Molecular Insight Pharmaceuticals’ discovery and preclinical efforts are presently focused on two areas of research aimed at further improving the therapeutic value of PSMA-targeted radiopharmaceuticals for treating men suffering with metastatic prostate cancer: the identification of second generation analogs of MIP-1095 for the delivery of alternative alpha and beta emitting radionuclides, and the identification of chemotherapeutic agents that will synergize with MIP-1095.
While preclinical data with MIP-1095 confirms that PSMA-targeted beta emitters may be effective for radiotherapeutic applications in metastatic prostate cancer, there are significant advantages to the development of second generation analogs with the same pharmacophore that exhibit similar tissue pharmacokinetic properties as MIP-1095, but are radiolabeled alternative alpha and beta emitting radionuclides. Particular radionuclides that lack the high energy gamma photons characteristic of iodine-131, are widely available, and offer the potential for on-site labeling of the product via kit formulation. Molecular Insight Pharmaceuticals has identified several classes of high affinity lead second generation PSMA inhibitors for targeted systemic radiotherapy of metastatic prostate cancer that enable labeling with alternative alpha and beta radionuclides. Ongoing optimization of pharmacokinetics to match the physical half-lives of these alternative radionuclides is currently under way .
While we anticipate that clinical trials with MIP-1095 may demonstrate anti-tumor activity against metastatic prostate cancer as a single agent, it is nonetheless predicted that the combination of MIP-1095 with chemotherapeutic agents targeting specific cellular pathways will be synergistic, enabling enhanced response rates and/or prolonged duration of response. Molecular Insight Pharmaceuticals is presently evaluating potential synergy of several classes of chemotherapeutic agents directed toward impacting cellular processes implicated in augmentation of radiation induced cellular damage, promotion of radiation mediated tumor cell death, or prevention of cellular repair in response to radiation in combination with MIP-1095.