Early Phase I/II data from San Diego-based Vironexis Biotherapeutics show that a single dose of an adeno-associated virus (AAV)-based gene therapy can produce measurable residual disease (MRD)-negative complete responses in patients with relapsed or refractory acute lymphoblastic leukemia (ALL) — and sustain them for months without repeat dosing. The finding, reported September 21, provide an early clinical signal that a systemically delivered, one-time in vivo gene therapy can generate durable antitumor activity in blood cancer patients, including those with extramedullary disease.
All three anti-AAV antibody-naive R/R ALL patients enrolled in the SENTRY-CD19 study achieved MRD-negative complete responses after a single infusion of VNX-101, confirmed by clonoSEQ. One patient with extensive extramedullary disease achieved complete responses at all disease sites on PET imaging within 28 days. All three patients remain MRD-negative, with the first patient maintaining complete response through Day 260 before proceeding to hematopoietic stem cell transplantation. The T-cell-engaging protein GP101 was still detectable at therapeutic levels post-transplant, demonstrating persistence of at least nine months following a single administration. Immune-mediated adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were observed during dose escalation but resolved with standard of care. Vironexis said the safety profile is informing ongoing dose optimization.
VNX-101 works by delivering an AAV vector that transduces hepatocytes to continuously secrete GP101, a CD19×CD3 bispecific T-cell engager that simultaneously binds CD19-positive cancer cells and CD3-expressing T cells, redirecting cytotoxic T cells to kill tumor cells. The approach is designed to combine the pharmacology of a bispecific T-cell engager with the convenience of a single administration.
Nine patients have been dosed across the broader SENTRY-CD19 study, spanning ALL, diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. Vironexis said it intends to prioritize development in antibody-naive R/R ALL based on the emerging clinical profile.