The ROR1 pathway holds great promise in terms of generating a new wave of first-in-class, targeted cancer therapies for patients with a number cancers, including leukemia, lymphoma, and solid tumors such as ovarian and breast cancers.

— Dr. Thomas J. Kipps, University of California San Diego —

Humanized mAb to ROR1

Cirmtuzumab is a humanized IgG1 monoclonal antibody designed and developed to bind with high affinity to a biologically important epitope on the extracellular domain of Receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1). Cirmtuzumab is currently being tested in a phase 1 trial for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the most common form of leukemia in adults that contributes to approximately 4,650 U.S. deaths annually. We’re also working to rapidly advance cirmtuzumab into additional clinical trials to bring forward this novel therapeutic to patients with other types of cancer.

ROR1 is a marker for many cancers

ROR1 is a type 1 transmembrane protein expressed on the plasma membrane with an extracellular domain that is essential for ligand binding and signal transduction. This novel target is highly expressed in many hematologic malignancies, including CLL and mantle cell lymphoma (MCL), as well as by a number of solid tumors, including lung, ovarian, and triple-negative breast cancer. Binding of cirmtuzumab to ROR1 on tumor cells inhibits Wnt5a signaling, a pathway important for blocking tumor-cell proliferation, migration, and survival. Blocked Wnt5a signaling leads to tumor cell death by apoptosis.

Unmet Need in CLL

CLL is the most common type of leukemia in adults, with approximately 15,000 new cases diagnosed per year in the US. A diagnosis of CLL has been shown to shorten the life expectancy of all patients and the disease is not curable with standard therapies. While many patients can live with CLL for years, there remains a strong need for therapies to manage CLL, particularly in patients with advanced disease who may face rapid progression and a median survival of not more than 2 years. As a highly targeted, first-in-class therapy, cirmtuzumab has the potential to be used either alone or in combination to treat CLL and other cancers where ROR1 is expressed.

Collaboration with University of California San Diego

Cirmtuzumab was developed at the University of California San Diego based on the pioneering scientific research of Thomas Kipps, MD PhD, and his colleagues at the Moores Cancer Center. Oncternal holds an exclusive worldwide license to develop and commercialize antibodies and antibody-related binding agents recognizing ROR1.

Working with UC San Diego, Oncternal is also conducting preclinical research on several potential ROR1-directed antibody drug conjugates (ADCs), with early evidence of promising anti-tumor efficacy and specificity. A further collaboration between Oncternal and UC San Diego focuses on a Chimeric Antigen Receptor T-cells (CAR-T) program, which is evaluating several potential CAR-T vectors that can be introduced into a cancer patient’s T-cells, directing them to recognize and kill tumor cells that express ROR1.

We are recruiting patients

  • With CLL for a Phase 1 study of Cirmtuzumab, our anti-ROR1 monoclonal antibody
  • With Ewing sarcoma for a Phase 1 study of TK216, our small molecule inhibitor of ets-family transcription factor oncoproteins
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