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Integral Molecular Enters Immuno-Oncology Target Discovery Collaboration with Daiichi Sankyo

PHILADELPHIA–(PR NEWSWIRE)–Integral Molecular, the industry leader in membrane protein solutions, today announced that it has entered into a collaboration to discover new therapeutic targets in immuno-oncology (I-O) with Daiichi Sankyo Co., Ltd. Integral Molecular will use its Membrane Proteome Array (MPA) platform to identify novel membrane proteins that regulate the human immune system’s ability to recognize and destroy cancer cells. Daiichi Sankyo will use the identified I-O targets to develop new therapeutics. Specific financial terms of the agreement have not been disclosed.

The MPA platform contains 5,300 different human membrane proteins, each individually expressed in live human cells. Each protein is screened for ligand binding and biological function using unfixed cells and flow cytometry, enabling high-sensitivity detection and high success rates. These features, particularly the ability to detect functional interactions in live cells, make the MPA ideally suited to the discovery of new therapeutic targets.

“By discovering new targets without preconceived biases, the MPA platform overcomes the disadvantages of current approaches for identifying novel immunomodulatory proteins,” said Benjamin Doranz, President and CEO at Integral Molecular. “We have already discovered more than a dozen novel I-O interactions and confirmed that several of these interactions regulate T cells. We are looking forward to a successful collaboration with Daiichi Sankyo.”

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters, and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, Integral Molecular’s technology suite enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

Contact
Integral Molecular, Inc.
Benjamin Doranz, President and CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Announces Antibody Discovery Collaboration with Ono Pharmaceutical

PHILADELPHIA–(PR NEWSWIRE)–Integral Molecular, the industry leader in the discovery of monoclonal antibodies (MAbs) against multipass membrane proteins, and Ono Pharmaceutical Co., Ltd. today announced that they have entered into a new collaboration for antibody discovery following a previously successful collaboration. This second collaboration involves the discovery of candidate MAbs against an undisclosed target and leverages the power of Integral Molecular’s MPS Antibody Discovery platform.

Integral Molecular has used the MPS platform to discover antibody assets targeting a number of other multipass membrane proteins, including GPCRs (CB1) and transporters (GLUT4). Many of these MAbs are the first of their kind to be isolated, as complex membrane proteins have historically been extremely difficult targets for antibody discovery.

“We have a proven track record discovering large panels of high-affinity antibodies against difficult membrane proteins. This has been driven by our innovative MPS platform and over 15 years of experience working with multipass membrane proteins, so we are confident in the success of this collaboration,” said Dr. Ross Chambers, VP of Antibody Discovery at Integral Molecular. “We are pleased that Ono, a global leader in innovative medicines, considers us to be a trusted partner in antibody discovery.”

“We have been impressed by Integral Molecular’s membrane protein expertise and their proven record in discovering antibodies against them,” said Hideaki Tada, Executive Director, Center of Oncology Research of Ono. “This is our second collaboration with Integral Molecular, and we are very pleased to deepen our engagement with them.”

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters, and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

About Ono
Ono Pharmaceutical Co., Ltd., headquartered in Osaka, is an R&D-oriented pharmaceutical company committed to creating innovative medicines in specific fields, centered on oncology and diabetes. For further information, please refer to the company’s website at www.ono.co.jp/eng.

Contact
Integral Molecular, Inc.
Benjamin Doranz, President and CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular’s Therapeutic MAbs Against CB1 to Treat NASH Enter New Development Phase Following $1.4M NIH Award

PHILADELPHIA–(PR NEWSWIRE)–Integral Molecular, the industry leader in antibody discovery against multipass membrane proteins, was awarded $1.4M by the NIH to develop its lead antibodies against cannabinoid receptor 1 (CB1) for treating the liver disease nonalcoholic steatohepatitis (NASH) and metabolic disorders, including obesity and metabolic syndrome. With this Phase 2 SBIR grant, Integral Molecular builds on its successful Phase 1 SBIR program isolating antibodies with high specificity and high affinity for CB1. The goal of the Phase 2 project is to develop antibodies for initiating preclinical studies.

