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Research Publication Demonstrates Utility of Applied DNA’s LinearDNA™ in Non-Viral CAR T Manufacturing Systems

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.

Imvax Presents Data Showing Mechanisms for Broad Immune Activation by IGV-001

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.

"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.

Carevive Launches Clinical Oncology Program in Collaboration with NorthShore University HealthSystem to Improve Cancer Treatment

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.

"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.

Wugen Announces Data Presentation at The Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting

On November 9, 2021 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf memory natural killer (NK) cell therapies to treat a broad range of hematological and solid tumor malignancies, reported it will present new data highlighting the preclinical development of Wugen’s lead product WU-NK-101 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting (Press release, Wugen, NOV 9, 2021, View Source [SID1234594939]).

The data highlight Wugen’s proprietary large-scale feeder-cell free manufacturing process and demonstrate WU-NK-101’s robust memory phenotype and enhanced anti-tumor activity. Further, the data demonstrate that in combination with monoclonal antibodies, WU-NK-101 exhibits enhanced efficacy against solid tumor cell lines. In summary, the data provide support for development of WU-NK-101 as an off-the-shelf cell therapy for the treatment of acute myelogenous leukemia (AML) and solid tumors.

The details of Wugen’s presentation at SITC (Free SITC Whitepaper) are as follows:

Title: Development of WU-NK-101, a feeder cell-free expanded allogeneic memory NK cell product with potent anti-tumor activity
Presenting Author: Mary E. Mathyer, Ph.D.
Abstract Number: 188
Abstracts will be available Tuesday, November 9, 2021, at 8:00 a.m. ET
Additional meeting information can be found on the SITC (Free SITC Whitepaper) website at:
View Source

Noxopharm Announces DARRT-2 Clinical Trial in U.S.

On November 9, 2021 Australian clinical-stage drug development company Noxopharm (ASX:NOX) reported its DARRT-2 Phase 2 clinical trial has commenced with patient enrollment in the U.S (Press release, Noxopharm, NOV 9, 2021, View Source [SID1234594938]).

DARRT (Direct and Abscopal Response to Radiotherapy) is an experimental immunotherapy cancer treatment based on the concept of Veyonda combining with a well-tolerated, low dosage of external beam radiotherapy to trigger an immune response — known as an abscopal response — which may lead to the resolution of tumors.

DARRT treatment has the potential to revolutionize cancer treatment by achieving cancer reduction without many of the unwanted side effects, cost limitations, and logistical challenges associated with other immunotherapies.

Since low dose radiotherapy is a common form of cancer therapy, the therapeutic and commercial opportunities of adding Veyonda to transform symptomatic relief into a meaningful tumor response are substantial. Noxopharm is confident of securing the value of this opportunity by patents, starting with the allowance of claims by the U.S. Patent Office.

The inaugural sites are the Beverly Hills Cancer Center and the MD Anderson Cancer Center, with remaining sites in North America, Europe, and Australia.

Noxopharm Chief Medical Officer, Dr. Gisela Mautner, said, "The participation of institutions with prestigious radiation and medical oncologists is testament to the potential of the DARRT-treatment."