On March 26, 2019 Integral Molecular, the industry leader in discovering antibodies against multipass membrane proteins, reported that it will showcase updated data on its discovery of highly specific Claudin 6 MAbs at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference in Atlanta on Monday, April 1 (Press release, Integral Molecular, MAR 26, 2019, View Source [SID1234534628]). Claudin 6 is an established membrane protein target expressed in multiple cancers, including ovarian and gastric tumors, and absent from healthy adult tissues. Until now, the structural complexity of Claudin 6 and its similarity to proteins expressed on healthy tissue have limited its exploitation for targeted oncology therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"There is a strong need for therapeutic monoclonal antibodies that can provide more specific and less toxic treatments for ovarian cancer," said Ross Chambers, VP of Antibody Discovery. "Our lead antibody, isolated using our MPS Antibody Discovery platform, shows best-in-class Claudin 6 specificity. We are currently looking for partners to further develop these exciting assets."

Integral Molecular’s MPS Antibody Discovery platform encompasses a comprehensive technology suite that overcomes the obstacles of working with highly conserved and structurally complex membrane protein targets, like Claudin 6. This suite includes antigen engineering and presentation on Lipoparticles, immunization of divergent species, and the use of B-cell cloning to recover rare antibodies. Integral Molecular is currently isolating MAbs against dozens of membrane protein targets and welcomes antibody licensing opportunities and discovery partnerships.

On March 26, 2019 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing a new class of potent and selective miniature drug conjugates (Pentarins) for the treatment of patients with a wide range of solid tumors, reported that the company will present nonclinical data on PEN-221 at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, occurring March 29 – April 3, 2019 in Atlanta, GA (Press release, Tarveda Therapeutics, MAR 26, 2019, View Source [SID1234534644]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

PEN-221 is a miniature drug conjugate designed to rapidly penetrate deep into solid tumors where it is highly selective for somatostatin receptor 2 (SSTR2) and accumulates its potent DM1 cytotoxic payload. The presenter will demonstrate the effectiveness of PEN-221 in combination with epigenetic modulation by an HDAC inhibitor in nonclinical models of human cancer. The data show that an HDAC inhibitor increases the tumor expression of SSTR2 with synergy of efficacy.

Details of the poster presentation are as follows:

Title: Epigenetic modulation of SSTR2 expression provides the potential to broaden PEN-221 treatment population
Date: Tuesday, April 2, 2019
Time: 1:00pm Eastern Time
Location: Georgia World Congress Center, Atlanta, GA

On March 26, 2019 Akrevia Therapeutics, a privately held biopharmaceutical company focused on developing highly-potent, tumor-targeted immuno-oncology therapeutics, and City of Hope, an independent research and treatment center for cancer, diabetes and other life-threatening diseases, reported that they have entered into an exclusive licensing agreement that will allow Akrevia to utilize innovative technology to engineer potent immune-activating cytokines that can be selectively activated in the tumor microenvironment (Press release, Akrevia Therapeutics, MAR 26, 2019, View Source [SID1234554019]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The tumor microenvironment has distinct physiological characteristics that can be exploited to help develop tools to deliver therapies that are more precise and potent than existing treatments. The new technology, licensed from the lab of John Williams, Ph.D., at City of Hope, is suited to a broad spectrum of cytokines – molecules for which current tumor activation approaches are not applicable. This novel Switchblade allows inactivated proteins to "flick open" at the point of attack, releasing potent anti-tumor agents precisely where they are needed, thus maximizing efficacy and minimizing the peripheral side effects that limit current cytokine therapies. This new platform can be applied to other highly potent biologic architectures, including diverse cytokine family members, chemokines and agonistic immune modulators which to date have proved intractable in clinical development. This new technology will augment Akrevia’s existing Aklusion platform technologies, and augments the existing technology previously licensed from City of Hope.

"Cytokines have immense promise as highly potent cancer immunotherapeutics, with well-understood biology – but their extreme potency and lack of tumor targeting have thwarted attempts to exploit this clinically," said Tim Clackson, Ph.D., president and executive vice president, R&D, Akrevia Therapeutics. "The new technology licensed from City of Hope will substantially complement our current platform portfolio, providing the ability to target tumor activation of the full range of potent, immune-stimulating molecules. Akrevia will use the newly licensed technology to aggressively advance our pipeline and build towards the next generation of targeted cancer treatments."

Under the agreement, Akrevia gains exclusive commercial rights for application of the technology to the development of proprietary products. City of Hope, internationally recognized for pioneering technology that enabled the creation of numerous breakthrough cancer drugs, developed this technology to help investigators and researchers shield their selected antibodies for targeted therapies and to improve drug delivery. The nonprofit institution is working to improve precision medicine for all patients.

