Avilar Therapeutics to Present MTAC Preclinical Data at AAI Annual Meeting

Avilar Therapeutics, a biopharmaceutical company based in Waltham, Massachusetts, is making strides in the field of extracellular protein degradation. The company has announced that it will present preclinical proof-of-concept data for its MTAC (M6PR Targeting Chimera) protein degrader platform at the IMMUNOLOGY™ 2024 conference, hosted by the American Association of Immunologists in Chicago, Illinois, from May 3-7.

MTACs are innovative bifunctional molecules that include a proprietary Avilar ligand for the mannose 6-phosphate receptor (M6PR) and a second ligand that targets a protein for degradation. This development represents a significant expansion of Avilar’s capabilities in extracellular protein degradation, complementing their existing ATAC (ASGPR Targeting Chimera) platform. While the ATAC platform uses the asialoglycoprotein receptor (ASGPR) for protein degradation in hepatocyte endolysosomes, MTACs utilize the M6P receptor to degrade pathogenic proteins in the endolysosome of M6PR-expressing cells. These cells include not only hepatocytes but also a broader range of cell types.

Avilar's scientific team has created new high-affinity ligands for both ASGPR and M6PR. These ligands form the foundational chemistry for ATACs and MTACs, respectively. The design of these ligands enables the creation of highly efficient degraders with streamlined monovalent designs, lower molecular weight, and better physicochemical properties compared to previous methods. While ATACs are used to degrade circulating proteins and hepatocyte membrane proteins, MTACs provide a complementary technology for targeting non-hepatocyte membrane proteins involved in various human diseases.

Effie Tozzo, PhD, Chief Scientific Officer at Avilar, highlighted the company’s success in demonstrating in vivo proof-of-concept for ATACs as effective degraders of extracellular proteins. She emphasized that while their primary focus remains on advancing ATACs, MTACs offer an additional strategy with an expanded target range for extracellular protein degradation.

The MTAC data to be presented at the conference will cover several key points:
- The development of novel M6PR ligands with enhanced affinity for M6PR through structure-based computational design methods.
- Evidence that monovalent MTACs with high-affinity M6PR ligands achieve robust ternary complex formation, efficient uptake, and degradation.
- Comparative performance analysis of monovalent MTACs against tridentate and monodentate bifunctional molecules with weaker M6PR affinity.

The poster presentation, titled "In Vitro and In Vivo Proof-of-Concept Studies of Extracellular Protein Degradation Using Novel M6PR-Targeting Chimeras (MTACs)," will be presented by Lisa Molz, PhD, Vice President of Research, on Saturday, May 4, 2024, from 3:15 p.m. to 4:30 p.m. CT. The poster will also be available on the Avilar website after the presentation.

Avilar Therapeutics is dedicated to pioneering the discovery and development of extracellular protein degraders. The company’s ATACs are a new class of protein degraders that transport disease-causing proteins from circulation to the endolysosome for degradation. Avilar has developed a proprietary discovery platform featuring novel, high-affinity, small molecule ASGPR ligands and advanced modeling of the biophysics, pharmacokinetics, and pharmacodynamics of ATAC-mediated endocytosis and degradation. This platform supports the modular design and synthesis of ATACs, extendable across the extracellular proteome to target a wide range of disease-related proteins. Avilar is leveraging this platform to develop a diverse pipeline of first-in-class extracellular protein degraders.