Ara-290, also known by its INN cibinetide and the chemical descriptor pyroglutamic acid helix B surface peptide (pHBSP), is an 11-amino-acid synthetic peptide derived from the helix B domain of erythropoietin (EPO). Researchers engineered it to retain EPO's tissue-protective and anti-inflammatory properties while completely eliminating its hematopoietic (red blood cell production) activity. This separation of EPO's two functional roles — erythropoiesis and tissue protection — is the central innovation Ara-290 represents. It has progressed to Phase 2 clinical trials in small-fiber neuropathy and diabetic neuropathy. It is not FDA-approved.
Ara-290 is derived from the helix B surface region of EPO (approximately residues 58–82), engineered for selective IRR binding without EPOR homodimer activation.
Length: 11 amino acids. Classification: EPO-derived helix B peptide; IRR-selective agonist. Developer: Araim Pharmaceuticals (Netherlands). Research stage: Phase 2 completed; not FDA-approved.
Full-length EPO signals through two receptor complexes: the EPOR homodimer (responsible for erythropoiesis) and the innate repair receptor (IRR) — a heterodimer of EPOR and the β-common receptor (βcR/CD131). The IRR is upregulated by injury, inflammation, and metabolic stress.
Ara-290 selectively activates the IRR without meaningful activation of the EPOR homodimer. IRR activation drives: anti-inflammatory signaling (suppression of TNF-α, IL-6, NF-κB), NLRP3 inflammasome suppression in Schwann cells, cytoprotection against neuronal apoptosis, and neuroregenerative signaling — promotion of small nerve fiber regrowth evidenced by measurable increases in corneal nerve fiber density in clinical trials.
Sarcoidosis Small-Fiber Neuropathy (Phase 2, ARAIM): Subcutaneous Ara-290 at 4 mg/day for 28 days in patients with sarcoidosis-associated SFN produced improvements in neuropathic pain scores, functional capacity, and — critically — measurable increases in corneal nerve fiber density via in vivo confocal microscopy. Corneal nerve fiber density is an objective biomarker of small-fiber nerve health; its improvement indicates actual peripheral nerve regeneration rather than symptomatic relief alone.
Diabetic Neuropathy (Phase 2): In patients with type 2 diabetes and painful neuropathy, Ara-290 (4 mg/day × 28 days) improved PainDetect questionnaire scores, reduced HbA1c, improved lipid profiles, and increased corneal nerve fiber density in participants with baseline deficits.
Peripheral Nerve Injury (Preclinical, 2025, Eur J Pharmacol): Ara-290 inhibition of NLRP3 inflammasome activation in Schwann cells following sciatic nerve injury in rats — reducing early neuroinflammation and supporting nerve repair, with effects comparable to EPO but without hematopoietic consequences.
Ara-290 is studied in: peripheral neuropathy pharmacology, small-fiber neuropathy biomarker research, EPO/IRR receptor biology, neuroinflammation and Schwann cell biology, diabetic complication models, and cytoprotective peptide design.
Form: lyophilized powder. Purity: ≥98% HPLC verified. Storage: −20°C, desiccated, protected from light.
For research use only. Not for therapeutic use. Not FDA-approved.
EPO activates both the EPOR homodimer (causing erythropoiesis) and the IRR (tissue protection). Ara-290 activates only the IRR, providing tissue-protective and anti-inflammatory effects without stimulating red blood cell production — eliminating the cardiovascular risks associated with EPO.
Yes — Phase 2 trials in sarcoidosis-associated small-fiber neuropathy and type 2 diabetes with painful neuropathy have been completed. No large Phase 3 trials are registered as of mid-2026. It is not FDA-approved.
Small-fiber neuropathy (SFN) is a condition affecting thin unmyelinated C-fibers and lightly myelinated Aδ-fibers, causing burning pain, sensory disturbances, and autonomic dysfunction. Corneal nerve fiber density is an objective diagnostic biomarker.
In Phase 2 trials, Ara-290 produced measurable increases in corneal nerve fiber density via in vivo confocal microscopy — an objective measure of actual small-fiber nerve regeneration.