On July 30, 2025 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing difficult to treat cancers, reported that its collaboration partner, PeriNess Ltd. ("PeriNess"), has entered into a Clinical Study Agreement (the "Agreement") to support an exploratory clinical study of DNase I in combination with anti-CD19 CAR T cells in patients with large B cell lymphoma (Press release, Xenetic Biosciences, JUL 30, 2025, View Source [SID1234654644]).

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Dr. Ron Ram, Professor of Medicine and Head of the Bone Marrow Transplantation Unit at the Tel Aviv Sourasky Medical Center ("Sourasky Center"), will act as the principal investigator of the study.

The primary objective of this study is to explore the safety and tolerability of DNase I in combination with anti-CD19 CAR T therapy in subjects with stable or progressive large B-cell lymphoma when DNase I is given in an adjuvant setting. Secondary objectives include efficacy to be evaluated by the measure of complete response rate post CAR T infusion, duration of response and overall survival. The study has the potential for a strong translational component with a complex assessment of biomarker response and analysis of anti-CD19 CAR T expansion and persistence.

"Our data suggests that the degradation of Neutrophil Extracellular Traps (NETs) by DNase I plays a crucial role in maintaining CAR T-cell function and preventing premature CAR T-cell exhaustion. Our preclinical studies conducted show that co-administration of DNase I with anti-CD19 CAR T cells significantly reduce tumor burden, delay tumor relapse and substantially prolong survival compared to the anti-CD19 CAR T cell monotherapy groups in various syngeneic and xenogeneic experimental models of lymphoma and leukemia," stated Alexey Stepanov, PhD, Institute Investigator at the Scripps Research Institute, and a member of Xenetic’s Scientific Steering Committee.

"Progression of large B cell lymphoma (LBCL) is the major obstacle for the success of CAR T therapies, with approximately 40-60% of the patients relapsing in the first year, and 25-35% within 3 months after CAR T infusion, depending on the CAR T product used. While patients with partial or complete response before CAR T infusion have a 1-year progression free survival of 60-80%, those with stable or progressive disease at the time of CAR T infusion have a 1-year progression free survival of 20-30%. NETs facilitate several hallmarks of cancer biology at various stages, including progression, invasion, metastasis, immunosuppression, immune escape, and resistance to therapy. A high content of NETs in lymphoma tissue and blood of patients was associated with a negative outcome. The goal of this clinical study is to improve clinical response by administering DNase I to abrogate the negative effects of NETs on the performance of immune system and CAR T cells," added Dr. Ram.

James Parslow, Interim Chief Executive Officer and Chief Financial Officer of Xenetic concluded, "We are pleased with the continued progress of our DNase I program and the expansion of its development in another exploratory study to further evaluate its potential in various oncology indications. We look forward to garnering additional data to realize the full potential of DNase I."

As previously announced, in December 2024, Xenetic entered into a Clinical Trial Services Agreement with PeriNess, under which PeriNess will lead in the regulatory approval, operational execution and management of potential exploratory, investigator-initiated studies of recombinant DNase I as an adjunctive treatment in patients with pancreatic carcinoma and other locally advanced or metastatic solid tumors receiving chemotherapy and immunotherapy in Israeli medical centers.