PharmaDrug's Sairiyo Therapuetics Provides Strategic Plans to Advance PD-001 (Patented Reformulated Cepharanthine) for Viral Infectious Diseases

Rhea-AI Summary

PharmaDrug Inc. (CSE: PHRX) (OTC: LMLLF) has announced strategic plans to advance the clinical development of PD-001, its patented enteric-coated Cepharanthine formulation, for viral infectious diseases. Sairiyo Therapeutics Inc., 51% owned by PharmaDrug, received approval to initiate a first-in-human Phase 1 clinical study. This follows a $3.4 million contract from the Defense Threat Reduction Agency for the Ebola virus.

PD-001 aims to improve the bioavailability of Cepharanthine, a Japanese-approved drug with potential antiviral activity against various viruses, including coronavirus, HIV-1, and Zika. The new formulation addresses Cepharanthine's low solubility and bioavailability issues, potentially enabling oral administration and eliminating the need for frequent intravenous dosing.

Positive

• Approval received for first-in-human Phase 1 clinical study of PD-001
• $3.4 million contract awarded for Ebola virus research
• PD-001 shows improved oral bioavailability in animal models
• Patent protection for PD-001 until March 23, 2036

Negative

• No express claims of PD-001's ability to treat, eliminate, or cure infectious diseases at this time

Toronto, Ontario--(Newsfile Corp. - August 28, 2024) - PharmaDrug Inc. (CSE: PHRX) (OTC: 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 and previously approved drugs, is pleased to announce its strategic plans to advance the clinical development of its patented enteric-coated Cepharanthine formulation ("PD-001") for viral infectious diseases. As announced on August 19, 2024, Sairiyo Therapeutics Inc. ("Sairiyo"), a company that is fifty-one percent (51%) owned by PharmaDrug and fourty-nine percent (49%) owned by PharmaTher Holdings Ltd. (CSE: PHRM) (OTCQB: PHRRF) ("PharmaTher"), received approval by the Australian Human Research Ethics Committee to initiate a first-in-human Phase 1 clinical study (the "Study") to support PD-001 as a potential treatment for viral infectious diseases. This builds on PD-001 previously being awarded a $3.4 million contract from the Defense Threat Reduction Agency for the Ebola virus. Upon successful completion of the Study, Sairiyo will seek to advance the clinical development of PD-001 towards FDA approval through pharmaceutical partnerships or continuing government support, including approaching the Biomedical Advanced Research and Development Authority having a focus on public health medical emergencies such as pandemic influenza and emerging infectious diseases.

Robert Steen, CEO of PharmaDrug commented, "We are excited to finally be ready to advance PD-001 for clinical development as an anti-viral. In a world that we believe needs a larger arsenal to combat viral infectious diseases, cepharanthine has been highlighted in several studies and publications for the potential treatment of several viruses ranging from Ebola, to SARS/COVID and even the Zica Virus. The limiting factor has been its bioavailability. We believe that PD-001, with its patented enhanced bioavailability of cepharanthine, can potentially serve as a multi-indication anti-viral. We look forward to further explore cepharanthine's therapeutic prospects for a wide spectrum of viral infectious diseases including Mpox."

PD-001's potential for viral infectious diseases

Cepharanthine is a Japanese approved drug used to successfully treat a variety of acute and chronic diseases. Cepharanthine's anti-inflammatory, antibacterial, antioxidant, antihemolytic and immunomodulatory effects have recently made it a promising therapeutic molecule for viral and/or infectious diseases¹.

Cepharanthine has been shown in the literature to have antiviral activity against the coronavirus (e.g. COVID-19, SARS-CoV, MERS Middle East Respiratory virus)^2-4, HIV-1 virus⁵, hepatitis B virus⁶, herpes zoster virus⁷, T-lymphotropic virus⁸, nipah virus⁹, ebola virus and Zika virus¹⁰.

Cepharanthine's limitation

Cepharanthine's current commercial formulation in Japan is a simple tablet for oral administration. It is provided in large doses due to its low solubility in water and bioavailability. However, the potential for Cepharanthine as an antiviral therapeutic molecule makes it important to explore new dosage forms¹. In a recent publication, Cepharanthine effectiveness in the treatment of SARS-CoV-2 infection was clearly demonstrated; however, the low oral bioavailability suggested intravenous administration was the likely way to support further clinical application¹¹.

