New data shows that CAR T cells engineered in vivo with VivoVec particles mediate durable antitumor activity
Potent and durable anti-tumor activity demonstrated with a universal TagCAR targeted against folate receptor expressing tumor cells when used with the TumorTag UB-TT170
Gene-engineering iPSCs to express the RACR platform enables differentiation and expansion of cytotoxic innate lymphocytes with potent anti-tumor activity in vivo
SEATTLE, November 10, 2022 – Umoja Biopharma, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells to treat patients with solid and hematologic malignancies, announced today new data from three poster presentations at the 2022 Society for Immunotherapy of Cancer 37th Annual Meeting, being held November 11-14, 2022, in Boston, Massachusetts. The presentations provide updates on the development of Umoja’s integrated in vivo chimeric antigen receptor (CAR) T cell platform technologies including:
- VivoVec™, a surface-engineered lentiviral vector-based platform for the generation of CAR T cells in vivo,
- RACR™ (rapamycin-activated cytokine receptor), a synthetic receptor designed to selectively provide survival signals to CAR T cells in the presence of rapamycin,
- TumorTags™, bispecific small molecule adapters intended to help overcome the innate heterogeneity of solid tumors and support cells, and,
- iCIL (induced cytotoxic innate lymphoid) cells differentiated using the Synthetic Receptor Enabled Differentiation (ShRED™) manufacturing process.
“The SITC conference this year was a showcase of our integrated platforms and provides a glimpse at our potential to overcome multiple challenges facing the industry. This highlights the opportunity we have to make a meaningful impact to patients beyond developing better therapeutics alone, but by directly addressing critical patient access needs,” said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. “New data highlights multiple components of our platform, including preclinical validation of in vivo cell therapy transduction using VivoVec particles, the power that universal small-molecule bispecific adapters could have in simplifying solid tumor targeting and the possibility of creating a nearly unlimited supply of off-the-shelf therapeutic cells.”
Umoja’s three posters highlight recent preclinical advancements across their integrated suite of technologies. To overcome the challenges and major limitations associated with current CAR T cell therapies, such as patient access, cost, and manufacturing, Umoja has developed their VivoVec platform harboring a CAR transgene that is being developed for off-the-shelf use for generation of CAR T cells in vivo. Previous data has shown that the VivoVec platform is able to generate CAR T cells in vivo that mediate antitumor activity. New preclinical data presented at SITC details the advancement of the VivoVec platform through incorporation of costimulatory molecules into the surface of VivoVec particles. The advanced particle design demonstrates enhanced T cell binding and activation in vitro and in vivo, along with the capacity to generate greater numbers of CAR T cells, resulting in enhanced antitumor activity at lower doses.
A second poster shared new data supporting the use of the Company’s bispecific small molecule adapters called TumorTags intended to overcome the challenges of eradicating solid tumors that stem from their innate heterogeneity. TumorTags are designed to work in concert with a CAR T cell called a TagCAR T cell which can be engineered using VivoVec to identify and eradicate tumor cells marked by TumorTags. New data shows that VivoVec can mediate in vitro transduction of T cells to express the TagCAR and Umoja’s proprietary rapamycin-activated cytokine receptor (RACR), which selectively provides survival signals to TagCAR T cells in the presence of rapamycin. Functional analyses showed that treatment with rapamycin enriches and expands TagCAR T cells, and that TagCAR T-cells exhibit enhanced solid tumor cell killing in vitro and potent anti-tumor activity in vivo.
A third poster highlights Umoja’s best-in-class iPSC-based allogeneic cell therapy platform that utilizes a Synthetic Receptor Enabled Differentiation (ShRED) manufacturing process which employs RACR to direct differentiation and expansion of RACR-induced cytotoxic innate lymphocytes (iCILs). The iCIL ShRED process is feeder cell free, minimizing the need for complex raw materials, and eliminates the need for in-process cell selection or enrichment. ShRED generates unprecedented yields of highly pure hematopoietic progenitor (HP) cells and RACR-iCILs. Furthermore, RACR-iCILs retain full proliferative capacity and functionality even after 100 days in feeder-free culture, and RACR activation of RACR-iCILs enhances both serial killing of a breast tumor cell line in vitro and tumor clearance in an in vivo breast cancer mouse model.
Presentation highlights:
Presentation Title: VivoVec lentiviral vector surface-engineered with T cell activating and co-stimulatory ligands enhance in vivo CAR T cell generation and antitumor activity
Presenting Author: Chris Nicolai, Ph.D.
Poster Number: 1230
Key Highlights:
- Second-generation VivoVec particles developed through the incorporation of costimulatory molecules into the particle surface, in addition to the anti-CD3 scFv and Cocal fusion glycoprotein, exhibit enhanced T cell binding and activation, resulting in increased transduction and greater numbers of CAR+ T cells in vitro
- CAR T cells generated with second-generation VivoVec particles exhibited a less-differentiated, central memory-like phenotype and enhanced CAR-antigen-specific polyfunctionality, including cytokine production, proliferation, and tumor cell killing in vitro
- In a humanized NSG mouse model of B cell malignancy, second-generation VivoVec particles generated greater numbers of CAR T cells in the blood, resulting in enhanced antitumor activity at lower doses compared to first-generation particles in vivo
- Results demonstrate that second-generation VivoVec particles efficiently generate large numbers of highly functional CAR T cells able to mediate durable tumor control in a preclinical model of B cell malignancy
Presentation Title: In vivo generation of universal CAR T cells that mediate durable anti-tumor immunity through combinatorial targeting with bispecific small molecule adapters
Presenting Author: Kristen Mittelsteadt, Ph.D.
