LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hi fellow warriors! After two weeks of indigestion from new clinical trials and preclinical studies due to the international conferences AACR 2025 and AUA 2025, we’re back to a more modest amount of information—but no less interesting because of it! Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• JANX007: Phase 1b Expansion Underway​
  Phase 1b expansion studies started for JANX007, a PSMA-targeting Tumor Activated T Cell Engager (TRACTr) designed for patients with metastatic castration-resistant prostate cancer (mCRPC). This follows promising outcomes from the earlier Phase 1a dose-escalation trial (ENGAGER-PSMA-01), which involved 16 mCRPC patients. In that study, JANX007 demonstrated a median radiographic progression-free survival (rPFS) of 7.5 months, with a slightly longer rPFS of 7.9 months observed in those receiving higher doses (6 mg and 9 mg). The six-month rPFS rates were 65% overall and 78% for the higher-dose group. The drug is engineered to remain inactive in the bloodstream and become active only within the tumor microenvironment, a strategy intended to reduce off-tumor toxicity. The safety profile remained consistent with earlier updates. Phase 1b trials will evaluate two dosing regimens in taxane-naïve patients, with additional studies planned to assess JANX007 in combination with AR inhibitors, as monotherapy in patients resistant to PARP inhibitors, and in those previously treated with next-generation hormone therapies and taxanes.
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• NTS071: A Precision Strike Against the p53 Y220C Mutation​
  The FDA has approved an Investigational New Drug (IND) application for NTS071, a first-in-class oral small molecule designed to target the p53 Y220C mutation. The drug, set to begin Phase 1 trials in the latter half of 2025, works by binding to and stabilizing the mutant p53 protein, helping to restore its DNA-binding function and tumor-suppressing capabilities. Developed via an AI-powered discovery platform, NTS071 has demonstrated 20-fold greater potency than existing alternatives and superior pharmacokinetics, while avoiding common drug-drug interactions like CYP3A4 inhibition. Toxicology studies support a favorable safety profile. While the Y220C mutation is relatively rare in prostate cancer, its presence opens the door to inclusion in future trials. Preclinical models showed dose-dependent tumor shrinkage, with greater efficacy at lower doses compared to existing candidates. NTS071 is being positioned as a tumor-agnostic treatment option, with potential applicability to ovarian, lung, breast, pancreatic, and prostate cancers.
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Preclinical Research

• • Penetrium: Tackling Cold Tumors and Metastatic Disease​
    Unveiled at the 2025 AACR Annual Meeting, Penetrium is a novel therapy developed to address the treatment failure often seen in cold tumors. Unlike resistance driven by genetic mutations, these tumors fail to respond due to the stiffening of the extracellular matrix (ECM), which physically impedes immune cell and therapeutic agent infiltration. Penetrium targets and remodels the ECM, restoring access for treatments and potentially resensitizing tumors to previously ineffective therapies. Researchers are actively expanding clinical trials for Penetrium, including a Phase 1 study for prostate cancer in South Korea and preparations for an investigator-initiated trial for AML in France. Preclinical studies showed promising results across multiple cancer types, particularly in combination therapies, leading to tumor burden reduction, full metastasis elimination, and enhanced chemotherapy efficacy without increased toxicity.
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  • UTRxM1-18: Targeting c-MYC with Engineered mRNA Destabilization​
    An IND application has been submitted for UTRxM1-18, a next-generation mRNA therapy aimed at degrading c-MYC transcripts in tumor cells. Although initial Phase 1 trials (expected in 2026) will focus on non-prostate cancers, this therapy could be particularly impactful in prostate cancer, where c-MYC overexpression is linked to aggressive and treatment-resistant disease. UTRxM1-18 employs proprietary 3’UTR engineering to destabilize c-MYC mRNA, triggering selective degradation in cancer cells while sparing healthy tissue. Targeting c-MYC—a gene involved in over 75% of all cancers—has been historically difficult, making this approach potentially transformative. Preclinical results demonstrated significant tumor growth suppression and metastasis reduction in animal models, all without dose-limiting toxicities.
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  • Pioglitazone: A Familiar Drug with New Potential​
    Recent findings published in Molecular Cancer highlight the potential of pioglitazone, a drug commonly used for type 2 diabetes, in the treatment of prostate cancer. The study identifies the protein PPARγ as a key link between diabetes and prostate cancer.Pioglitazone, a thiazolidinedione that activates PPARγ, was found to alter tumor cell metabolism and inhibit their proliferation in both cell culture and prostate tissue samples. Early patient data is encouraging: among diabetic prostate cancer patients treated with PPARγ agonists like pioglitazone, none showed signs of relapse during the observation period. While these results are preliminary and further clinical trials are necessary—especially in non-diabetic populations—the prospect of repurposing an existing drug with a well-established safety profile could accelerate new treatment options for prostate cancer patients.

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And…that’s all folks! For today at least!
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Have a great weekend!

Max