Rexahn Pharmaceuticals, Inc. a clinical stage biopharmaceutical company developing best-in-class therapeutics for the treatment of cancer, today announced that it will have two poster presentations at the 2014 American Association for Cancer Research (AACR) Annual Meeting. The conference will take place in San Diego, California, on April 5-9, 2014 at the San Diego Convention Center.
The first poster entitled, “A novel small molecule cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to treatment with gemcitabine,” will be presented on Sunday, April 6, 2014, during the “Experimental and Molecular Therapeutics 6” poster session from 1:00 pm – 5:00 pm in Hall A-E, Poster Section 34. The second poster entitled, “Synthesis of targeted docetaxel-polymer conjugate and its anti-tumor efficacy,” for RX-21101 will be presented on Tuesday, April 8, 2014, during the “Chemistry 8” poster session from 1:00 pm – 5:00 pm in Hall A-E, Poster Section 27.
Peter D. Suzdak, Ph.D., CEO of Rexahn, commented, “The inhibition of tumor growth produced by RX-3117 in human cancer cells already resistant to gemcitabine is a very important finding. Approximately 25% of patients treated with gemcitabine become resistant after one cycle of therapy, representing a large unmet medical need and a significant opportunity for the clinical development and potential commercialization of RX-3117.” Rexahn initiated a Phase Ib clinical trial of RX-3117 in cancer patients with solid tumors in January 2014.
RX-21101 is the first development candidate derived from the Company’s Nano-Polymer-Drug Conjugate Systems (NPDCS) platform. This technology targets the delivery of currently marketed chemotherapeutic agents directly into cancerous tumors. RX-21101 is a polymer conjugated form of docetaxel, a common chemotherapy agent that is now generic but is marketed worldwide under the trade name Taxotere® and had annual sales of $3.1 billion when still under patent.
“In preclinical studies, RX-21101 has demonstrated increased efficacy and reduced toxicity, as compared to intravenously administered free docetaxel,” explained Dr. Suzdak. “RX-21101 contains a signaling moiety that directs the delivery of docetaxel into tumor cells while minimizing the free circulating levels of docetaxel. This approach reduces potential adverse events and maximizes the anti-tumor activity of docetaxel.”
“The NPDCS platform has the potential to generate multiple development candidates using other pharmaceutical companies’ cytotoxic anticancer compounds, transforming them into cancer cell specific compounds with reduced side effects and increased efficacy. This represents a clinical development approach for Rexahn with lower risk, using FDA approved anticancer compounds. Rexahn looks forward to utilizing the NPDCS platform to develop multiple development candidates for either internal development or out licensing,” Dr. Suzdak concluded.
RX-3117 is a next generation nucleoside analog that is activated (phosphorylated) by the enzyme Uridine Cytidine Kinase (UCK) and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. UCK is overexpressed in multiple human tumors, but has a limited presence in normal tissues. This unique specificity for cancer cells may lead to an improved efficacy and safety profile in cancer patients. RX-3117 also mediates the downregulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown RX-3117 to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance.
RX-3117 has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, RX-3117 still retains its full anti-tumor activity in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of RX-3117 in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of RX-3117 demonstrated an oral bioavailability of 56% and a plasma half-life (T1/2) of 14 hours. In addition, RX-3117 was safe and well tolerated in all subjects throughout the dose range tested.
RX-21101 was developed using the Nano-Polymer-Drug Conjugate Systems (NPDCS) platform jointly discovered with the University of Maryland at Baltimore. This technology targets the delivery of currently marketed chemotherapeutic agents directly into cancerous tumors. The direct delivery of chemotherapeutic drugs into the tumors has been shown to result in increased efficacy and reduced toxicity. The NPDCS platform combines existing chemotherapeutic agents with a proprietary polymer carrier that contains a signaling moiety which directs the drug into the tumor. This approach minimizes the levels of freely circulating anti-cancer agents in the body, which can dramatically reduce potential adverse events, and maximizes anti-tumor activity by accumulating in the cancer tumor. NPDCS is a broad platform that has the potential to generate multiple therapeutic candidates going forward.
RX-21101 (HPMA-docetaxel-folate) is a polymer conjugated form of docetaxel, a common chemotherapy agent. In preclinical studies, RX-21101 demonstrated increased efficacy and reduced toxicity, as compared to intravenously administered free docetaxel. Docetaxel is now generic but is marketed worldwide under the trade name Taxotere® for the treatment of breast, ovarian, prostate, and non-small cell lung cancer. Despite its commercial success, docetaxel is toxic to all dividing cells in the body and is associated with a high incidence of adverse events including anemia, infection, fever, neutropenia, neuropathy, asthenia, edema, alopecia, nausea and vomiting. These adverse events are the result of high concentrations of free docetaxel in the blood. By minimizing the circulating concentration of free docetaxel in the blood and maximizing the concentration in the cancer tumor, RX-21101 may increase anti-tumor activity and a lower incidence of adverse events.