Talapo Therapeutics — Department of Health and Human Services SBIR Phase I: 102

Description

Metastasis is the most common cause of cancer related mortalityyet there are currently no therapeutic options that can be used to stop the spread of malignant cellsRecentlytwo members of the Transforming Growth Factorfamilythe secreted ligands Nodal and Bone Morphogenetic ProteinBMPhave been linked with increased metastasis in breast and other cancersThese cytokines activate stem cell programs in cancers that enable malignant cells to leave the primary tumor and colonize distant organsInhibitors of Nodal or BMPare therefore potential therapeutics for some metastatic cancershowever to date none have been developedWe have produced a novel inhibitor of Nodal and BMPtermed CerberusFcThis protein based inhibitor is a variant of the embryonic Nodal BMP antagonistCerberusfused to IgGFcWe previously found Cerberus Fc binds both Nodal and BMPwith high affinityabrogates Nodal and BMPsignalingand profoundly suppresses migrationinvasionand colony formation of two triple negative breast cancer cell lines that express these ligandsAdditionallyin human breast cancer patients high Cerberus expression is strongly associated with increased relapse free survival ratesTaken togetherthese findings suggest that Cerberus Fc could inhibit metastasis of breast and potentiallyother cancersWe envision this therapeutic couldtreat or prevent metastasisbe used in combination with existing cancer therapies that target the primary tumor or immune responseorbe used in conjunction with surgical removal of the primary tumor to help prevent spread of cancer cells that may lead to metastasisIn this phaseprojectwe will focus on breast cancer metastasisusing an orthotopicpatient derived xenograftPDXmouse model of breast cancer to demonstrate the in vivo activity of Cerberus Fc on spontaneous metastasis to the lung and liveras well as tumor burdenWe will additionally verify acceptable pharmacokinetic behavior of the constructIf successfulthese studies will provide proof of concept for the efficacy of Cerberus Fc in the treatment of breast cancer metastasis and pave the way for more thorough preclinical developmentincluding testing on additional PDX mouse models of breast and other cancers that express varying levels of Nodal and or BMPThis project is a collaboration between Talapo Therapeutics and DrErik Martinez HackertAssistant Professor at Michigan State University and the discoverer of Cerberus Fcandapos s inhibiting functions Metastatic disease is the most lethal and least treatable facet of cancerWe have developed a novel agenttermed Cerberus Fcthat inhibits breast cancer metastasis like programs in vitroThis project will employ a preclinical model of breast cancer to establish Cerberus Fcandapos s utility in inhibiting metastasis in vivo