TECH OUTLOOKSeptember - 20199some of the technologies being used alone or in combination for repurposing: Phenotypic screeningEHR dataIn silico-screeningMetabolic ModelingGene signatures/Drug signaturesSimilarities ModelingMultiomicsNatural Language ProcessingGWASDeep LearningPheWAS/SNPsMachine LearningIn each of these technology categories, there are different companies and labs using their own proprietary techniques to move repurposing forward. Notable Labs and Recursion Pharmaceuticals both rely on phenotypic screening, but they use different screening technology to achieve different repurposing outcomes. BioVista and IBM Research/Watson use different natural language processing and machine learning technologies to search existing scientific and medical literature for obvious and non-obvious repurposing opportunities. Vanderbilt University and University of Kansas Medical Center are both doing screening in different ways using proprietary HER and other databases.As technology continues to advance, and as we find ways to clinically validate the multitude of repurposing candidates discovered through screening and other techniques, we will be able to add more repurposing research opportunities to clinical practice that can impact patients' lives more quickly and effectively.Technology also supports precision medicine drug repurposing. A number of companies and academic labs are now able to perform a variety of evaluations on cells or tissue from individual patients, including phenotypic or genomic screens. These technologies detect cellular changes in patient samples when subjected to single drugs or nutraceuticals, as well as combinations of drugs and/or nutraceuticals, allowing these testing entities to quickly make targeted drug repurposing recommendations to physicians for their individual patient. These screens detect shifts in the cells maturity, surface antigens, senescence, defense mechanisms, pro- or anti-apoptotic pathways and other cellular functions, and gather the data to predict how the patient's disease will react to these already available compounds. For patients with diseases that have no available and effective standard treatment regimens, and for those patients who have exhausted all potentially effective therapies, these predictive therapeutic repurposing regimens can be life-saving. These technologies can provide therapeutic predictions that differ markedly from what a clinician might expect, based on what is known about the disease and the drugs or nutraceuticals from the scientific literature and from clinical observations. And because these tests can often be performed using blood and other easily secured patient samples, the predictions can be quickly and economically delivered to a physician.For example, Notable Labs has a drug testing service to help oncologists identify actionable treatment options for people with blood cancers. A physician sends a blood or bone marrow sample to Notable Labs and based on the patient's diagnosis, Notable chooses a panel of FDA-approved oncology drugs and non-oncology drugs that might impact that patient's disease. They test the sample against thousands of drug combinations, and within several days, they provide a report to the physician of the phenotypic improvements to certain combinations. The physician decides which, if any, of the repurposed treatment options might help the patient. Physician has reported successes with Notable recommended drug combinations, including for pediatric leukemia patients who had exhausted all standard therapeutics options.These technological advancements are powerful for patients, especially since there is no regulatory or commercial ability to immediately design and develop a new drug to impact each individual patient using personalized medicine techniques. But we do have existing drugs and nutraceuticals that can be repurposed easily to treat patients. In the U.S. and in some other countries, physicians can prescribe these drugs off-label, so repurposed therapies suggested by the precision medicine predictions are immediately available for patient use. We expect these kinds of precision medicine technologies to rapidly proliferate, and become more sensitive, predictive, affordable, accessible, and widely used by physicians and patients. It is likely that physicians will expand their use of these technologies earlier in the treatment cycle for patients, helping to use the regimen most likely to help the patient as soon as possible. Physicians also may repeat these technology assessments at regular intervals to make sure the repurposed therapies are working for the patient, and to change them if they are not. These technological advances will make repurposing of existing drugs and nutraceuticals for individual patients an even more critical part of clinical care and these precision medicine methods might influence the way new drugs are developed and clinically tested. Bruce Bloom
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