ARA-290 (Cibinetide)
Also known as: Cibinetide · Helix-B Surface Peptide · HBSP · pyroglutamate helix B surface peptide
An 11-amino-acid non-erythropoietic EPO analogue, studied for tissue-protective and neuroprotective effects mediated by the innate repair receptor (IRR) — a distinctive mechanism separated from EPO's erythropoietic activity.
ARA-290 (cibinetide) is an 11-mer non-erythropoietic EPO analogue that selectively activates the innate repair receptor for tissue-protective effects without erythropoietic activity; Phase II positive in sarcoidosis SFN.
Evidence tier: B — clinical evidence (trials or approved use in some jurisdictions)
- Category
- Neurogenesis
- Half-life
- Short plasma half-life; sustained receptor-mediated pharmacodynamic effects
Section 1
Overview
ARA-290 (cibinetide) is an 11-amino-acid peptide derived from a surface-exposed region of the erythropoietin (EPO) protein — specifically helix B, which is not involved in EPO's binding to the classical erythropoietin receptor but does contribute to binding to the innate repair receptor (IRR), a heterodimeric receptor composed of the classical EPO receptor and the beta common receptor (βcR).
The compound's engineering exploits a distinctive pharmacological insight: EPO's tissue-protective effects (in ischaemic, oxidative, and inflammatory injury) are mediated by the IRR, whereas the erythropoietic effects (red blood cell production) are mediated by the classical EPO receptor. By designing a peptide that binds IRR without significantly binding the classical receptor, cibinetide separates the tissue-protective effects from the erythropoietic effects, potentially enabling therapeutic use in tissue-injury indications without the cardiovascular and haematological risks associated with EPO administration.
The compound has been evaluated in multiple clinical trials in sarcoidosis-associated small fibre neuropathy, diabetic macular oedema, and neuropathic pain indications, with mixed but generally positive results. The developer (Araim Pharmaceuticals) has continued the clinical-development programme through the 2010s and 2020s. Cognitive-endpoint research is emerging.
Section 2
Discovery & History
- Identified by the Cerami/Brines laboratory in the early 2000s as part of a systematic effort to separate EPO's tissue-protective and erythropoietic effects through peptide-fragment engineering.
- Licensed to Araim Pharmaceuticals for clinical development.
- Multiple Phase II clinical trials completed in sarcoidosis-associated small fibre neuropathy, with reported positive effects on neuropathic pain and small fibre nerve function endpoints.
- Additional clinical evaluation in diabetic macular oedema and neuropathic pain indications.
- Continued academic research has extended the mechanistic characterisation into CNS applications including ischaemic stroke, traumatic brain injury, and neuroprotection generally.
Section 3
Mechanism of Action
- 1Selective binding to the innate repair receptor (IRR) — the heterodimeric receptor composed of the EPO receptor and the beta common receptor (βcR) — mediating tissue-protective effects distinct from the classical erythropoietin receptor pathway that drives red-blood-cell production.
- 2Anti-apoptotic effects in stressed tissue — preservation of mitochondrial membrane potential, reduced caspase-3 activation, cytochrome-c release attenuation, and improved cell survival in ischaemic, oxidative, and metabolic injury models across multiple tissue systems.
- 3Anti-inflammatory effects — reduction of pro-inflammatory cytokine expression (TNF-α, IL-1β, IL-6), modulation of macrophage and microglial activation phenotype toward the resolution-oriented state, and reduced neuroinflammation in CNS injury models.
- 4Preservation of small fibre nerve function in the sarcoidosis-associated neuropathy indication — the flagship clinical-endpoint finding and the mechanism-of-action demonstration in a specific patient population where the compound's IRR-mediated effect on nerve fibres is directly measurable.
- 5Angiogenic effects in some tissue contexts, contributing to post-injury recovery through endothelial-cell mobilisation and neovascularisation.
- 6Neurogenic effects in some preclinical models, adding a synaptogenic-adjacent research angle to the tissue-protective core mechanism and extending the compound's positioning into cognitive-plasticity research.
- 7Absence of significant erythropoietic activity — the mechanism-of-action distinction from parent EPO, allowing chronic administration without the cardiovascular and haematological risks (hypertension, thromboembolism, hyperviscosity) that limit chronic EPO administration.
- 8Reported effects on nerve-fibre regeneration and preservation of small-fibre function extending beyond the sarcoidosis SFN indication into diabetic neuropathy and other peripheral-neuropathy research contexts.
- 9Immunomodulatory effects on T-cell and macrophage populations, extending the anti-inflammatory mechanism beyond direct tissue-cell effects into systemic immune-modulation research applications.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Tissue-protective effects mediated by a distinctive receptor mechanism (IRR) not shared by any other peptide on this reference — a mechanistically differentiated research tool.
- 2Substantial clinical trial evidence in sarcoidosis-associated small fibre neuropathy — Phase II positive results on nerve-function and pain endpoints provide the primary clinical evidence base.
- 3Separation of tissue-protective effects from erythropoietic effects, enabling chronic administration without EPO's haematological and cardiovascular risks — the mechanistic property that makes chronic dosing clinically feasible.
- 4Reported neuroprotective effects in preclinical CNS injury models (ischaemic stroke, traumatic brain injury) with reduced infarct volume and improved functional outcomes.
- 5Anti-inflammatory effects with broad tissue applicability across musculoskeletal, gastrointestinal, and CNS injury models.
- 6Well-tolerated in the completed clinical evaluations at doses studied, with acute-safety database supporting continued research applications.
