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Integral Molecular Announces Breakthrough in Understanding the Functionality of GPCRs, the Largest Class of Drug Targets in Human Disease

Philadelphia, PA–(BUSINESS WIRE)–Integral Molecular, an industry leader in membrane protein antibody discovery, has announced a major advancement in understanding the functionality of G protein-coupled receptors (GPCRs), the largest protein superfamily in the human genome, providing unprecedented insight for human disease therapeutics.

The work answers the fundamental question of how GPCRs, a complex class of membrane protein on the cell surface, transmit signals across the outer membrane to orchestrate internal signaling events implicated in diseases including HIV, heart disease, and cancer. This work published by Wescott et al., appears in the current issue of Proceedings of the National Academy of Sciences. The study employed Integral Molecular’s Shotgun Mutagenesis platform for the most detailed and comprehensive study of the GPCR CXCR4 completed to date.

“Integral Molecular’s ability to exhaustively study complex proteins through mutagenesis, coupled with our structural insights, has propelled our understanding of CXCR4 and other GPCRs,” said Dr. Tracy Handel, collaborator and co-author from the University of California in San Diego and a leading expert in chemokine receptor structural biology. “CXCR4 has been studied for over two decades, but the detailed mechanism for how it and other GPCRs receive and transmit information to trigger cellular responses had yet to be fully described.”

“Using our Shotgun Mutagenesis platform, we’ve successfully mapped key molecular interactions within CXCR4 that can be manipulated to manage diseases such as cancer and HIV,” said Dr. Benjamin Doranz, President and Chief Scientific Officer at Integral Molecular. “GPCRs comprise about a third of existing drug targets, so our results have significant implications for the discovery of new, as well as improved, therapeutics”

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelope proteins, using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. Integral Molecular discovers antibodies for partners in parallel with its own independent work developing antibodies for licensing. The company currently has therapeutic programs focused on pain, autoimmunity, and infectious diseases.

Integral Molecular Develops B-Cell Cloning Technology to Discover Rare Antibodies against Membrane Proteins

Integral Molecular, a leader in antibody discovery, announces the development of an ultra high-throughput microfluidic B-cell cloning technology that can interrogate tens of millions of immune cells (B-cells), enabling deep mining of entire immune repertoires to discover rare and diverse monoclonal antibodies for therapeutic purposes.

B-cell cloning represents a pivotal expansion of the company’s MPS Discovery Engine® platform for isolating monoclonal antibodies against membrane protein targets. Combined with the company’s proprietary Lipoparticle technology for display of concentrated membrane proteins, antibodies are isolated that recognize membrane proteins in their native conformation, these being the most useful class of antibodies for therapeutics. In addition, specialized screening assays can be incorporated to isolate antibodies with desired functional properties for targeted therapeutic applications.

The technology entails encapsulating individual antibody secreting B-cells, together with antigen displaying Lipoparticles, into picoliter-sized droplets. Fluorescent signals are emitted when antibody recognition occurs within the droplet, allowing laser-sorting of droplets and B-cell isolation. This approach enables rapid interrogation of a host animal’s entire immune repertoire, antibody isolation directly from host cells for natural heavy and light-chain pairing, and isolation of diverse antibodies.

“This technology transforms antibody discovery for membrane protein targets,” says Dr. Ross Chambers, Director of Antibody Discovery and developer of the B-cell cloning technology. “The combination of antigen display on Lipoparticles, use of evolutionarily divergent species for antibody elicitation against conserved targets, and now B-cell cloning for rapid isolation of rare antibodies enable us to deliver first-in-class therapeutic candidates to our discovery partners.”

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelope proteins, using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. Integral Molecular discovers antibodies for partners in parallel with its own independent work developing antibodies for licensing. The company currently has therapeutic programs focused on pain, autoimmunity, and infectious diseases.

Integral Molecular Expands Intellectual Property Landscape with International Patents Protecting Key Lipoparticle technology

Integral Molecular, a leader in membrane protein antibody discovery, has announced the issuance of two key patents in Europe and the U.S., strengthening the company’s rapidly expanding patent portfolio for its Lipoparticle technology which enables antibody discovery against challenging membrane protein targets.

Patent EP166038 marks the company’s first issued European patent, providing broad coverage for the company’s Lipoparticle technology and its numerous applications to antibody discovery and characterization. U.S. patent 9,213,027 is directed towards applications of Lipoparticles in antibody screening and isolation.

