Applied DNA Subsidiary LineaRx Licenses CAR T Drug Candidate and Initiates Pre-Clinical Development of Non-viral, Plasmid-free CAR T Manufacturing Platform
Novel DNA Manufacturing Platform Pioneering a New Generation of Faster, More Affordable CAR T Therapeutics. Offering Available to CRO/CMO Customers
STONY BROOK, N.Y., October, 16, 2018 – Applied DNA Sciences Inc. (NASDAQ: APDN) (“Applied DNA” or the “Company”), the leader in large-scale PCR-based DNA manufacturing, announced today that LineaRx, Inc. (“LineaRx”), its wholly-owned subsidiary focused on next-generation biotherapeutics, has initiated pre-clinical development of a non-viral, plasmid-free (NVPF) chimeric antigen receptor (CAR) modified T cell (CAR T) manufacturing platform which will be made available to CAR T developers worldwide. Concurrently, LineaRx announced the signing of an exclusive North American licensing agreement and research services agreement with iCell Gene Therapeutics, Inc. (iCell) under which iCell licensed to LineaRx an anti-CD19 CAR T therapy for non-viral delivery. LineaRx will utilize its NVPF platform, along with the in-licensed anti-CD19 CAR T therapy, to develop, manufacture and commercialize LinCART19, a non-viral, plasmid free anti-CD19 CAR T drug candidate.
“Since their initial FDA approval in 2017, CAR T therapies have shown unrivaled efficacy against several forms of cancer, but they remain extremely complex to manufacture and are often cost prohibitive,” stated Dr. James Hayward, president and CEO of Applied DNA. “With our expertise in the large-scale PCR-based production and modification of DNA constructs, we believe we are in a unique position to offer a disruptive, inexpensive and safer alternative to established CAR T manufacturing platforms that rely on viral vectors and plasmids. We are excited to have begun pre-clinical development of our NVPF CAR T manufacturing platform to enable a new generation of cell therapies, including our own LinCART19 CAR T therapy, and offering CAR T developers worldwide access to our manufacturing platform upon completion of development.”
Said Dr. Stephen Hughes, Director of DNA Programs at Applied DNA: “CAR T therapies are changing the treatment of cancer, but they must be affordable and accessible to all patients. We believe the approach of the LineaRx team will alter the manufacturing of these life-changing therapies, increasing the speed and safety of production, while lowering the costs.”
LineaRx believes its novel NVPF construction of CAR Ts provides a manufacturing format that would be attractive to many developers of these therapies. Despite costly and inefficient manufacturing platforms, the CAR T market is currently experiencing rapid growth and investment, with over $20 billion in recent M & A activity , and is expected to yield a CAGR of 32.5% at least through 2028 .
The NVPF LineaRx CAR T manufacturing platform under development leverages Applied DNA’s expertise in large-scale PCR-based production and chemical modification of DNA to produce expression vectors for CAR T therapy, without the use of viral vectors or plasmids. LineaRx believes that a NVPF CAR T manufacturing platform confers numerous potential advantages over existing viral/plasmid-based CAR T platforms, including:
Streamlined manufacturing processes will yield reduced cost and lead times, lessening patient morbidity and mortality through shorter “vein-to-vein” times. As seen in the registrational trials for Kymriah® (Novartis International AG) and Yescarta® (Kite Pharma Inc.), the two currently US FDA approved CAR T therapies, up to 31% of intended patients ultimately did not receive treatment primarily due to patient complications during disease progression which evolved during the long manufacturing time required or from manufacturing failures, 
Reduction in the risk of permanent genetic integration/recombination into target cells, reducing the risk of insertional mutagenesis,
The potential mitigation of some current CAR T therapy side effects such as cytokine release syndrome (CRS) and on-target off-tumor toxicity,
The eventual ability to target neoantigens (quickly enough to impact the patient), or the patient-specific protein mutations that accrue in an individual patient’s cancer, and other disease epitiopes beyond cancer, that will allow a patient’s immune system to be the instrument of diverse therapies, and,
The eventual ability to develop CAR T therapies at the point-of-care, obviating complex and burdensome distributed supply chains, and consequently, speeding therapy.
LinCART19 CAR T therapy, which targets the CD19 B cell surface protein expressed on nearly all B-cell malignancies, is the focus of a research agreement between LineaRx and iCell Gene Therapeutics. Development of LinCART19 will benefit from iCell Gene Therapeutics experience in bringing the virally transfected CD19 targeted CAR-T successful into human clinical study as well as their technological leadership in engineering novel, first in class adoptive cell therapies.
