ONCT-808

ONCT-808, our ROR1 targeting autologous CAR T cell therapy, is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment.

Chimeric Antigen Receptor (CAR) T Cell Therapies

Immuno-oncology approaches to treating cancer involve redirecting one of the pillars of the immune system, the adaptive immune system, so that it specifically and efficaciously recognizes cancerous cells that might previously have escaped immune recognition. A key element in the adaptive immune response is the T cell that can recognize and kill infected and abnormal cells. T cells also act to signal other immune cells to respond to threats. T cells recognize their targets because they are selected in a way that allows them to specifically recognize foreign antigens on the surface of other cells.

CAR T cells are generated by isolating T cells from patients and modifying them to recognize specific antigens on tumors. T cells have potent cell killing activity that is directed to target cells that are recognized by specific T cell receptors, or TCRs, that are expressed on the surface of these T cells. While some T cells have TCRs that can recognize cancer cells leading to their killing, potent T cells do not develop against all tumor targets. In some cases, the potential cancer cell target is also a protein that has an essential role in other tissues or at other stages of development, and TCRs that recognize these targets are eliminated during normal T cell development.

ROR1 is an Attractive Target for Cell Therapy

ROR1 is highly expressed on many hematologic and solid malignancies but is not often expressed on healthy adult tissue. We believe that the selective expression of ROR1 on many tumor cells, and its absence on normal cells, make it an ideal target for a CAR T cell therapy approach. Importantly, ROR1 expression confers a survival advantage to the tumor cells, making ROR1-negative relapses less likely. Our first generation autologous ROR1 CAR T cells specifically lysed ROR1-expressing target cells and inhibited ROR1-positive tumors in vivo.

Unmet Needs for Cell Therapies

Remarkable clinical responses have been observed in patients treated with FDA-approved CAR T cells therapies, but they exhibit undesirable labeled warnings including cytokine release syndrome (CRS) and neurological toxicity, both of which can be severe and sometimes fatal. A CAR T cell treatment that is not activated by normal cells expressing the target antigen might reduce some of these toxicities. Patients who have responded to CAR T cell therapy sometimes experience relapses of their cancer with loss of or a mutated target tumor antigen (such as is seen with CD19). The prognosis of these patients after progressing is very poor, with an average progression free survival of 3 months and an overall survival of 5 months.

Targeting the CAR T cell to a tumor antigen that is important to the cancer cell’s survival or aggressiveness might offer a decreased likelihood of antigen-negative relapses developing.

ONCT-808 ROR1 Targeting CAR T Cell Therapy

ONCT-808, our autologous ROR! targeting CAR T, is advancing into a Phase 1/2 clinical trial for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. ONCT-808 is being developed under agreements with Lentigen Technology, Inc. (lentivirus manufacturing), Miltenyi Biotec B.V. & Co. KG. (cell processing) and the Dana-Farber Cancer Institute (cGMP cell preparation and manufacturing activities).