“These new patents represent a significant milestone in our global business strategy and complement our existing patent portfolio,” said Dr. Benjamin Doranz, President and CEO of Integral. “Our intellectual property estate now expands into Europe, a key market where we have built a large base of clients and strategic partners, including all the top pharmaceutical companies. The broadened patent coverage in the U.S. and Europe further enhances our position for licensing and partnership opportunities.”

Membrane proteins are the targets of more than 50 percent of FDA-approved drugs yet are notoriously challenging for antibody discovery. Integral Molecular’s proprietary antibody discovery platform, the MPS Discovery Engine® overcomes many challenges associated with membrane protein targets. Lipoparticles represent a key component of MPS, consisting of virus-like particles that present highly-concentrated membrane proteins in their native conformation. MPS is built around an exclusive technique of optimally combined Lipoparticle and DNA immunizations in chickens, thus providing a superior strategy for eliciting monoclonal antibodies even for structurally-complex, evolutionarily conserved targets. MPS has been successfully used to discover potent monoclonal antibodies against a variety of difficult membrane protein targets such as the P2X3 ion channel, GLUT4 transporter, and Chikungunya virus envelope protein.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelope proteins, using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. Integral Molecular discovers antibodies for partners in parallel with its own independent work developing antibodies for licensing. The company currently has therapeutic programs focused on pain, autoimmunity, and infectious diseases.

DNA Immunization Expert Dr. Ross Chambers Joins Integral Molecular to Lead Antibody Discovery

Integral Molecular, a leader in membrane protein antibody discovery, announced today the appointment of DNA immunization expert Ross Chambers, Ph.D., as Director of Antibody Discovery.

Dr. Chambers will lead the company’s rapidly expanding Antibody Discovery business, which includes its proprietary MPS Discovery Engine® platform that delivers high performance monoclonal antibodies (MAbs) against difficult membrane protein targets. MPS includes target engineering, MAb discovery, antibody engineering, and characterization through animal proof of concept.

Dr. Chambers is a pioneer in the field of DNA immunization. In 2003 he adapted DNA immunization for application to antibody discovery, a platform published in Nature Biotechnology. Since then Dr. Chambers has revolutionized the strategies used for antibody elicitation, completing over 2,000 immunization projects.

“I look forward to helping Integral Molecular accelerate antibody discovery by combining its cutting-edge technologies in antigen presentation with advances in DNA immunization, and to working at a company that is committed to doing such advanced scientific work,” Dr. Chambers said.

Before joining Integral Molecular, Dr. Chambers was the Director of R&D at SDIX, a biotechnology company that designed, developed, and produced novel antibodies. Under his leadership of over 10 years, the MAb discovery team created and commercially launched three platforms – Genomic Antibody Technology (GAT), MAb discovery for membrane proteins, and Picodroplet technology for B cell cloning.

“We are pleased to welcome Ross Chambers to the team at Integral Molecular,” said Ben Doranz, President and CEO of Integral Molecular. “Adding Ross’s DNA immunization experience to our MPS platform underscores our commitment to being the leader in identifying therapeutic antibodies against membrane protein targets, and represents the deep scientific expertise that our partners rely on.”

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelope proteins, using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. Integral Molecular discovers antibodies for partners in parallel with its own independent work creating antibodies for licensing. The company currently has therapeutic programs focused on pain, autoimmunity, and infectious diseases.

Integral Molecular Identifies Key Molecular Interactions Responsible for the Effectiveness of the ZMapp™ Anti-Ebola Virus Cocktail

To support the creation of Ebola virus vaccines and treatments, Integral Molecular, a leader in membrane protein antibody discovery, has identified the key molecular interactions that mediate the effectiveness of the anti-Ebola ZMapp™ therapeutic cocktail, which is in clinical trials after being used to treat select patients during the 2014 Ebola virus outbreak.

Using its proprietary Shotgun Mutagenesis mapping platform, Integral Molecular identified the exact binding sites, or epitopes, of the therapeutic antibodies in the ZMapp, ZMAb, and MB-003 cocktails. This work helps explain why ZMapp has been more effective than other cocktails in treating disease, and provides a design pathway for improved therapeutic drug cocktails. This work is published in the November 2015 issue of the Journal of Virology and was presented at the American Society of Tropical Medicine and Hygiene (ASTMH) annual meeting in October.

“To accelerate research during the global health threat of Ebola, we made it a priority to apply our high-throughput mapping technology to identify the epitopes of ZMapp,” said Benjamin Doranz, President and CEO of Integral Molecular. “These antibodies are the most important Ebola therapeutics developed to date, but prior to our work there was not enough information about where and how these antibodies acted on their target to prevent infection.”

