Off-the-shelf CAR cell therapy to enter SLE trial next year

Patients without response to at least 2 immunosuppressives will be enrolled

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has cleared Century Therapeutics to start a Phase 1 clinical trial that will test its off-the-shelf cell therapy CNTY-101 in people with systemic lupus erythematosus (SLE).

The Phase 1 study will enroll people with moderate to severe SLE who’ve failed to respond to at least two standard immunosuppressive medications. Century expects the trial will start in the first half of 2024, with initial data expected by year’s end.

“Today marks an important milestone in Century’s evolution as a company,” Brent Pfeiffenberger, Century’s CEO, said in a company press release.

In lupus, the immune system produces self-reactive antibodies that attack healthy tissue. This abnormal immune attack is driven in part by B-cells, the type of immune cell that makes antibodies.

Several CAR therapies, which have the ability to direct immune cells toward a specific molecular target, are in development for lupus, particularly targeting B-cells.

Most use an autologous approach, meaning immune cells (usually T-cells) are harvested from a patient and equipped with a chimeric antigen receptor, or CAR, before being infused back into the patient.

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What is CNTY-101 designed to do?

CARs are human-made cell surface proteins that prompt the modified immune cells to recognize a particular molecule of the surface of other cells, promoting a deadly attack against them.

Using a patient’s cells may help reduce the risk of abnormal reactions to foreign cells, but that imposes technical and logistical constraints on these types of therapies.

CNTY-101 is designed to destroy B-cells. It’s made of immune natural killer (NK) cells derived from a single stem cell source that are engineered with a CAR that targets CD19, a B-cell protein. A type of cell therapy that doesn’t use a patient’s own cells is called allogeneic.

“We believe the unique profile of CNTY-101, which incorporates multiple precision edits including our Allo-Evasion technology, positions it as an off-the-shelf allogeneic treatment option that could meaningfully improve outcomes for patients with SLE for whom existing therapies fall short,” Pfeiffenberger said.

In addition to the CD-19-targeting CAR, the modified NK cells are equipped with a suite of other molecular tweaks to improve cell function and survival, once infused. These include Allo-Evasion edits that are designed to evade recognition and destruction by the immune system and a molecular safety switch that lets the delivered NK cells be quickly eliminated in the body through administration of a specific medication.

In the upcoming Phase 1 trial, people with hard-to-treat SLE will receive one to two cycles of three weekly doses of CNTY-101. Before the first dose, participants will undergo a lymphodepletion regimen where chemotherapies are given to wipe out the patient’s immune cells.

The study will evaluate the therapy’s safety, tolerability, pharmacokinetics, and effectiveness. Pharmacokinetics refer to a therapy’s movement into, through, and out of the body.

The FDA’s clearance for a CNTY-101 trial in SLE marks the second indication the therapy is being tested in. The CAR NK cell therapy is in a Phase 1 trial (NCT05336409) for hard-to-treat cancers associated with the overgrowth of B-cells. Data from this study helped support Century’s application for a trial in SLE.

“The expansion of the CNTY-101 program into SLE represents a significant achievement for the company, and, importantly, serves as a testament to the unwavering dedication of our team as we continue to execute on our mission to advance differentiated and potentially curative cell therapies to patients with cancer and autoimmune and inflammatory diseases,” Pfeiffenberger said.