MBX 2109

MBX Biosciences' canvuparatide, a once-weekly fatty-acylated prodrug of parathyroid hormone(1-32) for chronic hypoparathyroidism, met its phase 2 Avail responder endpoint in 2025 and entered the pivotal phase 3 oPTimize trial in August 2026.

Also referenced as: Canvuparatide, MBX-2109, MBX2109

Also appears in: Metabolic

COA Public product evidence No certificate records are bound to a tracked MBX 2109 product page A record counts here only when a vendor publishes a certificate against one of its own tracked MBX 2109 product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is MBX 2109?

MBX 2109, now assigned the nonproprietary name canvuparatide, is a synthetic 35-residue peptide prodrug of parathyroid hormone discovered at Indiana University and developed by MBX Biosciences as a once-weekly hormone replacement for chronic hypoparathyroidism. Its core is the first 32 amino acids of human PTH. The N-terminus is extended by two residues, a D-lysine at position −1 and a sarcosine at position 0, and the C-terminus by a single lysine at position 33; a C18 fatty diacid is attached through a spacer at each end of the molecule, using linker chemistry similar to that of semaglutide (Zhang et al., Molecular Metabolism, 2026;107:102345). The N-terminal fatty-acylated dipeptide makes the injected molecule biologically inert. Under physiologic temperature and pH that dipeptide cyclizes off as a diketopiperazine at a fixed first-order rate, leaving the active drug: PTH(1-32) carrying a single fatty diacid on Lys33, which binds albumin reversibly and circulates for more than a week (Carney et al., Journal of Clinical Endocrinology and Metabolism, 2025;110(4):940–950). The clinical formulation is held at pH 2.1 so that conversion does not begin before injection.

The compound is a synthetic peptide, distinct from teriparatide (PTH(1-34), dosed daily), from recombinant PTH(1-84) and from palopegteriparatide, the once-daily PEG-carrier prodrug of PTH(1-34). It is intended to replace the short-lived PTH exposure of daily injections with flat, infusion-like exposure from one weekly injection. As of November 2026 it is not approved anywhere, holds orphan designations in the US and the European Union, and is in a pivotal phase 3 trial. It has no presence in the research-peptide market.

How it works

• A chemically timed prodrug, not an enzymatic one. The release of active peptide depends only on an intramolecular cyclization governed by temperature and pH, so conversion proceeds at the same rate in every patient rather than depending on plasma proteases; in phosphate-buffered saline at 37 °C the prodrug’s conversion half-life was 102.7 hours. In cells overexpressing the PTH type 1 receptor, the intact prodrug raised cAMP with an EC50 about 1,000-fold higher than synthetic PTH(1-34), a non-convertible control analog (MBX 2101, with glycine at position 0) was inactive, and the released singly acylated PTH(1-32) peptide matched PTH(1-34) in potency and selectivity (Zhang et al., Molecular Metabolism, 2026;107:102345).
• Albumin binding extends the active peptide to a multi-day half-life. In cynomolgus monkeys a 5 nmol/kg intravenous bolus of prodrug had a half-life of 78 hours and generated active peptide with a half-life of 149 hours; in healthy adults given four weekly subcutaneous doses, prodrug half-lives were 79 to 95 hours and active-peptide half-lives 184 to 213 hours, with prodrug concentrations peaking roughly two to three days after each injection and active-peptide peak-to-trough ratios of only 1.47 to 1.79 at the fourth dose (Zhang et al., Molecular Metabolism, 2026;107:102345; Carney et al., Journal of Clinical Endocrinology and Metabolism, 2025;110(4):940–950).
• Classic PTH1R pharmacodynamics in people with intact glands. In the phase 1 study, weekly doses of 400 µg or more raised albumin-adjusted serum calcium, endogenous PTH(1-84) fell within a day of the first injection even at 200 µg, 1,25-dihydroxyvitamin D decreased relative to placebo in every dose group, and the resorption marker CTx rose dose-dependently, while the formation markers P1NP and bone-specific alkaline phosphatase dipped transiently and returned to near baseline by day 25; 24-hour urinary calcium rose relative to placebo only at the highest 900 µg dose (Carney et al., Journal of Clinical Endocrinology and Metabolism, 2025;110(4):940–950).
• Calcium normalization and bone formation in a hypoparathyroid model. In parathyroidectomized rats, canvuparatide at 10 to 40 nmol/kg normalized serum calcium and increased bone formation in proportion to dose, and prodrug and active-peptide exposure rose dose-proportionally in healthy rats, cynomolgus monkeys and humans (Zhang et al., Molecular Metabolism, 2026;107:102345).

