Evidence of Drug Accumulation in Metastatic Lesions
BOSTON, Oct. 24, 2023 (GLOBE NEWSWIRE) — TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology firm dedicated to extra successfully treating most cancers utilizing RNA therapeutics, right this moment introduced preliminary outcomes with its lead therapeutic candidate, TTX-MC138, within the first affected person enrolled in its Phase 0 medical trial geared toward demonstrating supply of TTX-MC138 to metastatic most cancers, together with metastases past these discovered within the liver. These preliminary information confirmed that radioactivity per accumulation of TTX-MC138 was detected by noninvasive imaging within the areas of the metastatic lesions beforehand recognized by fluorodeoxyglucose (FDG)/positron emission tomography (PET) (FDG/PET). In addition, radiolabeled TTX-MC138 had pharmacokinetic conduct per that anticipated based mostly on non-clinical IND-enabling research. The affected person tolerated the dosing with no reported antagonistic reactions. Metabolite evaluation indicated circulation of intact radiolabeled TTX-MC138 for greater than 20 hours, equal to that predicted by Drug Metabolism and Pharmacokinetics (DMPK) modelling, and that the drug candidate analyzed within the blood was similar to that of the manufactured drug candidate, demonstrating in vivo stability. Complete evaluation of information from this primary affected person is in course of and can be included within the closing report for all sufferers enrolled within the examine.
TransCode’s Chief Technology Officer, Zdravka Medarova, PhD, commented, “We believe these preliminary clinical data support our thesis that TTX-MC138 can be delivered successfully to metastatic lesions for the potential treatment of metastatic cancer. Preclinical evidence pointing towards miRNA-10b’s critical role in metastatic progression across a number of major cancer types suggests that inhibition of miRNA-10b in patients with advanced disease could have a dramatic impact on their disease.”
The Phase 0 trial is an open-label, single-center, microdose examine supposed to display supply of the radiolabeled model of TTX-MC138 to radiographically-confirmed metastases in topics with superior stable tumors. Up to 12 topics could also be enrolled on this medical examine, every of which is anticipated to obtain a single microdose of radiolabeled TTX-MC138 adopted by positron emission tomography/magnetic resonance imaging (PET-MRI) and blood analyses. The trial is meant to quantify the quantity of TTX-MC138 delivered to metastatic lesions, particularly past the liver, and the pharmacokinetics of the therapeutic candidate in these sufferers. The trial is meant to yield vital information relating to TTX-MC138 supply to medical metastases that would inform dose choice and frequency, for additional medical growth. The trial will not be supposed to display a therapeutic impact.
In the sooner IND-enabling research performed in non-human primates (NHP), TTX-MC138 demonstrated lengthy circulation and tissue distribution per hepatic clearance. Data from the NHP examine have been included right into a DMPK mannequin, supposed to mannequin the pharmacokinetics and tissue distribution of TTX-MC138 in people. The mannequin predicted circulation and tissue distribution in people per outcomes from TransCode’s nonclinical research through which quite a few full regressions of metastatic illness have been noticed.
TTX-MC138 consists of an iron oxide nanocarrier conjugated to a nucleic acid particularly designed to inhibit the oncogenic RNA, microRNA-10b. MiRNA-10b has been described because the grasp regulator of most cancers development in a variety of superior stable tumors. TransCode believes that TTX-MC138 has the potential to turn out to be a therapy for a lot of of those cancers. Administration of TTX-MC138 has demonstrated full regression of metastatic illness in a variety of mouse fashions of pancreatic and breast most cancers. In addition, TTX-MC138 was efficiently delivered and demonstrated bioactivity in a case examine of spontaneous feline mammary carcinoma.
“Our Phase 0 trial involves a single microdose of radiolabeled TTX-MC138 followed by noninvasive PET-MRI imaging and metabolite analysis. Given the similarities between humans and non-human primates relative to anatomy, physiology, and molecular biology, we anticipated results in trial patients comparable to those observed in the DMPK model based on our NHP studies, as evidenced by the preliminary data we announced today,” added Michael Dudley, Chief Executive Officer of TransCode.
This examine was executed in collaboration with Andreas Varkaris, MD, PhD, an attending doctor and investigator for the Termeer Center for Targeted Therapies at Massachusetts General Hospital and the principal investigator of TransCode’s examine.
