Proof of Concept Study of AX-158 in Patients With Mild to Moderate Plaque Psoriasis

Summary

Proof of concept study to assess the safety and tolerability of AX-158 in patients with mild to moderate psoriasis. Patients will be evaluated for a 28-day treatment period with either AX-158 or Placebo and then followed for an additional 30 days for safety.

Timeline

Start

2023-11-30

Primary completion

2024-09-04

Completion

2024-10-04

Publications

• Background Borroto A, Reyes-Garau D, Jimenez MA, Carrasco E, Moreno B, Martinez-Pasamar S, Cortes JR, Perona A, Abia D, Blanco S, Fuentes M, Arellano I, Lobo J, Heidarieh H, Rueda J, Esteve P, Cibrian D, Martinez-Riano A, Mendoza P, Prieto C, Calleja E, Oeste CL, Orfao A, Fresno M, Sanchez-Madrid F, Alcami A, Bovolenta P, Martin P, Villoslada P, Morreale A, Messeguer A, Alarcon B. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases. Sci Transl Med. 2016 Dec 21;8(370):370ra184. doi: 10.1126/scitranslmed.aaf2140.
• Background Roy E, Togbe D, Holdorf AD, Trubetskoy D, Nabti S, Kublbeck G, Klevenz A, Kopp-Schneider A, Leithauser F, Moller P, Bladt F, Hammerling G, Arnold B, Pawson T, Tafuri A. Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15529-34. doi: 10.1073/pnas.1009743107. Epub 2010 Aug 13.
• Background Roy E, Togbe D, Holdorf A, Trubetskoy D, Nabti S, Kublbeck G, Schmitt S, Kopp-Schneider A, Leithauser F, Moller P, Bladt F, Hammerling GJ, Arnold B, Pawson T, Tafuri A. Fine tuning of the threshold of T cell selection by the Nck adapters. J Immunol. 2010 Dec 15;185(12):7518-26. doi: 10.4049/jimmunol.1000008. Epub 2010 Nov 15.
• Background Gil D, Schamel WW, Montoya M, Sanchez-Madrid F, Alarcon B. Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell. 2002 Jun 28;109(7):901-12. doi: 10.1016/s0092-8674(02)00799-7.
• Background Juraske C, Wipa P, Morath A, Hidalgo JV, Hartl FA, Raute K, Oberg HH, Wesch D, Fisch P, Minguet S, Pongcharoen S, Schamel WW. Anti-CD3 Fab Fragments Enhance Tumor Killing by Human gammadelta T Cells Independent of Nck Recruitment to the gammadelta T Cell Antigen Receptor. Front Immunol. 2018 Jul 9;9:1579. doi: 10.3389/fimmu.2018.01579. eCollection 2018.
• Background Borroto A, Arellano I, Blanco R, Fuentes M, Orfao A, Dopfer EP, Prouza M, Suchanek M, Schamel WW, Alarcon B. Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo. J Immunol. 2014 Mar 1;192(5):2042-53. doi: 10.4049/jimmunol.1203414. Epub 2014 Jan 27.
• Background Borroto A, Arellano I, Dopfer EP, Prouza M, Suchanek M, Fuentes M, Orfao A, Schamel WW, Alarcon B. Nck recruitment to the TCR required for ZAP70 activation during thymic development. J Immunol. 2013 Feb 1;190(3):1103-12. doi: 10.4049/jimmunol.1202055. Epub 2012 Dec 24.
• Background Lettau M, Pieper J, Gerneth A, Lengl-Janssen B, Voss M, Linkermann A, Schmidt H, Gelhaus C, Leippe M, Kabelitz D, Janssen O. The adapter protein Nck: role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes. Protein Sci. 2010 Apr;19(4):658-69. doi: 10.1002/pro.334.
• Background Yiemwattana I, Ngoenkam J, Paensuwan P, Kriangkrai R, Chuenjitkuntaworn B, Pongcharoen S. Essential role of the adaptor protein Nck1 in Jurkat T cell activation and function. Clin Exp Immunol. 2012 Jan;167(1):99-107. doi: 10.1111/j.1365-2249.2011.04494.x.

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Indications