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Investigational topical IL-1 blockade intended to treat dry eye
The formulation features rapid onset, optimal dosing and convenience, according to a presentation at the Ophthalmology Innovation Summit.
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A novel topical interleukin-1 blockade to treat dry eye is scheduled to begin human clinical trials this year.
EBI-005 is a potent interleukin-1 (IL-1) antagonist “with optimal product characteristics,” Abbie Celniker, PhD, CEO of Eleven Biotherapeutics, said at the Ophthalmology Innovation Summit in Orlando, Fla.
“[IL-1] is a potent cytokine involved in the regulation of inflammatory processes and pain sensitization,” Dr. Celniker said. “IL-1 alpha and IL-1 beta have also been shown to be elevated in the tears and tissues of dry eye patients.”
In a dry eye mouse model, IL-1 inhibition reduced corneal staining.
“An in vivo mouse model recapitulates the up-regulation of IL-1 and corneal staining,” Dr. Celniker said. “Blockade of IL-1 alpha and IL-1 beta signaling, via topical IL-1 receptor antagonist (Ra), protects against dry eye in a murine model of desiccating stress.”
A proof-of-concept human investigational study has already been conducted. An IL-1 receptor agonist was given to patients for 12 weeks, with follow-up to 16 weeks, in a double-masked, vehicle-controlled trial. In the trial there was fast onset of action, significant improvement in symptoms over vehicle with a strong trend toward significant improvement in signs, and good tolerance with no change in bacterial growth. The therapy was also found to be effective in a diverse population group.
Features of the product
Ideal product features of a novel IL-1 blocker for dry eye are rapid onset of action, optimal frequency of dosing of twice daily with no more than three times daily, no increase in IOP or infection risk, no burning or stinging, stable dosage and competitive material costs.
Eleven Biotherapeutics believes EBI-005 fills these needs because it rapidly blocks inflammation and pain sensitization. Optimal dosing is addressed by a potent blockade and long receptor occupancy.
“The IL-1 mechanism does not affect IOP, has not increased infection and has very low systemic bioavailability safety,” Dr. Celniker said.
The aqueous, non-preserved formulation has well-tolerated excipients. It has a single-use vial with high thermal and agitation stability and room-temperature storage.
High productivity manufacturing is “comparable to small molecule handling,” Dr. Celniker said.
“By using structural insights into the IL-1 receptor/ligand complex, our company has engineered a chimera of IL-1 beta and IL-1 Ra that is superior to anakinra and has no agonist activity,” Dr. Celniker, who joined Eleven Biotherapeutics in September 2011, said. Her background includes many years of late-stage protein therapeutic discovery.
The company has intellectual property through 2031. – by Bob Kronemyer
- Abbie Celniker, PhD, can be reached at 215 First St., Suite 400, Cambridge, MA 02142; 617-871-9911; email: abbie.celniker@elevenbio.com.
- Disclosure: Dr. Celniker is CEO at Eleven Biotherapeutics.