"At City of Hope, our research teams focus on rapidly developing technologies that can quickly move from laboratory research to clinical treatment," said Williams, professor of Molecular Medicine, City of Hope. "Our team has developed a novel approach to unlock the potential of multiple important immuno-oncology mechanisms to deliver potent, targeted agents to patients. We look forward to our continued collaboration with Akrevia to harness the therapeutic potential of this technology with the goal of improving treatment for patients."

On March 26, 2019 BioInvent International AB (OMXS: BINV), a biotech company focused on the discovery and development of novel immuno-regulatory antibodies to treat cancer and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported the extension of their collaboration to co-develop multi-functional oncolytic viruses (OV) encoding for undisclosed antibodies sequences capable of treating a broad range of solid tumors (Press release, Transgene, MAR 26, 2019, View Source [SID1234534629]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the extension agreement, Transgene will contribute its industry-leading OV design and engineering expertise, some non-antibody transgenes, as well as its proprietary engineered vaccinia virus (TK-, RR-) backbone, which forms the basis of its Invir.IO platform. BioInvent will provide its cancer biology and antibody expertise to the collaboration as well as one or more antibodies sequences, generated through its proprietary n-CoDeR/F.I.R.S.T. platforms. Certain sequences for an undisclosed target will be selected for encoding within Transgene’s Invir.IO backbone to create a multi-functional OV.

In November 2018, Transgene and BioInvent presented positive data from their initial collaboration at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These initial data covered the collaboration’s work on an anti-CTLA-4 antibody-armed oncolytic vaccinia virus, based on Transgene’s proprietary vaccinia virus (TK-, RR-) backbone. This enhanced oncolytic vaccinia virus demonstrated its ability to ensure the expression of BioInvent’s anti-CTLA-4 antibody in the tumor with low systemic exposure. It also showed improved efficacy and a better safety profile when compared to the combination of the antibody and the non-armed corresponding oncolytic virus given individually in pre-clinical models.

Consistent with the initial collaboration, research and development costs as well as revenues and royalties from the multifunctional OVs generated as a result of the new collaboration will be shared 50:50.

Encoding BioInvent’s antibodies sequences in Transgene’s proprietary Invir.IO platform, for a direct expression into the tumor, promises to optimize the efficacy and tolerability of these antibodies. Both Transgene and BioInvent believe that these novel multifunctional OVs could be significantly more effective than co-administering an OV and an antibody together.

Commenting on the agreement, Martin Welschof, CEO of BioInvent, said: "The extension of our collaboration with Transgene opens up further opportunities for both companies to combine their expertise and knowledge to develop antibody oncolytic virus combinations capable of treating a broad range of solid tumors. By leveraging BioInvent’s unique and proprietary n-CoDeR/F.I.R.S.T. platforms, we will be able to develop a number of novel first-in-class antibodies that could be delivered directly into the tumor via Transgene’s vaccinia viral backbone, potentially enhancing their efficacy and improving their side effect profile."

Philippe Archinard, PhD, Chairman and CEO of Transgene, said: "We are pleased to extend the scope of our highly productive collaboration with BioInvent. We believe that the next generation of multi-functional oncolytic viruses expressing BioInvent’s highly targeted immune modulators directly in the tumor micro-environment will deliver much improved overall survival outcomes in patients with solid tumors. This agreement further expands Transgene’s broad portfolio of oncolytic viruses in development, the first of which is expected to enter the clinic in 2020."

On March 26, 2019 Charles River Laboratories International, Inc. (NYSE: CRL) reported that its team of oncology experts will attend the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, with 19 scientific posters and two oral presentations to highlight its enhanced oncology portfolio (Press release, Charles River Laboratories, MAR 26, 2019, View Source [SID1234534645]). The meeting is taking place from March 29-April 3, 2019, at the Georgia World Congress Center in Atlanta, Georgia.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Charles River’s team of industry-leading oncology experts have been named as co-inventors on more than 60 patents secured by clients for compounds with an oncology indication, including one launched product, and have produced numerous development candidates in this therapeutic area. Additionally, the Company worked on over 85 percent of all oncology therapies approved by the FDA in 2018. At the AACR (Free AACR Whitepaper) Annual Meeting, researchers will present recent work utilizing emerging tools and approaches for cancer research.

Combination Therapies for Breast Cancer

PARP inhibitors have shown promise when used in combination with immunotherapy in women with breast and ovarian cancers who carry the BRCA mutations. In an oral presentation at the AACR (Free AACR Whitepaper) Annual Meeting, Julia Schueler, DVM, PhD, Research Director at Charles River, will discuss the crosstalk identified between PARP inhibitors and immune checkpoint inhibitors in cell and research models expressing the BRCA mutation. The crosstalk suggests this drug combination might be effective in women suffering from BRCA1-driven malignancies.

