This episode explores targeted protein degradation (TPD), a cutting-edge approach in drug discovery that uses the body’s natural recycling system to eliminate disease-causing proteins. Andrew Hirsch, CEO of C4 Therapeutics (C4T), discusses how their proprietary Torpedo™ platform is pushing the boundaries of precision medicine, especially in oncology.

Key Points:

C4T is pioneering oral drugs that trigger the body to break down harmful proteins at the source. With several clinical trials underway, TPD could be a transformative leap in treating cancer and other diseases.

• Targeted Protein Degradation: Most drugs inhibit bad proteins, but TPD takes it further by marking harmful proteins for destruction using the cell’s own disposal system. This approach can result in more selective, potent, and potentially safer treatments.
• C4T’s Torpedo™ Platform: C4T’s proprietary platform designs degraders that harness the ubiquitin-proteasome system to target disease-causing proteins with remarkable precision. The degraders are catalytic—one molecule can destroy thousands of bad proteins.
• Different Strategies- PROTACs, Molecular Glues & Antibody Conjugates: C4T uses various strategies depending on the disease and target protein, including heterobifunctional degraders (PROTACs), molecular glues, and degrader-antibody conjugates that combine high specificity with intracellular targeting.
• Promising Clinical Trials in Cancer: Their lead candidate, CFT1946, showed encouraging results in early trials for cancers with BRAF V600 mutations. Another program, focused on multiple myeloma and non-Hodgkin lymphoma, aims to improve on existing therapies using optimized degraders.
• The Road Ahead: While early hype led to some missteps in the field, TPD now shows realistic, data-driven promise. With partnerships across Biogen, Roche, and Merck, and a robust drug pipeline, TPD is poised to become a mainstream therapeutic approach.