Success Of Rexahn's Nano-Sized Taxotere Can Help Big Pharma Ease Patent Cliff

| About: Rexahn Pharmaceuticals (RNN)
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RX-21101, a nanopolymer formulation of popular cancer drug Taxotere, showed encouraging results in mice models that suggest more specific tumor targeting, less toxicity, and better survival rates.

Lead drug Archexin is ready for Phase IIa trials for advanced renal cell carcinoma; Phase Ib trials in solid tumors with Supinoxin showed good safety and efficacy data, mirroring preclinicals.

Speculative and micro-cap company risks remain, as do regulatory goals.

Company transformation begun last year continues: the pipeline progresses, fundamentals improve, management remains confident.

Rexahn may be able to offer pharmaceutical firms a new way to deal with imminent patent expirations.

Cancer treatment's most prized goal has been and continues to be the selective death of tumor cells while keeping surrounding tissue unharmed. Chemotherapy does a fine job attacking malignancy, but drug molecules are so tiny they enter and poison healthy cells, the basis for noxious and sometimes fatal side effects. For years, scientists have theorized that attaching anti-cancer compounds to larger molecules would deliver the intended effect while preserving everything else. This is the basis for research into nano-sized cancer therapy.

Only a handful of researchers worldwide are pursuing the use of nano-materials in cancer as the technology to create sophisticated drug delivery platforms catches up, and Rexahn Pharmaceuticals, Inc. (NYSEMKT:RNN) took its place among nano innovators with data on its drug RX-21101 presented at the American Association for Cancer Research (AACR), one of the world's largest venues for disseminating findings among scientists and industry.

In a poster session titled "Synthesis of targeted docetaxel-polymer conjugate and its anti-tumor efficacy", Rexahn showed that the chemotherapy agent docetaxel, or Taxotere, when coupled with a nanopolymer to become RX-21101 stopped tumor growth and aided tumor regression in mice compared to docetaxel alone. Weight of the subjects did not change significantly, suggesting the absence of bad side effects. The best news: more mice treated with RX-21101 survived much longer versus docetaxel, with almost 60% alive after 90 days.

Like other experimental nano compounds for cancer, RX-21101is highly soluble in water, gaining the drug better access to cells and better able to deliver drugs directly to targets. Most anti-cancer agents show poor solubility in water and thus exhibit more of a scatter-shot approach in treatment. Even in laboratory bench studies RX-21101proved valuable: when the nanopolymer/docetaxel combination was added to human cancer cell lines, cancer's spread was stalled.

RX-21101 is the result of intensive studies in collaboration with the University of Maryland at Baltimore who, with Rexahn, discovered a new technology, the Nano-Polymer-Drug Conjugate Systems (NPDCS) platform for making nano-sized drugs out of available chemotherapeutics for focused targeting of tumors. RX-21101's preclinical efficacy and survival data are validation of the platform's ability to produce new drug candidates based on FDA-approved chemotherapies, without as many, if any, adverse effects, effectively lowering clinical development risk.

Taxotere, once a multi-billion dollar darling of oncologists, remains marketed exclusively by Sanofi (NYSE:SNY) and although the branded version has been subject to generic competition, docetaxel is still widely used for cancer of the prostate, breast and lungs. Even with sales of approximately $560 million in 2013, down 82% from the drug's peak, Taxotere remains Sanofi's top revenue producer in oncology and Jevtana and Zaltrap, two recent Sanofi anti-cancer products, have not come close to blockbuster status since approval. Timing is advantageous for Rexahn to offer an improved version of Taxotere to help it reclaim its revenue potential, particularly if the version lacks onerous side effects that include nausea, neutropenia, anemia, and hair loss.

As more data is gathered showing how nanotechnology can improve the targeted efficacy and lower risks of cancer drugs, pharmaceutical companies will take notice. Leading the pack is biochemist Andy Tao of Purdue University, whose team developed a way to coat existing drugs with nanopolymers to see which proteins inside the cell are affected, to tell which drugs are hitting targets. Chemotherapy agents by nature come in contact with a number of different proteins, so increasing their specificity would in effect reduce side effects, greatly improving the drug's marketability. Drug companies would also benefit from a reduction in clinical trial cost as knowledge of which proteins are affected allows them to test only those compounds that target the protein they want.

Last August, a team of scientists in Tel Aviv demonstrated conclusively that because effective cancer treatment typically involves coordination of different drugs by different routes, raising therapeutic complexity, use of polymers as a drug delivery system improves absorption and metabolism, resulting in greater efficacy and lower toxicity. More drug accumulates at the tumor site, so less is needed. They concluded that these new delivery systems will improve patient compliance and providing better patient results.

