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“3 Key Trends” with Louise Duffy

Abzena’s Chief Technical Officer offers her thought leadership.

What are “3 Key Trends” shaping the CDMO industry in 2023 and beyond? Abzena’s chief technical officer, Louise Duffy, shares her thoughts with Contract Pharma.

The rise of antibody-drug conjugates (ADCs)
Antibody-drug conjugates (ADCs) are promising therapeutics that have received considerable attention this past year, with over 50 ADCs in the pre-clinical stage and a total of 190 active clinical trials.1 Complex to produce, ADCs are composed of a highly potent payload covalently linked to an antibody. As a fast-growing therapeutic for treating cancer, ADCs can be used to specifically deliver potent cytotoxic pharmaceuticals directly to cancer cells. In addition, optimization to strengthen targeted antibody binding, increase ADC half-life, and reduce immunogenicity, have only increased their desirability as potential treatments for a range of diseases, including Alzheimer’s.2 Aided by innovation in antibody engineering and with increasingly complex ADCs being developed, the number of ADC-based therapeutics is expected to increase further. However, as their complexity increases, manufacturing becomes more challenging, leading to many CDMOs investing in more robust and efficient ADC manufacturing processes.

Optimizing downstream development
As stated above, manufacturing challenges increase as a product becomes more complex. This is due to production techniques and processes often requiring extensive optimization, which can lengthen the development process and lead to a longer timeline to reach the market. An increasing number of protein-drug conjugates (PDCs)—for which ADCs are an example—are currently in development. Significant investment to simplify manufacturing focus on streamlining downstream development by introducing new chromatography-based purification techniques. Some examples include using a new resin, running conventional chromatography steps in a series, or altering the chromatography mode used. Advancements in artificial intelligence and machine learning technology are also aiding timeline acceleration by helping to implement automated manufacturing processes.

Increasingly potent compounds
Highly potent active pharmaceutical ingredients (HPAPI) can be linked to an antibody to form a potent ADC. The ability of HPAPIs to deliver beneficial pharmacological effects at lower concentrations means a lower dose can be given to get the desired result, reducing the risk of side effects, and making HPAPI-based drugs an attractive target for treating various chronic diseases. However, many safety risks are associated with potent compounds, and strict procedures must be followed by manufacturers. This includes completing extensive risk assessments and using specialized equipment to ensure safe handling. CDMOs often have these capabilities in place and can develop and manufacture these products at speed. Potential risks are further mitigated as experts with experience in HPAPI handling are used. Therefore, many pharma companies are outsourcing the manufacture of HPAPIs, including those used for HPAPI-based ADCs, to CDMOs for efficient manufacture.


References
1. Antibody Drug Conjugate Global Market Report 2023: 190 Active Clinical Trials Bodes Well for Acceptance and Growth (yahoo.com)
2. Punyakoti, P. et al. (2023) “Postulating the possible cellular signalling mechanisms of antibody drug conjugates in alzheimer’s disease,” Cellular Signalling, 102, p. 110539. Available at: https://doi.org/10.1016/j.cellsig.2022.110539.

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