Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
DEVELOPMENT PROGRAMS
MTL-CEBPA
MTL-CEBPA is a new medicine initially being developed as a combination therapy in cancer. The first small activating RNA (saRNA) therapeutic to be tested in a clinical study, MTL-CEBPA is designed to activate the CEBPA gene. MTL-CEBPA comprises a double stranded RNA payload formulated inside a liposomal nanoparticle that is delivered into certain immune cells around the body including subpopulations of myeloid cells.
The CEBPA gene encodes CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of cell lineage determination and differentiation of myeloid cells and other cells types around the body. Myeloid cells are frequently dysregulated in the microenvironment of solid tumours and are understood to be an important resistance hurdle for many anti-cancer medicines. Restoring CEBPA expression in myeloid cells is hypothesised to alter immune cell populations in the tumour microenvironment and improve the efficacy of cancer therapies in solid tumour malignancies.
For more information on MTL-CEBPA check out these publications:
MTL-CEBPA is designed to reactivate the CEBPA gene and consequently restore C/EBP-α protein levels to normal levels in myeloid cells. MTL-CEBPA has been tested in a range of pre-clinical cancer models and has been shown to enhance the anti-tumour activity of kinase inhibitors, checkpoint inhibitors and radiofrequency ablation.
In a Phase I clinical trial MTL-CEBPA was evaluated as a monotherapy in 39 patients with advanced liver cancer. In the study, MTL-CEBPA was generally well tolerated in patients with both healthy and impaired liver function and provided evidence of anti-tumour activity. MTL-CEBPA was also found to mediate RNA Activation in patients’ white blood cells and induce immunological changes in tumour biopsies. Investigators reported complete tumour responses in patients when administered approved liver cancer therapies subsequent to treatment with MTL-CEBPA.
MTL-CEBPA is currently being evaluated in the OUTREACH Phase 1b clinical trial.
MTL-CEBPA DRUG PRODUCT
OUTREACH CLINICAL TRIAL
OUTREACH is a multi-centre Phase Ib clinical study of MTL-CEBPA in combination with Sorafenib in patients with primary liver cancer. The study is assessing the safety, tolerability, pharmacology and anti-tumour activity of MTL-CEBPA in combination with Sorafenib. The study is ongoing in the United Kingdom, Singapore and Taiwan.
To learn more about the OUTREACH clinical trial, please visit ClinicalTrials.gov.
PRIMARY LIVER CANCER
Liver cancer is the second leading cause of cancer-related deaths worldwide with approximately 745,000 deaths each year and the fastest growing cause of cancer deaths in the United States. The majority of liver cancer patients have limited treatment options, with a five-year survival rate of less than 15%. In 2007 Sorafenib, a tyrosine kinase inhibitor, became the first approved therapy for advanced liver cancer and remains the frontline standard of care.