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Umoja Biopharma’s technology is designed to overcome the key limitations of CAR-T therapy, eventually making it possible to have “off-the-shelf” CAR-Ts that are more accessible to patients. Umoja Biopharma’s VivoVec platform has generated in vivo chimeric antigen receptor T cells, or CAR-T cells, in nonhuman primates, according to new data presented by the company Sept. 1 during the annual CAR-TCR Summit in Boston. The CAR-Ts also appeared to have activity against target cells and continued proliferating for more than a month in one of the animals. "Our hope is that the replication of these data in our early clinical trials will lead to a new class of in vivo CAR-T cell therapeutics that expand the breadth of reach of CAR-T cell therapies by reducing costs and logistical complexity of delivery and by offering an immediate, off-the-shelf, product that generates autologous, patient-specific CAR-T cells," Andy Scharenberg, M.D., Umoja's co-founder and CEO, told Fierce Biotech Research via email. Umoja’s technology programs a patient's T cells against their cancer in vivo—that is, without ever having to remove the T cells from their body, as currently approved therapies require, or transferring them from donors as occurs with next-generation allogeneic therapies like Allogene's. Instead, Umoja uses lipid nanoparticles it's dubbed VivoVec particles to activate, integrate and express the CAR in a patient’s own T cells. This replaces the expensive, time-consuming process of extracting and transducing the cells with CARs using viral vectors before re-implanting them back into the patient, steps that can be marred by vector shortages and the possibility of manufacturing failure or low yields. The platform also negates the need for chemotherapy to clear out a patient’s blood cells. Back in May at the American Society of Gene & Cell Therapy’s annual conference, Umoja reported preclinical data on VivoVec in mice. In the new studies, the researchers injected four male and female pigtail macaque monkeys in the groin-area lymph nodes with a single, clinically relevant dose of the VivoVec particles designed to generate anti-CD20 CARs, the type used to target B-cell lymphoma. The team then monitored the animals for CAR-T cell activation and expansion as well as toxicity. None of the monkeys received chemotherapy beforehand. In three of the primates, CD20 CAR-T cells peaked at about 40% to 60% of total circulating T cells at their peak. The same three monkeys also had persistent B-cell aplasia, a sign that the CAR-Ts were working. The numbers for most of the animals exceeded the benchmark for ex vivo CAR-T therapies in a similar primate model, Scharenberg told Fierce. In a 2018 study on rhesus macaque monkeys that underwent chemotherapy followed by CAR-T infusion, the engineered cells proliferated to a peak of 272 to 4,450 CAR-T cells per microliter; their B-cell aplasia lasted between 35 and 42 days.  In Umoja's latest study, the CAR-T cells in two of the monkeys peaked at between 5,000 and 10,000 cells per microliter and their B-cell aplasia lasted beyond 42 days. In another, the researchers detected a large secondary CAR-T cell expansion around Day 49 or 50, "suggesting that VivoVec may capture aspects of memory T cell biology that are difficult or impossible to capture with ex vivo CAR-T cell manufacturing processes," Scharenberg wrote. While the therapy was largely well tolerated, there were a few side effects in two of the animals—though none out of the ordinary for CAR-T therapy, and less serious than what was seen in the 2018 study on an ex vivo treatment. The most serious was a mild cytokine release syndrome and neurotoxicity event that culminated in a single seizure, to which the monkey responded to single doses of the appropriate medications. The primate experiments are ongoing; more data from them will be presented at medical conferences in the fall, Umoja said in the release. The company currently has a piece of its technology in clinical trials at Seattle Children’s Hospital and plans to submit a request to the FDA in the first half of 2024 to take its first VivoVec-based therapy into human studies. Editor's note: This story has been updated to clarify the technology in clinical trials at Seattle Children's Hospital and the timeline for submitting a request for its first VivoVec-based therapy. 

Preliminary data from ongoing preclinical study include rapid, durable chimeric antigen receptor (CAR) T cell generation in vivo after a single infusion of VivoVec particles Additional data to be presented at future medical conferences SEATTLE, Sept. 01, 2023 (GLOBE NEWSWIRE) -- Umoja Biopharma, Inc., a transformative immuno-oncology company creating off-the-shelf treatments for solid and hematologic cancers, today announced new data from an ongoing non-human primate (NHP) study demonstrating effective, durable, and well tolerated in vivo chimeric antigen receptor (CAR) T cell generation using the Company’s VivoVec™ platform technology at the 8th CAR-TCR Summit taking place in Boston, MA, August 29 - September 1, 2023. The data include results from the first four NHPs treated in an ongoing study and demonstrate rapid and efficient in vivo generation of anti-CD20-targeting CAR T cells following a single infusion of Umoja’s multidomain fusion (MDF) VivoVec particles without the administration of pre-conditioning lymphodepleting chemotherapy. Additionally, these data suggest that the CAR T cells generated in vivo demonstrated on-target activity and persistent T cell memory. “In vivo CAR T technology has the potential to transform the cell therapy paradigm by providing an off-the-shelf, patient-specific solution for those with serious conditions, including cancers,” said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. “These data highlight the incredible progress Umoja has made and the potential of our unique delivery platform to effectively generate CAR T cells in vivo. Beyond a single therapeutic, our platform could enable the delivery of virtually any CAR construct, creating the opportunity for Umoja to address a broad range of cancers and unlock the true potential of CAR T cell therapies.” Executive Vice President of Discovery Research & Vector Biology, Byoung Ryu, Ph.D., added, “These results build on our previously presented preclinical data and highlight the ability of our VivoVec particles to efficiently generate CAR T cells in vivo. Beyond the generation of CAR T cells, we are observing on-target CAR activity and durable cell survival, which could potentially translate to significant clinical benefits for patients. We look forward to providing updates on this study at a future medical conference.” Key results include: Following a single VivoVec administration, anti-CD20 CAR T cells were generated in vivo with peak levels of CAR T expansion occurring between days 7-10 CD20 CAR T demonstrated on-target activity resulting in durable B-cell aplasia In three animals treated at the planned clinical dose—and without preconditioning chemotherapy— peak CD20 CAR+ cells comprised ~40-60% of total circulating T-cell volume, including the demonstration of central memory T-cell responses In the first animal, additional independent CAR T cell expansions were observed after day 30 No toxicity was associated with VivoVec administration About Umoja Biopharma Umoja Biopharma, Inc. is an early clinical-stage company advancing an entirely new approach to immunotherapy. The Company is a transformative multi-platform immuno-oncology company founded with the goal of creating curative treatments for solid and hematological malignancies. Founded based on pioneering work performed at Seattle Children’s Research Institute and Purdue University, Umoja’s novel approach is powered by integrated cellular immunotherapy technologies including the VivoVec™ off-the-shelf in vivo delivery platform and the RACR™/CAR in vivo cell expansion/control platform. Designed from the ground up to work together, these platforms are being developed to create and harness a powerful immune response in the body to directly, safely, and controllably attack cancer. Umoja believes that its approach can provide broader access to the most advanced immunotherapies and enable more patients to live better, fuller lives. To learn more, visit . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements about Umoja Biopharma, Inc. (the “Company,” “we,” “us,” or “our”). The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results to vary materially, including, among others, the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of the Company’s current and future research and development programs, preclinical and clinical trials, as well as any economic, market and social disruptions. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Umoja Media Contact: Karissa Cross, Ph.D. LifeSci Communications kcross@lifescicomms.com