Precision medicine for the treatment of cancer and other human diseases will require new targeted therapeutics and rational concepts for guiding their clinical use. Profiling transcriptional responses to drug treatment is a key method in both pre-clinical and clinical drug development. However, conventional profiling techniques such as microarrays and RNA-seq lack time resolution and thus cannot distinguish between direct and secondary transcriptional responses. We have developed SLAMseq as a rapid, precise, and highly scalable method for measuring direct transcriptional responses to cell perturbations. The overall goal of SLAM-Dx was to establish experimental proof-of-concept, assess market opportunities, and develop a business plan for applying SLAMseq “transcriptional fingerprinting” as a diagnostic tool in drug development and precision medicine. Using small-molecule inhibitors of the FLT3 oncogene in acute myeloid leukemia (AML), we have established proof-of-concept that SLAMseq can be used to (1) define direct transcriptional drug responses in AML models independent of mRNA turnover, (2) identify convergent and drug-selective effects of different agents, and (3) distinguish responsive and resistant disease contexts. We further simplified, automatized, and miniaturized protocol steps and demonstrated that SLAMseq is feasible with limited sample material, laying the groundwork for high-throughput applications (e.g. compound screening in drug development or diagnostic profiling). In parallel, we performed a market assessment and FTO analysis, devised a business strategy and IP strategy, and developed a business plan. Based on the experimental and commercial strategy and proof-of-concept established in SLAM-Dx, we could acquire two major investors – the Boehringer Ingelheim Venture Fund (BIVF) and Evotec SE – and have founded a spin-off company (Quantro Therapeutics GmbH) that is meanwhile operational at the Vienna BioCenter (www.quantro-tx.com).