More than 10 million people in the United States have NASH, a chronic inflammatory condition that can lead to liver cirrhosis and liver failure. Although CB1 is a validated GPCR target for NASH and metabolic disorders, small-molecule CB1 inhibitors cause adverse psychoactive effects. By contrast, monoclonal antibodies (MAbs) do not cross the blood-brain barrier and have superior specificity and target selectivity over small-molecule drugs. Using its MPS Antibody Discovery platform that addresses the challenges of MAb discovery against GPCRs, Integral Molecular has isolated extremely rare inhibitory MAbs against CB1 for treating NASH.

“The MPS technology delivers large panels of diverse MAbs against membrane proteins, which was required to find highly specific inhibitory CB1 MAbs,” said Benjamin Doranz, CEO of Integral Molecular. “Given the historic failure of small-molecule drugs targeting CB1, we are excited to offer an ideal therapeutic antibody discovery solution for NASH.”

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in multipass membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. Integral Molecular discovers antibodies for partners in parallel with independent work developing antibodies for licensing. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

For more information, please contact:
Integral Molecular, Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Awarded NIH Grant to Discover Neuroimmune Drug Targets in Alzheimer’s Disease

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, the industry leader in membrane protein technologies, was awarded a Small Business Innovation Research (SBIR) grant from the NIH to initiate a target discovery program for Alzheimer’s disease. Under the grant, Integral Molecular will use its highly successful Membrane Proteome Array (MPA) platform to discover novel neuroimmune targets for treating Alzheimer’s and other neurodegenerative diseases.

Neurodegenerative diseases are a leading cause of death and disability for 6.5 million older Americans. A major roadblock in the development of new treatments has been the lack of druggable targets. Recent research suggests that dysregulation of the immune system can cause or exacerbate many neurodegenerative diseases. The identification of new proteins that can regulate the neuroimmune system could enable the discovery of an entirely new generation of therapeutics with the potential to treat, delay, or even prevent Alzheimer’s disease.

“The lack of effective targets in Alzheimer’s disease has held back the discovery of new drugs to treat it,” says Benjamin Doranz, CEO of Integral Molecular. “We have already identified new targets in the immuno-oncology and infectious disease fields using our MPA platform, so we are excited to expand our work to include neurodegenerative diseases.”

Integral Molecular’s MPA technology is composed of 5,300 human membrane proteins expressed in their functional form on the surface of live human cells, allowing signaling and binding assays to detect functional interactions. Integral Molecular has already used the MPA to identify novel targets and protein interactions in various therapeutic areas, as well as to obtain off-target binding profiles to de-risk drug development.

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters, and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. Integral Molecular discovers antibodies for partners in parallel with independent work developing antibodies for licensing. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

For more information, please contact:
Integral Molecular, Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Partners with Merus to Discover Novel Therapeutic Monoclonal Antibodies

PHILADELPHIA – (BUSINESS WIRE) – Integral Molecular, the industry leader in the discovery of monoclonal antibodies (MAbs) against membrane proteins, and Merus N.V. (Nasdaq:MRUS), a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutics, today announced that they have entered into a collaboration on multiple undisclosed targets.

The collaboration leverages the power of Integral Molecular’s proprietary technologies: the MPS Discovery Engine®, a technology suite for discovering MAbs against structurally complex proteins; and Lipoparticles, virus-like particles displaying high concentrations of membrane proteins. Using the MPS platform, Integral Molecular has discovered antibody assets targeting membrane proteins important in oncology (Claudin 6) and metabolic diseases (CB1, GLUT4), among others. Many of these MAbs are the first of their kind to be isolated, as complex membrane proteins have historically been extremely difficult targets for antibody discovery.

Cecile Geuijen, PhD, Vice President, Oncology Research of Merus, stated: “Having worked with Integral Molecular for many years, we are excited to formalize this collaboration. Access to Integral Molecular’s capabilities will complement our ability to advance our therapeutic pipeline, which is dedicated to delivering novel antibody therapeutic candidates to patients.”

“Integral Molecular’s technologies are uniquely suited for discovering diverse antibodies against complex membrane proteins, which are the most compelling targets for treating disease,” said Ross Chambers, VP of Antibody Discovery at Integral Molecular. “Our MPS platform can be used to discover cross-reactive MAbs against both human and rodent targets, enabling partners such as Merus to advance into preclinical studies as quickly as possible.”

