A startup dream has been realized, while an old pharma company tries to turn a new leaf.
On Monday, 60-year-old Purdue Pharma announced a strategic partnership with Exicure, a 2009 startup that could pull as much as $790 million and royalties if its drug candidates succeed.
For that investment, Purdue gets an option and licensing agreement for an investigational psoriasis drug and three other molecules based on the same novel nucleic acid platform.
Perhaps more importantly, the villainized owner of the widely abused painkiller Oxycontin gets to turn a new leaf with R&D. It can associate itself with something other than the opioid epidemic.
Success for both parties hinges on Exicure’s Spherical Nucleic Acid (SNA) technology.
While other companies, such as Ionis Pharmaceuticals and Alnylam work with single or double-stranded RNA, Exicure takes short-stranded RNA molecules and wraps them into a three-dimensional spherical shape. According to Exicure CEO David Giljohann, this allows the molecules to be ‘avidly’ absorbed by scavenger receptors on the surface of different cells.
Absorption is key, as the RNA has to bind and suppress a target gene within the nucleus of the cell. Until now it has been a major roadblock in the field, preventing the technology from moving far beyond liver cells, which are an easier target for standard nucleic acid strands.
“What that receptor has allowed us to do is think about different organs that we can target in the nucleic acid space, beyond the traditional liver-type indications,” Giljohann explained in a phone interview, referring to the scavenger receptors.
“What we’ve been interested in is, because we can leverage this high uptake in the cells and tissues, we can think about local, topical delivery of nucleic acids in areas like the skin, the G.I. tract, and the eye.”
Giljohann said psoriasis, an autoimmune skin disease, made the most appealing target for two reasons.
“We were looking for a place where we could demonstrate rapid proof of concept,” Giljohann said.
Seeing is believing with psoriasis, a condition that can visibly demonstrate the failure or success of a treatment. It also represents somewhat of an unmet need.
Patients typically use one of two major therapy classes; topical steroids, or systemic antibodies, such as Enbrel and Humira — the top-selling drug in 2016 with over $16 billion in sales.
“The concept that we had was, what if we could use the biology of the systemic antibodies such as Humira and Enbrel to target topical treatments,” Giljohann said.
The result was AST-005. It’s a gel-based spherical nucleic acid that targets TNF-alpha, an inflammatory pathway that helps fuel psoriasis.
Unfortunately for both Exicure and Purdue, AST-005 won’t be biting into Humira’s sales anytime soon. The aim is to treat individuals with mild to moderate disease, who don’t typically qualify for the systemic treatments.
In October, Exicure presented results from a Phase 1 proof of concept trial in Germany, which tested AST-005 in mild to moderate psoriasis. The drug demonstrated safety and tolerability, as well as the mechanism of action, assessed by looking at gene expression levels after the treatment.
With the new deal, Exicure will continue to advance the compound with guidance from Purdue. Giljohann said the company is also very excited to partner with Purdue’s commercialization team, should it progress through to the market.
It has not yet been disclosed what genes and diseases the other compounds will target.
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