JUR-003 Enters Phase 1 Trial in Metastatic Prostate Cancer

A new first-in-human phase 1 trial,has been posted for JUR-003 in metastatic prostate cancer. The study plans to enrol up to 210 patients and includes dose-escalation and dose-expansion cohorts in mCRPC, metastatic hormone-sensitive prostate cancer (mHSPC) and oligometastatic disease. JUR-003 will be given intravenously, with the initial goals of defining safety, pharmacokinetics and a recommended dose for expansion.

The most intriguing part is that the public trial record does not yet disclose JUR-003’s molecular target. However, there is strong circumstantial evidence linking it to EM1031, a preclinical KLK2×CD3 bispecific T-cell engager developed specifically for prostate cancer. EM1031 was publicly listed as a prostate-cancer KLK2/CD3 programme, while the newly posted JUR-003 study is the sponsor’s first clinical prostate-cancer programme appearing shortly afterwards. The connection is further strengthened by a 2025 licensing agreement between the developer of EM1031 and the group now advancing JUR-003, which granted exclusive worldwide rights to develop and commercialise the KLK2×CD3 programme for metastatic prostate cancer.

The rationale for targeting KLK2 is strong. KLK2 is a prostate-lineage protein regulated by the androgen receptor and expressed mainly in prostate epithelial and prostate cancer cells. A T-cell engager directed at KLK2 and CD3 would work by binding the tumour cell on one side and a T cell on the other, physically bringing them together and triggering immune-mediated killing.

The preclinical data for EM1031 were particularly encouraging. In laboratory studies, the molecule activated T cells only when KLK2-positive prostate cancer cells were present. It maintained strong tumour-cell killing while producing less cytokine release than a clinical-stage KLK2 T-cell-engager comparator, an important feature because excessive cytokine activation remains one of the major limitations of CD3-directed therapies.

The mouse data were even more striking: in KLK2-positive prostate cancer xenograft models, EM1031 produced complete tumour eradication, again with lower cytokine release than the reference T-cell engager. These results remain preclinical and cannot predict what will happen in patients, but they provide a clear rationale for moving the programme into human testing.

Another interesting feature of the new JUR-003 trial is that development is not limited to heavily pretreated mCRPC. Expansion into mHSPC and oligometastatic prostate cancer is already planned, suggesting that the strategy may eventually be tested much earlier in the disease course, where prostate-lineage targets such as KLK2 may be more consistently expressed.

Clinical trial.