Preclinical data shows use of megalin receptors for intracellular delivery of a ligand-siRNA conjugate to silence production of target mRNA in the kidney
Megalin-binding genetic medicines are specifically directed to proximal tubular epithelial cells (PTECs) in the kidney to target genes that regulate systemic diseases
Data supports development of megalin-STRIKERs as the first drug programs to emerge from the company’s STRIKE platform for ligand-siRNA therapeutics to the kidney
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Judo Bio, a biotechnology company pioneering oligonucleotide medicines delivered to the kidney, today announced the presentation of preclinical data that demonstrate the use of megalin receptors for intracellular delivery of ligand-siRNA therapeutics to the kidney to reduce expression of the target genes. The data will be presented at the 20th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) taking place on October 6-9 in Montreal.
STRIKE (Selectively Targeting RNA Into KidnEy) is Judo Bio’s platform to develop and discover ligand‑siRNA conjugates that harness the natural endogenous process of receptor-mediated endocytosis for uptake of oligonucleotide therapeutics to specific kidney cell populations. The data presented at OTS are from studies with ligand-siRNA conjugates that bind to megalin, a cell-surface recycling receptor that is expressed at high levels on the apical side of proximal tubule epithelial cells (PTECs), resulting in internalization and degradation of the target mRNA.
“Achieving gene silencing in the kidney has been eagerly pursued due to the central role that this organ plays in regulating normal physiology. However, selective and efficient delivery of oligonucleotide therapeutics to the kidney has been a stubborn challenge, primarily because oligonucleotides reach the kidney as a matter of course but are typically excreted without therapeutic benefit,” said Alfica Sehgal, PhD, Chief Scientific Officer of Judo Bio. “We believe that Judo Bio has demonstrated for the first time the ability to leverage an endogenous function – in this case via megalin – for receptor-mediated transport into the cytoplasm, enabling our ligand-siRNA conjugates to achieve therapeutic gene silencing in the kidney.”
The preclinical data presented at OTS showed delivery of megalin ligand-conjugated siRNA, or megalin-STRIKERs, selectively to PTECs in the mouse kidney, and the resulting silencing of the target genes. Key findings include:
- Megalin ligand-conjugated siRNA resulted in 5-30 fold increased exposure selectively in the mouse kidney compared to unconjugated naked siRNA.
- Single administration of the ligand-siRNA conjugate leads to 50-70% knockdown of target genes.
- Target gene knockdown with the ligand-siRNA conjugate was durable up to 4 weeks.
Judo Bio’s OTS poster presentation is available here on the company’s website.
“The clear and compelling data we presented for a new therapeutic approach of megalin-mediated delivery of siRNAs to the kidney opens up a host of opportunities for Judo Bio to build a pipeline of megalin-STRIKERs, initially targeting solute carrier proteins for systemic diseases,” said Dr. Sehgal. “We are excited to build on the success of our scientific progress as we bring genetic medicines to the kidney.”
About Judo Bio
Judo Bio is pioneering oligonucleotide medicines delivered to the kidney, opening the way for new genetic medicines for systemic and renal diseases. With its STRIKE (Selectively Targeting RNA Into KidnEy) platform, the company is using a proprietary approach to create ligand-RNA conjugate drugs designed for receptor-mediated update by specific kidney cell types, resulting in gene silencing of disease-modifying target genes. Judo Bio’s initial pipeline programs are megalin-STRIKERs that use the megalin receptor family to selectively deliver siRNA therapeutics to the proximal tubule of the kidney to silence mRNA expression of specific solute carrier proteins (SLCs), thereby inhibiting the uptake of circulating solutes linked to systemic diseases. Located in Cambridge, MA, Judo Bio’s team and advisors include experts in oligonucleotide therapies and innovative drug development. For more information, visit www.judo.bio and follow us on LinkedIn.
Contacts
Media:
Kathryn Morris
The Yates Network LLC
914-204-6412
kathryn@theyatesnetwork.com
