The small U.K. biotech MiNA Therapeutics has begun the first human trial of a small activating RNA drug to help liver cancer patients as it eyes future studies in the lucrative NASH space.
The London-based startup said it has this week treated its first patient in the Phase I OUTREACH trial for candidate MTL-CEBPA in severe, advanced liver cancer for those who can’t use--or are resistant to--current therapies.
The study is the first-in-human trial of a small activating RNA (saRNA) and is designed to assess the safety and tolerability of MTL-CEBPA, an saRNA restoring the expression of CCAAT/enhancer binding protein alpha (C/EBP-α).
C/EBP-α plays an important role in normal liver function and the benefits of increasing its expression have been shown in preclinical models of disease, according to the biotech.
Robert Habib, CEO of MiNA Therapeutics, said: “There is increasing excitement about the possibility of using RNA to induce therapeutic protein production. We believe our unique approach, here applied to the upregulation of C/EBP-α protein, may provide to patients significant benefits over conventional medicines.”
MTL-CEBPA consists of a double stranded RNA formulated into a “Smarticles” liposomal nanoparticle and is designed to activate the CEBPA gene. The Smarticles tech is also used by Bothell, WA-based biotech Marina Biotech ($MRNA), which has also out-licensed some of this tech to ProNAi Therapeutics.
Smarticles uses amphoteric liposomes composed of unique combinations of lipids having anionic and cationic groups that work together to enable cell uptake, provide serum stability, and provide pH-triggered endosomal escape. It is designed to deliver both single-stranded and double-stranded nucleic acid payloads.
The CEBPA gene encodes for the CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of cell lineage determination and differentiation in several tissues including liver, myeloid cells and adipose tissue. In the liver, C/EBP-α plays an important role in normal hepatocyte function and response to injury.
A proof of concept using an early tool compound was published in Hepatology and its preclinical data on MTL-CEBPA in liver cirrhosis were presented at the 2015 AASLD Liver Meeting.
Nanoparticle research in cancer has, however, had a tough ride of late after the pioneering biotech in the field, Bind Therapeutics ($BIND), filed for bankruptcy a month ago amid some weak trial results which saw it cut more than a third of its staff in April--and left a lingering question mark over its methodology.
MiNA came to life from the 2006 work by Long-Cheng Li (who worked for UCSF at the time) and David Corey (UT Southwestern) who found that double strand RNA can not only silence gene expression (RNAi), but also activate it (RNAa).
The company was founded by John Rossi (City of Hope), Pål Sætrom (Norwegian University of Science and Technology) and Nagy Habib (Imperial College London) to apply these research ideas in specific gene activation by double strand RNA to drug discovery and development.
The biotech exclusively in-licensed the original Li and Corey patents--which had previously been licensed to Alnylam Pharmaceuticals ($ALNY).
The company is privately owned and backed by angel investors. It currently owns its programs but Habib told FierceBiotech, when asked about whether he wanted a Big Pharma partner, that that he believes: “The breadth of our product engine lends itself to both internal development and partnering.”
Habib said that the first target is liver cancer, which has few therapies outside of Bayer’s Nexavar and comes with poor survival rates, but will also pursue testing in liver cirrhosis and fatty liver disease NASH--the potential blockbuster $40 billion market currently being pursued by Gilead ($GILD), Intercept ($ICPT) and the small French biotech Genfit.
Habib said that his company will in fact be presenting its data on NASH at the EASL Liver Fibrosis meeting later this month.
In terms of a timeline for its liver cancer trial, Habib said: “We expect to complete the Part 1 dose escalation around the end of the year and Part 2 dose expansion in the second half of 2017. Early data from the trial will likely be presented in 2017.”