Where others have failed, Rexahn Pharmaceuticals (RNN) is making rapid progress manipulating the elusive cancer fighting Akt-1 pathway in clinical trials for solid tumors. Akt is an enzyme that modifies proteins by altering the biochemical signals they receive in the body, and has been identified as a leading molecular contender to disrupt a route that leads to tumor development. Rexahn created Archexin, an Akt-1 inhibitor, and successfully used it with the chemotherapy agent Gemzar (gemcitabine) in clinical trials that raised pancreatic cancer survival to almost double that of Gemzar alone.
For Rexahn, a more substantial Phase II with Archexin is set to commence soon with an enrollment goal of 150 patients who express the Akt pathway; this will make the clinical trial that much more precise and improve the chances of patient response. Another protocol for Phase II with Archexin combined with two chemotherapy agents in ovarian cancer is approved and awaiting enrollment. In addition to pancreatic and ovarian, Rexahn has FDA Orphan Drug status in renal, stomach and brain cancer.
Despite the value of an Akt inhibitor in cancer, competition is small. Rights for the compound under the name perifosine had bounced between AEterna Zentaris (AEZS) and Keryx Pharmaceuticals (KERX) until it failed trials in colon cancer and multiple myeloma; in the latter instance studies had progressed to Phase III before an influential review board looking at interim data found no significant extension of progression-free survival, prompting AEterna to scrap further plans.
Merck & Co.'s (MRK) experience with the esoteric Akt inhibitor is vast but inconclusive. First-in-man trials of an Akt inhibitor oral version, Merck's MK-2206, reached public awareness around 2009. That year, Merck reported the results of a thin trial of 33 patients with solid tumors. The best response was 'stable disease', an ambiguous result in only 18% of those tested. Since then, over 50 human clinical trials either have been or are in the process of being conducted in multi-site studies involving in some cases over 30 states from Connecticut to California. Most of them are no further than Phase II in solid tumors including endometrial, prostate, breast, gastric, and head and neck, and most include another agent like chemotherapy, an anti-androgen, or a kinase inhibitor (for an enzymatic response). There are two studies recruiting for pancreatic cancer in Phase I and II using another agent along with the Merck Akt inhibitor; neither these, or the others, have not posted results to show their science as superior in using Akt inhibitors as effective solid tumor reducers.
A valuable Akt inhibitor is not all Rexahn offers in its oncology pipeline. There is RX-3117, a small molecule acting on DNA synthesis to disrupt the metabolism of cancer where a successful Phase I proved it to sufficiently entered the bloodstream to cause a therapeutic effect. Rexahn is partnered with Teva Pharmaceutical Industries (TEVA), the world's largest maker of generics with a vested interest in both branded cancer drugs and Rexahn itself. Two years ago, Teva solidified its diversification into non-generics with the $6.8 billion purchase of Cephalon. Threats from Momenta Pharmaceuticals (MNTA) and Mylan, Inc. (MYL) have forced Teva to pay more attention to its worldwide dominance in several product categories. Since 2009, it supports Rexahn in broadening the scope of RX-3117 with development in solid tumors and blood cancer and is a 6.3% owner of Rexahn's outstanding shares with more milestone payments expected.
The third cancer-fighting compound Rexahn studies, RX-5902, inhibits an enzyme known as RNA helicase p68 that performs intercellular splicing governing cell growth and cell division and plays a critical role in early organ development. Its expression is correlated with tumor progression and transformation and suppression of p68 has been shown to lessen tumors formation in vivo (in test-tubes). Studies with p68 have the advantage of efficiency because it is not present in non-cancerous tissue, making for clearer targets. Phase I trials with a pill version in various cancers should start this year pursuant to an investigational new drug (IND) application submitted to the FDA in July 2012.
Besides drug development, Rexahn has a drug discovery platform that screens compounds before expensive clinical trials, giving them good vertical integration for potential cost savings. Further, Rexahn is using liposomal and polymer nano-technology to increase therapeutic absorption of its compounds in the body while reducing side effects. A second-generation nano-version of Archexin is being developed to more effectively target tumor cells.
