Alizé Pharma 3, a company specialized in developing therapeutic peptides for the treatment of rare endocrine and metabolic diseases, announced a key addition to its leadership team and the structuring of its product portfolio in line with its ambition to become a leading global rare disease company.
Alizé Pharma 3 is the third venture within the Alizé Pharma organization, whose first two companies were acquired by Jazz Pharmaceuticals in 2016 and Millendo Therapeutics in 2017.
“It is Alizé Pharma 3’s intention to build a biopharmaceutical company with operations in both Europe and North America. This will enable us to support the global development of our portfolio products through to regulatory approval,” said Thierry Abribat, founder and CEO of Alizé Pharma 3.
The first two assets of Alizé Pharma 3 are AZP-3601, a best-in-class parathyroid hormone (PTH) analog uniquely designed for the treatment of hypoparathyroidism, which originated at the Massachusetts General Hospital in Boston, and AZP-3404, a small peptide leveraging the biology of Insulin-like Growth Factor Binding Protein-2 (IGFBP2) for the treatment of syndromes of severe insulin resistance and monogenic obesities, which originated at the University of North Carolina at Chapel Hill and the University of Maine. Both programs are 12-18 months away from entering clinical development.
“There are still substantial unmet medical needs in rare endocrine and metabolic diseases,” said AJ van der Lely, head of the Division of Endocrinology and professor of endocrinology at the Erasmus University MC in Rotterdam, and medical advisor for Alizé Pharma 3. “Alizé Pharma 3’s current portfolio of programs targets several significant problems with innovative but solid rationales for patients with hypoparathyroidism, severe insulin resistance and monogenic obesities.”
Hypoparathyroidism, a severe disease resulting from insufficient parathyroid hormone (PTH) to maintain normal circulating calcium levels, affects over 80,000 patients in the US. It is associated with a large spectrum of symptoms, including mild to debilitating neuromuscular irritability, as well as neurocognitive and neuropsychiatric manifestations, due to low blood calcium levels. Conventional therapy is based on direct calcium and vitamin D supplementation, which is cumbersome, is ineffective in controlling the disease in a significant number of patients and which carries increased risk of kidney disease due to excess renal excretion of calcium in the urine. PTH replacement therapy is an obvious solution to overcome these limitations, but presents many challenges related to specificity, safety, and efficacy.
AZP-3601 is a unique PTH analog designed specifically for PTH replacement therapy in hypoparathyroidism by academic partners at the Massachusetts General Hospital and Harvard Medical School. AZP-3601 potently interacts with a specific configuration of the PTH receptor that results in prolonged activation and effect on calcium metabolism. Preclinical studies have demonstrated that AZP-3601 is far more effective and longer-acting than natural PTH in increasing and maintaining circulating calcium levels without increasing urinary calcium excretion. It is anticipated that the unique mechanism of action of AZP-3601 will translate into an enhanced safety and efficacy profile and will make it a best-in-class therapy for treatment of this rare, but severe, endocrine disorder.
AZP-3404 is the first compound to harness the biology of Insulin-like Growth Factor Binding-Protein 2 (IGFBP-2), a physiological protein with key regulatory effects on glucose and fat metabolism that are independent from its IGF-binding properties. Alizé Pharma 3 and its academic partners at the University of North Carolina at Chapel Hill and the University of Maine have identified and optimized short peptide fragments of IGFBP-2 that retain its biological activities on metabolism and bone. AZP-3404 is a stabilized analog of one of these IGFBP-2 fragments with an improved pharmacokinetic profile.
As a result, AZP-3404 is highly potent in restoring glucose control and in decreasing fat deposition in preclinical models, including models of severe insulin resistance. Based on its pharmacological profile, AZP-3404 is set to become a first-in-class therapy for the treatment of syndromes of severe insulin resistance and monogenic obesities, that include a range of ultra-rare to more prevalent orphan diseases associated with high mortality and morbidity.
(Source: Alizé Pharma 3)
Filed Under: Orphan Drugs