1st lupus patient treated with off-the-shelf FT819 CAR T-cell therapy

Phase 1 trial expected to enroll 32 adults with moderate to severe SLE

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by Steve Bryson PhD |

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A 27-year-old woman with hard-to-treat systemic lupus erythematosus (SLE), the most common type of lupus, became the first patient treated in an early clinical trial evaluating FT819, Fate Therapeutics’ off-the-shelf CAR T-cell therapy candidate.

The Phase 1 study (NCT06308978), taking place at the University of Minnesota Medical School and the University of Nebraska Medical Center, aims to assess FT819’s safety, pharmacological properties, and initial activity in as many as 32 adults with moderate to severe SLE.

In what Fate called a “first-of-kind” experiment, researchers collected blood samples from the woman — diagnosed more than 10 years earlier with SLE — before treatment was administered. They then added FT819 to those samples and waited 24 hours to see the effects the cell therapy might have.

T819 was found to rapidly eliminate B-cells, which are immune cells that drive lupus by producing antibodies, called autoantibodies, that wrongly target healthy tissues.

Three days after treatment, the patient was discharged from the hospital without any notable adverse events, according to a company press release.

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Fate’s CAR T-cell therapy targets protein found on B-cells’ surface

With CAR T-cell therapies, immune T-cells isolated from patients or healthy donors are modified to carry a lab-made chimeric antigen receptor (CAR) that directs them to attack a specific target. FT819’s CAR targets CD19, a protein found on the surface of B-cells. The therapy is designed to deplete B-cells, lower the levels of autoantibodies, control lupus symptoms, and prevent organ damage.

Before receiving a one-time infusion of the cell therapy, patients must undergo a lymphodepletion regimen with chemotherapy agents to eliminate disease-driving immune cells.

A CAR T-cell approach targeting CD19 was recently validated in an academic investigator-sponsored study, which showed that all patients with lupus-related kidney complications achieved drug-free, durable remission.

“The seminal data with autologous CAR-T cell therapy demonstrating early and long-lasting remissions in patients with certain B cell-mediated autoimmune diseases is remarkable, and we are very excited to bring potentially novel therapeutic solutions with disease-modifying potential to our patients,” said Jennifer Medlin, MD, the trial’s principal investigator at the University of Nebraska.

Unlike some other CAR-T cell therapies that require a patient’s own T-cells — known as an autologous treatment — Fate uses a proprietary method to create CAR T-cells from induced pluripotent stem cells (iPSCs). These iPSCs are a type of stem cells that can be created by reprogramming different types of adult cells back to a state in which they can give rise to any type of cell in the body.

According to the company, iPSC-derived CAR T-cells are uniform in composition and can be stored for so-called off-the-shelf use, potentially reaching more patients.

“These solutions may extend to off-the-shelf cell products, such as FT819, which may have the potential to overcome critical challenges that could limit patient access to CAR-T for autoimmune diseases,” Medlin said, citing conditioning chemotherapy and extended hospitalization, among other factors.

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Fate’s platform aims to treat patients with hard-to-treat disease

Fate presented recent data supporting the use of FT819 in lupus at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting, held May 7-11 in Baltimore.

In preclinical studies using blood from lupus patients, FT819 rapidly depleted CD19-positive B-cells in a dose-dependent manner.

The company presented translational data from a Phase 1 study of FT819 in people with hard-to-treat cancers affecting B-cells, or B-cell malignancies (BCM). These data highlighted key therapeutic mechanisms of FT819 for treating autoimmune diseases driven by B-cells.

From blood samples collected from 23 treated BCM patients, FT819 led to the rapid and sustained depletion of CD19-positive B-cells. This was followed by the recovery of naïve and immature healthy B-cells, with little or no recovery of B-cells that produce disease-driving autoantibodies. The therapy also eliminated CD19-positive B-cells in tissues, including bone marrow, lymphoid tissue, and the liver.

We are excited to bring our iPSC product platform and our first product candidates to patients with autoimmune diseases, where preclinical and translational data from our off-the-shelf FT819 CAR T-cell program … demonstrate key therapeutic mechanisms of activity for autoimmunity.

Fate also is developing FT522, a similar CD19-targeted, off-the-shelf CAR therapy using immune natural killer (NK) cells instead of T-cells, for patients with B-cell lymphoma, a type of blood cell cancer. A novel re-challenge assay using blood from lupus patients showed that FT522 rapidly depleted CD19-positive B-cells. Similar results were found using blood from the first two lymphoma patients from a Phase 1 study,

“We are excited to bring our iPSC product platform and our first product candidates to patients with autoimmune diseases, where preclinical and translational data from our off-the-shelf FT819 CAR T-cell program and our FT522 CAR NK cell program demonstrate key therapeutic mechanisms of activity for autoimmunity,” said Scott Wolchko, president and CEO of Fate.

“We believe these programs have a favorable safety profile, offer patient access and convenience, and can deliver the breadth and depth of B cell depletion necessary to induce immune reset in patients with B-cell mediated autoimmune diseases,” Wolchko added.