DURHAM – Precision BioSciences, a genome-editing company based in Durham, has received authorization from the U.S. Food and Drug Administration to advance its second genome-edited cancer therapy to clinical trials.

The FDA has accepted Precision’s Investigational New Drug application for PBCAR20A to treat non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CCL), and small lymphocytic lymphoma (SSL).

Precision’s technology is part of a new approach to fighting cancer using T cells – a type of immune system cell that recognizes invading germs or cancer cells. T cells are engineered to carry a cancer bullet called a tumor-targeting chimeric antigen receptor (CAR). These engineered cells have the potential to save the lives of many patients unresponsive to traditional chemotherapy and radiation regimens.

Precision Biosciences

Precision Biosciences

Autologous CAR T therapies currently on the market rely on patient-derived T cells, which are extracted and individually manufactured for each patient using that patient’s own cells. They require a complex and lengthy process.

Precision’s allogeneic CAR T product candidates use T cells derived from qualified donors. The T cells are manufactured in large batches and are cryopreserved (safely preserved, intact, at extremely low temperatures) for shipment, storage and off-the-shelf use.

These allogeneic CAR T product candidates rely on Precision’s ARCUS genome-editing platform to remove the T cell receptor to prevent graft versus host disease without the need for donor-patient matching. ARCUS editing also enables targeted insertion of the CAR gene into a single, specific location in the T cell genome for more controlled, consistent expression.

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The company said it will begin a Phase1/2a clinical trial later this year in non-Hodgkin lymphoma patients, including a subset of patients with a cancer called mantle cell lymphoma, for which Precision has received the FDA’s Orphan Drug designation.

PBCAR20A is Precision’s second “off-the-shelf” cell therapy. The company is also studying the precursor to PBCAR20A – PBCAR0191 – in adult patients who are not responding to other therapies. Technically, these are designated as patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

Both of Precision’s treatments use the company’s ARCUS genome editing technology to produce CAR T cells derived from healthy donors, rather than relying on cancer patients’ own blood. The development of these allogeneic CAR Ts is designed to overcome the manufacturing limitations of traditional autologous CAR T therapies, to target a broader range of malignancies, and to increase the number of patients who can potentially benefit.

“FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf therapy candidate is a significant milestone for Precision,” said Matt Kane, the company’s CEO and co-founder. “Today’s announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and highly differentiated manufacturing process developed in-house.”

Precision uses ARCUS to remove T cell receptors to prevent graft versus host disease, thus avoiding the need for donor-patient matching that is required in traditional tissue donation procedures. And the ARCUS technology also provides for the targeted insertion of the CAR gene into a single, specific location in the T cell genome for controlled, consistent expression. Precision’s product candidates can be made in advance, manufactured in large batches and then cryopreserved for shipment, storage and off-the-shelf use.

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PBCAR20A, if approved, will fill an important gap in current cancer treatments. In the United States, B-cell malignancies account for 85 percent of all non-Hodgkin lymphoma. And CLL and SLL represent 25 to 30 percent of leukemia cases. Precision said that, while front-line treatments benefit more than half of newly diagnosed NHL patients, at least a third of those achieve only partial remission or relapse after remission.  And patients with CLL have limited success with autologous CAR T therapies. An allogeneic CAR T like PBCAR20A may overcome treatment resistance and offer the possibility of combination treatments.

“It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains,” said David Thomson, Precision’s chief development officer.

Precision Biosciences is a 2006 Duke University spin-out dedicated to improving life by using its ARCUS gene editing technology to treat human diseases and create healthy and sustainable food and agriculture solutions.

In 2018 the company created a new name and brand identity for its food and agriculture business, Elo Life Systems. The business is using Precision’s ARCUS platform and other new technologies for applications in crop improvement, animal genetics, industrial biotechnology and sustainable agriculture.

(C) N.C. Biotech Center