PharmaDrug Inc. announced that the Company intends to pursue a first-in-human study of its lead development candidate, PD-001, enteric coated cepharanthine-2HCL (for oral administration), in Australia during the second half of 2023. The proposed first-in-human study aims to be a prospective multi-site open label randomized controlled clinical investigation of the safety, tolerability, and pharmacokinetics of PD-001 in esophageal cancer subjects. The Company's decision to pursue clinical development of PD-001 for esophageal cancer initially in Australia derives from a streamlined regulatory framework established by Australia's Therapeutic Goods Administration (TGA) that permits a sponsor to bypass the lengthy and costly process of filing an IND application that would be required by the FDA, while also allowing a sponsor to evaluate its investigational drug prior to committing to larger clinical studies in the U.S. and Europe.

In addition to the world-class facilities and deep clinical trial expertise located in Australia, the Company intends to take advantage of Australia's Research and Development (R&D) tax incentive program which will provide the Company with up to a 43.5% refund on all R&D expenditures. Strict adherence to guidelines set forth by TGA ensures that the Company's clinical trial data will be acceptable to other regulatory bodies including the FDA. For the Company, human clinical data generated from Australia would de-risk PD-001's clinical development plan and support further investigation of PD-001 in subsequent Phase 2 and confirmatory studies in the U.S. under an IND with the FDA.

PharmaDrug's investigational drug, PD-001, has been granted orphan drug designation by the FDA for the treatment of esophageal cancer. Efforts to support clinical evaluation of PD-001 for esophageal cancer are currently underway. A large- scale cGMP lot of cepharanthine-2HCL has been completed and specific test methods required by the FDA for the quantification of drug attributes have been developed during Fourth Quarter of 2022 to support the issuance of the certificate of analysis and master batch record.

Final release testing is ongoing and the Company plans to transfer this material to its contract manufacturer, Genvion Corporation. Material transfer is planned for March, 2023 and once complete, Genvion will execute all necessary ICH- compliant stability testing and forced degradation studies in support of future filings to the TGA and FDA. Downstream manufacturing efforts required to produce the orally bioavailable clinical drug product, PD- 001 will also be completed by Genvion Corporation.

The proposed first-in-human study aims to be a prospective multi-site open label randomized controlled clinical investigation of the safety, tolerability, and pharmacokinetics of PD-001 in esophageal cancer subjects. The Company's decision to pursue clinical development of PD-001 for esophageal cancer initially in Australia derives from a streamlined regulatory framework established by Australia's Therapeutic Goods Administration (TGA) that permits a sponsor to bypass the lengthy and costly process of filing an IND application that would be required by the FDA, while also allowing a sponsor to evaluate its investigational drug prior to committing to larger clinical studies in the U.S. and Europe. In addition to the world-class facilities and deep clinical trial expertise located in Australia, the Company intends to take advantage of Australia's Research and Development (R&D) tax incentive program which will provide the Company with up to a 43.5% refund on all R&D expenditures.

Strict adherence to guidelines set forth by TGA ensures that the Company's clinical trial data will be acceptable to other regulatory bodies including the FDA. For the Company, human clinical data generated from Australia would de-risk PD-001's clinical development plan and support further investigation of PD-001 in subsequent Phase 2 and confirmatory studies in the U.S. under an IND with the FDA. PharmaDrug's investigational drug, PD-001, has been granted orphan drug designation by the FDA for the treatment of esophageal cancer.

Efforts to support clinical evaluation of PD-001 for esophageal cancer are currently underway. A large- scale cGMP lot of cepharanthine-2HCL has been completed and specific test methods required by the FDA for the quantification of drug attributes have been developed during Fourth Quarter of 2022 to support the issuance of the certificate of analysis and master batch record. Final release testing is ongoing and the Company plans to transfer this material to its contract manufacturer, Genvion Corporation.

Material transfer is planned for March, 2023 and once complete, Genvion will execute all necessary ICH- compliant stability testing and forced degradation studies in support of future filings to the TGA and FDA. Downstream manufacturing efforts required to produce the orally bioavailable clinical drug product, PD- 001 will also be completed by Genvion Corporation. 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 responsive cancers and COVID-19. 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.

The Company endeavours to develop an efficacious oral therapeutic to potentially improve outcomes for infectious disease and oncology applications. PharmaDrug's oncology program is based on cepharanthine's known anti-cancer activities. Cepharanthine has been shown in over 160 peer-reviewed publications 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).