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Rexahn Pharmaceuticals, Inc. ( AMEX:  RNN)| ^[1]develops clinical stage drugs that address unmet medical needs in the treatment of cancer, central nervous system (CNS) disorders, and sexual dysfunction. Rexahn Pharmaceuticals is located in Rockville, Maryland (MD), USA, and runs a research facility in Germantown, MD, USA. Rexahn has recently completed Phase II clinical trials for major depressive disorders (MDD) and erectile dysfunction (ED). It is also testing Archexin™ for the treatment of metastatic pancreatic cancer.

History

2001 – Founded by Dr. Chang H. Ahn, based in Rockville, Maryland, USA

2005 – FDA orphan drug designation of Archexin

2006 – Archexin Phase I trial completion ^[2], an anti-cancer drug candidate

2008 – American Stock Exchange listing, subsequently merged to New York Stock Exchange (NYSE) ( AMEX:  RNN)|

2009 – Completion of Phase II clinical trial of Zoraxel for erectile dysfunction

2009 – Completion of Phase II clinical trial of Serdaxin for major depressive disorder

2009 – License and investment agreement on an anti-cancer drug RX-3117 with Teva Pharmaceutical Industries

Management

Chang H. Ahn, Ph.D., Chief Executive Officer, Founder, and Chairman

Dr. Chang H. Ahn is an internationally recognized drug development expert with over 20 years of experience in the fields of pharmacology and biotechnology. He founded Rexahn in 2001, and currently serves as the company’s Chairman and Chief Executive Officer. Prior to founding Rexahn, Dr. Ahn held dual positions as Expert Regulatory Officer and Laboratory Chief at the FDA’s Center for Drug Evaluation and Research. While at the FDA, Dr. Ahn represented the agency in the fields of Antisense Oligonucleotide Therapeutics and Multi-Drug Resistance, and served a key role as an author of several FDA guidance documents. Before joining the FDA, Dr. Ahn conducted cancer research at the National Cancer Institute and Emory University’s School of Medicine. Dr. Ahn chaired the U.S.-Korea Bio Business and Partnership Forum, a working group between Korean biopharmaceutical companies, State of Maryland and Montgomery County. He has also served as the president of the Society of Biomedical Research since 2000. He was named as “Maryland’s 25 CEOs You Need to Know” in 2006 by Gazette News and Rexahn was honored “2006 Biotechnology Company of the Year” in 2007 by the Monte Jade Science and Technology Association. Dr. Ahn earned his Ph.D. in pharmacology at Ohio State University in 1985. He also holds two B.S. degrees in pharmacy from Creighton University and Seoul National University, Seoul, Korea

Rick Soni, M.B.A., President and Chief Operating Officer

Rick Soni has held several leadership and executive positions throughout his 25-year career in the pharmaceutical industry. He has extensive U.S. and international experience in drug commercialization, pharmaceutical sales, marketing, new product planning and business development. Prior to joining Rexahn in 2008, Rick worked at Otsuka Pharmaceuticals for 10 years in corporate and business development roles of increasing responsibility, and in sales and marketing at Novartis and Schering-Plough Corp.

Tae Heum (Ted) Jeong, M.S., Chief Financial Officer

Ted Jeong oversees all aspects of finance, accounting, operations, and Sarbanes-Oxley regulatory compliance reporting for Rexahn. After 2002, he serves as the company’s Chief Financial Officer. He is also responsible for investor relations, and played a key role in Rexahn’s 2008 listing on the American Stock Exchange (AMEX). Ted has extensive experience in venture capital, and spent six years as a Senior Investment Manager at Hyundai Venture Investment Corporation where he managed the Biotechnology investment team.

Portfolio & Clinical Trials

Rexahn's product portfolio consists of Archexin for the treatment of metastatic pancreatic cancer; Serdaxin, for depression and mood disorders; and Zoraxel, for sexual dysfunction. The company's pre-clinical pipeline products include RX-0201-Nano, a nanoliposomal anti-cancer Akt-1 inhibitor; RX-0047-Nano, a nanoliposomal anti-cancer HIF-1 alpha inhibitor; and Nano-polymer anticancer drugs.

Serdaxin™ – Depression and Parkinson’s disease ^[3]

Unlike other mood disorder treatments, Serdaxin tackles three disease mechanism simultaneously; serotonin, dopamine, and neuronal survival. Serotonin is a traditional pillar in understanding depression. Previous researches indicate loss of serotonin in brain underlies common symptoms such as anxiety. Recent findings, however, point that dopamine plays a central role in other aspects of the disease, including anhedonia (loss of pleasure) and lack of motivation. In preclinical studies, Serdaxin supports both serotonergic and dopaminergic systems in brain, enabling a multi-prong approach to depression.

