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.
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 microenvironment. Activating CEBPA expression in the tumour microenvironment is hypothesised to improve the efficacy of cancer therapies in solid tumour malignancies.
For more information on MTL-CEBPA check out these publications:
By restoring C/EBP-α mRNA and protein expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse disease in a range of pre-clinical studies including various models of solid tumours. In pre-clinical studies MTL-CEBPA was shown to enhance the anti-tumour activity of standard of care treatments for liver cancer including sorafenib, anti-PD1 checkpoint inhibition and radiofrequency ablation.
In a Phase I clinical trial MTL-CEBPA was evaluated as a monotherapy in 38 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. Investigators reported complete tumour responses in patients when administered approved liver cancer therapies subsequent to treatment with MTL-CEBPA.
In the future we expect to initiate multiple additional clinical trials of MTL-CEBPA.
MTL-CEBPA DRUG PRODUCT
OUTREACH
THE FIRST-IN-HUMAN CLINICAL STUDY OF A saRNA THERAPEUTIC
OUTREACH is a Phase Ib clinical study of MTL-CEBPA, our lead saRNA therapeutic, in patients with liver cancer.
The multi-centre, Phase Ib study is assessing the safety, tolerability and anti-tumour activity of MTL-CEBPA in combination with Sorafenib in patients with advanced primary liver cancer. Sorafenib is the 1st line standard of care in liver cancer. The study is recruiting patients in the United Kingdom, Singapore and Taiwan.
To learn more about the OUTREACH clinical trial, please visit ClinicalTrials.gov or contact us at clinicaltrials@minatx.com.
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.
Due to complicating liver diseases as well as late detection, the majority of liver cancer patients have limited treatment options, with a five-year survival rate of less than 15%.