Our goal is to develop Precision Endocrine Peptide (PEP) therapeutics to help people with endocrine disorders live fuller and healthier lives.
We are advancing a pipeline of PEP candidates with clinically validated targets, defined regulatory pathways and unmet medical needs.
Additional Lead Candidates
MBX 2109 is an investigational parathyroid hormone (PTH) peptide prodrug in development as a long-acting hormone replacement therapy for hypoparathyroidism (HP). Under physiological conditions, MBX 2109 (prodrug) is designed to release the active PTH peptide, referred to as MBX 2099, at a precisely controlled rate. Both MBX 2109 (prodrug) and MBX 2099 (active peptide) are designed to have extended half-lives with the potential to enable once-weekly administration. Our goal is to restore PTH physiology, correct the mineral imbalances to alleviate symptoms of the disorder, and enable patients to live healthier lives.
Investigational new drug activities have been successfully completed. MBX 2109 is currently undergoing evaluation in healthy subjects in a Phase 1 trial (NCT05158335).
Parathyroid hormone (PTH) is a peptide hormone secreted by the parathyroid glands that regulates calcium and phosphate levels in the blood through its effects on bone, kidneys and intestines. The parathyroid glands are located behind the thyroid gland in the neck.
Hypoparathyroidism (HP) is a rare condition in which the parathyroid glands fail to produce sufficient amounts of PTH. It affects more than 260,000 persons throughout the United States, Europe and Japan.1-3 HP is often caused by damage to or removal of the parathyroid glands during surgery for another condition but it can be caused by an autoimmune process or other etiologies. Insufficient PTH results in a lowering of blood calcium levels (hypocalcemia) and an increase in phosphate levels (hyperphosphatemia).
Hypocalcemia can cause a variety of symptoms ranging in intensity from mild to severe, including muscle cramps and spasms in the hands and feet and numbness or tingling around the mouth and fingers and toes.4 Depression, confusion and loss of memory have been reported5 and certain individuals may develop calcium deposits in the brain or the kidneys, which can lead to impairment of kidney function.4,6,7 Persons with HP may also be more prone to developing kidney stones.4,7 Less often, more serious complications can occur including seizures or cardiac arrhythmias (abnormal heartbeat).7,8 Consequently, HP can greatly impact a person’s quality of life, interfere with their daily lives, and negatively impact their ability to work.9
Treatment of HP is aimed at raising calcium levels in the blood to provide relief of symptoms without causing abnormally high levels of calcium in the blood (hypercalcemia) or urine (hypercalciuria). The mainstay of treatment is calcium supplements and active vitamin D. Long-term use of these can contribute to the development of calcium deposits and kidney stones.
1. Clarke B. et al. JCEM 2016
2. Powers J. et al. JBMR 2013
3. Shishiba Y. et al. J of Japan Endo Society and Thyroid Surgery 2017.
4. David K. et al. European J of Endocrinology. 2019; 180:71-78.
5. Underbjerg L et al, JBMR 2014;29(11):2504-2510.
6. Mitchel DM et al. JCEM. 2012;97(12):45074514.
7. Underbjerg L et al JBMR 2013; 28(11): 2277-2285
8. Gosmanova EO et al. Adv Ther 2021.
9. Hadker N et al. Endocrine Practice. 2014; 20:671-679.
MBX 1416 is an investigational therapy in development as a potential treatment for post-bariatric hypoglycemia (PBH). We aim to prevent the occurrence of severe hypoglycemia (very low blood sugar) in individuals with PBH so they can lead healthier lives. MBX 1416 is undergoing evaluation in preclinical studies in support of investigational new drug application enabling activities.
Post-bariatric hypoglycemia (PBH; low blood sugar) is rare but increasingly recognized complication of bariatric surgery, occurring after both Roux-en-Y gastric bypass and vertical sleeve gastrectomy. Most patients present within 1 to 4 years of surgery.1
Hypoglycemia (low blood glucose) can occur 1-3 hours after ingestion of a carbohydrate-rich meal. In some individuals, neuroglycopenic symptoms may develop, which can include confusion, weakness, dizziness, blurred vision and loss of consciousness or seizure. These symptoms can result in trauma to the individual. Often individuals experiencing neuroglycopenic symptoms are refractory to conservative therapy with dietary changes. Medications such as acarbose, diazoxide or octreotide may be used off-label by doctors, but poor tolerability limits their use, and none are approved to treat PBH. There remains a significant unmet need to develop therapies to address this condition.
1. Salehi M et al. JCEM 2018; 103: 2815-2826.
Our Discovery Programs
We are pursuing additional discovery of PEP candidates to address unmet needs in other endocrine disorders.