Oncternal is developing ONCT-808, a ROR1 targeted autologous CAR-T cell therapy, which is currently in preclinical development, initially as a potential treatment for hematologic malignancies.

ROR1 is an Attractive Target for Cell Therapy

Chimeric antigen receptor-T cell (CAR-T) and chimeric antigen receptor NK-cell (CAR-NK) therapies are immune cells that have been engineered to target and engage a specific marker on cancer cells  to direct an immune response against those cancer cells. There are several CAR-T cell therapies that have shown dramatic anti-cancer effects, for example the FDA approved CAR-T treatments for patients with CD19-expressing leukemias and lymphomas, and BCMA-expressing myeloma.

ROR1 is highly expressed on many hematologic and solid malignancies, but is not often expressed on healthy adult tissue. 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+ target cells and inhibited ROR1+ 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 a mutated or loss of target tumor antigen (such as seen with CD19). 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.

Currently approved CAR-T cell therapies are “autologous”: a therapeutic intervention that uses a patient’s own cells, which are then cultured and expanded outside the body and reintroduced back into the patient. The complexity and cost of this process remain significant barriers to effective implementation and patient access. At Oncternal we are committed to developing “off-the-shelf” allogeneic CAR-T and CAR-NK cell therapies to improve patient access to these important therapeutic options.

We are enrolling patients:

  • With relapsed/refractory mantle cell lymphoma (MCL) for a Phase 1b/2 study of zilovertamab in combination with ibrutinib
  • With chronic lymphocytic leukemia (CLL) for a Phase 2 clinical study of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor 
  • With Ewing sarcoma for a Phase 1 study of ONCT-216, our small-molecule inhibitor of ETS-family transcription factor oncoproteins, in combination with vincristine
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