Monday, April 1, 3:35-3:50 p.m.: Modulation of the tumor infiltrating lymphocyte population by PARP inhibitor Talazoparib in combination with anti-PD1 treatment significantly enhances overall survival in a murine BRCA1-/- breast cancer model
Collaboration in Pediatric Oncology

Cancer remains the leading cause of death from disease among children, making a continued focus on research in this field extremely important. Charles River has partnered with Meds4Kids Pharma (M4K), an organization using open science to revolutionize how affordable new treatments are discovered and developed.

Since 2017, Charles River has donated drug discovery services to M4K, including medicinal and synthetic chemistry. Working collaboratively with M4K and their open science partners, the team has made progress towards the identification of potent, selective, brain-penetrant ALK2 inhibitors.

At the AACR (Free AACR Whitepaper) Annual Meeting, Sue Cramp, PhD, Team Leader, Chemistry at Charles River, will give an oral presentation on work conducted with M4K, the Ontario Institute for Cancer Research, and the Structural Genomics Consortium. She will discuss their combined efforts to generate an orally-available, brain-penetrant therapeutic to treat Diffuse Intrinsic Pontine Glioma (DIPG), a rare, aggressive, and uniformly fatal childhood brain cancer.

Tuesday, April 2, 3:00-5:00 p.m.: Open science medicinal chemistry: Towards a treatment for DIPG
Additionally, Charles River is a part of the Innovative Therapies for Children with Cancer Paediatric Preclinical Proof-of-Concept Platform (ITCC-P4), a public-private partnership with 21 members focused on establishing 400 new patient-derived xenografts (PDX) of high-risk pediatric tumors. By establishing and characterizing these PDXs, the consortium, funded under IMI2 Grant Agreement No. 116064, aims to build a sustainable, comprehensive platform for more translational drug testing.

Tuulia Huhtala, PhD, Head of Biomarkers and Molecular Imaging at Charles River, will present a poster based on the work done in characterizing these PDXs, which demonstrates the essential role of imaging in both clinical diagnosis and monitoring therapy response. The presentation will review volumetric, metabolic, and functional changes in an orthotopic PDX brain tumor model using MRI, MRS, and PET imaging.

Monday, April 1, 1:00-5:00 p.m.: Translational imaging findings in a pediatric patient-derived orthotopic xenograft brain tumor model
Charles River Launches New Drug Discovery Platforms

At the AACR (Free AACR Whitepaper) Annual Meeting Charles River is also launching a new model for oncology research. The HuPBMC-NCG Humanized Model is a humanized, PBMC-engrafted NCG mouse. This study-ready model eliminates the time, energy, and resources spent validating and humanizing a model, enabling researchers to quickly initiate short-term in vivo studies.

Humanized mice, which harbor human immune cells, can be utilized to test the safety and efficacy of compounds that manipulate the immune system to fight cancer. The HuPBMC-NCG Humanized Model will be commercially available in April 2019.

In addition, Distributed Bio scientists will join the Charles River team to highlight their recently announced partnership. A combination of Distributed Bio’s antibody discovery platform and Charles River’s extensive drug development expertise creates an elite end-to-end solution for therapeutic antibody discovery and development. With access to the Distributed Bio’s SuperHuman, AbGenesis, and Tumbler technologies, clients can discover, analyze, and engineer therapeutic antibodies with unprecedented speed.

A full schedule of Charles River’s activities during AACR (Free AACR Whitepaper) 2019 is available online. Reprints of each poster will be available in Booth 2914 during the conference, and Charles River experts will be available for meetings to discuss how an integrated approach can support drug discovery and development programs from hit identification to IND (Investigational New Drug) filing.

Throughout the conference, Charles River will be providing live updates on the Eureka Blog, including reviews of scientific sessions and input on the research being presented.

Approved Quotes

"Cancer remains a leading cause of death by disease across the globe. Our researchers are committed to finding novel treatments by harnessing innovative tools and methodologies." – Birgit Girshick, Corporate Executive Vice President, Discovery & Safety Assessment, Biologics Testing Solutions, and Avian Vaccine Services at Charles River
"The AACR (Free AACR Whitepaper) Annual Meeting affords us a unique opportunity to share our research in oncology and learn from our peers. I am hopeful that our presentation on the use of combination therapies in breast cancer treatment will inspire continued research in this promising area." – Julia Schueler, DVM, PhD, Research Director at Charles River
"For pediatric cancer patients, time is essential. I am proud that Charles River is part of collaborative groups, like M4K and ITCC-P4, that unite the best minds in the industry to focus on finding the most promising targets." – Ian Waddell, PhD, Executive Director, Biology at Charles River