BOSTON, May 27, 2026
TransCode Therapeutics, Inc., a clinical-stage biotechnology company focused on RNA-based cancer therapeutics, has announced the initiation of its Phase 2a clinical trial evaluating TTX-MC138 in patients with circulating tumor DNA (ctDNA)-positive colorectal cancer following curative-intent treatment. The study is being conducted in collaboration with Quantum Leap Healthcare Collaborative (QLHC) through the PRE-I-SPY clinical trial platform and is expected to further advance precision oncology strategies targeting minimal residual disease (MRD) in high-risk colorectal cancer patients.
The Phase 2a study represents an important milestone for TransCode Therapeutics and the broader field of RNA therapeutics in oncology. Researchers increasingly believe that ctDNA-guided treatment approaches may help identify patients at elevated risk of cancer recurrence even after surgery, chemotherapy, or radiation therapy appears successful through conventional imaging scans. By targeting molecular evidence of residual cancer before visible recurrence occurs, scientists hope to improve long-term survival outcomes and potentially prevent metastatic disease progression.
According to the company, the study plans to enroll up to 45 colorectal cancer patients who have completed standard curative-intent therapy and show no radiographic evidence of disease but remain or become ctDNA-positive, indicating the presence of minimal residual disease. Persistent ctDNA positivity is increasingly recognized as a highly sensitive marker of residual microscopic cancer cells that conventional imaging technologies may fail to detect. The trial will be led by principal investigators Dr. Emil Lou of the University of Minnesota and Dr. Zhaohui Jin of the Mayo Clinic Comprehensive Cancer Center, while Dr. Paula Pohlmann of MD Anderson Cancer Center will serve as study chair. Several participating clinical sites are part of the National Comprehensive Cancer Network (NCCN) and are considered leaders in precision oncology and colorectal cancer treatment research.
TTX-MC138 Targets Metastatic Cancer Pathways
TTX-MC138 is a first-in-class RNA therapeutic candidate designed to inhibit microRNA-10b (miR-10b), a molecular biomarker strongly associated with cancer metastasis and aggressive tumor progression. According to TransCode Therapeutics, miR-10b plays a critical role in enabling tumor cells to invade surrounding tissues and spread throughout the body. The company believes inhibiting this pathway may significantly reduce recurrence risk and metastatic disease development in patients with minimal residual disease after initial therapy.
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The therapy previously demonstrated encouraging findings during the company’s earlier Phase 1a first-in-human clinical trial, which achieved its primary safety endpoint and established a recommended Phase 2 dose. Those findings were presented at ESMO 2025, further strengthening scientific confidence in the therapeutic approach. Daniel Vlock, MD, consulting clinician for TransCode Therapeutics, stated that the favorable safety profile and durable anti-tumor effects observed in earlier studies provide strong support for advancing TTX-MC138 into more rigorous efficacy evaluation in the MRD setting.
ctDNA-Guided Precision Oncology Gains Momentum
The trial also highlights the rapidly expanding role of ctDNA testing within precision oncology. ctDNA analysis enables clinicians to detect fragments of tumor-derived DNA circulating in a patient’s bloodstream, providing a highly sensitive and real-time assessment of residual disease activity. In colorectal cancer, ctDNA testing is increasingly being explored as a tool for recurrence prediction, treatment monitoring, and earlier therapeutic intervention.
Researchers believe patients who remain ctDNA-positive after standard therapy face substantially higher risks of recurrence compared with ctDNA-negative patients. The ability to intervene during the MRD phase — before overt metastatic disease develops — could significantly transform future cancer treatment strategies. The PRE-I-SPY platform, operated by Quantum Leap Healthcare Collaborative, was specifically developed to accelerate biologically targeted therapies into earlier disease settings where intervention may produce stronger long-term benefits.
RNA Therapeutics Continue Expanding in Oncology
The launch of the Phase 2a study reflects growing pharmaceutical and biotechnology industry investment in RNA-based therapeutics for cancer treatment. RNA-targeting approaches, including antisense oligonucleotides, siRNA therapies, and microRNA inhibitors, are emerging as promising new treatment modalities capable of targeting molecular pathways previously considered difficult to address using traditional small molecules or biologics.
Industry analysts believe ctDNA-guided precision medicine and RNA therapeutics may become increasingly integrated within future oncology care as researchers seek earlier, more personalized interventions for high-risk cancer patients. If successful, TTX-MC138 could potentially establish a new therapeutic strategy aimed at reducing recurrence risk in colorectal cancer patients with minimal residual disease and improving long-term clinical outcomes.
Source: TransCode Therapeutics press release
