The Expanding Universe of Targeted Biologics
Biologic drugs continue to push boundaries, moving beyond simple monoclonal antibodies (mAbs) toward more complex and targeted therapies. In 2025, Antibody-Drug Conjugates (ADCs) and bispecific antibodies (BsAbs) are at the forefront of this evolution, offering enhanced precision and efficacy.
Antibody-Drug Conjugates (ADCs)
ADCs represent a hybrid therapeutic class that combines the precise targeting capabilities of a monoclonal antibody with the potent cell-killing power of a cytotoxic agent. The antibody directs the payload specifically to cancer cells, minimizing damage to healthy tissue. A prime example is Datroway (datopotamab deruxtecan), an ADC approved in January 2025 for certain breast cancers, demonstrating a significant improvement in progression-free survival over traditional chemotherapy. The ADC pipeline has shown robust growth, with a 40% increase in expected pipeline value over the past year.
Bispecific Antibodies (BsAbs)
Unlike conventional mAbs that bind to a single target, bispecific antibodies can bind to two different antigens simultaneously. This dual-targeting mechanism allows BsAbs to bridge immune cells (like T-cells) and cancer cells, effectively engaging the immune system to fight tumors. The forecasted pipeline revenue for BsAbs has seen a 50% increase over the past year, reflecting strong industry interest and pipeline progress.
The Resurgence of Gene and Nucleic Acid Therapies
Following the success of mRNA vaccines during the COVID-19 pandemic, RNA-based therapies have found broader applications, while gene therapies, despite some challenges, continue to hold immense promise.
RNA-based Therapies
- RNA interference (RNAi): These therapies use small interfering RNA (siRNA) to specifically silence the expression of a disease-causing gene. Products like Fitusiran for hemophilia demonstrate steady progress and pipeline growth.
- Antisense Oligonucleotides (ASOs): ASOs target specific RNA sequences to alter gene expression and are driving significant revenue growth, with recent approvals for ASOs like Rytelo and Izervay bolstering the field.
- mRNA: While mRNA's pipeline value has decreased post-pandemic, innovation continues, with researchers exploring new delivery methods and applications beyond vaccines.
Gene Therapies
Gene augmentation therapies, which aim to correct a genetic defect by adding a functional gene, have faced clinical and commercialization hurdles in 2025, including safety issues leading to trial pauses. However, the field remains a focus for potentially curative treatments for rare diseases, with regulatory bodies and developers working to navigate these challenges.
Cellular Medicine: Advancing CAR-T and Beyond
Cell therapies, which genetically modify or utilize a patient's own cells, represent the pinnacle of personalized medicine. Chimeric Antigen Receptor (CAR) T-cell therapy continues its rapid pipeline expansion, primarily in hematological cancers. However, development is also underway to extend its application to solid tumors.
Other Emerging Cell Therapies
- Tumor-Infiltrating Lymphocytes (TILs): Focused on solid tumors, the TIL pipeline has seen steady growth, with Amtagvi being a notable approval.
- T-cell receptor (TCR-T) therapies: These therapies target intracellular proteins expressed on cancer cells. While Tecelra was approved in 2024 for synovial sarcoma, broader adoption has been limited.
- Mesenchymal stromal therapies: Ryoncil, approved in 2025, is a significant milestone for this type of stem cell therapy.
Precision and Degradation: New Frontiers
One of the most exciting new frontiers in drug discovery is targeting proteins and pathways previously considered 'undruggable'.
Targeted Protein Degradation
Instead of blocking a protein's function, targeted protein degraders like PROTACs (proteolysis-targeting chimeras) and molecular glues use the body's natural cellular machinery to eliminate the protein entirely. This offers a powerful new approach for tackling complex diseases like neurodegenerative disorders.
AI-Powered Drug Discovery
Artificial Intelligence is no longer a futuristic concept but a foundational tool in modern R&D.
- Accelerating Discovery: AI is being used to predict molecular interactions, optimize lead compounds, and shorten development timelines.
- Targeting 'Undruggable' Proteins: AI's analytical power helps researchers identify potential ways to target proteins and pathways that traditional small molecules or biologics cannot.
- Computational Screening: In silico screening methods powered by AI enable the rapid triaging of large compound libraries, improving efficiency.
Comparison of Drug Modalities
| Feature | Small Molecules | Biologics (mAbs, Recombinants) | Targeted Protein Degraders (PROTACs) | RNAi (siRNA) |
|---|---|---|---|---|
| Mechanism | Inhibits/activates specific protein function | Binds to specific protein targets | Induces protein degradation | Silences gene expression |
| Size | Small, synthetic molecules | Large, complex molecules | Medium-sized, synthetic bifunctional molecules | Nucleic acid strands |
| Target Class | Enzymes, receptors, ion channels | Cell surface proteins, secreted proteins | Intracellular proteins (including 'undruggable' targets) | RNA |
| Specificity | Can be less specific, leading to off-target effects | High specificity | High specificity, but with potential for off-target degradation | Highly specific to target RNA sequence |
| Oral Availability | High | Low (typically injected) | Improving, but can be challenging | Low (typically injected) |
| Manufacturing | Standard chemical synthesis | Complex, expensive manufacturing (e.g., cell cultures) | Standard chemical synthesis | Automated synthesis |
Conclusion
The pharmaceutical landscape in 2025 is undergoing a radical transformation, with new drug modalities representing the next generation of therapeutics. From targeted biologics like ADCs and BsAbs to the resurgence of nucleic acid therapies and the promise of cellular medicine, innovation is accelerating at an unprecedented pace. The integration of artificial intelligence is further fueling this revolution, enabling researchers to tackle previously 'undruggable' targets and personalize treatments for patients. While challenges remain, the progress made with these new modalities signifies a promising future for more effective and precise treatments across a wide range of diseases. For more insights into the evolving landscape, visit the BCG website.
Future Outlook
The trajectory of these new modalities points toward an era of hyper-personalized medicine, where treatments are precisely tailored to a patient's genetic makeup and disease profile. Continued investment and innovation in these platforms, coupled with advancements in AI, will be critical to overcoming current limitations and expanding the reach of these life-changing therapies.
