Exicure, a company developing a new class of immunomodulatory and gene-silencing drugs including Spherical Nucleic Acid (SNA), has just announced the dosing of the first patient in its Phase 1 clinical trial of AST-005 gel for chronic plaque psoriasis – a disease that causes an inflammatory reaction with outbreaks of red, scaly patches on patients’ skin.
The Phase 1 trial is designed to assess the safety, tolerability and pharmacodynamics of AST-005 in chronic plaque psoriasis patients. Researchers leading the study aim to enroll up to 15 participants and primary endpoints are the study of safety and tolerability of the drug candidate. Secondary endpoints are in situ inflammatory infiltrate thickness and evaluation of target knockdown in the psoriatic skin that received treatment, using gene expression analysis. Exicure expects to have topline results available before the end of 2016.
“With the initiation of this Phase 1 trial, Exicure crosses an important milestone in the development of SNA technology as an approach to address the problem of chronic plaque psoriasis as well as other diseases in the skin,” said Exicure CEO Dr. David Giljohann in a press release. “This clinical trial will enable our team to study safety and tolerability of AST-005 while demonstrating that the SNA technology can be used to treat diseases locally using a nucleic acid therapy. We are excited to bring this approach to patients in need.”
Psoriasis has few approved treatments currently available and they are all limited to biologics. These treatments are usually administered systemically or orally. There are also a variety of non-drug solutions that psoriasis patients can count on, like phototherapy and non-targeted topical treatments.
Spherical nucleic acids (SNAs) are nanoscale, spherical arrangements of densely packed and radially oriented nucleic acids. SNAs can be designed to be significantly effective and highly targeted gene-regulation and immune-modulatory agents. This particular design allows medical scientists to overcome one of the hardest obstacles in nucleic acid-based therapies and be capable of delivering therapeutics in a safe and effective manner, without the need for further physical or chemical methods or products.
Exicure is taking advantage of this SNA unique ability — to penetrate the skin when applied topically, so that AST-005 can combine the targeted benefits of biologics with the easy topical application. AST-005 is a topically-applied SNA that targets tumor necrosis factor (TNF), a pro-inflammatory cytokine that has been shown to be a crucial mediator of psoriasis. In previous preclinical studies, Exicure has shown that AST-005, when topically applied, led to robust TNF knockdown in viable human psoriatic skin samples.