공시 • Apr 03
Pharmadrug Inc. Provides an Update on Multiple Activities Currently Underway Which Support the Company's 'Pipeline-In-A-Pill' Approach in the Development of PD-001
Pharmadrug Inc. provided an update on multiple activities currently underway which support the Company's 'pipeline-in-a-pill' approach in the development of PD-001, its patented, orally bioavailable version of cepharanthine for the treatment of cancer and infectious disease. Following submission of its Type B pre-IND meeting request and briefing package to the U.S. Food and Drug Administration, the Company received a written response regarding its clinical development plan for PD-001, as a potential oral antiviral pill for COVID-19 and variants of concern. PharmaDrug believes the feedback provides a path to agreements on IND-enabling studies, the design of a Phase 1/2 clinical study, and the overall clinical development plan to move PD-001 forward as an oral treatment for COVID-19. By extension, the FDA guidance also provided important insights on advancing PD-001 as a potential treatment for oncology indications as part of the Company's ongoing strategy of targeting prostate and esophageal cancers. The Company remains focused on completing the remaining IND- enabling studies to support its planned clinical studies. Based on positive feedback from the FDA on the Company's proposed Chemistry and Manufacturing Control program, PharmaDrug has initiated cGMP production at Southwest Research Institute of a quantity of PD-001 that is expected to be sufficient to support development activities through to the end of phase II assessment. Since the Company's press release on January 26th, 2022, bulk active pharmaceutical ingredient has been received by SwRI and the drug substance, cepharanthine-2HCL, is being manufactured. Completion date is expected to be Q2, 2022. Following full characterization of the drug substance for critical quality attributes the drug product manufacturing will commence. The material produced under these tasks will support IND-enabling activities, such as stability, safety, toxicology, pharmacokinetic and non-clinical efficacy studies, required by the FDA prior to proceeding to human clinical studies. Work completed thus far on the parent molecule, cepharanthine by PharmaDrug and others, potentially de-risks and expedites several aspects of these studies. The Company is focused on advancing the clinical development of an improved and patented enteric- coated oral formulation of cepharanthine 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 . 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. In 2021 the Company initiated a series of cancer screening studies aimed at uncovering therapeutic opportunities for cepharanthine when used alone or in combination with standard of care chemotherapy drugs. Results from these in vitro studies revealed that the combination of cepharanthine and cabazitaxel, a SoC used for castration-resistant, metastatic prostate cancers, provided unexpectedly synergistic reduction in prostate tumor cell survival. The Company previously reported that a once-per-day oral regimen of PD-001, in combination with cabazitaxel provided statistically significant benefit at the scheduled end of dosing in its recently completed prostate efficacy study. Specifically, PD-001 delivered at doses of 3, 9, or 27 mg/kg/day combined with cabazitaxel provided up to a 64% tumor growth inhibition compared to 37% noted for treatment with cabazitaxel alone. Based on these results, the addition of PD-001 to the SoC, cabazitaxel was found to improve tumor growth inhibition by 73% compared to cabazitaxel-alone. Since releasing interim results from this study, the Company has been provided a final study report. Currently, the Company's intellectual property counsel is working on a provisional patent submission that aims to provide new evidence to support and potentially expand its claim set around the use of PD-001 and cabazitaxel to treat prostate cancer. Agents such as PD-001 which show synergistic benefit when combined with taxanes for the treatment of prostate cancer are sorely needed. The Company plans to provide an update on the final in vivo study outcome soon. In addition to its ongoing investigations of PD-001 for prostate cancer, the Company plans to fully leverage the streamlined path to approval which comes by way of a recently granted FDA Orphan Drug Designation for PD-001 for the treatment of esophageal cancer. To that end, PharmaDrug has now initiated an IND-enabling study to evaluate efficacy and tolerability of orally administered PD-001 in an esophageal cancer model. For this study, PD-001 will be administered alone and in combination with a SoC chemotherapy drug and tumor growth will be monitored. Results of this study are expected in Q2, 2022. Collectively the Company's panning approach of going from very broad to very specific cancer types which are highly responsive to PD-001 has yielded two high impact hits and has laid a strong foundation for continued development in the oncology space. For reference to previous press releases which detail PharmaDrug's ongoing efforts in oncology please see the Company's press releases dated March 9, Feb. 1, 2022 and Nov. 18, Oct 15, July 28, 2021. 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 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, . 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 drugs1-4. o date, several third party validated library screens of approved and investigational drugs have dentified cepharanthine as a forerunner candidate molecule in the treatment SARS-CoV-2, the virus that auses COVID-195-7. In fact, cepharanthine has now been shown to be highly effective at blocking cell eath following exposure to multiple different coronaviruses, including COVID-19, lab-attenuated SARS- CoV and the virus that causes Middle East respiratory syndrome 5-7.