Corbus Pharmaceuticals Holdings, Inc.: CRB-701. Clinical-Stage Nectin-4 Targeted Cancer Treatment

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Advancing the future of Nectin-4 ADC's

A Novel Nectin-4 Antibody-drug Conjugate

While traditional cancer treatments like surgery, radiation, and chemotherapy have helped many patients, they often come with significant limitations and side effects. Antibody-drug conjugates (ADCs) have emerged as a powerful approach, selectively targeting cancer cells to deliver potent anti-tumor agents. Corbus Pharmaceuticals is advancing CRB-701, a next-generation ADC designed to treat cancers expressing the protein Nectin-4. Our aim is to improve on efficacy whilst reducing toxicities.

Understanding the Science

Nectin-4 is a protein typically involved in cell adhesion - the process that helps cells stick together and is mostly found in normal epithelial tissues. However, certain solid tumors, including bladder and cervical cancers, produce very high levels of Nectin-4. This elevated expression is linked to aggressive tumor growth, increased likelihood of cancer spreading (metastasis), and poorer patient outcomes, making Nectin-4 a compelling target for cancer treatment.

Currently, therapies targeting Nectin-4 have shown effectiveness but are limited to treating only a single type of cancer. Additionally, they can cause severe side effects, including skin reactions and nerve damage, which significantly impact patient quality of life.

The CRB-701 Mechanism

CRB-701 is a next-generation ADC carefully engineered to improve upon earlier therapies. It combines three key components:

Targeted antibody: Preferentially binds to Nectin-4 present mostly on cancer cells.
Stable linker: Uses innovative site-specific transglutaminase technology to reliably attach the chemotherapy-like drug, ensuring a stable drug-to-antibody ratio of 2. This linker includes a glutamine-peptide bond for improved stability and precise drug release.
Potent cytotoxic payload (MMAE): Once CRB-701 binds to cancer cells, the ADC is internalized, releasing MMAE inside the tumor cells and inducing targeted cell death. Monomethyl auristatin E (MMAE) is one of the most commonly used payloads for developing antibody–drug conjugates.

This precise targeting helps minimize damage to healthy tissues and may significantly reduce side effects compared to existing therapies.

Progress and Potential

Initial Phase 1 clinical data suggests CRB-701 is generally safe and well tolerated in patients. Its next generation ADC technology potentially reduces severe side effects such as skin toxicity and nerve damage (peripheral neuropathy), common in other treatments targeting Nectin-4. Additionally, CRB-701 offers the convenience of less frequent dosing.

CRB-701 is designed to target and treats multiple types of solid tumors, potentially even those with lower Nectin-4 expression. Its enhanced specificity may help to reduce off-target effects, potentially allowing it to overcome resistance mechanisms that limit other therapies.

Our Commitment

Corbus Pharmaceuticals remains dedicated to developing treatments with a clear, meaningful impact on patients' lives. With CRB-701, our goal is to improve patient outcomes and quality of life, providing an effective therapeutic option across a broader range of solid tumor cancers.