to make it clear that is not making any express or implied claim that PD-001 or cepharanthine can treat, prevent, cure or eliminate hantavirus, HFRS, HCPS or any other infectious disease at this time.

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 effects. However, historically cepharanthine's low oral bioavailability has represented a major obstacle to realizing its full clinical potential.

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, remove the undesirable requirement for frequent intravenous dosing to maintain therapeutic levels of drug in circulation. Sairiyo endeavours to develop an efficacious oral therapeutic to potentially improve outcomes for infectious disease and oncology applications.

PD-001 is protected by U.S. patent US10576077, with a patent expiration date of March 23, 2036.

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 and previously approved drugs. Pharmadrug owns 51 per cent of Sairiyo Therapeutics, 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 United States 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.

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