Marina Biotech this week presented early results from in vivo studies in rodent cancer models demonstrating effective delivery of a microRNA mimetic using the company's di-alkylated amino acid, or DiLA2, delivery system.
The initial results showed that miRNA copies per tumor cells in liver, lung, and heart tissues increased by as much as 100-fold compared to baseline levels. They mark the first data that the company has provided on its work on microRNA therapeutics since first signaling its interest in the field in June (GSN 6/10/2010).
At the Rodman & Renshaw Healthcare Conference in New York this Week, Michael French, president and CEO of Marina, noted that the work, which was conducted with Mirna Therapeutics, also showed downregulation of the intended gene targets.
In one case, the miRNA mimetic delivered via the company's DiLA2 liposomes demonstrated sustained 60-percent knockdown for 72 hours, French said.
He also stressed that the molecules do not appear to cross the blood-brain barrier.
The data "support our plans to expand our therapeutic reach beyond our proprietary UsiRNA-based therapies to include both microRNA mimetics and antagomirs," French said in a statement.
Marina, formerly MDRNA, has to date focused on using the DiLA2 technology to deliver siRNAs, but the company has been exploring the possibility of using the technology to deliver microRNA as well. These initial steps led miRNA therapeutics developer Mirina to recently file a trademark-infringement suit against the company for offering nearly identical services under a very similar name (GSN 9/2/2010).
However, at the Rodman & Renshaw conference French stressed that Marina intends to build a technology portfolio that will allow it to develop a broad range of RNA-based therapeutics, from RNAi- to miRNA- and antisense-based drugs.
In particular, French noted that the company's recent acquisition of Cequent Pharmaceuticals, which gave it the orally delivered transkingdom RNAi, or tkRNAi, technology (GSN 4/1/2010), combined with its purchase in July of Novosom's Smarticle delivery technology (GSN 7/29/2010), creates a broad portfolio of delivery technologies that will help it address a range of challenges in the RNAi drugs space.
"Our philosophy on this is that there's not one single delivery technology that's going to open up the opportunity of RNAi-based therapeutics," French said. "We started with our lipid-based system DiLA2, and DiLA2 is going to be great for some things, good for others, and terrible for other things."
As an example, he said that DiLA2 is "great for local delivery to the bladder" but "is never going to be orally administered," which would limit the company's ability to target certain disorders.
"Hence our acquisition of Cequent," which provided "a new drug-discovery engine, orally administered, so we can go after [gastrointestinal] disorders — whether inflammatory disorders like Crohn's or [other inflammatory bowel diseases], or oncology disorders like [familial adenomatous polyposis], or potentially colon cancer or Barrett's esophagus," a condition that often leads to esophageal cancer.
Likewise, he said that the company next acquired Novosom's delivery IP assets as part of its strategy to accumulate "multiple lipid-based delivery systems."
French said that Marina is currently beginning to integrate Novosom's Smarticle technology into its research pipeline. "We think Smarticles has its place and what we're trying to do now is identify where that is and exploit it, and find it in conjunction with our DiLA2 technology."
Rather than staying focused on a single technology, which can be akin to "putting a square peg into a round hole" when it comes to solving RNAi delivery issues, French said that the company's broad suite of tools should give it an edge when it comes to pharma partnerships.
"If a pharma company comes and says, 'Here's my target that I can't get to with small molecules or a monoclonal antibody,' we say, 'Well, here are the choices: we can take an siRNA approach, going after the RNAi pathway … so if we can get it there with the delivery capability that we have, [it's] a great therapeutic agent.'"
Or, "if we have delivery challenges, we might have to go to an antisense approach, where delivery is not so much of an issue, but it's a therapeutic indication where a one-to-one relationship can be therapeutic."
To be sure, Marina isn't putting all of its eggs in the pharma-partnership basket. During the Rodman & Renshaw conference, French stressed that the company plans to commercialize its lead candidate — Cequent's CEQ508, for familial adenomatous polyposis — entirely on its own, though it is not entirely ruling out a partner for it.
"If you're depending upon a partner, then that's another set of dice you have to roll," he said. "So as we look at programs that we want to advance to the clinic, I think they have to be programs that we're prepared to take all the way."
French said that Marina plans to begin enrolling patients for a phase 1b/2a clinical trial of CEQ508 "in the coming weeks, and dose shortly thereafter."
He noted that Pfizer was able to get Celebrex approved for FAP after a pivotal phase 2 trial because it is an orphan drug and was therefore granted an expedited review. French said that fact, combined with the compound's "low cost of goods," leads him to believe that Marina can get CEQ508 through the approval process for between $5 million and $10 million.
Marina is not entirely ruling out a partner for the drug, however. "If someone comes along and opportunistically wants to license it, we would certainly entertain that, but we feel confident that we can take this compound into the market," he said. "It's a unique opportunity for us."