Rise’s R-2487 moves toward clinical testing as Sjögren’s treatment
Company secures funding to test immunotherapy
Rise Therapeutics plans to launch a Phase 1 clinical trial testing R-2487, its experimental oral therapy for autoimmune diseases, in people with Sjögren’s disease.
R-2487, which leverages bacterial proteins to suppress the abnormal immune responses in autoimmune diseases like Sjögren’s, “is disease-modifying, focusing on long-term immune correction rather than short-term symptom relief,” Christian Furlan Freguia, PhD, senior vice president of research at Rise, said in a company press release.
A $429,158 grant from the National Institute of Dental and Craniofacial Research will support preparations for the launch and completion of the proof-of-concept trial.
Rise has met with the U.S. Food and Drug Administration to align requirements for a future submission of an application seeking clearance to advance R-2487 into clinical trial testing in the country.
The Sjogren’s trial will build on positive interim findings from a Phase 1 clinical trial evaluating the experimental therapy in people with rheumatoid arthritis, another autoimmune disease.
Targeting the cause
In Sjögren’s disease, the immune system mistakenly attacks the body’s own healthy cells, most commonly the glands that produce tears and saliva. Many patients experience dry eyes and mouth, but Sjögren’s symptoms can be found throughout the body.
Current treatments primarily focus on easing symptoms rather than targeting the underlying causes of Sjögren’s.
Dendritic cells, a type of immune cell, detect potential threats and recruit other immune cell types, allowing inflammation and other immune responses to eliminate the threat. Research suggests that dendritic cells may play a role in developing Sjögren’s and other autoimmune disorders.
“When [dendritic cell] function is impaired, it leads to breakdown of tolerance and the onset of autoimmune diseases such as [rheumatoid arthritis] and SjD [Sjögren’s disease],” Freguia said.
R-2487 aims to counteract these responses. The first-in-class medication contains a harmless bacterium engineered to produce colonization factor antigen I (CFA/I), a protein derived from the Escherichia coli bacterium that engages dendritic cells in the digestive system.
The protein causes dendritic cells to promote the growth and activation of regulatory T-cells (Tregs), a type of immune cell that helps keep immune activity in check and resolve inflammation.
By increasing Treg activity, Rise hopes R-2487 will “[correct] the immune dysfunction underlying overreactive self-immune response that causes autoimmunity,” Freguia said.
In mouse models of Sjögren’s, six weeks of treatment with the CFA/I protein helped reduce infiltration of inflammatory cells in tear and salivary glands, levels of pro-inflammatory molecules, and maintain saliva flow. These results suggest that leveraging this protein may allow R-2487 to slow or halt Sjögren’s progression.
Similar findings in models of rheumatoid arthritis, an autoimmune disorder that causes inflammation and pain in the joints, prompted Rise to launch a Phase 1 trial (NCT05961592) to test the therapy in that condition.
The study is still recruiting participants, who may also include those with Sjögren’s associated with rheumatoid arthritis. Early results have suggested a favorable safety profile and positive clinical and biomarker responses that “validate the product’s first-in-class immunomodulatory mechanism, and gut-restricted oral delivery,” Rise said.
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