On August 24, 2023 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported the dosing of the first subject in its First-in-Human Phase 0 clinical trial (Press release, TransCode Therapeutics, AUG 24, 2023, View Source [SID1234634685]). The Phase 0 trial is an open-label, single-center, microdose study intended to demonstrate delivery of the radio-labeled version of TransCode’s lead therapeutic candidate, TTX-MC138, to radiographically-confirmed metastases in subjects with advanced solid tumors.
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The subject received a single subtherapeutic dose of radiolabeled TTX-MC138 and appeared to tolerate the dosing well. Analysis and monitoring of data from this subject is ongoing including results of positron emission tomography-magnetic resonance imaging (PET-MRI), to determine uptake of TTX-MC138 to the subject’s metastatic lesions. Enrollment of additional subjects is also currently underway.
TTX-MC138 is designed to inhibit the pro-metastatic RNA, microRNA-10b, described as the master regulator of metastasis in a number of advanced solid tumors. TransCode believes that TTX-MC138 could be used as a treatment for many of these cancers.
"We are pleased to have commenced our First-in-Human (FIH) clinical trial," said TransCode’s Chief Executive Officer and co-founder, Michael Dudley. "The capability to deliver nucleic-acid based therapeutics to cancer represents a major turning point in the field of RNA because it opens up the possibility of developing an entire new class of drugs against most previously undruggable genetic targets. Overcoming this challenge could constitute an unprecedented step in unlocking therapeutic access to a range of cancers and beyond. Demonstrating successful delivery to cancer using TransCode’s proprietary TTX delivery platform could also enable progress towards more personalized cancer therapy guided by genetic profiling."
The Company believes that TTX-MC138 has the potential to dramatically improve clinical outcomes in a range of cancers, including breast, pancreatic, ovarian and colon cancer, glioblastomas and others. In a preclinical murine model of triple-negative breast cancer (TNBC), treatment with TTX-MC138 eliminated pre-existing local metastases in 100% of treated animals representative of stage II/III metastatic cancer. In a more aggressive murine model representative of stage IV metastatic cancer, treatment with TTX-MC138 resulted in elimination of distant metastases in 65% of animals treated. In a murine model of pancreatic adenocarcinoma, administration of TTX-MC138 as monotherapy resulted in complete responses, manifested as regression without recurrence, in 40% of treated animals. In addition to murine models of cancer, TTX-MC138 was successfully delivered and demonstrated preliminary efficacy in spontaneous feline mammary carcinoma.
TransCode’s Chief Technology Officer and co-founder, Dr. Zdravka Medarova, said, "TTX-MC138 is a first-in-class therapeutic candidate against cancer, not only because of its molecular mechanism of action as an inhibitor of a noncoding RNA, but also because of its novel relevance to metastatic disease. There is currently a lack of drugs in cancer therapy that specifically exploit features unique to drivers of metastatic disease. If successful, TTX-MC138 could help demonstrate the potential for treatments specific to metastatic progression offering new hope for advanced cancer subjects who often have limited options for long-term disease remission."
A Phase 0 clinical trial is an exploratory study conducted under an Investigational New Drug application. Up to 12 subjects may be enrolled in this clinical trial, each of which is intended to receive a single microdose of radiolabeled TTX-MC138 followed by 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 subjects, but not to have a therapeutic effect. The trial could yield critical data regarding therapeutic dosing, timing, and potential safety that could inform later clinical trials, including a Phase 1 trial planned to commence in 2024.