In addition, Serdaxin prevents neuronal death, a disease mechanism implicated in many brain disorders from depression to Parkinson’s and Alzheimer’s disease. In a Parkinson’s disease animal model, Serdaxin protects dopamine-releasing neurons from environmental insults. This result supports our hypothesis that Serdaxin is a long-awaited neuroprotective agent, a tool for the next-generation treatment beyond the dopamine replacement scheme. Functional magnetic resonance imaging (fMRI) study also exhibited stronger neuronal activity in dopamine and serotonin systems in Serdaxin treated animals. Targets identified in these studies are under further investigation to elucidate the neuroprotective mechanism of Serdaxin.

Clinically, Serdaxin lacks common side effects in other mood disorder drugs, such as motor impairment, insomnia, and sexual dysfunction. These characteristics ensure greater patient compliance and efficacy. As of January 2010, Phase IIa clinical trial for the use of Serdaxin in major depressive disorder (MDD) proved the safety as well as efficacy of Serdaxin in human patients. Clinical trial of Serdaxin for Parkinson’s disease is also under preparation.

Archexin™ - Cancer ^[4]

Archexin is a first-in-class, potent inhibitor of the Akt-1 protein kinase in cancer cells. Archexin is in Phase II trials for treatment of pancreatic cancer and has US FDA orphan drug designations for five cancers (RCC, glioblastoma, and cancers of ovary, stomach and pancreas). Multiple indications for other solid tumors can also be pursued. Archexin^TM is an antisense oligonucleotide (ASO) compound that is complementary to Akt mRNA, and highly selective for inhibiting mRNA expression and production of Akt protein. Akt activation leads to cancer cell survival, proliferation, and angiogenesis. Both native and activated forms of Akt are involved in cancer cell signaling. Activated Akt also play a role as a drug resistance mechanism, in particular, of targeted therapies.

Archexin is the first anticancer drug that inhibits both forms of Akt, with the potential to inhibit cancer survival and proliferation, angiogenesis and drug resistance. In the Archexin Phase I clinical study, grade 3 (G3) fatigue was the only dose limiting toxicity observed.

The Archexin Phase II goals are to assess efficacy and safety in treating metastatic pancreatic cancer. The primary study endpoints are tolerability and survival. Other endpoints include AKT-1 and VEGF biomarkers evaluation and tumor response using RECIST criteria. Global clinical trials are under way for multiple indications.

Zoraxel™ - Erectile Dysfunction ^[5]

Zoraxel is a developmental stage drug for erectile dysfunction (ED) that directly modulates the sexual activity control center in brain. Zoraxel enhances action of serotonin and dopamine, brain signaling molecules that play a key role in three phases of sexual activity: arousal, erection and release. Zoraxel is the first ED therapeutic to affect all three of these phases. Preclinical studies demonstrated that Zoraxel improves sexual performance via enhanced motivation and arousal. Its central-action mechanism also warrants potential use in the treatment of female sexual dysfunction.

Erectile dysfunction (ED) causes consistent inability to attain and maintain an erection sufficient for satisfactory sexual intercourse. Erectile problems may be due to ‘psychogenic’ causes (e.g., depression or stress), 'organic' causes, or both. Launch of the first orally available phosphodiesterase (PDE)-5 inhibitor, Viagra™, in 1998 established a new standard care for ED, and pioneered a new market. Cialis™ and Levitra™ were subsequently launched in 2003 as second-generation PDE-5 inhibitor drugs. However, 30% of patients are refractory to the leading PDE-5 inhibitor drugs. PDE-5 inhibitors also increase the risk of variety of cardiovascular diseases, including heart attack and sudden death.

Zoraxel has superior safety to PDE-5 inhibitors. Contrary to peripheral acting PDE-5 inhibitors, Zoraxel is centrally acting in brain to affect all three functions of sexual activity; arousal, erection, and release. Phase IIa clinical trial of Zoraxel is now complete with positive results and Phase IIb trial is under way.

Preclinical Stage Drug Candidates

RX-3117 is co-developed with Teva Pharmaceutical Industries for the treatment of gemcitabine-resistant lung cancer. RX-3317 showed potent anti-tumor effects in xenograft human tumor models. Preclinical studies revealed the high bioavailability and superior toxicity profile compared to gemcitabine, the current first-line therapy for pancreatic and other cancers.

RX-0183 is a quinazoline analogue that suppresses protein kinase Akt and c-Fos, critical components of tumor growth and metastasis. Preclinical studies showed RX-0183 inhibits tumor growth in xenograft models.

RX-0047 ^[6]is a potent inhibitor of HIF-1α, a key transcription factor involved in cancer cell survival, metastasis, and angiogenesis. HIF-1α is over-expressed in a broad range of human cancers, and associated with increased cancer mortality and resistance. RX-0047 inhibits proliferation of cancer cells of human origin at low nanomolar concentrations by lowering mRNA level of HIF-1α. It is also effective in radiation-resistant cancer cells. Studies in xenografted model showed RX-0047 inhibits tumor growth in lung and prostate and blocks metastasis.

