Company   Alize Pharma SAS
Program   AZP-531, a stabilized peptide analog of unacylated ghrelin
Stage of development  

Phase II in hyperphagia in the Prader-Willi syndrome

Phase Ib in type 2 diabetes

Preclinical in ischemia-related diseases

Status   Unpartnered

initiative Octalfa


Sham Innovation Santé

Innobio (Bpifrance)

TAB Consulting


The aim of the UAG program is to develop AZP-531, a stabilized peptide analog of unacylated ghrelin, the first product of a new therapeutic class for the treatment of metabolic and cardiovascular disorders.


ALIZE PHARMA AZP 531 UAG programThe launch of this clinical program follows five years of collaborative research between Alizé Pharma and its academic partners at the Erasmus Medical Center in Rotterdam, in the Netherlands, and the University of Turin, in Italy. This research has led to the identification of unacylated ghrelin as a new therapeutic class, and to the design of AZP-531. The unique pharmacological profile of AZP- 531 differentiates it from ghrelin antagonists and all existing therapeutic classes. Preclinical and clinical data suggest that unacylated ghrelin and its analogs have the therapeutic potential to address unmet medical needs in the treatment of type 2 diabetes, the Prader-Willi syndrome and some ischemia-related conditions, via a novel mechanism of action.


The clinical program started in 2013. A Phase Ia trial in healthy volunteers and a Phase Ib trial in obese/overweight subjects have been completed so far. A phase Ib trial in type 2 diabetes patients and a Phase II trial in Prader-Willi syndrome are underway.

Results from the Phase Ia trial in healthy volunteers and from the Phase Ib trial in obese/overweight subjects were presented at the 75th scientific sessions of the American Diabetes Association in Boston on June 5-9, 2015 :

 See poster presentation


Alizé Pharma owns a portfolio of 37 pending and granted patents which protect the UAG analogs and their therapeutic applications at an international level.



  • Broglio F, C Gottero, F Prodam et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab. 89(6):3062-5, 2004
  • Togliatto G, Trombetta A, Dentelli P et al. Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes. Diabetes 59(4):1016-25, 2010
  • Benso A, St-Pierre DH, Prodam F et al. Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans. Eur J Endocrinol. 166(5):911-6, 2012
  • Özcan B, Neggers SJCMM, Miller AR et al. Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels? Eur J Endocrinol. 170(6):799-807, 2014.
  • Granata R, F Settani, F Catapano and al. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 148(2):512-29, 2007
  • Granata R, Settanni F, Nano R et al. Unacylated ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats, J Med Chem. 22;55(6):2585-96, 2012
  • Julien M et al. Pharmacokinetic parameters of unacylated ghrelin analogs, European Journal of Pharmaceutical Sciences, 25;47(4):625-635, 2012
  • Delhanty PJ, Sun Y, Visser JA et al. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS One 26;5(7):e11749, 2010
  • Delhanty PJ, Huisman,M, Baldeon-Rojas LY et al. Des-acyl ghrelin analogs prevent high fat diet induced dysregulation of glucose homeostasis. FASEB J 27(4):1690-700, 2013
  • Inhoff T, Monnikes H, Noetzel S and al. Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats. Peptides 29(12):2159-68, 2008
  • Granata R, Volante M, Settanni F et al. Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. J Mol Endocrinol 45(1):9-17, 2010
  • Togliatto G, Trombetta A, Dentelli P et al. Unacylated ghrelin promotes skeletal muscle regeneration following hindlimb ischemia via SOD-2-mediated miR-221/222 expression. J Am Heart Assoc. 5;2(6), 2013
  •  Kuppens RJ, Diène G, Bakker NE et al. Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader-Willi syndrome. Endocrine [May 20, Epub ahead of print], 2015
  •  Togliatto G, Trombetta A, Dentelli P et al.: Unacylated ghrelin (UnAG) induces oxidative stress resistance in a glucose intolerance mouse model and peripheral artery disease by restoring endothelial cell miR-126 expression. Diabetes. 64(4):1370-82, 2015
  • Lear PV, Iglesias MJ, Feijóo-Bandín S et al. Des-acyl ghrelin has specific binding sites and different metabolic effects from ghrelin in cardiomyocytes. Endocrinology 151(7):3286-98, 2010