Each year the BioAgilytix team attends the PEGS Summit in Boston, MA to participate in discussions around the latest advancements in biotherapeutic protein drug development and how they impact the work we do with large molecule biologics. It is important for our company to make attendance at leading events like this a priority, because it enables us to stay on the pulse of bioanalytical innovation, share our own perspectives on how to best address key testing challenges, and gain insights from other colleagues that will ultimately help us all better our work – and collectively support improved patient outcomes.

PEGS was extremely content-rich this year and touched on a variety of hot topics that are top-of-mind among our team today, from improving efficacy of CAR-T cell therapies to managing the challenges of immunogenicity testing. We felt it would be valuable to summarize some of the key points discussed in different PEGS sessions and in our conversations with other scientific thought leaders:

Troubleshooting Antibodies for Cancer Therapy
It was not surprising that CAR-T cell therapies were a major topic of discussion throughout the entire event. At BioAgilytix, we have seen a significant increase in requests for projects involving cell therapies, and while such treatments are helping our industry make exciting progress in the fight against cancer, there are still many challenges that scientists must deal with when working in this relatively new area of drug development.

A particularly insightful session during PEGS focused on anti-angiogenic agents used in cancer therapy (VEGF). Much of the conversation surrounded key issues that come along with these agents, including limited efficacy as angiogenesis persists in the face of therapy, and toxicities that cannot discriminate between physiological and pathological angiogenesis. Potential solutions to these issues were presented as well, with one approach involving the use of antibody-drug conjugates (ADCs) to target tumor microenvironments as opposed to the tumor directly. Tumor response was found to be better when the ADC targets tumor cells and tumor vasculature.

Optimizing Processes Associated with Bioassays
One of the most interesting discussions in the area of biological activity measurement optimization centered around potency assays, where it was reinforced that combining estimates of potency is an important statistical practice. For example, for relative potency value to be meaningful, the two compared dose-response curves must share similar parameters (i.e., upper/lower asymptotes and slope). Because of the inherent variability of biological test systems, an absolute measure of potency is going to be more variable than a measure of activity that is relative to a standard. It was clear that quality statistics enable the most appropriate results of relative potency, and new statistical tools for addressing bioassay specificities were highlighted.

In addition, this session discussed how to streamline the cell-based assay (NAb assays) process using thaw-and-use effector and target cells. It was noted that cryopreserved, pre-labeled cells offer a convenient and cost-effective alternative to freshly labeled target cells and provide consistent and comparable performance in the ADCC using either fresh PBMC or thaw-and-use NK cells as effector cells.

The Critical Nature of Immunogenicity Assessments
Contending with immunogenicity risk is exceptionally challenging due to inherent complexity stemming from both intrinsic and extrinsic factors. This is compounded by the fact that Phase I and Phase II trials are small and can fail to detect major immunogenicity roadblocks early on. In fact, immunogenicity issues have been the cause of several major drug failures since the proliferation of large molecule biotherapeutics. At PEGS, the benefits of using molecules specifically designed to mitigate those risks were discussed at length. In addition to highlighting ways to design the molecule to reduce immunogenicity, the presentation also touched on the need to ensure neo-epitopes are not engineered in, as it could otherwise lead to development of ADAs.

Of note, the stratification of patient data by HLA type was called out as essential when evaluating the immunogenicity of sequence-modified drugs. Sample pretreatment, using either analytical purification to neutralize the interference or by removing interfering factors, was also discussed.

These were just a few of the exciting topics covered at PEGS, and our team is excited to apply what we’ve learned to further innovate our bioanalytical techniques and endure as a leading-edge CRO.

If you would like to hear more about BioAgilytix’s perspective on these and other important topics in bioanalysis today, feel free to reach out to me to continue to conversation.