ReachBio LLC announced today the launch of HemoRANK(TM)-TKI, an in vitro assay service package that helps predict the potential of novel therapeutic tyrosine kinase inhibitors (TKIs) to cause clinical hematotoxicity (myelotoxicity or neutropenia). This assay system is designed to help biotechnology and pharmaceutical companies that are developing novel therapeutic TKIs gain insight into the likelihood and degree to which their compounds might cause neutropenia in patients and thus aid in lead candidate selection, structure-toxicity relationship research, and other areas of non-clinical and investigative toxicology research.
The HemoRANK(TM)-TKI contract assay service package is a standardized test system in which one or more novel TKIs are run in robust in vitro human bone marrow progenitor assays (CFU-GM assays) in parallel with a standard panel of up to 6 TKIs that are currently approved for therapeutic use. The TKIs available for the standard panel (Lapatinib, Erlotinib, Sorafenib, Imatinib, Sunitinib and Dasatinib) have known different levels of clinical myelotoxicity, as reported in the medical literature. The rank order of in vitro IC(50) values for these compounds obtained by the HemoRANK(TM) system correlates with the degree to which they cause neutropenia in the clinic. Novel compounds tested within the system are ranked against the standard panel and informed predictions can then be made regarding the likely level of clinical neutropenia they will cause. Testing against a reduced panel of the client's choosing or against blinded or unblinded controls provided directly by the client is also an option.
According to Dr. Emer Clarke, Chief Scientific Officer for ReachBio, "we have found that in our hands, the in vitro human CFU-GM assay is both very reproducible and highly predictive of clinical myelotoxicity for a variety of different compound classes, including kinase inhibitors. Specifically for the marketed TKIs that we tested during the development of the HemoRANK-TKI service package, the rank order of the in vitro IC(50) values that we generated correlated extremely well with the degree that these compounds have been reported to cause clinical myelotoxicity - with an R(2) value of 0.81. We believe that this type of correlation between the in vitro and clinical findings allows the system to be used to rank the myelotoxic potential of novel TKIs against the members of the same drug class that are currently on the market and to therefore predict the potential incidence, degree and severity of clinical neutropenia that the novel compounds might be expected to cause."