- 7Emerging cognitive-endpoint research applications extending from the CNS neuroprotective and anti-neuroinflammatory mechanism angles.
- 8Diabetic neuropathy research relevance extending the SFN-indication evidence into broader peripheral-neuropathy contexts.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration | Source |
|---|---|---|---|---|
| Subcutaneous injection (clinical trials and research) | 1 mg, 4 mg or 8 mg per day (three dose arms), doses used in Culver et al., 2017 (PMID 28475703), a trial in sarcoidosis-associated small nerve fibre loss with neuropathic pain | Daily (doses are given per day in the abstract) | 28 days | Culver et al., 2017 (PubMed 28475703) |
Note: No cognitive-endpoint clinical protocol exists; cognitive-relevance research applications are entirely investigational. A related trial reports 28 days of daily subcutaneous administration (Dahan et al., 2013, PMID 24136731). Doses shown are those tested in the cited trial, not recommendations.
Section 6
Administration Routes
- Subcutaneous injection — the primary route in the clinical trial programme.
- Intranasal delivery has been explored preclinically for CNS-directed applications.
- Intravenous administration in some acute-injury research contexts.
- Oral administration is not viable — the peptide is degraded by gastrointestinal proteases.
Section 7
Safety Profile
Commonly reported
- · Well-tolerated in the completed clinical trials at the doses studied.
- · Injection-site reactions with subcutaneous administration.
- · The absence of erythropoietic activity means the compound does not raise the cardiovascular and haematological safety concerns that limit chronic EPO administration.
- · No dependence, tolerance, or withdrawal phenomena documented.
Rare / theoretical
- · Long-term chronic-use safety beyond the trial evidence base is limited to the short clinical trials reported to date; multi-year chronic-use safety has not been characterised.
- · Theoretical off-target IRR-signalling effects in tissues where the receptor is expressed but not the intended target for therapeutic effect.
- · Rare hypersensitivity reactions — theoretical concern based on peptide chemistry.
- · No documented cardiovascular safety concerns despite the EPO-derived origin, reflecting the successful separation of tissue-protective from erythropoietic activity in the analogue design.
- · Theoretical interaction with anti-inflammatory or immunomodulatory pharmaceuticals given cibinetide's own anti-inflammatory mechanism.
Contraindications
- · No entry for ARA-290 was found in the electronic medicines compendium (emc) on 17 October 2026. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product.
- · Pregnancy and lactation — no controlled human data.
- · Known hypersensitivity to peptide components.
- · Concurrent EPO administration — pharmacodynamic redundancy at the IRR mechanism.
Section 8
UK & EU Regulatory Context
United Kingdom
No entry for ARA-290 was found in the electronic medicines compendium (emc) on 17 October 2026. The emc is not a complete record of UK authorisations, so check the MHRA Products database.
European Union
Not approved by the EMA. Development-programme evaluations completed in specific indications.
Section 9
Clinical Studies Summary
ARA-290 in sarcoidosis-associated small fibre neuropathy
Phase II randomised placebo-controlled trial in sarcoidosis-associated small fibre neuropathy reporting significant improvement in small fibre nerve function endpoints and neuropathic pain scores (measured by quantitative sudomotor axon reflex testing, intraepidermal nerve fibre density, and standardised neuropathic pain inventories) following daily subcutaneous cibinetide over 28 days. The flagship clinical evidence for the compound and the mechanism-of-action demonstration in a specific patient population where the IRR-mediated effect on nerve fibres is directly measurable.
Cibinetide mechanism — IRR-selective agonism
Molecular pharmacology characterisation of cibinetide's selective binding to the innate repair receptor (IRR) with minimal activity at the classical erythropoietin receptor at pharmacologically-relevant concentrations, providing the mechanism-of-action scaffold for the separation of tissue-protective from erythropoietic effects and enabling the compound's clinical-development trajectory that native EPO could not follow.
ARA-290 in cerebral ischaemia preclinical models
Rodent middle-cerebral-artery-occlusion stroke-model studies with cibinetide administration reporting reduced infarct volume by MRI, preserved neurological function on standardised behavioural scoring, and improved histological outcomes in cibinetide-treated cohorts versus vehicle controls. Extends the mechanism-of-action framework into CNS neuroprotective applications directly relevant to cognitive-recovery research.
ARA-290 anti-inflammatory effects in CNS injury
Preclinical characterisation of cibinetide's anti-inflammatory effects in traumatic brain injury and lipopolysaccharide-driven neuroinflammatory disease models, reporting reduced microglial activation markers, decreased pro-inflammatory cytokine expression, and improved functional cognitive outcomes in treated cohorts. Extends the tissue-protective mechanism into neuroinflammation-driven cognitive-decline research applications.
ARA-290 in diabetic neuropathy
Clinical research extending the SFN-indication evidence into type-2 diabetic peripheral neuropathy populations, reporting nerve-function improvement and neuropathic-pain reduction in cibinetide-treated cohorts. The evidence provides context for the broader peripheral-neuropathy research applicability of the compound beyond the primary sarcoidosis indication.
Section 10
Frequently Asked Questions
Section 10a
Practical Research Guidance
Cycle guidance
Reconstitution & storage
UK sourcing notes
Section 11
Sourcing for Laboratory Research
Sourcing ARA-290 (Cibinetide) for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain ARA-290 (Cibinetide) from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: this page is educational. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product, and some compounds on this site, such as semaglutide, are authorised prescription-only medicines in the UK.