Oncology Market Opportunity Overview

• Worldwide, an estimated 24.6 million people are living with cancer (within three years of diagnosis)¹
• Approximately 10.5 million Americans are living with cancer²
• There is a need for novel, targeted therapies with potentially greater efficacy and less toxicity

We have a broad-based R&D program focused on the design and development of small-molecule inhibitors of mitogen-activated ERK kinase (MEK) for the treatment of cancer. Since defects in the RAS/RAF/MEK/ERK signaling pathway are closely associated with the development of human tumors, such as melanoma, colon, lung and thyroid cancers, inhibiting MEK signaling has promise in the treatment of many types of cancer.

RDEA119, our lead product candidate from this program, currently in clinical development both as a single agent and in combination with Nexavar^® (sorafenib), is a potent, non-ATP competitive, highly-selective inhibitor of MEK, which is believed to play an important role in cancer cell proliferation, apoptosis and metastasis.

Preclinical and clinical data suggest that RDEA119 has favorable properties, including oral dosing, excellent selectivity and limited retention in the brain, which may result in a reduced risk of central nervous system (CNS) side effects, a problem associated with other members of this class of compounds. In addition, RDEA119 has been shown to suppress tumor cell growth in vitro and in vivo. Phase 1 data have demonstrated that RDEA119 has a long half-life and favorable pharmacokinetic properties, allowing for once daily oral dosing. Preclinical in-vitro and in-vivo oncology studies with RDEA119 have demonstrated significant potential synergy across multiple tumor types when these product candidates are used in combination with other approved anti-cancer therapeutics. RDEA119 is currently being evaluated in a Phase 1/2 clinical trial in combination with Nexavar in advanced cancer patients.

Our second-generation MEK inhibitors include a broad range of compounds from several distinct chemical classes, representing new chemical entities. We have selected RDEA436 as our second-generation product candidate from this program. Preclinical data show that RDEA436 is a potent in vitro and in vivo inhibitor of MEK with low CNS penetration. The results of a human micro-dose pharmacokinetic study demonstrate that RDEA436 has favorable pharmacokinetic properties and a long half-life, indicating the potential for once daily dosing in humans.

For more information regarding these programs please click here to view our most recent company presentation.