Eleven Biotherapeutics Presents Data on Novel Protein Therapeutics for Treatment of Front and Back of Eye Diseases at ARVO 2014 Annual Meeting

Eleven Biotherapeutics Presents Data on Novel Protein Therapeutics for Treatment of Front and Back of Eye Diseases at ARVO 2014 Annual Meeting

May 6, 2014

 Clinical Data on EBI-005 Demonstrated Improvements in Signs and Symptoms in Patients with Dry Eye Disease through IL-1 Inhibition

Preclinical Data on EBI-029 Demonstrated Inhibition of IL-6 as a Validated Target for Treating Diabetic Macular Edema

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Eleven Biotherapeutics (NASDAQ: EBIO), a clinical-stage biopharmaceutical company discovering and developing protein therapeutics to treat diseases of the eye, today announced the presentation of data for two of its novel, protein therapeutics demonstrating the key role of cytokine biology to target both front and back of eye diseases at the Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting in Orlando, FL. Clinical data on Eleven’s lead drug candidate, EBI-005, the first IL-1 (Interleukin-1) signaling inhibitor designed for topical ocular administration, demonstrated improvements in signs and symptoms of dry eye disease (DED), including reduction in ocular pain and artificial tear use. In addition, preclinical data on EBI-029, an IL-6 (Interleukin-6) inhibitor optimized for localized ocular administration in diabetic macular edema (DME), has demonstrated that EBI-029 potently inhibits IL-6 signaling in vitro. IL-6 is a cytokine that has previously been shown to be upregulated in DME, contributing to the angiogenic and inflammatory components of the disease and correlating with disease severity. By inhibiting IL-6, EBI-029 could offer an alternative to current standard of care, including anti-VEGF therapies.

“Proteins designed specifically as ophthalmic therapies represents an innovative approach to treating diseases of the eye with high unmet need,” said Abbie Celniker, PhD, Chief Executive Officer of Eleven Biotherapeutics. “These data demonstrate Eleven’s ability to target both front and back of eye disease by leveraging our extensive cytokine biology expertise.”

Dr. Celniker continued, “The data we are presenting on our lead product candidate, EBI-005, underscores its potential utility in treating dry eye disease by inhibiting the cytokine IL-1, a key mediator of inflammation in the eye. Likewise, a correlation has been previously observed between increased IL-6 levels and disease severity in diabetic macular edema, including scenarios where VEGF inhibition treatment has been suboptimal. These data suggest the potential of IL-6 blockade with EBI-029 in treating diabetic macular edema and support further development of EBI-029 either as a stand-alone drug or in combination with VEGF blockade.”

EBI-005, a topical IL-1 receptor antagonist for the treatment of ocular surface disease, is currently being evaluated in a pivotal Phase 3 clinical study in subjects with DED and a Phase 2 clinical study in subjects with allergic conjunctivitis. EBI-029, an IL-6 receptor antagonist for localized intravitreal treatment of back of eye disease, is currently in preclinical development for the treatment of DME.

In a poster presentation entitled “Optimized IL-6 Blockade for the Treatment of Diabetic Macular Edema,” Eleven Biotherapeutics researchers presented preclinical data which demonstrated that local IL-6 inhibition potently inhibits IL-6 signaling.

  • Local IL-6 inhibition with a surrogate anti-IL-6 antibody significantly reduced abnormal neovascularization in a rat model of choroidal neovascularization (CNV), supporting the role of IL-6 in pathologic ocular angiogenesis.
    • Intravitreal (IVT) administered anti-IL-6 antibody significantly reduced lesion size compared to the vehicle control (p = 0.0054 on Day 15 and p = 0.0005 on Day 22).
    • There was no significant difference between the IL-6 inhibition and anti-VEGF positive control.
  • EBI-029, a novel antibody against human IL-6, potently inhibits IL-6 signaling and has novel biophysical properties, including improved stability and solubility and minimized systemic exposure, for high-concentration IVT administration.
    • The humanized antibody EBI-029 binds human IL-6 with 200 pM affinity and potently blocks IL-6 signaling in cellular assays.
    • EBI-029 is thermally stable (Tm ~ 80 °C) and has no measurable aggregation at 20 mg/mL.
    • Full-length variants of EBI-029 have been engineered to further extend vitreal residence and reduce systemic exposure.

