RARE Daily

Amolyt Enters Rare Disease Research Agreement and Licensing Option with Xoma

January 24, 2023

Amolyt Pharma has entered into a research agreement and licensing option with Xoma to evaluate a set of Xoma’s monoclonal antibodies as potential treatments for two rare endocrine disorders.

Photo: Thierry Abribat, CEO of Amolyt Pharma

Amolyt has the option to license one or more of these candidates from Xoma for further clinical development worldwide.

Primary hyperparathyroidism (PHPT) and humoral hypercalcemia of malignancy (HHM) are rare endocrine diseases with high unmet needs and a common target, the parathyroid hormone 1 receptor (PTHR1), and are characterized by the hypersecretion of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP), respectively, resulting in continuous stimulation of the PTHR1, leading to bone loss, hypercalcemia, and hypophosphatemia. The objective of the research agreement is to test the anti-PTHR1 antibodies in relevant animal disease models with the aim of selecting a candidate that can successfully halt the over-stimulation of the PTHR1 caused by excess PTH and PTHrP and eliminate the debilitating symptoms and serious complications associated with PHPT and HHM.

“We are continuing to build our portfolio for rare endocrine and related diseases while moving, in parallel, our lead program for hypoparathyroidism into a pivotal trial,” said Thierry Abribat, CEO of Amolyt Pharma. “This new program for primary hyperparathyroidism and humoral hypercalcemia of malignancy represents a natural expansion of our pipeline and leverages our clinical expertise in the field of calcium and bone metabolism and in the biology of parathyroid hormone and its receptor.”

PHPT involves excessive PTH production due to enlargement of one or more of the parathyroid glands located at the front and base of the neck that leads to hypercalcemia. Excess serum calcium affects multiple body systems including the skeletal, gastrointestinal, renal (kidney), muscular, cardiovascular, and central nervous systems. Most commonly, primary hyperparathyroidism is seen in people over 60 years of age and is more common in women. Radiation to the head and neck increases the risk of developing the disease as does rare parathyroid carcinoma. In approximately 85 percent of cases, PHPT is caused by a single adenoma. In approximately 15 percent of cases, multiple glands are involved and management of the disease is more challenging.

Approximately 20 percent of all cancer patients develop hypercalcemia during their clinical course, and 80 percent of those cases are caused by excessive secretion of PTHrP from tumor cells (HHM). Squamous cell carcinomas of the head, neck, esophagus and lung, and cancers of the cervix, lung, and colon are most commonly involved, in addition to renal cell, bladder, breast, endometrial, and ovarian cancers. It is associated with a wide spectrum of symptoms including nausea, vomiting, anorexia, abdominal pain, constipation, polyuria, hypotension, bone pain, bone loss, fatigue, and confusion. Renal failure or coma can occur; thus, this condition may be considered an oncologic emergency. Current standard of care is focused on bone anti-resorptive therapy, and intravenous hydration to enhance urinary calcium excretion. However, there are many limitations to available therapy and unwanted effects include fever, bone pain, renal toxicity, hypocalcemia, and osteonecrosis of the maxilla and mandible. A better tolerated systemic therapy that directly targets the interaction between PTHrP and the PTHR1, rather than the downstream effect on bone resorption, has the potential to provide a safer, more effective alternative. Based on a prevalence study in the United States, HHM represented about 57,000 cases in 2013.

Author: Rare Daily Staff

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