Oncternal Therapeutics, a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, announced that the United States Food and Drug Administration (FDA) has granted the company orphan drug designations of cirmtuzumab for treatment of mantle cell lymphoma (MCL) and for treatment of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL).

Cirmtuzumab is an investigational anti-ROR1 monoclonal antibody being evaluated in clinical trials in patients with MCL, CLL and HER2-negative breast cancer.

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs or biologics intended to treat rare diseases or conditions, which are defined as diseases or conditions that affect fewer than 200,000 people in the United States or that affect more than 200,000 people but where there is no reasonable expectation that the costs of developing and marketing the drug will be recovered through future sales of the drug in the United States. Orphan drug designation for cirmtuzumab qualifies Oncternal for certain benefits including tax credits for qualified clinical trials, exemption from certain FDA application fees, and the potential for market exclusivity upon regulatory approval, if received, for an orphan-designated indication.

“We are pleased to receive orphan drug designations for cirmtuzumab, our potentially first-in-class investigational ROR1 antibody,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “We are excited about cirmtuzumab’s potential for the treatment of patients with ROR1-expressing cancers, including MCL, CLL, HER2-negative breast cancer and other solid tumors, and look forward to further advancing its development to benefit patients with significant unmet medical needs.”

MCL is an aggressive form of non-Hodgkin’s lymphoma. MCL prevalence is estimated to be approximately 13,000 to 21,000 patients in the United States. MCL is an aggressive cancer that carries a poor prognosis, with a median survival of about two to five years and a 10-year survival rate of approximately 5%-10%.

CLL is the most common form of leukemia in adults, accounting for 25-30% of all leukemias in the United States. CLL prevalence is estimated to be approximately 158,000 to 178,000 patients in the U.S. Despite various recently approved therapies, CLL generally remains incurable.

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL or MCL, in a collaboration with the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with HER2-negative metastatic breast cancer is being conducted at the UC San Diego School of Medicine.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues.