SARcode announces results of phase 1 trial of SAR 1118 ophthalmic solution in healthy adult subjects

SARcode Corporation announced today the results of its Phase 1 randomized, double-masked, placebo-controlled trial of the safety, tolerability, and pharmacokinetics of single- and multiple-escalating doses of SAR 1118 Ophthalmic Solution in healthy volunteers.

SAR 1118 was well-tolerated and demonstrated a favorable safety profile when administered by topical ocular instillation up to three times daily at dose strengths of up to 5%.

The Phase 1 trial was designed to evaluate the local and systemic safety and pharmacokinetic parameters of SAR 1118 Ophthalmic Solution in the plasma and tear of 28 healthy adults at four dose strengths (0.1, 0.3, 1.0, and 5.0%). The dosing schedule was divided into 3 periods in which subjects received SAR 1118 as a single dose, twice daily for 10 days and then three times daily for 10 days with a 72-hour wash-out interval between study periods and a 2 week observation period following dosing completion. Ocular assessments including slit-lamp examination, visual acuity, Schirmer tear test, tear film break-up time, and intraocular pressure were obtained at screening as well as at the beginning and completion of each period. Masked safety data was reviewed by a Safety Committee prior to allowing dose-escalation.

All subjects completed the trial and no doses were missed. There were no discontinuations, no significant treatment-related changes in ocular assessments or laboratory parameters, and no serious or severe ocular or non-ocular adverse events at any dose strength or dose schedule. The pharmacokinetic parameters demonstrated adequate ocular exposure at all three dose schedules with minimal systemic exposure.

Based upon these results, SARcode has selected dose strengths and dose schedules for its Phase 2 programs in allergic conjunctivitis and dry eye (keratoconjunctivitis sicca). Data for these programs is expected in 2009. With emerging data in preclinical animal models, SARcode may choose to pursue other ocular inflammatory conditions including diabetic retinopathy and age-related macular degeneration in the near future.

"We are pleased with the results of our initial human clinical study to characterize the safety and tolerability of SAR 1118. This compound represents the first-in-class novel anti-inflammatory agent to be advanced as an ocular therapy," said Charles Semba, MD, Chief Medical Officer of SARcode Corporation. "The Phase 1 data suggests that SAR 1118 is well-tolerated with an acceptable pharmacokinetic profile to treat patients with ocular inflammatory conditions. We look forward to Phase 2 clinical trial results later this year."

SAR 1118 is a potent novel small molecule antagonist of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; αLβ2) that can be targeted against a broad range of ocular inflammatory conditions including dry eye, allergies, uveitis, diabetic retinopathy and age-related macular degeneration. LFA-1 is member of the integrin family of adhesion receptors found on the surface of all leukocytes and represents a therapeutic target of the immune system central to a number of inflammatory stimuli, whether mediated by cytokines, prostaglandins, leukotrienes or complement. SAR 1118 has demonstrated significant potency in in vitro models in inhibiting cell adhesion, cytokine production, and cellular proliferation. Topical ophthalmic solution of SAR 1118 has shown a significant reduction of ocular surface inflammation and improved aqueous tear production in canine dry eye disease. SAR 1118 was discovered by Sunesis Pharmaceuticals, Inc. and the intellectual property and other assets related to the Sunesis LFA-1 program have been recently acquired by SARcode Corporation.