PD-001's solution to Cepharnathine

The clinical development of PD-001 is aimed at improving the solubility, stability, release profile, and ultimately bioavailability of the drug, positioning it to be evaluated further as an antiviral therapy. 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 oral and intravenous dosing to maintain therapeutic levels of drug in circulation. PD-001 is protected by US Patent US10576077, with a patent expiration date of March 23, 2036.

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 any infectious diseases 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^12,13. 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, removes 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 US 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% of 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 infectious disease and rare cancers. Sairiyo is also conducting R&D in the psychedelics space for the treatment of non-neuropsychiatric conditions. PharmaDrug also owns 100% of SecureDose Synthetics Inc. ("SecureDose"), a pharmaceutical research and development company focused on the development of synthetic formulations of currently existing drugs for potential commercialization and distribution.

For further information, please contact:

Robert J. Steen, Chairman and CEO
rob@pharmadrug.ca
(416) 400-7086

Caution Regarding Forward-Looking Information:

THE CANADIAN SECURITIES EXCHANGE HAS NOT REVIEWED NOR DOES IT ACCEPT RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE.

This news release may contain forward-looking statements and information based on current expectations. These statements should not be read as guarantees of future performance or results of the Company. Forward looking statements in this press release relate to the potential for cepharanthine as a treatment for Mpox and the development of the Company's business. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by such statements.

Forward-looking information is subject to known and unknown risks, uncertainties and other factors that may cause the actual results, level of activity, performance or achievements of the Company to be materially different from those expressed or implied by such forward-looking information. Such risks and other factors may include, but are not limited to: general business, economic, competitive, political and social uncertainties; general capital market conditions and market prices for securities; the actual results of the Company's future operations; competition; changes in legislation affecting the Company; the ability to obtain and maintain required permits and approvals, the timing and availability of external financing on acceptable terms; lack of qualified, skilled labour or loss of key individuals..

A description of additional risk factors that may cause actual results to differ materially from forward-looking information can be found in the Company's disclosure documents on the SEDAR+ website at www.sedarplus.ca. Although the Company has attempted to identify important factors that could cause actual results to differ materially from those contained in forward-looking information, there may be other factors that cause results not to be as anticipated, estimated or intended. Accordingly, readers should not place undue reliance on forward-looking information. Readers are cautioned that the foregoing list of factors is not exhaustive. Readers are further cautioned not to place undue reliance on forward-looking information as there can be no assurance that the plans, intentions or expectations upon which they are placed will occur. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated.

The Company's securities have not been registered under the U.S. Securities Act of 1933, as amended (the "U.S. Securities Act"), or applicable state securities laws, and may not be offered or sold to, or for the account or benefit of, persons in the United States or "U.S. Persons", as such term is defined in Regulations under the U.S. Securities Act, absent registration or an applicable exemption from such registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in the United States or any jurisdiction in which such offer, solicitation or sale would be unlawful.

Forward-looking information contained in this press release is expressly qualified by this cautionary statement. The forward-looking information contained in this press release represents the expectations of the Company as of the date of this press release and, accordingly, are subject to change after such date. However, the Company expressly disclaims any intention or obligation to update or revise any forward-looking information, whether as a result of new information, future events or otherwise, except as expressly required by applicable securities law.

References:

