In 2024, the global antibody drug market is expected to experience explosive growth. According to IQVIA, global spending on biopharmaceuticals is projected to exceed $892 billion by 2028, with antibody drugs holding a significant share. In the fields of oncology and autoimmune diseases, three major technological routes—bispecific antibodies (BsAbs), antibody-drug conjugates (ADCs), and proteolysis-targeting chimeras (PROTACs)—are forming a competitive landscape. These innovative therapies break through traditional treatment bottlenecks through different mechanisms, but which one will dominate the next decade?
Bispecific Antibodies: The “Dual-Action” Regulators of the Immune System
Technological Breakthroughs and Clinical Value
At the 2024 ASH Annual Meeting, AstraZeneca’s CD19/CD3 bispecific antibody AZD0486 attracted attention. This drug achieves a 95% objective response rate (ORR) and an 85% complete response rate (CR) in the treatment of follicular lymphoma through a unique IgG4 structural design, with safety significantly superior to CAR-T therapies. Its innovations include:
Low-affinity CD3 binding domain: Reduces the risk of cytokine release syndrome (CRS)
Long half-life design: Supports intermittent dosing, enhancing patient compliance
Coverage for CD20-negative patients: Breaks through the target limitations of traditional monoclonal antibodies
Market Landscape and Challenges
The global bispecific antibody market has reached a scale of tens of billions of dollars, but the success rate of R&D is only about 30%. Chinese pharmaceutical companies have shown impressive performance: Kanyin Biopharma’s PD-1/CTLA-4 bispecific antibody Cadonilimab has been approved for market, and Innovent Biologics’ IBI-318 has shown potential in non-small cell lung cancer. However, the development of bispecific antibodies still faces three major challenges:
Structural complexity: Two different antibody chains are prone to mispairing, requiring the use of “knob-in-hole” technology for forced pairing
Immunogenicity risk: Early bispecific antibodies were forced to terminate clinical trials due to high rates of anti-drug antibody positivity
Target combination validation: Over 60% of global projects are terminated due to ineffective target combinations
ADCs: Revolutionary “Biological Missiles” for Precise Delivery
Market Explosion and Technological Iteration
The global ADC market is expected to exceed $10 billion in 2024, with Daiichi Sankyo’s Enhertu leading with sales of $3.48 billion. This drug achieves breakthroughs in HER2-low expressing breast cancer through a cleavable linker design:
Toxin selection optimization: Uses the topoisomerase inhibitor DXd, which is 10 times more potent than traditional toxins
Linker stability: The four-peptide structure ensures precise release in the tumor microenvironment
Indication expansion: Extends from breast cancer to lung cancer, gastric cancer, and other malignancies
Breakthroughs by Chinese Innovators
Rongchang Biopharma’s RC48 has pioneered domestic ADCs, with key success factors including:
Differentiated target selection: Targeting HER2 low-expressing patient populations
Production process breakthroughs: Achieving uniform antibody-toxin conjugation through mass spectrometry screening
Medical insurance access strategy: Rapid market expansion after entering medical insurance in 2023
However, ADC development still faces challenges: The toxin dosage must be precisely balanced between “effective killing” and “systemic toxicity,” with early projects failing due to linker instability exceeding a 40% failure rate.
PROTAC: The Rise of Disruptive Degradation Technology
Clinical Breakthroughs and Mechanistic Advantages
In 2024, three PROTAC drugs entered Phase III clinical trials:
ARV-471 (Arvinas/Pfizer): An ER degrader significantly extends PFS in breast cancer treatment
BMS-986365 (Bristol-Myers Squibb): An AR degrader achieves a 32% PSA50 response rate in prostate cancer
BGB-16673 (BeiGene): A BTK degrader achieves a 78% ORR in CLL
Technological Breakthroughs
PROTAC achieves protein degradation through an “event-driven” mechanism, offering three major advantages over traditional small molecule inhibitors:
Overcoming resistance: Degrades the entire target protein rather than just inhibiting the active site
Targeting undruggable targets: Such as transcription factors and scaffold proteins
Catalytic action mode: Low doses can continuously clear pathogenic proteins
Commercialization Challenges
Despite over 170 PROTAC candidates globally, the commercialization process is still limited by:
Oral bioavailability: Most candidates require high doses and multiple administrations
Linker optimization: Balancing protein binding affinity and degradation efficiency
Patent barriers: The U.S. is 2-3 years ahead of China in core patent positioning
The Next Decade: Technological Integration and Regulatory Innovation
Competitive Landscape Predictions
Bispecific antibodies: Forming advantages in hematological malignancies, but need to overcome solid tumor target combination bottlenecks
ADCs: Expected to dominate the solid tumor market with “precision strike” characteristics, with a projected global scale exceeding $66 billion by 2030
PROTAC: Opening new battles in hormone-dependent tumors and autoimmune diseases
Impact of Regulatory Policies
In 2024, 38% of the 50 new drugs approved by the FDA are biopharmaceuticals. China’s NMPA is accelerating the approval of innovative drugs, with the domestic ADC Trelagliptin receiving FDA approval in 2024, marking a new phase for Chinese innovative drugs going global.
Conclusion
Bispecific antibodies, ADCs, and PROTACs are not simply alternatives but form a complementary therapeutic matrix:
Bispecific antibodies: As “precision switches” for immune modulation, continue to exert influence in hematological malignancies and autoimmune diseases
ADCs: With “missile-level” lethality, become the main force in solid tumor treatment
PROTAC: With disruptive degradation mechanisms, explore the blue ocean of “undruggable” targets
In the next decade, technological integration may be key. For example, developing a “bispecific antibody-ADC” platform or combining PROTAC with ADCs to enhance efficacy. The ultimate winner in this innovation race will be the technology route that most precisely meets unmet clinical needs.
ProMabio
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