Rexahn Pharmaceuticals Announces Initiation of Phase Ib/IIa Clinical Trial of Novel Oral Anti-Cancer Therapeutic

Rexahn Pharmaceuticals, Inc. recently announced that is has enrolled the first patient in its Phase Ib/IIa clinical trial of a the novel oral anti-cancer agent, RX-3117, in patients with relapsed and refractory pancreatic cancer and advanced bladder cancer.

“We selected pancreatic and bladder cancers as initial indications in the Phase Ib/IIa clinical trial of RX-3117 for several reasons,” said Dr. Ely Benaim, Chief Medical Officer for Rexahn. “First, options for patients with these types of cancers are limited, and prognosis is very poor, hence there remains significant unmet medical need for effective next generation therapies like RX-3117. In addition, RX-3117 has a novel mechanism of action, which is highly specific for cancer cells versus healthy cells. Results from our clinical and preclinical studies suggest that RX-3117 is effective at inhibiting the growth of a wide variety of solid cancer tumors, including gemcitabine resistant pancreatic and bladder cancers. Resistance to gemcitabine is a significant problem in cancer therapy – in fact, between 25% and 40% of cancer patients receiving gemcitabine rapidly become resistant, diminishing the treatment benefit and leaving patients with few or no options. We are excited by the data we have obtained thus far for RX-3117 showing its potential efficacy and favorable safety profile in the Phase Ib clinical study, and therefore look forward to evaluating its activity further in these select patient populations with significant unmet medical need.”

The Phase Ib/IIa clinical trial is a multicenter, open-label single-agent study of RX-3117 being conducted at 10 clinical centers in the US. RX-3117 will be administered orally 5 times weekly on a 3 weeks on, 1 week off dosing schedule. The study will follow a two-stage design. In the initial stage, 10 patients with relapsed or refractory pancreatic cancer and 10 patients with advanced bladder cancer will be enrolled. If responses are observed within the first 10 response-evaluable subjects, 40 additional subjects could be enrolled. The primary endpoint is an assessment of the progression free survival rate or an objective clinical response rate and reduction in tumor size. Secondary endpoints include time to disease progression, overall response rate and duration of response, as well as pharmacokinetic assessments and safety parameters.

“The initiation of a Phase Ib/IIa clinical trial marks a major milestone in the RX-3117 clinical development program,” commented Peter D. Suzdak, PhD, Chief Executive Officer. “Preliminary results from the Phase Ib clinical trial were presented at the joint 18th ECCO – 40th ESMO European Cancer Congress in late 2015. They showed that RX-3117 appeared to be safe and well tolerated and demonstrated evidence of single agent activity, specifically tumor reduction and stable disease persisting for up to 276 days. The completed clinical data from the Phase Ib clinical trial will be presented at a clinical oncology meeting during 2016. We are encouraged by these results and look forward to evaluating the potential anti-cancer effects of RX-3117 more comprehensively in this Phase Ib/IIa clinical trial.”

RX-3117 is a novel, investigational small molecule nucleoside compound. Once intracellularly activated (phosphorylated) by UCK2, it is incorporated into the DNA or RNA of cells and inhibits both DNA and RNA synthesis, which induces apoptotic cell death of tumor cells. UCK2 is highly overexpressed in various human cancer cells. Preclinical studies have shown that RX-3117 inhibits the growth of various human cancer xenograft models, including pancreatic, bladder, lung, cervical and colon cancers, as well as gemcitabine resistant cancer cells.
RX-3117 has demonstrated broad spectrum anti-tumor activity against over 100 different human cancer cell lines and efficacy in 17 different mouse xenograft models. Notably, the efficacy of RX-3117 in the mouse xenograft models was superior to that of gemcitabine. Importantly, 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 a 50 mg dose of RX-3117 demonstrated an oral bioavailability of 56% and a plasma half-life (T1/2) of 14 hours. In addition, RX-3117 appeared to be safe and well tolerated in all subjects throughout the dose range tested.

RX-3117 is currently being evaluated in a Phase Ib/IIa clinical trial in cancer patients with relapsed or refractory pancreatic cancer or advanced bladder cancer. The Phase Ib/IIa clinical trial is a multi-center study that will evaluate the safety and efficacy of RX-3117 in these target patient populations. Secondary endpoints include safety and pharmacokinetic analyses. Patient enrollment has been initiated. Patients in the trial will be receiving a daily oral dose of RX-3117 of 700 mg, five times weekly for 28 days and 4 treatment cycles, or until their disease progresses.

Rexahn Pharmaceuticals Inc. is a clinical-stage biopharmaceutical company dedicated to developing novel, best-in-class targeted therapeutics for the treatment of cancer. The company’s mission is to improve the lives of cancer patients by developing next generation cancer therapies that are designed to maximize efficacy while minimizing the toxicity and side effects traditionally associated with cancer treatment. Rexahn’s product candidates work by targeting and neutralizing specific proteins believed to be involved in the complex biological cascade that leads to cancer cell growth. Pre-clinical studies indicate that certain of Rexahn’s product candidates may be effective against multiple types of cancer, drug resistant cancers, and difficult-to-treat cancers, and others may augment the effectiveness of current FDA-approved cancer treatments. The Company has a broad oncology pipeline that includes three anti-cancer compounds currently in clinical development: Supinoxin; RX-3117; and Archexin, and a novel nanopolymer-based drug delivery platform technology that may increase the bio-availability of FDA-approved chemotherapies. For more information, visit www.rexahn.com.