Developing First-in-Class RNA Oncology Therapeutics and Diagnostics
TransCode Therapeutics has developed a modular, iron oxide nanoparticle–based nanocarrier system for the delivery of RNA therapeutics to tumors. The platform's design is intended to overcome issues of stability, efficiency, and immunogenicity faced by existing lipid and liposomal nanoparticle platforms while optimizing targeting of and accumulation in tumor cells and metastatic sites. The company’s lead therapeutic candidate, TTX-MC138, targets microRNA-10b (miRNA-10b), a master regulator of metastatic cell viability in a range of cancers, including breast, pancreatic, ovarian, colon cancer, glioblastomas and others. The company intends to file an exploratory investigational new drug (eIND) application to conduct its first-in-human clinical trial scheduled to be completed in 2H of 2022. Additionally, the Company will finalize IND-enabling studies for TTX-MC138 in order to file an IND for its Phase I/II clinical trial expected in 2023.
The company’s other preclinical programs include two solid tumor programs—TTX-siPDL1, a small interfering RNA (siRNA)–based modulator of programmed death-ligand 1 (PD-L1), and TTX-siLin28b, an siRNA-based inhibitor of RNA-binding protein LIN28B. TransCode also has three cancer agnostic programs—TTX-RIGA, an antisense RNA–based agonist of the retinoic acid-inducible gene I (RIG-I)–driven immune response in the tumor microenvironment, TTX-CRISPR, a CRISPR/Cas9–based therapy platform for the repair or deletion of cancer-causing genes inside tumor cells, and TTX-mRNA, an mRNA-based platform for the development of cancer vaccines that activate cytotoxic immune responses against specific tumor cells.
Our initial FIH clinical study is intended to provide positive proof-of-mechanism for the TTX platform. We believe that demonstrating our ability to overcome the challenge of RNA delivery to genetic targets outside of the liver would represent a major step forward in unlocking therapeutic access to genetic targets involved in a range of cancers. We intend to build a broad and diverse pipeline of therapeutics and diagnostics with the potential to reach well documented previously undruggable genetic targets .
The company’s other preclinical programs include two solid tumor programs—TTX-siPDL1, a small interfering RNA (siRNA)–based modulator of programmed death-ligand 1 (PD-L1), and TTX-siLin28b, an siRNA-based inhibitor of RNA-binding protein LIN28B. TransCode also has three cancer agnostic programs—TTX-RIGA, an antisense RNA–based agonist of the retinoic acid-inducible gene I (RIG-I)–driven immune response in the tumor microenvironment, TTX-CRISPR, a CRISPR/Cas9–based therapy platform for the repair or deletion of cancer-causing genes inside tumor cells, and TTX-mRNA, an mRNA-based platform for the development of cancer vaccines that activate cytotoxic immune responses against specific tumor cells.
Our initial FIH clinical study is intended to provide positive proof-of-mechanism for the TTX platform. We believe that demonstrating our ability to overcome the challenge of RNA delivery to genetic targets outside of the liver would represent a major step forward in unlocking therapeutic access to genetic targets involved in a range of cancers. We intend to build a broad and diverse pipeline of therapeutics and diagnostics with the potential to reach well documented previously undruggable genetic targets .
We utilize a modular drug design employing tools from the drug discovery toolbox we have created to develop product candidates that we believe can efficiently deliver RNA therapeutics to genetic targets. There are four distinct RNA strategies that we are developing to treat cancer including RNA interference, or RNAi, Pattern Recognition Receptors, or PRRs, Clustered Regularly Interspaced Palindromic Repeats, or CRISPR, and messenger RNA, or mRNA, vaccines. The first approach we are developing is using RNAi to “silence” or turn off the production of specific genes that cause cancer. RNAi is a natural biological process that regulates gene expression by “interfering” with mRNA, the carrier of DNA’s instructions for making new proteins. To date, we have utilized this approach to develop novel product candidates for treatment of metastasis and additional therapeutic areas in oncology. Our lead therapeutic candidate, TTX-MC138, is focused on treating metastatic cancer which has been shown to cause the majority of all cancer deaths.
RNAi Therapeutic Candidates
Lead Therapeutic Candidate
TTX-MC138 - Targeting miR-10b to treat metastatic cancer
Lead Therapeutic Candidate
TTX-MC138 - Targeting miR-10b to treat metastatic cancer
- Targets microRNA-10b, or miR-10b, believed to be the driver of metastasis
- Validated in preclinical studies
- Broad applicability across multiple solid tumors
Other RNAi Therapeutic Candidates
TTX-siPDL1 - Checkpoint inhibitor targeting PDL1
TTX-siPDL1 - Checkpoint inhibitor targeting PDL1
- Currently conducting preclinical studies
- Broad applicability across multiple solid tumors
TTX-siLin28b - Targeting Lin28b protein
- Currently conducting preclinical studies
- Broad applicability across multiple solid tumors
Pattern Recognition Receptor (PRR) Therapeutic Candidate
The second RNA approach we are developing targets the Retinoic acid-inducible gene I (RIG-I) which is a cytosolic nucleic acid sensing Pattern Recognition Receptor (PRR) of the innate immune system. Our therapeutic candidate TTX-RIGA is intended to initiate RIG-I activation with the potential to program a lasting immune response against cancer.
TTX-RIGA - Activates RIG-I signaling pathway
The second RNA approach we are developing targets the Retinoic acid-inducible gene I (RIG-I) which is a cytosolic nucleic acid sensing Pattern Recognition Receptor (PRR) of the innate immune system. Our therapeutic candidate TTX-RIGA is intended to initiate RIG-I activation with the potential to program a lasting immune response against cancer.
TTX-RIGA - Activates RIG-I signaling pathway
- Activates RIG-I signing pathway to generate an immune response against a designated cancer type
- Currently in development
- Potential to treat any form of solid tumor
CRISPR and mRNA Therapeutic Candidates
Our next RNA approaches are in early stages of discovery and consists of two candidates, TTX-CRISPR and TTX-mRNA, which are designed to treat cancer using the RNA approaches of CRISPR and mRNA vaccine technologies.
TTX-CRISPR - Potential to repair or delete cancer causing genes
Our next RNA approaches are in early stages of discovery and consists of two candidates, TTX-CRISPR and TTX-mRNA, which are designed to treat cancer using the RNA approaches of CRISPR and mRNA vaccine technologies.
TTX-CRISPR - Potential to repair or delete cancer causing genes
- Currently in early stage discovery
- Potential to treat any form of solid tumor
- Currently in early stage discovery
- Potential use in all cancer types