SNIPRx Platform: Our Proprietary, Genome-wide, CRISPR-enabled Discovery Platform

Our SNIPRx platform begins with a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines, which are cell lines that are identical with the exception of a single genomic alteration, to identify novel Synthetic Lethal (SL) gene pairs. Our systematic and comprehensive screening approach has been optimized to significantly reduce false negatives, providing the opportunity to identify a larger and more accurate set of SL interactions as compared to what has been reported with other CRISPR-based screening technologies.

We have systematically analyzed genomic data from approximately 60,000 tumor samples and identified an initial set of clinically relevant tumor genomic alterations, which we refer to as tumor lesions, that are linked to genomic instability. These tumor lesions are present in approximately 30% of tumors and are largely mutually exclusive. For each of these tumor lesions, we have completed a SNIPRx screen campaign to identify both previously reported and unreported targets that are SL with the tumor lesion of the campaign. Our SNIPRx screen campaigns have identified multiple potential targets, which allows us to prioritize and select targets to advance into drug discovery based on a systematic and proprietary set of criteria.

Once a SL product candidate is identified, we perform our STEP2 screen to identify additional genomic alterations that are SL with our product candidate. We believe the identification of these new SL pairs will allow us to rationally expand our targeted patient populations by enabling us to potentially treat patients with tumors across multiple genomic alterations with the same product candidate.

For our clinical trials, we plan to enroll patients with tumors that contain either the original tumor lesion or any one of the genomic alterations identified by our STEP2 screens. We believe this strategy will allow us to enroll only those patients who are most likely to achieve clinical benefit from our product candidates.

This approach can be divided into six steps, as depicted in the graphic.

Repare_6 step process_generic