Vyriad Receives FDA Clearance to Begin Phase 1 Trial of VV169 In Vivo CAR T Therapy for Multiple Myeloma
Vyriad, Inc., a clinical-stage biotechnology company developing targeted genetic therapies for cancer and other serious diseases, announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for VV169, an investigational off-the-shelf in vivo CAR T-cell therapy targeting B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma.
Following the FDA clearance, Vyriad has opened its Phase 1 clinical trial of VV169 for enrollment at Mayo Clinic. The study represents an important milestone for the company as it advances an alternative approach to CAR T-cell therapy that is designed to generate therapeutic CAR T cells directly inside a patient’s body rather than manufacturing the cells outside the body before infusion.
The development of VV169 is based on Vyriad’s proprietary in vivo lentiviral platform, which is designed to deliver genetic payloads directly to selected cell populations. For VV169, the technology is being used to deliver an anti-BCMA chimeric antigen receptor (CAR) payload to T cells following intravenous administration.
If successful, the approach could potentially address some of the logistical and manufacturing challenges associated with conventional autologous CAR T-cell therapies, particularly for patients with aggressive or rapidly progressing cancers who may not be able to wait for an individualized cellular product to be manufactured.
FDA Clearance Marks Important Development Milestone
The FDA’s clearance of the VV169 IND application enables Vyriad and investigators at Mayo Clinic to begin clinical evaluation of the investigational therapy in patients with relapsed or refractory multiple myeloma.
Luke Russell, Ph.D., MBA, President of Vyriad, described the clinical trial opening as a significant milestone for the company and highlighted the collaborative work involved in bringing the program into clinical development.
“VV169 is designed to create CAR-T cells directly inside the body, offering a new way of delivering this powerful therapeutic approach to patients with multiple myeloma,” Russell said.
He noted that the Phase 1 trial being open for enrollment represents an important achievement for Vyriad and its collaborators at Mayo Clinic, including Yi Lin, M.D., Ph.D., and her research team.
Russell also recognized the contributions of investigators, clinical study staff, research and development personnel and manufacturing teams involved in advancing VV169.
The clinical program represents the culmination of years of research and development focused on developing a targeted genetic medicine approach capable of generating CAR T cells directly within the patient.
Developing CAR T Cells Inside the Body
Conventional CAR T-cell therapy generally involves collecting a patient’s own T cells, genetically modifying those cells in a specialized manufacturing facility, expanding the modified cells and subsequently administering them back to the patient.
Although this approach has demonstrated significant therapeutic potential in certain blood cancers, the individualized manufacturing process can be complex and time-consuming. Patients may need to wait while their personalized cell product is prepared, creating challenges for people with rapidly progressing disease.
Vyriad’s VV169 is designed to take a different approach.
Rather than removing T cells from the patient for external modification, VV169 is intended to deliver a CAR genetic payload directly to T cells inside the body. The resulting CAR T cells can then recognize and target cancer cells expressing BCMA.
This in vivo strategy could potentially simplify the delivery of CAR T-cell therapy by eliminating the need for individualized ex vivo cell manufacturing.
The approach is particularly relevant in relapsed or refractory multiple myeloma, where patients may have already received several lines of treatment and may face aggressive disease progression.
Targeting BCMA in Multiple Myeloma
VV169 is designed to target BCMA, a protein expressed on malignant plasma cells and widely studied as a therapeutic target in multiple myeloma.
Multiple myeloma is a cancer of plasma cells that develops primarily in the bone marrow. The disease can cause complications including bone damage, anemia, kidney dysfunction and other serious health problems. Although treatment options have expanded significantly, patients with relapsed or refractory disease continue to face substantial treatment challenges.
BCMA-directed therapies have emerged as an important area of multiple myeloma treatment. Several therapeutic approaches have been developed around the target, including CAR T-cell therapies and other immune-based treatments.
Vyriad’s strategy is to combine BCMA targeting with its in vivo lentiviral delivery technology. The objective is to generate functional CAR T cells within the patient after intravenous administration of VV169.
The company believes this could potentially offer a more accessible approach to CAR T-cell treatment while reducing some of the logistical complexity associated with conventional cell therapies.
Proprietary Targeted Lentiviral Platform
VV169 was developed using Vyriad’s proprietary in vivo lentiviral platform, which is centered on blinded and retargeted VSV-G pseudotyping.
The technology is designed to enable targeted delivery of genetic material to specific cell types. For VV169, the targeted lentiviral vector carries a potent anti-BCMA CAR payload.
Following intravenous administration, the investigational vector is intended to selectively target and transduce T cells. Once the genetic payload is delivered, the T cells can begin expressing the CAR and develop into functional CAR T cells capable of recognizing BCMA-expressing malignant cells.