This research was funded by contracts recently awarded to Integral Molecular from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Under this award the company is identifying how antibodies protect against viral diseases, aiding in the discovery of effective treatments and vaccines.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating innovative technologies and a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelopes. Committed to understanding the biology of infectious viruses, the company utilizes its Shotgun Mutagenesis platform technology to rapidly map antibody binding sites on structurally complex targets. Integral Molecular offers Shotgun Mutagenesis services for customer-specified targets on a fee-for-service basis. Pre-validated Shotgun Mutagenesis target libraries are also available for several human membrane and viral envelope proteins, including Ebola virus glycoprotein.

Integral Molecular Awarded $5.5M by the National Institutes of Health to Study Ebola Antibodies to Aid in Vaccine Discovery

With a new $5.5M award from the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH), Integral Molecular, Inc. is expanding its current efforts to discover antibodies against Ebola virus and identify how they prevent Ebola virus infection, research that will significantly impact the development of Ebola therapeutics and vaccines.

This funding follows an initial five-year, $3.5 million NIH contract awarded to Integral Molecular by NIAID to study the immune response to Ebola and Hepatitis C viruses. The expanded funding enables the company to identify how different antibodies bind to the viral surface and to correlate these with anti-viral protection.

Insights into the immune response generated by patients who survive a deadly Ebola virus infection, together with the precise binding sites of their antibodies, will provide a remarkable resource for developing vaccines and curative therapies for Ebola virus disease. To date, the company has obtained over 100 antibodies against Ebola virus, including a large collection isolated from a survivor of the 2014 outbreak in West Africa. Over the last seven years, Integral Molecular has mapped over 300 novel antibody binding sites on the surface of viral pathogens. These studies are being conducted in collaboration with Dr. James Crowe, Director of the Vanderbilt Vaccine Center.

“Our 15 years of experience with pathogenic viruses including Dengue, Chikungunya, Hepatitis C, Respiratory Syncytial Virus, HIV, and Ebola, has expanded our understanding of how antibodies protect against these viruses,” said Benjamin Doranz, CEO of Integral Molecular. “This recent support from NIH validates our approach, allows us to broaden the scope of our studies, and will provide new insights that will result in improved therapeutics and vaccines against Ebolaviruses.”

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating innovative technologies and a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelopes. Committed to understanding the biology of infectious viruses, the company utilizes its Shotgun Mutagenesis platform technology to rapidly map antibody binding sites on structurally complex targets. Integral Molecular offers Shotgun Mutagenesis services for customer-specified targets on a fee-for-service basis. Pre-validated Shotgun Mutagenesis target libraries are also available for several human membrane and viral envelope proteins, including Ebola virus glycoprotein.

Cat Got Your Tongue? Not According to New Research

The ability to detect bitter chemicals is thought to have evolved because it helps animals avoid toxic compounds often found in plants. All cats, from pets to wild tigers, eat little plant material. But domestic cats may still encounter bitter flavors in food and medicines.

Pet cats have a reputation for being rather unpredictable in their dietary choices. This could be explained by their perception of bitter, which differs from other mammals because of variations in their repertoire of bitter receptors.

In a new study, the behavior of two different cat bitter taste receptors were studied in cell-based experiments, investigating their responsiveness to bitter compounds, and comparing them to the human equivalents.

TAS2R38 is a bitter taste receptor in humans of which some people have ‘supertaster’ variants that give them an extreme sensitivity to bitter compounds, explaining some people’s strong aversions to broccoli and brussels sprouts.

Compared with the human TAS2R38 receptor, the cat version, Tas2r43, was 10-fold less sensitive to a key bitter compound known as PTC and didn’t respond at all to another bitter compound, PROP.

Like its human counterpart, the cat bitter taste receptor was activated by the bitter compounds aloin (found in the aloe plant) and denatonium (used to deter children and pets from consuming chemicals such as antifreeze) but responded differently to the compounds.nd comparing them to the human equivalents.

The cat receptor was less sensitive to aloin and more sensitive to denatonium than the human receptor. It also differed from the human taste receptor by being insensitive to saccharin, an artificial sweetener that tends to have a bitter aftertaste in humans.

Co-author Nancy Rawson from AFB International, a pet food flavor company, said: “We confront the challenge of ‘finicky cats’ every day. As such, it is exciting to find an unexpected receptor response to bitter compounds that has never been described in the literature to date for any other species.

“These insights and future discoveries will be invaluable in formulating appealing food for cats, as well as enhancing the acceptability of their medications.”

Joseph Rucker, also a co-author, from Integral Molecular, a biotechnology company, said: “Feline bitter taste has not been well studied. We applied our experience in studying membrane proteins, such as taste receptors, to enable this first glimpse into how domestic cats perceive bitterness in food at a molecular level.

