Vironexis Biotherapeutics has announced FDA clearance of its Investigational New Drug (IND) application for VNX-101, an adeno-associated virus (AAV) vector-based gene therapy, paving the way for a Phase 1/2 clinical trial in patients with CD19+ acute lymphoblastic leukemia (ALL). This clearance marks a significant step forward in the development of novel immunotherapies for hematologic malignancies.
VNX-101 is designed to transduce liver cells, prompting them to express a transgene that codes for a bispecific T-cell engager. This engager binds to CD19 on tumor cells and CD3 on T-cells, effectively bridging the two to facilitate targeted killing of cancer cells by endogenous T-cells. The therapy is based on Vironexis’s proprietary TransJoin platform, which the company is also exploring for application in other cancers.
TransJoin Platform and Clinical Development
The TransJoin platform is designed to enable the expression of a secreted T cell engager that binds the tumor cell on one side and T cells via CD3 on the other side. Following a single, one-time intravenous infusion, the TransJoin technology instructs the liver to continuously secrete the bispecific protein into the bloodstream to redirect T cells to tumor cells.
The IND clearance coincides with Vironexis emerging from stealth mode, backed by a $26 million seed financing round. Samit Varma, co-founder and CEO of Vironexis, stated, “Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as CAR-T and bispecific antibodies. We believe we have the opportunity to dramatically improve upon the safety, efficacy and durability of these drug classes, while streamlining manufacturing and significantly lessening the burden of treatment for patients.”
The Phase 1/2 trial is expected to commence in the fourth quarter of 2024. VNX-101 has received both Fast Track Designation and Rare Pediatric Disease Designation from the FDA, underscoring the unmet need in this patient population.
Mechanism of Action and Preclinical Data
Preclinical research on the TransJoin platform, led by Timothy Cripe, MD, PhD, at Nationwide Children’s Hospital, was published in Science Advances. The study highlighted the potential of long-term, stable expression of biotherapeutics achieved through gene transfer to address the challenges of fluctuating drug levels and cumbersome administration routes associated with traditional therapies.
Cripe and colleagues wrote, “For cancer, the advantage of our strategy is not only the single therapeutic administration rather than frequent clinic and hospital visits but also the prospect of long-term, consistent pressure on tumor cells that could address persistent micrometastatic disease that mediates relapse.”
Context within AAV Gene Therapy Landscape
While VNX-101 represents a novel approach in AAV vector-based immunotherapy for cancer, it is not the first AAV-based gene therapy to be applied to cancer. Nadofaragene firadenovec (Adstiladrin), an AAV vector-based gene therapy encoding interferon alfa-2b, was approved by the FDA in 2022 for high-risk, Bacillus Calmette-Guerin-unresponsive non-muscle invasive bladder cancer.
