Off-target binding can be a significant hurdle in the development of antibody-based therapies, contributing to both drug attrition and adverse events in patients. Recent analysis of a panel of preclinical and clinical stage antibodies identified a surprisingly high off-target rate across the industry, with up to one-third of antibody drugs displaying off-target binding. Limitations of conventional screening methods, mainly tissue cross-reactivity (TCR) studies, have contributed to polyspecificity going undetected. So, what are the alternatives?
Join our webinar to learn about a better approach to specificity profiling using new, innovative cell-based protein arrays. We’ll take a deep dive into the Membrane Proteome Array (MPA), a 7,000-protein array platform that tests binding of biotherapeutics across the full human membrane and secreted proteome, expressed in unfixed cells.
Participants will learn how:
Integral Molecular’s MPA rapidly and accurately identifies potential off-target binding liabilities
MPA data support both lead selection and IND submissions with advantages over tissue cross-reactivity studies
Cell-based protein arrays, like the MPA, are rapidly progressing towards FDA endorsement
Philadelphia – Integral Molecular, a leader in antibody discovery technologies, is proud to announce that the FDA has accepted their Membrane Proteome Array™ (MPA) Qualification Plan for advancement as a Drug Development Tool (DDT) to assess antibody binding specificity. Antibody drug developers already routinely include MPA data in regulatory packages, and qualification as a DDT will allow them to further rely on the MPA in the approval process. Integral Molecular’s MPA is the industry-leading technology for antibody specificity testing and is the only specificity platform under FDA consideration as a DDT.
Learn more about the Membrane Proteome Array™, and how it enables the precise identification of off-target binding interactions
Non-specific drug binding is a significant cause of adverse events in patients that can lead to severe complications or even death, and early specificity testing can de-risk drug development and enhance patient safety. Recent research has demonstrated that up to one-third of antibody drugs exhibit non-specific binding to unintended targets.
The MPA assesses binding across ~6,000 structurally intact membrane proteins and is the only platform of its kind that screens membrane proteins in their native conformation. The MPA has been used to screen over 2,000 preclinical antibody therapeutics for customers worldwide, and MPA specificity data has been accepted by regulatory bodies globally, including the FDA, EMA, and NMPA.
“This milestone towards MPA qualification reflects the continued dedication of our team to set a new standard in testing antibody drug specificity. Our continued improvements to the MPA—including statistical analyses, bioinformatic comparisons, and enhanced quality systems—have been critical to our qualification plan and have supported ISO 9001 certification of our processes. We thank the FDA for their confidence in our approach and commitment to advancing the safety of biologics.”
-Benjamin Doranz, CEO, Integral Molecular
The MPA is progressing toward DDT qualification under the FDA’s ISTAND Pilot Program, which promotes Innovative Science and Technology Approaches for New Drugs. As part of this process, Integral Molecular has been invited to submit a Full Qualification Plan (FQP) for the MPA, which is the final step in achieving DDT status.
About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in creating transformative technologies that advance the discovery of therapeutics against difficult protein targets. With 20+ years of experience focused on membrane proteins, viruses, and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 600 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders, and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue viruses.
Thursday, February 27, 2025
8 am PT, 10 am CT, 11 am ET View the recording
Limitations of conventional specificity tools have contributed to undetected polyspecificity in antibody drugs. We performed a systematic specificity analysis of preclinical and clinical antibodies and identified a surprisingly high rate of off-target binding throughout the industry, with up to one third of antibody drugs displaying off-target binding. Our findings across different phases of drug development suggest polyspecificity is a major source of drug attrition, and better tools could help to improve drug approvals and patient safety.
In this webinar, we will discuss the emergence of cell-based protein arrays as an alternative and improved technology to evaluate antibody specificity.
Key takeaways:
Cell-based protein arrays, including Integral Molecular’s Membrane Proteome Array™ (MPA), enable precise assessment of binding interactions
The MPA identified off-target binding interactions that were missed in tissue cross-reactivity studies
Early detection of off-target antibody binding can mitigate drug toxicity and attrition
Integral Molecular, a leader in antibody discovery and characterization, has been awarded $2.7 million by the NIH Commercialization Readiness Pilot (CRP) Program. This funding will support FDA-qualification of Integral Molecular’s Membrane Proteome Array™ (MPA), a next-generation technology that provides critical safety data required for Investigational New Drug (IND) filings of biologic drugs. The MPA is a cell-based protein array designed for specificity testing of antibody-based therapeutics and the only platform that screens for specificity using native protein conformations.