About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters, and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

About Merus N.V.
Merus is a clinical-stage immuno-oncology company developing innovative full-length human bispecific antibody therapeutics, referred to as Biclonics®. Biclonics®, which are based on the full-length IgG format, are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, www.merus.nl.

For more information, please contact:
Integral Molecular, Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Celebrates Epitope Mapping Milestone of 1,000 Epitopes

PHILADELPHIA-(BUSINESS WIRE)-Integral Molecular, the industry leader in the discovery and characterization of antibodies against membrane proteins, celebrates a milestone of mapping 1,000 epitopes for customers, collaborators, and the NIH.

Integral Molecular is a trusted partner to numerous companies who require antibody epitope data for lead selection based on mechanism of action, or for value enhancement through intellectual property. Integral Molecular has been awarded more than $20 million from the NIH to map and understand the epitopes for high-priority pathogenic viruses, resulting in over 40 publications in Cell, Nature, PNAS, and other high-profile journals.

Integral Molecular’s proprietary Shotgun Mutagenesis Epitope Mapping technology is the only high-throughput method available for mapping conformational epitopes at amino-acid resolution, having a success rate of >95%, even for complex targets. Shotgun Mutagenesis epitope mapping results have been used in 25 patents, and 7 antibodies mapped by Integral Molecular have entered clinical trials.

“As an antibody discovery company, we understand the need for the detailed characterization and protection of antibody assets,” says Benjamin Doranz, President and CEO of Integral Molecular. “Our targets are structurally complex and difficult to map using standard techniques. To fulfill our needs, we developed a high-throughput method of epitope mapping at the amino-acid level, which has now been widely adopted throughout industry.”

The patent landscape for antibodies has become increasingly complex. Epitope data support antibody patents by demonstrating antibody novelty, differentiating from prior art, and supporting the patent’s written description requirement. Benjamin Doranz shares insights on the value of epitope mapping in a panel discussion on functional antibody claims at the BIO International Convention in June. A recent publication co-authored by Dr. Doranz and colleagues, entitled “Enhancing antibody patent protection using epitope mapping information,” was recently published in the journal mAbs (Deng et al., 2018).

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. Integral Molecular discovers antibodies for partners in parallel with independent work developing antibodies for licensing. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

Contact
Integral Molecular, Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular’s MPS Antibody Discovery Platform Yields Therapeutic Assets for Oncology and Metabolic Syndrome

Integral Molecular, the industry leader in membrane protein antibody discovery, announces the development of antibody assets targeting membrane proteins important in oncology (Claudin 6) and metabolic syndrome (GLUT4 and CB1). These therapeutic assets are among the first released in a pipeline of antibodies being isolated with the MPS Antibody Discovery platform, which is tailored for the discovery of rare, functional antibodies against complex membrane protein targets.

In a paper published in PNAS (Tucker et al., May 2018), the company revealed the discovery of the first functional MAbs against GLUT4, an insulin-responsive glucose transporter important in diabetes. Epitope mapping showed that MAbs LM043 and LM048 are rare state-specific MAbs, selectively binding only certain active forms of the GLUT4 transporter.

Last month at the PEGS protein engineering conference, Integral Molecular presented their discovery of antagonist MAb IM-102 against CB1 for NASH (inflammatory liver disease). IM-102 inhibits CB1 with 23 times greater potency than a benchmark MAb currently in phase 1 clinical trials. At the AACR conference this spring, the company presented its discovery of highly specific antibodies against Claudin 6, an established membrane protein target in ovarian cancer.

Ross Chambers, VP of Antibody Discovery, attributes the company’s 95% success rate in MAb isolation to optimization of its antibody discovery platform: “Our proprietary technologies allow us to obtain hundreds of diverse, high-affinity antibodies against complex targets, enabling us to discover antibodies with rare functional properties.”

Integral Molecular’s MPS Antibody Discovery platform encompasses a technology suite that overcomes the obstacles of working with highly homologous and structurally complex targets. This suite includes antigen engineering and presentation on Lipoparticles, immunization of divergent species, and use of B-cell cloning to recover rare antibodies. Integral Molecular is currently isolating MAbs against dozens of membrane protein targets.

