Novartis Pioneers ‘Induced Proximity’ in Cancer Drug Discovery

Novartis is at the forefront of a new wave in oncology drug discovery, focusing on a strategy called “induced proximity” to target cancers previously considered untreatable. This approach, spearheaded by teams in San Diego, California, and integrated with global research sites in Cambridge, Massachusetts, and Basel, Switzerland, aims to revolutionize cancer treatment by manipulating disease-causing proteins at a fundamental level. Novartis is investing $23 billion in U.S. Research and development and advanced manufacturing to accelerate these efforts.

Understanding ‘Induced Proximity’

Induced proximity represents a shift from traditional drug discovery methods. Instead of relying on chemical compounds to bind to specific sites on disease-causing proteins, it focuses on bringing these proteins into close physical proximity with other biomolecules to alter their function. This strategy encompasses techniques like targeted protein degradation (TPD) and regulated induced proximity targeting chimeras (RIPTAC).

What is RIPTAC?

RIPTAC, or “Regulated Induced Proximity Targeting Chimeras,” employs a “catch-and-kill” mechanism. It utilizes a molecule that attaches to a tumor-specific protein and simultaneously captures another essential protein within the cancer cell, ultimately leading to cell death while sparing healthy cells. This targeted approach holds the potential for transformative cancer therapies.

Focus Areas: Prostate, Breast, and Gastrointestinal Cancers

The Novartis team in San Diego concentrates on disease-focused areas, prioritizing prostate cancer and breast cancer, building upon existing treatments to address unmet patient needs. They are also heavily invested in gastrointestinal (GI) cancers, including colorectal and pancreatic cancers, recognizing the lack of transformative medicines available for these diseases.

Evolution of Oncology Drug Discovery

Oncology drug discovery has evolved significantly, with clinical learnings now informing and refining the discovery process. This iterative approach allows researchers to understand unmet medical needs directly from patient experiences, identifying vulnerabilities in specific cancers and targeting the most impactful proteins or genes.

Addressing ‘Undruggable’ Targets

Many established cancer targets, such as HER2, BRAF, and EGFR, have been extensively studied. The current challenge lies in finding new breakthroughs, particularly in targeting proteins previously considered “undruggable,” like β-catenin and MYC. Induced proximity offers a potential solution to overcome these hurdles.

Future Directions: Tumor Suppressors

Looking ahead, Novartis is exploring the potential of reactivating tumor suppressors, such as P53, which is frequently mutated in cancer. This innovative approach could open new avenues for cancer treatment.

A Vision for the Future

The ultimate goal is to achieve transformational breakthroughs in challenging cancers like pancreatic and other GI cancers, offering curative therapies and improving the lives of patients worldwide. The new San Diego research center, expected to be operational in 2029, will house approximately 1,000 employees and play a crucial role in realizing this vision. The 466,000-square-foot facility will be equipped with AI-enabled discovery capabilities.