Vironexis's One-Time In Vivo Therapy Drives Complete Responses in Relapsed ALL

Vironexis Biotherapeutics announced encouraging early results from the ongoing SENTRY-CD19 study of VNX-101, its investigational one-time in vivo immunotherapy for CD19-positive hematologic malignancies.¹ Among the first three patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) who tested negative for anti-adeno-associated virus antibodies at baseline, all three achieved measurable residual disease (MRD)-negative complete responses following a single administration of VNX-101, confirmed by clonoSEQ.¹ One patient, who also had extensive extramedullary disease, achieved a complete response at all disease sites on PET imaging within 28 days.¹

How does VNX-101 work?

Rather than manufacturing engineered cells outside the body, VNX-101 is designed to turn a patient's own liver into a biofactory that produces GP101, a CD19/CD3 bispecific T-cell-engaging protein, following a single infusion.¹ The approach delivers the genetic instructions for a therapeutic protein directly in vivo, aiming to combine the potency of T-cell engagers with the convenience of a one-time treatment rather than repeated infusions.¹ VNX-101 has received FDA Fast Track, Orphan Drug, and Rare Pediatric Disease designations.¹

What do the early data show?

All three responding patients remain MRD-negative, with the first patient sustaining a complete response through day 260, at which point the treating physician proceeded to hematopoietic stem cell transplantation while the patient remained in MRD-negative complete response.¹ Notably, the T-cell-engaging protein was still detectable at therapeutic levels post-transplant, demonstrating durability through at least nine months post-infusion.¹ Vironexis said this marks a first for the field: evidence that a systemically delivered, one-time in vivo therapy can translate into durable clinical antitumor activity in blood cancer, including extramedullary disease.¹

"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/CD3 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. We believe the depth, consistency, and emerging durability of these responses provide important clinical validation of our in vivo therapeutic protein platform, and compelling proof of concept for its potential to transform the body into a meaningful, durable source of highly active cancer therapeutics."¹

Why does an in vivo approach matter for ALL treatment?

Adults with R/R ALL face a historically difficult prognosis: complete remission rates after first salvage therapy have hovered around 40%, dropping to roughly 21% after second salvage and 11% after third or later salvage, with three-year survival after first salvage around 11%.² The disease is also rare among adults, with an estimated 2,000 to 3,000 new US cases diagnosed annually.³

Vironexis's platform belongs to a broader push toward therapeutics generated inside the patient's own body rather than manufactured externally. Ryan Larson, PhD, SVP, head of research at Umoja BioPharma, addressed that broader shift in a 2025 interview, though speaking about in vivo chimeric antigen receptor (CAR) T-cell approaches generally rather than VNX-101 specifically: "Yet access to ex vivo autologous cell therapies continues to be a challenge wherein a large fraction of patients that may be eligible for those therapies are not able to gain access to them for a variety of reasons."⁴

What are the safety considerations?

The observed safety profile is consistent with the potent immune activation expected from a CD19/CD3 T-cell-engaging therapy.¹ Immune-mediated events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, occurred during dose escalation and fully resolved with standard-of-care management; Vironexis said dose and treatment-management approaches remain under evaluation.¹

What happens next?

The broader SENTRY-CD19 trial has dosed nine patients across US sites spanning ALL, diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, and Vironexis intends to prioritize development of VNX-101 in antibody-naive R/R ALL.¹ Study sites in South Korea have been approved and are expected to activate in the coming weeks.¹ Vironexis also named former Amgen CEO Kevin Sharer as board chairman and Nobel laureate James Allison, PhD, to its scientific advisory board.¹

References

1. Vironexis Biotherapeutics. Vironexis Announces Complete and Durable Responses in Relapsed/Refractory ALL Patients Treated with VNX-101. Press release. Published September 21, 2026. Accessed September 22, 2026.
2. Gökbuget N, Dombret H, Ribera J-M, et al. International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica. 2016;101(12):1524-1533. doi: https://doi.org/10.3324/haematol.2016.144311
3. Jabbour EJ, Park J. Relapsed Refractory B-Cell ALL: Patient Prognosis. OncLive. Published January 25, 2022. Accessed September 22, 2026.
4. Haigney S. ASGCT 2025: Emerging Modalities for Cancer Treatments. BioPharm International. Published May 12, 2025. Accessed September 212 2026.