Poster Number: 375
Key Highlights:
- TagCAR T cells can be generated in vitro with VivoVec particles alone, in the absence of additional T cell activating agents, and addition of rapamycin engages RACR and selectively enriches and expands TagCAR T cells
- TagCAR T cells repeatedly kill tumor targets in vitro with the matching TumorTag and expand in the presence of antigen, both functions of which are enhanced with addition of rapamycin
- Ex vivo manufactured TagCAR T cells demonstrate robust and rapid clearance of solid tumors in mice dosed biweekly with the first TumorTag, UB-TT170
- TagCAR T cells can 1) be generated in vivo with administration of VivoVec particles, 2) mediate tumor control and regression with TumorTag
Presentation Title: Synthetic Receptor Enabled Differentiation (ShRED), a novel platform for manufacturing of iPSC-derived cytotoxic innate lymphocytes for “off-the-shelf” cancer immunotherapies
Presenting Author: Samantha O’Hara, Ph.D.
Poster Number: 366
Key Highlights:
- The ShRED manufacturing process employs a synthetic receptor system to direct iPSC differentiation to cytotoxic innate lymphocytes at unprecedented yields and purity
- The engineered synthetic cytokine receptor can mimic the JAK/STAT signal that occurs downstream of important cytokine and growth factor receptors
- Embryoid bodies (EB) transition to >98% HP cells by ~2 weeks, generating >300 HPs per iPSC, and at ~5-weeks generates >95% pure RACR-iCILs
- In vitro results demonstrate that RACR-activation increases RACR-iCIL serial killing of a breast tumor cell line compared to untreated cells
- In vivo proof-of-concept results show that mice with breast adenocarcinoma tumors treated with rapamycin and RACR-iCILs have 100% survival after 60-days with markedly reduced tumor burden
About VivoVec™: In vivo Gene Delivery
VivoVec engineers patient T cells in vivo via surface-engineered lentivirus-mediated transduction using our proprietary 4th generation lentiviral vector technology. The VivoVec in vivo gene delivery system enables the patient’s body to generate a population of cancer fighting T cells, or chimeric antigen receptor (CAR) T cells, which are also genetically retooled with the RACR/CAR systems. This off-the-shelf technology eliminates the complexity, delay and expense of externally manufactured cellular therapies. VivoVec can also be applied in an ex vivo manufacturing setting where a traditional CAR T therapeutic approach is more appropriate. To learn more about Umoja’s VivoVec platform please visit https://www.umoja-biopharma.com/our-science/.
About RACR™/CAR: In vivo Cell Programming
CAR T cells generated by the body with VivoVec can be expanded and sustained with the rapamycin activated cytokine receptor (RACR) system, an engineered signaling system designed to improve chimeric antigen receptor (CAR) T cell persistence and produce durable anti-tumor responses. The RACR/CAR payload is integrated into the genomic DNA of a patient’s T cells. Rapamycin activates the RACR system resulting in preferential expansion and survival of cancer-fighting T cells. The RACR technology enables a patient’s cells to expand in a manner that resembles a natural immune response that does not require lymphodepletion, promoting durable T cell engraftment. RACR/CAR technology can also be used to enhance ex vivo manufacturing in support of more traditional autologous or allogeneic cell therapy manufacturing processes. To learn more about Umoja’s RACR platform please visit https://www.umoja-biopharma.com/our-science/.
About TumorTag™: Universal CAR Tumor Targeting
TumorTags are bispecific small molecules that consist of a moiety that selectively binds to tumor cells or immunosuppressive tumor stromal cells marking them for recognition and destruction by CAR T cells.TumorTags can be designed to have a tumor-binding moiety that is antigen-specific or antigen-independent, as needed, and multiple TumorTags could be combined as a cocktail to increase chances of labeling critical tumor elements. TumorTag is applicable to an array of cancer therapies and can be leveraged to use a universal CAR with ex vivo–manufactured cells (autologous or allogeneic) to increase targeting flexibility. To learn more about Umoja’s TumorTags and Universal TagCAR please visit https://www.umoja-biopharma.com/our-science/.
About iCIL™: RACR-Induced Cytotoxic Lymphocytes
The RACR-induced cytotoxic lymphocyte platform leverages Umoja’s RACR technology in a novel cell manufacturing process to generate synthetic cancer fighting cells from induced pluripotent stem cells at massive scale. These cells, termed induced cytotoxic innate lymphocytes or iCILs, can be administered to patients to augment their endogenous anti-tumor immune function, and to work together with VivoVec-generated in vivo CAR T-cells. Similar to VivoVec-generated CAR T-cells, iCILs leverage our RACR/CAR™ and TumorTag™ platforms respectively to support cell survival and target tumors and their stromal cells, potentially reducing adverse events and prolonging remissions for patients. To learn more about Umoja’s iCIL platform please visit https://www.umoja-biopharma.com/our-science/.
About Umoja Biopharma
Umoja Biopharma, Inc. is an early clinical-stage company advancing an entirely new approach to immunotherapy. Umoja Biopharma, Inc. 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, iCIL off-the-shelf cell therapy 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 the economic, market and social disruptions due to the ongoing COVID-19 public health crisis. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.
Media Contact:
Darren Opland, Ph.D.
LifeSci Communications
darren@lifescicomms.com