Objective To explore the safety and efficacy of CF101, an A3 adenosine receptor agonist, in patients with moderate-to-severe dry eye syndrome Design Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. Participants 68 patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. Intervention Patients were orally treated with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week post-treatment observation. Main Outcome Measures Efficacy an improvement of >25% over baseline at week 12 in one of the following parameters: (a) tear break-up time (BUT); (b) superficial punctate keratitis assessed by fluorescein staining (FS); (c) Schirmer tear test 1 (ST1). Safety clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements and monitoring of adverse events. Results A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. Conclusions CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate-to-severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome.

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e14731 Background: The A3 adenosine receptor (A3AR) is over-expressed in hepatocellular carcinoma (HCC) cells as well as in the peripheral blood mononuclear cells (PBMCs) of patients with HCC. The orally active drug candidate CF102, an A3AR agonist, induces in vivo apoptosis of HCC cells via de-regulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. Methods: The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally twice daily in continuous cycles of 28 days each. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives. Results: 18 patients received CF102, six at each dose level (1 mg, 5 mg and 25 mg BID). No serious drug-related adverse events or dose-limiting toxicity were observed. Most adverse events were of grade 1-2 severity. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom were sorafenib failures, was 7.8 months (range, 3·5-27·3 months) and for Child-Pugh B patients (28%) was 8.1 months. Stable disease (SD) by RECIST was observed in four patients for at least 4 months. CF102 had no adverse effect on routine measures of liver function over a 6 months period in 12 patients. A direct correlation between A3AR expression levels at baseline and patients’ response to CF102 was found. Conclusions: CF102 is safe and well-tolerated and shows favorable PK characteristics and hepatoprotective effects in patients with HCC. CF102 has shown preliminary evidence of clinical activity in Child-Pugh A and B HCC patients, justifying further clinical development.