1. Di Liang, Qi Li, Lina Du,Guifang Dou. Pharmacological Effects and Clinical Prospects of Cepharanthine. 2022. Molecules27(24) 8933
2. Ohashi H, Watashi K, Saso W, Shionoya K, Iwanami S, Hirokawa T, Shirai T, Kanaya S, Ito Y, Kim KS, Nomura T, Suzuki T, Nishioka K, Ando S, Ejima K, Koizumi Y, Tanaka T, Aoki S, Kuramochi K, Suzuki T, Hashiguchi T, Maenaka K, Matano T, Muramatsu M, Saijo M, Aihara K, Iwami S, Takeda M, McKeating JA, Wakita T. Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment. iScience. 2021 Apr 23;24(4):102367. doi: 10.1016/j.isci.2021.102367. Epub 2021 Mar 26. PMID: 33817567; PMCID: PMC7997640.
3. Chen CZ, Xu M, Pradhan M, Gorshkov K, Petersen JD, Straus MR, Zhu W, Shinn P, Guo H, Shen M, Klumpp-Thomas C, Michael SG, Zimmerberg J, Zheng W, Whittaker GR. Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles. ACS Pharmacol Transl Sci. 2020 Oct 19;3(6):1165-1175. doi: 10.1021/acsptsci.0c00112. PMID: 33330839; PMCID: PMC7586456.
4. Fan HH, Wang LQ, Liu WL, An XP, Liu ZD, He XQ, Song LH, Tong YG. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model. Chin Med J (Engl). 2020 May 5;133(9):1051-1056. doi: 10.1097/CM9.0000000000000797. PMID: 32149769; PMCID: PMC7147283.
5. He, C.L.; Huang, L.Y.; Wang, K.; Gu, C.J.; Hu, J.; Zhang, G.J.; Xu, W.; Xie, Y.H.; Tang, N.; Huang, A.L. Identification of bisbenzylisoquinoline alkaloids as SARS-CoV-2 entry inhibitors from a library of natural products. Signal Transduct. Target 2021, 6, 131
6. Zhou, Y.-B.; Wang, Y.-F.; Zhang, Y.; Zheng, L.-Y.; Yang, X.-A.; Wang, N.; Jiang, J.-H.; Ma, F.; Yin, D.-T.; Sun, C.-Y.; et al. In vitro activity of cepharanthine hydrochloride against clinical wild-type and lamivudine-resistant hepatitis B virus isolates. Eur. J. Pharmacol. 2012, 683, 10-15.
7. Liu, Y.; Tang, Q.; Rao, Z.; Fang, Y.; Jiang, X.; Liu, W.; Luan, F.; Zeng, N. Inhibition of herpes simplex virus 1 by cepharanthine via promoting cellular autophagy through up-regulation of STING/TBK1/P62 pathway. Antivir. Res. 2021, 193, 105143.
8. Toyama, M.; Hamasaki, T.; Uto, T.; Aoyama, H.; Okamoto, M.; Hashmoto, Y.; Baba, M. Synergistic inhibition of HTLV-1-infectedcell proliferation by combination of cepharanthine and a tetramethylnaphthalene derivative. Anticancer Res. 2012, 32, 2639-2645.
9. Maryam Ebrahimi, Mahdi Alijanianzadeh. Evaluation of the interaction between potent small molecules against the Nipah virus Glycoprotein in Malaysia and Bangladesh strains, accompanied by the human Ephrin-B2 and Ephrin-B3 receptors; a simulation approach. Molecular Diversity 2023 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9939871/pdf/11030_2023_Article_10624.pdf
10. Shaojun Zhang, Wenze Huang, Lili Ren, Xiaohui Ju, Mingli Gong, Jian Rao, Lei Sun, Pan Li, Qiang Ding, Jianwei Wang, Qiangfeng Cliff Zhang. Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. Cell Res. 32, 9-23 (2022)
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FAQ

What is PD-001 and how does it relate to PharmaDrug (PHRRF)?

PD-001 is PharmaDrug's patented enteric-coated Cepharanthine formulation designed to improve bioavailability for potential use in treating viral infectious diseases. PharmaDrug (PHRRF) owns 51% of Sairiyo Therapeutics, which is developing PD-001.

What recent milestone has PharmaDrug (PHRRF) achieved for PD-001?

PharmaDrug (PHRRF) announced that Sairiyo Therapeutics received approval from the Australian Human Research Ethics Committee to initiate a first-in-human Phase 1 clinical study for PD-001 on August 28, 2024.

What viral diseases is PD-001 potentially targeting?

PD-001 is being developed to potentially target a wide range of viral infectious diseases, including Ebola, coronavirus (COVID-19, SARS-CoV, MERS), HIV-1, hepatitis B, herpes zoster, Nipah virus, and Zika virus.

How does PD-001 improve upon the original Cepharanthine formulation?

PD-001 aims to improve the solubility, stability, release profile, and bioavailability of Cepharanthine, potentially allowing for oral administration and eliminating the need for frequent intravenous dosing to maintain therapeutic levels.