On November 9, 2021 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported preclinical data supporting the mode of action of BT-001, their novel dual mechanism-of-action oncolytic Vaccinia virus. The data demonstrate high intratumoral expression of an immune checkpoint-inhibiting antibody and robust anti-tumoral activity in several tumor models (Press release, Transgene, NOV 9, 2021, View Source [SID1234594944]).

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BT-001, developed by BioInvent and Transgene, is a clinical phase oncolytic virus engineered to deliver an anti-CTLA-4 antibody and human GM-CSF in a tumor-specific vehicle (the VVcopTK-RR- virus backbone) for the treatment of solid tumors.

The companies’ poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021) shows that BT-001 selectively replicates in tumor cells. The murine surrogate of BT-001 delivered sustained and high intratumoral levels of antibody accompanied by low systemic exposure. These differential expression levels were associated with high depletion of intratumoral regulatory T cells (Treg) but the absence of systemic Treg depletion. Similar effects in humans would allow BT-001 to deliver powerful antitumor immunity.

Patient inclusion into the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) is progressing well. The multicenter trial, authorized in Europe and in the U.S., is assessing BT-001 as single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab for the treatment of solid tumors. Initial Phase I data are expected in the first half of 2022.

Other data highlighted in the SITC (Free SITC Whitepaper) poster show improved survival in several syngeneic tumor models following treatment with a murine version of BT-001. There is also evidence of a positive synergistic effect between the murine ‘BT-001’ oncolytic virus expressing the CTLA-4 antibody and a systemic PD-1 checkpoint inhibitor.

"These impressive data, demonstrating the multiple mechanisms of action and anti-cancer properties of BT-001, played a key role in our decision to take this unique oncolytic virus into the clinic. We are pleased to be able to share them with our scientific and clinical peers at SITC (Free SITC Whitepaper)" said Martin Welschof, CEO of BioInvent and Hedi Ben Brahim, Chairman and CEO of Transgene.

SITC 2021 will take place on November 10–14, 2021, at the Walter E. Washington Convention Center in Washington, D.C. and virtually. The poster, entitled "Vectorized Treg-depleting aCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject "cold" tumors", will be presented on the Virtual ePoster Hall and presented in the Poster Hall (Hall E) on Saturday, November 13, 2021.

Authors: Monika Semmrich, Jean-Baptiste Marchand, Matilda Rehn, Laetitia Fend, Christelle Remy, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur and Björn Frendéus.

Abstract and poster number: 746

About BT-001
BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody will be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.

On November 9, 2021 Palleon Pharmaceuticals, a company pioneering the field of glyco-immunology to treat cancer and inflammatory diseases, reported data on a novel mechanism of action of the company’s EAGLE sialoglycan degradation therapeutic platform (Press release, Palleon Pharmaceuticals, NOV 9, 2021, View Source [SID1234594943]). Preclinical studies, presented in a poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), show that EAGLE therapeutic candidates’ desialylation of T cells enhances T cell anti-tumor immunity, and that lead candidate E-602 (Bi-Sialidase) is efficacious and safe in animal models.

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"The exciting package of data we are presenting at SITC (Free SITC Whitepaper) demonstrates for the first time that Palleon’s EAGLE platform could offer a novel immunomodulatory approach to enhancing T-cell immunity for cancer treatment," said Li Peng, Ph.D., Chief Scientific Officer of Palleon and the poster’s principal author. "These findings will bolster our upcoming IND filing for E-602 and continue to deepen our understanding of the therapeutic potential of the EAGLE platform."

Upregulation of sialoglycans on tumors has been observed for decades and correlates with poor clinical outcomes across many tumor types. Recent findings made possible by advances in the tools used to study glycobiology have shown that these sialoglycans are immunosuppressive. In addition to tumor cells, most immune cells present substantially more abundant sialoglycans than non-hematological healthy cells, which may also contribute to immunosuppression. Palleon utilized various assays to study the effect of E-602 on naïve, exhausted, and effector T cells. These studies found that desialylation by E-602 enhanced naïve T cell priming/activation, restored exhausted-like T cell functions, and enhanced effector T cell function.

Further studies evaluated the single-agent antitumor activity of E-602 in multiple syngeneic mouse tumor models, and its safety profile in rat and non-human primate models. These studies found that E-602 demonstrated single-agent antitumor activity and a wide safety margin.

