Applied DNA Subsidiary LineaRx Achieves Biotech Industry First with Anti-CD19 Expression in Human CAR T Cells via Proprietary Non-Viral, Plasmid-Free Platform

April 8, 2019 Off By BusinessWire

Novel DNA Manufacturing Platform Seeks to Pioneer New Generation of
Faster, More Affordable Cell-based Therapeutics for Patients

STONY BROOK, N.Y.–(BUSINESS WIRE)—Applied DNA Sciences, Inc. (NASDAQ:APDN) announced today that LineaRx,
(the “Company”), its subsidiary focused on next-generation
biotherapeutics, has achieved anti-CD-19 CAR (Chimeric Antigen Receptor)
expression in human T Cells via its proprietary, non-viral, plasmid-free
(NVPF) manufacturing platform. To the Company’s knowledge, this seminal
event represents the first time that a human T cell has been shown to
express an anti-CD19 CAR from a gene construct utilizing linear DNA
produced via a scalable PCR (Polymerase Chain Reaction) manufacturing
process. The Company views this development as an important option for
all gene therapies that currently use virus-delivery platforms, but
especially for immune-oncology therapies that use virus delivery of
synthetic genes to redirect a patient’s T cells, known as CAR therapy.

LineaRx’s unique PCR-based manufacturing technology created the linear
DNA amplicon encoding the anti-CD19 engager, and that construct was then
electroporated into human T cells ex vivo. Subsequent testing has
yielded anti-CD19 expression from these engineered cells. While these
preliminary data are encouraging, overall levels of expression were
initially low and LineaRx continues working on generating higher
transfection levels using the patent-pending High Expression Amplicon
(HEA™) and methods of transfection other than electroporation and will
report further progress on this significant achievement as it emerges.

Dr. James A. Hayward, president and CEO of Applied DNA, stated: “Our
goals are three-fold: 1) To establish the value of PCR-produced linear
DNA as a platform for the rapid design and production of therapeutic
nucleic acid constructs, including at the point of care; 2) To prove the
improved safety and therapeutic value of NVPF production streams, which
are distinct from industry-wide viral-based production; and, 3) To bring
our NVPF-based anti-CD19 CAR T cell therapy to the clinic with a future
partner.

This accomplishment builds upon another first instance of engineering
human T cells via a linear DNA amplicon produced, designed and
manufactured via LineaRx’s PCR technology in late 2018. The first
instance demonstrated a linear DNA amplicon that contained the complete
gene that encoded production of Green Fluorescent Protein (GFP). As seen
in the microscope image above, the uptake and subsequent expression of
the PCR-generated GFP gene fragment in hundreds of human T cells,
facilitated by high-throughput electroporation, created a
“constellation” of green fluorescent cells.

In October 2018, LineaRx
announced the signing of an exclusive North American licensing and
research services agreement with iCell Gene Therapeutics for an
anti-CD19 CAR T therapy. Leveraging Applied DNA’s expertise in
large-scale PCR-based production and chemical modification of DNA,
LineaRx will utilize its NVPF platform to develop and produce expression
vectors for CAR T therapies, including for LinCART19™, its non-viral,
plasmid-free anti-CD19 CAR T drug candidate.

As
discussed at the LinearRx Analyst Day in December 2018, the CAR-T
gene construct upon which LinCART19 is based, led to 3 of 3 complete
remissions in patients with acute lymphocytic leukemia (ALL) at 6 months
after a single low-dose treatment in a clinical trial conducted in China
under local regulations. While these promising clinical results provide
evidence in the value of the genetic code utilized, the CAR T cells were
transfected via viral vector. LinCART19 will utilize linear DNA
transfected by either electroporation, soluporation, or other mode of
delivery into T Cells.

Without the use of viral vectors or plasmids, LineaRx’s NVPF
manufacturing platform holds numerous potential advantages over existing
viral/plasmid-based CAR T approaches offering the possibility of more
efficient, affordable and safer gene therapies for patients.

Forward-Looking Statements

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 its history of net
losses, limited financial resources, limited market acceptance , the
uncertainties inherent in research and development, future clinical data
and analysis, including whether any of Applied DNA’s product candidates
will advance further in the preclinical research or clinical trial
process, including receiving clearance from the U.S. Food and Drug
Administration or equivalent foreign regulatory agencies to conduct
clinical trials and whether and when, if at all, they will receive final
approval from the U.S. FDA or equivalent foreign regulatory agencies,
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 18, 2018 and our subsequent quarterly report on Form 10-Q
filed on February 7, 2019, and other reports we file with the SEC, which
are available at www.sec.gov.
Applied DNA 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.

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 pre-clinical nucleic acid-based therapeutic drug
candidates.

Applied DNA makes 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.

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Common stock listed on NASDAQ under the symbol APDN, and warrants are
listed under the symbol APDNW.

About LineaRx

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.