Two famous quotes attributed to the Great One, ice hockey legend Wayne Gretzky, “I skate to where the puck is going, not where it has been,” and “you miss 100% of the shots you never take,” perfectly encapsulate the corporate strategy at EpicentRx. This strategy is, firstly, to try to anticipate where and in what indications the portfolio of EpicentRx clinical candidates are most likely to be successful — in other words, based on the available evidence, to skate to where the puck is going, not to where it is now or has been — and, secondly, to evaluate these clinical candidates as broadly as possible, in several related indications, simultaneously, on the premise that one or, optimistically, more than one of them may significantly benefit patients.
RRx-001, the lead clinical candidate in the CyNRGY platform, so named because the compounds therein bind to sulfur groups or cysteines, is a case in point. Originally developed as a selective tumor- and hypoxia-targeted anticancer agent, the preclinical and clinical data strongly suggested that RRx-001 was also endowed with anti-inflammatory and normal tissue-protective properties; and where the data led the company followed. Hence the decision was made to continue to evaluate RRx-001 in cancer as well as in several non-cancer indications including congestive heart failure, neurodegenerative diseases like Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), autoimmune disorders like inflammatory bowel disease, multiple sclerosis, and acute graft vs. host disease. As different as these indications are, the one common factor that underlies all of them, is inflammation.
The inflammatory response serves typically a positive function: to shorten biological ‘battles’ with viruses, parasites, cancer etc. and to initiate the repair sequence. However, when the fine balance between inflammation and resolution of inflammation is lost, then damage and disease result. The administration of RRx-001 may reset certain diseases through its anti-inflammatory activity and inhibitory effects at the level of large proteins called inflammasomes that orchestrate the inflammatory response.
A second case in point is AdAPT-001, the lead oncolytic virus from the ADAPT platform, which carries and expresses a TGF-beta trap. TGF-beta is a protein overexpressed in cancer whose function is to suppress or decrease the immune system’s activity and lay down or deposit scar tissue. The TGF-beta trap expressed by AdAPT-001 binds to and neutralizes TGF-beta, which increases or augments its anticancer activity. However, excessive scar tissue or fibrosis is a characteristic of many other diseases, including scleroderma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, myelofibrosis, and systemic lupus erythematosus. The neutralization of TGF-beta by the TGF-beta trap in AdAPT-001 may improve the outcomes of these non-cancer diseases.
Hence, the EpicentRx corporate strategy and “Gretzkian” focus, in a nutshell, is to go where the available evidence is leading, not to stagnate where it has been, and to critically and judiciously evaluate this evidence broadly in different but related indications in cancer and beyond, hopefully for the benefit of as many patients as possible.