Celgene Avilomics Research

Leadership in Targeted Covalent Drugs: Overview

Targeted covalent drugs: A new way to impact disease

Today’s medicines, while able to inhibit disease-causing proteins, are generally only able to form transient binding interactions with the disease targets.

Targeted covalent drugs have the unique opportunity not simply to inhibit disease-causing proteins, but to “silence” them completely. This is because targeted covalent drugs do not merely “bind” to a protein, but they form a durable “bond,” which shuts down the protein’s activity throughout the life of the protein, which is usually between a few hours and a few days. This unique covalent bonding mechanism leads to two primary benefits:

Precise selectivity: Each targeted covalent drug is highly selective as it is designed to form bonds only with the site found on the disease-causing protein to which it is directed. Furthermore, our drugs can also specifically attack disease targets that traditional approaches cannot selectively address. Due to this enhanced selectivity, targeted covalent drugs have the potential to achieve better efficacy and reduced side-effects.

Retained Efficacy Against Mutations: Disease-causing proteins often mutate, particularly in cancers and viral diseases. Conventional drugs have decreased ability to bind effectively to these mutated proteins as the binding site changes size and shape with each mutation. However, because targeted covalent drugs are able to form a resilient, enduring bond they will not readily disengage from a mutated protein, and thus, can retain efficacy in the face of mutational resistance, a common challenge in the treatment of cancers and infectious diseases.

At Avila, we believe our targeted covalent drugs will substantially improve health outcomes through improved and durable efficacy over existing therapies, providing constant inhibition of disease processes.