TD001 is a novel antibody-drug conjugate (ADC) that will be officially presented during AACR 2025. It was designed to treat prostate cancer by targeting prostate-specific membrane antigen (PSMA), a protein highly expressed in metastatic castration-resistant prostate cancer (mCRPC). It uses an antibody to deliver a chemotherapeutic agent, exatecan, directly to cancer cells, inducing DNA damage and cell death.

In animal models, TD001 showed promising results by effectively targeting tumors with varying levels of PSMA expression. This suggests it could be effective even in patients whose tumors don’t uniformly express high levels of PSMA—offering a flexibility that treatments like Pluvicto may lack, as they tend to work best on cancers with high PSMA expression. In different xenograf mouse models, TD001 results showed high free payload release within tumor tissue, triggering DNA damage, cell death, and growth arrest. Notably, tumor uptake and a very high tumor/plasma ratio (70-100 fold) of exatecan were similar 24 hours post-IV administration across all models, despite substantial differences in PSMA expression and heterogeneity.

Furthermore, TD001 was tested in castrated mice mimicking the hormonal conditions of mCRPC patients, using LNCaP-abl and 22Rv1 models, as well as a non-castrated C5 model. A single dose of TD001, even at levels up to 20 mg/kg, led to dramatic tumor shrinkage—over 90% in some cases—across all models, including those with intermediate PSMA expression. Splitting the dose into two or three administrations every 10 days extended tumor control for 60 to 70 days, significantly boosting survival compared to a single higher dose. Remarkably, tumors that regrew retained their PSMA levels and responded just as well to a second round of TD001, with no signs of resistance.  These results highlight TD001’s potential as a top-tier treatment, capable of tackling a broad spectrum of PSMA-expressing tumors. Clinical trials will be the next step.

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