Otsuka Pharmaceutical is acquiring Jnana Therapeutics, whose lead drug is a potential treatment for the rare metabolic disorder phenylketonuria (PKU). Jnana’s drug could provide an alternative to two FDA-approved PKU medicines from BioMarin Pharmaceutical.

By Frank VinluanOtsuka Pharmaceutical is broadening its scope in rare disease, striking a deal to acquire Jnana Therapeutics and its lead drug candidate, a small molecule on track for pivotal testing in a metabolic disorder with few treatments.
Per deal terms announced Thursday, Otsuka is paying $800 million up front to buy Boston-based Jnana. The Japanese pharma company could shell out up to $325 million more if the lead drug candidate of privately held Jnana achieves development and regulatory milestones.
Jnana’s lead program, JNT-517, is in development for phenylketonuria (PKU), an inherited disorder that leads to deficiency of an enzyme needed to break down phenylalanine, an amino acid found in certain foods. Buildup of phenylalanine in the body leads to complications including cognitive problems. PKU patients can manage phenylalanine levels with a restrictive diet that minimizes protein intake.
Two approved PKU therapies are also available, both from BioMarin Pharmaceutical: Kuvan is a small molecule that helps the process of breaking down phenylalanine while Palynziq is an engineered version of the enzyme needed to break down the amino acid. These therapies don’t work for all PKU patients and some who take Palynziq struggle to maintain the required regimen of daily injections. For 2023, BioMarin reported $484.7 million in combined revenue for the two products.
Jnana takes a different approach by drugging SLC transporters, a family of proteins whose role includes moving substances across biological membranes. JNT-517 is a small molecule that binds to an allosteric site on SLC6A19, a transporter responsible for absorption of phenylalanine in the intestines and reabsorption of the amino acid by the kidneys. Blocking SLC6A19 is intended to lead to an increase in phenylalanine secretion in the urine.
Jnana has said its drug has potential to treat the spectrum of PKU patients from mild to severe disease. The acquisition agreement comes six months after the biotech announced JNT-517 demonstrated clinical proof of concept in a Phase 1b trial, paving the way for a pivotal study planned for the second half of 2025. In addition to being safe and well tolerated, the interim results from 13 patients — eight dosed with the study drug and five with placebo — showed a statistically significant 51% average reduction in phenylalanine levels in the blood. Results also showed a rapid onset of effect that was sustained throughout the 28 days of dosing.
JNT-517 comes from RAPID, Jnana’s platform technology that discovers binding sites across the surface of a target protein and identifies small molecules that can hit those sites. Beyond Jnana’s lead program, RAPID has produced a preclinical pipeline in immune disorders, which have been difficult to drug with oral small molecules. Jnana also has partnerships with Roche in cancer, immunology, and neurological diseases, and with Neurocrine Biosciences in neurological diseases. Otsuka says Jnana’s technology capabilities complement those of Astex Pharmaceuticals, a Cambridge, U.K.-based subsidiary of the Japanese company. Astex, which is developing drugs for cancer and central nervous system disorders, was acquired by Otsuka in 2013.
Otsuka’s presence in rare disease includes therapies for kidney disorders. The FDA’s 2018 approval of Jynarque made that Otsuka small molecule the first drug to slow kidney function decline in adult patients with autosomal dominant polycystic kidney disease. Visterra, a Waltham, Massachusetts-based biotech acquired by Otsuka in 2018, has reached Phase 3 testing with sibeprenlimab. This antibody is an experimental treatment for immunoglobulin A nephropathy, an autoimmune disorder affecting the kidneys. Otsuka also has certain rights to volosporin, an experimental lupus nephritis drug developed by Aurinia Pharmaceuticals, and donidalorsen, an experimental Ionis Pharmaceuticals treatment for hereditary angioedema.
“The addition of Jnana’s drug discovery technology and small molecule pipeline in PKU and autoimmune diseases will strengthen our R&D in the Boston area of the U.S., one of the most important bio clusters in the world, and in a combined form will have a synergistic effect on Otsuka Pharmaceutical’s global expansion,” Makoto Inoue, president and representative director of Otsuka, said in a prepared statement.
Jnana launched in 2017, backed by an investor syndicate that includes Polaris Partners, Avalon Ventures, Versant Ventures, AbbVie Ventures, and Pfizer R&D Innovate. The startup’s most recent financing was a $107 million Series C round in late 2022 led by Bain Capital Life Sciences.
The boards of directors of both Otsuka and Jnana have approved the acquisition, but the deal may still need approval of Jnana shareholders and U.S. regulators. The companies expect to complete the transaction later in the current quarter. Afterward, Jnana will remain in Boston, operating as a wholly owned Otsuka subsidiary.
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