Efficacy in Gemzar-resistant cancer is proven
NEW YORK, NY / ACCESSWIRE / May 19, 2016 / In rapid-fire fashion, striking clinical trial results for Rexahn Pharmaceuticals' (RNN) drugs are hitting news. From preclinicals to people, in under four years, two anti-cancer therapies - Archexin and RX-3117 that target tumors at the cellular level to either shrink or kill, posted recent impressive results. Medical recognition is growing with each presentation of data, and the green light to continue larger clinical trials is lit.
Rexahn worked hard to uncover druggable targets for its compounds. Even before animal results, the drugs mentioned above showed strong anti-cancer potential in hundreds of human cancer cell lines. Moving from the laboratory to mice to humans, Rexahn's compounds are realizing the dream once found only in the test tube.
First up: Archexin, Rexahn's drug designed to deal a death blow to metastatic renal cell carcinoma, or kidney cancer, by disrupting genetic information that would otherwise cause disease. Last month, final data was shown from the first stage of a combined Phase Ib/IIa trial at the widely attended American Association for Cancer Research, the high point determination of best dose that proved safe, and importantly, effective. FDA does not look for efficacy in early stage trials, but if it's there, all the better for positive agency attention readied for the next phased study.
Dr. Tagawa, Medical Director at Weill Cornell Medicine and lead independent researcher, went on record to heartily endorse Archexin that, coupled with everolimus (an immunosuppressant that works in renal cell carcinoma), worked exceedingly well. Of patients treated, tumor reduction of 16%, 36% and 32%, respective of dosage load, was observed which led to the maximum tolerated dose of 250 mg/m2/day in six cycles of treatment, the one to be used in the next study.
Kidney cancer, a condition that claims mortality in more than two-thirds of patients in a very short time, did not progress for 383 days. All patients were in advanced disease states with no hope responding to other drugs. The most common adverse effects were low blood platelet count and fatigue. Interesting, because everolimus can be toxic, leading to infection, pneumonia, trouble breathing and, ironically kidney failure. Archexin blocked this side effect.
Success in this $5 billion market opens a vista of opportunities for Rexahn's novel compound. Having proven a dose-dependent beneficial effect over a defined time period, Rexahn's next step is signing 30 patients for part two of its kidney cancer study; this time a randomized trial with two groups: Archexin with everolimus versus everolimus alone. Both safety and efficacy will be examined, the primary endpoint how long patients stay free of progressive disease.
Current remedies for kidney cancer can be dangerous. Avastin by Genentech, Inc. hit the market seven years ago but sometimes causes hypertension and erratic heartrate. More recently, Exelixis, Inc. (NASDAQ: EXEL) got FDA approval for its kidney cancer drug when studies showed a significant delay in metastasis. A couple of problems: severe to fatal hemorrhage, mortal blockage of major veins servicing the heart, and harm to the unborn. The heavyweight among kidney cancer contenders is Bristol-Myers Squibb's (NYSE: BMY) wonder drug Opdivo, blessed by the FDA last March but carrying an onerous list of side effects like breathing problems, persistent vomiting, and tearing in the bowels.
Next - RX-3117, which works through DNA to attack tumors and disrupt cancer's metabolism, is set to enter a preliminary Phase II for pancreatic and bladder cancer in 10 clinical sites. Tumor shrinkage is its goal, pointing to progression-free survival and validating proof of concept. Here again, a maximum oral dose was determined in an earlier trial, with stabilized disease through tumor reduction lasting 276 days at last count, that should facilitate successful results in the upcoming study.
The first patient has been enrolled, a significant milestone. Rexahn's Chief Medical Officer, Dr. Ely Benaim, noted limited options for these classes of cancer sufferers and pointed to RX-3117's unique mechanism of action - targeting malignancy very specifically while leaving normal cells alone, much to the contrast of modern chemotherapy. In the upcoming trial, RX-3117 will be given orally five times per week for three weeks with one week deemed a drug holiday. If the initial 10 patients chosen based on extent of disease respond well, up to 40 more will be enrolled, a sizable study for its phased level. Like with Archexin, primary endpoints are progression free survival and tumor shrinkage.
