MBX Biosciences (MBX) Study result summary

Study background and design

• Canvuparatide is a once-weekly precision peptide therapy for chronic hypoparathyroidism, developed to address unmet needs in a population exceeding 250,000 in the US and EU, aiming to reduce daily treatment burden and improve quality of life.

• The AVAIL Phase II study was a multicenter, randomized, double-blind, placebo-controlled trial enrolling adults with hypoparathyroidism on stable calcium and vitamin D, followed by a one-year open-label extension (OLE) and up to two years of follow-up.

• Dose adjustments were allowed up to 1,600 micrograms, with patients transitioning from clinic to home administration in the OLE.

• The primary endpoint was a composite of normal serum calcium, independence from active vitamin D, and reduced oral calcium supplementation at 12 weeks, with secondary endpoints including bone metabolism and kidney function.

• 94% of patients entered the OLE, with 90% retention at one year, indicating strong adherence and satisfaction.

Key efficacy and clinical outcomes

• At one year, 57% of patients met the composite responder endpoint, comparable to 63% at 12 weeks.

• 98% achieved independence from active vitamin D, 85% from oral calcium, and 75% maintained normal serum calcium at one year.

• Canvuparatide maintained normal serum calcium, reduced urinary calcium excretion, improved eGFR, and restored bone metabolism, with bone turnover markers (CTX, P1NP) increasing then stabilizing.

• Bone mineral density improved and remained within normal ranges.

• Pharmacokinetics supported once-weekly dosing with a flat profile, low peak-to-trough ratio (1.3), and stable exposure.

Safety and tolerability

• Canvuparatide was generally well tolerated, with no new safety signals in the OLE and most adverse events being mild or moderate; 5% had severe TEAEs, and no treatment-related serious adverse events or deaths were reported.

• Injection site reactions occurred in 10% of patients.

• Immunogenicity was minimal, with only 1.7% developing low-titer anti-drug antibodies.

• Hypocalcemia events were mostly mild, often linked to self-administration errors, and are expected to decrease with the commercial device in Phase III.