Vyriad says the targeted approach is designed to achieve highly specific payload expression while minimizing the risk of infusional toxicities.
The ability to generate CAR T cells directly in the body is central to the company’s strategy for developing an off-the-shelf CAR T-cell therapy.
Potential Advantages of an Off-the-Shelf Approach
Stephen Russell, M.D., Ph.D., Chief Scientific Officer of Vyriad, emphasized the potential importance of an off-the-shelf CAR T-cell strategy for patients with aggressive multiple myeloma.
“For patients with aggressive multiple myeloma, waiting weeks for a therapy to be manufactured can be a significant barrier,” Russell said.
He explained that VV169 is designed to create CAR T cells directly inside the body, with the goal of making CAR T-cell therapy more accessible.
Unlike personalized CAR T products that require individual cell collection and manufacturing, an in vivo approach could potentially allow treatment to be administered directly from a ready-to-use therapeutic product.
However, the clinical trial will be important in determining whether the theoretical advantages of the approach translate into meaningful benefits for patients.
The Phase 1 study will provide the first clinical evaluation of VV169 in people with relapsed or refractory multiple myeloma and will generate important information about the therapy’s safety, tolerability, biological activity and preliminary efficacy.
Phase 1 Trial to Enroll Up to 40 Patients
The Phase 1 study is expected to enroll up to 40 patients with relapsed or refractory multiple myeloma.
The trial is being conducted at Mayo Clinic, with Yi Lin, M.D., Ph.D., serving as principal investigator. Lin leads the center’s in vivo CAR T program and will oversee the clinical investigation of VV169.
The primary objectives of the study are focused on establishing the safety profile of the investigational therapy. Investigators will assess overall safety, identify dose-limiting toxicities and determine the recommended Phase 2 dose.
These assessments are essential for determining how VV169 should be administered in subsequent clinical development.
The study will also examine preliminary signs of efficacy. Secondary objectives include evaluating the expansion and persistence of CAR T cells generated in vivo following administration of VV169.
Monitoring CAR T-cell expansion and persistence will be particularly important because these characteristics can provide insight into whether the therapy successfully generates functional CAR T cells within the body and how long those cells remain detectable.
Evaluating a New Model for CAR T-Cell Therapy
The VV169 clinical program represents an effort to address some of the limitations associated with conventional CAR T-cell manufacturing and delivery.
If the investigational therapy demonstrates an acceptable safety profile and evidence of biological activity, it could support further development of an in vivo CAR T-cell platform for multiple myeloma and potentially other cancers.
The Phase 1 trial will therefore provide information not only about VV169 itself but also about the feasibility of Vyriad’s broader genetic medicine approach.
The company’s technology is designed to deliver therapeutic genetic payloads directly to specific cell populations. Applying the platform to CAR T-cell generation could potentially create a new category of cell therapy in which the therapeutic cells are produced inside the patient rather than manufactured externally.
The FDA clearance of Vyriad’s IND application and initiation of Phase 1 enrollment mark significant milestones in the development of VV169.
The investigational therapy combines BCMA-directed CAR T-cell technology with Vyriad’s targeted in vivo lentiviral delivery platform. By generating CAR T cells directly within the body, the company aims to develop an off-the-shelf approach that could potentially overcome some of the manufacturing and logistical limitations associated with conventional autologous CAR T-cell therapies.
The Phase 1 trial at Mayo Clinic will evaluate VV169 in up to 40 patients with relapsed or refractory multiple myeloma. Investigators will focus initially on safety, dose-limiting toxicities and determining a recommended Phase 2 dose, while also assessing preliminary efficacy signals and the expansion and persistence of in vivo-generated CAR T cells.
The study’s results will help determine whether VV169 can safely generate functional BCMA-directed CAR T cells in patients and whether the approach warrants continued clinical development.
For Vyriad, the trial represents the transition of its in vivo genetic medicine platform into human clinical testing. As enrollment progresses, the company expects clinical data to provide important insights into the potential of VV169 and the broader feasibility of producing CAR T cells directly within the body.
The Phase 1 trial is registered on ClinicalTrials.gov under NCT07802717, where additional information regarding the study, enrollment criteria and trial design is available.
About Vyriad
Vyriad is a clinical-stage biotechnology company developing targeted genetic medicines for cancer and other serious diseases. The company uses engineered viruses, viral vectors, and viral envelope glycoproteins to deliver therapeutic genes directly to selected cells. Vyriad’s programs include oncolytic virotherapy, in vivo gene therapy, and gene editing applications, with ongoing Phase 1–2 trials in multiple cancer indications. Vyriad is a privately held company based in Rochester, Minnesota.