Medarex announces allowance of IND application for antibody-drug conjugate, MDX-1203

Medarex, Inc. has announced the allowance of an investigational new drug (IND) application filed with the U.S. Food & Drug Administration (FDA) for MDX-1203, the Company's first Antibody-Drug Conjugate (ADC) candidate generated from its proprietary technology.

MDX-1203 is comprised of a potent cytotoxic prodrug chemically linked with a fully human anti-CD70 antibody. CD70 is expressed in renal cell carcinoma (RCC), leukemias, lymphomas, and other cancers. The Phase 1 study will evaluate MDX-1203 for the treatment of advanced/recurrent RCC and relapsed/refractory B-cell non-Hodgkin's lymphoma (NHL).

"Antibody-drug conjugates are another important and innovative therapeutic approach used to fight cancer by effectively and selectively killing tumor cells over-expressing specific tumor antigens, so we are extremely excited in achieving the IND filing for MDX-1203, the first candidate from our proprietary ADC technology platform," said Howard H. Pien, Chairman and CEO of Medarex. "We developed our ADC technology to have significant competitive advantages over existing technologies and the Phase 1 trial for MDX-1203 will be the first study to evaluate these potential benefits."

An open-label, multi-dose, dose-escalation Phase 1 clinical trial will be conducted in patients with RCC and NHL. This trial is designed to establish and evaluate the safety, tolerability and maximum tolerated dose, as well as preliminary distribution, metabolism and pharmacokinetics of MDX-1203.

Medarex has enhanced its core UltiMAb(R) antibody platform with a suite of technologies that optimize or augment the therapeutic activity of antibodies, and one important technology expansion is the company's proprietary Antibody-Drug Conjugate platform. Medarex's proprietary ADC technology uses a cytotoxic agent that is a potent, synthetically manufactured prodrug (a DNA minor-groove binding alkylating agent) which is attached to an antibody using a stable peptide-based linker. Medarex believes that its ADC technology overcomes many of the key development challenges of drug conjugates, including issues of linker stability, potency and multi-drug resistance while maintaining a wide therapeutic window with minimal toxicity.

Medarex has conducted multiple preclinical studies on several investigational antibody-drug conjugate candidates in development demonstrating enhanced anti-tumor activity in xenograft models, even with single doses as low as 0.005 micro mol/kg, when compared to the anti-cancer antibodies alone. Preclinical studies have also demonstrated that anti-tumor activity is maintained in drug-resistant cancer cells. Additionally, Medarex's activatable prodrug has been shown to accumulate in the targeted tumor cells but not in normal tissue cells, thereby minimizing the toxicity profile but not the anti-tumor activity in animal and primate models.