Our initial clinical development has focused on advancing our core platforms, with the goal of integrating these into therapeutic regimens that can treat any tumor at any stage. Our approach is to validate our core technologies in parallel clinical trials, with the goal of bringing them all together in an integrated product capable of being applied across multiple indications. Strategically we will build additional value through partnering our component technologies to enable our collaborators to build best-in-class products via Umoja platforms.
UB-VV111 is our lead clinical program for hematologic malignancies. It comprises VivoVec particles for in vivo delivery of payloads that include our RACR synthetic cytokine receptor system and a CD19 CAR. The UB-VV111 program is currently at the IND-enabling data generation stage and will be partnered.
We anticipate bringing this program forward as an off the shelf therapeutic approach for CD19-expressing hematologic malignancies. UB-VV111 particles will be injected directly into a patient to generate CD19 CAR T-cells in vivo, and the expansion of the CD19 CAR T-cells will be supported by activation of the RACR synthetic cytokine receptor system. The CD19 CAR has a fixed specificity and will direct CD19 CAR T-cell mediated killing of CD19-expressing tumor cells including, DLBCL, CLL, FL and MCL.
Building on the results we will obtain from ENLIGHTen, UB-VV200 + UB-TT170 is our clinical program for gynecologic tumors.
UB-VV200 comprises VivoVec particles for in vivo delivery of payloads that include our RACR synthetic cytokine receptor system and a TagCAR.
The UB-VV200 + UB-TT170 clinical program is currently at the IND-enabling data generation stage. We anticipate bringing this program forward as an off the shelf therapeutic approach for folate receptor expressing solid tumors: UB-VV200 will be injected directly into the patient in order to generate TagCAR T-cells in vivo, and the expansion of TagCAR T-cells will be supported by activation of the RACR synthetic cytokine receptor system. Patients will receive infusions of UB-TT170, based on dosing defined in ENLIGHTen, to direct the TagCAR T-cell population to attack and kill folate receptor-expressing tumor cells and stromal elements. Gynecologic oncology is the planned indication for UB-VV200 + UB-TT170, as up to 80% of ovarian, cervical, and endometrial cancers (as well as triple negative breast cancers and non-small cell lung cancers) express folate receptor.
Following in vivo proof of concept for tumor targeting with a single TumorTag (UB-TT170) combined with VivoVec-generated TagCAR T-cells, our development plan will move forward to evaluate including multiple TumorTags as a cocktail to increase therapeutic effectiveness. A cocktail of multiple TumorTag adapters is planned to target cancer and stromal cells found in a high percentage of solid tumors. We currently have four adapters in development: UB-TT170/UB-TT440/CA IX, FAP. This approach is designed to establish a path to target any solid tumor cancers including breast, colorectal, and gynecologic cancers, among others.
Our initial clinical program following FDA approval of our first IND application is the Phase 1 ENLIGHTen trial (NCT05312411), an actively enrolling, open-label Phase 1 feasibility and safety study of our first TumorTag in patients with refractory/recurrent osteogenic sarcoma (aka osteosarcoma).
UB-TT170 TumorTag molecules are bispecific folate-fluorescein molecules that target the folate receptors expressed in up to 80% of osteosarcoma tumors and label them with fluorescein, a molecule not normally expressed in human cells which serves as a synthetic tumor associated antigen for targeting of CAR T-cells to the tumor.
UB-TT170 TumorTag molecules will be administered to patients along with autologous CAR T cells engineered to express an anti-fluorescein (anti-Tag) chimeric antigen receptor (TagCAR). The trial is being conducted in partnership with Seattle Children’s Therapeutics, a venture at Seattle Children’s Hospital that uses innovative, curative therapies to defeat pediatric cancer and other diseases impacting children.
UB-iC300 is an allogeneic, iPSC-derived cytotoxic innate lymphoid (iCIL) cell therapy targeting Acute Myeloid Leukemia (AML). UB-iC300 is engineered to express Umoja’s RACR synthetic cytokine receptor technology and an AML-specific CAR. UB-iC300 employs the RACR system in the manufacturing process to enable large-scale delivery of “off the shelf” cell therapy to patients. The RACR system also enables small-molecule rapamycin-controlled engraftment and expansion of UB-iC300 in the patient. UB-iC300 preclinical stage development efforts are in collaboration with IASO Biotherapeutics.
We anticipate leveraging the RACR-iCIL platform as a foundation for developing iPSC-derived “off the shelf” cell therapies for several hematologic malignancies. RACR-iCILs are engineered to express Umoja’s RACR synthetic cytokine receptor technology, which enables large-scale manufacturing of RACR-iCILs and small-molecule rapamycin-controlled engraftment and expansion of RACR-iCILs in the patient. RACR-iCIL’s unique memory-like and tumor-killing properties coupled with best-in-class CARs are anticipated to enable broad and diverse clinical development opportunities.