MBX Biosciences (MBX) Study result summary

Study background and rationale

• Canvuparatide is a once-weekly precision peptide designed for PTH replacement in chronic hypoparathyroidism, aiming to reduce daily treatment burden and improve patient quality of life for a population exceeding 250,000 in the US and EU.

• The AVAIL Phase II study and its open-label extension (OLE) evaluated safety, efficacy, durability, and patient-reported outcomes in adults with hypoparathyroidism, with most patients having long-standing post-surgical disease.

• The study targeted normalization of serum calcium, independence from active vitamin D and calcium supplements, and reduction of urine calcium.

• The OLE followed patients for up to two years, with endpoints including bone metabolism and kidney function.

• Avail Phase 2 was a multicenter, randomized, double-blind, placebo-controlled study with 64 patients across four arms.

Key efficacy and safety results

• At one year, 57% of patients met the composite responder endpoint, demonstrating sustained efficacy and durability compared 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 enabled most patients to maintain normal serum calcium, reduce or eliminate vitamin D and calcium supplements, and showed a favorable safety profile with mostly mild or moderate adverse events.

• Urinary calcium excretion decreased substantially, especially in patients with elevated baseline levels, while maintaining normal serum calcium and improved eGFR.

• Bone turnover markers increased as expected, indicating restoration of bone remodeling, and bone mineral density remained within normal range.

Safety and tolerability

• Canvuparatide was generally well tolerated, with no new safety signals in the OLE and no treatment-related serious adverse events reported.

• Most adverse events were mild or moderate; 5% had severe TEAEs, and injection site reactions occurred in 10% of patients.

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

• No deaths or treatment-related serious adverse events were reported.