Umoja Biopharma's In Situ CAR-T Therapy UB-VV111 Fast Tracked for Several R/R B-Cell Malignancy Indications

The FDA has granted fast track designation to Umoja Biopharma's UB-VV111, a gene therapy product intended to create CD19-directed chimeric antigen receptor (CAR) T-cells within the body, for the treatment of relapsed/refractory (r/r) large B-cell lymphoma that has previously been treated with at least 2 prior lines of therapy and for the treatment of r/r chronic lymphocytic leukemia that has previously been treated with at least 2 prior lines of therapy.¹

UB-VV111 is currently being evaluated in a phase 1 clinical trial (NCT06528301) for adult patients with r/r CD19+ B-cell malignancies. The study, which launched on March 10, 2025, includes 2 treatment arms: an arm in which patients receive UB-VV111 alone and an arm in which patients receive UB-VV111 and subsequent rapamycin.

UB-VV111, an off-the-shelf treatment, is intended to overcome some of the drawbacks associated with the standard ex vivo approach to CAR-T therapy, such as long wait times and high-cost manufacturing. Notably, under an existing agreement, the biopharmaceutical company AbbVie has the exclusive option to license UB-VV111 and Umoja’s other CD19-directed in vivo CAR-T therapy candidates.

“This fast track designation marks a key milestone in the advancement of in vivo CAR T-cell therapies,” Luke Walker, MD, the chief medical officer of Umoja Biopharma, said in a statement.¹ “UB-VV111 continues to lead the in vivo CAR T-cell field in the United States, and today’s announcement further reinforces its potential to address unmet needs in the treatment of those living with relapsed/refractory B-cell malignancies. This achievement is a testament to the dedication of our clinical trial sites and to the patients who inspire our mission every day.”

The investigational new drug (IND) application enabling the phase 1 trial was cleared by the FDA in July of last year.² UB-VV111 is based on Umoja’s VivoVecTM gene delivery platform, which utilizes third generation lentiviral vectors and a T-cell targeting and activation surface complex. Notably, preclinical data regarding UB-VV111 was previously presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.³ The data came from humanized mice and nonhuman primates (NHPs) treated with VivoVec particles.

“The data from these studies show efficient generation of CAR T-cells in vivo at the planned clinical trial dose,” Byoung Ryu, PhD, the executive vice president of discovery research & vector biology at Umoja, said in a December 2023 statement.³ “CAR T-cell expansion correlates with rapid and durable B-cell aplasia in NHPs within our study which exceeds the current ex vivo CAR T cell benchmarks. Importantly, we continue to see no acute toxicity associated with VivoVec particle administration.”

Although Umoja’s approach to in vivo CAR-T is based on the use of a lentiviral vector, there may be other viable ways to produce in vivo CAR-T products. Earlier this year, CGTLive® spoke to Robert Alexander Wesselhoeft, PhD, the director of RNA Therapeutics at the Gene and Cell Therapy Institute (GCTI) at Mass General Brigham (MGB), at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, about general trends in the field of RNA therapy. Wesselhoeft pointed out the potential of RNA for applications in in vivo CAR-T.

“With RNA in general, what I'm seeing is a huge number of companies that are working on in vivo CAR-T: basically making CAR T-cell therapy an injectable drug,” Wesselhoeft told CGTLive. “Of course, that will be revolutionary for the CAR-T space and pretty much every CAR-T drug that's been developed or in development, of which there are many, will likely switch over to using RNA as soon as that clinical proof of concept is there. My guess is that that's going to happen within the next 2 years or so.”

REFERENCES
1. Umoja Biopharma Announces that UB-VV111 Receives FDA Fast Track Designation for Relapsed/Refractory B-Cell Malignancies. News release. Umoja Biopharma. September 30, 2025. Accessed October 3, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-announces-that-ub-vv111-receives-fda-fast-track-designation-for-relapsed-refractory-b-cell-malignancies/
2. Umoja Biopharma Announces FDA Clearance of IND Application for UB-VV111, a CD19 Directed in situ CAR T for Hematologic Malignancies. News release. Umoja Biopharma, Inc. July 31, 2024. Accessed October 3, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-announces-fda-clearance-of-ind-application-for-ub-vv111-a-cd19-directed-in-situ-car-t-for-hematologic-malignancies
3. Umoja Biopharma presents preclinical data at the 65th American Society of Hematology annual meeting demonstrating in vivo CAR T cell generation with potent and highly durable activity. News release. Umoja Biopharma, Inc. December 11, 2023. Accessed October 3, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-presents-preclinical-data-at-the-65th-american-society-of-hematology-annual-meeting-demonstrating-in-vivo-car-t-cell-generation-with-potent-and-highly-durable-activity/