RESOURCES

Webinar: Combatting SARS-CoV-2 Variants: Neutralization Testing from Alpha to Mu

Date: November 30, 2021

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COVID-19 has united scientists with a shared mission, sense of collaboration, and urgency. Global lab meetings, prompt sharing of scientific results, and resource repositories will continue to advance the development of vaccines and therapeutics.

Join this GEN webinar to learn how SARS-CoV-2 Reporter Virus Particles (RVPs, pseudotyped viruses) enable researchers to rapidly test neutralization titers of antibodies and vaccinee sera in a safe BSL-2 environment. Additionally, our panelists will describe how access to Integral Molecular’s extensive collection of >65 SARS-CoV-2 variant RVPs enables them to test against emerging mutants and meet the most recent FDA recommendations for variant testing of vaccines and therapeutic antibodies.

Webinar: Comprehensive Specificity Profiling of Antibody-Based Therapeutics Using the Membrane Proteome Array

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

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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. She will also introduce alternative uses of the MPA, such as functional screening and target discovery.

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.

Integral Molecular’s Extensive Collection of SARS-CoV-2 Reporter Virus Variants Supports the Clinical Development of Vaccines and MAbs Against Coronavirus

PHILADELPHIA — To aid in the clinical development of new vaccines and monoclonal antibodies (MAbs) effective against emerging and highly infectious coronavirus variants, Integral Molecular has produced the most extensive catalog of SARS-CoV-2 pseudotyped reporter virus particles (RVPs), currently over 65 variants, which enables neutralizing antibodies or serum to be assessed in accordance with recent FDA guidances.

Integral Molecular has developed SARS-CoV-2 RVPs for all variants of concern and interest, including Delta, Delta Plus, Lambda, and Gamma, as classified by the Center for Disease Control (CDC) and World Health Organization (WHO). The company’s scientific team constantly monitors a range of sources to identify new SARS-CoV-2 variants, alert customers, and rapidly make RVPs available to researchers.

The FDA recognizes that current COVID-19 vaccines and therapeutic MAbs may provide reduced protection against emerging variants and has issued guidance for developers testing the efficacy of vaccines and MAbs against such variants. The recognition that a neutralizing antibody response is an important correlate of protection for COVID-19 vaccines further highlights the importance of studying serum neutralization using live virus or the safer alternative, RVPs.

Integral Molecular’s RVPs are “pseudoviruses” that lack the viral components required to cause disease and so can be safely handled under standard laboratory conditions. This greatly facilitates the testing of hundreds or thousands of samples from clinical trials, where RVPs are used to assess neutralizing antibodies against the virus.

“Virology is at the core of our company,” said Benjamin Doranz, CEO of Integral Molecular. “Throughout the last 20 years we have been developing technologies using viral components and have produced large-scale batches of quality-controlled RVPs as a critical reagent to support clinical trials. In the midst of this pandemic, we are proud to support the fight against COVID-19.”

Partners interested in using SARS-CoV-2 RVPs for vaccine or antibody development should contact Integral Molecular.

About Integral Molecular

Integral Molecular (integralmolecular.com) is the industry leader in developing and applying innovative technologies that advance the discovery of therapeutics against difficult protein targets. With 20 years of experience focused on membrane proteins and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 400 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.

The Science Center’s Esther Klein Gallery Reopens with Exhibit Exploring the Effects of SARS-CoV-2 and COVID-19

Philadelphia,Pa- The Science Center’s Esther Klein Gallery is reopening for the first time
since April, with Socius, a new solo exhibition by Philadelphia artist, Rebecca Rutstein
(https://rebeccarutstein.com/). Rutstein recently completed a BioArt Residency designed in partnership
between the Science Center and the biotech company Integral Molecular, where she spent three
months working alongside laboratory scientists. The culmination of this residency is an exhibit of large
and small-scale paintings and a multi-media installation.

Inspired by the Latin word for “bond” or “interaction” and deriving from societas, the derivative for
“society,” Rutstein’s work is an exploration of the effects of SARS-CoV-2 virus both at the cellular micro
level, and also at a macro level amongst the community.

Many of the works on view are inspired by microscopic observations of communities that living cells
create, as well as cells fluorescing as they are infected with the virus using Integral Molecular’s Reporter
Virus Particle (RVP) technology. Using fluorescence, RVPs allow us to visualize human cells being
infected upon interactions of viral spike proteins with receptors on the cell surface, and have been a tool
for discovering protective antibodies that neutralize the virus. At the macro level, two paintings which
track data of infections and deaths show racial inequities and disparities during the pandemic, and the
contrasting effects on different minority communities.