Research status

Phase 1 in healthy adults (NCT05158335). The first-in-human program is listed as running from November 10, 2021 to June 20, 2023 with 76 participants across a single-ascending-dose part (50 to 600 µg) and a multiple-ascending-dose part. In the multiple-dose part, 40 adults were randomized 4:1 to MBX 2109 at 200, 400, 600 or 900 µg or placebo, injected subcutaneously once weekly for four doses. Treatment-emergent adverse events occurred in 50 to 88% of drug-treated participants versus 25% on placebo, with no serious or severe drug-related events. Injection-site reactions, generally mild, flat, red, under 50 mm and resolving within three days, affected 10 of 32 treated participants (31.3%) and none on placebo. Asymptomatic hypercalcemia, peaking at 11.4 mg/dL or less and resolving without intervention, occurred in one participant at 600 µg and two at 900 µg and led to two discontinuations. Antidrug antibodies were infrequent and generally of low titer, without apparent clinical consequence. The authors noted that intact parathyroid glands in healthy volunteers blunt the calcium response and that longer studies in patients are needed to judge bone effects (Carney et al., Journal of Clinical Endocrinology and Metabolism, 2025;110(4):940–950; correction at 110(4):e1294).

Avail phase 2 (NCT06465108). The multicenter, double-blind trial ran from August 8, 2024 to June 4, 2025 and randomized 64 adults with chronic hypoparathyroidism to weekly starting doses of 400, 600 or 800 µg or placebo for 12 weeks, with four weeks at a fixed dose followed by eight weeks of titration in 200 µg steps. The primary composite endpoint at week 12 required albumin-adjusted serum calcium within 8.2 to 10.6 mg/dL, independence from active vitamin D, and elemental calcium of 600 mg/day or less. According to the sponsor’s September 22, 2025 announcement, 63% of canvuparatide-treated patients (30 of 48) met the endpoint versus 31% on placebo (5 of 16), p=0.042, with no contribution from rescue calcium. Bone turnover markers (BSAP, CTx and P1NP) rose relative to placebo, and among patients whose elevated screening urine calcium had normalized by week 12 the mean reduction was 48% on canvuparatide versus 33% on placebo. All 64 patients completed the 12 weeks; injection-site reactions occurred in 19% of pooled treated patients versus 13% on placebo, with no treatment-related serious adverse events or discontinuations. One-year data released by the sponsor on June 12, 2026 reported an active-peptide peak-to-trough ratio of about 1.3 across the weekly interval, a rise in mean estimated glomerular filtration rate from baseline at week 12 that persisted through one year, and 24-hour urine calcium that fell from baseline and stayed within the normal range. No peer-reviewed publication of Avail had appeared on PubMed as of November 2026.

Avail-Ext (NCT06531941). Sixty of the 64 participants (94%) entered the two-year open-label extension, which began October 31, 2024 and is listed as active, not recruiting, with completion estimated for May 2028. Sponsor-reported responder rates were 79% (44 of 56 evaluable) at six months, including patients originally randomized to placebo, and 57% (31 of 54) at one year with no rescue therapy in the final week; 90% of extension entrants remained in the study at one year, injection-site reactions were reported in 10%, and no new safety signals or treatment-related serious adverse events were reported.

