Platform

Powering our platform

Synthetic Lethality

The genetic principle of synthetic lethality offers a path to selectively kill cancer cells by identifying genes that when used as drug targets kill cells with specific tumor suppressor gene loss while sparing normal cells. PARP inhibitors are the first clinical example of synthetic lethal targeting and are active in cancers with BRCA mutations.

We are applying our approach in two core areas:

Tumor suppressor gene loss

Most cancers are fueled in part by genetic changes that disable the protective genes meant to suppress tumor growth called tumor suppressor genes. The loss of function those genes caused by genetic alterations allows the cancer to grow – but it also makes the cancer cells vulnerable to synthetic lethal drug targeting. Our integrated discovery platform uncovers the vulnerabilities that arise from the loss of a tumor suppressor gene in specific cancer types. We then leverage these insights to develop novel drugs that destroy cancer cells, but spare normal cells.

Immune evasion

A normal immune system should recognize cancer cells as foreign and destroy them. However, cancer cells have genetic changes that allow them to evade the immune system. We discovered that there are multiple known tumor suppressor genes that, when genetically altered, activate genes and pathways that result in immune evasion, manifest clinically as resistance to checkpoint inhibitors. This approach opens a target space with powerful potential in defined genetic subsets of cancer.

Patients drive our process

We have an efficient and productive discovery and development process that utilizes high-throughput CRISPR-based functional genomics screening to identify synthetic lethal vulnerabilities in cancer cells with specific tumor suppressor gene loss. We focus on diseases with high unmet need where patients share a common genetic context. We are committed to developing precise, effective and safe therapies for the people with cancer who need them most.

Explore our approach:

discovery and development in the same genetic context

Read our posters and publications.