Folate-Fluorescein

Looking at mice with xenografts of folate receptor-expressing tumor cells, researchers saw that UB-VV200 controlled solid tumor growth in a dose dependent manner—the more TagCAR T cells that were generated, the smaller the tumor volume. It’s a statistic that haunts David Fontana, Ph.D., chief operating officer of Umoja Biopharma: At a time when manufacturing space is hard to come by, as many patients die waiting for CAR-T cell therapy as are actually treated. “Physicians … are having to choose which patient [gets the therapy]. Do we go with the sick elderly one that has no hope, or the healthy one that can probably survive?” Fontana told Fierce Biotech at the American Society for Gene and Cell Therapy’s (ASGCT's) annual meeting. “I’ve started calling them the ‘Goldilocks patients’: The ones who aren’t too sick, not too well. You’re narrowly defining these patients simply because of these supply chain issues.” Umoja wants to offer a solution. The biotech is working on ways to confront all the major limitations of CAR T-cell therapy—the lengthy, pricey manufacturing process and the poor efficacy against solid tumors—with therapies that reengineer a patient’s T cells within their own body, rather than removing and redelivering them the way current autologous CAR T-cell therapy is administered today. It’s also in the process of establishing partnerships with Big Pharma companies that want to take their ex vivo therapies in vivo by pairing them with Umoja’s VivoVec gene delivery system, which the company is aiming to manufacture end-to-end at its forthcoming plant in Colorado. “We know we can manufacture 100% of our own supply chain, so that’s attractive to partners,” Fontana said, especially in light of the ongoing shortage of lentiviral vectors. Though no deals have been announced yet, Umoja is “actively pursuing” partnerships, he added. What the company has announced is new preclinical data validating its therapeutic approach in solid tumors. On May 17 at ASGCT, researcher Alyssa Sheih, Ph.D., showed how Umoja’s gene delivery platform UB-VV200, which uses the company’s VivoVec technology, combined with UB-TT170, a folate receptor-targeting version of its small-molecule adapter TumorTag technology, was able to generate CAR T cells in vivo and successfully control solid tumor growth in mice. A brief overview of how all the pieces work together: The scientists administer UB-VV200, an engineered lentiviral vector that encodes a universal CAR called a TagCAR along with the company’s synthetic cytokine system, RACR, which helps the CAR T cells expand and persist without the need for pre-treatment chemotherapy. UB-VV200 selectively binds, activates and transduces the T cells, resulting in TagCAR expression on their surface. The TagCAR-T cells will bind to the TumorTag coated folate receptor-expressing tumors—in this instance, the TumorTag UB-TT170, which binds to folate receptors. Looking at mice with xenografts of folate receptor-expressing tumor cells, the researchers saw that UB-VV200 controlled solid tumor growth in a dose-dependent manner. The more TagCAR T cells that were generated, the smaller the tumor volume. Umoja is conducting ongoing nonhuman primate studies, which the company described as “encouraging” so far. Details are to be presented at an upcoming medical conference, though Umoja declined to disclose which one.  The Seattle Children's Research Institute is currently testing Umoja's UB-TT170 in pediatric osteosarcoma, a folate receptor-expressing tumor type, with plans to expand into gynecological tumors. The company also intends to submit an investigational new drug application for human testing with the FDA for UB-VV200 by the second half of 2024. Other preclinical assets include UB-VV111, a CD-19 CAR T-cell therapy for hematological cancer. Meanwhile, the company is busy finishing up the manufacturing plant in Louisville, Colorado, dubbed The Colorado Laboratory & Innovative Manufacturing Building, or The CLIMB. The $70 million plant will span 77,000 square feet and is expected to open later this year. Producing an off-the-shelf, in vivo CAR T therapy rather than an ex vivo one allows the company to make more efficient use of its manufacturing space, Senior Vice President of Translational Sciences Ryan Larson explained. Autologous ex vivo CAR T cell therapies are produced for each individual patient, so each batch of CAR T cells must be produced one at a time. In contrast, “we can scale up—we don’t have to scale out,” Larson said. As demand for Umoja's therapies grows, along with the number of partners that want to use the VivoVec platform to convert their own CAR T cell therapies to in vivo products, “we can just increase the volume of our bioreactors.” Given the manufacturing challenges and other accessibility issues associated with autologous CAR T-cell therapies, it’s likely that the field more broadly is headed toward an in vivo approach, Larson said. There’s a precedent for this already in the gene therapy space. Gene therapies started out with genes being transduced into cells outside a patient’s body, then over time began to move in-patient as the technology improved. The same thing is happening with CAR T-cell therapies: As the treatment’s power has become clear, researchers are looking for ways to make it more accessible. “Now, to me, it’s an obvious next step if you can make a truly off-the-shelf product that engineers the patient’s own cells in vivo essentially an autologous product—it’s your T cells—and you bypass all the complexity of the ex vivo approach by going directly in vivo,” Larson said. “I would say yeah, it’s definitely the way of the future.”

