Drug discovery DX research using an interdisciplinary approach

Abstract

We identified Nelfinavir (NFV), an HIV-1 protease inhibitor, as a potential therapeutic agent through drug repositioning during the COVID-19 pandemic (Ohashi et al., iScience, 2021). At that time, there were no antiviral drugs available for novel coronaviruses, and international research groups were conducting clinical trials on various therapeutic candidates, yet no effective treatments had been identified. Beyond the challenge of finding candidates with strong antiviral efficacy, we contemplated whether the design of clinical trials itself could be optimized. To address this, we gathered extensive clinical data and employed a mathematical model to analyze virus dynamics in infected patients. Comprehensive simulations unveiled considerable individual variations in infection dynamics, demonstrating that the effectiveness of treatment heavily relied on the timing of drug administration (Kim et al., PLOS Biol., 2021). Moreover, incorporating these insights, we devised a quantitative simulator that emulated a randomized controlled trial, thereby refining the optimal clinical trial design (Iwanami et al., PLOS Med., 2021). The outcomes indicated that by focusing solely on cases within a few days of disease onset, the number of participants in the trial could be substantially reduced. Additionally, we fine-tuned the dosage and regimen of the therapeutic drug along with the primary endpoint, maximizing their alignment within practical constraints (Hosogaya et al., Trial, 2021). Harnessing digital twin technology, we remarkably initiated the clinical trial within a mere "4 months" after the commencement of drug repositioning (jRCT2071200023). Despite the termination of numerous clinical trials worldwide, we successfully concluded this trial (Miyazaki et al., Microbiol Spectr., 2023). In this presentation, we will elucidate our digital twin research, offering insights into drug discovery from a multifaceted perspective encompassing fundamental research, clinical exploration, and societal implementation.