The following has been taken from the BridgeBio Pharma's website:
ADH1 is a rare, inherited disease caused by gain-of-function mutations in the calcium sensing receptor (CaSR) resulting in abnormally low serum calcium and high urine calcium and a range of debilitating symptoms. Encaleret sulfate is an investigational oral therapy being studied to address ADH1 at its source by antagonizing the CaSR.
“Patients with ADH1 are currently treated with calcium supplements with a goal of raising their serum calcium levels toward the normal range. Unfortunately, conventional therapy can exacerbate patients’ high urine calcium levels and lead to kidney stones and long-term kidney injury,” said Michael Collins, M.D., Senior Investigator, Skeletal Disorders and Mineral Homeostasis Section of the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health. “We are working with BridgeBio and Calcilytix to investigate whether encaleret, a therapy that targets the root cause of this disease, could potentially be considered as a future treatment option for our patients.”
The Phase 2 trial will enroll up to 16 individuals with ADH1 in an open-label, dose-ranging study to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics, and efficacy of single and multiple doses of encaleret. This study will include two treatment cohorts evaluated over three study periods, including inpatient observation at the NIH. If doses of encaleret are observed to be well-tolerated and demonstrate the potential to normalize blood and urine calcium levels, participants may be treated for up to 26 weeks.
“Encaleret has been previously shown to be well-tolerated and increase serum calcium levels in healthy volunteers and individuals with osteoporosis, a profile that encouraged our investigation of the compound in ADH1 patients,” said Jonathan C. Fox, M.D., Ph.D., Calcilytix’s Chief Medical Officer. “If successful, this initial study will provide clear proof of concept that antagonizing the CaSR can address the underlying cause of ADH1. Our goal is to develop an approved treatment to substantially reduce the current unmet medical need for these patients.”
About Autosomal Dominant Hypocalcemia Type 1 (ADH1)
The protein produced by the calcium-sensing receptor gene forms the CaSR, which regulates the amount of calcium in the blood. The CaSR is a G-protein-coupled receptor for which extracellular calcium is the primary ligand. Conceptually, the major physiologic role of the CaSR is to function as a ‘calciostat’ and maintain serum calcium levels by regulating the release of PTH and renal calcium reabsorption.
ADH1 is caused by rare gain-of-function mutations in the calcium-sensing receptor gene. ADH1 is characterized by increased sensitivity of the CaSR to calcium levels, which results in a physiological ‘perception’ that normal blood calcium levels are high, leading to decreased production of parathyroid hormone and diminished reabsorption of calcium from the urine.
Individuals with ADH1 present with low serum calcium, low or low-normal parathyroid hormone levels and excess urinary excretion of calcium. Symptoms resulting from low levels of serum calcium, or hypocalcemia, may include severe muscle cramping, tetany and seizures. In addition, relatively high levels of calcium in urine, a condition called hypercalciuria, may result in kidney stone formation and impaired kidney function.
About Encaleret (CLTX-305)
Encaleret is an investigational small molecule antagonist of the calcium sensing receptor (CaSR) and is being studied as a potential treatment for ADH1.
About BridgeBio Pharma, Inc.
BridgeBio is a team of experienced drug discoverers, developers and innovators working to create life-altering medicines that target well-characterized genetic diseases at their source. BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers. BridgeBio’s pipeline of over 20 development programs includes product candidates ranging from early discovery to late-stage development. For more information, please visit www.bridgebio.com.
BridgeBio Pharma Forward Looking Statements
This press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to expectations, plans and prospects regarding the clinical development plans and timing, clinical trial designs, clinical and therapeutic potential, and strategy for encaleret (CaSRi) for autosomal dominant hypocalcemia type 1 (ADH1) reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, the success of clinical trials, regulatory filings, and approvals, and those risks set forth in the Risk Factors section of our most recent quarterly or annual periodic report filed with the SEC and our other SEC filings. Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio’s management as of the date of this release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
BridgeBio Pharma, Inc.