News pre|CISION Platform: Delivering Two Complementary Therapies from One Molecule

A novel dual payload peptide drug conjugate technology, known as the pre|CISION® platform, represents an advance in oncology by delivering two complementary anticancer therapies from a single molecule. This approach leverages the fibroblast activation protein (FAP), which is selectively present in the tumor microenvironment, especially in advanced prostate cancer such as castration-resistant prostate cancer (CRPC). Because FAP is predominantly expressed by cancer-associated fibroblasts within the prostate tumor stroma, the platform enables targeted delivery of therapeutic payloads directly to the tumor site while minimizing systemic toxicity.

The platform’s dual payload design combines mechanisms with strong relevance to prostate cancer treatment challenges. One combination involves microtubule inhibition by monomethyl auristatin E (MMAE) and topoisomerase I inhibition by exatecan. Both payloads maintain potent cytotoxic activity against tumor cells and are effective in androgen-independent prostate cancer models, addressing disease resistant to standard hormone therapies. Another strategy pairs topoisomerase I inhibition via exatecan with DNA damage response (DDR) inhibitors such as PARP or ATR inhibitors. Genetic defects in DNA repair pathways are common in metastatic prostate cancer, making these tumors vulnerable to DDR inhibition-induced synthetic lethality. This dual therapy approach shows a 4-5 fold increase in tumor cell killing compared to single-agent treatment, directly counteracting resistance mechanisms.

Preclinical data reinforces the high tumor specificity of the platform, with payload release initiated exclusively by FAP cleavage in the tumor microenvironment. Importantly, the release mechanism triggers a bystander effect whereby cytotoxic agents diffuse to kill adjacent FAP-negative cancer cells, which is crucial in the heterogeneous environment of prostate tumors. Biomarker studies confirm that both payloads reach their targets, inducing DNA damage markers, tubulin depolymerization, and cell cycle arrest signatures consistent with their mechanisms. Prior clinical evidence from related molecules highlights a tumor-to-plasma payload concentration ratio of 100:1, suggesting a favorable therapeutic window.

This technology offers promise for improving outcomes in prostate cancer, particularly in advanced stages where FAP expression is elevated and treatment resistance is prevalent.

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