Directed Evolution

Serial Rounds of Mutagenesis Fuel Our R&D Discovery Engine

We leverage state-of-the-art high throughput molecular cloning to iterate on membrane binding peptides in the context of peptide-antibody chimeras. Each round simultaneously optimizes multiple desirable features: stability/aggregation, membrane binding, internalization, lysosomal targeting, pharmacokinetics, and tumor shrinking activity. BioLoomics has developed industry leading throughput for iteration and testing of peptide-antibody designs

Multiple Selection Pressures For Super-ADC Evolution

The Challenge

There are 5,000+ known membrane binding peptides derived from organisms, but fusion of most in the context of peptide-antibody chimeras yield non-specific binding and unfavorable pharmacokinetics. We estimate the evolutionary and synthetic design space that we are exploring to be greater than 10^14 variants. We search this design space for ultra-rare developable variants that impact payload delivery.

Measuring Cell Binding

We screen mutagenized libraries of evolutionary derived membrane binding peptides using live human cell lines in the presence and absence of the antibody target to ensure target specificity.

Measuring Internalization and Lysosomal Trafficking

ADCs only release their payload if trafficked to the lysosome. We leverage lysosome accumulation assays to ensure Super-ADCs not only go the the right cell, but also the right organelle.

Measuring Manufacturability

We assess designs for their ability to be manufactured in mammalian cells, as well as their aggregation potential, hydrophobicity, and thermal stability.

Building A Unique Dataset

The predictive models created by AI rely on high quality data for high accuracy predictions. We are trailblazing the application of AI at the interface of protein design and membrane binding by building a highly specialized multi modal dataset around Super-ADC designs.

Partner With Us

Our approach has the potential to improve the therapeutic index of existing assets, to unlock novel targets with low internalization, and to enable lower potency payloads to be effective in the ADC field. We aim to leverage Super-ADCs in co-development partnerships to broadly propel ADCs toward first line therapy by dramatically impacting their safety profile.