Utrecht, The Netherlands, September 27, 2021 – Sapreme, a biotechnology company focused on improving the delivery and efficacy of macromolecule therapeutics, will be presenting new preclinical in vivo data on improving oligo delivery to the liver in an online poster presentation at the 17th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS), held virtually from September 26th to 29th, 2021. These data highlight the capability of its proprietary endosomal escape platform to significantly improve intracellular target engagement both in vitro as well as in vivo.
“Returning to OTS this year with promising in vivo data in the liver demonstrates the significant progress Sapreme has achieved in developing and validating its innovative platform,” stated Guy Hermans, Ph.D., Chief Executive Officer of Sapreme. “These proof-of-concept data enable us to confidently accelerate investment in our therapeutics pipeline and improve existing, or to unlock new, macromolecule therapeutics.”
The large majority of therapeutic oligonucleotide formats struggle to achieve sufficient levels of cytoplasmic or nuclear target engagement while maintaining low toxicity due to compounds becoming trapped, and thereby rendered ineffective, by the endosome. Sapreme’s endosomal enhancers strive to overcome this industry hurdle by enabling improvements in potency through efficient endosomal escape and by providing superior tissue- or cell-selective targeting. This is accomplished through use of targeting ligands, including GalNAc for hepatic targeting and antibodies or other ligands for non-hepatic tissues.
Sapreme’s 2020 in vitro data showcased SPT001’s ability to improve intracellular release of targeted antisense oligonucleotides (ASOs) and enhance the delivery of other targeted payloads such as antibody-conjugated toxins. Conjugating SPT001 to liver or tumor targeted ASOs led to significantly improved silencing with positive implications for targeted drug development. Building on last year’s data, the new in vivo data revealed high gene expression knockdown levels in the liver at reduced oligonucleotide doses when applying SPT001 conjugation technology. This was confirmed by reduced target protein levels in circulation, as well as by downstream efficacy biomarkers. Persistence of these pharmacodynamic effects throughout the study further indicated that improved cytoplasmic delivery does not necessarily imply more frequent dosing schedules. These data, added to the technology’s demonstrated low toxicity profile, present an attractive and broad development opportunity to improve the macromolecule therapeutic landscape.