Learn how the Membrane Proteome Array™ enables the precise identification of off-target binding interactions, a primary determinant of drug safety
Integral Molecular’s recently published data show that up to one-third of antibody drugs have non-specific binding, and suggests that off-target binding is a significant cause of drug failure (Norden et al., 2024). Non-specific binding was detected even for drugs currently on the market that were previously screened using tissue cross-reactivity (TCR), an older and less precise technology. The new NIH funding will support efforts to validate the MPA as a more accurate alternative to TCR.
“We thank the NIH for their ongoing commitment to advancing drug safety tools. Their continued support—from early-stage grants to this advanced-stage CRP award—has been essential in making our Membrane Proteome Array the industry standard for in vitro specificity testing of biologics.”
– Benjamin Doranz, CEO, Integral Molecular
MPA processes are ISO 9001 certified, and the technology is under FDA review for qualification as a Drug Development Tool (DDT). Once qualified within its context-of-use, DDTs can be relied upon in IND, NDA, or BLA applications without needing the FDA to reconsider and reconfirm their suitability. The newly awarded CRP funds will support the company’s ISO 9001 commitment to quality assurance, continuous process improvement, and the MPA’s pathway to qualification.
About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in creating and commercializing transformative technologies that advance the discovery of therapeutics against difficult protein targets. With 20+ years of experience focused on membrane proteins, viruses, and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 600 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders, and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue viruses.
Integral Molecular’s Membrane Proteome Array™ Reveals Pervasive Binding of Antibody-Based Drugs to Unintended Targets
An Integral Molecular scientist screens antibody drugs for specificity using the Membrane Proteome Array™, a high-throughput, cell-based, protein array technology. Photo credit: CreativeOutfit
Philadelphia– Integral Molecular, a leader in antibody discovery and characterization, has published new research in the journal mAbs, revealing that as many as one-third of antibody-based drugs exhibit nonspecific binding to unintended targets. A serious concern, off-target drug binding is a significant cause of adverse events in patients, with the potential to even cause death. Analysis of antibody off-target binding across different phases of clinical development suggests this to be a major cause of drug attrition. Early specificity testing could improve drug approvals and patient safety.
Learn how antibody developers can use the Membrane Proteome Array™ to assess specificity and de-risk drug development
In this study, Norden et al. present the first empirical assessment of antibody specificity, quantifying the prevalence of off-target binding across the drug pipeline. They accomplished this through retrospective specificity analyses of leading antibody candidates from biopharmaceutical companies and a prospective study of clinically administered antibody drugs (including those that are given to patients in advanced clinical trials, FDA-approved, or withdrawn). The molecules were tested using the Membrane Proteome Array™ (MPA), a cell-based protein array representing the human membrane proteome, that was developed to test specificity and improve drug safety.
18% of the 83 clinically administered antibody drugs tested showed off-target interactions.
22% of the antibody drugs withdrawn from the market, often due to safety issues, showed nonspecific binding.
33% of the 254 lead molecules tested showed nonspecific binding, a predictor of failure in future stages of development.
These findings challenge the long-held belief in the absolute specificity of antibodies and underscore the critical need for more rigorous testing.
“Nonspecific drug binding can lead to adverse events or even death” said Diana Norden, PhD, lead study author. “The presumption that every antibody confers absolute specificity is simply not accurate. New technologies like the MPA provide a detailed assessment of antibody specificity and can significantly de-risk drug development.”
About the Membrane Proteome Array™
Integral Molecular’s Membrane Proteome Array™ is the industry-leading technology for antibody specificity testing used by hundreds of customers worldwide. The MPA assesses binding across ~6,000 proteins, representing the full human membrane proteome. Each protein within the array is individually presented in its biological conformation. MPA processes are ISO 9001 certified, and its specificity data has been accepted by regulatory bodies globally, including the FDA. The MPA is currently under review by the FDA for qualification as an accepted Drug Development Tool.
