Supinoxin™ (RX-5902)

Supinoxin – A Potential First-in-Class Inhibitor of a Unique Cancer Protein

Supinoxin (RX-5902) is an orally administered, potential first-in-class, small molecule inhibitor of a unique cancer protein – phosphorylated-p68 (P-p68) which is selectively overexpressed in cancer cells and absent in normal tissue. P-p68 is believed to increase the activity of multiple cancer related genes including, cyclin D1, c-jun and c-myc, and play a prominent role in tumor progression and metastasis. Over-expression of P-p68 has been observed in many solid tumors, including, melanoma, colon, ovarian and lung tumors.

In preclinical studies, Supinoxin has been shown to inhibit proliferation of cancer cells in over 100 different human cancer cell lines, including, breast, ovarian, colon, pancreas, and stomach cancers, and has shown potent activity in drug-resistant cancer cells. In preclinical animal models, where human cancer cells from triple negative breast cancer, ovarian, melanoma, pancreas, or renal tumors were grafted into animals, treatment with Supinoxin resulted in a significant reduction in tumor growth.

Supinoxin is currently being evaluated in a Phase I multi-center, dose-finding, open-label, single agent clinical study in patients with advanced or metastatic solid tumors.

Interim results from the Phase I clinical trial were presented at the European Cancer Congress in September 2015. The results showed that, at the dose levels tested to date, clinical evidence of single-agent activity of Supinoxin was observed in approximately 29% of patients (4/14 patients) who showed stable disease persisting from between 255 and 497 days (as of September 14, 2015.)

In addition, Supinoxin, administered orally, appeared to be safe and well tolerated with no Grade 3 or Grade 4 adverse events and only one unrelated Grade 2 adverse event. The most frequently reported drug related adverse events were mild nausea, vomiting and fatigue. Pharmacokinetic analyses of the current data show both a predictable and desirable pharmacokinetic profile for an orally-administered route of therapy.

The Phase I study of Supinoxin is currently ongoing and Rexahn anticipates commencing a Phase Ib/IIa Proof-of-Concept clinical trial in mid-2016 in patients with triple negative breast cancer and platinum resistant ovarian cancer to more comprehensively evaluate Supinoxin’s clinical activity.

Young Bok Lee et. al. Synthesis and anticancer activity of new 1-[(5 or 6-substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4- (hetero)arylpiperazine derivatives. Bioorganic & Medicinal Chemistry 2010 (18): 7966–7974.

Young Bok Lee Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives. Bioorganic & Medicinal Chemistry 2012 (20): 1303–1309

Antitumor activity of a new quinoxalinyl-piperazine compound. Y.B. Lee, G. Chun, D.J. Kim, C.H. Ahn, Y. D. Kong, M.K. Jeon, J.Y. Kong (2011). American Association for Cancer Research (AACR) 102nd Annual Meeting, Orlando, FL, April 02-06, 2011. Abstract No: 1371.

Mechanistic study of a new 4-(3,5-dimethoxyphenyl)-N-(7-fluoro-3-methoxyquinoxalin-2-yl)piperazine-1-carboxamide compound (RX-5902). Y.B. Lee, D.J. Kim, G.C. Kost, J. Frank, C.H. Ahn, Z.R. Liu (2013). American Association for Cancer Research (AACR) 104th Annual Meeting, Washington, D.C., April 06-10, 2013. Abstract No: 5507.