Vironexis Biotherapeutics’ AAV Vector-Based Immunotherapy VNX-101 Cleared for US Trial in Acute Lymphoblastic Leukemia
VNX-101 is intended to transduce cells of the liver, causing them to express a transgene coding for a bispecific T-cell engager.
Vironexis Biotherapeutics has received clearance of its investigational new drug (IND) application from the FDA for VNX-101, an adeno-associated virus (AAV) vector-based gene therapy, enabling a phase 1/2 clinical trial in CD19+ acute lymphoblastic leukemia.1
VNX-101 is intended to transduce cells of the liver, causing them to express a transgene coding for a bispecific T-cell engager. This T-cell engager, which binds to CD19 on tumor cells and CD3 on T-cells, is intended to facilitate the targeted killing of the cancer cells by endogenous T-cells. It is based on the company’s TransJoin platform, which it is also working on applying to a variety other cancers through different investigational products; these other therapeutic candidates currently remain in preclinical development. The announcement of the IND clearance also coincides with the company’s exit from stealth, and follows a $26 million round of seed financing.
“We’re excited to launch Vironexis from stealth and reveal our noteworthy progress advancing AAV-delivered T-cell immunotherapy,” Samit Varma, the cofounder and chief executive officer of Vironexis, said in a statement.1 “Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as chimeric antigen receptor T-cell (CAR-T) therapy 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. Our focus on execution has yielded an expansive pipeline and a clinic-ready lead program in just 3 years. We’re working as quickly as possible to transform the future of cancer treatments for patients.”
In light of the IND clearance, Vironexis anticipates initiation of the planned phase 1/2 trial within the final quarter of this year. According to Vironexis, VNX-101 will be the first AAV vector-based immunotherapy for the treatment of cancer to enter clinical trials. Preclinical research regarding technology key to the TransJoin platform, carried out by Timothy Cripe, MD, PhD, the chief of the division of pediatric hematology/oncology/bone and marrow transplant at Nationwide Children’s Hospital, and cofounder and board member of Vironexis, and colleagues, was previously published in Science Advances in 2022.2
“In summary, we propose that long-term stable expression of biotherapeutics achievable by gene transfer can be leveraged to solve both the problem of fluctuating drug levels inherent to traditional administration routes and the cumbersome mechanics that accompany continuous intravenous infusions,” Cripe and colleagues wrote in the journal publication.2 “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. We also developed a companion TransSkip on-switch that enables on-demand expression for scenarios in which only short-term or intermittent expression is preferable. These technologies conceptually open a broad new area of gene therapy to solve therapeutic challenges extending well beyond the correction of single-gene disorders.”
Notably, VNX-101 is not the first AAV vector-based gene therapy in general to be applied to cancer.3 Ferring Pharmaceuticals’ nadofaragene firadenovec (Adstiladrin), an AAV vector-based gene therapy that encodes a transgene for interferon alfa-2b protein, was approved by the FDA in 2022 for the treatment of adult patients with high-risk, Bacillus Calmette-Guerin-unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors. In 2024, Ferring launched 3 new postmarketing clinical trials for the therapeutic.4
