Ignyta, Nerviano sign license deal for two first-in-class kinase inhibitors

RXDX-103 is an inhibitor of the cell division cycle 7-related (Cdc7) protein kinase, and RXDX-104 is a program to identify a highly selective inhibitor of the rearranged during transfection (RET) tyrosine kinase.

Each of these programs is in preclinical development for the potential treatment of multiple cancers. Ignyta previously licensed exclusive rights to its RXDX-101 product candidate and its RXDX-102 back-up product candidate from Nerviano.

"We are thrilled to bolster our pipeline with these additional development programs from Nerviano, each of which has the potential to become a first-in-class oncology therapeutic," said Jonathan Lim, M.D., Chairman and CEO of Ignyta.

"This deal expands upon our Rx/Dx strategy of interrogating molecular alterations that drive cancer, then treating patients who have these alterations with precisely targeted therapeutics, further advancing our vision of becoming a leading precision medicine biotechnology company."

"We are very pleased to expand our collaboration with Ignyta," said Dr. Luciano Baielli, CEO of Nerviano Medical Sciences. "Both Nerviano and Ignyta share the common goal of developing innovative new drugs for cancer patients."

Under the terms of the license agreement, Ignyta will assume sole responsibility for global development and commercialization of the RXDX-103 product candidate immediately, and for the RXDX-104 program upon the earlier of December 31, 2014 or the identification of a lead development candidate.

Nerviano will receive an upfront payment of $3.5 million, as well as development- and regulatory-based milestone payments and tiered royalty payments on future net sales of RXDX-103 or RXDX-104.

Loss of cell cycle control is a hallmark of cancer, and interfering with the DNA replication process is a proven strategy for cancer therapy. Currently available chemotherapies, such as anti-metabolites, topoisomerase inhibitors, and crosslinking and intercalating agents, classically take a broad-based approach to inhibiting the elongation step of DNA replication.

This strategy has led to successful treatment outcomes, but off-target effects can lead to dose-limiting toxicity. Cdc7 is a serine/threonine protein kinase essential for the initiation step of DNA replication during the synthesis (S) phase.

Ignyta and Nerviano believe that inhibiting the initiation step rather than the elongation step of DNA replication by targeting Cdc7 could offer a more targeted therapeutic strategy for disrupting DNA replication. For example, inhibition of Cdc7 has been demonstrated to selectively kill tumor cells in a P53-independent manner, while sparing non-cancerous cells. RXDX-103 is a highly targeted cell cycle inhibitor, with high potency and selectivity against Cdc7 in vitro, and demonstrated anti-tumor effects both alone and in combination with chemotherapy in vivo.

The RET proto-oncogene is a receptor tyrosine kinase prone to gene rearrangements and other mutations, which can become oncogenic drivers in cancers such as non-small cell lung cancer and medullary thyroid cancer.

While some marketed and development stage multi-kinase inhibitors induce non-selective RET inhibition that confers anti-tumor efficacy in cancer patients with RET rearrangements, such compounds often have limiting toxicities from their other mechanistic effects, such as VEGF inhibition. Ignyta believes, based on input from its oncologist advisors, that there is a compelling clinical need for a highly selective RET inhibitor such as RXDX-104.