Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
MTL-CEBPA is the first small activating RNA (saRNA) therapeutic to be tested in a clinical study. Designed to activate the CEBPA gene, MTL-CEBPA comprises a double stranded RNA payload formulated inside a SMARTICLES® liposomal nanoparticle.
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 in several tissues including myeloid cells, liver cells and adipose tissue. In cancer, C/EBP-α plays an important role in regulating tumour growth and the tumour immune microenvironment.
For more information on MTL-CEBPA check out these publications:
MTL-CEBPA DRUG PRODUCT
THE FIRST-IN-HUMAN CLINICAL STUDY OF A saRNA THERAPEUTIC
OUTREACH is a first-in-human Phase I clinical study of MTL-CEBPA, our lead saRNA therapeutic, in patients with liver cancer.
The multi-centre, Phase I study is assessing the safety and tolerability of MTL-CEBPA in patients with advanced primary liver cancer who are ineligible or resistant to standard therapies. MTL-CEBPA has been dosed as a single agent in 38 patients with liver cancer. The study will evaluate the combination of MTL-CEBPA and Sorafenib, the 1st line standard of care.
PRIMARY LIVER CANCER
Liver cancer is the second leading cause of cancer-related deaths worldwide with approximately 745,000 deaths each year.
The overwhelming majority of primary liver cancer (HCC) patients also suffer from an underlying liver disease such as alcoholic liver disease, non-alcoholic fatty liver disease, Hepatitis C virus or Hepatitis B virus which can all progress to fibrosis and cirrhosis of the liver.
The abnormal liver function is a co-morbidity that independently predicts patient survival and reduces eligibility for standard of care therapy. Due to complicating liver diseases as well as late detection, the majority of liver cancer patients have limited treatment options and poor survival.