TransCode Therapeutics, Inc. (NASDAQ: RNAZ) announced the completion of initial dosing for all three patients enrolled in Cohort 3 of its Phase 1 clinical trial evaluating TTX-MC138, a first-in-class therapeutic candidate, for metastatic solid cancers.
The Safety Review Committee (SRC), composed of clinicians and experts, unanimously approved the opening of Cohort 3 after reviewing safety and pharmacokinetic (PK) data from Cohorts 1 and 2. The SRC continues to monitor Cohort 3 as preliminary data becomes available. The dose administered to patients in Cohort 3 is approximately double the dose administered in the second cohort, reflecting a dose-escalation strategy based on the observed safety profile.
Favorable Safety Profile Observed
According to the company, several patients from the first and second cohorts remain on the study, receiving additional doses of TTX-MC138 over 28-day cycles. To date, no significant safety or dose-limiting toxicities have been reported across the nine patients treated in the Phase 1 trial.
Promising Pharmacokinetic and Pharmacodynamic Data
Ongoing analyses of PK and pharmacodynamic (PD) activity from Cohorts 1 and 2 suggest that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical studies and TransCode's prior Phase 0 clinical trial. Specifically, Cohort 1 results confirmed the Phase 0 observation that TTX-MC138 exhibits pharmacodynamic activity in the presence of high baseline expression of miR-10b, achieving a 66% inhibition 24 hours post-infusion, mirroring results from the Phase 0 trial. Furthermore, TTX-MC138 activity increased with the escalated dose in Cohort 2 and remained consistent across subsequent administrations, indicating a favorable pharmacokinetic profile.
About TTX-MC138 and the Phase 1 Trial
TTX-MC138 is designed to inhibit microRNA-10b (miR-10b), a microRNA believed to play a critical role in the emergence and progression of various metastatic cancers. TransCode's Phase 0 trial in 2023 demonstrated delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose, suggesting a broad therapeutic window.
The Phase 1 trial (NCT06260774) is a multicenter, open-label study with dose-escalation and dose-expansion phases. It aims to evaluate the safety and tolerability of TTX-MC138 in patients with diverse metastatic solid cancers. While not a primary endpoint, the trial may offer early indications of clinical activity. The dose-escalation stage focuses on assessing the safety and tolerability of escalating doses, while the dose-expansion stage will further evaluate safety, tolerability, and anti-tumor activity in specific tumor types based on initial results.
