Dicerna Pharmaceuticals and Boehringer Ingelheim today announced a research collaboration and license agreement to discover and develop novel RNAi therapeutics for the treatment of chronic liver diseases.  Dicerna can get up to $201 million in upfront and success-based development and commercialization milestones for an undisclosed target.

Coming off $70 million in financing, Dicerna Pharmaceuticals Chief Executive Officer Douglas Fambrough said the company is moving forward with its RNA interference (RNAi) programs, taking three through human proof-of-concept studies.

In an exclusive interview with BioSpace, Fambrough said Dicerna is at “a very interesting place.”

“We’ve had some ups and downs, but things are looking up as we’re going forward,” he said, referring to the financing round and the proof-of-concept studies. “We’re about to press the accelerator on this company.”

RNA interference is a natural mechanism of gene silencing. Much of the interest in RNAi is based on the fact that the RNAi mechanism operates upstream of protein production by silencing the mRNA that codes for such proteins, thereby preventing the disease-causing proteins from being made in the first place. Fambrough said the technology is very precise in the way it can be used to deactivate a gene that carries a disease.

Using its GalXC RNAi technology platform, Dicerna will take on various liver diseases and cardiovascular disease. Dicerna’s GalXC enables subcutaneous delivery of Dicerna’s RNAi therapies to hepatocytes in the liver, where they are designed to specifically bind to receptors on target cells, potentially leading to internalization and access to the RNAi machinery within the cells

The belief is that some treatments using RNAi will be a one-time thing, an effective cure. It’s very promising technology, but Fambrough said the broader pharmaceutical industry is looking for companies that specialize in RNAi to prove its efficacy. That’s now the goal of Fambrough – to move from a technology-based company to a clinically-based company.

“They want us to prove it. We have the capital, we have the molecules. We have everything we need, so we are going to prove it,” he said.

Dicerna is planning to launch studies of two orphan diseases and hepatitis B. Now in its second generation, Fambrough said the GalXC platform is outperforming. He said the benefits are more potent and last longer. When dosing patients with GalXC, Fambrough said they expect it to be monthly, but it’s proving so effective, dosing could only be required quarterly.

“We’re very excited about this technology. We’ve shown that it’s robust against different genes,” Fambrough said.

One disease the company plans to take on with its RNAi platform is primary hyperoxaluria, a genetic disease that causes the liver to make too much oxalate. Patients diagnosed with the disease are unable to absorb the oxalate. Their body attempts to expel it through the urine. However, the oxalate tends to build up inside the body in the form of crystals, which can eventually shut down the kidneys.

“Even when your kidneys shut down the liver is pumping out the oxalate and it gets throughout your body and becomes a debilitating disorder,” Fambrough said. “The only way left now to treat it is with a kidney and liver transplant.”

With liver and kidney patients, Fambrough said the outlook for those patients isn’t that optimistic. Scientists know what causes primary hyperoxaluria, now it’s a matter of learning how to silence the gene, he said.

In addition to its clinical advancements, Fambrough said Dicerna is in talks with pharma companies for possible collaborations. Fambrough declined to name the companies, but said the opportunities are exciting.

Fambrough also addressed an ongoing lawsuit filed by competitor RNAi company, Alnylam. In 2015, Alnylam charged Dicerna with a trade secret misappropriation in a lawsuit regarding the company’s GalNAc conjugate technology. In its complaint, Alnylam said beginning in 2013 Dicerna attempted to acquire the “assets, research and development advances and intellectual property” of RNAi therapeutics developed by Sirna Therapeutics, a subsidiary of Merck & Co., which Alnylam acquired in 2014. The company alleges Dicerna, which unsuccessfully competed for the acquisition of Sirna, “resorted to other means to obtain the confidential information and trade secrets” to “establish itself as a viable competitor to scientific innovators such as Alnylam in the field of siRNA therapies and delivery technologies.”

Dicerna has objected to the lawsuit and Fambrough described it as “harassment” by the larger company. But, he said it was something that was likely to turn out to be nothing in the long term.

Despite the lawsuit, Fambrough said Dicerna is ready to show the industry what it’s got in its pipeline and is out to prove it to any doubters.

“For people who say ‘it’s not in the clinic,’ or ‘there’s a lawsuit,’ we just had some savvy investors invest tens of millions of dollars with us. They bet their money on us. I think that’s an important thing to remember.”