MAP3K12

WALTHAM, Mass.--(BUSINESS WIRE)-- Minerva Biotechnologies Corporation, a private company developing 1st-in-human therapies for the treatment of solid tumor cancers, announced today that the FDA has approved their IND (Investigational New Drug) application to conduct clinical trials with huMNC2-CAR22, aka MUC1*-CAR-1XX, for the treatment of metastatic breast cancers. huMNC2-CAR22 targets MUC1* (muk 1 star), the growth factor receptor that drives the growth and metastasis of most solid tumor cancers. Minerva’s first CAR T that targets MUC1*, huMNC2-CAR44, is already in a clinical trial for metastatic breast cancers. Initial results show CAR T cell expansion, patients going from Progressive Disease to Stable Disease and Partial Response. However, for a durable response, we needed to overcome CAR T cell exhaustion, which is common to CAR T cell treatment of solid tumor cancers. This second MUC1* CAR T, huMNC2-CAR22, bears the “1XX” mutations in the T cell’s CD3-z signaling domain. These four Tyrosine to Phenylalanine mutations block tyrosine phosphorylation in two of the three signaling domains of CD3-z, which slow signaling and dramatically increase persistence. Unexpectedly, the 1XX mutations give the CAR T cells the added benefit of being able to recognize and kill the low antigen expressing cancer cells that lead to cancer recurrence. “These 1XX mutations solve the two hurdles that have thus far stood in the way of an effective CAR T treatment for solid tumor cancers: 1) CAR T cell exhaustion; and 2) failure to kill the low antigen expressing cells,” said Minerva’s CEO Dr. Cynthia Bamdad, “Together with our MUC1* antibodies that recognize an epitope only available on cancer cells, huMNC2-CAR22 promises to be a big leap ahead in our fight against cancers.” We thank our scientists, collaborators, and the patients and their families for their courage. Minerva holds a license from Memorial Sloan Kettering for use of the 1XX technology. About the trial NCT04020575 is a first-in-human trial of huMNC2-CAR22 and huMNC2-CAR44, autologous CAR T cells targeting MUC1* in metastatic breast cancer in patients with MUC1* positive tumors.

Minerva Biotechnologies Corporation announced today that its trial of huMNC2-CAR44 T cells (NCT04020575) has now opened at City of Hope, Duarte, California. This is a first-in-human trial targeting the tumor-associated form of MUC1, called MUC1* (muk 1 star). MUC1* is the transmembrane cleavage product that is a growth factor receptor that drives growth of an estimated 93% of breast cancers. The antibody that targets Minerva’s CAR T to the tumor binds to an ectopic site that is only exposed after cleavage and release of the tandem repeat domain. Other attempts at targeting MUC1 with antibodies, ADCs, or CAR Ts have targeted the tandem repeat domain, which is cleaved in the tumor microenvironment and shed from the cell surface. The huMNC2-CAR44 therapy was developed by, and is proprietary to, Minerva Biotechnologies. The targeting head of the CAR, the antibody MNC2, recognizes a unique conformation of MUC1 after cleavage by a specific enzyme in the tumor microenvironment. “The ability of our antibody to bind specifically to the cancerous form of MUC1 without binding to MUC1 on normal tissues is a real breakthrough,” said Dr. Cynthia Bamdad, CEO of Minerva Biotechnologies. “Demonstration of safety and early signs of efficacy of huMNC2-CAR44 represent a significant milestone for Minerva. We have a broad, deep pipeline that includes next generation CAR Ts, with enhanced in vivo persistence, and the ability to target cells with much lower antigen density, allowing us to challenge the persistence issues seen elsewhere in the field. We can now progress these to the clinic with increased confidence. We are also developing therapeutics that target the onco-embryonic growth factor, NME7, that activates the MUC1* growth factor receptor across many different types of solid tumors and the preclinical results are very encouraging,” said Minerva Chief Business Officer, Michael Crowther. We would like to express our gratitude to our collaborators, our scientists, and the patients and their physicians for their support and participation in this trial. About the trial NCT04020575 is a first-in-human trial of huMNC2-CAR44, an autologous CAR T therapy targeting MUC1* in metastatic breast cancer in patients with MUC1* reactive tumors.