About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in creating and commercializing transformative technologies that advance the discovery of therapeutics against difficult protein targets. With 20+ years of experience focused on membrane proteins, viruses, and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 600 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders, and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue viruses.
Assessment of antibody off-target reactivity is a regulatory requirement for clinical development. However, conventional screening methods, such as tissue cross-reactivity studies, are often ineffective in screening newer therapeutic modalities, and their predictive value for in vivo safety and toxicity is poor. So, what are the alternatives?
Join our webinar to learn about the new, innovative cell-based protein array approach to specificity profiling. We’ll take a deep dive into the Membrane Proteome Array (MPA), a 6,000-protein array platform that tests binding of biotherapeutics across the full human membrane proteome expressed in unfixed cells.
Attendees will learn how:
Integral Molecular’s MPA is used to rapidly and accurately identify potential off-target binding liabilities
MPA data support both lead selection and IND submissions with advantages over tissue cross-reactivity studies
Cell protein arrays, like the MPA, are rapidly progressing towards FDA endorsement through inclusion in CAR-T development guidelines and qualification as an antibody Drug Development Tool
ISO 9001 certification validates Integral Molecular’s quality processes for its Membrane Proteome Array, reflecting the company’s commitment to quality.
Philadelphia – Integral Molecular, a leader in antibody discovery and characterization, proudly announces the achievement of IS0 9001 certification for the quality systems and processes used in its Membrane Proteome Array™ (MPA) specificity testing services. This platform is a vital tool for biotechnology and pharmaceutical companies to assess the safety and off-target reactivity of therapeutic antibodies and other biologics.
Despite their reputation for ‘exquisite specificity’, antibodies and antibody-based therapies, such as CAR-T cells, frequently demonstrate unexpected off-target binding. The MPA utilizes its collection of over 6,000 native-conformation membrane proteins that encompass nearly the entire human membrane proteome to de-risk therapeutics and reveal unintended off-target liabilities early in drug development.
ISO 9001 is a globally recognized standard for quality management systems (QMS) that encompass process controls, comprehensive documentation, plans for corrective action, and continuous improvement.
“Integral Molecular has maintained a culture of commitment to delivering exceptional quality products and services for over 20 years. As the industry increasingly relies on MPA specificity profiling to support drug safety, we are delighted to receive ISO 9001 Certification to reinforce our commitment to quality for our customers.”
-Rachel Fong, Director of Sales and Alliances, Integral Molecular
With the ability to pinpoint the identity of unanticipated protein interactions that could pose safety consequences, the MPA was accepted by the FDA to participate in the agency’s ISTAND program to qualify new drug development tools for IND, NDA, or BLA applications. The MPA qualification plan was submitted to the FDA in 2023 and is currently under review.
About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in creating and commercializing transformative technologies that advance the discovery of therapeutics against difficult protein targets. With 20+ years of experience focused on membrane proteins, viruses, and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 600 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders, and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue viruses.
Rigorous specificity analysis is critical for successful drug development and a safety requirement for antibody-based therapies, such as CAR-T, entering IND. Tissue cross-reactivity (TCR) studies have been traditionally used to screen for off-target binding; however, their predictive value for in vivo safety and toxicity is poor. Integral Molecular has developed the Membrane Proteome Array (MPA) platform to de-risk antibody-based therapeutics by testing specificity across the full human membrane proteome expressed in live cells. Using sensitive high-throughput flow cytometry to identify binding interactions on a protein level, this technology has emerged as the leading solution for antibody specificity profiling.
In this GEN webinar, our panelists will discuss their experiences using the MPA to rapidly identify potential off-target interactions, resulting in successful IND filings for CAR-T cell therapies where conventional approaches did not suffice. We will also describe the newest additions to this 6,000-protein cell array and the status of its consideration by the FDA as a qualified Drug Development Tool.
With a focus on specificity screening, this webinar assembles experts in antibody discovery and development and features presentations from Integral Molecular, Cabaletta Bio, and The University of Pennsylvania.
Understand how Integral Molecular’s MPA is used to identify potential off-target binding liabilities
Learn how MPA data supports IND submissions with advantages over traditional tissue cross-reactivity studies
Discover how the MPA was used to rapidly evaluate the specificity of novel CAR-T cell therapies for autoimmunity and cancer
