Revolution Medicines is a clinical-stage precision oncology company focused on developing novel targeted therapies to inhibit elusive frontier targets within notorious growth and survival pathways, with particular emphasis on RAS and mTOR signaling pathways.
We are utilizing our deep understanding of genetic drivers and adaptive resistance mechanisms in cancer, coupled with robust drug discovery and medicinal chemistry capabilities, to build a portfolio of compounds that inhibit critical signaling nodes within the RAS and mTOR pathways. In doing so, we leverage sophisticated structure-based drug discovery capabilities to access unconventional sites on these challenging targets with differentiated approaches such as intra-molecular allosteric binding, tri-complex formation as a form of inter-molecular allostery, and bi-steric binding.
Our cohesive approach of focusing on targets within the RAS and mTOR pathways underpins our clinical strategy of exploring mechanism-based dosing paradigms and in-pathway combinations to optimize treatment for cancer patients.
Our most advanced product candidate is RMC-4630, a clinical-stage drug candidate that potently and selectively inhibits SHP2, a central node in the RAS signaling pathway. In collaboration with our partner, Sanofi, we are evaluating RMC-4630 in a multi-cohort Phase 1/2 clinical program for a range of tumor types featuring specific oncogenic mutations. Additionally, we are developing a portfolio of mutant-selective RAS inhibitors that we believe are the first potent, selective, cell-active inhibitors of the active, GTP-bound form of RAS, or RAS(ON). Our pipeline also includes inhibitors of other frontier oncology targets within the RAS and mTOR pathways. These include SOS1 and 4EBP1/mTORC1, with a development candidate for the latter, RMC-5552, currently advancing into IND-enabling studies.
Preclinical and clinical research has demonstrated that cancers caused by RAS pathway mutations exhibit a phenomenon called “oncogene addiction,” in which tumor cells become highly dependent on signaling through the RAS pathway to survive. As a result, these cells can eventually develop adaptive resistance, whereby they lose sensitivity to treatment by hijacking other cell signaling circuitry to circumvent inhibition and restore RAS-dependent signaling. The need to overcome resistance has led to use of combination regimens designed to inhibit the RAS signaling pathway at multiple nodes simultaneously in an attempt to prolong the depth and durability of clinical benefit for treatment of RAS-dependent tumors. With this in mind, we are concurrently pursuing combination therapy and monotherapy development strategies for our programs.