December 4, 2022

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RNA activation therapy for advanced liver cancer enters the clinic trials

Innovative combination of RNA activation therapy for first-line treatment of advanced liver cancer enters the clinic trails



RNA activation therapy for advanced liver cancer enters the clinic trials.

Innovative combination of RNA activation therapy for first-line treatment of advanced liver cancer enters the clinic trails

On December 1, 2021, the Cancer Institute of the National University of Singapore (NCIS) and MiNA Therapeutics jointly announced that MiNA’s small-activated RNA therapy MTL-CEBPA, combined with standard treatments atezolizumab and bevacizumab (bevacizumab), is the first-line treatment for advanced liver The phase 1 clinical trial for patients with cell carcinoma (HCC) has completed the first patient’s administration.

Atezolizumab is a PD-L1 inhibitor. The combination of treatment with anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is the first first-line immunotherapy for liver cancer approved by the FDA.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. According to statistics, more than 750,000 people worldwide suffer from hepatocellular carcinoma each year.

The main causes of HCC are chronic hepatitis caused by hepatitis B or C virus infection, and liver cirrhosis caused by drinking or non-alcoholic steatohepatitis.

The phenomenon that can specifically up-regulate targeted genes is called RNA activation (RNAa), and those small double-stranded RNAs with RNAa function are called small activating RNA (saRNA).

The chemical structure of saRNA is similar to siRNA, it recruits the endogenous transcription complex to the target gene, resulting in increased mRNA expression and up-regulation of target protein expression.

The press release pointed out that MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α). CCAAT/enhancer binding protein alpha is a transcription factor that determines the lineage of myeloid cells. The main regulator of differentiation.

Disorders of myeloid cells are related to many diseases. MTL-CEBPA aims to restore C/EBP-α protein to normal levels through the RNA activation mechanism and reduce the immunosuppressive effect of myeloid cells.

It is composed of double-stranded RNA encapsulated by liposomal nanoparticles.

In preclinical studies, it has been proven that MTL-CEBPA can improve the anti-tumor activity of cancer treatment by targeting dysregulated myeloid cells and reducing their inhibitory effect in the tumor microenvironment.

The open-label Phase 1 trial will enroll approximately 30 patients with unresectable or advanced HCC who have not received systemic therapy in the past.

The main purpose of the dose escalation phase is to determine dose-limiting toxicity, and the primary end point of the dose extension phase is the patient’s objective response rate (ORR). The trial is expected to obtain data in 2023.

Reference:

[1] National University Cancer Institute, Singapore and MiNA Therapeutics Announce Initiation of a Phase 1 Clinical Study of MTL-CEBPA in Combination With First-line Standard of Care in Advanced Liver Cancer. Retrieved December 1, 2021

RNA activation therapy for advanced liver cancer enters the clinic trials

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