ARA-290

ARA-290 (cibinetide) is a small, 11-amino-acid peptide engineered from a surface region of erythropoietin (EPO). Unlike EPO, it does not stimulate red blood cell production. Instead, it selectively activates a receptor combination called the “innate repair receptor,” which is linked to tissue protection, nerve repair, and inflammation control rather than blood-cell growth. It has been tested in registered human clinical trials for sarcoidosis-associated small fiber neuropathy and for painful neuropathy in type 2 diabetes, with the developer, Araim Pharmaceuticals, holding FDA orphan drug and fast track designations for the sarcoidosis indication.

Research snapshot

Category	Current information
Peptide category	Erythropoietin-derived, non-hematopoietic peptide (innate repair receptor agonist)
Primary research interest	Neuropathic pain and small fiber neuropathy associated with sarcoidosis; neuropathy/metabolic control in type 2 diabetes
Highest available evidence	Published, randomized, placebo-controlled Phase 2 human clinical trials
Human research available	Yes, limited — small Phase 2 trials, tens of subjects each
Development status	Investigational; led by Araim Pharmaceuticals; no known active registration trial identified as of this review
Regulatory status	Not FDA-approved; has received FDA orphan drug and fast track designations for sarcoidosis-associated small fiber neuropathy (per company press releases, not an approval)
Last reviewed	September 27, 2026

Peptide category: erythropoietin-derived, non-hematopoietic peptide (innate repair receptor agonist). Primary research interest: neuropathic pain and small fiber neuropathy associated with sarcoidosis, and neuropathy/metabolic control in type 2 diabetes. Highest available evidence: published, randomized, placebo-controlled Phase 2 human clinical trials. Human research available: yes, limited (small Phase 2 trials, tens of subjects each). Development status: investigational; led by Araim Pharmaceuticals; no known active registration trial identified as of this review. Regulatory status: not FDA-approved; has received FDA orphan drug and fast track designations for sarcoidosis-associated small fiber neuropathy (per company press releases, not an approval). Last reviewed: 2026-09-20.

Technical identity

Technical property	Information
Primary name	ARA-290
Alternative names	Cibinetide (INN), Innate Repair Receptor agonist, GRT3983Y
Peptide sequence	pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (11 residues; sometimes abbreviated pGlu-QEQLERALNSS depending on notation convention)
Amino-acid length	11 residues
Molecular formula	C51H84N16O21
Molecular weight	Approximately 1,257.32 g/mol
CAS Registry Number	1208243-50-8
PubChem CID	91810664
Chemical modifications	N-terminal pyroglutamate (cyclized glutamine), increasing resistance to exopeptidase degradation
Peptide class	Engineered linear peptide derived from the “helix B surface peptide” region of erythropoietin
Primary biological target	The innate repair receptor, a heteroreceptor complex of the erythropoietin receptor (EPOR) and the beta common receptor subunit (CD131), distinct from the classic (EPOR)2 homodimer that drives red blood cell production
Developer or originator	Araim Pharmaceuticals (New York, USA), building on earlier tissue-protective erythropoietin research led by Michael Brines and Anthony Cerami
Development status	Investigational, Phase 2 clinical stage (DrugBank DB13006)

Primary name: ARA-290. Alternative names: cibinetide (INN), Innate Repair Receptor agonist. Peptide sequence: pyroglutamyl (pGlu)-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (11 residues; sometimes abbreviated pGlu-QEQLERALNSS or similar depending on notation convention). Amino-acid length: 11. Molecular formula: C51H84N16O21. Molecular weight: approximately 1,257.32 g/mol. CAS Registry Number: 1208243-50-8. PubChem CID: 91810664. DrugBank ID: DB13006. Chemical modifications: N-terminal pyroglutamate (cyclized glutamine), a modification that increases resistance to exopeptidase degradation. Peptide class: engineered linear peptide derived from the “helix B surface peptide” region of erythropoietin. Primary biological target: the innate repair receptor, a heteroreceptor complex formed from the erythropoietin receptor (EPOR) and the beta common receptor subunit (CD131), distinct from the classic (EPOR)2 homodimer that drives red blood cell production. Developer: Araim Pharmaceuticals (New York, USA), building on earlier tissue-protective erythropoietin research led by Michael Brines and Anthony Cerami. Development status: investigational, Phase 2 clinical stage.

