RESOURCES

Where research scientists come to find up to date resources on antibody discovery against challenging membrane protein targets.

Category: news

Integral Molecular Partnership: Context Therapeutics® Nominates CTIM-76 Bispecific Antibody Candidate to Develop Treatment for Claudin 6-Positive Solid Tumors

CTIM-76 named as lead candidate to target Claudin 6 positive cancers

IND submission expected in Q1 2024

Context to host webinar on Thursday, December 1, 2022, at 11 a.m. ET

PHILADELPHIA, Nov. 29, 2022 (GLOBE NEWSWIRE) — Context Therapeutics Inc. (“Context” or the “Company”) (Nasdaq: CNTX), a women’s oncology company developing novel treatments for breast and gynecologic cancers, today announced the selection of CTIM-76, a T cell-engaging bispecific antibody, as its lead clinical development candidate to target Claudin 6 (CLDN6) positive cancers, resulting from its research collaboration and licensing agreement with Integral Molecular.

CLDN6 is differentially expressed on cancer cells with no or very low expression in normal, healthy tissue. CLDN6-enriched cancers include ovarian, endometrial, testicular, and gastric, among others. With the potential to reach a large patient population and selective expression on cancer cells, CLDN6 has emerged as an exciting drug target.

Context’s lead candidate, CTIM-76, is a CLDN6 x CD3 bispecific antibody that incorporates a highly selective CLDN6 binding arm and a CD3 binding single-chain Fv domain in an IgG format with a silenced Fc that is designed to be functionally monovalent to avoid aberrant T-cell activation and to enhance the safety profile. Research has demonstrated that CTIM-76 is potent with specific lysis of CLDN6+ cancer cells over normal cells and can activate cytotoxic T cells without concomitant activation of free cytokines – critical determinants of immunotherapy safety and activity. Preclinical studies suggest the potential for convenient dosing with low immunogenicity risk and manufacturing can be scalable to address the significant number of patients who are potentially eligible for CTIM-76 therapy.

“This year has been marked by several exciting and significant milestones for Context, culminating in naming our lead CLDN6 clinical development candidate, CTIM-76, a bispecific antibody showing high selectivity for CLDN6,” said Martin Lehr, CEO of Context Therapeutics. “We selected this bispecific based on the specificity which suggests its potential to address the need for potent therapeutic modalities for cancer without compromising patient safety. With the selection of CTIM-76 as our lead CLDN6 candidate, we are well-positioned to rapidly advance our clinical development plan in CLDN6-positive tumors including, but not limited to, ovarian cancer. We have initiated IND-enabling studies and expect to submit our Investigational New Drug Application (IND) for CTIM-76 to the U.S. Food and Drug Administration in Q1 2024.”

“Despite being an attractive target, therapeutic monoclonal antibodies (MAbs) targeting CLDN6 are difficult to discover due to an abundance of closely related family members and an absolute need for high specificity. Context and Integral Molecular have been able to isolate and optimize rare antibodies against CLDN6 that do not cross-react with other CLDN family members,” said Joseph Rucker, Ph.D., VP of R&D at Integral Molecular.

R&D Webinar
On Thursday, December 1, 2022, at 11 a.m. ET, members of the Context team, including management, and Integral Molecular will host a webinar to discuss the selection process and nomination of CTIM-76. There will be a question-and-answer period following the formal presentation. To register for the webinar, please visit https://edisongroup.zoom.us/webinar/register/WN_Am1qwkDwRiSYJm51SpP-TQ.

About Context Therapeutics®
Context Therapeutics Inc. (Nasdaq: CNTX) is a clinical-stage biopharmaceutical company committed to advancing medicines for female cancers. The Company’s pipeline includes small molecule and bispecific antibody drug candidates that target cancer signaling pathways. Onapristone extended release (ONA-XR), a novel, first-in-class potent and selective progesterone receptor antagonist, is currently in three Phase 2 clinical trials and one Phase 1b/2 clinical trial in hormone-driven breast, ovarian, and endometrial cancers. Context is also developing CTIM-76, a selective Claudin 6 (CLDN6) x CD3 bispecific antibody for CLDN6 positive tumors, currently in preclinical development. Context is headquartered in Philadelphia. For more information, please visit www.contexttherapeutics.com or follow the Company on Twitter and LinkedIn.

Forward-looking Statements
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. These include, without limitation, statements regarding (i) the selectivity, dosing convenience, potency, binding, scalable manufacturing, and safety profile of CTIM-76, (ii) the expectation to have an IND submission for CTIM-76 in the first quarter of 2024, (iii) the results of our IND-enabling studies and clinical trials, (iv) the potential benefits of our product candidates, (v) the likelihood data will support future development, and (vi) the likelihood of obtaining regulatory approval of our product candidates. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise.