In a poster presentation entitled “Topical Interleukin-1 (IL-1) Receptor Inhibition Reduces Ocular Pain” Eleven Biotherapeutics researchers presented clinical data which demonstrated that inhibition of IL-1 reduced frequency of painful or sore eyes suggesting that inhibiting IL-1 signaling in the eye with EBI-005 may directly affect ocular pain associated with DED.

  • A Phase 1a/Phase 2b clinical study of 74 subjects with moderate to severe DED treated topically with EBI-005 resulted in a clinically meaningful improvement in Ocular Surface Disease Index (OSDI)-Pain/Sore eye score at six weeks compared to baseline scores.
  • In this Phase 1a/2b study, treatment with EBI-005 for six weeks resulted in a clinically relevant reduction in the frequency of painful or sore eye compared to vehicle treatment.
    • Treatment with EBI-005 was safe and well-tolerated and importantly, did not decrease corneal sensation.
    • The effect was seen as early as two weeks post initiation of therapy with no plateau of effect at 6 weeks
    • The effect was greater over time compared to the vehicle control.
  • The EBI-005 Phase 3 co-primary endpoint in Dry Eye is the painful or sore eyes question of the OSDI.

In a poster presentation entitled “Reduced Rescue Artificial Tear Use in Subjects Using a Topical Interleukin-1 (IL-1) Receptor-1 (R1) Blocker for Ocular Treatment of Dry Eye Disease (DED)” Eleven Biotherapeutics researchers presented data from a Phase 1/2b study which demonstrated that EBI-005 treated subjects used fewer rescue artificial tears than vehicle-control treated subjects.

  • Subjects treated with EBI-005 used fewer rescue artificial tears than vehicle control treated subjects over the six week study period.
    • Mean rescue artificial tear use over the six week study period was 11.1 vials for subjects receiving EBI-005 and 31 vials for subjects receiving vehicle control (p value=.005).
    • Median rescue artificial tear use over the six week period was 1 vial for subjects receiving EBI-005 and 10.5 vials for subjects receiving vehicle control.
    • There was a lower percentage of users of large amounts of rescue artificial tears (defined as user of more than 50 vials during the six week study period) among subjects receiving EBI-005 (5% or 2 of 39) compared with vehicle control (35% or 9 of 26) (p value= .005).
    • Of the 10 heaviest artificial tear users, eight (80%) were subjects receiving vehicle.
    • Vehicle control treated subjects used more rescue artificial tears than those who received EBI-005 at all time points, with the largest difference seen at four weeks.
    • Rescue artificial tear use was similar between EBI-005 treated and those treated with vehicle control at two weeks for subjects with baseline OSDI scores of less than 50 (EE50 population). At four and six weeks, however, subjects receiving vehicle control used more rescue artificial tears than those who received EBI-005.

About EBI-005

Eleven Biotherapeutics’ most advanced product candidate is EBI-005, which was designed, engineered and generated using the Company’s AMP-Rx platform and is being developed as a topical treatment for dry eye disease and allergic conjunctivitis. In 2013, Eleven Biotherapeutics completed a Phase 1b/2a clinical trial of EBI-005 in patients with moderate to severe dry eye disease. The EBI-005 program is based on the role that elevated levels of the inflammatory cytokine interleukin-1, or IL-1, play in the initiation and maintenance of the inflammation and pain associated with dry eye disease and the redness and itching associated with allergic conjunctivitis. EBI-005 is currently being evaluated in a pivotal Phase 3 clinical study in subjects with dry eye disease and a Phase 2 clinical study in subjects with allergic conjunctivitis.

About Eleven Biotherapeutics

Eleven Biotherapeutics, Inc. is a clinical-stage biopharmaceutical company with a proprietary protein engineering platform, called AMP-Rx, that it applies to the discovery and development of protein therapeutics to treat diseases of the eye. The Company’s therapeutic approach is based on the role of cytokines in diseases of the eye, the Company’s understanding of the structural biology of cytokines and the Company’s ability to rationally design and engineer proteins to modulate the effects of cytokines. Cytokines are cell signaling molecules found in the body that can have important inflammatory effects.