What is ARA-290?

ARA-290 is a synthetic peptide designed by scientists at Araim Pharmaceuticals to reproduce one specific tissue-protective activity of erythropoietin (EPO) — the hormone best known for stimulating red blood cell production — while removing EPO’s blood-related effects entirely. Researchers had observed that EPO also has protective, anti-inflammatory, and nerve-regenerative properties in animal injury models, but using full EPO for these purposes is impractical because it also raises red blood cell counts, which carries cardiovascular risk with chronic use.

To separate these effects, the Araim team identified a short surface loop of the EPO molecule (“helix B”) that appeared responsible for tissue protection, and engineered ARA-290 as an 11-amino-acid peptide modeled on that region. It is not naturally occurring; it is a laboratory-designed derivative rather than a fragment isolated directly from the body. The peptide carries an N-terminal pyroglutamate modification, which helps it resist rapid breakdown by exopeptidase enzymes in the blood.

ARA-290 was developed specifically to activate what the developers termed the “innate repair receptor” (IRR) — a receptor complex made of the erythropoietin receptor paired with the beta common receptor (CD131) — rather than the classic erythropoietin receptor homodimer responsible for red blood cell production. Because most tissues that benefit from EPO’s protective signaling (nerve, retina, kidney, heart) express this heterodimeric receptor combination, while red blood cell precursors mainly express the classic homodimer, this design strategy aimed to keep the protective signal while avoiding the hematopoietic (blood-cell-stimulating) effect.

Current research interest centers on two areas: reducing neuropathic pain and nerve fiber loss associated with sarcoidosis (an inflammatory disease that can damage small nerve fibers), and improving neuropathic symptoms and metabolic markers in people with type 2 diabetes. It remains an investigational compound; it has not been approved for any indication.

How does it work?

Plain-English explanation

ARA-290 is built to mimic one specific “repair” message that erythropoietin sends to injured or stressed tissue, without sending the separate “make more red blood cells” message. By binding a receptor combination found mainly on nerve, immune, and other non-blood-forming cells, it appears to help calm inflammation and support the regrowth of small nerve fibers, without affecting red blood cell counts the way EPO itself does.

Technical explanation

ARA-290 selectively binds and activates the innate repair receptor, composed of the erythropoietin receptor (EPOR) in combination with the beta common receptor subunit (CD131/CSF2RB), rather than the (EPOR)2 homodimer that mediates erythropoiesis. Downstream signaling through the innate repair receptor has been reported in preclinical work to activate cytoprotective and anti-apoptotic pathways (including AMPK and related signaling) without triggering the JAK2/STAT5 erythropoietic cascade associated with the classic EPOR homodimer. In human trials, this has translated into measurable increases in corneal nerve fiber density and area (assessed by corneal confocal microscopy) and intraepidermal GAP-43-positive nerve fiber regeneration, alongside improvements in patient-reported neuropathic pain scores, without the hematocrit increases associated with erythropoietin-stimulating agents.

Potential benefits and research applications

Small fiber nerve regeneration and pain relief in sarcoidosis-associated neuropathy

What is being investigated: whether ARA-290 can regenerate damaged small nerve fibers and reduce neuropathic pain in patients with sarcoidosis, a granulomatous inflammatory disease that can cause small fiber neuropathy (SFN). How the effect might occur: through innate repair receptor-mediated reduction of local inflammation and support of nerve fiber regrowth. Evidence: a randomized, double-blind, placebo-controlled Phase 2 pilot trial (Heij et al., 2012, n=22) reported significant improvement in the small fiber neuropathy screening list score and select SF-36 quality-of-life domains with intravenous ARA-290 versus placebo. A larger Phase 2b trial (Culver et al., 2017, NCT02039687, n=64) found a significant placebo-corrected increase in corneal nerve fiber area at the 4 mg/day dose, along with increased regenerating epidermal nerve fibers and improved pain intensity across groups. Strength: this is genuine published human clinical trial evidence (Tier 1/2), though from small trials run predominantly by the drug’s developer. Limitation: both trials were small (22 and 64 subjects), of short duration (28 days of dosing), and the primary trial’s pain endpoint reached significance mainly in a subgroup (moderate-to-severe pain, 4 mg dose); independent replication in larger populations has not been identified.

