ReachBio Launches HemoRANK-TKI Service Package for Predicting Myelotoxicity of New Tyrosine Kinase Inhibitors
In vitro test ranks novel compounds against approved TKIs for likelihood to cause clinical neutropenia
Seattle, WA September 15, 2009
ReachBio LLC announced today the launch of HemoRANKTM-TKI, an in vitro assay service package that helps predict the potential of novel therapeutic tyrosine kinase inhibitors (TKIs) to cause clinical hemotoxicity (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 HemoRANKTM-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 IC50 values for these compounds obtained by the HemoRANKTM 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 IC50 values that we generated correlated extremely well with the degree that these compounds have been reported to cause clinical myelotoxicity – with an R2 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.”
Dr. Eric Atkinson, president of BroadReach BioSystems, Inc and strategic advisor to ReachBio, added: “There’s often a balance between drug toxicity and efficacy, and the tipping point can shift, depending upon the disease indication. As a drug class, TKIs are known to have significant myelotoxic liabilities. However, these drugs are currently being used to treat patients with certain types of cancer, and when life-threatening diseases like that are being treated, a certain degree of drug-induced neutropenia is going to be acceptable – although it’s definitely an advantage to have as low a myelotoxic potential as possible even for oncology indications, since significant myelotoxicity will be dose-limiting. An emerging issue in the TKI space, however, is that these compounds have a lot of potential to be used in inflammation and other immune system diseases. The life-threatening potential of these types of diseases is generally lower than that of cancer, so the risk/benefit equation changes and the bar for an acceptable degree of toxicity will be higher. There will therefore be more and more pressure on companies developing TKIs for non-oncology applications to come up with compounds with lower levels of myelotoxicity. Being able to accurately predict the myelotoxic potential of new TKIs and especially being able to rank the potential clinical neutropenia in relation to the degree of neutropenia already established for marketed drugs of the same class, such as ReachBio’s new HemoRANK-TKI test offers, is going to be extremely useful during the development of new TKIs for both oncology and non-oncology indications.”
ReachBio LLC is a boutique life sciences organization based in Seattle, WA. It provides specialized contract assays, contract research, educational and consulting services to pharmaceutical, biotechnology, agrichemical, and related organizations worldwide. The company’s focus is on the clinical, industrial and research uses of primary cell biology – in particular the use of stem cell and progenitor cell assays and model systems for high value applications such as drug screening and drug discovery.
For more information please contact:
Rob Chaney, Chief Operations Officer