Travere Therapeutics (TVTX) Study Update summary

Study status and enrollment

• Enrollment in the phase III HARMONY study for pegtibatinase in classical HCU has been voluntarily paused to address commercial manufacturing scale-up process improvements.

• Enrollment was initiated using small-scale batches, with plans to expand upon successful commercial-scale manufacturing.

• All patients currently enrolled will continue on small-scale study medication and may roll over into the ENSEMBLE portion of the study.

• Enrollment to restart is estimated for 2026, pending completion and validation of process improvements, with related investments delayed beyond 2025.

• No structural changes to the trial design or protocols are anticipated due to the pause.

Manufacturing and process improvements

• Scale-up process did not achieve the desired drug substance profile, prompting the enrollment pause.

• Process improvements are being addressed with internal teams, external experts, and multiple CDMO partners.

• No patients have received large-scale manufactured drug; all dosing to date used small-scale batches.

• The objective is to match the clinical profile of small-scale material at commercial scale, with no expected change in safety or efficacy.

• Regulatory engagement with the FDA is ongoing and will continue as process improvements are implemented.

Clinical data and patient impact

• Positive safety and efficacy data from the phase I/II COMPOSE study support continued confidence in pegtibatinase.

• The COMPOSE study showed a 67.1% mean relative reduction in total homocysteine at 12 weeks for the 2.5 mg/kg dose, and the drug was generally well-tolerated.

• Data from current patients will be included in the BLA and are important for the regulatory package.

• Patients in ongoing studies will have the option to continue treatment and transition to long-term extension studies.

• Pegtibatinase has received Breakthrough Therapy, Rare Pediatric Disease, Fast Track, and Orphan Drug designations in the U.S. and Europe.