Next-Generation Modalities Drive New Antibody Discovery

The biopharmaceutical landscape is currently undergoing a significant shift from traditional therapies toward more specialty-driven modalities. In the past two years, for instance, the development pipeline for antibody therapeutics has been defined by distinct clinical trends, manufacturing scalability, and regulatory acceleration (1).

As the biopharma industry moves into 2026, the focus is increasingly on multifunctional and next-generation antibody formats designed to address hard-to-treat diseases and unmet medical needs. This transition is critical for the industry as it seeks to replace revenue lost to upcoming patent cliffs, while simultaneously improving patient outcomes through more targeted and potent interventions (2).

How are emerging preclinical strategies accelerating the discovery of novel antibody therapeutics?

Early-stage discovery is increasingly reliant on integrated tools and innovative platform technologies to identify viable targets and optimize molecule design. One prominent trend is the use of proteomics-driven oncology target discovery (3). In late 2025, GSK and Oxford BioTherapeutics initiated a large-scale collaboration to leverage proteomics technology for advancing antibody therapeutics (4).

Such partnerships are vital for the industry because they allow for the identification of novel targets at a speed and scale previously unattainable through traditional methods. Beyond traditional discovery, the establishment of programmable biology is reshaping how engineered biologics are designed.

By combining programmable biology with integrated discovery tools, companies aim to speed the development of treatments for complex diseases (5). Furthermore, new biotechnology entities are emerging with substantial financial backing specifically to develop multifunctional antibody modalities. For instance, Avidicure was launched with $50 million in seed financing to focus on this area, illustrating the industry’s commitment to exploring beyond standard monoclonal antibodies (mAbs) into more complex, multi-target formats (6).

Which next-gen antibody modalities are receiving accelerated regulatory designation in oncology development?

The clinical pipeline is currently dominated by high-potency molecules, specifically bispecific antibodies and antibody-drug conjugates (ADCs). Regulators are responding to the potential of these modalities with accelerated designations to expedite their arrival on the market (see Table).

In August 2025, FDA granted breakthrough therapy designation to iza-bren, a bispecific ADC candidate targeting epidermal growth factor receptor-mutant non-small cell lung cancer (7). This designation was supported by efficacy and safety data from global trials, highlighting the priority given to novel ADC mechanisms. Similarly, ifinatamab deruxtecan received breakthrough therapy status for small cell lung cancer after showing promising results in patients who had failed prior chemotherapy (8).

The industry is also seeing a resurgence in the application of mAbs for complex central nervous system disorders and infectious diseases (9). For example, Eli Lilly and Company’s (Lilly’s) donanemab-azbt demonstrated clinical success in Phase III trials by slowing the decline in patients with early symptomatic Alzheimer’s disease (10). Meanwhile, in the field of infectious disease, human clinical trials have been initiated for MBP1F5, a novel Nipah mAb. This therapeutic is designed to offer immediate protection for at-risk populations in India and Bangladesh, representing a major step in using biologics to contain viral outbreaks with high lethality (11).

How can manufacturing infrastructure support the anticipated growth in antibody production capacity?

To support the influx of new antibody candidates, the biopharma industry is undergoing a massive expansion of manufacturing infrastructure and technological capabilities. It is projected that contract manufacturing organizations and hybrid companies will hold 54% of global biologics capacity by 2028 (12). This shift highlights the industry's reliance on outsourcing to manage the complexity and scale of next-generation production.

In addition, major investments are being made to strengthen regional production hubs. Sanofi, for example, invested €40 million (US$46 million) in its Lyon Gerland site in France in November 2024 to boost antibody bioproduction (13). Similarly, in September 2024, Lilly committed $1.8 billion to expand its biologics footprint in Ireland, emphasizing the global nature of the supply chain (14).

Furthermore, the industry is moving toward more integrated, de-risked workflows. Collaborations such as those between Orion and Abzena and Rentschler and Coriolis are focused on streamlining the pathway from formulation to commercial-scale manufacturing (15,16). These integrated partnerships are essential for reducing development delays and ensuring that complex molecules, such as multispecific antibodies and ADCs, can be manufactured consistently at high quality.

How is the biosimilar pipeline impacting the commercial landscape of reference mAbs?

As reference biologics lose patent protection—a phenomenon often called the patent cliff—the biosimilar market is expanding rapidly. Over the coming decade and beyond, a large wave of biologics is expected to lose exclusivity, which would put hundreds of billions of dollars in annual revenue at risk, creating substantial opportunities for biosimilars and next‑generation competitors (17). This has led to intense competition and strategic licensing agreements, such as the August 2025 partnership between Polpharma Biologics and Fresenius Kabi to develop a biosimilar for Takeda’s Entyvio (18).

A key commercial milestone for biosimilars is achieving interchangeable status from FDA. An interchangeable designation allows pharmacists to substitute a biosimilar for the reference mAb without consulting with the prescribing physician.

This designation is a major driver of market penetration and cost savings (19). Notable recent examples include FDA's designation of Yuflyma (adalimumab-aaty) as an interchangeable, high-concentration, citrate-free biosimilar to Humira (adalimumab) (20).

