Insiders in the contract development and manufacturing organization industry expect to witness significant changes in 2024, driven by technological advancements. The CDMO industry has grown significantly in recent years, with more drug developers relying on outsourcing services to CDMOs, as well as biologics becoming increasingly prevalent as leading therapeutic candidates for a range of conditions. Experts expect these trends to continue this year, with developments spanning domains such as bispecific antibodies, antibody-drug conjugates, and increasing use of automation and artificial intelligence in biopharmaceutical development and manufacturing practices.
“Innovative thinking has already led to the design of powerful advanced therapeutics, such as bispecific antibodies, fusion proteins, and antibody-drug conjugates,” said Kevin Sharp, senior vice president and head of sales for CDMO Samsung Biologics, in a recent interview with Drug Development & Delivery. “We are seeing a drive toward developing these novel materials, which often provide enhanced performance, with improved efficacy and binding specificity compared with monoclonal antibody counterparts.”
Bispecific Antibodies
Bispecific antibodies represent a significant leap forward in the pursuit of more effective treatments for complex diseases such as cancer. BsAbs engage two distinct targets simultaneously, potentially outperforming conventional monoclonal antibodies that target a single epitope.
This dual targeting mechanism allows for the simultaneous blockade of two pathways critical to tumor growth and survival, which may reduce the likelihood of resistance developing through compensatory pathways. A BsAb might target both a growth factor receptor that’s driving tumor growth and a checkpoint inhibitor that’s preventing the immune system from attacking the tumor, thereby combating the cancer on two fronts.
The strategic design of BsAbs enables the recruitment of immune cells to cancer cells, a process known as immune cell retargeting. This not only helps in directly killing cancer cells, but also activates the patient’s immune response against the tumor. The versatility of BsAbs extends beyond oncology, with potential applications in autoimmune diseases, infectious diseases, and beyond, where dual targeting can offer novel therapeutic avenues.
“BsAbs have shown promise for treating severe cancers, such as multiple myeloma, non-small cell lung cancer, and cervical cancer, and the number of novel [drug products] like BsAbs entering clinical trials is expected to increase further,” said Sharp.
Advancements in the development of BsAbs have spurred innovation within the CDMO industry, necessitating new manufacturing and production technologies. The complex structure of BsAbs presents unique challenges in production, requiring precise control over the assembly of the antibody to ensure that each molecule can engage with its intended targets. This has led to the adoption of sophisticated expression systems and purification processes to achieve high yields of functional, therapeutically effective BsAbs.
Antibody-Drug Conjugates
Antibody-drug conjugates present a fusion of targeting capability and cytotoxic firepower, embodying a therapeutic strategy that’s increasingly central to oncology. The specificity of antibodies directed at tumor-associated antigens, coupled with the cell-killing efficiency of cytotoxic drugs, form the basis of ADCs. This approach ensures that the toxic payload is delivered directly to cancer cells, sparing healthy tissues and minimizing side effects associated with conventional chemotherapy.
Recent trials have demonstrated the effectiveness of ADCs in treating a variety of cancers, including Hodgkin lymphoma and breast cancer, showcasing its potential to become a cornerstone in oncology treatment protocols.
The continuous evolution of ADC technology has been marked by significant advancements in linker chemistry and the potency of cytotoxins. Early generations of ADCs faced challenges related to stability, with premature release of the cytotoxic drug before reaching the target cell. However, recent innovations have led to the development of more stable linkers, ensuring that the therapeutic payload is released only upon reaching the tumor environment. This has significantly improved the therapeutic index of ADCs.
For the CDMO industry, these developments signal a growing demand for expertise in ADC manufacturing. The complexity of ADCs, which involves the conjugation of a biologic component with a synthetic cytotoxic drug, requires specialized capabilities, including handling highly potent cytotoxic agents and executing sophisticated conjugation processes. Companies with the ability to navigate these complexities are well positioned to support the growing pipeline of ADCs.
Automation and AI
The integration of automation and AI into biologic manufacturing processes marks a pivotal shift toward more efficient and streamlined operations. These technologies play a crucial role in optimizing production lines, ensuring consistency and quality in biologic production. Automation, in particular, is instrumental in reducing manual intervention, minimizing the risk of errors and increasing the throughput of manufacturing processes. AI and machine learning algorithms are increasingly being employed to predict and manage complex bioprocessing parameters, leading to improved decision-making and operational efficiency.
CDMOs that implement high-throughput screening can accelerate drug discovery and optimization. High-throughput screening allows for the rapid evaluation of thousands to millions of compounds or genetic constructs, offering a scalable method to identify promising candidates for further development. This technology is particularly crucial in the early stages of biologic and pharmaceutical development, where the need to efficiently sift through vast libraries of molecules or genetic variants is paramount.
“The advancements in manufacturing efficiency and productivity as a result of technological advances can lead to a significant competitive market advantage,” said Sharp.