On December 13, 2021 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported the presentation of new preclinical data on vecabrutinib, a reversible inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK), in oral and poster presentations at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Viracta Therapeutics, DEC 13, 2021, View Source [SID1234596984]).
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The oral presentation featured preclinical data indicating that vecabrutinib may enhance the efficacy and safety of CD19-targeted chimeric antigen receptor T (CART19) cell therapy. Though CART19 cell therapy has been shown to effectively treat certain hematological malignancies, rates of long-term durable response after therapy are low and the majority of patients develop resistance. Additionally, CAR T-cell therapies are associated with significant safety concerns such as cytokine release syndrome and neurotoxicity.
Key findings from the oral presentation include:
Vecabrutinib increased the cytotoxic activity of CART19 cells and maintained their proliferation capacity
Vecabrutinib enhanced CART19 cell anti-tumor activity in a murine mantle cell lymphoma model
Vecabrutinib reduced the level of pro-inflammatory cytokines known to cause toxicities associated with CAR T-cell therapy; these observations were consistent with data from a prior Phase 1 clinical trial evaluating vecabrutinib as a treatment for patients with B-cell malignancies
In a direct comparison with ibrutinib, only vecabrutinib continued to induce CAR-T cell proliferation at high doses
"These compelling preclinical findings demonstrate the potential of vecabrutinib to improve the efficacy of CAR T-cells while ameliorating many of the concerns that currently prevent their use outside of inpatient settings," said Ayman Elguindy, Ph.D., Chief Scientific Officer of Viracta. "If translated to the clinic, the positive effects of vecabrutinib could potentially expand the use and tolerability of CAR T-cell therapies and improve the outlook for patients with a variety of cancers."
In addition to the oral presentation, a poster presentation detailed preclinical findings of vecabrutinib in a murine model of sclerodermatous cGVHD, a complication occurring in patients following allogeneic stem cell transplantation. Data showed that vecabrutinib significantly reduced cGVHD symptoms including skin irritation, redness, alopecia, and diarrhea via modulation of pathogenetic B- and T-cell subsets.
Ivor Royston, M.D., President and Chief Executive Officer of Viracta, commented, "We believe vecabrutinib’s differentiated reversible kinase inhibitory profile and ability to modulate immune-related signaling pathways give it the potential to overcome the shortcomings of ibrutinib when combined with CAR T-cell therapy. Looking ahead, we are strategically evaluating clinical development options to assess the combination of vecabrutinib and CART19 cell therapy."
A copy of the ASH (Free ASH Whitepaper) presentations will be available by visiting the Events and Webcasts page of the Viracta website following the conference’s conclusion.
About Vecabrutinib
Vecabrutinib is a well-tolerated, selective, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Vecabrutinib is being studied as a potential enhancer of efficacy and safety of CAR T-cell therapy.