ARA-290 (cibinetide)

Overview

ARA-290, whose international name is cibinetide, is an eleven-amino-acid peptide derived from part of erythropoietin (EPO) — the hormone that drives red-blood-cell production. What is special is that ARA-290 does not stimulate blood production.

Beyond blood production, EPO turns out to have a protective, anti-inflammatory action on tissues, via a different receptor. ARA-290 is engineered to mimic only that tissue-protective part — the innate repair receptor — without the risks that come with full EPO.

At Peptalis, ARA-290 is available strictly for research use only — in-vitro, not for human or animal use.

Mechanism of action

ARA-290 engages the innate repair receptor — a heteromer of the EPO receptor and the beta-common receptor (CD131) — giving tissue protection and anti-inflammatory effects, without erythropoiesis.

Innate repair receptor

• EPO's tissue-protective action runs via a separate receptor (an EPO-receptor/CD131 heteromer), not the classical EPO receptor that drives blood production.
• ARA-290 selectively activates that first route, dampening inflammation and promoting repair without raising red-cell production (Nairz 2017).

Human evidence

• In phase 2 studies in sarcoidosis with small-fibre neuropathy, ARA-290 improved neuropathic symptoms and nerve-fibre measures (Heij 2012; Culver 2017).
• In type 2 diabetes it improved metabolic control and neuropathic symptoms (Brines 2015).

Research findings

• Human (phase 2, T2D): improved metabolic control and neuropathic symptoms (Brines 2015)
• Human (phase 2b, RCT): improvement of corneal nerve fibres in sarcoidosis SFN (Culver 2017)
• Human (pilot RCT): safety/efficacy in sarcoidosis small-fibre neuropathy (Heij 2012)
• Mechanism (animal): ARA-290 dampens innate immune cell functions and ameliorates experimental colitis (Nairz 2017)

Mechanism & preclinical

• ARA-290 acts via the innate repair receptor; in animal models (including experimental colitis) it dampens the innate immune response and protects tissue (Nairz 2017).

Human studies

• In a pilot RCT in sarcoidosis with small-fibre neuropathy, ARA-290 improved neuropathic symptoms (Heij 2012).
• A phase 2b RCT showed an increase in corneal nerve fibres in sarcoidosis patients with neuropathic pain (Culver 2017).
• In type 2 diabetes, ARA-290 improved metabolic control and neuropathic symptoms (Brines 2015).

Research context

This profile describes what has been done and found in research. Regulatory and clinical facts are facts about the respective trials and authorities, not claims about a Peptalis product; the compound is for in-vitro laboratory research only (RUO).

Open questions

• The human evidence consists of phase 2 studies with limited cohorts; large phase 3 confirmation and approval are lacking.
• The optimal dose and the durability of the effect have not been established.
• The full molecular characterization of the innate repair receptor is an active area of research.

Research outlook

ARA-290 is a well-characterized tool to study the non-erythropoietic, tissue-protective action of EPO.

It broadens the immune domain with a new anti-inflammatory target, distinct from the thymic and antimicrobial peptides.

Scientific interest

A new anti-inflammatory mechanism: the innate repair receptor, separate from blood production.

EPO-derived yet non-erythropoietic — an elegant design.

Multiple published human phase 2 RCTs.

Specifications

References

1. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study · Heij L, et al. · Mol Med · 2012
2. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes · Brines M, et al. · Mol Med · 2015
3. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis · Nairz M, et al. · Sci Rep · 2017
4. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain · Culver DA, et al. · Invest Ophthalmol Vis Sci · 2017

Availability

Not in catalogue · Profile complete · verification and sourcing not yet finished