Vyriad's 'In-Body' CAR T Aims to Revolutionize Myeloma Therapy

ROCHESTER, MN – December 16, 2025 – By Daniel Thomas

A potential new era in cancer treatment may be on the horizon as Vyriad, Inc., a Rochester-based biotechnology firm, unveiled striking preclinical data for a novel therapy that could overcome the most significant hurdles facing today’s revolutionary CAR T-cell treatments. At the 67th American Society of Hematology (ASH) Annual Meeting, the company presented findings on its lead candidate, VV169, an in vivo CAR T therapy that completely eliminated multiple myeloma in mouse models without inducing the severe side effects that often complicate current approaches.

The therapy represents a paradigm shift from existing treatments. Instead of a complex, weeks-long process of removing, engineering, and re-infusing a patient's own T cells, VV169 is designed as a single intravenous injection that performs this genetic modification directly inside the body. If proven successful in humans, this “off-the-shelf” approach could dramatically expand access to CAR T therapy, a powerful tool that has so far been limited to specialized medical centers due to its complexity, cost, and risk.

A New Paradigm for CAR T Therapy

Currently, two FDA-approved CAR T-cell therapies, Abecma and Carvykti, have offered new hope for patients with relapsed or refractory multiple myeloma. Both have demonstrated remarkable efficacy by engineering a patient’s T cells to recognize and attack cancer cells expressing a protein called B-cell maturation antigen (BCMA). However, this ex vivo (outside the body) process is a major logistical and clinical challenge.

Patients must undergo apheresis to collect their T cells, which are then cryopreserved and shipped to a central manufacturing facility. There, they are genetically modified with a virus, multiplied into the hundreds of millions, and shipped back to the hospital for infusion into the patient, who has undergone chemotherapy to prepare their body. The entire process can take several weeks, a critical delay for patients with aggressive disease. Furthermore, the treatment carries risks of life-threatening side effects, including Cytokine Release Syndrome (CRS) and neurotoxicity, requiring intensive inpatient monitoring.

Vyriad aims to bypass this entire external manufacturing chain. The company’s in vivo approach uses a specially engineered lentiviral vector—a disabled virus adept at inserting genetic material into cells—to deliver the BCMA-targeting CAR gene directly to a patient’s T cells within their own body. This could transform a bespoke, high-cost procedure into a more scalable, readily available medicine.

“While we have recently seen remarkable proof-of-concept for in vivo CAR T in heavily pretreated multiple myeloma, the next hurdle is eliminating infusional toxicities, so that we can truly unlock the promise of this modality,” said Dr. Stephen Russell, CEO of Vyriad, in a statement. “Our singular focus is solving this technology challenge.”

Impressive Preclinical Results and Safety Signals

The data presented at ASH provides the strongest evidence yet that Vyriad may be on the right track. In humanized mouse models with disseminated multiple myeloma, a single intravenous injection of VV169 led to what the company described as a complete and durable resolution of the disease. Remarkably, 100% of the treated mice cleared their tumors within 28 days, a result that held true even at the lowest dose tested. These mice remained tumor-free for the duration of the 84-day study and were even able to resist a subsequent re-introduction of cancer cells, suggesting the creation of a lasting immunological memory.

Perhaps more importantly, the treatment was exceptionally well tolerated. A key concern with any therapy that powerfully activates the immune system is the risk of a cytokine storm, where inflammatory proteins spiral out of control. Vyriad’s analysis confirmed that while the expected therapeutic T-cell expansion occurred, key inflammatory markers associated with severe CRS, such as IL-6 and TNFα, were “barely detectable.”

This promising safety profile is attributed to key design features. The company utilizes a proprietary T-cell-specific promoter, which acts as a genetic “on switch” to ensure the CAR protein is only produced in T cells. This prevents the CAR from being expressed on the surface of the viral vector itself, minimizing the risk of the therapy being misdirected to other cells or neutralized by the immune system before it can do its job.

The Science Behind Precise Targeting

Delivering a gene therapy precisely to its target inside the human body is a monumental scientific challenge. Vyriad, leveraging its deep expertise in virology and oncolytic viruses, has developed a sophisticated platform to achieve this. The company detailed three distinct strategies for retargeting its lentiviral vectors to selectively transduce T cells.

The approach used for VV169, called “Direct Covalent Display,” involves modifying the virus’s outer envelope protein (VSV-G) so that it no longer binds to its natural receptors on many cell types. Instead, it is engineered to display a ligand that specifically seeks out the CD3 protein, a marker found on the surface of T cells. This acts like a biological key, ensuring the viral vector primarily enters and modifies the correct immune cells.

This focus on precise engineering and safety is critical for gaining regulatory approval. “The preclinical data is striking, but the true test for any in vivo gene therapy is proving safety and controlled activity in humans,” commented one oncology researcher not affiliated with the company. “The regulatory bar is, and should be, incredibly high, with a major focus on off-target effects and long-term safety.”

Navigating the Path from Bench to Bedside

Despite the promising results in mice, the road to clinical use is long and fraught with challenges. The jump from animal models to human patients often reveals unexpected hurdles in safety and efficacy. The U.S. Food and Drug Administration (FDA) imposes stringent requirements on gene therapies, demanding extensive data on manufacturing consistency, vector biodistribution, potential for immune reactions against the vector, and the long-term risk of insertional mutagenesis—where the inserted gene could disrupt a cell’s normal function.

Nonetheless, the potential reward is enormous. Multiple myeloma remains an incurable disease, and patients who have relapsed after multiple lines of therapy face a grim prognosis. The complexity and toxicity of current CAR T options mean many eligible patients are unable to receive them due to poor health, age, or lack of access to a specialized treatment center. An effective, well-tolerated, and scalable in vivo therapy like VV169 could address this profound unmet need.

With a $25 million Series B financing round secured in 2023, Vyriad appears to have the financial runway to advance its lead candidate into the next critical phase. The company announced it is continuing preclinical work and plans to initiate a U.S.-based clinical trial for VV169 in patients with multiple myeloma in 2026. That trial will be the first true test of whether the remarkable promise shown in the lab can translate into a transformative new medicine for patients.