Amolyt Pharma

Programs

Pipeline

discovery and research Lead Optimization IND-Enabling Phase 1 azp-3601 azp-3404

PROGRAMS

AZP-3601: Hypoparathyroidism

AZP-3601 (red) bound to the PTH1 receptor. Adapted from Zhao et al. Science 364:138, 2019.

Image generated with the PyMOL Molecular Graphics System, Version 2.3.2 Schrödinger, LLC.

AZP-3601 is a peptide analog of parathyroid hormone (PTH) that targets a specific configuration of the PTH1 receptor to safely produce sustained levels of calcium in the blood and thereby control the symptoms of hypoparathyroidism.1

AZP-3601 has been designed to prevent chronic kidney disease by limiting the amount of calcium eliminated in the urine, and to preserve bone integrity, an important benefit since a large proportion of patients with hypoparathyroidism are middle-aged women often at an increased risk of developing osteoporosis.

AZP-3601 has already demonstrated an optimal pharmacological profile in several preclinical studies.2,3 We have successfully completed pre-investigational new drug activities and a Phase 1 clinical study has been initiated in September 2020.

  1. Hattersley G, et al. “Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling.” Endocrinology 2016; 157:141.
  2. Shimizu, et al. “Pharmacodynamic Actions of a Long-Acting PTH Analog (LA-PTH) in Thyroparathyroidectomized (TPTX) Rats and Normal Monkeys.” J Bone Miner Res. 2016 Jul;31(7):1405-12.
  3. Bi, et al. “Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.” J Bone Miner Res. 2016 May;31(5):975-84.

Publications

2020
“Optimization of PTH/PTHrP Hybrid Peptides to Derive a Long-Acting PTH Analog (LA-PTH).” JBMR Plus (WOA). 2020 July;4(7):1-10.
— Noda, et al.

2016
“Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.” J Bone Miner Res. 2016 May;31(5):975-84.
— Bi, et al.

2016
“Pharmacodynamic Actions of a Long-Acting PTH Analog (LA-PTH) in Thyroparathyroidectomized (TPTX) Rats and Normal Monkeys.” J Bone Miner Res. 2016 Jul;31(7):1405-12.
— Shimizu, et al.

AZP-3404

AZP-3404 is the first therapeutic peptide to leverage the biology of insulin-like growth factor binding protein 2 (IGFBP2), and to utilize multiple, well-established pathways to restore the body’s regulation of fat and glucose metabolism.

IGFBP2 is a protein that carries out the actions of leptin, a hormone that regulates fat and glucose metabolism. The ability of IGFBP2 to do this resides in a small peptide sequence within its structure. AZP-3404 is a stabilized peptide analog of this sequence and is the first drug candidate to reproduce and utilize the unique biology of IGFBP2.4,5,6

We are currently conducting pre-investigation new drug activities and exploring target indications for AZP-3404.

insulin like growth factor binding protein 2
  1. Xi G, et al. “The Heparin-Binding Domains of IGFBP-2 Mediate Its Inhibitory Effect on Preadipocyte Differentiation and Fat Development in Male Mice.” Endocrinology. 2013 Nov; 154(11): 4146–4157.
  2. Xi G, et al. “A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats.” Bone Res. 2018; 6, 23.
  3. Kawai M, et al. “The heparin-binding domain of IGFBP-2 has insulin-like growth factor binding-independent biologic activity in the growing skeleton.” J Biol Chem. 2011 Apr 22;286(16):14670-80.

Publications


2019
ENDO 2019 oral presentation.
— Culler, et al.

2013
“The Heparin-Binding Domains of IGFBP-2 Mediate Its Inhibitory Effect on Preadipocyte Differentiation and Fat Development in Male Mice.” Endocrinology. 2013 Nov; 154(11): 4146–4157.
— Xi G, et al.

2010
“Antidiabetic effects of IGFBP2, a leptin-regulated gene.” Cell Metab. 2010 Jan;11(1):11-22.
— Hedbacker K, et al.

partnerships

Massachusetts General Hospital (MGH)

New Paradigm Therapeutics

The University of North Carolina at Chapel Hill

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