RXi Pharma Inks Research Deal with Sweden’s Karolinska Institute

Sweden's Karolinska Institute_Editorial_Isaac Mok

Sweden's Karolinska Institute. Credit: Isaac Mok / Shutterstock.com

RXi Pharmaceuticals, headquartered in Marlborough, Mass., signed a research collaboration deal with Sweden’s Karolinska Institute. They will work to develop cancer therapies using RXi’s sd-rxRNA compounds against targets involved in T-cell and NK cell differentiation.

RXi Pharma focuses on next-generation immuno-oncology products based on its self-delivering (sd) RNA interference (RNAi) technology platform. The company’s approach uses immune cells that are isolated from the patients or allogeneic immune cell banks, and then expands them or processes them to express tumor-binding receptors. This is all very standard for immuno-oncology.

What differentiates RXi’s approach occurs in ex-vivo processing using sd-rxRNA. This process eliminates the expression of immunosuppressive receptors from the immune cells, which makes them less sensitive to cancer cells’ ability to hide from the immune cells. As the company states, “Essentially, we aim to maximize the power of our sd-rxRNA therapeutic compounds by weaponizing therapeutic immune effector cells to attack cancer and ultimately provide patients battling terminal cancers with a powerful new treatment option that goes beyond current treatment modalities.”

The research collaboration will continue recently published work showing that an sd-rxRNA targeting PD-1 can improve TIL antitumor activity against melanoma cells.

“We are pleased to expand our collaboration with Dr. Kiessling’s group, to further harness their expertise in oncology and to expand on the successful research they have previously done with our sd-rxRNA technology platform in immuno-oncology,” said Gerrit Dispersyn, RXi’s chief development officer, in a statement. “The combination of their prior results and the anticipated research results from this new collaboration are critical elements for a rapid advancement of sd-rxRNA immuno-oncology therapeutics into the clinic, further supported by our prior clinical experience with sd-rxRNA in other indications.”

On August 1, RXi announced positive results with RXI-109 in a Phase I/II clinical trial in patients with advanced neovascular age-related macular degeneration (NVAMD) and the accompanying subretinal fibrosis. RXI-109 also uses the company’s sd-rxRNA technology platform, but in January 2018, the company announced it planned to exclusively focus on using its technology for immuno-oncology. As such, it was actively looking for partners or companies to out-license both its Dermatology and Ophthalmology franchises.

The primary objective of this study was to evaluate dosing, with clinical effects a secondary endpoint. The trial met its primary objective with an absence of dose-limiting and serious toxicities and only mild to moderate procedure-related side effects. On the clinical end, the trial showed positive effects in the change from baseline in subretinal fibrosis lesion size, which was measured with several different techniques.

“This study is exciting on several levels,” said Dispersyn in a statement at the time. “First, the impressive safety and tolerability of intravitreal injections of RXI-109 and the promising clinical data, support further development of this compound in retinal scarring. In addition, these positive findings also open significant avenues for the use of our platform technology in ophthalmology, with sd-rxRNA targeting other proteins for other ocular indications. Also, the results contribute to an already extensive set of data that RXI-109, by preventing the overexpression of connective tissue growth factor, can result in a positive impact in various indications where excessive fibrosis is seen. Even though this is a small study, it is encouraging that some of the summary statistics on ocular assessments performed in the study eye at the last follow-up visit, suggest a more pronounced change over baseline in the highest dose group (Cohort 3), compared to other groups.”

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