Aro Biotherapeutics

CIC Philadelphia

3675 Market Street, Suite 200

Philadelphia, PA 19104

Email: info@arobiotx.com 

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Centyrin Platform

Centyrins: Engineered to Develop Medicines with New Mechanisms of Action

With their unique biophysical properties and exquisite specificity in cell targeting, Centyrins are next generation protein therapeutics that have potential to achieve new therapeutic mechanisms of action. Leveraging its early scientific leadership position, Aro Biotherapeutics is at the forefront in fulfilling the true promise of Centyrins: to deliver bold new medicines that treat diseases in ways never before possible.

Centyrins Go Beyond Antibody Therapeutics

Targeting Unmet Needs of Patients

Centyrins have the potential to improve the treatment of human diseases by overcoming the limitations of antibody therapeutics, which typically target a single antigen, or are engineered to bind to two antigens in a fixed conformation within the antibody structure. We have derived large libraries of Centyrins built on a consensus human Tenascin FN3 framework, with randomized amino acids within the loops and strands (β-sheets). The rapid screening via CIS display of multiple large libraries with different antigen binding surfaces has enabled discovery of high affinity Centyrins that bind to a diversity of unique epitopes on target proteins, and that do not require affinity maturation. Centyrins can be readily expressed in mono-, bi-, tri- or multi-specific formats with flexible architecture, enabling recognition and modulation of multiple target antigens on tumors or immune cells to achieve the desired therapeutic effect. 

 

Centyrins are ideal for the targeted delivery of complex drug payloads, including oligonucleotide therapeutics and nanoparticles. We have mapped the Centyrin amino acid residues that are tolerant to cysteine mutations, enabling site-specific covalent conjugation to drug payloads, without impacting biohpysical properties or biological activity. Centyrin - targeted drug payloads will enable tissue - specific delivery of medicines directed to intracellular targets that have been previously undruggable. 

 

Centyrins have been shown to effectively penetrate and distribute in solid tissues because of their relatively small size. As small proteins (10 KDa per Centyrin domain), Centyrins have an inherently short in vivo half-life, and are cleared by the kidney. We have developed Centyrins specific for human serum proteins that enable us to extend exposure and tune the pharmacokinetics to the desired in vivo profile.

Crystal structure of EGFR binding Centyrin 83v2; β strands labelled A through G; N and C termini labelled as blue and red spheres, respectively.

Optimal cysteine locations. The 26 positions determined to be potential conjugation sites are shown in blue. The Cα-Cβ bond of each residue is shown as a stick. N- and C-termini are shown as blue and red spheres, respectively.

Optimizing Drug Development

Centyrins are inherently small, simple, stable, soluble and highly target antigen specific proteins which are optimized for efficient drug development. This unique combination of properties enable creation of new therapeutic mechanisms which have not been achieved with other targeting platforms.

SIZE 1/15th the size of antibodies allows for high concentrations in solid tissues, while preserving high affinity and specific binding.

 

SIMPLICITY Site-specific conjugation of diverse, complex drug payloads, such as nucleic acids or lipid nanoparticles carrying payloads.

 

STABILITY Stable to heat and extremes of pH, including the low pH environment of the early endosome, where certain drug payloads must escape the endosome into the cytosol and avoid degradation pathways.

 

SOLUBILITY Highly soluble which enables high concentration formulations, good bioavailability and high expression in bacterial and mammalian production systems.

Centyrins Go Beyond Antibody Therapeutics