TransCode Therapeutics Initiates Phase 2a Clinical Trial with TTX-MC138 in Patients with ctDNA Positive Colorectal Cancer
Rhea-AI Summary
TransCode Therapeutics (NASDAQ: RNAZ) initiated a Phase 2a trial of lead candidate TTX‑MC138 in patients with ctDNA‑positive colorectal cancer after curative‑intent therapy and no radiographic disease. The study, in collaboration with Quantum Leap Healthcare Collaborative’s PRE‑I‑SPY platform, plans to enroll up to 45 patients.
The FDA‑submitted, IRB‑approved trial uses leading NCCN centers to assess TTX‑MC138’s biological and clinical activity in minimal residual disease, building on Phase 1a safety and durable anti‑tumor effects reported by TransCode.
AI-generated analysis. Not financial advice.
Positive
- Phase 2a trial of TTX‑MC138 initiated in ctDNA‑positive colorectal cancer
- Planned enrollment of up to 45 minimal residual disease colorectal cancer patients
- Collaboration with Quantum Leap Healthcare Collaborative’s PRE‑I‑SPY platform
- FDA submission and IRB approval enabling site activation and enrollment
- Use of NCCN‑affiliated centers with strong colorectal cancer expertise
- Phase 1a data showed encouraging safety and durable anti‑tumor effects per company
Negative
- None.
News Market Reaction – RNAZ
On the day this news was published, RNAZ declined 5.57%, reflecting a notable negative market reaction. Argus tracked a peak move of +11.8% during that session. Our momentum scanner triggered 3 alerts that day, indicating moderate trading interest and price volatility. This price movement removed approximately $320K from the company's valuation, bringing the market cap to $5.42M at that time. Trading volume was above average at 1.8x the daily average, suggesting increased trading activity.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Market Reality Check
Peers on Argus
RNAZ fell 13.62% while close biotech peers showed mixed moves: INAB +1.2%, BOLT +4.91%, EPIX +0.6%, APRE -5.21%, CYCCP -5.61%, suggesting a stock-specific reaction rather than a sector-wide move.
Previous Clinical trial Reports
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Feb 05 | IND amendment filed | Positive | +16.2% | IND amendment for Phase 2a TTX-MC138 colorectal cancer trial with up to 45 patients. |
| Dec 11 | Phase 2a collaboration | Positive | +20.7% | Launch of PRE-I-SPY Phase 2a TTX-MC138 MRD colorectal cancer collaboration with Quantum Leap. |
| May 08 | Phase 1a dosing update | Positive | -1.4% | Completion of Cohort 4 initial dosing in Phase 1a with no dose-limiting toxicities. |
| May 01 | Phase 1a progress | Positive | +38.7% | Positive Phase 1a TTX-MC138 tolerability and PK/PD data supporting expansion to Phase 1b. |
| Mar 27 | Cohort 4 initiated | Positive | -5.8% | Initial dosing of first patient in Cohort 4 of Phase 1 TTX-MC138 trial with no DLTs. |
Clinical trial updates for TTX-MC138 have often triggered sizeable moves, with several strong positive reactions but also occasional negative or muted responses.
Over the past year, TransCode has repeatedly reported progress on its lead candidate TTX-MC138, including Phase 1 dosing milestones and the planned Phase 2a colorectal cancer trial. Clinical updates on safety and target engagement in metastatic cancer and minimal residual disease settings have frequently coincided with large one-day moves, both positive and negative. Today’s initiation of the Phase 2a ctDNA‑guided colorectal cancer trial extends this trajectory from early safety cohorts toward more rigorous efficacy-focused studies.
Historical Comparison
In the past year, TTX-MC138 clinical trial updates moved RNAZ by an average of 13.69%, often upward. Today’s -13.62% reaction to Phase 2a initiation contrasts with that generally positive pattern.
Clinical news has progressed from early Phase 1 safety and dosing cohorts of TTX-MC138 to the PRE-I-SPY Phase 2a MRD colorectal cancer trial, moving from initial tolerability and target engagement toward efficacy-focused evaluation in ctDNA-positive patients.
Regulatory & Risk Context
An effective S-3 shelf dated April 30, 2026 permits resale of up to 15,955,543 common shares by selling stockholders. The company will not receive proceeds from these resales, but the registration increases liquidity for existing holders and potential supply in the market.
Market Pulse Summary
The stock moved -5.6% in the session following this news. The decline reflects a divergence from prior TTX‑MC138 trial updates, which on average moved the stock about 13.69% and often positively. Despite progression to a Phase 2a ctDNA‑guided colorectal cancer trial, recent 8-K filings flag Nasdaq stockholders’ equity noncompliance, and an effective S-3 registering up to 15,955,543 resale shares adds potential supply overhang. These structural factors may have weighed more heavily than the otherwise constructive clinical milestone.
