- Provisional patent filed (April 14, 2022) to support use of PD-001 plus cabazitaxel for primary, metastatic and chemotherapy-resistant prostate cancer
- Final study results show that oral cepharanthine (PD-001) plus cabazitaxel combination therapy significantly reduced tumor volume and increased tumor growth inhibition
- Dose range finding demonstrates that oral cepharanthine-alone was well tolerated
- Addition of PD-001 to cabazitaxel dosing regimen did not increase toxicity
Toronto, Ontario–April 19, 2022 – PharmaDrug Inc. (CSE: PHRX) (OTCQB: 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, cannabis and naturally-derived approved drugs, is pleased to announce that the Company’s enteric coated, oral formulation of cepharanthine (PD-001), when combined with cabazitaxel, significantly reduces tumor volume and provides improved prostate cancer tumor growth inhibition. Accordingly, the Company has filed a second provisional patent application to support new claims specifically related to the in vivo dosing of cepharanthine in combination with taxane-family members for the treatment of prostate cancer. The current patent application aims to complement the previous provisional patent filing, built around the Company’s in vitro study findings, which set forth claims related to the use of cepharanthine plus cabazitaxel and/or other taxane family members used in combination to treat primary, metastatic and chemotherapy-resistant prostate cancer.
Daniel Cohen, CEO and Chairman of PharmaDrug commented, “With our new provisional patent filing we continue to broaden the use case for PD-001 as a treatment for prostate cancer. While esophageal cancer continues to be our main focus with a goal to move towards an FDA clinical trial, we believe that cepharanthine will ultimately show a wider potential use in the treatment of cancers, specifically in combination with the current standard of care chemotherapies”.
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 (SoC) 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. Here the Company is pleased to report that a once-per-day oral regimen of PD-001, in combination with cabazitaxel provided statistically significant benefit from day 10 through to the end of dosing (day 21) in its recently completed prostate efficacy study. Throughout the study, the degree of tumor growth inhibition continued to improve for those groups receiving the combination of PD-001 and cabazitaxel versus cabazitaxel-alone, suggesting that perhaps a more sustained dosing regimen might result in greater efficacy. Upon completion of study dosing, PD-001 delivered at doses of 3, 9, or 27 mg/kg/day combined with cabazitaxel (3mg/kg/Q3D) 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. These results were deemed to be highly statistically significant, with a p-value less than 0.001 (day 21). Addition of PD-001 to cabazitaxel did not notably increase toxicity compared to cabazitaxel alone.
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 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. Despite enormous research efforts, metastatic prostate cancer has a 5-year survival of only 31%3. Through subsequent rounds of refinement to optimize PD-001 dose and dose interval, the Company endeavours to develop an efficacious, oral therapeutic add-on option to potentially improve outcomes for prostate cancer patients using SoC treatment.
The Company is not making any express or implied claims that its product has the ability to eliminate, cure or contain the Covid-19 (or SARS-2 Coronavirus) at this time.
PD-001 for Cancer
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 (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). 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 drugs4–7. Collectively the two in vitro screening studies already completed by the Company and the interim in vivo efficacy results provided here, continue to reinforce the potential therapeutic opportunities in oncology for PD-001 when used in combination to provide additive or synergistic benefit to existing SoC treatments. For reference to previous press releases related to PharmaDrug’s ongoing efforts in the oncology space please see previous press releases dated Feb 1, 2022 and Nov 18, Oct 15, July 28, 2021. 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 FDA Orphan Drug Designation PD-001 for the treatment of esophageal cancer.
Potential of PD-001 to treat Prostate Cancer
According to the American Cancer Society, in 2021 there were approximately 248,530 new cases of prostate cancer and about 34,130 deaths from prostate cancer in the United States, and it is the second leading cause of cancer death in American men. Metastatic prostate cancer is commonly treated using androgen deprivation therapy (ADT), including surgical or medical castration, but metastatic castration-resistant prostate cancer (mCRPC) commonly emerges8. The taxanes docetaxel and cabazitaxel are approved for the treatment of mCRPC, however resistance to taxanes is known to develop over time. Agents such as PD-001 which show synergistic benefit when combined with taxanes for the treatment of prostate cancer are sorely needed. The Company’s forthcoming in vivo studies are specifically designed to address the potential of PD-001 to overcome taxane-based chemoresistance in vivo.
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, cannabis and naturally-derived approved drugs. PharmaDrug owns 100% of Pharmadrug Production GmbH (“Pharmadrug Production”), a German medical cannabis distributor, with a Schedule I European Union narcotics license and German EuGMP certification allowing for the importation and distribution of medical cannabis to pharmacies in Germany and throughout the European Union. PharmaDrug owns 100% 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 Covid-19 and rare cancers. Sairiyo is also conducting R&D in the psychedelics space for the treatment of non-neuropsychiatric conditions. The Company also owns 100% of Super Smart, a company building a vertically integrated retail business with the goal to elevate the use of functional mushrooms, and psilocybin mushrooms where federally legal, as natural based medicines.