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2 TRAVERE ™ THERAPEUTICS Travere Therapeutics Announces Positive Topline Results from the Ongoing Phase 1/2 COMPOSE Study of Pegtibatinase in Classical Homocystinuria December 15 , 2021 Treatment with highest dose pegtibatinase led to a clinically meaningful 55 % mean reduction in total homocysteine from baseline and was generally well - tolerated after 12 weeks of treatment Results provide clinical proof of concept for first potential therapy targeting the underlying enzyme deficiency in classical homocystinuria Company to host conference call and webcast today at 8:30 a.m. ET SAN DIEGO , Dec. 15 , 2021 ( GLOBE NEWSWIRE ) -- Travere Therapeutics , Inc. ( NASDAQ : TVTX ) today announced positive topline results from the ongoing Phase 1/2 COMPOSE Study of pegtibatinase , a novel investigational enzyme replacement therapy being evaluated for the treatment of classical homocystinuria ( HCU ) . In the highest dose cohort to date evaluating 1.5mg / kg of pegtibatinase twice weekly ( BIW ) , treatment with pegtibatinase resulted in rapid and sustained reductions in total homocysteine ( tHcy ) through 12 weeks of treatment , including a 55.1 % mean relative reduction in tHcy from baseline as well as maintenance of tHcy below a clinically meaningful threshold of 100 μmol . To date in the study , pegtibatinase has been generally well - tolerated . " These promising topline results from the ongoing COMPOSE Study show that pegtibatinase has the potential to improve overall metabolic function and provide clear proof of concept for pegtibatinase as a potential novel therapy for patients living with HCU , " said Bill Rote , Ph.D. , senior vice president of research and development at Travere Therapeutics . “ With the strength of these data , we are furthering efforts to refine our formulation and explore pegtibatinase dosing , while in parallel engaging with regulators to establish next steps for a pivotal development program designed to ultimately support potential approvals pegtibatinase for the treatment of HCU . " " Most patients with HCU are at high risk of developing long term and often devastating complications from HCU because they cannot sustain low levels of toxic homocysteine with currently available treatment options , " said Harvey Levy , M.D. , senior physician in medicine / genetics , Division of Genetics and Genomics , Boston Children's Hospital , professor of pediatrics , Harvard Medical School . " The data from the ongoing COMPOSE Study are highly encouraging and provide promise for a potentially novel approach to targeting the underlying enzymatic defect in HCU . " To date in the COMPOSE Study , a total of 19 patients with HCU have been randomized 3 : 1 to receive either pegtibatinase or placebo in independent ascending subcutaneous dose cohorts , ranging from 0.33mg / kg once weekly to 1.5mg / kg BIW . The study protocol provided for an unblinded assessment to evaluate safety , tolerability , pharmacokinetics ( PK ) , pharmacodynamics ( PD ) and clinical effects after twelve weeks of treatment had been completed in the fifth cohort ( 1.5mg / kg BIW ) . Key findings from the topline results : • To date in the COMPOSE Study , pegtibatinase has been generally well - tolerated . • There were no discontinuations due to treatment - related adverse events . There was one serious adverse event , moderate acute urticaria ( hives ) , that was categorized by the treating physician to be likely related to pegtibatinase treatment but did not lead to treatment discontinuation and resolved following a single dose interruption . • Pegtibatinase demonstrated dose - dependent reductions in tHcy during the 12 weeks of treatment . • At the two highest doses , pegtibatinase appeared to reduce tHcy regardless of starting baseline tHcy levels or background therapy . • In the highest dose cohort to date of 1.5mg / kg BIW , treatment with pegtibatinase resulted in rapid and sustained reductions in tHcy , resulting in a maintenance of tHcy below a clinically meaningful threshold of 100 µmol from week 2 through week 12 of treatment . • In the 1.5mg / kg BIW dose cohort , treatment with pegtibatinase resulted in a mean relative reduction from baseline of 55.1 % ( n = 3 , mean baseline tHcy = 187.0 μmol ) , compared to a mean relative reduction from baseline of 4.8 % for all patients receiving placebo in the study ( n = 5 , mean baseline tHcy = 131.1 µmol ) . • In a dose - dependent manner in the study to date , methionine levels were substantially reduced and cystathionine levels were substantially elevated following treatment with pegtibatinase , suggesting that pegtibatinase acts in a manner similar to the native CBS enzyme . • The Company plans to present additional detailed study results at an upcoming medical meeting or in a peer - reviewed publication .