“We were surprised to see that one of the cat taste receptors responded to a more limited range of bitter compounds compared to humans, suggesting that cats may be detecting a narrower, or at least a different, repertoire of bitter-tasting compounds.”

Integral Molecular Identifies Potent Inhibitory Antibodies Against Chikungunya Virus

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, a leader in membrane protein antibody discovery, in conjunction with Blood Systems Research Institute (BSRI), has identified potent inhibitory human antibodies against the debilitating mosquito-borne Chikungunya virus (CHIKV). The lead candidate, IM-CKV063, is one of the most potent antibodies against CHIKV isolated to date, and protects animals from CHIKV-induced lethality and arthritis. This work, described by Fong et al., appears in the current issue of the Journal of Virology (December 2014).

The generation and characterization of anti-CHIKV antibodies was enabled by Integral Molecular’s MPS Discovery Engine®, its proprietary strategy for antibody isolation against membrane protein targets. Antibodies from patients naturally infected with virus were isolated by phage display using Integral Molecular’s Lipoparticle reagents. Epitope mapping using Integral Molecular’s Shotgun Mutagenesis technology identified the antibodies’ molecular binding sites on viral surface proteins, providing critical insights for vaccine design. A team of scientists headed by Dr. Graham Simmons at BSRI in San Francisco demonstrated that IM-CKV063 protects animals from CHIKV infection and disease.

“The discovery of potent antibodies with therapeutic potential against Chikungunya virus is an exciting application of the MPS Discovery Engine®,” said Benjamin Doranz, CEO of Integral Molecular. “Given the rapid spread of this virus and the lack of specific treatment options, we are committed to developing this fully human antibody into a first-in-class therapeutic.”

CHIKV recently emerged in the Americas, infecting over one million people across the Caribbean and South America, and infections are now spreading into the United States. The discovery and characterization of CHIKV antibodies stems from a successfully completed five-year contract awarded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Under a subsequent NIAID contract, Integral Molecular is focusing on antibodies that target hepatitis C and Ebola viruses.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelope proteins using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 10 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, autoimmunity and infectious diseases.

Integral Molecular
Benjamin Doranz, 215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Awarded $3.5M Contract from NIH to Study Ebola and Hepatitis C Virus Antibody Response

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, Inc. has been awarded a five year $3.5 million contract to study the human immune response to Ebola virus and hepatitis C virus (HCV). This award enables Integral Molecular to understand how human antibodies protect (or fail to protect) against these viruses. Using its proprietary Shotgun Mutagenesis Epitope Mapping technology, Integral Molecular will identify how antibodies target binding structures, or epitopes, on Ebola and HCV, which will facilitate the development of vaccines and therapeutics against these major health threats.

This award from the National Institute of Allergy and Infectious Diseases (NIAID, part of the National Institutes of Health) is the second NIAID contract awarded to Integral Molecular for epitope mapping. Under the recently completed first contract, Integral Molecular used Shotgun Mutagenesis to map over 280 antibody epitope binding sites on the envelope proteins of dengue virus, chikungunya virus, and HCV, exceeding the original project goals and providing some of the largest epitope data sets available for any viral pathogen. Many of these epitopes have now been published in major scientific journals and deposited in NIAID’s central Immune Epitope database (immuneepitope.org). Among the antibodies discovered and characterized by Integral Molecular are some of the most potent antibodies against chikungunya virus isolated to date, providing a potential therapeutic treatment for this debilitating viral disease.

“Understanding the full range of antibody epitopes targeted by the human immune system is vital for designing effective vaccines and antibody-based therapeutics against viruses,” said Dr. Benjamin Doranz, President of Integral Molecular. “With this contract we will isolate and characterize new human antibodies against Ebola and HCV envelope proteins. High resolution epitope maps that describe how the most effective antibodies bind and neutralize these viruses will increase our understanding of how these viral proteins function and how they can be inhibited.”

Shotgun Mutagenesis Epitope Mapping analyzes hundreds to thousands of variants of a target protein, each with a single defined amino acid substitution, to rapidly identify the binding residues that form antibody epitopes. The technology analyzes proteins directly within living human cells, allowing epitope mapping of complex proteins in their native conformation. Integral Molecular also offers Shotgun Mutagenesis services for epitope mapping and protein engineering on a fee-for-service basis to the research community.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelope proteins using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 10 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, autoimmunity and infectious diseases.

Integral Molecular, Inc.
Benjamin Doranz, 215-966-6061
bdoranz@integralmolecular.com