Follow Integral Molecular on LinkedIn
Follow Integral Molecular on Twitter

Press Contact:
Integral Molecular, Inc.
Soma Banik, PhD, Director of Public Relations
215-966-6061
info@integralmolecular.com
www.integralmolecular.com

Integral Molecular Launches New Product Lines of Safe Reporter Viruses for Vaccine Development and Pandemic Preparedness

PHILADELPHIA–Using its extensive experience gained fighting COVID-19 and other virus threats for over 20 years, Integral Molecular has launched an expanded collection of its Reporter Virus Particles (RVPs) that offer a safe and rapid method to study some of the most virulent pathogens including influenza, Ebola virus, and SARS-CoV-2. These critical reagents are used to safely screen patient sera for neutralizing antibody responses generated by protective vaccines.

Integral Molecular’s new RVP offerings feature influenza A H5N1, Ebola virus, and Marburg virus. The company also offers over 70 SARS-CoV-2 RVPs covering all variants of concern and interest, including Omicron BA.4, BA.5 and BA.4.6 subvariants. Integral Molecular has also created custom variants, as well as thousands of mutations in this safe RVP format to enable prediction of viral escape and the creation of better vaccines.

RVPs are “pseudoviruses” that lack the viral components required to replicate and cause disease. Because they can’t replicate, RVPs are safe to use under standard (BSL2) laboratory conditions. In contrast, studying the most deadly ‘live’ strains of viruses such as Ebola virus or pandemic strains of influenza requires highly restrictive (BSL4) facilities, which relatively few laboratories in the world possess.

“With 20 years of experience studying viruses and vaccines, we are excited to launch new products that enable faster and safer vaccine development against the world’s deadliest viruses,” said Sharon Willis, PhD, co-founder of Integral Molecular. “With these safe research tools, the greater scientific community can ramp up studies of new viral threats as soon as they emerge.”

Integral Molecular’s broad range of RVPs also includes a selection of influenza A and B seasonal strains, dengue, Zika, and chikungunya viruses. The company will host a virtual panel discussion of RVP tools for virology research on November 10, 2022.

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.

Follow Integral Molecular on LinkedIn
Follow Integral Molecular on Twitter

Press Contact:
Integral Molecular, Inc.
Soma Banik, PhD, Director of Public Relations
215-966-6061
info@integralmolecular.com
www.integralmolecular.com

Genetic Engineering and Integral Molecular Present – Reporter Virus Tools to Combat Current Viral Threats and the Next Pandemic

 

Thursday, November 10, 2022

The COVID-19 pandemic has brought virology to the forefront of many research programs. But how do we get ahead of the next viral threat? Limited commercial labs are licensed to conduct research using BSL-3 or BSL-4 pathogens. However, reporter virus tools such as ready-to-use Reporter Virus Particles (RVPs, i.e., pseudoviruses) have enabled virus research in a BSL-2 environment, allowing testing of sera and antibodies in high-throughput, safe neutralization assays to accelerate virology research.

In this GEN webinar, of our distinguished speakers, Dr. Hayley Crawford, will discuss Integral Molecular’s broad catalog of RVPs, including influenza A and B, Marburg virus, and the latest variants of SARS-CoV-2. Moreover, she will discuss Integral Molecular’s expertise in custom RVP projects. Additionally, panelists Dr. Sheila Keating and Dr. Natalie Anosova will describe how Integral Molecular’s extensive collection of SARS-CoV-2 variant RVPs enabled them to meet the most recent FDA guidance for variant testing of vaccines and therapeutic antibodies.

Learn more about how RVPs have enabled therapeutic research during the COVID-19 pandemic and how they can enhance virology research on current and emerging viral targets.

GEN and Integral Molecular 2022 webinar

Integral Molecular Licenses Claudin 18.2 Monoclonal Antibodies to CARTEXELL for Oncology Cell Therapies

PHILADELPHIA—Integral Molecular, the industry leader in discovering antibodies against complex membrane protein targets, has licensed a panel of monoclonal antibodies (MAbs) to CARTEXELL, enabling CARTEXELL to develop CAR-T cell therapies using Integral Molecular’s Claudin 18.2 (CLDN18.2) MAbs.

Under the terms of the agreement, Integral Molecular will provide an exclusive worldwide license to CARTEXELL to use the panel of high-affinity, high-specificity, and fully humanized CLND18.2 MAbs for the development of CAR-T cell therapies against solid tumors including gastric, lung, pancreatic and esophageal cancers. CARTEXELL will be solely responsible for all research, development, and commercial activities.

The CLND18.2 MAbs were isolated using Integral Molecular’s MPS Antibody Discovery platform which is uniquely tailored to deliver high-specificity, high-affinity antibodies against the most structurally challenging membrane protein targets including GPCRs, ion channels, transporters, and tight junction proteins.

