Ractigen’s RAG-01 becomes second saRNA drug globally to advance to clinical stage: GlobalData

Ractigen Therapeutics, headquartered in China, submitted a clinical trial application for RAG-01 in Australia. This application paves the way for Phase I trial of RAG-01 in patients with non-muscle-invasive bladder cancer (NMIBC) who have not responded to Bacillus Calmette-Guérin (BCG) therapy, making it globally the second saRNA drug to advance into the clinical stage, says GlobalData.

This development signifies a remarkable advancement in RNA-based therapeutic applications, especially in the context of challenging cancer treatments. RAG-01 has shown promising results in preclinical tumor suppression and a solid safety profile. The classes of RNA-based therapies are small-interfering RNAs (siRNA), antisense oligonucleotides (ASOs), small activating RNA (saRNA), circular RNA (circRNA), mRNA therapies, and aptamers.

Nelluri Geetha, Pharma Analyst at GlobalData, comments, “The current marketed drug space of RNA-based therapies has been dominated by mRNA drugs, followed by ASOs and siRNA drugs. The mRNA drugs are approved for infectious disease (COVID-19) and metabolic disorders. ASOs are approved for genetic, metabolic, and central nervous system disorders, and siRNA drugs are approved for metabolic disorders and genito urinary system diseases.”

According to GlobalData’s Pharmaceutical Intelligence Center, the highest development phase of RNA-based therapies for the treatment of oncology is still Phase III for mRNA vaccines (mRNA-4157) and Phase II for both siRNA (lixadesiran with pixofisiran) and saRNA (MTL-CEBPA) drugs. As there are no approved RNA-based therapies for oncology yet, mRNA, siRNA, and saRNA drugs become more noteworthy within this therapy area from a research and development (R&D) perspective.

Mina Therapeutics’ MTL-CEBPA is the first saRNA to advance into clinical trials globally. Currently, it is being tested in Phase II clinical trials in combination with sorafenib for hepatocellular carcinoma (HCC) as second-line therapy in the US and Phase I clinical trials in combination with pembrolizumab for solid tumors. MTL-CEBPA demonstrated an acceptable safety profile and potential synergistic efficacy with sorafenib in HCC. Further, in combination with pembrolizumab, it is safe and well tolerated in heavily pre-treated patients across multiple tumor types.

Geetha concludes, “While most of the RNA-based therapies target infectious diseases and metabolic disorders, the advancement of saRNA therapy would pave the way for new treatment approaches for cancer. Notably, saRNA’s advance into clinical trials can be seen as a major development for RNA-based therapies as well as for the oncology landscape.”