Our Science
Precision Endocrine Peptides (PEPs)™ – Transforming Native Hormones into Innovative Medicines
At MBX Biosciences, we are pioneering PEPs to overcome the limitations of native peptide therapeutics. Our intent is to transform the treatment landscape for endocrine and metabolic diseases with efficacious, safe and convenient treatments.
Disclaimer: PEPs are investigational; none are approved drugs.
Endocrine organs secrete peptide hormones (a chain of amino acids) that bind to cell surface receptors and trigger intracellular effects. Peptide hormones can disrupt appropriate biological function. In these instances, therapeutic peptides acting as hormones have been used to replace or block endogenous biology with the goal of restoring homeostasis and appropriate endocrine function.
HOW PEPs WORK
Pioneering Precision Endocrine Peptides (PEPs)
Therapeutic proteins have traditionally been developed to mimic naturally occurring hormones, but when developed as medicines they often have some potentially significant drawbacks. Native peptide therapeutics often have short half-lives. They are rapidly degraded by enzymes and swiftly cleared (within minutes to hours) by the liver and kidney. This often necessitates frequent injections, which can result in high variability in peptide plasma concentrations that can promote undesired biological effects of the drug. To overcome these challenges, MBX Biosciences is pioneering PEPs. PEPs are engineered to have optimized pharmaceutical properties that we believe will allow us to transform native peptides into innovative, ground-breaking therapeutics.
ADVANCED CHEMICAL MODIFICATIONS
With a goal to provide:
- Enhanced physical properties including stability and solubility
- Increased potency
- Multiple mechanisms of action in a single peptide
PROGRAMMABLE PRODRUG
- Designed to precisely time chemical conversion of prodrug to active drug to reduce peak-to-trough ratios and improve clinical outcomes
Fatty
Acylation
Aims to provide:
- Increased duration of action (convenient dosing regimen)
- Compatibility with non-injectable formulations (e.g. oral)
Platform
Our Proprietary Peptide Delivery Platform
Potential Benefits of PEP™ Platform Technology
- Extended half-life
- Deliver consistent drug concentrations (reduce peak-to-trough)
- Consistent exposure to target tissue potentially leading to better outcomes
- Infrequent dosing
We have created a proprietary technology platform to design PEPs. PEPs are innovative peptide hormone analogs and are designed to overcome key limitations of native peptide therapeutics.
The biological activity of a peptide hormone is intimately related to its chemical structure. Understanding the chemistry is key to knowing how and where to modify the peptide to enhance its pharmacologic effects.
By developing groundbreaking new approaches, our Scientific Co-Founder Richard DiMarchi PhD and his research team are recognized as global leaders in the field of peptide drug design. Leveraging this expertise, we are advancing a pipeline of PEPs that have been selectively modified using state-of-the-art and proprietary chemical modifications to enhance stability and improve pharmacokinetics compared to the native peptide hormone. Further, we aim to extend the duration of action of the PEP thereby potentially enabling less frequent administration.
Through the use of our platform technology, we are actively pursuing discovery opportunities in a variety of endocrine and metabolic disorders. Visit our pipeline page for more information about some of our current PEP product candidates.
Our PipelinePotential Once-Weekly PTH Replacement Therapy for Hypoparathyroidism
- Potential best-in-class PTH replacement therapy
- Sustained PTH pharmacology
- Normalize serum and renal calcium
- Eliminate pill burden
- Convenient once-weekly dosing
- Reduce complications
Treatment of hypoparathyroidism 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. Left untreated or improperly managed, HP can lead to tetany, seizures, cardiac arrhythmia, and more.
MBX 2109 is an investigational new drug (delivered via sub-cutaneous injection), designed to offer a precision-based approach to help people with hypoparathyroidism achieve continuous and consistent exposure to parathyroid hormone (PTH). We are hopeful that the outcome will be restoration of normal PTH physiology, correcting mineral imbalances, and alleviating the symptoms of the disorder.
Potential first-in-class therapy to treat Post-Bariatric Hypoglycemia
- Prevent severe hypoglycemia and associated risks
- Convenient once-weekly dosing
- Improve Quality of Life
- Eliminate need for rescue therapy (glucagon) and surgical intervention
Post-bariatric hypoglycemia (PBH; low blood sugar) is a rare but increasingly recognized complication of bariatric surgery, occurring after both Roux-en-Y gastric bypass and vertical sleeve gastrectomy. In some individuals, neuroglycopenic symptoms may develop, which can include confusion, weakness, dizziness, blurred vision and loss of consciousness or seizure. Often individuals experiencing neuroglycopenic symptoms are refractory to conservative therapy with dietary changes. Certain medications may be used off-label by doctors, but poor tolerability often limits their use, and none are approved by the FDA to treat PBH.
MBX 1416 is an investigational therapy in development as a potential treatment for PBH and is undergoing evaluation in clinical studies. We aim to prevent the occurrence of severe hypoglycemia (very low blood sugar) in individuals with PBH so they can lead healthier lives.
Potential LONG-ACTING GLP-1/GIP Receptor CO-AGONIST for Obesity
- Help those who are obese lose weight and improve their overall health
- Reduced dose complexity
- Less frequent administration
- Improved GI tolerability
Obesity is a common problem that has risen to epidemic proportions. It’s a chronic health condition that is caused by any number of factors from eating patterns and lack of physical activity to quitting smoking, genetics, and more. It contributes to at least 200 health issues including type 2 diabetes, high blood pressure, depression, certain cancers, and heart disease. Beyond the health challenges to the obese individual, weight has become a global health problem on a variety of levels.
Weight stigma is also a factor that has the potential to impact development of appropriate solutions to tackle this issue and can cause further struggles to someone with obesity. The complexity of this condition requires a comprehensive, multifaceted approach.
MBX 4291, our long-acting GLP-1/GIP Receptor co-agonist, is an investigational therapy in development as a potential treatment for obesity. We aim to develop a safe and efficacious medicine that helps patients achieve their weight loss goals and improve their overall health.