Key Terms
circulating tumor dna (ctdna) medical
minimal residual disease medical
institutional review board regulatory
AI-generated analysis. Not financial advice.
The Phase 2a clinical trial is expected to enroll up to 45 patients with colorectal cancer who have completed standard curative-intent therapy and have no radiographic evidence of disease, but remain or become ctDNA-positive, indicating the presence of minimal residual disease.
Principal investigators are Dr. Emil Lou of the University of
The trial leverages clinical sites currently participating and actively recruiting in QLHC's PRE‑I‑SPY platform trial. Several of those clinical sites are part of the National Comprehensive Cancer Network (NCCN). Those centers have considerable expertise and are at the forefront defining standard-of-care practices for the treatment of cancer.
It is anticipated that the trial will produce new data about the importance of ctDNA testing and the role of TTX-MC138 in reducing the risk of cancer recurrence in this at-risk patient population. The trial has been submitted to the
This clinical trial aims to evaluate the biological and clinical activity of TTX-MC138 in the minimal residual disease setting where therapeutic intervention may have the greatest opportunity to improve long-term outcomes. ctDNA testing is becoming increasingly important in oncology, particularly in colorectal cancer, because it provides a highly sensitive, real-time measure of residual disease and information about tumor biology that traditional methods often fail to detect. This approach has recently been successfully employed in the treatment of patients with muscle invasive bladder cancer.
"TTX-MC138's safety profile, coupled with the durability of its anti-tumor effects, observed in TransCode's Phase 1a clinical trial is particularly encouraging. These findings are consistent with the drug's mechanism of action and provide a basis for a more rigorous efficacy evaluation. This positions TransCode and its collaborators to potentially intervene earlier in a patient's disease, and may in the future offer a new therapeutic option for patients at risk of developing metastatic disease" noted Daniel Vlock, MD, TransCode's Consulting Clinician.
About TTX-MC138
TTX-MC138 is a first-in-class therapeutic candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA widely believed to be critical to the emergence and progression of many metastatic cancers. TransCode's Phase 1a first-in-human clinical trial achieved its primary safety endpoint and established a recommended Phase 2 dose, as announced at ESMO 2025.
About TransCode Therapeutics
TransCode Therapeutics is a clinical stage company pioneering immuno-oncology and RNA therapeutic treatments for high risk and advanced cancers. The company's lead therapeutic candidate, TTX-MC138, is focused on treating metastatic tumors that overexpress microRNA-10b, a unique, well-documented biomarker of metastasis. In addition, TransCode has a portfolio of other first-in-class therapeutic candidates designed to mobilize the immune system to recognize and destroy cancer cells. For more information, visit www.transcodetherapeutics.com.
About the I-SPY TRIALs
The I-SPY ("Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis") Trials were designed to rapidly screen promising experimental treatments and identify those most effective for biologically defined patient subgroups. The trials represent a unique collaboration among the
About Quantum Leap Healthcare Collaborative
Quantum Leap Healthcare Collaborative is a 501(c)(3) nonprofit organization founded in 2005 by UCSF researchers and Silicon Valley innovators. Its mission is to integrate clinical care with research, advance high-impact platform trials, and improve patient outcomes through adaptive learning systems, enhanced data infrastructure, and widespread trial accessibility. Quantum Leap sponsors and manages the I-SPY Trial programs. For additional information, visit www.quantumleaphealth.org.
Forward-Looking Statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements concerning the timing, conduct and results of TransCode's collaborations, TransCode's Phase 1a clinical trial, and TransCode's planned Phase 2a clinical trial, statements about microRNAs and their involvement in cancer, and statements concerning the therapeutic potential of TransCode's TTX-MC138 and other therapeutic candidates. Any forward-looking statements in this press release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risks associated with drug discovery and development; the risk that the results of clinical trials will not be consistent with TransCode's preclinical studies or expectations or with results from previous clinical trials; risks associated with the conduct of clinical trials; risks associated with TransCode's financial condition and its need to obtain additional funding to support its business activities, including TransCode's ability to continue as a going concern; risks associated with the timing and outcome of TransCode's planned regulatory submissions; risks associated with obtaining, maintaining and protecting intellectual property; risks associated with TransCode's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; risks of competition from other companies developing products for similar uses; risks associated with TransCode's dependence on third parties; and risks associated with geopolitical events and pandemics, including the COVID-19 coronavirus and military actions. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause TransCode's actual results to differ from those contained in or implied by the forward-looking statements, see the section entitled "Risk Factors" in TransCode's Annual Report on Form 10-K for the year ended December 31, 2025, as well as discussions of potential risks, uncertainties and other important factors in any subsequent TransCode filings with the Securities and Exchange Commission. All information in this press release is as of the date of this release; TransCode undertakes no duty to update this information unless required by law.
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SOURCE TransCode Therapeutics, Inc.