LineaRx initiates development of non-viral, plasmid-free CAR T manufacturing platform 17th October 2018
Applied DNA Sciences, the leader in large-scale PCR-based DNA manufacturing, announced yesterday that 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, 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,3
- 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.”