Cancer of the pancreas is tricky to manage. Malignant cells have a protective covering that renders them resistant to drugs, so metastasis occurs rapidly. Drug companies haven't had much luck; most were abandoned in Phase II with a major blunder by Amgen, Inc. (NASDAQ: AMGN) several years ago when a Phase III was halted because its drug did not show a significant survival benefit. Many compounds used now are chemotherapies with their attendant nasty side effects.
Last December, Momenta Pharmaceuticals (NASDAQ: MNTA) resumed Phase II of its drug used in combination with paclitaxel and gemcitabine after an independent safety monitoring board called for a hold in enrollment after clinical trial reports of bleeding risk and formation of potentially life-threatening blood clots. Earlier, OncoGenex Pharmaceuticals (NASDAQ: OGXI) stumbled with a disappointing Phase II combining its drug for pancreatic cancer with Celgene Corp.'s (NASDAQ: CELG) Abraxane and gemcitabine, where survival benefit was not found compared to Abraxane and gemcitabine alone and severe toxicities associated with OncoGenex' drug caused many clinical subjects to abandon the trial.
By contrast, Rexahn's work with RX-3117 is notable because the drug has shown anti-tumor effects in vitro over human cancer cell lines and in vivo efficacy in mouse models. In-vitro, or test-tube data, may or may not translate to mammals, either mice or humans. In Rexahn's case, it did; that's why the drug graduated to humans. RX-3117 further distinguishes itself with efficacy in pancreatic and bladder cancer patients who have failed gemcitabine, branded Gemzar by Eli Lilly (NYSE: LLY) before going generic, and a much-used therapy that, unfortunately, builds resistance in up to 40% of users. Therefore, RX-3117's value rests heavily in those with advanced stages of disease where gemcitabine doesn't work.
Rexahn moves efficiently and effectively toward very large medical markets: renal cell carcinoma costs $5 billion per year in the US; pancreatic another $8,000 to $200,000 per month per patient, or $3 billion at the low end; and bladder cancer weighs in at $5 billion total cost. It's clear Rexahn chose its disease indications wisely, preparing to return to investors a generous reward for risking funds in a small, pre-revenue stock.
In addition to its micro-cap status that carries its own blend of risks - less than robust liquidity, sparse news flow - specific risks apply including negative or statistically insignificant clinical data that emerges in larger sample sizes, resistance toward Rexahn's drugs through cancer mutation, and regulatory hurdles the company may encounter on its way to approval.
Cash as of 1Q16 (ended March 31) was $24.5 million, enough to support Rexahn through the second half of next year. Research and development expenses rose 21% from the comparable quarter in 2015, to $3.5 million, as would be expected for a company embarking on larger trials. Other operating costs declined as key personnel hiring was completed. Net loss remained flat, at $4.1 million, or ($0.02) per share.
Two solid tumor cancer targets with large markets, positive preclinical data translating to humans, dedicated researchers and strong, focused management characterize Rexahn. Its low valuation belies its ultimate potential which is to provide the world with novel, effective compounds that are safe to use. I view this stock as an attractive addition to a portfolio designed to share in one of the most spectacular areas of cancer medicine in its earlier stages, for a pronounced reward in the near future.
About Small Cap Forecasting, Inc.
Sharon di Stefano has spent 20 years as an analyst, beginning her career at Smith Barney, Harris Upham & Co. specializing in medical devices, pharmaceuticals, healthcare information technology, and bio-pharmacology. Ms. di Stefano had also served as Senior Venture Officer for the Edison Innovation Fund, implemented through the New Jersey Economic Development Authority that provided funding for early-stage life sciences companies. Industry experience includes laboratory research for Johns Hopkins Hospital and the Department of Defense. Ms. di Stefano received a Master's of Science degree, in Business, from Johns Hopkins University in 1986, and a Bachelor of Arts from the University of Delaware in 1984 with a minor in biology.
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Jackie Rodriguez
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SOURCE: Small Cap Forecasting, Inc.
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