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) is the industry leader in membrane protein antibody discovery, with a pipeline of therapeutic antibodies against GPCRs, ion channels, transporters and immuno-oncology targets. Built on the company’s extensive experience optimizing membrane proteins, this platform enables the isolation, characterization, and engineering of MAbs against otherwise intractable targets. Integral Molecular discovers antibodies for partners in parallel with independent work developing antibodies for licensing. The company currently has therapeutic programs focused on cancer, pain, immunity, and metabolic disorders.

Contact
Integral Molecular, Inc.
Ross Chambers, VP of Antibody Discovery
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular’s Protein Engineering Technology Facilitates HIV Vaccine Development

PHILADELPHIA–(BUSINESS WIRE)-Integral Molecular, the industry leader in engineering membrane proteins, has extended its protein engineering capabilities to stabilize viral proteins and produce more effective candidate vaccines against HIV and other viruses.

The company’s protein engineering approach is based on its successful high-throughput Shotgun Mutagenesis technology. Using this approach, Integral Molecular can identify viral protein variants that have improved stability but retain their native protein structures. This strategy results in stabilized proteins that can elicit protective immune responses.

In collaboration with researchers at Weill Cornell Medical College, Integral Molecular developed stable trimeric HIV glycoproteins (Sullivan et al., 2017 Journal of Virology). Using a combination of rational design and empirical high-throughput screening, researchers created and tested over 800 individual mutants of the HIV envelope protein in human cells. Effective mutations were combined to produce an envelope glycoprotein variant with improved stability and native-like conformation.

“The unstable nature of viral envelope glycoproteins has been a major hurdle in the development of an effective vaccine against HIV and other viruses,” said Benjamin Doranz, President and CEO of Integral Molecular. “The high-throughput protein stabilization strategy developed here is a groundbreaking step in developing more effective vaccines.”

About Integral Molecular
Integral Molecular (staging.integralmolecular.com) 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 Antibody Discovery technology. 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, immunity, metabolic disorders, and infectious diseases.

Contact
Integral Molecular Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com

Integral Molecular Expands its Epitope Mapping Platform to Identify Small Molecule Binding Sites on Multipass Membrane Proteins

PHILADELPHIA–(BUSINESS WIRE)– Integral Molecular, the industry leader in the expression and characterization of multipass membrane proteins, has expanded its mapping capabilities to include small molecules. This was achieved using Integral Molecular’s Shotgun Mutagenesis platform, now the leading industry technology for understanding how antibodies interact with complex membrane proteins, with over 500 epitopes mapped at a >95% success rate. By combining this platform with its functional analysis capabilities, Integral Molecular has now extended this mapping capability to small molecules, which comprise 50% of drugs in development.

A recent study, published by Integral Molecular in Scientific Reports (Thomas et al., 2017), identified the precise binding sites for four different small molecules that bind to a human GPCR protein (TAS2R16). Small molecule binding sites are usually very difficult to map in the absence of protein co-crystal structures, as is the case for TAS2R16 and most other multipass membrane proteins. This study extends similar work that Integral Molecular has completed internally and for partners, mapping small molecule drug binding sites on GPCRs and other multi-pass membrane proteins, including mapping the binding site of a peptide on the GPCR CXCR4 (Wescott, et al, 2016 PNAS).

“This method for identifying individual amino acids that are critical for binding or function in structurally complex proteins is particularly valuable since it does not require traditional structural information,” said Dr. Joseph Rucker, VP of Research and Development at Integral Molecular. “The small molecules we mapped are also very low affinity, making them even more challenging for more traditional analytical techniques. With this new ability, our mapping expertise now covers antibodies, peptides, and small molecules.”

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, immuno-oncology targets, and viral envelope proteins. Integral Molecular has a long-standing interest in the structure and function of taste receptors such as TAS2R16, which are important for taste but also have specific roles in numerous non-taste physiological processes. The company utilizes its Shotgun Mutagenesis Epitope Mapping platform technology to rapidly map binding sites on structurally complex targets. Integral Molecular offers Epitope Mapping services on a fee-for-service basis, for mapping antibody, ligand, or small molecule binding sites.

Contact
Integral Molecular Inc.
Benjamin Doranz, President & CEO
215-966-6061
info@integralmolecular.com
staging.integralmolecular.com