FDA OKs Phase 1 study of two-component immunotherapy

First patient should be enrolled in clinical trial in second half of 2024

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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The U.S. Food and Drug Administration (FDA) has approved a clinical trial to evaluate the safety and effectiveness of Synthekine‘s two-component immunotherapy for the treatment of certain patients with lupus, without using lymphodepletion, a process in which chemotherapy is used beforehand to eliminate disease-causing immune cells.

The multicenter, dose escalation Phase 1 clinical trial will assess the safety and effectiveness of SYNCAR-001 plus STK-009 in systemic lupus erythematosus (SLE) patients without kidney involvement, as well as in those with lupus nephritis, a lupus complication marked by kidney inflammation and damage. The first patient is expected to enroll in the study in the second half of the year.

Patients enrolled in the trial will receive a single dose of SYNCAR-001 and a limited course of STK-009, which will be administered weekly as an under-the-skin (subcutaneous) injection.

In lupus, immune B-cells produce self-reactive antibodies that target the body’s own healthy tissues. Lupus nephritis is among the disease’s most severe manifestations, with up to 30% of patients progressing to kidney failure.

SYNCAR-001 is a CAR T-cell therapy that targets CD19, a protein found on B-cells that are involved in various autoimmune diseases, including lupus and blood cancers. This CAR T-cell therapy uses a patient’s own immune T-cells, which are engineered in the lab to express a lab-made receptor, or chimeric antigen receptor (CAR), that’s specifically designed to recognize CD19.

Generally, before undergoing treatment with a CAR T-cell therapy, patients must undergo a process called lymphodepletion, in which chemotherapy agents are given to wipe out a patient’s disease-causing immune cells. However, lymphodepletion is associated with significant side effects.

“Lymphodepleting chemotherapy may increase the risk to patients with SLE who already have significant comorbidities. This requirement also limits access to many patients who have marrow and organ dysfunction related to their underlying SLE,” Amit Saxena, MD, associate professor of medicine at NYU Grossman School of Medicine, said in a company press release.

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STK-009 is given with SYNCAR-001

Current limitations of CAR T-cell therapies also include the risk of low activity and/or short persistence once cells are infused back into a patient. To overcome these limitations, STK-009 is given in combination with SYNCAR-001. STK-009 is an engineered version of interleukin (IL)-2, a signaling molecule that’s important for T-cell expansion, survival, and function.

STK-009 was designed with Synthekine’s proprietary orthoIL-2 technology to specifically stimulate the CAR T-cells in SYNCAR-001, which are equipped with a unique IL-2 receptor that can only receive a signal from STK-009.

“Synthekine’s cytokine-inducible CD19 CAR-T cell therapy has the potential to address critical segments of the patient population who face these barriers and offer them the remarkable potential benefit of this breakthrough approach to treating a devastating disease,” Saxena said.

According to Synthekine, the two-component immunotherapy increases the activity of CAR T-cells and enhances their persistence, which contributes to better and more durable clinical responses. Additionally, this approach allows the use of lower doses of CAR T-cells to reduce toxicity and eliminate the need for lymphodepletion.

“Recent studies have shown that CD19 targeted cell therapies can make a meaningful impact on non-renal SLE, [lupus nephritis] and other autoimmune conditions,” said Naiyer Rizvi, MD, chief medical officer at Synthekine. “However, successful treatment with CD19 CAR-Ts requires patients to be lymphodepleted, a significant burden on the patient, physician and healthcare system. By leveraging Synthekine’s orthoIL-2 technology, STK-009 has the potential to drive SYNCAR-001 cell engraftment and controlled cell expansion without lymphodepletion. We look forward to bringing our highly differentiated treatment option to patients.”

The two-component immunotherapy is also being tested in a multicenter, dose-escalation Phase 1 study (NCT05665062) in patients with distinct types of lymphoma, a type of blood cancer.