Webinar Description:

Rigorous specificity analysis is critical for drug development success, as even minimal off-target binding can lead to preclinical failures or serious adverse effects in clinical trials. Long believed to be highly specific, recent clinical data and our own profiling of lead panels indicate that antibodies frequently (~25%) display cross-reactivity.

Specificity profiling is an FDA requirement for monoclonal antibodies (MAbs) and other antibody-based biotherapeutics, such as CAR-T cells. Tissue cross-reactivity (TCR) studies have traditionally been used to screen for off-target binding. However, TCR studies are poorly predictive of in vivo safety and toxicity and the results of TCR studies have limited influence on the development strategy. As a result, cell-based arrays are increasingly used to fulfill specificity profiling and regulatory requirements.

Integral Molecular has developed the Membrane Proteome Array (MPA) as a novel approach to test the specificity of biotherapeutics and identify any off-target interactions. The MPA is a cell-based array containing the largest comprehensive library of human membrane proteins. With 6,000 membrane proteins presented in their native conformation, the MPA encompasses 94% of the human membrane proteome. The MPA platform is highly sensitive, using high-throughput flow cytometry to identify binding interactions on a protein level, and has emerged as the leading solution for antibody specificity profiling.

Learning Objectives:

With a focus on specificity screening, this webinar assembles experts in antibody discovery and development and features presentations from Integral Molecular, Novartis, and Abound Bio.

• Understand how Integral Molecular’s MPA is used to select leads that do not display off-target binding liabilities
• Learn how cell-array data, such as the MPA screen, supports IND submissions either without or in conjunction with traditional tissue cross-reactivity studies
• Discover how the MPA was used to rapidly evaluate the specificity of a novel antibody-based SARS-CoV-2 therapeutic

Speakers:

Rachel Fong
Senior Project Leader
Alliance Management, Integral Molecular

Rachel Fong is Integral Molecular’s Senior Alliance Manager, with over 10 years of experience at the company. Rachel manages relationships with customers, collaborators, and partners, for MPA projects. As a founding member of the scientific team that launched this platform, she brings a unique perspective that helps guide partners from initial discussions to successful project completion. Rachel joined Integral Molecular in 2010 and is a co-author on over a dozen publications. In this webinar, Rachel will give an overview of the Membrane Proteome Array (MPA) technology and its uses. She will briefly discuss case studies of clinical MAb safety failures that could have been averted by prudent specificity testing on Integral Molecular’s MPA.

Timothy MacLachlan, PhD, DABT
Executive Director, PCS TA Head – Cardiovascular and Metabolism
Novartis Institutes for BioMedical Research

Dr. MacLachlan is currently an Executive Director in the department of Preclinical Safety (PCS) at the Novartis Institutes for Biomedical Research (NIBR). He serves as the therapeutic area head within PCS for the Cardiovascular/Metabolic Disease Area of NIBR. He also oversees safety assessment for biotherapeutics and gene and cell therapies within the NIBR portfolio. Dr. MacLachlan has founded, led and participated in several industry and academic consortia focused on the nonclinical development of biotherapeutics and cell/gene therapies for organizations such as BIO, EFPIA, PhRMA, SOT and ASGCT. Dr. MacLachlan received his PhD from Thomas Jefferson University and did his postdoctoral research in the Howard Hughes Medical Institute at the University of Pennsylvania. In this webinar, Dr. MacLachlan will give an introduction on specificity profiling of biotherapeutics for regulatory submissions. He will discuss results of a recent survey of industry developers on their methods used for profiling specificity, comparing traditional immunohistochemistry Tissue Cross-Reactivity (TCR) studies with emerging cell array technologies such as the MPA.

Dimiter Dimitrov, PhD, ScD
EVP and CSO
Abound Bio

Dr. Dimitrov is the Executive Vice President and Chief Scientific Officer of Abound Bio, a biotechnology company dedicated to developing novel antibody-based biological therapeutics for cancer and infectious diseases. Dr. Dimitrov is a world-leading antibody scientist and engineer with more than 30 years of experience. He co-founded Abound Bio in 2019 and is also currently a Professor of Medicine and Director of the Center for Antibody Therapeutics at the University of Pittsburgh Medical School. Prior to this, he was tenured Senior Investigator in the National Cancer Institute and appointed the Senior Biomedical Research Service at the NIH. Dr. Dimitrov received his PhD from the University of Sofia, Sofia, Bulgaria, and a ScD from the Bulgarian Academy of Sciences. He has over 400 publications cited more than 30,000 times, 100 patents, and multiple discoveries leading to one therapeutic antibody approval, several others in multiple clinical trials, and many more in preclinical development. In the webinar, Dr. Dimitrov will discuss Abound Bio’s antibody engineering project for SARS-CoV-2. Their therapeutic compound, a bivalent VH, VH-Fc ab8, potently neutralized SARS-CoV-2 in animals and showed high specificity with no off-targets identified by screening on the MPA. Their findings were published in Cell in September 2020 and this was one of the first potential therapeutics identified for COVID-19 back in February 2020.

Cost: No Cost!