Atlas spin-off aims to develop siRNA-ligand conjugates for the kidney

The venture capital firm Atlas Venture is launching a start-up that aims to develop antisense oligonucleotides for a historically difficult organ to drug: the kidney.

Judo Bio debuted Monday after about 3 years in stealth. The company has designed a drug candidate that combines a ligand with small interfering RNA (siRNA) that should silence messenger RNA (mRNA) and, in turn, reduce certain solute carrier proteins that are involved in disease.

While siRNA is a proven therapeutic approach, getting it to the right cell types is challenging. The kidney is a “very complex tissue,” says Chief Scientific Officer Alfica Sehgal, a former head scientistat Camp4 Therapeutics and Alnylam Pharmaceuticals, the latter of which is widely credited with establishingsiRNA as a drug. The organ consists of multiple tissue types, making specificity difficult. The glomerulus, a network of blood vessels in the kidney, also filters out molecules by size; it excretes antisense oligonucleotides (ASOs) like siRNA by default.

“It’s not an easy bean to crack,” Sehgal says.

But Judo has proposed an elegant solution. The ligand acts as a hook on the ASO so that, on itsway out, the conjugatelatches on to the kidney’s proximal tubule epithelial cells via a receptor called megalin. From that perch, the siRNA can act on the mRNA.

Judo began as a project of Atlas in summer 2021. Atlas partner Steven Robinette founded the firm in Atlas’s company creation arm and served as its CEO until September, when Judo brought on Rajiv Patni to take over the corner office. It’s Patni’s first time as CEO; he previously held chief medical and chief R&D officer positions at various biotechnology firms. Sehgal joined in July 2023.

The start-up recently closed a series A investment round that, when combined with its seed funding, comes out to $100 million. Atlas, The Column Group, and Droia Ventures co-led the series A.

Judo will present data on how its siRNAs work in rodents at the Oligonucleotide Therapeutics Society annual meeting this week. The start-up says the ligand-conjugated siRNAs were exposed in the kidney 5- to 30-fold over siRNAs alone. The conjugates also led to a 50–70% knockdown of target genes, and that knockdown was sustained for 4 weeks in the rodents, per a press release.

Patni declines to go into detail about Judo’s first disease target or say when it might begin testing its drug candidates in humans. Broadly speaking, Patni and his 15-person team will explore genetic metabolic diseases, gout, diabetes, hypertension, heart failure, disorders of calcium, and disorders of phosphate. Solute carrier proteins are involved in all these diseases since they help stabilize circulating substances like amino acids and metabolites.

“There’s a real therapeutic opportunity here to add to what’s available for these diseases,” Patni says.