Amolyt Pharma

Programs

Pipeline

discovery and research Lead Optimization IND-Enabling Phase 1 azp-3601 azp-3404 azp-38xx

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.

AZP-38XX: Acromegaly

AZP-38XX Acromegal

Amolyt Pharma is currently testing a series of novel, small peptide antagonists of the growth hormone (GH) receptor to select a lead development candidate for treatment of acromegaly, under a research collaboration with Peptidream. Acromegaly is a rare disease characterized by abnormally high levels of GH, which in turn causes excess production of insulin-like growth factor-1 (IGF-1). By preventing the interaction between GH and its receptor, the antagonist peptides are expected to normalize the excess IGF-1 in patients with acromegaly. To date, there have been over 140 peptides designed from the originally discovered GH antagonist peptide, and that have been optimized to provide greater potency and efficacy.

HUMAN GROWTH HORMONE AND EXTRACELLULAR DOMAIN OF ITS RECEPTOR: CRYSTAL STRUCTURE OF THE COMPLEX. de Vos, A.M., Ultsch, M., Kossiakoff, A.A. (1992) Science 255: 306-312. Image created with Mol* (D. Sehnal, A.S. Rose, J. Kovca, S.K. Burley, S. Velankar (2018) Mol*: Towards a common library and tools for web molecular graphics MolVA/EuroVis Proceedings. doi:10.2312/molva.20181103). RCSB Protein Data Bank, PDB ID: 3HHR.

partnerships

Massachusetts General Hospital (MGH)

New Paradigm Therapeutics

The University of North Carolina at Chapel Hill

Peptidream Inc.

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