Precision Targeting

Navigo Proteins supports its biopharmaceutical and life sciences partners with proprietary affinity protein ligands for use as unique Precision Targeting molecules in therapeutics and diagnostics.
This includes the flexible genetic fusion of unique Precision Targeting moieties with certain carrier domains, readily creating “targeted carrier” proteins. These carriers carry precisely defined payloads, similar as Antibody Drug Conjugates, yet benefit from a much more straightforward, cheaper and quicker development process. Readily adjustable in-vivo half-lives of such Precision Targeting Affilin®-carriers allow easy adjustment to individual therapeutic and/or diagnostic needs.

RADIO CONJUGATES

The long-standing, successful use of radiopharmaceuticals in imaging of diseased tissues is based on targeted carrier-based diagnostics for oncology, i.e. in colorectal cancer, breast cancer, neuroendocrine tumor, small-cell lung cancer, prostate cancer, as well as in cardiovascular diseases. Over 10,000 hospitals worldwide use radioisotopes for in-vivo diagnosis or treatment, reaching around 35 million patients each year. The steady technological progress will continuously drive the demand for better radiopharmaceuticals. The ideal cancer imaging tool is a homogenous conjugate with a precisely defined payload-to-carrier ratio, to allow specific tumor-targeting with minimal side-effects and a fast clearance from the body. Antibody Radio Conjugates (ARCs) however, are complex to develop and to produce, and moreover suffer from a number of disadvantages, such as non-specific conjugation, heterogeneous isotope-to-antibody ratios, as well as long residence time in the circulation and non-tumorigenic tissues. Navigo’s Precision Radio Conjugates in contrast, solved all these disadvantages, as they are homogenous site-specific conjugates of a Precision Targeting ligand with an isotope-loaded chelator and thus a therapeutic product with defined isotope-to-carrier ratio. On top of that, any specific half-life can be readily adjusted, to balance optimal tumor residence time with minimal circulation residence, for maximized imaging contrast with minimal side effects. Thus, Precision Radio Conjugates promise significantly improved diagnostic and therapeutic performance.

TECHNOLOGY

Our long-standing expertise in protein engineering is at the heart of our Precision Targeting protein ligands platform. We have implemented and continuously optimized over many years a powerful scaffold technology platform, which yields high-quality binder proteins against literally any target structure, for multiple purposes. Among them a major focus for us is the development of Precision Radio Conjugates for biologics.
Starting point is a scaffold protein with favorable characteristics such as:

• small size (<10kDa)
• very high thermal, proteolytic and caustic stability
• no post-translational modifications
• no cysteines
• cost effective production in E.coli

Libraries
High quality and diverse libraries are generated from the starting scaffold by randomization of a number of surface-exposed residues at the genetic level. Each randomized position now comprises all amino acids (except Cysteine) which leads to large combinatorial libraries with complexities of 1010 to 1012, depending on the specific display format used.

Selection and Screening
For the subsequent selection process, both phage display and ribosome display are available. The following automated, robotics-assisted high-throughput screening (HTS) key technology identifies Precision Targeting ligand-enriched selection pools. Further rigorous screening rounds finally yield those Precision Targeting ligands or Precision Radio Conjugates with the desired properties and suitable for large-scale industrial use.
As foundation for all this, Navigo Proteins has tailored an HTS platform optimized for flexible assay design and selection based on multiple parameters. Rapid screening of well beyond 10.000 Affilin® binders per day identifies a set of diverse Precision Targeting candidates from which we select the most promising leads for further development.

State-of-the-art screening: Robotic characterization of well bevond 10.000 protein variants per day

HPLC protein characterization
Format development
The development of innovative biotherapeutic or diagnostic protein molecules is often based on their chemical or genetic modification to modulate or extend their functionality. Examples are multi-specific binding molecules, e.g. fusions of Precision Targeting binders with antibodies or Fab fragments. Innovative fusion proteins for instance are created by connecting Precision Targeting molecules with certain carrier domains, to introduce a precise number of functional/coupling/binding sites at defined positions to the carrier. The adjustable size of the carrier then determines a custom-tailored in vivo half-life. The functional spectrum is further broadened by introduced specific chemical modifications, such as coupling of chelators for radio nucleotides. Our scientists at Navigo Proteins apply their expert know-how to design the optimal molecule format for every specific task.
Functional characterization
An in-depth functional characterization of the lead ligands along the development process is crucial to identify the optimal Precision Targeting Ligands. The characterization comprises a range of biochemical, biophysical as well as functional protein assays in house, such as cell-based assays, flow cytometry or immune histochemistry, to meticulously select the optimal Precision Targeting Affilin® molecules.
Navigo affinity ligands bind specifically on tissue embedded targets

Cell culture: Navigo Precision Targeting affinity ligands bind specifically to their target on a tumor cell line

Navigo ligands are stable in serum

BIOINFORMATICS

In-house development of customized software supports all processes from early cloning of libraries through screening and data storage and analysis of thousands of variants. Individual programs address specific needs of molecular biology, sequence analysis or tracking of variants through high-throughput screening as well as monitoring project work packages and flow.

INTELLECTUAL PROPERTY

Navigo Proteins pursues a stringent policy of patenting its proprietary products and technology. Over 100 patents are granted and dozens of applications have been filed. This is the basis to secure our assets in all major markets and provides customers with a solid protection and exclusivity of the licensed products and technology.

PARTNERING

Precision medicine ties together early diagnosis, precisely designed therapeutics as well as treatment-monitoring tools. The best way to guarantee a successful and seamless treatment flow from disease identification to the decision on the best suitable therapy is the availability and leverage of one single universal molecular format during all stages. This is precisely what Navigo’s Precision Targeting platform delivers: the comprehensive Theranostic solution for translating the idea of precision medicine into effective molecules: Selecting one suitable Precision Targeting molecule and arming that with different carriers for the entire cycle from early diagnosis, over effective treatment, up to close and rapid monitoring of therapy success and disease reversal.Navigo Proteins offers flexible deal structures which can include co-development and risk-sharing approaches or plain licensing deals, as well as fee-for-service arrangements. Revenues will be driven by FTE-funding, milestones and royalties. A clear focus for Navigo Proteins’ partnering efforts is the formation of strategic alliances and programs with experts and stakeholders in the precision medicine field.