Research indicates that the CCR5 receptor is the “GPS” system of a cancer cell that promotes metastatic disease. Preclinical studies have shown that Leronlimab blocks the calcium channel signaling of the CCR5 receptor and has the potential to disable the GPS system. CCR5 inhibition may disrupt signaling and ultimately the spread of CCR5+ Circulating Tumor Cells (CTC’s). Current therapies are directed to the primary tumor, rather than the movement or spread of cancer in the bloodstream. Metastatic disease, not the primary tumor, is the cause of death in the vast majority of cancer patients.
Research showed three key properties of the CCR5’s Mechanism of Action (MOA) in cancer. The first is that the CCR5 receptor on cancer cells was responsible for the migration and invasion of cells into the bloodstream, which leads to metastasis of breast, prostate, and colon cancer. Research also discovered that > 50% of 2,200 patients had increased CCR5 expression in their breast cancer. Increased CCR5 expression is an indicator of disease status in several cancers. The second is that blocking the CCR5 receptor also turns on anti-tumor fighting properties restoring immune function. The third key finding was that blockage of the CCR5/CCL5 interaction had a synergistic effect with chemotherapeutic therapy and controlled cancer progression. Chemotherapy traditionally increased expression of CCR5 so blocking it is expected to reduce the levels of invasion and metastasis.
On November 23, 2018, CytoDyn received FDA approval of its IND submission and is allowed to initiate a Phase 1b/2 clinical trial for metastatic triple-negative breast cancer (mTNBC) patients. On February 18, 2019, CytoDyn announced it will begin 8 pre-clinical studies on melanoma cancer, pancreatic, breast, prostate, colon, lung, liver, and stomach cancer. This has the potential to lead to 8 phase 2 clinical studies with Leronlimab in the cancer arena. On February 20, 2019, CytoDyn announced that Leronlimab was able to reduce by more than 98% the incidence of human breast cancer metastasis in a mouse xenograft model for cancer through six weeks with Leronlimab (PRO 140). The temporal equivalency of the murine 6 weeks study may be up to 6 years in humans. In May 2019, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for Leronlimab (PRO 140) for use in combination with carboplatin for the treatment of patients with CCR5-positive mTNBC.