Vironexis Reports MRD-Negative Complete Responses in All Three Antibody-Naive R/R ALL Patients Treated With One-Time AAV Therapy VNX-101
核心洞察
All three anti-AAV antibody-naive patients with relapsed or refractory ALL in the Phase 1/2 SENTRY-CD19 (搜索) trial achieved MRD-negative complete responses after a single VNX-101 administration.
Responses showed durability, with the first patient remaining MRD-negative through Day 260 and the T-cell engager GP101 still detectable at therapeutic levels beyond nine months.
VNX-101 delivers an AAV vector that transduces hepatocytes to secrete GP101, a CD19xCD3 bispecific T-cell engager, aiming to replace repeated or continuous protein infusions.
Vironexis Biotherapeutics (搜索) reported that all three anti-AAV antibody-naive patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (搜索) (ALL) enrolled in the ongoing Phase 1/2 SENTRY-CD19 (搜索) trial achieved measurable residual disease (MRD)-negative complete responses after a single administration of VNX-101, the company's investigational one-time in vivo immunotherapy. All three responses were confirmed by clonoSEQ. The data were announced on September 21, 2026.
One of the three patients, who also had extensive extramedullary disease, achieved a complete response at all disease sites on PET imaging by Day 28.
Durability Through at Least Nine Months
The responses have shown encouraging durability in this difficult-to-treat population. All three patients remain MRD-negative. The first patient maintained complete response through Day 260, at which point the treating physician elected to proceed to hematopoietic stem cell transplantation while the patient was in MRD-negative complete response. The T-cell-engaging protein was still detected at therapeutic levels post transplant, demonstrating durability through at least nine months after infusion.
These observations are notable because VNX-101 is given once rather than through repeated or continuous protein infusions.
"While early, these results are highly encouraging after delivering just a single, off-the-shelf administration of VNX-101, which enables the body to produce a CD19 (搜索)/CD3 (搜索) T-cell-engaging protein," said Samit Varma, Chief Executive Officer of Vironexis. "These three patients have tried multiple lines of therapy and, sadly, exhausted available treatment options."
Mr. Varma said the depth, consistency and emerging durability of the responses provide clinical validation of the company's in vivo therapeutic protein platform. He added that VNX-101 has achieved what the company believes is a first for the field: demonstrating that a systemically delivered, one-time in vivo therapy can translate into clinical antitumor activity in patients with blood cancer and extramedullary disease.
Mechanism: Liver as a Biofactory
VNX-101 is designed to turn a patient's own liver into a "biofactory" capable of producing GP101, a CD19 (搜索)/CD3 (搜索) bispecific T-cell-engaging protein, following a single administration. The AAV vector transduces hepatocytes to continuously secrete GP101, which simultaneously binds CD19-positive cancer cells and CD3-expressing T cells, redirecting cytotoxic T cells to kill tumor cells. The approach is intended to combine the potency of T-cell-engaging therapeutics with the potential convenience and durability of a one-time treatment.
Safety and Dose Optimization
The safety profile observed to date is consistent with the potent immune activation expected from a CD19 (搜索)/CD3 (搜索) T-cell-engaging therapy and is informing ongoing dose optimization. Immune-mediated events, including cytokine release syndrome (搜索) (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS (搜索)), were observed during dose escalation and completely resolved with standard of care. The company continues to evaluate dose and treatment-management approaches within the ongoing study.
Trial Design and Expansion
SENTRY-CD19 (搜索) (NCT06533579) is a Phase 1/2, first-in-human, open-label, dose-escalating study assessing the safety and efficacy of VNX-101 in patients with relapsed or refractory CD19-positive hematologic malignancies. The trial is active across nine national clinical sites, with the core principal site at UT MD Anderson Cancer Center. Nine patients have been dosed across the broader study, spanning ALL, diffuse large B-cell lymphoma (搜索), follicular lymphoma (搜索) and chronic lymphocytic leukemia (搜索).
Based on the emerging clinical profile, Vironexis intends to prioritize development of VNX-101 in antibody-naive R/R ALL. International expansion is underway, with SENTRY-CD19 (搜索) sites in South Korea approved and expected to activate in the coming weeks.
Regulatory Status and Pipeline
VNX-101 holds U.S. FDA (搜索) Fast Track, Orphan Drug and Rare Pediatric Disease designations. Vironexis emerged from stealth in September 2024 with USD 26 million in seed financing and described VNX-101 as the first AAV-delivered cancer immunotherapy to enter clinical testing. The company's second program, VNX-202, is enrolling adult patients in a Phase 1/2 study targeting HER2 (搜索)-positive malignancies.
Board and Advisory Appointments
Vironexis also announced the appointment of Kevin Sharer, former chief executive officer of Amgen, as Chairman of its Board of Directors, and Nobel Prize laureate James Allison, Ph.D., to its Scientific Advisory Board. Dr. Allison is the Regental Professor and Chair of Immunology, Vice President of Immunobiology and Founding Director of the James P. Allison Institute at The University of Texas MD Anderson Cancer Center.
"I'm delighted to join Vironexis' Board of Directors as Chairman at this exciting time for the company, as it unveils highly encouraging initial clinical data demonstrating the potential of its revolutionary new approach to one-time, off-the-shelf in vivo immunotherapy," Mr. Sharer said.
Competitive Context in R/R ALL
The R/R ALL landscape includes Amgen's Blincyto (blinatumomab), the only approved CD19xCD3 bispecific T-cell engager, which shares the same pharmacological mechanism as GP101 but requires continuous intravenous infusion over 28-day cycles. Autologous CAR-T therapies, including Kite Pharma (搜索)'s Tecartus (brexucabtagene autoleucel), Novartis's Kymriah (tisagenlecleucel) and Autolus (搜索)'s Aucatzyl (obecabtagene autoleucel), can produce durable responses after a single infusion but require individualized ex vivo manufacturing that typically takes three to six weeks, a constraint in rapidly progressing R/R ALL. VNX-101's off-the-shelf, pre-manufactured and systemically administered approach could address this access gap, although the current dataset of three antibody-naive ALL patients is too small to draw comparative conclusions.