MBX Biosciences Announces Once-Weekly Canvuparatide Achieved Primary Endpoint in Phase 2 Trial with 63% Responder Rate at 12 Weeks; 79% Responder Rate at 6 Months in Open-Label Extension

Statistically significant responder rate achieved at 12 weeks with zero contribution from rescue therapy (PRN) and further improvement sustained in open-label extension (OLE)

Positive findings in bone and kidney biomarkers

All patients completed the 12-week AvailTM trial and 94% entered the OLE

Once-weekly canvuparatide was generally well tolerated, with no treatment-related serious adverse events or discontinuations during the 12-week trial

Preparation underway to initiate Phase 3 trial in 2026

Company to host conference call at 8:00 am ET today

CARMEL, Ind., Sept. 22, 2025 (GLOBE NEWSWIRE) -- MBX Biosciences, Inc. (Nasdaq: MBX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders, today announced once-weekly canvuparatide achieved the primary endpoint with statistical significance at Week 12 in its Phase 2 Avail™ trial, and demonstrated positive 6-month results from the OLE, in adult patients with chronic hypoparathyroidism (HP). All patients (n=64) completed the 12-week study, and 94% of patients elected to enroll in the OLE.

In the 12-week randomized portion of the trial, 63% of canvuparatide-treated patients met the prespecified primary composite endpoint with zero contribution from PRN rescue therapy. In the OLE, 79% of patients receiving once-weekly canvuparatide achieved responder status at 6 months. Responders were defined as patients who maintained serum calcium levels in the normal range (8.2–10.6 mg/dL) and independence from conventional therapy (active vitamin D and >600 mg/day of calcium supplements).

Based on these positive results, MBX is preparing to initiate a Phase 3 clinical trial of once-weekly canvuparatide in 2026.

“The results from the Avail trial are encouraging. A once-weekly therapy could simplify administration and help address important unmet medical needs of patients with hypoparathyroidism,” said Mishaela Rubin, MD, MS, Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and an investigator in the Avail clinical trial. “Hypoparathyroidism poses a substantial burden to patients, who often face complex treatment regimens and unpredictable swings in calcium levels that can lead to serious complications. The 12-week and 6-month data provide promising early evidence that this investigational therapy may offer a potential option for long-term management, pending further study.”

“We are very pleased with the clinically meaningful and statistically significant topline results from our once-weekly canvuparatide Phase 2 trial. These data reinforce our conviction that canvuparatide could become a potential best-in-class treatment for hypoparathyroidism and demonstrate the value of our novel Precision Endocrine Peptide platform technology,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “We believe the totality of the data support a once-weekly product profile with continuous infusion-like PTH exposure. These 12-week and 6-month results represent the potential for a meaningful improvement over current treatment options for HP patients and provide a strong foundation for further development. We look forward to sharing additional once-weekly canvuparatide clinical data at an upcoming medical meeting as we prepare for initiation of our Phase 3 trial.”

Phase 2 Avail Topline Results

12-week and 6-month Responder Rates:

• At 12 Weeks: The primary composite endpoint (maintaining albumin-adjusted serum calcium levels in the normal range (8.2–10.6 mg/dL) and independence from conventional therapy (active vitamin D and >600 mg/day of calcium supplements)) was achieved in 63% of canvuparatide-treated patients (30/48) compared with 31% in placebo-treated patients (5/16) (p=0.042) at Week 12
• At 6 Months: In the OLE, 79% of patients (44/56 evaluable) who received treatment achieved responder status at 6 months, including patients initially randomized to placebo

Select Secondary and Exploratory Endpoints

• Pharmacokinetics: Pharmacokinetic (PK) findings were consistent with the Phase 1 results, supporting a once-weekly dosing schedule
• Bone Activity: Bone turnover and formation markers (BSAP, CTx and P1NP) increased over 12 weeks compared to placebo, consistent with enhanced bone remodeling
• Kidney Activity: In patients with elevated urine calcium at screening that normalized at Week 12, mean urine calcium was reduced by 48% in patients treated with once-weekly canvuparatide compared with 33% on placebo

Safety Summary

• All doses of canvuparatide were generally well-tolerated with no discontinuations related to canvuparatide
• Most treatment emergent adverse events were categorized as mild or moderate
• No SAEs related to canvuparatide were reported
• Injection site reactions (ISRs): 19% in the pooled treatment group versus 13% in placebo
• No deaths were reported

“We are thrilled with these trial results,” said Patty Keating, Executive Director of the HypoPARAthyroidism Association. “For so many in our community, life with hypoparathyroidism means living with constant symptoms and the limitations of daily supplements. A once-weekly treatment option that maintains stable calcium control while reducing the day-to-day burden would be a major step forward.”

The Company will present additional data from the Phase 2 trial and OLE at an upcoming major medical meeting.

Conference Call

The Company will host a conference call and webcast today at 8 am ET to discuss the results from the Avail™ Phase 2 trial. Those who would like to participate may access the live webcast here or dial 1-877-407-0779 (US) or 1-201-389-0914 (international). The live and archived webcast of the call and slide presentation will be available in the Investors section of the Company’s website at https://investors.mbxbio.com/news-events/events.

About the Avail™ Trial

The Avail™ Phase 2 trial (NCT06465108) is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics, and efficacy of canvuparatide in patients with hypoparathyroidism. The study randomized 64 patients into four treatment arms: canvuparatide 400ug, 600ug, 800ug administered by subcutaneous once-weekly injection, and a placebo arm. The 12-week treatment period includes a four-week fixed dose period followed by an 8-week titration period during which canvuparatide dosing may be adjusted every two weeks in 200ug increments. The primary endpoint for efficacy is normalization of albumin adjusted serum calcium while independent from active vitamin D and calcium supplements (