“Claudin 18.2 is an exciting target for oncology therapeutics since it’s highly expressed in cancers such as gastric and esophageal cancers that are difficult to treat”, said Joseph Rucker, PhD, Vice President of R&D at Integral Molecular. “We look forward to the synergy of our high-specificity MAbs with CARTEXELL’s CAR-T cell therapy technology to bring new therapies to patients.”

“CAR-T cell therapy has revolutionized treatment options for blood cancers, but has been ineffective for solid tumors”, said Jehee Suh, CEO of CARTEXELL. “We are excited by the promise of these Claudin 18.2 antibodies for targeting our CAR-T 2.0 technology which uses engineered cells and vectors to overcome the tumor microenvironment and provide more effective therapies.”

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.

About CARTEXELL
CARTEXELL was established by Helixmith’s immunocyte therapy team, which has developed CAR-T treatment technology since 2013, and is the first bio company in Korea to export CAR-T products to biotech companies in the United States. As a leader in the development of next-generation CAR-T treatments for the cancer, we selectively introduce more effective strategies than existing CAR-Ts, such as comparing and selecting the CAR structure, introducing additional genes other than CAR, and selecting the route of administration. CARTEXELL will continue to grow into a global biotech company in the field of gene and cell therapy.

Follow Integral Molecular on LinkedIn
Follow Integral Molecular on Twitter

Press Contact:
Integral Molecular, Inc.
Soma Banik, PhD, Director of Communications
215-966-6061
info@integralmolecular.com
www.integralmolecular.com

FDA Accepts Integral Molecular’s Letter of Intent (LOI) on Membrane Proteome Array Antibody Specificity Test Into ISTAND Drug Development Tools Pilot Program

PHILADELPHIA—Integral Molecular, the leader in antibody discovery against membrane proteins, has been accepted into the U.S. Food & Drug Administration (FDA)’s ISTAND pilot program. This program supports Innovative Science and Technology Approaches for New Drugs and was created to expand the drug development tool types listed in the 21st Century Cures legislation. A major goal of the pilot program is to qualify these tools, thus facilitating regulatory review by allowing them to be used in regulatory (IND, NDA or BLA) applications without needing the FDA to reconsider and reconfirm their suitability.

Despite their reputation for ‘exquisite specificity’, antibodies and antibody-based therapies, such as CAR-T cells, frequently demonstrate unexpected off-target binding. Integral Molecular’s Membrane Proteome Array (MPA) for antibody specificity and safety profiling intends to address ICH-FDA’s in vitro testing recommendations to assess unintended binding of monoclonal antibodies that can result in safety and toxicity issues.

The MPA is one of the largest collections of membrane proteins used for specificity profiling of antibody-based therapeutics, with over 6,000 native-conformation membrane proteins encompassing nearly the entire human membrane proteome. This technology is intended to be compatible with numerous biotherapeutic modalities, including monoclonal antibodies, bispecifics, and CAR-T therapeutics.

“We are thrilled to be working with the FDA’s ISTAND program,” said Benjamin Doranz, CEO of Integral Molecular. “We share the FDA’s interest in developing in vitro technologies to better assess the safety of antibody drugs at an earlier and less costly stage of development.”

FDA has posted a statement on this LOI acceptance to the ISTAND Pilot Program: https://www.fda.gov/drugs/drug-safety-and-availability/drug-alerts-and-statements#statements

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.

Follow Integral Molecular on LinkedIn
Follow Integral Molecular on Twitter

Press Contact:
Integral Molecular, Inc.
Soma Banik, PhD, Director of Communications
215-966-6061
info@integralmolecular.com
www.integralmolecular.com

FDA Announcement: CDER and CBER accept first submission to ISTAND Pilot Program

See statement on FDA website.

[9/7/2022] FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) have accepted the agency’s first submission into the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program.

FDA launched ISTAND in 2020 to support development of drug development tools (DDTs) that are considered novel to be used in regulatory applications for new medical products.

DDTs are methods, materials or measures that can facilitate drug development. Certain DDTs, such as biomarkers and clinical outcome assessments, have clearly established pathways for evaluation and application. ISTAND opens additional opportunities for unconventional approaches to be reviewed and accepted by FDA. If qualified, these tools can help optimize drug development and evaluation, potentially expediting the availability of safe and effective drug and biologic products.

ISTAND’s first accepted Letter of Intent (LOI) submission is for a tool that proposes to evaluate off-target protein binding for a variety of biotherapeutic modalities, potentially reducing or eliminating the need to conduct some of the more standard nonclinical toxicology tests. The tool’s developers hope it will improve the accuracy, sensitivity and overall utility of specificity testing of biotherapeutics to support investigational new drug applications.

