On January 8, 2020 CohBar, Inc. (NASDAQ: CWBR), a clinical stage biotechnology company developing mitochondria based therapeutics (MBTs) to treat chronic diseases and extend healthy lifespan, reported the discovery of a series of novel mitochondrial peptide analogs with potent in vitro activity as selective inhibitors of C-X-C Chemokine Receptor Type 4 (CXCR4) and with preliminary in vivo efficacy in a mouse model of melanoma, including substantial reduction in tumor growth as compared to control animals (Press release, CohBar, JAN 8, 2020, View Source [SID1234552863]). CXCR4 is a key regulatory receptor involved in tumor growth, invasion, angiogenesis, metastasis, and resistance to therapy.
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"This new discovery offers the potential to develop novel therapeutics for difficult-to-treat cancers, based on peptides encoded in the mitochondrial genome," said Ken Cundy, Ph.D., CohBar’s Chief Scientific Officer. "Inhibition of this key regulatory pathway is potentially applicable to a wide range of cancers, as well as orphan indications where CXCR4 signaling is dysregulated."
Novel peptide analogs of a mitochondrially encoded peptide (MBT5) demonstrated potent and selective inhibition of human CXCR4 receptor in cell-based assays, with IC50 values in the low nanomolar concentration range. In a difficult-to-treat in vivo mouse model of melanoma, the B16F10 syngeneic tumor model, the combination of an analog of MBT5 administered subcutaneously with the chemotherapeutic temozolomide showed enhanced antitumor activity, reducing tumor growth after 11 days by 61% compared to control animals. The reduction in tumor growth produced by the combination exceeded the effect of either temozolomide used as a single agent, which reduced tumor growth by 38% compared to control, or the murine checkpoint inhibitor anti-PD-1 antibody, which had no effect on tumor growth in this model.
CohBar plans to further explore the efficacy of this new family of peptides in additional animal models with the goal of identifying a new clinical development MBT candidate.
"These new data further expand our understanding of the broad regulatory influence exerted by mitochondria and the therapeutic potential of analogs of peptides encoded in mitochondrial DNA," said Steve Engle, CohBar CEO. "We are just beginning to scratch the surface of this previously untapped field."
CXCR4 is overexpressed in more than 75% of cancers and high levels of the receptor are associated with poor survival prognosis. Inhibition of the CXCR4 receptor has been shown to mobilize immune cells, enhance the effects of chemotherapy and immunotherapy in various cancers, and reduce the development of metastatic tumors by blocking the ability of tumor cells to evade immune surveillance. CXCR4 also regulates the homing and retention of hematopoietic stem cells and malignant cells in the bone marrow.