Transcode Therapeutics announces results of TTX-MC138 in non-human primates

TransCode Therapeutics announced results with its lead therapeutic candidate, TTX-MC138, in non-human primates, showing that the therapeutic effectively engaged its target and showed favorable pharmacokinetics and tissue distribution. In the study, non-human primates were injected with a microdose of radiolabeled TTX-MC138 and imaged by positron emission tomography-magnetic resonance imaging to determine the pharmacokinetics and tissue distribution of the therapeutic. In addition, the pharmacodynamic activity of radiolabeled TTX-MC138 following a microdose injection was determined by measuring inhibition of the therapeutic target, miRNA-10b, using qRT-PCR. TTX-MC138 demonstrated a long circulation half-life and tissue distribution consistent with hepatic clearance. Importantly, even at a microdose, the therapeutic showed lasting activity and significantly inhibited its target, miRNA-10b, known to be a driver of metastatic progression in a number of cancers. Data from the NHP study were incorporated into a Drug Metabolism and Pharmacokinetics model, intended to model human exposure to TTX-MC38. The model predicted a long circulation and tissue distribution in humans, similar to results seen in preclinical studies of cancer in which complete regressions of metastatic disease were seen. TTX-MC138 consists of an iron oxide nanocarrier conjugated to a nucleic acid designed to inhibit the oncogenic RNA, microRNA-10b. MiRNA-10b is described as the master regulator of cancer progression in a number of advanced solid tumors. TransCode believes that TTX-MC138 could become a treatment for many of these cancers. Administration of TTX-MC138 has resulted in complete regression of metastatic disease in mouse models of pancreatic and breast cancer. In addition, TTX-MC138 was successfully delivered and demonstrated preliminary efficacy in a case study of spontaneous feline mammary carcinoma. The study was done in collaboration with Dr. Peter Caravan, co-director of the Institute for Innovation in Imaging at Massachusetts General Hospital and a Professor of Radiology at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital and Harvard Medical School. TransCode is enrolling patients in a first-in-human clinical trial with TTX-MC138 in patients with advanced solid cancers. In this clinical trial, up to 12 patients will be given a single microdose of radiolabeled TTX-MC138 followed by noninvasive PET-MRI. The trial is intended to quantify the amount of TTX-MC138 delivered to metastatic lesions and the pharmacokinetics of the therapeutic candidate in cancer patients. The trial could yield important data regarding TTX-MC138 delivery to clinical metastases that could inform dose selection, dosing frequency, and patient selection to expedite the path to success in later stage clinical trials. This trial is not intended to have therapeutic efficacy.