Discovery Platform

Vor Bio is researching additional cell surface targets in the fight against cancer

We believe our approach can extend beyond CD33 to other potential target candidates for our eHSCs and CAR-T therapies. We believe our approach shows significant promise when potential targets fulfill three important criteria:

1. These targets are expressed on cancer cells

2. These targets are expressed on cells of hematopoietic lineage

3. There is evidence these protein targets are biologically dispensable

We have generated data exploring targets such as CD123, EMR2, and CD5 which all currently show promise fulfilling these criteria.

Other Myeloid Targets: CD123 and EMR2

CD123 and EMR2 are targets expressed strongly in various myeloid blood cancers including AML. These CD123 and EMR2 targets are expressed both in bulk AML cells as well as leukemic stem cells. We have the ability to genetically engineer HSCs in human cells to remove expression of these targets with good efficiency. As such, we continue to research these targets as potential target candidates for our eHSCs and CAR-T therapies.

Beyond Myeloid Diseases: CD5

As HSCs differentiate, there are two distinct lineages: myeloid and lymphoid. The lymphoid lineage differentiates into important immune cells such as T cells, B cells, and natural killer cells, which are important for fighting infection and preventing development of cancer. Lymphoid cells also have the potential to crease cancerous cells.

CD5 is a cell surface protein that is ubiquitously expressed on T cells. CD5 is also expressed on the majority of T cell malignancies, and therefore could be an attractive target to eliminate cancer cells with two important concerns. Firstly, elimination of all cells expressing CD5 could result in decreased T cell counts which is called lymphopenia, which is not compatible with long-term survival. Secondly, since the CAR-T cells themselves express CD5, CAR-T cells attacking CD5 can also attack themselves, a phenomenon known as fratricide.

Our approach may address both of these concerns. Elimination of CD5 from HSPCs would result in a lymphoid cell compartment lacking CD5 expression, therefore T cells may be protected from CD5-targeted therapies. Secondly, CAR-T cells can be made from CD5-deleted cell populations which may address the issue with fratricide. Our preliminary data shows that CD5 may show similar biological dispensability characteristics to CD33 as well as our ability to delete CD5 expression from HSPCs with good efficiency.

Manufacturing

We are investing in our own manufacturing facilities and have designed a highly efficient process for manufacturing our eHSCs
and CAR-Ts.