UB-VV200 preclinical data highlight successful generation of TagCAR T cells, which demonstrate dose-dependent anti-tumor activity when used in combination with TumorTag™ technology in an in vivo model Optimization of VivoVec particles increases anti-tumor activity and enables multiple routes of administration for VivoVec-mediated CAR delivery in in vivo models SEATTLE, May 17, 2023 (GLOBE NEWSWIRE) -- Umoja Biopharma, Inc., a transformative immuno-oncology company creating off-the-shelf treatments for solid and hematologic cancers, today announced the presentation of new preclinical data at the American Society of Gene and Cell Therapy (ASGCT) 26th Annual Meeting demonstrating potent in vivo CAR T cell generation and robust anti-tumor activity using its VivoVec™ platform. “Our new preclinical data at ASGCT represent the significant progress we have made in our platform development and IND-enabling studies and bring VivoVec one step closer to delivering on the promise of off-the-shelf in vivo CAR T cell therapies,” said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. “These data exemplify our continued efforts to push beyond the limitations of today’s CAR T cell therapies and showcase the advances we’ve made in our VivoVec platform together with promising results from our in vivo UB-VV200 solid tumor program. We look forward to bringing our product candidates to the clinic in the coming year.” Umoja’s oral and poster presentations highlight preclinical data demonstrating efficient in vivo CAR T cell generation and anti-tumor activity using its off-the-shelf surface-engineered lentiviral VivoVec platform. Specifically, the preclinical data highlight advancements made in vector design by incorporating a multidomain fusion (MDF) protein that improves activity via multiple routes of administration. Additionally, preclinical data from the Company’s solid tumor program, UB-VV200, demonstrate efficient in vivo generation of TagCAR T cells, the ability to control their expansion using the RACR™ system, and specific tumor targeting using TumorTag™ technology. Cumulatively, these data represent significant progress toward an Investigational New Drug application (IND). Presentation highlights: Abstract #: 53Title: UB-VV200 is a novel surface-engineered lentiviral product candidate for in vivo engineering of universal TagCAR T cells for the treatment of solid tumors Presenter: Alyssa Sheih, Ph.D., Senior Scientist, Umoja Biopharma Presentation Date, Time: Wednesday, May 17, 2023, 3:45 PM – 4:00 p.m. PTKey Highlights: Oral presentation describes the development of UB-VV200 drug product with a payload encoding a universal CAR (TagCAR) and a synthetic cytokine receptor for the generation of TagCAR T cells in vivo and results from preclinical in vivo studies of UB-VV200 in combination with UB-TT170, a bispecific adaptor targeting folate receptors. Surface engineered UB-VV200 selectively binds, activates, and efficiently transduces T cells in a dose-dependent mannerResulting TagCAR T cells mediate antigen-specific cytolytic activity, cytokine release, and proliferation through engaging UB-TT170 bound tumor cellsThe RACR system selectively enriches and expands TagCAR T cells through rapamycin administrationEngineered in vivo TagCAR T cells combined with UB-TT170 control aggressive FRα+ tumor cells in mice in a dose-dependent manner Abstract #: 1441Title: Potent in vivo CAR T cell generation and durable anti-tumor activity in preclinical models using VivoVec, a surface-engineered lentiviral vector drug platform Presenter: Christopher Nicolai, Ph.D., Principal Scientist, Umoja BiopharmaPresentation Date, Time: Friday, May 19, 2023, 12:00 p.m. PTKey Highlights: Poster presentation details the optimization of VivoVec particles, Umoja’s novel surface-engineered lentiviral vectors for in vivo CAR T cell generation that promote high avidity T-cell binding and transduction. Addition of costimulatory molecules to VivoVec particles increases T-cell binding, activation, and transduction of T-cells in vitro and dose-dependent T-cell transduction and anti-tumor immunity in vivo.VivoVec particles that incorporate a multidomain fusion (MDF) molecule show enhanced T-cell binding and transduction in vitro, compared to particles containing separate costimulatory molecules.MDF VivoVec particles demonstrate improved anti-tumor response in vivo and at a lower dose compared to particles containing separate costimulatory molecules.MDF-engineered VivoVec particles delivered using Lupagen’s extracorporeal system generate functional CAR T cells in vivo that mediate durable anti-tumor responses in preclinical tumor xenograft models. Presentations can be accessed from the ASGCT website at https://annualmeeting.asgct.org/. About Umoja BiopharmaUmoja 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, the RACR™/CAR in vivo cell expansion/control platform, and the TumorTag™ targeting 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 http://umoja-biopharma.com/. 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 Communicationskcross@lifescicomms.com