Alexis & Jackson; ADH1
Alexis & Jackson; ADH1
Calcilytix is developing a targeted therapy for disorders of calcium homeostasis.
Science
Calcium Regulation
Calcium is the most abundant mineral in the body and is essential for the strengthening of bones and teeth, muscle contraction, the normal functioning of many enzymes, blood clotting and normal heart rhythm.1 As such, blood levels of calcium are tightly controlled.
One mechanism to control calcium levels involves the calcium-sensing receptor (CaSR), which is an integral component of a feedback system that also involves parathyroid hormone and reabsorption of calcium in the kidneys.2
Role of the CaSR in Calcium Regulation
Calcium-sensing receptor helps maintain calcium homeostasis
PTH: Parathyroid Hormone
Ca2+: Calcium
CaSR: Calcium-Sensing Receptor
What is Hypoparathyroidism?
Hypoparathyroidism, or low parathyroid hormone, is a rare disease that most commonly occurs when the parathyroid glands are damaged either due to surgery, an autoimmune disease or a genetic disorder.3 Given these causes, it is more frequently seen in adult women who are more likely than others to undergo thyroid surgery, with an estimated 200,000 affected individuals in the US and EU.4 Symptoms of hypoparathyroidism can range from paresthesias and muscle cramps to seizures.5 The goal of treatment for hypoparathyroidism is to maintain blood calcium levels in the low end of the normal range, which can often require careful monitoring.6
Hypoparathyroidism can cause physical, cognitive and emotional symptoms that can interfere with activities of daily living. Patients with hypoparathyroidism typically receive oral calcium supplements and active vitamin D, which require regular monitoring of calcium in blood and calcium in the urine.7
What is 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. 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.8
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.5 In addition, relatively high levels of calcium in urine, a condition called hypercalciuria, may result in impaired kidney function and can cause kidney stone formation.9
Calcilytix Approach
Calcilytix is investigating encaleret, a small molecule antagonist of the CaSR, as a potential therapeutic for hypoparathyroidism and ADH1. The CaSR is a G-protein-coupled receptor for which extracellular calcium is the primary ligand.10
The major physiologic role of the CaSR is to function conceptually as a ‘calciostat’ and maintain serum calcium levels by regulating the release of PTH and calcium reabsorption.11
*Hendy G. et al., Front Physiol., 2016
*Hendy G. et al., Front Physiol., 2016
Calcilytix in the clinic
Encaleret is currently being studied in a Phase 3 clinical trial in individuals ages 16 and older who have been diagnosed with ADH1.
- PROGRAMS
- PHASE 1
- PHASE 2
- PHASE 3
CALIBRATE for ADH1
NCT05680818
Patients, Caregivers & Advocates
We put patients first.
At Calcilytix, we work to establish and build relationships within the hypoparathyroidism and ADH1 communities. We are committed to approaching these relationships with honesty, integrity and transparency.
We respect the independence of patient organizations and the unique perspective of every advocate, patient and family member.
We actively seek to include the perspective of patients, families and advocates in the drug development process by listening and learning from them.
Patient Stories
Meet Alexis
Alexis is a determined wife, mother and self-proclaimed “social butterfly” who has been living with autosomal dominant hypocalcemia type 1 (ADH1) for over 25 years… read more.
Meet Jackson
Eight-year-old Jackson lives with his parents and younger brother in the Midwest of the United States. Jackson’s story starts at birth… read more.
Resources
Hypoparathyroidism &
Autosomal Dominant Hypocalcemia (ADH)
Expanded Access Policy
Currently, Calcilytix does not offer an expanded access program and is unable to make its investigational products available to patients outside of clinical trials at this time.
If you are a healthcare provider and have questions about Calcilytix’s expanded access policy please contact ExpandedAccess@calcilytix.com. You should expect a response within 5 business days. If you would like to learn more about the Expanded Access process, the FDA provides information here.
To learn about potential eligibility for Calcilytix investigational products within clinical trials, please reference this link:
www.clinicaltrials.gov
Leadership
JF
Jonathan Fox, M.D., Ph.D., FACC
Chief Medical Officer
US
Uma Sinha, Ph.D.
Chief Scientific Officer
AS
Ananth Sridhar
Corporate Development
SA
Scott Adler, M.D.
Clinical Development
MR
Mary Scott Roberts, M.D.
Clinical Development
RP
Roberta M. Pantani
Regulatory Affairs
About Us
Calcilytix is a clinical-stage biopharmaceutical company focused on developing a targeted therapy for disorders of calcium homeostasis. Our product candidate, encaleret, is an investigational orally-administered small molecule designed to specifically inhibit the calcium-sensing receptor, hypothesized to restore normal serum calcium and lower urine calcium.
Calcilytix is led by a team of industry veterans who have been responsible for developing over 30 molecules through Initial New Drug (IND) applications and more than 10 approved drugs. Together with physicians and patients, we aim to develop a safe and effective treatment option for patients with hypoparathyroidism and ADH1.
Parent Company
Calcilytix is a member of the bridgebio family
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.
News & Publications
News
Publications
References
1. Beto, JA. “The role of calcium in human aging.” Clinical nutrition research 4.1 (2015): 1-8.
2. Alexander, SP, et al. “The Concise Guide to Pharmacology 2017/18: G protein‐coupled receptors.” British Journal of Pharmacology 174 (2017): S17-S129.
3. Clarke, BL, et al. “Epidemiology and diagnosis of hypoparathyroidism.” Journal of Clinical Endocrinology & Metabolism 101.6 (2016): 2284-2299.
4. Bilezikian, JP, et al. “Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target‐organ involvement, treatment, and challenges for future research.” Journal of Bone and Mineral Research 26.10 (2011): 2317-2337.
5. Schafer, AL, and Shoback, DM. “Hypocalcemia: Diagnosis and treatment.” Endotext. 2016.
6. Bilezikian, JP, et al. “Management of hypoparathyroidism: present and future.” Journal of Clinical Endocrinology & Metabolism 101.6 (2016): 2313-2324.
7. Gafni, RI, and Collins, MT. “Hypoparathyroidism.” New England Journal of Medicine. 380 (2019): 1738-1747.
8. Roszko, KL, et al. “Autosomal dominant hypocalcemia (hypoparathyroidism) types 1 and 2.” Frontiers in physiology 7 (2016): 458.
9. Taylor, JM, et al. “Urinary Calcium Excretion and Risk of Chronic Kidney Disease in the General Population.” Kidney international reports 2.3 (2017): 366-379.
10. Roberts, MS, et al. “Treatment of autosomal dominant hypocalcemia type 1 with the calcilytic NPSP795 (SHP635).” Journal of Bone and Mineral Research 34.9 (2019): 1609-1618.
11. Conigrave, AD. “The Calcium-Sensing Recepto and the Parathyroid: Past, Present, Future.” Frontiers in Physiology 7:563 (2016).
