ARA-290

ARA-290, also known as cibinetide, is a 11-amino-acid cyclic peptide engineered to selectively activate the Innate Repair Receptor (IRR) — a tissue-protective receptor complex distinct from the classical erythropoietin receptor (EPOR). The IRR is a heteroreceptor comprising EPOR and the beta common receptor (βCR), and is expressed on a wide range of non-hematopoietic cells including neurons, macrophages, endothelial cells, and pancreatic beta cells. ARA-290 was designed by Araim Pharmaceuticals to capture the tissue-protective effects of erythropoietin (EPO) without triggering erythropoiesis or other hematopoietic effects.

The scientific rationale behind ARA-290 stems from research by Brines, Cerami, and colleagues demonstrating that EPO has two distinct sets of biological activities: hematopoietic (mediated through the classical EPOR homodimer) and tissue-protective (mediated through the IRR heterodimer). By designing a peptide that binds the IRR selectively, ARA-290 enables tissue-protective signaling without the cardiovascular risks associated with elevated hematocrit from EPO itself.

Research has documented ARA-290's effects in neuropathy models, with several studies from Leiden University Medical Center reporting reduction in pain behavior and nerve fiber loss in animal models of painful peripheral neuropathy, including sarcoidosis-related neuropathy and experimental diabetic neuropathy. Phase II clinical data in sarcoidosis-related small fiber neuropathy showed statistically significant improvements in pain and corneal nerve fiber density — a structural marker of small fiber neuropathy.

ARA-290 is available for research use only. Investigators studying peripheral neuropathy, innate repair signaling, EPO receptor biology, or anti-inflammatory mechanisms will find ARA-290 an important research tool with both extensive preclinical literature and Phase II clinical data.