Self-Delivering RNAi Compounds: A Unique Therapy for a Wide Range of Diseases

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(DGIwire) – When several biotech companies are pursuing a common goal, the company that eventually winds up in front can usually point to a unique innovation for its success. In the hot research area of RNA interference (RNAi), this secret sauce might be found in the form of something called “self-delivering RNAi” (sd-rxRNA®)—and its innovator, RXi Pharmaceuticals, could be at the forefront of making the research a reality.

First of all, what is RNAi? It is a naturally occurring process by which a particular “messenger RNA” can be destroyed before it is translated into protein. Since the overexpression of certain proteins plays a role in many disease conditions, the ability to inhibit gene expression with RNAi provides a potentially powerful tool to treat a range of human diseases. A recent article in Scrip Intelligence outlined why RXi Pharmaceuticals believes sd-rxRNA could give it an edge over other attempts to commercialize RNAi.

Using its proprietary form of RNAi, reports Scrip Intelligence, the company thinks it can overcome a set of thorny challenges linked to the delivery of RNAi into cells that have plagued other attempts to create specific therapies. Positive results followed from the company’s work to design a smaller, asymmetric RNAi compound that could more easily enter cells than those described in most RNAi patents involving longer duplexes.

“Innovations in delivery methods are the key to success in the RNAi field,” says Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. “We believe we have zeroed in on a path to development that could lead to fruitful results in a range of disease areas amenable to local, direct administration.”

Specifically designed sd-rxRNA therapeutic compounds have been developed to reduce the expression of connective tissue growth factor (CTGF), a critical regulator of fibrosis. The company’s first clinical candidate, RXI-109, is currently in a Phase 2 clinical trial to reduce the formation of hypertrophic scars after scar revision surgery. RXI-109 has been shown to be safe and well-tolerated in all trials to date and preliminary results have indicated an improved scar appearance with RXI-109 treatment.

Additionally, RXi is conducting a Phase 1/2 clinical trial to evaluate treatment with RXI-109 in patients with subretinal scarring associated with advanced wet age-related macular degeneration. The primary objective is to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of RXI-109 when administered by intravitreal injection. The overarching objective of this clinical research is to evaluate the potential of RXI-109 to block the formation of further subretinal scarring in these patients, with the goal of maintaining vision for a longer period of time than with anti-VEGF treatment alone, the current standard of care.

The company has also begun an immuno-oncology program, which will initially focus on cell-based therapies using sd-rxRNA compounds to treat cancer. Cell-based cancer immunotherapy, also known as Autologous Immune Enhancement Therapy (AIET), is a treatment that uses a patient’s own immune cells (e.g., peripheral blood-derived NK cells, cytotoxic T lymphocytes and others). These cells are taken out of the body, cultured, processed to become activated, and in this case treated with RXi’s sd-rxRNA compounds, before they are then reinfused back into the patient to attack cancer cells. Researchers have found that this type of cell therapy primarily targets cancer cells and not healthy cells. This approach differs from chemotherapy and radiotherapy where healthy cells are also destroyed.

“Time will tell which path forward is most beneficial for those working in the RNAi space, and we are confident we are pursuing ideas that could lead to significant advances,” adds Cauwenbergh.

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