The LOI acceptance is the first step of the three-step qualification process in the DDT qualification programs, and it is based on several factors, including the scientific merit of the submission, the ability of the DDT to address a specified drug development need, the availability of information and resources that support the proposed qualification effort and demonstration that the DDT is feasible and practical within the proposed context of use. FDA will now work with the applicant to provide feedback on the next qualification step—a qualification plan.

CDER and CBER are excited to kickstart the future of novel DDT development with the first ISTAND LOI acceptance. We look forward to ISTAND’s continued support of innovative approaches to drug development and to the program’s contributions to bringing effective therapies to patients faster.

Genetic Engineering and Integral Molecular Present – Towards IND: Specificity Profiling of Antibody-Based Therapies

 

Thursday, July 14, 2022
Watch video

Rigorous specificity analysis is critical for successful drug development and a safety requirement for monoclonal antibody (mAb) based therapies, such as CAR-T, entering IND. Tissue cross-reactivity (TCR) studies have been traditionally used to screen for off-target binding, however, with poor predictive value for in vivo safety and toxicity.

Integral Molecular has developed the Membrane Proteome Array (MPA) platform to de-risk mAb-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.

Towards IND: Specificity Profiling of Antibody-Based Therapies SPeakers

Integral Molecular and Optimeos Life Sciences Enter Partnership to Develop mRNA and DNA-Based Gene Therapies Using Molecular Targeting

PHILADELPHIA—Integral Molecular and Optimeos Life Sciences announce a partnership to develop next-generation mRNA and DNA therapeutics that will use antibody-based molecular targeting to direct vaccines and gene therapies to relevant tissues in a patient’s body. This partnership combines Integral Molecular’s experience in antibody discovery and mRNA immunization with Optimeos’ technology for nanoparticle-based drug delivery systems.

DNA and mRNA therapeutics harness a patient’s own molecular machinery to encode proteins. Integral Molecular and Optimeos plan to encapsulate these therapeutic molecules within nanoparticle spheres that are decorated with antibodies on the outer surface. The antibodies can then target the particles to specific tissues. Currently, gene therapies and mRNA vaccines are delivered into the body via infusion or injection, but only a fraction of the molecules arrive at their intended site. The proposed molecular targeting strategy has the potential to transform the delivery of vaccines and therapeutics by dramatically reducing dosages, decreasing toxicity, and enabling scalable administration.

Integral Molecular will apply its industry-leading antibody discovery expertise against complex cell-surface proteins to provide targeting moieties for the therapies. Its specialized MPS Antibody Discovery platform is tailored to work with challenging membrane protein targets and routinely uses mRNA-based immunization strategies. “Precision targeting of an isolated cell type with gene therapy holds great promise for genetic diseases and may provide brand-new directions in cancer immunotherapy including in vivo CAR-T cell therapeutics,” said Joseph Rucker, Co-founder and VP of R&D at Integral Molecular.

Optimeos’ technology allows the robust and scalable incorporation of mRNA and DNA therapeutics and other biologics into customizable nanoparticles. “We are excited to work with Integral Molecular towards the next generation of gene-therapy that no longer relies on viral-based delivery systems,” said Robert Prud’homme, Co-founder and Chief Technical Officer of Optimeos.

Integral Molecular and Optimeos will be attending BIO International Convention in San Diego later this month.

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.

About Optimeos Life Sciences
Optimeos Life Sciences (optimeos.com) has developed a novel, highly differentiated, non-viral, nanoparticle technology, (iFNP) for delivery of new therapeutic drugs to address important unmet medical needs. The technology is a patented and scalable polymeric drug delivery system, which was developed and refined in Professor Prud’homme’s lab at Princeton University over 20 years. Optimeos’ technology enables encapsulation of mRNA, DNA, peptides, proteins or small molecules, as well as their targeted delivery to cells and tissues beyond the liver.

Pfaff-Kilgore and colleagues describe a comprehensive mutagenesis and functional study of the E1E2 protein of Hepatitis C virus in Cell Reports

Cell Reports Publication HCVPublished in Cell Reports, Pfaff-Kilgore and colleagues describe a comprehensive mutagenesis and functional study (545 individual mutants) of the E1E2 protein of Hepatitis C that enabled us to develop a model of how each amino acid is used in the function of this virus.

Thank you to our scientific team at Integral Molecular and collaborators in the laboratories of Drs. Nicasio Mancini, Justin Bailey, James Crowe, and Mansun Law who made this study possible.

Highlights

  • Test 545 hepatitis C virus (HCV) E1E2 envelope mutations for infectivity and antibody binding
  • Identify residues important for HCV E1E2 folding, interaction and infectivity
  • HCV E1E2 is a fragile protein complex where most mutations compromise function
  • Functional residues of E1E2 are highly conserved across genotypes

See article online