A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)

An Open-Label, Phase 3 Long-Term Extension (LTE) Study To Assess The Safety, Tolerability, And Efficacy Of Treatment With Pegtibatinase In Participants With Classical Homocystinuria (HCU) Due To Cystathionine Beta Synthase Deficiency (ENSEMBLE)

The goal of this long-term extension (LTE) study is to evaluate the safety and efficacy of pegtibatinase in patients with classical homocystinuria (HCU). Patients who are active in the Phase 1/2 COMPOSE study or those who complete the 24 weeks of blinded treatment in the Phase 3 HARMONY are eligible to participate.

Participants will be in this clinical study for a minimum of 108 weeks including:

• a treatment period of up to 104 weeks
• a 4-week safety follow-up period

Overall Design:

This is a global, multicenter, single-arm, open-label study. Participants who meet all eligibility criteria may transition from other pegtibatinase studies and enroll into this LTE study for long-term safety, efficacy, and clinical assessments of pegtibatinase treatment.

All participants will follow a protocol of self-administration of pegtibatinase unless exempted. During the study, pegtibatinase pharmacokinetic assessments will be conducted. An optional protein tolerance modification (PTM) sub-study will also be conducted for eligible participants.

Inclusion Criteria:

• Participants active in the COMPOSE study or who completed the 24-week blinded period on study intervention (pegtibatinase or placebo) in the Phase 3 HARMONY study

Exclusion Criteria:

• Participant permanently discontinued from study intervention treatment in a previous pegtibatinase study due to serious AE (SAE) or intolerance