Why TPD Is Biotech's Next Big Bet

Targeted Protein Degradation (TPD) is an emerging therapeutic approach that allows the removal of disease-causing proteins once considered 'undruggable'.

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Targeted protein degraders (TPD) are rapidly moving from niche science to mainstream drug development, with few therapies approved and many more advancing through late-stage trials.

TPD today rests on two pillars: PROTACs and molecular glues. PROTACS (proteolysis-targeting chimeras), proposed over two decades ago, work by bringing disease-causing proteins into proximity with the cell's degradation machinery. While none have yet reached the market, the field is gaining momentum with more than 40 candidates in clinical testing for cancers and autoimmune disorders, according to Biopharma PEG blog. These include inhibitors targeting the androgen receptor (AR), estrogen receptor (ER), Bruton's tyrosine kinase (BTK), and IRAK4. Three PROTACS are already in late-stage trials: Arvinas/Pfizer's ARV-471 (ER), Bristol Myers Squibb's BMS-986365 (AR), and BeiGene's BGB-16673 (BTK). Industry is closely watching Arvinas/Pfizer's ARV-471, with USFDA acceptance of its NDA in August 2025 and approval expected by June 2026. If approved, ARV-471 could become the first PROTAC therapy to reach the market, marking a major milestone for targeted protein degradation.