Judo Bio Presents Data Demonstrating Mechanism of Receptor-mediated Delivery of Oligonucleotides Resulting in Gene Silencing in the Kidney

Preclinical data show intracellular uptake of a ligand-siRNA conjugate in vitro using megalin, an endogenous, endocytic recycling receptor on proximal tubular cells of the kidney

Megalin-mediated delivery of siRNA leads to significant, durable knock-down in vivo

 

CAMBRIDGE, Mass., October 26, 2024 – Judo Bio, a biotechnology company pioneering oligonucleotide medicines delivered to the kidney, today announced the presentation of preclinical data that demonstrate a mechanism of uptake and trafficking of ligand-siRNA conjugates using megalin receptors to achieve targeted gene knockdown in proximal tubule epithelial cells (PTEC) of the kidney. The data is being presented at Kidney Week 2024, the annual meeting of the American Society of Nephrology, taking place in San Diego, CA on October 24-27.

These data represent the capabilities of the Company’s STRIKE (Selectively Targeting RNA Into KidnEy) platform to discover ligand‑siRNA conjugates that harness the natural, endogenous process of receptor-mediated endocytosis to deliver oligonucleotide therapeutics to specific kidney cell populations. Megalin-STRIKERs are ligand-siRNA conjugates that bind to megalin on PTECs, resulting in drug uptake to the kidney and gene silencing of the target mRNA. In its initial drug programs, Judo Bio is designing megalin-STRIKERs to silence mRNA expression of specific solute carrier (SLC) proteins, thereby inhibiting the uptake of circulating metabolites linked to systemic diseases.

“Our understanding of endocytic trafficking in kidney proximal tubule cells has advanced rapidly in recent years,” said Ora A. Weisz, PhD, an author of the poster presentation and Professor of Medicine, Cell Biology, and Clinical and Translational Science in the Division of Renal-Electrolyte at the University of Pittsburgh. “This approach to harness the endocytic pathway to selectively target delivery of RNA to specific kidney cells provides an opportunity to target and silence solute carrier proteins in order to address numerous systemic diseases.”

The preclinical data presented at Kidney Week studied megalin ligand-conjugated siRNA, or megalin-STRIKERs, in a differentiated, opossum kidney PTEC cell line that recapitulates proximal tubule morphology and is functionally similar to kidneys in animals. Key findings include:

  • Ligand-siRNAs were taken up by opossum kidney cells in both a time and concentration dependent manner, predominantly from the apical surface.
  • Uptake of ligand-siRNA conjugates was megalin dependent and achieved with different megalin ligands.
  • Megalin ligand-siRNA conjugates led to significant gene knock-down across multiple targets and was durable for up to 40 days in mice.

Judo Bio’s Kidney Week poster presentation is available here on the company’s website.

“We are pleased to share data describing the use of megalin’s endogenous receptor-mediated endocytosis to enable gene silencing in PTECs,” said Alfica Sehgal, PhD, Chief Scientific Officer of Judo Bio. “Understanding the mechanism that leads to gene silencing directs the optimization efforts on our first megalin-STRIKERs that target SLC proteins. Modulating function of specific SLCs is an established approach for the treatment of various systemic diseases, and an RNAi approach opens vast therapeutic opportunities because of its specificity.”

 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.

Media contact:
Kathryn Morris
The Yates Network LLC
914-204-6412
kathryn@theyatesnetwork.com

Judo Bio to Present Data at the ASN Kidney Week 2024 Demonstrating Receptor mediated Delivery of Oligonucleotides to the Kidney

CAMBRIDGE, Mass., October 11, 2024 – Judo Bio, a biotechnology company pioneering oligonucleotide medicines delivered to the kidney, today announced that the company will present mechanistic and preclinical data that demonstrate the use of megalin receptors for intracellular delivery of ligand conjugated-siRNA therapeutics to silence production of target mRNA in the kidney. These conjugated siRNA are developed by Judo Bio’s proprietary STRIKE (Selectively Targeting RNA Into KidnEy) platform, and are internalized by the recycling receptor megalin. The data will be presented at the American Society of Nephrology (ASN) Kidney Week taking place October 23-27 in San Diego.

Details of the poster presentation are as follows:

Title: Targeted Delivery of siRNA to Proximal Tubule Cells in Kidney
Session Name: Genetic Kidney Diseases: Models, Mechanisms, and Therapies [PO1202-3]
Session Date and Time:  October 26, 2024 from 10:00 a.m. to 12:00 p.m. PT
Location: San Diego Convention Center, Exhibit Hall
Poster Number: SA-PO637

 

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.

Media contact:
Kathryn Morris
The Yates Network LLC
914-204-6412
kathryn@theyatesnetwork.com

Judo Bio Unveils Data Demonstrating Receptor-mediated Delivery of Oligonucleotides to the Kidney

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., October 7, 2024 – 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.