Additionally, Bkemv (eculizumab-aeeb) was approved as the first interchangeable biosimilar for Soliris (eculizumab), targeting rare blood and immune disorders (21). These developments are crucial for the industry because they facilitate broader patient access.

What does the future look like for antibody R&D?

The R&D pipeline for new antibodies is currently characterized by a high degree of technical sophistication and a push toward global scalability. From the use of machine learning to design novel ADCs to the establishment of multi-billion-dollar manufacturing sites, every stage of the pipeline is being optimized to meet future demand.

The industry’s ability to navigate regulatory pathways—such as priority review and regenerative medicine advanced therapy status—will determine how quickly these next-generation antibody therapies reach patients. As the market prepares for a surge in biosimilars and the commercialization of multifunctional antibodies, the focus remains on maintaining analytical excellence and manufacturing consistency to ensure the long-term safety and efficacy of these complex biological medicines.

References

1. Crescioli, S.; Kaplon, H.; Chenoweth, A.; et al. Antibodies to Watch in 2024. mAbs 2024, 16 (1), 2297450. DOI: 10.1080/19420862.2023.2297450
2. Mirasol, F. Emerging Modalities and Strategic Innovation in the Biopharma R&D Landscape. BioPharm International Next-Generation Biotherapeutics eBook, April 2025.
3. Wu, Q.; Zheng, J.; Sui, X.; et al. High-Throughput Drug Target Discovery Using a Fully Automated Proteomics Sample Preparation Platform. Chem. Sci. 2024, 15 (8), 2833–2847. DOI: 10.1039/d3sc05937e
4. Oxford BioTherapeutics. Oxford BioTherapeutics Enters into a Strategic Collaboration with GSK to Discover Novel Targets for Antibody-Based Therapeutics for the Treatment of Cancer. Press Release. Dec. 10, 2025.
5. Teng, F.; Cui, T.; Zhou, L.; et al. Programmable Synthetic Receptors: The Next-Generation of Cell and Gene Therapies. Signal Transduction Targeted Ther. 2024, 9, 7. DOI: 10.1038/s41392-023-01680-5
6. Avidicure. Avidicure Launches with $50 Million in Seed Financing to Develop New Multifunctional Antibody Modality to Treat Cancer. Press Release. April 24, 2025.
7. Bristol Myers Squibb. Izalontamab Brengitecan (EGFRxHER3 ADC) Granted Breakthrough Therapy Designation by US FDA for Patients with Previously Treated Advanced EGFR-Mutated Non-Small Cell Lung Cancer. Press Release. Aug. 18, 2025.
8. Daiichi Sankyo. Ifinatamab Deruxtecan Granted Breakthrough Therapy Designation by US FDA for Patients with Pretreated Extensive-Stage Small Cell Lung Cancer. Press Release. Aug. 18, 2025.
9. Lu, R. M.; Chiang, H. L.; Yuan, J.P.; et al. Technological Advancements in Antibody-Based Therapeutics for Treatment of Diseases. J. Biomed. Sci. 2025, 32 (1), 98. DOI: 10.1186/s12929-025-01190-2
10. Eli Lilly and Company. Lilly’s Kisunla (donanemab-azbt) Showed Growing Benefit Over Three Years in Early Symptomatic Alzheimer’s Disease. Press Release. July 30, 2025.
11. CEPI. CEPI Signs New Collaborative Agreement with US Dept of Defense to Expand Protection Against Disease Outbreaks. Press Release. May 28, 2025.
12. CPHI. CPHI Annual Report 2024. cphi-online.com. October 2024.
13. Sanofi. Sanofi Strengthens Antibody Bioproduction in France with an Investment of More Than 40 Million Euros on Its Lyon Gerland Site. Press Release. Nov. 15, 2024.
14. Eli Lilly and Company. Lilly Expands Manufacturing Footprint in Ireland with $1.8 Billion Investment. Press Release. Sept. 12, 2024.
15. Abzena. Orion and Abzena Announce Exclusive Commercial License for Abzena’s Antibody. Press Release. Oct. 23, 2025.
16. Rentschler Biopharma. Rentschler Biopharma and Coriolis Pharma Announce Strategic Collaboration for Integrated Biopharma Solutions. Press Release. Dec. 2, 2025.
17. DrugPatentWatch. The Multi-Billion Dollar Countdown: Decoding the Patent Cliff and Seizing the Generic Opportunity. DrugPatentWatch.com. Sept. 9, 2005.
18. Polpharma Biologics. Polpharma Biologics and Fresenius Kabi Sign Licensing Agreement for Proposed Vedolizumab Biosimilar PB016. Press Release. Aug. 5, 2025.
19. FDA. 9 Things to Know About Biosimilars and Interchangeable Biosimilars. FDA.gov. Current as of June 20, 2024 (accessed Jan. 15, 2026).
20. Celltrion. US FDA Grants Interchangeable Designation to YUFLYMA (adalimumab-aaty), Celltrion's Biosimilar to Humira (adalimumab). Press Release. April 14, 2025.
21. FDA. FDA Approves First Interchangeable Biosimilar for Two Rare Diseases. Press Release. May 28, 2024

About the author

Feliza Mirasol is the science editor for BioPharm International®.