Our Science

Adnectin Product Class

Adnectins™ are our novel, proprietary class of targeted biologics that we derive from a well-characterized protein, fibronectin, that is prevalent throughout the human body.

We believe that our Adnectins offer superior therapeutic and commercial promise across multiple therapeutic applications currently dominated by first-generation targeted biologic approaches.

We believe that our phase 1 clinical trial results to date for Angiocept™ in regards to safety, tolerability and immunogenicity have helped to establish the initial clinical foundation for our Adnectin class.

What is an Adnectin? We derive Adnectins from a well-characterized protein, fibronectin, that is prevalent throughout the human body. Like antibodies, fibronectin resides outside of cells where it is exposed to and tolerated by the human immune system. Fibronectin binds to other proteins using protein structures called "targeting domains."

An Adnectin consists of a backbone of the natural amino acid sequence of a certain domain of human fibronectin and one to three targeting loops which our scientists redirect to enable an Adnectin to specifically recognize a therapeutic target of interest.

Our Adnectin class is a distinct and separate targeted biologics class from antibodies. Although Adnectins and antibodies have targeting domains with three-dimensional shapes that resemble each other, the amino acid sequences of each protein class are distinctly different.

Advantages of Adnectins. Adnectins have a simple amino acid sequence. The amino acid sequence of a targeted protein biologic determines its properties, including efficacy, safety, formulation and ease of manufacturing. We believe we have the potential to generate a pipeline of products across multiple therapeutic areas with the following advantages:

  • Potent, specific therapeutics: high affinity, specific binding to a therapeutic target with only a single Adnectin domain
  • Enhanced efficacy: greater potential to specifically modulate multiple therapeutic targets for multiple therapeutic effects in a single drug molecule
  • Opportunity to pursue patent-protected, first generation targeted biologics markets: potential avoidance of antibody patents enables pursuit of antibody-validated products and pathways prior to patent expiration
  • Broad therapeutic applications: creating Adnectins to many target types, including targets that are hard to drug by antibodies or small molecules
  • Potential for more convenient dosing: using Adnectins designed with different systemic half-lives in humans (for example, as long as a month or as short as hours) or with properties for administration of long-lasting, concentrated doses
  • Faster and lower risk manufacturing: manufacturing in E. coli, permitted by the relatively simple Adnectin amino acid sequence compared to an antibody, may result in higher probability of success and greater speed to the clinic and market
  • Potential for improved tissue penetration: an Adnectin domain is about 15 times smaller than a full length antibody
  • Reduced immunogenicity potential: the Adnectin backbone is designed from a naturally occurring human fibronectin protein that has evolved to be tolerated by the human immune system

Comparison of the Shape of the Targeting Domain of Adnectins and Antibodies. The targeting domain of human antibodies and of Adnectins evolved with a similar shape, when considered three dimensionally, to specifically bind to other proteins. This shared shape of the Adnectin targeting domain provides a unique scientific, clinical and commercial precedent for Adnectins that differentiates this class from other new targeted biologics classes of which we are aware.

Using Adnectins' particular targeting domain, we create product candidates for antibody-validated targets, as well as challenging targets that have been difficult to "drug" with other approaches.

How do we design the right Adnectin product candidate for a disease or medical condition? We generate Adnectins from human fibronectins by applying our proprietary protein engineering system, PROfusion™. It capitalizes on the inherent advantages of the Adnectin class through the rapid and efficient engineering, evaluation and optimization of Adnectin product candidates. Our scientists use our proprietary PROfusion system to simultaneously engineer trillions of Adnectin protein variations at a time in order to find the optimal product candidate.

How do we produce Adnectins? Our internal process development group creates E. coli cell lines and production processes. We have the internal capability to produce Adnectins in multi-gram quantities for use in our preclinical studies, and we currently contract with third parties for the materials used in our toxicology studies and clinical trials.