Financing oncology is heating up with corporate partner money for compounds showing proof of concept. Last year, Endocyte, Inc. (ECYT) sold the rights to vintafolide, in Phase III trials for ovarian cancer, to Merck for $1 billion including milestones. Not long after, Denmark-based Genmab signed with Johnson & Johnson (JNJ) to license human monoclonal oncology compound daratumumab in relapsed and refractory multiple myeloma, for an upfront payment of $55 million, potential double digit royalties, and a complete package reaching a possible $1.1 billion.
Rexahn's work in pancreatic cancer is notable because the disease, by virtue of a protective cancer cell covering that proves resistant to drugs, tends to enter metastasis before it is diagnosed, making other drug firms shy away from committing money to its treatment. Most results fizzle in Phase II, and Amgen, Inc. (AMGN) halted a Phase III trial last August when its compound did not show a significant survival benefit at an examination of interim results.
Pancreatic cancer kills almost 40,000 Americans each year and despite the problems with studies, companies pursue the indication because the global pancreatic cancer market is expected to rise to $1.2 billion within two years. Cashing in, Celgene Corp. (CELG) offers Abraxane, a redesigned form of the standard chemotherapy agent paclitaxel, as a first-line defense coupled with gemcitabine that passed all Phase III trials and now sits in a supplemental New Drug Application ((sNDA)) at the FDA for priority review in pancreatic cancer that could see approval this September. The drug, however, extended progression-free survival only two months versus gemcitabine alone.
In another attempt, Threshold Pharmaceuticals (THLD) combined gemcitabine with its TH-302 to attack pancreatic cancer cells at the genetic level in a complex chemical reaction intended to further starve tumors of oxygen. Mid-stage trials showed promise in progression-free survival but no overall survival benefit, and a Phase III is being funded by partner Merck KGaA of Germany with a better design. Interim results won't be ready until next year. Peregrine Pharmaceuticals (PPHM) is testing bavituximab, an immunosuppressant agent used in a convoluted approach to support the body's natural defense system to fight the development of solid tumors, but is not without its troubles. Last year an analysis of double-blind trial results with bavituximab in lung cancer revealed a miscounting of patients receiving the drug versus placebo, negating past data that had shown a doubling of survival.
Rexahn is favorably positioned to continue its work, with a recent raise of $6.6 million by biotech research leaders Maxim Group, and the appointment of a pharmaceutical veteran, Peter Suzdak, Ph.D. whose past positions include Director of Neurobiology for Novo Nordisk A/S (NVO:NYSE), V.P. of Research and Development at Guilford Pharmaceuticals, where he was involved with work on pancreatic cancer, founder of start-up Cardioxyl Pharmaceuticals, CEO of Artesian Therapeutics, and Chief Scientific Officer of Corridor Pharmaceuticals. Dr. Suzdak is busy moving Rexahn away from its former development endeavors and into oncology.
The primary risk to investing in Rexahn, in addition to the fact that it is a microcap biotechnology concern with all of the usual dangers involved, is the task of successfully treating solid tumor cancer with an Akt-1 inhibitor, a compound that has alluded past attempts by other investigators. I find confidence in the fact that Merck is conducting so many trials with its own inhibitor that it must see a future value. Competition from Celgene in pancreatic cancer is more an advantage than a risk because it should pave the way for oncologists to try an alternative to suboptimal Gemzar. The support of Teva is also strong assurance of RX-3117's potential worth.
With its financing last December, Rexahn has a pristine balance sheet showing cash on hand of $12 million plus and no debt. I believe that Rexahn is in a good position to continue trials without money concerns for the next 18 months. Additionally milestone payments from partner Teva should be forthcoming in the next several months when an IND for RX-3117 is submitted and patient enrollment for a Phase I trial commences.
Rexahn is a stock to take notice of. Solid tumor oncology solutions always deserve attention but a new approach to using the Akt-1 inhibitor pathway does not come along often. An investment in Rexahn at current prices is a smart way to capitalize on the hottest area of cancer development while banking on a high future return.