RX-5902 is a novel piperazine-based small molecule that interferes with microtubule structure and G2/M cell cycle in cancer cells. Studies demonstrated drug-resistant tumors recede in xenografted model by oral administration of RX-5902

RX-8243 is a novel isoquinolinamine analogue that inhibits Ark1 (Aurora A) kinase and other Ser/Thr kinase in caner cells. RX-8243 is a multikinase inhibitor that downregulates signal molecules of RAS as well as PI3K pathways such as activated forms of ERK, p38 and Akt. Preclinical studies showed RX-8243 blocks tumor growth in xenograft models at low nanomolar concentrations.

Nano-polymer Conjugate Drugs Among the prominent nano-polymer drugs in Rexahn, HPMA-gemcitabine and HPMA-docetaxel are anticancer drugs that can overcome the downside of cytotoxic compounds, such as poor solubility, stability, and severe adverse reactions. Conjugating water-soluble and non-toxic HPMA to conventional anticancer compounds bolster efficacy while lowering toxicity by specific tumor targeting and increased stability in body.

Discovery Platforms ^[7]

TIMES (The Inhibitors of Multi-Expression Signals) Platform In treating cancers, the combinational use of multiple cytotoxic drugs significantly increases the types and severity of harmful adverse reactions that patients experience. To address this issue, we utilize compound screening technology to streamline the drug discovery process prior to laboratory experimentation. Rexahn’s proprietary TIMES small molecule signaling technology has enabled us to discover more than a dozen targets that control expression of at least 5 genes/proteins involved in cancer proliferation. TIMES has already identified a target that controls up to 13 signaling molecules - compounds that inhibit each target are considered as a first-in-class type due to the nature of multi-targeting signal molecules. Using TIMES, we can more efficiently develop compounds with significantly increased efficacy, yet less side-effects.

3D-GOLD (3D-Gateway Of Ligand Discovery) Platform 3D-GOLD is an integrated computational modeling tool of 3D-finger printing/pharmacophore, 3D-QSAR/proprietary QCID, 3D-ligand constructs, and 3D-dockings, that helps to predict the structural activity relationship of molecules using 3-dimensional models. 3D-GOLD is actively working to help Rexahn discover novel lead compounds, regardless of available 3D crystal structures of a target protein. Leveraging this system, we are able to more effectively develop predictive models, formulate and test hypotheses for optimizing efficacy and increasing drug safety and bioavailability early in the process of drug discovery.

Nanoliposome Rexahn is actively collaborating with world-renown nano technology innovators to develop unique nanoscale delivery systems that increase the availability of a drug at a disease site, minimize adverse reactions, and/or provide longer duration of action. Rexahn is currently developing drug products utilizing multiple nanoliposome- and nanopolymer-based technologies

Partners & Investors

In September 2009 Rexahn closed on licensing and stock purchase agreements with Teva Pharmaceutical Industries for the development RX-3117, anovel anti-cancer compound. Rexahn also has a joint research collaboration agreement with TheraTarget, Inc., a developer of innovative polymer therapeutics for the treatment of cancer. In addition, Rexahn is in a licensing partnership with Korea Research Institute of Chemical Technology (“ KRICT”) to develop a synthetic process for Quinoxalines compounds. Other partners include Korean Research Institute of Bioscience and Biotechnology, Ewha ^[8] Womans University, and Revaax Pharmaceuticals LLC.

References

Bibliography

1. J. S. Chan, et al., "Clavulanic acid stimulates sexual behaviour in male rats," Eur. J. Pharmacol. 609(1-3), 69 (2009).

2. Z. G. Dikmen, et al., "In vivo and in vitro effects of a HIF-1alpha inhibitor, RX-0047," J. Cell Biochem. 104(3), 985 (2008).

3. J.Marshall, et al., "A Phase I Trial of RX-0201 (Archexin; Akt-1 Antisense) in Patients With An Advanced Cancer,"in 2007).

4. D. J. Kim, et al., "Clavulanic acid: a competitive inhibitor of beta-lactamases with novel anxiolytic-like activity and minimal side effects," Pharmacol. Biochem. Behav. 93(2), 112 (2009).

5. D. S. Park, et al., "QSID Tool: a new three-dimensional QSAR environmental tool," J. Comput. Aided Mol. Des 22(12), 873 (2008).

6. N. K. Soung, et al., "Requirement of hCenexin for proper mitotic functions of polo-like kinase 1 at the centrosomes," Mol. Cell Biol. 26(22), 8316 (2006).

7. L. X. Zhao, et al., "Design, synthesis, and anticancer activity of fluorocyclopentenyl-pyrimidines," Nucleic Acids Symp. Ser. (Oxf) (49), 107 (2005).

External links

• Rexahn Company Website
• Rexahn on Yahoo Finance
• Active clinical trials by Rexahn
• Clavulanic acid