Nucleonics announced last month that it has signed a deal to evaluate Novosom’s Smarticles technology as a way to deliver its expressed interfering RNAi drug candidates for hepatitis B and C, expanding the RNAi-based drug developer’s stable of potential delivery techniques to three.
According to Novosom, Smarticles are fully charge-reversible liposome particles: Under normal physiological conditions, the particles are negatively charged, but as pH drops during endocytosis, the particicles’ surfaces become neutral, and eventually positive. This, Novosom states on its website, ensures “stable and aggregate-free travel within the bloodstream, but the acidification from endocytosis switches the charge of Smarticles leading to membrane fusion and the escape of the cargo from the endosome.”
Under the terms of the companies’ agreement, Nucleonics will provide its RNAi drug candidates to Novosom, which will formulate them with the Smarticle technology. Nucleonics will then evaluate the resultant compound in animal models.
Nucleonics has the option to exclusively license the Smarticles technology for the delivery of RNAi-type gene therapy treatments for hepatitis B and C. The option agreement “is strictly for expressed-interfering RNA or, if you’re talking in our competitors terminology, ddRNAi,” Nucleonics president and CEO Robert Towarnicki said, referring to the RNAi technology made by Benitec.
In exchange, Nucleonics has agreed to pay an undisclosed fee to cover Novosom’s costs associated with making drug formulations, Towarnicki told RNAi News. Additionally, if Nucleonics exercises its option, Novosom stands to receive undisclosed fees, milestones, and royalties, he said.
“[Novosom has] some unique and patented technology that looks very efficient for liver delivery — we think its strongest suit is the liver,” Towarnicki said. “We decided to evaluate it as a backup [to our other delivery technologies] and a second-generation opportunity for us to deliver our hepatitis B and hepatitis C products.”
Smarticles, if licensed, would join two other delivery technologies Nucleonics is working with. The company has already licensed or is in the process of licensing from Wyeth a bipuvicaine and a spermine delivery technology, Towarnicki noted. Wyeth is the former home of Nucleonics co-founders Catherine Pachuk and C. Satishchandran, and it is the company from which Nucleonics licensed its core eiRNA technology.
“Bipuvicaine is a local anesthetic [that] complexes with the DNA, and … the liver metabolizes [it],” he said. “Importantly, it [also] stabilizes the DNA. Bipuvicaine/DNA complexes have been stable for over seven years at room temperature.” Towarnicki added that the complexes have already been used in more than 500 patients in clinical trials so its safety is established, but that it is an inefficient delivery method.
Nucleonics is also considering using a modified spermine, which complexes with DNA and is attached to a targeting ligand, Towarnicki said. “When we put the appropriate ligands for hepatocytes on … the spermine system [can deliver] 100 percent of the DNA in the first pass,” he said. “It’s cleared out of the bloodstream in an IV bolus in the first pass through the liver.”
Towarnicki said that Nucleonics anticipates selecting one of the three delivery technologies for its hepatitis B and C programs by the end of the year.