Targeted protein degradation (TPD) is rapidly transitioning from experimental science to a cornerstone of modern drug development, with the field poised for its first major regulatory milestone as Arvinas and Pfizer's ARV-471 approaches potential FDA approval by June 2026. This estrogen receptor-targeting PROTAC could become the first of its kind to reach market, marking a watershed moment for the technology that promises to unlock previously "undruggable" therapeutic targets.
The momentum behind TPD reflects a fundamental shift in how the pharmaceutical industry approaches intractable diseases. Unlike conventional drugs that inhibit protein function, TPD therapies eliminate disease-causing proteins entirely by hijacking the cell's natural degradation machinery. This approach has attracted unprecedented investment, with major pharmaceutical companies committing over $10 billion in partnerships and acquisitions since 2024.
Industry Giants Drive Multi-Billion Dollar Investment Wave
The scale of pharmaceutical industry commitment to TPD became evident through a series of blockbuster deals in 2024 and 2025. AbbVie struck a partnership with U.S. biotech Neomorph valued at up to $1.64 billion, focusing on molecular glue degraders across oncology and immunology. LEO Pharma entered a $1.7 billion alliance with Gilead Sciences to advance STAT6 inhibitors and degraders for inflammatory diseases, while Magnet Biomedicine partnered with Eli Lilly in a $1.25 billion deal to apply its TrueGlue platform in oncology.
These recent agreements built upon significant transactions from late 2024, including Takeda's $1.2 billion commitment to collaborate with China's Degron Therapeutics, Eisai's $1.5 billion research pact with SEED Therapeutics, and Novartis's acquisition of global rights to Monte Rosa's MRT-6160 for $150 million upfront with potential milestones exceeding $2.1 billion. Biogen also entered a $1.45 billion collaboration with Neomorph to access its glue discovery platform.
Clinical Pipeline Reaches Critical Mass
The TPD field now encompasses two primary approaches: PROTACs and molecular glues. More than 40 PROTAC candidates are currently in clinical testing for cancers and autoimmune disorders, targeting key proteins including the androgen receptor (AR), estrogen receptor (ER), Bruton's tyrosine kinase (BTK), and IRAK4. Three PROTACs have advanced to late-stage trials: Arvinas/Pfizer's ARV-471 for ER, Bristol Myers Squibb's BMS-986365 for AR, and BeiGene's BGB-16673 for BTK.
The FDA's acceptance of ARV-471's New Drug Application in August 2025 represents a pivotal moment for the field. If approved by the June 2026 target date, ARV-471 would establish the first commercial precedent for PROTAC therapies and validate the approach for investors and developers worldwide.
Molecular glues have already achieved commercial success, with Bristol Myers Squibb's portfolio including Revlimid, Pomalyst, and Thalomid approved for adult multiple myeloma patients. The molecular glue landscape has expanded dramatically, with over 50 companies advancing more than 60 candidates, including BMS's mezigdomide and golcadomide, Eisai's E7820, and Nurix's NX-5948 and NX-2127.
Asia-Pacific Emerges as Global TPD Hub
The Asia-Pacific region has established itself as a major center for TPD innovation, with China and South Korea leading development efforts. In South Korea, SK Biopharmaceuticals acquired a 60% stake in Proteovant Sciences (now SK Life Sciences Labs), focusing on anti-cancer and central nervous system therapies using AI-enabled target identification and proprietary MOPED molecular glue screening technology.
Yuhan Corporation has pursued partnerships with multiple biotech firms including Uppthera, Cyrus Therapeutics, and Ubix Therapeutics to expand its TPD pipeline. Daewoong Pharmaceutical partnered with Pin Therapeutics in 2023, advancing PIN-5018, a first-in-class CK1α molecular glue degrader that received IND clearance in May 2025 for colorectal cancer, adenoid cystic carcinoma, and relapsed/refractory AML.
Several South Korean biotech companies have achieved significant clinical milestones. Ubix Therapeutics received IND approval for UBX-303-1 from both the U.S. FDA and Korean MFDS, conducting global clinical trials while establishing partnerships including a February 2025 agreement with Y-Biologics for degrader antibody conjugates. Orum Therapeutics, which raised ₩50 billion in a Korea Exchange IPO in February 2025, is developing ORM-1153, a GSPT1 degrader for acute myeloid leukemia, with preclinical data expected this year.
Chinese Companies Advance Late-Stage Programs
China has rapidly established itself as a TPD hub with multiple companies progressing candidates through advanced clinical trials. BeiGene is advancing its Chimeric Degradation Activation Compound (cDAC) in phase 3 trials for patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
Kintor Pharma achieved a significant milestone when its GT20029, claimed as the world's first dermatological topical AR degrader, met its Phase II primary endpoint in September 2024 for treating male androgenetic alopecia. The company is now preparing for Phase III trials. Jiangsu HengRui is developing HRS-5041, an ER-targeting degrader for metastatic castration-resistant prostate cancer, and HRS-1358, an AR-targeting degrader for breast cancer, both currently in Phase II trials.
GluBio Therapeutics completed phase I trials for GLB-002, an IKZF1/3-selective molecular glue degrader, in patients with relapsed or refractory non-Hodgkin lymphoma, demonstrating strong pharmacokinetics, pharmacodynamics, safety, and target degradation. Phase II recruitment is now open.
Technological Advances Drive Innovation
The current momentum in TPD stems from foundational discoveries identifying versatile binders to E3 ligases such as VHL (Von Hippel-Lindau) and CRBN (Cereblon). According to Kristin Riching, Senior Research Scientist at Promega, "We have made significant advances in our understanding of the chemical features governing neo-substrate recruitment with CRBN-based molecular glues and PROTACs, aiding more rational design of selective degraders."
Chinatsu Sakata, Head of Oncology Research at Astellas Pharma, highlighted the expanding technological landscape: "There is explosive growth in novel degradation strategies that go beyond traditional PROTACs, expanding the modalities available for TPD and enhancing its versatility. Rapid advances in computational tools and AI are helping us design molecules that can not only form the ternary complex but also reach their targets deeper in tissues—two of the toughest challenges in TPD development."
Market Outlook and Future Prospects
The global TPD market, currently valued at $1 billion, is projected to surge to $6.94 billion by 2035, reflecting the technology's potential to address previously intractable therapeutic targets. As more TPD assets progress through trials and approach regulatory milestones, the field is entering a decisive phase where real-world clinical data will define its ultimate potential.
Sakata noted that the next phase will bring greater scientific clarity: "This next chapter will bring greater clarity on resistance mechanisms, informing more refined development strategies and helping identify optimal patient populations. We expect continued expansion of heterobifunctional molecules and growing interest in molecular glue-type degraders, both of which offer promising avenues for enhanced efficacy and broader disease applicability."
The maturation of the TPD ecosystem, including the rise of specialized contract research organizations particularly in Asia-Pacific, has shortened development cycles and lowered barriers for startups and smaller biotechs to enter the space. With computational advances enabling more accurate prediction of ubiquitination and degradation efficiency, the field appears positioned for continued rapid growth and clinical success.