Renal impairment study (NCT06496217). An open-label, single-dose phase 1 study in 25 adults with normal or impaired renal function completed on September 4, 2025 and is unpublished.

oPTimize phase 3 (NCT07699471). The pivotal trial, registered under sponsor code MBX-2H1005 and EU CTIS number 2026-525326-37-00, started on August 26, 2026, and the sponsor announced dosing of the first patient on August 27, 2026. It plans to randomize about 160 adults with chronic hypoparathyroidism 3:1 to weekly canvuparatide or placebo for 26 weeks: four weeks at 600 µg, an 18-week individualized titration up to 1,600 µg, and a four-week maintenance period with no increases in study drug, active vitamin D or calcium. The primary endpoint is the proportion of responders at week 26, defined by two consecutive normal albumin-adjusted calcium values (8.3 to 10.6 mg/dL), independence from active vitamin D, calcium supplementation of 600 mg/day or less and no dose increase in the preceding four weeks; key secondary endpoints are normalization of urinary calcium in patients with hypercalciuria at baseline and improvements in physical functioning and hypocalcemia symptoms. A 78-week open-label extension follows. The registry lists 22 sites in the US and Canada, recruiting as of its October 29, 2026 update, with primary completion estimated for January 2028 and study completion for August 2029.

Regulatory position. Drugs@FDA and DailyMed list no canvuparatide application or label. The sponsor reports US orphan drug designation for hypoparathyroidism, and the European Medicines Agency granted orphan designation EU/3/25/3182 for treatment of hypoparathyroidism on January 9, 2026. No marketing application has been filed in any jurisdiction as of November 2026.

Common dosage forms

• Investigational lyophilized vial (phase 2). Single-use vials containing 1.5 mg of MBX 2109 as a lyophilized powder, for subcutaneous injection, supplied only to Avail and Avail-Ext trial sites.
• Investigational drug-device combination (phase 3). A single-use integral drug-device combination product containing one vial of lyophilized canvuparatide and delivering 1 mL by manual subcutaneous injection, available in strengths of 400, 600, 800, 1,000, 1,200, 1,400 and 1,600 µg/mL and supplied only to oPTimize trial sites.
• Investigational solution (phase 1). A 1 mg/mL liquid in vials for subcutaneous injection, used in the healthy-volunteer studies.
• No marketed presentation. No approved product, pen, generic or compounded form exists anywhere.

Key considerations

• Regulatory status. The Investigational status reflects the active, recruiting phase 3 oPTimize trial (NCT07699471) sponsored by MBX Biosciences at US and Canadian sites. No application has been filed with the FDA; the compound holds US and EU orphan designations, and the trial’s estimated primary completion is January 2028.
• The efficacy claim rests on a small, sponsor-reported phase 2. The 63% versus 31% responder result comes from 48 treated and 16 placebo patients, reached p=0.042, and has been reported only in company announcements; the one-year extension figure of 57% is open-label and uncontrolled.
• Weekly exposure is the design premise and the open question. A peak-to-trough ratio of about 1.3 removes the daily calcium swings of teriparatide, and the sponsor attributes the extension-study reductions in urine calcium and the rise in eGFR to restored PTH action, but whether a continuously flat PTH signal produces the same long-term bone behavior as intermittent daily dosing is unknown beyond one year of open-label treatment.
• Expected on-target and injection-site effects. Hypercalcemia appeared at the two highest phase 1 doses and resolved without intervention, injection-site reactions were the most common drug-related event in phase 1 and were reported in 19% of treated phase 2 patients, and low-titer antidrug antibodies occurred in phase 1; no treatment-related serious adverse events have been reported across the program.
• Naming. MBX 2109 and canvuparatide are the same molecule; the active circulating species is a fatty-acylated PTH(1-32), so it is neither teriparatide nor PTH(1-84), and palopegteriparatide uses a different prodrug chemistry with daily dosing.