Also on view is Rutstein’s immersive sculpture, light and sound installation. Sub Surficiem, inspired by
the artist’s observance of living cells through a microscope, is a sculptural installation backlit with LED
lights programmed to simulate a video time-lapse of living cells fluorescing as they become infected
with SARS-CoV-2 using Integral Molecular’s RVP technology. Confluence is the sound component to Sub
Surficiem and its macro counterpart. This five-minute piece is a sonification of data that tracks COVID-19
cases, deaths and vaccinations in Philadelphia, each set of data its own track layered into the
composition. The digital rendering of a full range of stringed instruments was created in collaboration
with Mexican composer Mauricio Rodriguez, NEA fellow and Doctor of Musical Composition from
Stanford University. Philly-based musician, Frank Masciocchi (part of the Integral Molecular team) also
contributed interpretive guitar sounds creating ambient dissonance within the piece.

This immersive installation takes the viewer beyond the microscope lens while “listening” to the
macrodata of the Philadelphia community, reflecting on the positive impact of vaccines yet
acknowledging the uncertainty that remains.

Socius opens on August 5th with a reception and artist talk at the gallery by Rutstein herself. A closing
reception with a live performance will be held on September 23rd.
https://sciencecenter.org/events/socius-rebecca-rutstein-ekg

The BioArt Residency is made possible through a grant from the Edna Andrade Fund of the Philadelphia
Foundation.

About the Artist
Multidisciplinary artist Rebecca Rutstein works at the intersection of art, science and technology. For
over twenty years she has created painting, sculpture, interactive installation and public art inspired by
geology, microbiology and marine science, and has joined scientists on several expeditions exploring the
deep sea. Rutstein is passionate about creating visual and immersive experiences that connect the
viewer with hidden environments, deepening their connection with the natural world. Her collaborations
have been funded by the National Science Foundation, National Academies of Science / Keck Futures
Initiative, Ocean Exploration Trust, Schmidt Ocean Institute and the Edna Andrade Fund of the
Philadelphia Foundation. She has received a Pew Fellowship in the Arts, Independence Foundation
Fellowship, PA Council on the Arts grant, is an MIT Ocean Discovery Fellow, and was recently named the
Delta Visiting Chair for Global Understanding at the University of Georgia. Rutstein’s work can be found
in the collections of the Philadelphia Museum of Art, Georgia Museum of Art, Pennsylvania Academy of
the Fine Arts Museum, Yale University, University of New Mexico and the US Department of State. She
has been represented by Bridgette Mayer Gallery in Philadelphia since 2001.

About the Science Center
Established in 1963, the Science Center is a mission-driven nonprofit that commercializes promising
technology, cultivates talent, and convenes people to inspire action. With partnerships across top
academic and research institutions, industry, and healthcare systems, the Science Center is helping lifesaving technologies transition from bench to bedside and nurturing a workforce that supports a 21st
century economy. For more information, visit sciencecenter.org sciencecenter.org and follow @UCScienceCenter.

About the Esther Klein Gallery
The Esther Klein Gallery (EKG), which opened in 1977, uses the creative arts as a platform to explore
relationships between art, science and technology. EKG seeks to positively impact the cultural life of both
its immediate neighborhood of West Philadelphia and the broader Philadelphia community. EKG
programming is designed to explore the range of art, science and technology exhibitions, and includes
gallery talks, panel discussions, and education programs. For more information, visit
www.sciencecenter.org/discover/ekg

About Integral Molecular
Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing
therapeutic antibodies against membrane proteins, an important group of drug targets found on the
surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug
discovery pipelines of over 400 biotech and pharmaceutical companies to help discover new therapies for
cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue
viruses.

Integral Molecular Launches Transgene Protein Engineering Platform to Address Challenges in Gene Therapy

PHILADELPHIA – Integral Molecular, the industry leader in membrane proteins, announces the launch of GeneCanvas™, its proprietary protein engineering platform to optimize transgenes and other gene therapy elements.

GeneCanvas can achieve 10 to 100 fold increases in gene activity by improving transgene protein expression, trafficking, stability, and function. These enhancements will ultimately result in better efficacy, smaller doses, and improved safety for patients.

The GeneCanvas platform is built on Integral Molecular’s 20 years of experience in optimizing the most challenging and structurally complex proteins known, such as GCPRs, ion channels, transporters, and viral envelopes. GeneCanvas incorporates the company’s proprietary high-throughput mutagenesis and human cell screening platforms that enable the creation and screening of large libraries of variants, which have been used in hundreds of projects internally and for partners.

“Our scientists bring an unrivaled mix of deep expertise in protein engineering, cell biology, and virology to develop a customized strategy for each engineering challenge,” said Joseph Rucker, PhD, Vice-president of Research and Development at Integral Molecular.

Integral Molecular showcased its GeneCanvas platform during the digital BIO International Convention that took place in June 2021.