On November 9, 2021 Applied DNA Sciences, Inc. (NASDAQ: APDN) (Applied DNA or the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, reported the publication of a study in Molecular Therapy: Methods and Clinical Development on a methodology for the manufacture of novel types of CAR constructs that employ the Company’s LinearDNA as part of a manufacturing process for the efficient generation of CD19-specific CAR T-cells (CAR19 T-cells) based on co-electroporation of a LinearDNA transposon and mRNA encoding of piggyBac transposase (Press release, Applied DNA Sciences, NOV 9, 2021, View Source [SID1234594942]). PCR-produced LinearDNA is manufactured by LineaRx, the Company’s majority-owned subsidiary, to serve as a pure, fast, and flexible alternative to plasmid DNA (pDNA) for biotherapeutic applications.

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The study, titled "Enzymatically produced piggyBac transposon vectors for efficient non-viral manufacturing of CD19-specific CAR T cells", details the utility of LinearDNA in the cost-effective production of preclinical CAR T cells. Its authors, members of the Institute of Hematology and Blood Transfusion (ÚHKT) in Prague, Czechia, and the Faculty of Natural Sciences at Charles University, also in Prague, propose that the combination of LinearDNA and a transposon/transposase system offers therapy developers an effective research tool for making experimental CAR T cells rapidly and efficiently without the need for complicated virus production or the use of pDNA.

Pavel Otáhal, contributing author and Head of the Gene Immunotherapy Research Department at ÚHKT, stated, "Our study compares the manufacture of CAR19 T-cells via PCR-made transposon DNA (LinearDNA) with mRNA encoding of the transposase against a conventional plasmid approach. We found CAR T efficacy of the LinearDNA system versus the plasmid system to be identical. Further, we found no mutations in the coding sequence of LinearDNA and with >99% purity that obliviated the need for purification typical of a plasmid approach. As an institution dedicated to diagnosing and treating serious blood diseases and with the ability to pursue investigational medicines from development to manufacture and clinical trial for patients who have exhausted all approved treatment options, having a cost-effective and rapid production chain is integral to ÚHKT’s mission. We find LinearDNA to be an excellent platform for CAR T-cell therapy development."

Dr. James A. Hayward, president and CEO of Applied DNA, said, "The clinical successes of CAR T-cell therapy against blood cancers have been impressive, though limited by the complex production of viral vectors that are currently needed for T-cell genetic transformation and the use of pDNA. These manufacturing complexities have likewise hindered research on CAR T-cell therapies. As described in the publication, the use of LinearDNA, coupled with non-viral transfection systems, we believe, overcomes many of the existing manufacturing complexities associated with pDNA and viral vectors, thereby offering therapy developers a rapid and cost-effective tool for manufacturing preclinical CAR T cells. The authors’ findings as it relates to LinearDNA coincide with the industry’s growing interest in alternatives to pDNA for CAR T-cell therapies with approximately 50% of recent CRO orders coming from CAR T cell developers."

The detailed study write-up can be found at: Molecular Therapy: Methods and Clinical Development, the leading journal for research in the areas of gene transfer, vector development and design, stem cell manipulation, development of gene-, peptide-, protein-, oligonucleotide-, and cell-based therapeutics to correct genetic and acquired diseases, vaccine development, preclinical target validation, safety/efficacy studies, and clinical trials.

About LineaRx, Inc., and LinearDNA

LineaRx seeks to commercialize the biotherapeutic value of Applied DNA’s deep expertise and experience in the design, manufacture, and chemical modification of DNA by large-scale polymerase chain reaction ("PCR") via its LinearDNA Platform.

The LinearDNA Platform is a proprietary large-scale PCR-based manufacturing platform that allows for the large-scale production of specific high-fidelity DNA sequences. Unlike plasmid-derived DNA, LinearDNA is free of adventitious DNA sequences and can be chemically modified to optimize the DNA for specific applications. The LinearDNA platform is currently being used by customers to manufacture DNA as components of in vitro diagnostic tests and for preclinical nucleic acid-based drug development in the fields of adoptive cell therapies (CAR T and TCR therapies), DNA vaccines (anti-viral and cancer), RNA therapies, clustered regularly interspaced short palindromic repeats-based (CRISPR) therapies and gene therapies, as well as the Company’s COVID-19 veterinary vaccine candidate.

On November 9, 2021 Imvax, Inc., a clinical-stage biotechnology company developing personalized, whole tumor-derived immunotherapies, reported data showing the mechanisms by which IGV-001 produces broad immune activation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Imvax, NOV 9, 2021, View Source [SID1234594941]). The data from in vitro and in vivo studies highlight the effects of IGV-001 on inducing both innate and adaptive immune responses to tumor cells and point to the potential mechanism behind observed clinical activity for IGV-001 in the treatment of glioblastoma.