About TransCode Therapeutics
TransCode is an RNA oncology firm created on the assumption that most cancers might be extra successfully handled utilizing RNA therapeutics. Using its iron oxide nanoparticle supply platform, the Company has created a portfolio of drug candidates designed to focus on quite a lot of tumor varieties with the target of considerably enhancing affected person outcomes. The Company’s lead therapeutic candidate, TTX-MC138, is targeted on treating metastatic most cancers, which is believed to trigger roughly 90% of all most cancers deaths totaling over 9 million per yr worldwide. The Company believes that TTX-MC138 has the potential to dramatically enhance medical outcomes in a spread of cancers, together with breast, pancreatic, ovarian and colon most cancers, glioblastomas and others. Another of the Company’s drug candidates, TTX-siPDL1, focuses on treating tumors by concentrating on a protein referred to as Programmed death-ligand 1 (PD-L1). TransCode additionally has three cancer-agnostic packages: TTX-RIGA, an RNA–based mostly agonist of the retinoic acid-inducible gene I designed to drive an immune response within the tumor microenvironment; TTX-CRISPR, a CRISPR/Cas9–based mostly remedy platform for the restore or elimination of cancer-causing genes inside tumor cells; and TTX-mRNA, an mRNA-based platform for the event of most cancers vaccines designed to activate cytotoxic immune responses towards tumor cells.
Forward-Looking Statements
This launch accommodates “forward-looking statements” inside the which means of the Private Securities Litigation Reform Act of 1995, together with, with out limitation, statements regarding preliminary first affected person outcomes of the Phase 0 medical trial of radiolabeled TTX-MC138, statements regarding anticipated medical outcomes of TransCode’s therapeutic candidates, statements in regards to the outcomes of RNA analysis, statements in regards to the potential for treating most cancers with RNA therapeutics, statements in regards to the timing and consequence of anticipated regulatory filings and medical trials, together with the present first-in-human examine of TTX-MC138, and whether or not this examine will display proof-of-mechanism, and statements regarding TransCode’s portfolio of drug candidates and TTX know-how platform typically. Of observe, a Phase 0 medical trial is an exploratory examine, performed underneath an exploratory Investigational New Drug (eIND) software. Exploratory IND research normally contain very restricted human publicity to a therapeutic candidate to judge mechanism of motion with a purpose to inform potential medical analysis in future medical research, however in any other case haven’t any therapeutic intent. Further, warning needs to be taken when deciphering the preliminary outcomes of the Phase 0 trial. This information could differ from future outcomes of this examine, or totally different conclusions or concerns could qualify such outcomes, as soon as further information have been acquired and absolutely evaluated. Preliminary information additionally stays topic to audit and verification procedures which will outcome within the closing information being materially totally different from the preliminary information beforehand printed. Any forward-looking statements on this press launch are based mostly on administration’s present expectations of future occasions and are topic to a variety of dangers and uncertainties that would trigger precise outcomes to vary materially and adversely from these set forth in or implied by such forward-looking statements. These dangers and uncertainties embody, however usually are not restricted to: the chance related to drug discovery and growth; the chance that the outcomes of medical trials we conduct won’t be per our pre-clinical research or expectations; dangers related to the timing and consequence of TransCode’s deliberate regulatory submissions; dangers related to TransCode’s deliberate medical trials for its product candidates; dangers related to acquiring, sustaining and defending mental property; dangers related to TransCode’s means to implement its patents towards infringers and defend its patent portfolio towards challenges from third events; the chance of competitors from different corporations creating merchandise for related makes use of; dangers related to TransCode’s monetary situation and its must get hold of further funding to help its business actions, together with TransCode’s means to proceed as a going concern; dangers related to TransCode’s dependence on third events; and dangers related to the COVID-19 coronavirus. For a dialogue of those and different dangers and uncertainties, and different vital components, any of which might trigger TransCode’s precise outcomes to vary from these contained in or implied by the forward-looking statements, see the part entitled “Risk Factors” in TransCode’s Annual Report on Form 10-Ok for the yr ended December 31, 2022, in addition to discussions of potential dangers, uncertainties and different vital components in any subsequent TransCode filings with the Securities and Exchange Commission. All info on this press launch is as of the date of the discharge; TransCode undertakes no responsibility to update this info except required by regulation.
For extra info, please contact:
TransCode Therapeutics, Inc.
Alan Freidman, VP Investor Relations
[email protected]
