MTAC platform expands company’s protein degradation capabilities to wider set of targets and complements ATAC degrader technology
WALTHAM, Mass., May 1, 2024 – Avilar Therapeutics, a biopharmaceutical company focused on extracellular protein degradation, today announced it will present preclinical proof-of-concept data for the company’s MTAC (M6PR Targeting Chimera) protein degrader platform at IMMUNOLOGY™ 2024, the American Association of Immunologists annual meeting taking place May 3-7 in Chicago, Illinois.
MTACs are novel bifunctional molecules containing a proprietary Avilar ligand to the mannose 6-phosphate receptor (M6PR) conjugated to a second ligand that binds to a protein of interest for degradation. MTACs represent an expansion of Avilar’s capabilities for extracellular protein degradation, building on the company’s ATAC (ASGPR Targeting Chimera) platform, which utilizes the asialoglycoprotein receptor (ASGPR) for degradation of proteins in the hepatocyte endolysosome. As a complementary approach, MTACs harness the M6P receptor and work by degrading pathogenic proteins in the endolysosome of M6PR-expressing cells, which include hepatocytes but also encompass multiple additional cell types.
Avilar scientists invented novel high affinity ligands to both ASGPR and M6PR, and these ligands form the chemistry backbone for ATACs and MTACs, respectively. In both cases, Avilar’s chemistry enables the design of highly efficient degraders with more streamlined monovalent designs, lower molecular weight, and improved physicochemical properties versus previous approaches. While Avilar leverages ATACs for degrading circulating proteins and hepatocyte membrane proteins, MTACs offer a new and complementary technology for degrading non-hepatocyte membrane proteins involved in the pathogenesis of human diseases.
“We are building multiple technologies for protein degradation and have successfully demonstrated in vivo proof-of-concept for ATACs as potent degraders of extracellular proteins,” said Effie Tozzo, PhD, Chief Scientific Officer of Avilar. “While our primary focus continues to be on ATACs as we advance a pipeline of first-in-class degrader medicines, MTACs represent an additional strategy with expanded target reach for extracellular protein degradation.”
Highlights from the MTAC data to be presented at the conference include:
- Development of novel M6PR ligands with enhanced affinity for M6PR through structure-based computational design methods
- Demonstration that monovalent MTACs containing these high affinity M6PR ligands achieve robust ternary complex formation and efficient uptake and degradation
- Benchmarking the performance of monovalent MTACs versus tridentate and monodentate bifunctional molecules containing ligands with weaker affinity for M6PR
Details of the poster presentation are as follows:
Title: In Vitro and In Vivo Proof-of-Concept Studies of Extracellular Protein Degradation Using Novel M6PR-Targeting Chimeras (MTACs)
Session Date and Time: Saturday, May 4, 2024, 3:15 p.m. – 4:30 p.m. CT
Poster #: 848
Presenter: Lisa Molz, PhD, Vice President, Research
The poster will be available on the publications page of the Avilar website following the presentation.
About Avilar Therapeutics
Avilar Therapeutics is a biopharmaceutical company pioneering the discovery and development of extracellular protein degraders, a new frontier in targeted protein degradation. Avilar develops ATACs (ASGPR Targeting Chimeras), a new class of protein degraders that shuttle disease-causing proteins from circulation to the endolysosome where the unwanted proteins are degraded. Avilar has built a proprietary discovery platform that includes novel, high-affinity, small molecule ASGPR ligands and advanced modeling of the biophysics, pharmacokinetics, and pharmacodynamics of ATAC mediated endocytosis and degradation. This platform enables the modular design and synthesis of ATACs extendable across the extracellular proteome to a wide range of proteins involved in the pathogenesis of human diseases. Avilar is leveraging its ATAC platform to create a broad and diverse pipeline of first-in-class extracellular protein degraders. Avilar is based in Waltham, MA. For more information, please visit www.avilar-tx.com and follow us on LinkedIn.
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