After recently announcing a cancer vaccine will utilize its technology, LineaRx is leveraging its NVPF manufacturing platform for its LinCART19 CAR T therapy. This demonstrates the potential breadth of the NVPF platform to produce various biotherapeutics, including gene and cellular therapies as well as vaccines, subject to FDA approval.
Dr. Hayward continued, “We believe our NVPF approach to generate important biotherapeutics without using viruses and plasmids using portable devices can redefine “bench to bedside” therapy. Our Linear DNA PCR devices can be located on site, so the supply chain will never leave the building. We anticipate partnering with other developers to generate fundamentally new drugs from CAR Ts, including using custom epitopes and neoantigens to help usher personalized cancer therapy from a dream to reality.”
2 Coherent Market Insights
3 Allogene Therapeutics, Inc. Form S-1, filed September 14, 2018
CAR T Therapies
CAR T therapies are a revolutionary DNA based approach to destroy cancer cells by harnessing the power of a patient’s own immune system. CD19 is a protein that is expressed on the vast majority of B cell cancers. By targeting CD19 expressing B cells with CAR modified T cells, various B cell malignancies can be addressed. Since 2017, the FDA has approved two CAR T-based therapies targeting the CD19 epitope, opening a new frontier in the fight against cancer.
About iCell Gene Therapeutics, Inc.
iCell Gene Therapeutics is developing proprietary technologies and a pipeline of Chimeric Antigen Receptor (CAR) engineered cell therapies designed to be first in class, cost effective and life saving. Our development operations are focused on creative and efficient paths to bring novel, cost effective therapies to patients. First in human clinical trials are ongoing in US & China, supported by our US research & development organization and a state-of-the-art GMP facility in Zhongshan to manufacture precision-based therapeutics.
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”). Linear DNA is a form of DNA distinct from the circular form of DNA most commonly produced in plasmids and grown in bacteria. Plasmids are extrachromosomal DNA found in bacteria and are associated with the genes for antibiotic resistance which are often exchanged between bacteria and consequentially, are seen by many to embody a serious threat to global health. In addition, many nucleic acid-based therapies also rely on viral vectors for efficient transfection and expression of plasmid DNA. These viral vectors carry additional nontrivial risks and are extremely time consuming and expensive to manufacture.
In all forms of gene therapy, DNA exerts its influence from within the nucleus. Recombinant events for circular DNA are permanent and alter the genomes of the affected cells and their progeny. The fundamental challenge of all gene and cellular therapies is safety. Recent studies have elaborated “unintended consequences” when plasmid and viral vectors are combined that may pose future risks for treated patients.
When linear DNA enters the nucleus, it does not need to be incorporated into the genome to be temporarily expressed as the intended protein product. LineaRx posits that for the effectiveness of genetic vaccines or genetic immune therapies, transient expression may be sufficient.
About Applied DNA Sciences
Applied DNA is a provider of molecular technologies that enable supply chain security, anti-counterfeiting and anti-theft technology, product genotyping and DNA mass production for diagnostics and therapeutics.
We make life real and safe by providing innovative, molecular-based technology solutions and services that can help protect products, brands, entire supply chains, and intellectual property of companies, governments and consumers from theft, counterfeiting, fraud and diversion. The proprietary DNA-based “CertainT®” platform can be used to identify, tag, test, and track products, to help assure authenticity, origin, traceability, sustainability and quality of products.
SigNature® DNA describes the core technology ingredient that is at the heart of a family of uncopyable, security and authentication solutions such as SigNature® T and fiberTyping®, targeted toward textiles and apparel, BackTrac™ and DNAnet®, for anti-theft and loss prevention, and digitalDNA®, providing powerful track-and-trace. All provide a forensic chain of evidence, and can be used to prosecute perpetrators. Applied DNA Sciences is also engaged in the large-scale production of specific DNA sequences using the polymerase chain reaction.
The Company’s common stock is listed on NASDAQ under the symbol APDN, and its warrants are listed under the symbol APDNW.
The statements made by Applied DNA in this press release may be “forward-looking” in nature within the meaning of the Private Securities Litigation Act of 1995. Forward-looking statements describe Applied DNA’s future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to our history of losses, limited financial resources, limited market acceptance and various other factors detailed from time to time in Applied DNA’s SEC reports and filings, including our Annual Report on Form 10-K filed on December 28, 2017 and our subsequent quarterly reports on Form 10-Q filed on February 8, 2018, May 3, 2018 and August 13, 2018, which are available at www.sec.gov. APDN undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof to reflect the occurrence of unanticipated events, unless otherwise required by law.
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