Neuropathic symptoms and metabolic control in type 2 diabetes

What is being investigated: whether ARA-290 improves painful diabetic neuropathy symptoms and metabolic markers (HbA1c, lipids) in people with type 2 diabetes. How the effect might occur: proposed innate repair receptor-mediated nerve protection/regeneration plus possible metabolic effects not yet fully mechanistically explained. Evidence: a published randomized, double-blind, placebo-controlled Phase 2 trial (Brines et al., 2015, PMID 25387363) in patients with type 2 diabetes and painful neuropathic symptoms, using daily self-administered subcutaneous ARA-290 (4 mg) for 28 days, reported significant improvement in HbA1c and lipid profiles and significant improvement in neuropathic symptoms (PainDetect questionnaire) versus placebo, with an increase in corneal nerve fiber density in subjects with reduced baseline density. Strength: Tier 1/2 published human clinical trial evidence. Limitation: trial size and duration were limited, and the authors themselves describe the findings as warranting continued clinical evaluation rather than as established treatment evidence.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Sarcoidosis-associated small fiber neuropathy	Intravenous infusion	2 mg	Three times weekly (12 total doses)	4 weeks	Published human clinical trial (Heij et al. 2012, PMID 23168581)
Sarcoidosis-associated neuropathy, dose-ranging	Not specified in this table (subcutaneous per trial design)	1, 4, or 8 mg/day	Daily	28 days	Published human clinical trial (Culver et al. 2017, PMID 28475703; NCT02039687)
Type 2 diabetes with painful neuropathy	Subcutaneous injection	4 mg	Daily	28 days	Published human clinical trial (Brines et al. 2015, PMID 25387363)
General online/vendor framing	Not consistently reported	Largely echoes the 1-8 mg published trial range rather than an independent community-derived protocol	Not established	Not established	Community / vendor reported

Amounts studied in human research

Sarcoidosis-associated small fiber neuropathy (Heij et al., 2012, PMID 23168581): ARA-290 2 mg administered by intravenous infusion, three times weekly, for 4 weeks (12 total doses), compared with placebo, in 22 subjects. Sarcoidosis-associated small fiber neuropathy, dose-ranging (Culver et al., 2017, PMID 28475703, NCT02039687): ARA-290/cibinetide at 1 mg, 4 mg, or 8 mg administered daily (route as “mg/day,” consistent with subcutaneous self-administration used in the developer’s other trials of this era) for 28 days, compared with placebo, in 64 subjects; the 4 mg/day dose showed the most consistent significant effects on corneal nerve fiber area. Type 2 diabetes with painful neuropathy (Brines et al., 2015, PMID 25387363): ARA-290 4 mg self-administered subcutaneously once daily for 28 days, followed by a 28-day observation period without treatment, compared with placebo.

Amounts studied in animal research

Not consistently reported in the sources reviewed for this entry. Preclinical erythropoietin-derived peptide research (predating and supporting ARA-290’s clinical development) used a range of doses in rodent models of nerve injury, ischemia, and diabetes, but specific comparable figures were not verified from primary sources for this entry and are not repeated here to avoid inaccuracy.

Practitioner and community-reported protocols

ARA-290 is discussed in online peptide-research communities and sold by research-peptide vendors, sometimes citing the same approximate 1-8 mg range reported in the clinical trials above. Widely repeated online, but in most vendor and community sources these figures simply restate the published Phase 2 trial doses rather than reflecting independent community experimentation, so they should not be treated as separately validated “community protocols.” No distinct, independently sourced practitioner or community dosing protocol beyond the published clinical trial doses was identified.

