DEVELOPING DIFFERENTIATED T CELL THERAPIES FOR SOLID AND HEMATOLOGIC CANCERS
We have built a robust pipeline of TRuC™ programs for solid and hematologic cancers. Each program is designed for the given tumor target(s) and indication(s) using a specific TRuC™ vehicle either by itself or with built-in immune and tumor modulators (providing multiple formats). Our lead program TC-210 is expected to enter the clinic in 2018. A second solid tumor program (Program X) will be nominated in 2018 and subsequently undergo IND-enabling studies.
TC-210 is our lead TRuC™-T cell program targeting mesothelin-expressing solid tumors including ovarian, pancreatic, lung, mesothelioma and cholangiocarcinoma. Mesothelin is a glycosylphosphatidylinositol (GPI) anchored surface protein that is overexpressed in a range of solid tumors, making it an attractive therapeutic target for our TRuC™ platform. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis.
TC-210 TRuC™-T cells contain engineered T cell receptors that integrate a CD3ε subunit fused with a humanized anti-mesothelin single domain antibody. Preclinical data conducted in mouse xenograft models demonstrated superior anti-tumor activity for TC-210 compared to CAR-T cells targeting the same antigen. Our scientists also showed that TC-210 can eradicate solid tumors and protect mice from a later tumor re-challenge for over 100 days due to its prolonged persistence. Based on the superiority data in vivo, we are conducting IND-enabling studies for TC-210, which is expected to enter the clinic in 2018.
TC-210 + PD1 Switch
We have built into the TC-210 TRuC™-T cell vehicle a PD1 Switch accessory to further enhance the T cells, if needed in a specific hostile tumor microenvironment. This may be applicable in tumors such as NSCLC where PD1/PDL1 play a role in the immune response. Our proprietary PD1 Switch is a fusion of the extracellular portion of PD1 and the intracellular portion of CD28. By building the PD1 switch into TC-210 or other TRuC™-T cells, we can turn what is typically a suppressive signal (PD1) to a positive signal (CD28) to enhance T cell functions.
In addition to TC-210, we have five TRuC™-T cell discovery programs targeting five different solid tumor targets. Based on in vitro and in vivo proof-of-concept data, one program (Program X) will be prioritized as our second lead solid tumor program and advance into IND-enabling studies in 2018.
We are developing a CD19/22 TRuC™-T cell program to improve upon and address the unmet needs of current CD19-directed CAR T cell products. By simultaneously targeting CD19 and CD22 with a single TRuC™-T cell product, we aim to overcome antigen escape mechanisms and provide a more durable response. Our preclinical data with CD19-TRuC™-T cells indicate that our TRuC™ vehicle is superior to currently available CD19-CAR-T cell approaches (either carrying 4-1BB or CD28 co-stimulatory domains) both in terms of efficacy as well as the level of cytokine release.