Covalent Drugs: Bonding to Targets, Silencing the Disease

Most human diseases are rooted in the improper activity of specific proteins. The ability to silence the activity of these specific proteins in a particular disease process using Avila’s covalent drugs represents a major advance for improving therapeutic outcomes for patients.

Today’s medicines, while able to inhibit disease-causing proteins, are generally only able to form transient binding interactions with their disease targets. Depending upon the disease, and the protein target, such transient binding may require that patients be dosed frequently, which can increase the risk of side effects and can still leave the patient vulnerable to persisting disease through mutations.

Avila’s covalent drugs have the unique opportunity not simply to inhibit disease-causing proteins, but to ‘silence’ them completely. This is because covalent drugs do not merely “bind” to a protein, but form a durable “bond” and completely shut down the protein’s activity.

This covalent bonding mechanism leads to protein silencing with three benefits:

• Increased selectivity: Avila’s covalent drugs are highly selective due to their ability to form bonds with sites that are unique to disease-causing proteins. Due to the enhanced selectivity, covalent drugs should produce better efficacy and reduce side-effects.
  
  
• Prolonged duration of action: Through their unique ability to completely ‘bond’ with a protein drug target – even through brief exposure - Avila’s drugs effectively ‘silence’ these targets, and these targets remain silenced until a new protein is synthesized. Thus, Avila’s drugs lead to a prolonged duration of action, in contrast to most current drugs which need to maintain high exposure as the protein-drug interaction is transient. The benefits of this include the potential for better efficacy, less frequent dosing and less overall drug exposure that should improve safety.
  
  
• Mutational resistance: As disease-causing proteins often mutate, conventional drugs have decreasing ability to bind effectively to proteins as the binding site changes size and shape. However, because covalent drugs only must engage with the protein once to form a resilient bond, they will not readily disengage from a mutated protein and can retain efficacy. Therefore Avila’s covalent drugs are particularly well-suited to the treatment of cancers and infectious diseases – situations where mutations present an important challenged to patients and physicians.

The ultimate benefit of covalent drugs will be vastly improved health outcomes through the improved and durable efficacy over existing therapies, providing constant inhibition of disease processes.

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