Side effects, risks, and limitations

In the published Phase 2 trials, ARA-290 was reported as generally well tolerated, with no major safety signals identified by the study authors over the trial durations (up to 28 days of dosing). Because ARA-290 is designed specifically to avoid activating the classic erythropoietin receptor homodimer, it is not expected to raise hematocrit or red blood cell counts the way erythropoiesis-stimulating agents do, though long-term human safety data beyond these short trials have not been established. As with any peptide sourced outside a regulated pharmaceutical supply chain, research-grade or vendor-sourced material carries risks of impurity, incorrect concentration, and lack of sterility assurance that are unrelated to the peptide’s pharmacology itself. No large-scale, long-duration human safety trial was identified, so uncommon or delayed adverse effects remain unknown.

Regulatory and developmental status

ARA-290/cibinetide is not approved by the FDA or any other major regulator for any indication. According to company press releases from Araim Pharmaceuticals (a primary-source but non-peer-reviewed source type), the FDA granted orphan drug designation and fast track designation to ARA-290 for sarcoidosis-associated small fiber neuropathy, reflecting its status as an investigational therapy for a rare, unmet-need condition rather than an approval. Completed registered trials include NCT02039687 (Phase 2, sarcoidosis-associated neuropathy, completed 2015). No currently active, later-phase registered trial for cibinetide was identified as of this review; development activity should be considered dormant or early-stage pending new registrations. Status verified: 2026-09-20.

Frequently asked questions

What is ARA-290 (cibinetide)?

ARA-290 is a small peptide engineered from a segment of erythropoietin that activates a tissue-repair receptor pathway without the blood-cell-boosting effects of erythropoietin itself.

How does ARA-290 work?

It selectively activates the “innate repair receptor” (a combination of the erythropoietin receptor and the beta common receptor), which is linked to reduced inflammation and nerve fiber regeneration, rather than the receptor pairing responsible for making red blood cells.

What dosage has been studied for ARA-290?

Published Phase 2 trials have used 2 mg intravenously three times weekly for 4 weeks, and 1-8 mg per day (with 4 mg/day most consistently effective) for 28 days, depending on the study and condition.

What dosage commonly circulates online for ARA-290?

Online and vendor sources generally repeat the same 1-8 mg range from the published clinical trials rather than describing a separate community-derived protocol.

Has ARA-290 been studied in humans?

Yes. It has been tested in randomized, placebo-controlled Phase 2 trials for sarcoidosis-associated small fiber neuropathy and for painful neuropathy with type 2 diabetes.

What were the results of ARA-290’s clinical trials?

Trials reported improvements in nerve fiber density/area, neuropathic pain scores, and (in the diabetes trial) HbA1c and lipid measures compared with placebo, though trial sizes were small and durations short.

What side effects have been reported for ARA-290?

Published trials reported no major safety concerns over the study periods, but long-term human safety data have not been established.

Is ARA-290 approved by the FDA?

No. It is investigational. It holds FDA orphan drug and fast track designations for sarcoidosis-associated small fiber neuropathy, which speed up development review but are not approvals.

What remains unknown about ARA-290?

Long-term safety and efficacy beyond short Phase 2 trials, whether larger confirmatory trials will be conducted, and the durability of nerve fiber regeneration effects after treatment stops are all unresolved.

Bottom line

ARA-290 (cibinetide) is one of the better-studied peptides in this educational compilation in terms of genuine human clinical trial evidence: it has been through multiple randomized, placebo-controlled Phase 2 studies for sarcoidosis-associated small fiber neuropathy and for diabetic neuropathy, with published results showing measurable nerve fiber regeneration and symptom improvement over short treatment periods. What is not established is long-term safety, durability of effect, or efficacy in larger confirmatory trials — the existing evidence comes from small trials, largely involving the drug’s own developer. Its FDA orphan drug and fast track designations reflect investigational priority status, not approval. Community and vendor dosing information available online largely echoes the published trial doses rather than adding independent evidence.