About Integral Molecular

Integral Molecular (integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 400 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 Rapid SARS-CoV-2 Epitope Mapping Supports Regulatory Requirements for the Development of Therapeutic Antibodies Effective Against Viral Variants

PHILADELPHIA – At the forefront of the fight against COVID-19, Integral Molecular’s rapid Epitope Mapping technology is being used to pinpoint precise binding sites of therapeutic SARS-CoV-2 antibodies under development and can help determine their effectiveness against emerging viral variants. These efforts are important in keeping pace with the ever-changing virus and the requirements of regulatory agencies such as the FDA in testing new therapeutics against the virus.

Using its Shotgun Mutagenesis Epitope Mapping technology, Integral Molecular identifies the specific amino acids bound by antibodies on all regions of the Spike protein, including the receptor binding domain (RBD), N-terminal domain (NTD) and S2 regions. In most cases, complex conformational epitopes can be mapped in 4 weeks. Integral Molecular can also assess an individual antibody’s binding to Spike variants of greatest concern, including UK B.1.1.7 (Alpha), South African B.1.351 (Beta), Brazilian P.1 (Gamma), and Indian B.1.617.2 (Delta) variants.

“As emerging variants continue to devastate much of the world, it is important to remain vigilant with therapeutics that are effective against the evolving virus,” said Edgar Davidson, PhD, Virologist at Integral Molecular. “We are proud to support scientists in their FDA filings, providing data quickly to better understand their antibodies’ mechanisms of action and potential for viral resistance.”

Epitopes mapped by Integral Molecular have been essential in studies examining how antibodies fight COVID-19. These include characterization of NTD-targeting antibodies that provided prophylactic or therapeutic protection in animals (Suryadevara et al., Cell, 2021), development of a cocktail of anti-RBD antibodies resistant to viral escape when used in combination (Ku et al., Nature Communications, 2021), and identification of commonly occurring antibodies in the population that target Spike regions including S2 (Chen et al., bioRxiv, 2021). In addition to epitope mapping, Integral Molecular offers pseudotyped SARS-CoV-2 reporter virus particles to test antibody neutralization against over 30 reference strains and emerging variants.

About Integral Molecular
Integral Molecular is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 400 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 Expands Partnership with Japan’s Life Sciences Distributor Funakoshi to Provide Access to Antibody Specificity and Epitope Mapping Services

PHILADELPHIA – Integral Molecular has expanded its partnership with Funakoshi, a leader in distributing life science research reagents and services, to be the exclusive provider of Integral Molecular’s therapeutic antibody characterization technologies in Japan. The partnership will provide researchers with access to antibody characterization technologies optimized to deliver IND-ready results in as little as 4 weeks, including off-target specificity profiling using the Membrane Proteome Array and high-resolution epitope mapping using Shotgun Mutagenesis.

Detailed specificity and epitope analysis are critical for therapeutic antibody success and intellectual property protection. Integral Molecular’s antibody characterization platforms are designed to succeed even with structurally complex targets such as membrane proteins, have been used by over 400 companies, and are published in over 300 peer-reviewed publications.

“We have a long-standing partnership with Integral Molecular, having distributed their Lipoparticle products for more than 8 years,” said Tetsuya Ikeda, President and CEO of Funakoshi. “We are pleased to extend our offerings to include Integral Molecular’s unique antibody characterization services.”

Off-target antibody binding can result in severe adverse events, especially when antibodies are used to direct cell killing, as with CAR-T therapeutics. The Membrane Proteome Array (MPA) was developed by Integral Molecular to detect binding of antibodies, cells, and other biologics to 6,000 native proteins, comprising 94% of the human membrane proteome.

Epitope data support antibody patents by demonstrating antibody novelty, differentiating from prior art, and supporting written description requirements. Integral Molecular’s Epitope Mapping platform provides mapping at single amino acid resolution using comprehensive mutagenesis and is >95% successful even when working with complex targets and conformational epitopes.

About Integral Molecular

Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 400 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.

About Funakoshi

Funakoshi Co., Ltd. (www.funakoshi.co.jp) is the leader in distributing reagents and instruments for researchers in the life science fields. Their corporate mission is to provide high quality products to a broad range of customers throughout their domestic and international network.

Integral Molecular Webinar & User Group Towards IND: Specificity Profiling of Antibody Therapies Using the Membrane Proteome Array

Tuesday, June 15, 2021
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Mistargeted therapies can cause serious side effects and clinical failures. Learn about using the Membrane Proteome Array to identify off-target reactivities of antibody and cell therapies and the importance of these data for lead selection and regulatory submissions.

Webinar Agenda

• Re-examine the long-held assumption that antibodies are exquisitely specific
• Learn what to do next if your molecule shows detectable off-target binding
• Discover how Membrane Proteome Array specificity data is used to satisfy regulatory requirements

We share your commitment to developing therapeutics for difficult-to-treat diseases. With 20 years of experience, our research team is dedicated to helping programs like yours succeed.