Allena Pharmaceuticals, Inc. provided progress updates on its clinical programs: ALLN-346, a first-in-class, oral urate degrading enzyme in development for the treatment of patients with hyperuricemia and gout in the setting of chronic kidney disease (CKD) and reloxaliase (ALLN-177), a first-in-class, oral oxalate degrading enzyme in development for the treatment of patients with enteric hyperoxaluria. ALLN-346: Phase 1b Study Results and Planned Phase 2A Program: ALLN-346 is an investigational first-in-class, non-absorbed, orally administered enzyme for the treatment of hyperuricemia and gout, a metabolic disorder characterized by high systemic levels of uric acid that can lead to several complications, including arthritis, kidney stones, and chronic kidney disease. The company recently completed a Phase 1b multiple ascending dose study of ALLN-346. The study included 18 healthy volunteers, who received either ALLN-346 or placebo (2:1 randomization) for seven days. There were two cohorts consisting of nine subjects each, with the first receiving three capsules of ALLN-346 three times daily, and the second receiving five capsules of ALLN-346 three times daily. ALLN-346 was well tolerated with no evidence of systemic absorption, as confirmed by an enzyme-linked immunosorbent assay (ELISA). Evaluation of clinical and laboratory parameters revealed no significant safety signals and no serious adverse events were reported. As previously reported, the Company is preparing to initiate two randomized, double-blind, placebo-controlled Phase 2a studies to obtain initial bioactivity data and additional safety data for ALLN-346 in patients with hyperuricemia and gout during the third quarter of 2021. Initial results from the Phase 2a program are expected during the fourth quarter of 2021. An inpatient study (Study 201) is planned to initially enroll 12 patients with hyperuricemia randomized (2:1) to receive either five capsules of ALLN-346 or matching placebo three times daily during a one-week treatment period. Key bioactivity endpoints will include serum uric acid level, 24-hour urine uric acid level, and renal clearance of uric acid. Following evaluation of the data from the initial 12 patients, the Company will make a determination regarding potentially extending the study to include up to an additional 12 patients, either to obtain additional data at the five-capsule, three-times-daily dose, or to evaluate a different dose. An outpatient study (Study 202) is planned to enroll 24 hyperuricemic patients with gout and mild-to-moderate chronic kidney disease randomized (2:1) to receive either five capsules of ALLN-346 or matching placebo, three times daily, during a two-week treatment period. Two cohorts of 12 patients each are planned, with the first cohort consisting of patients with an eGFR (estimated glomerular filtration rate, a measure of renal function) of 60-89 mls/minute, and the second consisting of patients with an eGFR of 30-59 mls/minute. Key bioactivity endpoints will include serum uric acid level, 24-hour urine uric acid level, and renal clearance of uric acid. The limitations of existing gout treatments were highlighted in the Company's recent KOL Webinar. Specifically, managing gout in the setting of advanced chronic kidney disease remains a significant challenge for clinicians because currently available agents are either dose-limited or contraindicated in these patients. There are approximately 500,000 patients with gout and advanced chronic kidney disease in the United States. Reloxaliase: Revised Plan for First Interim Analysis: Reloxaliase is an investigational, first-in-class, non-absorbed, orally administered enzyme for the treatment of enteric hyperoxaluria, a metabolic disorder characterized by high levels of urinary oxalate (UOx), which can lead to kidney stone disease and chronic kidney disease. There are currently no approved therapies for this disorder, which affects approximately 250,000 patients in the United States. Reloxaliase exerts its effect by breaking down oxalate in the gastrointestinal (GI) tract, reducing the absorption of dietary oxalate. The Company previously completed the URIROX-1 trial, the first of two pivotal Phase 3 clinical trials of reloxaliase, which demonstrated a statistically significant reduction in UOx levels during weeks 1-4, the primary endpoint of the study. The Company is currently studying reloxaliase in the adaptive-design URIROX-2 trial, the second of two pivotal Phase 3 clinical trials in its URIROX program. URIROX-2 is a multicenter, global, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of reloxaliase in patients with enteric hyperoxaluria over a minimum treatment period of two years. The trial is designed to enroll 200 patients with 24-hour UOx excretion greater than or equal to 50 mg/day and a history of kidney stones, and includes patients with both normal kidney function and reduced kidney function up to Stage 3 chronic kidney disease (eGFR > 30 mL/min). The primary efficacy endpoint of URIROX-2 is the percent change from baseline in 24-hour UOx excretion during weeks 1-4, the same primary endpoint as URIROX-1. Secondary endpoints in URIROX-2 include the percent change from baseline in 24-hour UOx excretion during weeks 16-24 and the proportion of subjects with a = 20% reduction from baseline in 24-hour UOx excretion during Weeks 1-4. The primary long-term efficacy endpoint to confirm clinical benefit is kidney stone disease progression, defined as a composite of either symptomatic kidney stones or finding of new or enlarged kidney stones using imaging, over a minimum treatment period of two years. Secondary long-term efficacy endpoints to confirm clinical benefit include change in eGFR from baseline and resource utilization for the management of kidney stones. URIROX-2 incorporates adaptive design elements that could, if necessary, allow for increasing the sample size and/or duration of treatment based upon the results of two interim analyses. As part of the URIROX-2 adaptive design, the Company had previously planned to conduct the first interim analysis after 130 subjects had been treated for at least six months and had estimated the timing of this analysis to be in the second or third quarter of 2022. Given the adverse impact of the COVID-19 global pandemic on the rate of patient enrollment in this global study, and considering as well that enrollment in the study began in early 2019, the Company has modified its plans and now expects to conduct the first interim analysis, which will include all subjects who were enrolled in the trial as of the end of November 2021, during the first quarter of 2022.