Eloxx Pharmaceuticals, Inc. provided an update on progress in its Phase 2 clinical programs and its pipeline of novel ERSG (eukaryotic ribosomal selective glycoside) compounds. The Phase 2 Cystic Fibrosis clinical trial program for ELX-02 is actively dosing patients in the U.S. and Israel and continuing to enroll patients at leading global investigator sites. The company expected full enrollment to be achieved during the first quarter of 2020 and to report topline results during the first half of 2020. In the U.S., the Cystic Fibrosis Foundation is providing funding for a portion of the trial. The company continue to progress ERSG pipeline in inherited retinal disorders (IRD) and ADPKD. In ocular, the company recently reported on a critical milestone demonstrating that several of library compounds successfully reach retinal disorder-relevant tissue layers and can restore protein production in an animal model. The company plans to present these data at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting May 3-7, 2020 in Baltimore, MD. There are over 300 IRD associated with nonsense mutations. ADPKD is a relatively common inherited genetic kidney disease occurring in between 1:400 and 1:1000 patients and the 4th leading cause of end stage renal disease in the United States. Over 25% of the primary genetic changes that cause ADPKD are nonsense mutations, where a premature stop codon in the gene leads to a truncated, often unstable, protein. The company has evaluated the three most relevant ADPKD nonsense mutations in an in vitro read-through assay and have demonstrated significant levels of read-through for ELX-02 and several library compounds which is the first step in preclinical development toward IND. In Cystinosis, Eloxx announced positive data from the first cohort of the Phase 2 study of ELX-02, a novel ERSG, in the treatment of patients with nonsense mutation-mediated nephropathic cystinosis. The first cohort enrolled three homozygous W138X male and female patients ages 23 to 38, with prior kidney transplants and varying degrees of renal insufficiency. The primary endpoint for this study was safety. This study also evaluated other parameters including white blood cell (WBC) cystine levels. Following completion of the first cohort, an independent Safety Review Committee met to review the pharmacokinetic and safety results and approved progressing to the second cohort that would enable enrolling patients ages 12 and older. Following one week of treatment, all three patients in dose group 2 (DG2, nominal dose 1.0 mg/kg/day) had shown a significant decrease (p < 0.05) in WBC cystine levels. After a three-week period of no treatment, followed by two weeks of treatment, two of three patients in dose group 3 (DG3, nominal dose 2.0 mg/kg/day) also showed reductions in WBC cystine levels. All three patients in dose group 1 (DG1, nominal dose 0.5 mg/kg/day, 1 week of treatment) had increases in WBC cystine levels. For cystinosis patients, the targeted goal of therapy is to reduce WBC cystine levels to below 1 nmol of ½ cystine/mg protein. Across all dose groups, patients had elevated and uncontrolled pretreatment WBC cystine levels ranging from 2.2 to 9.5 nmol of ½ cystine/mg protein, representing a substantial therapeutic challenge. In prior clinical studies of cysteamine, patients typically had pretreatment WBC cystine levels less than 2 nmol of ½ cystine/mg protein. Reductions in WBC cystine were apparent across the 1.0 and 2.0 mg/kg/day doses in the first cohort but none of these reductions were to levels below 1 nmol of ½ cystine/mg protein. These promising reductions in WBC cystine provide a clear indication of ELX-02 biologic activity at nominal doses > 0.5mg/kg/day. The pharmacokinetics of ELX-02 administered daily were consistent with those expected based on the prior SAD, MAD and renal impairment studies and the emerging safety profile of ELX-02 in patients supports continued development. In this study, ELX-02 was generally well tolerated with no deaths, nephrotoxicity, ototoxicity or serious adverse events potentially related to ELX-02. The only reported adverse events related to ELX-02 were injection site reactions that were mild in severity. Consistent with the absence of meaningful changes or negative trends in serum creatinine or eGFR, kidney function was preserved in these post-transplant patients. In other clinical trials, changes in serum creatinine and eGFR have been used as important study endpoints. Eloxx is reviewing these data with a panel of cystinosis scientific and clinical experts to determine if protocol modifications would be appropriate before initiating cohort 2 of this study. The clear indications of biologic activity at nominal doses > 0.5mg/kg/day provide human clinical proof of concept for ELX-02 and de-risk other clinical applications of ERSG library using this dosage range. These encouraging results also provide a basis for expansion to studies of additional kidney diseases caused by nonsense mutations such as ADPKD. This study was conducted with the support of nondilutive funding from Genome Quebec and Genome Canada.