Media contact:
Kathryn Morris
The Yates Network LLC
914-204-6412
kathryn@theyatesnetwork.com

 

Judo Bio Launches with $100 Million Financing to Develop Oligonucleotide Therapies Delivered to the Kidney and Appoints Rajiv Patni as CEO

STRIKE platform to deliver siRNA and other genetic medicines to the kidney for the treatment of systemic diseases and renal diseases

 Lead pipeline programs use megalin receptors for intracellular delivery of ligand-siRNA conjugates to specific kidney cells to target and silence genes, including solute carrier proteins

 

CAMBRIDGE, Mass., October 7, 2024 — Judo Bio, a biotechnology company pioneering oligonucleotide medicines delivered to the kidney, today announced the company’s launch and $100 million in initial financing, including seed financing and Series A. Atlas Venture founded and incubated Judo Bio with The Column Group joining the seed financing. The Series A was recently closed and co-led by Atlas Venture, TCG and Droia Ventures, with participation from Digitalis Ventures, Euclidean Capital, Alexandria Venture Investments, YK Bioventures, and other undisclosed funds. Judo Bio also announced the appointment of biopharma industry veteran Rajiv Patni, M.D., as the company’s Chief Executive Officer and Board director.

Judo Bio has discovered a novel approach to create oligonucleotide medicines targeted to the kidney, an organ that has been challenging to access for genetic medicines. The company has completed preclinical studies successfully demonstrating receptor-mediated delivery of oligonucleotides to the kidney with proprietary ligand-siRNA conjugates that silence multiple target genes.

The proceeds from the financing will be used to advance the lead ligand-siRNA conjugate to the clinic and to further build the company’s proprietary STRIKE (Selectively Targeting RNA Into KidnEy) platform. Judo Bio’s initial pipeline programs are megalin-STRIKERs that use the megalin receptor family to selectively deliver siRNA therapeutics to the proximal tubule epithelial cells of the kidney. These megalin-STRIKERs are designed to silence mRNA, resulting in reduction of specific solute carrier proteins (SLCs). SLCs contribute to the homeostasis of circulating substances, including amino acids, electrolytes, glucose, and other metabolites. Targeting SLCs is an established approach for the treatment of various systemic diseases.

Kevin Bitterman, Ph.D., Partner at Atlas Venture, commented, “The Judo team should be applauded for their achievements to date. In a short period, the company has developed a novel platform, demonstrated potent and selective gene knockdown in specific kidney regions, and constructed a pipeline of compelling programs that we are excited to see advanced towards the clinic.”

Judo Bio has appointed Rajiv Patni as its CEO. Dr. Patni is a 25-year veteran of the pharma and public biotech ecosystem. Most recently, he served at Chief R&D Officer at Reata Pharmaceuticals until its acquisition by Biogen in 2023. Previously, he served as Chief Medical Officer at several successful public small-cap biotech companies, including Global Blood Therapeutics and Portola Pharmaceuticals. He joined these companies at inflection points in their R&D trajectory. During his tenure, Dr. Patni supported team efforts for initial drug approvals, indication expansions, and acquisitions by larger companies. Earlier in his career, Dr. Patni held roles at Pfizer, Roche, and Actelion.

“I am humbled to join an outstanding and very supportive leadership team, board and advisory group. They are bona-fide experts in oligonucleotide science and therapeutics, as well as company creation. With the Series A funding in hand, Judo can build on its solid foundation and nominate a series of development candidates, with efficient and timely proof-of-concept data readouts,” said Dr. Patni.

World class team of oligonucleotide drug developers and business leaders

John Maraganore, Ph.D., founder and former CEO of Alnylam, commented, “The promise of renally-targeted oligonucleotide medicines has been a long-standing challenge. With Judo Bio’s discovery of novel ligands that result in oligonucleotide delivery to specific kidney cells, diseases that were intractable to this approach may now be within reach.”

Judo Bio’s leadership team, scientific advisors and Board of directors bring unparalleled knowledge of oligonucleotide therapies and a proven track record of discovering and developing transformative therapies. The company’s scientific team is led by Alfica Sehgal, Ph.D., Chief Scientific Officer, who has more than 15 years of experience working on leading-edge RNA and siRNA therapeutic programs at CAMP4 Therapeutics and Alnylam Pharmaceuticals.

Concurrent with the Series A financing, Judo Bio’s Board of directors includes the following members:

  • Kevin Bitterman, Ph.D. – Partner, Atlas Venture
  • Samuel Bjork – Partner, Digitalis Ventures
  • Jeff Goater – Partner, the Column Group – Executive Chair
  • George Golumbeski, Ph.D. – Partner, Droia Ventures
  • Ankit Mahadevia, M.D. – Independent Director
  • Rajiv Patni, M.D. – CEO, Judo Bio

Judo Bio’s advisors include world-renowned experts with collectively decades of experience understanding oligonucleotide drugs, targeting the kidney for innovative therapeutics, and building and scaling biotech companies.

  • Andrew Fraley, Ph.D. – Judo Bio Co-Founder
  • Chelsea Place Johnson, Ph.D. – Judo Bio Co-Founder, Principal at Atlas Venture
  • Niranjan Kameswaran, Ph.D. – Entrepreneur-in-Residence at Atlas Venture
  • John Maraganore, Ph.D. – Alnylam Founder and former CEO
  • Peter Mundel, M.D. – Nephrology physician-scientist, Goldfinch Bio Founder
  • Steven Robinette, Ph.D. – Judo Bio Founder and former Interim CEO, Venture Partner at Atlas Venture
  • Ora Weisz, Ph.D. – Professor of Medicine, University of Pittsburgh

 

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.

Media contact:
Kathryn Morris
The Yates Network LLC
914-204-6412
kathryn@theyatesnetwork.com

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