Allo-Glue™ Platform

Breakthroughs in Molecular Glue Discovery and Design

Our proprietary chemical biology platform enables unprecedented, high throughput and high complexity drug ligand screening and genome-scale mapping of drug-protein interactions directly in living cells. This is further complemented by a suite of computational tools, numerical and machine learning models, and rational drug design for molecular glues.

Monovalent glues have unique potential to address historically elusive disease targets. We apply these capabilities to a broad spectrum of small molecule discovery and optimization paradigms, with a major focus on monovalent glues that act through allosteric mechanisms (Allo-Glues™) to reach, modulate, inhibit or degrade novel and traditionally hard-to-drug disease targets. We are pursuing a diversity of molecular glues in our pipelines and strategic partnerships, including with Novartis and Genentech.

For monovalent glues, and as disease protein degraders, our platform enables three major approaches at unique scale:

  • Ligase centric approach: determining the ability of a ligase ligand (candidate glue) to promote interactions with any one of ~20,000 proteins encoded by the human genome
  • Reverse target centric approach: determining the ability of a target ligand to differentially promote interaction of its target with any one of 400+ qualified ligases to promote its self-degradation
  • Target centric approach: discovery of glues, through chemical diversity library screens, that promote interaction of a target of interest with any one of a set of qualified ligases

Distal mechanism of action

Allo-Glue small molecule can bind to a specific protein and promote target recruitment distal to its binding site in an allosteric manner

Artboard 1Protein + Allo-GlueTargetProtein + Allo-Glue+BINDINGPROTEIN COMPLEXAllo-Glue+Protein

Proximal mechanism of action

Allo-Glue molecule complex may also bind to a specific protein and promote target recruitment proximal to its binding site (and directly participate in interaction)

Artboard 1 copyProtein + Allo-GlueBINDINGPROTEIN COMPLEXAllo-GlueProtein+TargetProtein + Allo-Glue+

Possible outcomes on targets

Allo-Glue molecule-induced interaction can lead to several possible biological effects on target proteins

Artboard 1 copy 2TargetdegradationTargetinhibitionTargetfunctionchange

Reprogramming protein functions

Allo-Glues can reach and impact disease targets in numerous ways

Monovalent glues can trigger protein-protein interactions by distal and proximal mechanisms of action. Reprogramming protein functions in this manner can lead to diverse functional outcomes, including target modulation, inhibition, or degradation by invoking cellular machineries specialized in natural disposition of proteins in cells to maintain homeostasis

Screening platform

The Orionis platform enables quantitative ligase-centric discovery of glue targets across ~20,000 human proteins, and target-centric discovery using complex chemical libraries

Artboard 1 copy 301234LogIntensityThousands of Allo-Glues~20.000 targets

Molecular interaction fingerprints

Genome-scale and select target panel fingerprints provide unique perspectives in glue discovery and form the basis for numerical modeling and chemistry optimization

Artboard 1 copy 4Thousands of Allo-Glues~20.000 targetsOrionis NumericalMethod for Rational Glue Design