Significant progress has been made in the clinical development of TTX-MC138, a novel RNA-based therapeutic targeting solid metastatic cancers(including prostate cancer). The therapeutic candidate, designed to inhibit microRNA-10b (miR-10b), a key driver of cancer metastasis, has reached a pivotal milestone with the initiation of dosing in its fourth cohort of a Phase 1 clinical trial.

The approach focuses on miR-10b, a microRNA identified as a master regulator of metastatic tumor cell viability. By using antagomirs—synthetic molecules that inhibit miR-10b—delivered via a specialized nanoparticle platform, the therapy aims to disrupt the progression of metastatic disease. Preclinical studies demonstrated that this approach achieved complete and persistent regression of metastases in cancer models, offering a promising new avenue for treatment.

Extensive non-clinical studies supported the advancement of this therapeutic candidate.

In 2023, a Phase 0 trial evaluated a radiolabeled version of TTX-MC138 in patients with advanced metastatic cancer. Imaging confirmed the therapeutic’s accumulation in metastatic lesions, with lesion-to-blood radioactivity ratios indicating successful targeting. A single microdose achieved 66% inhibition of miR-10b within 24 hours, suggesting a broad therapeutic window. The first patient tolerated the dosing well, with no adverse reactions reported, and the therapeutic demonstrated a 20-hour circulation half-life.

In this Phase 1 clinical trial, no significant safety issues have emerged in the first four cohorts, and the Safety Review Committee approved expanded enrollment in Cohort 3 to further assess tolerability. Early pharmacokinetic (PK) and pharmacodynamic (PD) data align with preclinical and Phase 0 results, reinforcing the therapeutic’s stability and target engagement.

Source.

Clinical trial.