Sanofi is not the only manufacturer to possibly benefit from nano-sized chemotherapy drugs; besides a meaningful reduction in side effects, drug makers could be offered a solution to upcoming patent expirations where their replacement compounds may not fill the vacuum or be perceived by doctors as no better than similar offerings. Shortly after Zaltrap's approval Sloan Kettering refused to use the drug due to its cost of $11,000 per month, choosing instead Avastin by Roche Holding AG (OTCQX:RHHBY). The choice was made easier when prescribing oncologists considered Zaltrap's list of adverse effects that include severe internal bleeding of the brain or lungs, holes in the stomach or intestines, and wounds that won't heal.

Roche's Xeloda generated $1.6 billion in revenue in 2012, the last year before Teva Pharmaceuticals (NYSE:TEVA) was granted approval for its generic. In 2013, Xeloda's sales were more than cut in half, to $736 million. Novartis' Gleevec, a $4.7 billion seller in 2012, goes off-patent starting this year and has had the company desperate to show that new compound Tasigna is better for the same indication, despite a cost of $40,000 per year that may negate any increased efficacy of the new drug over the old.

Monoclonal antibodies ((mAbs)), valued for their inhibition of cancer cell proliferation and blood vessels that feed tumors, may or may not lend themselves to nano-sizing but recent evidence shows that nanomaterials like polymers may bind effectively with mAbs to deliver a superior therapeutic value, like focused tumor targeting and better patient absorption, metabolism and elimination. This is good news for Roche, whose Rituxan faced a European patent cliff at the end of 2013 after posting revenue of $8 billion that year, and loses patent protection in the US in 2018. Erbitux, jointly owned by Bristol-Myers Squibb Co. (NYSE:BMY) and Eli Lilly and Co. (NYSE:LLY) with sales in excess of $700 million, will be eligible for generic competition in Europe this June and in the US in 2016.

Big Pharma has several strategies to manage the loss of patent protection like buying pipelines through acquisition or cutting back on research and development, although that can ultimately hurt a competitive edge. Rexahn's nanomaterial innovation that would extend a drug's franchise through reformulation is a much more attractive solution.

In other clinical news, lead drug Archexin is set to enter Phase IIa trials for metastatic renal cell carcinoma (RCC) in conjunction with Novartis AG's (NYSE:NVS) Afinitor with an endpoint of progression-free survival. Determination of maximum dosage will lead to testing in another cohort of patients randomized to the combination therapy or Afinitor alone. Mixture of the two drugs should prove especially interesting because Afinitor's anti-tumor action may be enhanced by Archexin's property as an Akt-1 inhibitor. If trials are successful, Archexin, upon approval, might become an adjunct therapy to Afinitor, expanding market presence as use of Afinitor grows.

Safety and efficacy data from a Phase Ib clinical trial with orally-administered Supinoxin in solid tumors that have failed other treatment regimens was revealed in March where results seen in preclinical studies were repeated - a good sign. In addition, Rexahn is conducting Phase Ib trials with its DNA synthesis inhibitor RX-3117 in solid tumors to illustrate apoptosis (programmed cell death). New data for RX-3117 was also displayed in a poster session at AACR where the compound showed strong anti-tumor activity in cancer of the colon, lung, pancreas, kidney, ovaries and cervix, including those resistant to gemcitabine, in animal models transplanted with human cancer cells.

Regardless of achievements in early clinical trials, Rexahn, considered as a small-cap stock, is a speculative play although shares trade actively and progress reports are plentiful. Like any biopharmaceutical firm big or small, ongoing studies may fail, particularly later ones with greater sample size and more opportunities for adverse events or missed endpoints. As time goes on, however, Rexahn should further define its clinical goals and has great potential in filling its pipeline with compounds born of its NPDCS platform. Fund-raising efforts have been fruitful and culminated in a recent deal that brought $20 million in gross proceeds, making for a strong balance sheet with $40.3 million in cash and investments as of March 21, 2014; however, at its current quarterly burn rate Rexahn has approximately five years of cash, which may not be enough as trials progress and become larger.

Rexahn's regulatory progress has been rapid in 2014 and a clearer focus on its oncology efforts have given the company a more cohesive mission of finding better drugs in the $48 billion plus worldwide cancer market. Investors have recognized positive developments and shares have responded with an 81% increase year-to-date. With unique compounds in clinical trials and the advantage of a drug discovery platform that might benefit other industry players that fear patent cliffs, Rexahn promises to provide plenty of near-term catalysts to boost valuation.

Disclosure: I am long RNN. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.