We recently hosted The Eighth Annual Biologics Symposium (ABS) in New Jersey, where experts shared groundbreaking advancements in biotherapeutics over the last year. It was great to have a dedicated forum where scientists could share ideas and explore practical ways to progress their drug development goals.
The symposium highlighted areas such as immunological assessment, species selection, drug delivery, efficacy and safety and clinical aspects. Here are five things we learned about biological product development at ABS 2018.
1. Adverse immune events
Dr Bannish firstly expressed that immunomodulatory biotherapeutics are an exciting class of drugs for treatment of many diseases including oncology but also stressed how dangerous and difficult they are to develop. He helped delegates to understand the importance of drug pharmacology and immune responses during preclinical safety evaluation to lower the risk when developing these drugs.
Dr. Curtis Maier, GlaxoSmithKline, went on to offer valuable insights on vascular inflammation and what happens when it’s observed on nonclinical repeat dose toxicology studies with human biopharmaceuticals.
Dr Maier expressed the importance of understanding the clinical relevance in this instance and explained anti-drug antibodies (ADA) in animals may be associated with immune complex deposition in vessel walls.
He said "It can be argued that ADA-mediated pathology generally has little clinical relevance and can be managed by characterizing immunogenicity potential in humans. However, biopharmaceuticals with immunoenhancing or immuno-modulatory properties may produce similar findings independently of ADA, which can confound the prediction of clinical risk”.
Both sessions started a long, audience participated discussion about the dangers of immunestimulatory biologics in safety toxicology studies and how to handle them.
A consensus emerged that there are vastly different approaches being employed and there is a lot of toxicity observed due to immune stimulation that can prevent study completion and delay/terminate further drug development. One leading toxicologist said they were “between a rock and a hard place” when trying to dose high enough to overcome ADA and ensure drug exposure, while at the same time trying to prevent drug-elicited immunestimulatory adverse events.
2. The pathology of inhaled biologics
Dr. Boyle discussed inhalation route physiology, and the prospects for treating local respiratory disease and systemic conditions with inhaled biologics.
The session also addressed challenges associated with formulation and delivery as well as complex and diverse anatomy across nonclinical species.
It was interesting to learn more about the pathologist’s role, using a weight-of-evidence approach, and microscopic characterizations of the most common findings related to inhaled biologics.
Dr. Boyle went on to share a case example highlighting the importance of data interpretation, presentation, and transparent communication with regulatory authorities.
3. Developing a monoclonal antibody with no relevant nonclinical species is possible
Safety evaluation of biotherapeutics is frequently challenged by drug candidates that specifically bind to the human target, thus precluding the use of standard animal models for safety assessment.
Dr. Eunice Musvasva, Boehringer Ingelheim, presented a case study where the use of a relevant animal model to test the clinical candidate was not possible, therefore, a mouse surrogate antibody was used for preclinical safety and efficacy studies in compliance with ICH S6 (R1) addendum.
4. Manipulating B cell responses via custom-designed epitope surfaces
Despite the unparalleled success of vaccines at reducing the burden placed on the global population from infectious diseases, vaccines for a number of pathogens remain elusive.
Dr Kulp went on to identify structure-based immunogen designs to stabilize viral proteins into a specific conformation and germline-targeting vaccines attempting to re-elicit broadly neutralizing antibodies as two promising vaccine approaches for HIV-1 and other infectious diseases.
5. Real life stories of benchtop to bedside
Dr Lynch, Lynch Biologics, recounted true stories of the ups and downs of biotechnology, medical device research, discovery, translation and products that have been used to help millions of patients. He gave attendees an insight into how he led and developed innovative medicines through multicenter clinical trials, FDA approval, large-scale manufacturing and commercialization.
Dr Lynch also described how he incorporated his experience in the corporate world to co-found a highly successful STEM charter school now serving over 900 mostly minority and low income students grade 5-12 and in his mission work in Central America.
Take home messages
All the sessions at ABS stemmed great discussion which resulted in clear take home messages. The significance of careful pharmacology assessment and understanding/testing the biology of the biologic through the drug development process was thought to be more important now than ever.
Discussions on species selection further emphasized the importance of pharmacology in biological safety development, and how various immunological evaluations can now be incorporated into traditional studies.
It was also evident that biomarkers were playing a more valuable role in many areas including immunoassay, cell biology and pathology and how the incorporation of all these results would provide the best interpretation of study data.
If you have a question for our speakers or would like more information on biological product development, contact us.