Liberating Data:

The process starts with patient data! The rareSHIFT project is catalyzing a collaborative effort for patient families and foundations to generate RNAseq patient datasets to power drug discovery. Unravel has developed a home collection kit for patient RNAseq data generation that enables international patient communities to directly and cost-effectively participate in rareSHIFT. Using simple, non-invasive nasal swabs, we bring patients into cutting-edge drug repurposing and target discovery research.

Patient Stratification:

RNAseq data are analyzed using BioNAV™, Unravel’s AI platform, to identify similarities in the mechanisms of different diseases. These similarities in treatment, which we term Therapeutic Response Groups (TRGs), group together different diseases/disorders by finding shared drug targets and candidate treatments to pursue in future studies. Even the most common disorders have patients who don’t respond to standard treatments, so every patient is stratified regardless of the prevalence of the disorder. This step enables even the most rare of patients to have a chance at effective therapeutics by linking individual patients to larger groups. Stratification also enables undiagnosed patients to find paths to effective treatments.

Drug Repurposing:

Unravel uses BioNAV™ to identify therapeutic mechanisms and predict existing FDA-approved drugs and supplements to restore health. The discovery engine is built on RNA networks used to generate a foundational model of human health, enabling in silico screening of over 40,000 drugs and other compounds. Unravel is working with foundations and individual clinicians to rapidly identify potential treatments ready for off-label prescription or clinical trials.

New Drug Development:

Since Unravel’s target and drug predictions often involve entirely new targets, Unravel developed entirely new molecules to more effectively act on the discovered targets. With a medicinal chemist and screening capabilities, Unravel develops proprietary, highly potent molecules to improve patient care.

Drug Screening:

Evaluating drug candidate efficacy and safety can be a bottleneck for traditional workflows. Unravel screens drug candidates in CRISPR-engineered tadpoles that serve as patient avatars. We are able to evaluate whether drug candidates work using clinically-relevant metrics like motor function, behavior, seizures, sleep, and cognition. The SquishyWare™ in vivo screening platform is customized for one or more disorders of interest in as little as 3 weeks. Unravel partners to develop patient-derived iPS lines for in vitro screens. Using in silico-predicted drug candidates has a 40% hit rate. Being more than 200x better than traditional screening, in silico predictions drastically limit the number of candidates necesary to screen compared to other methods, reuslting in faster, less expensive studies.

Rapid Clinical Translation:

With a dedicated Chief Medical Officer experienced in conducting repurposed and reformulated drug trials, Unravel partners with foundations to rapidly translate discovered repurposed drugs to their patients. Our predictions are about to enter two clinical trials, one in as little as 8 months from the start of the discovery program.