WE ARE REFLEXION
AN ENTIRELY NEW CLASS OF THERAPEUTICS: SYNTHETIC D-PROTEINS
Reflexion Pharmaceuticals has developed a novel platform utilizing the tools of synthetic biology to discover, develop and deliver an exciting new class of drug products: proteins composed entirely of D-amino acids. Synthetic D-proteins retain the benefits of antibodies while overcoming many of their limitations including reduced visibility, reduced size, improved stability and unique functionality. We believe our platform has enormous potential as synthetic D-proteins can be made to over 80% of the proteins currently targeted by antibody drugs, as well as additional targets.
Reflexion has developed a platform utilizing the tools of synthetic chemical biology to discover, develop and deliver an entirely new class of therapeutics: novel synthetic D-proteins. These synthetic D-proteins are expected to exhibit many of the benefits of monoclonal antibodies while overcoming many of their limitations, including reduced “biological visibility”, reduced size, improved stability and unique functionality.
The chemical synthesis of proteins was pioneered by our co-founder Dr. Stephen Kent. In a landmark paper, Dr. Kent showed that a chemically made protease comprised entirely of D-amino acids recognized and broke down its D-amino acid target peptide. Importantly, D-proteins are not broken down by naturally evolved proteases and are therefore “biologically invisible”, suggesting that a D-amino acid world (a parallel molecular universe) can be created to be less visible to human proteases and the human immune system.
Reflexion believes it has opened a window between these mirror image worlds and can now discover synthetic D-proteins that can interact with drug targets in the L-world to create an entirely new class of therapeutics.
OUR SYNTHETIC BIOLOGY PLATFORM
ENGINEERING THE D-PROTEIN SPACE
Our novel platform integrates advanced chemical protein synthesis methods with in vitro and in silico protein engineering technologies to explore vast libraries of potential D-proteins. Using state of the art structure-guided chemistry and function-guided screening technologies, we are able to quickly design, optimize and fine-tune the features we want into D-proteins.
Synthetic D-proteins are resistant to proteases, extending their half-lives, preventing activation of an anti-drug immune response (ADAs), and enabling subcutaneous dosing
REDUCED MOLECULAR SIZE
Synthetic D-proteins are 10 to 20-times smaller than antibodies yet have potencies equivalent to antibody drugs and are able to effectively block receptors, resulting in increased molar doses and better drug exposures
Synthetic D-proteins can be designed to have improved thermal stability, reducing need for cold chain and increasing their stability
Based upon these attributes, synthetic D-proteins open up new opportunities for bi-, tri- and quad-specifics, half-life control, tumor penetration, blood-brain-barrier (BBB) penetration, and potential intracellular uptake
OUR THERAPEUTIC PIPELINE
Our PD-1 program explores several potential advantages in the competitive I-O market. In in vitro studies, our synthetic D-protein inhibits PD-1 binding to PD-L1 comparable to Opdivo. However, in contrast to Opdivo, our synthetic D-protein did not induce an anti-drug antibody response in a stringent animal model of immunogenicity. We are now poised to explore a variety of bi- and tri-specific opportunities
Our most advanced program is an improved inhibitor of VEGF-A for ophthalmology indications. In in vitro studies, our synthetic D-protein inhibited VEGF-A binding to the VEGF receptor comparable to Eylea and was over 10-fold more potent than Avastin. In contrast to Avastin, our synthetic D-protein did not induce an anti-drug antibody response in an animal model of immunogenicity. In an animal model of wet AMD, our synthetic D-protein was able to suppress VEGF-A-induced vascularization and vascular leakiness in the retina of rabbits with a durability similar to Eylea.
We are proceeding with vendor selection and commencement of IND enabling CMC and non-clinical studies and will be holding a pre-IND meeting with the FDA prior to initiating clinical development in early 2022.
MACULAR DEGENERATION, ONCOLOGY