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"These exciting mechanistic data substantiate the anti-tumor effects we’ve observed in prior clinical trials of IGV-001. The insights reported here will inform our ongoing clinical development of IGV-001 for glioblastoma, a disease in great need of effective new treatments," said John P. Furey, Chief Executive Officer. "Importantly, these studies also underscore the potential expansion of Imvax’s approach to a wide range of solid tumors and bolster our ongoing preclinical work in hepatocellular, ovarian, pancreatic, and other cancers."

For these in vitro studies, IGV-001 was prepared with patient tumor cells. It was then co-cultured with patient-derived peripheral blood mononuclear cells (PBMCs) to evaluate activated and memory T cell subsets and responses. These studies found an elevated percentage of activated potentially anti-tumor CD4 and CD8 T cells as well as increased central and effector memory phenotypes in both T cell subsets compared to IMV-001-treated PBMC controls. Tumor cells treated with Insulin-like Growth Factor-1 Receptor antisense ‘IMV-001’ also released significantly more (p<0.01) ATP than untreated or sense oligonucleotide-treated controls, suggesting immunogenic cell death.

In vivo studies were performed on C57BL/6 albino mice. Biodiffusion chambers were loaded with either IMV-001 or a saline control, plus GL261-Luc cells, irradiated and implanted into the mice’s flanks for 48 hours, similar to the combination product dosed in investigator-initiated Phase 1 studies of IGV-001 and planned for dosing in the Company’s upcoming Phase 2 clinical trial (NCT04485949). GL261-Luc intracranial tumor challenge was conducted 28 days after chamber implantation. At the termination of the study, 58 days post–intracranial tumor challenge, 59% of IGV-001-treated mice were alive and continued to gain weight, whereas all mice in the control group died by day 24 (p<0.001). Additionally, IGV-001-treated mice with lower tumor burden had less circulating IL-6 (P<0.01), pointing to a means of quantifying IGV-001’s suppression of tumor growth. Finally, Elispot assays demonstrated that mice treated with IGV-001 showed enhanced T cell IFNγ responses to tumor cell antigens, compared to controls.

On November 9, 2021 Carevive Systems ("Carevive") the leading oncology-focused health technology company centered on understanding and improving the experience of patients with cancer, reported that it has entered into a clinical research collaboration with NorthShore University HealthSystem (NorthShore) to utilize Carevive’s Patient Reported Outcomes Mobile Platform (PROmpt) system in the collection of critical patient data (Press release, Carevive Systems, NOV 9, 2021, View Source [SID1234594940]). Part of Carevive OPT-IN, a consortium of clinician investigators utilizing PROmpt, the NorthShore partnership will capture real-world patient data that will help improve the overall patient experience during treatment. PROmpt will summarize clinical, anecdotal, and demographic information associated with patient treatment, in an effort to positively improve patient outcomes.

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"The patient information accumulated during our collaboration with NorthShore will enable the PROmpt system to collect patient data in real-time that is critical to understanding both medical and quality of life needs of cancer patients, and learn where care improvements are necessary," said Debra Wujcik, PhD, RN, FAAN, VP, Research and Clinical Operations with Carevive. "Our PROmpt platform offers a highly efficient and fully-integrated data capture system that allows our clinical partners at NorthShore to gather knowledge about the entire patient experience and use that information to make the necessary care and treatment modifications. It is our hope that the patient registries developed during these studies will enable us to impact future patient care within other clinical settings."

The PROmpt patient self-assessment platform system, allows cancer patients the ability to receive important information once they report they are experiencing a new symptom. This information will help guide each patient on their care journey and on what steps to take next with their clinical care team. Using the PROmpt system, clinicians now have the tools to care and monitor patients remotely using the system’s platform. The data capture consists of a simple-to-use process that includes a direct patient registration, initial and weekly surveys, automated program response, and clinical notification. Each data set retrieved through this process will be used by NorthShore’s clinicians to not only improve overall patient care, but to also tailor modifications that are unique to each patient and address those impediments to treatment success.

"Carevive’s integrated patient platform holds great promise in capturing and understanding the data that is essential for the development of successful cancer treatment programs by our clinical teams," stated Nicklas Pfanzelter, M.D. and Oncologist, NorthShore University HealthSystem. "Our alliance with Carevive underscores NorthShore’s commitment to those cancer patients receiving treatment within our hospital network and, also those newly-diagnosed who may present themselves in the future. We look forward to partnering with Carevive and the application of our integrated clinical and technical capabilities to help improve cancer treatment."

Anyone interested in learning more about Carevive OPT-IN or benefits of the PROmpt system, can visit the Carevive website.