ARA-290

Graded C: several double-blind randomized trials exist, but they are small (22–64 patients), short (28 days) and largely developer-run, and it is not approved anywhere.

Strengths: 10, 16 mg
Also known as: Cibinetide, pHBSP (pyroglutamate helix B surface peptide), Helix B surface peptide
Molecule: 11-amino-acid EPO-derived peptide
Formula: C51H84N16O21
Mol. weight: 1257.3 g/mol
CAS: 1208243-50-8
Sequence: pGlu-EQLERALNSS

Origin

Developed by Araim Pharmaceuticals and modeled on one outward-facing surface (helix B) of the hormone erythropoietin (EPO), designed to keep EPO's tissue-protective signaling without raising red blood cell counts.

How it works

Reported to bind only the innate repair receptor, a complex of the EPO receptor with the beta-common receptor (CD131) that signals anti-inflammatory and tissue-protective effects. It does not activate the classic EPO receptor that drives red-cell production. Animal work suggests it dampens innate immune cells such as macrophages.

What the research shows

Small 28-day phase 2 trials in sarcoidosis-related and diabetes-related small-fiber neuropathy reported improved symptom checklists and some regrowth of corneal nerve fibers, though pain scores often did not separate from placebo. A diabetes trial also reported small drops in HbA1c and triglycerides. A small open-label eye study found no vision improvement. Mouse studies reported benefits in colitis, wound healing, islet transplants and bone. Durability, independent confirmation and current development status are open questions.

Key studies

Dahan et al., Molecular Medicine 2013 Sarcoidosis, 38 patients: symptom score fell 12.2 vs 3.8 points; corneal nerve fiber area +14.5%.
Brines et al., Molecular Medicine 2014 Type 2 diabetes, 48 patients: small HbA1c and lipid improvements, modest neuropathic-pain gains.
Culver et al., IOVS 2017 Sarcoidosis phase 2b, 64 subjects: studied corneal nerve fiber abundance.
Lois et al., J Clin Med 2020 Diabetic macular edema, 9 patients: no group improvement in vision or retinal thickness.

Safety findings

Trials mostly reported no difference from placebo, no anti-drug antibodies and no rise in hemoglobin. Isolated serious events included worsening kidney function in one patient and suicidal ideation in one person with a depression history. Long-term safety is unknown.

Regulatory status

Not approved anywhere. FDA places it in 503A Category 3 (nominated without adequate support), so it is not lawfully compoundable. Prohibited at all times by WADA as an innate repair receptor agonist (S2.1.5) and under S0.

Catalog notes

Available in 10 and 16 mg; the 10 mg strength has a certificate (lot ARA2901-0803, 99.72% purity, COA7616), and none is published for 16 mg. Check the lot's certificate for the exact formula and molecular weight; reference sources list C51H84N16O21 and 1257.3 g/mol.