Novo Nordisk has moved into sickle cell disease through a licensing deal with EpiDestiny. The $400 million deal gives Novo worldwide rights to an epigenetic treatment of the disease that is closing in on the start of a phase 2 trial.

Researchers at the Cleveland Clinic and the University of Illinois began testing the oral combination of tetrahydrouridine and decitabine in humans in 2012. That led to the publication of data from a small, eight-week trial that linked the combination to increased levels of fetal hemoglobin, a biomarker that correlates to improved outcomes in sickle cell patients.

The trial only featured five cohorts of five patients, randomized three-to-two between the study drug and placebo, so the usual caveats about early-stage data apply. But Novo has seen enough in the results and their preliminary validation of the rationale for the combination to strike a deal.

Exactly how much Novo is handing over immediately is unknown publicly. The overall deal is valued at $400 million, but that includes development and sales milestones. Given that the combination, known as EPI01, has yet to advance beyond early-phase tests, the upfront fee may make up a relatively small slice of the $400 million.

In return for the outlay, Novo is gaining worldwide rights to EPI01 in sickle cell disease and beta-thalassemia. EpiDestiny is keeping hold of the right to develop the drug in cancer indications.

EPI01 entered the clinic in sickle cell on the strength of evidence its component parts jointly enable the inhibition of DNMT1, an enzyme that epigenetically silences fetal hemoglobin. Fetal hemoglobin improves outcomes in sickle cell patients by interfering with the polymerization of mutated sickle hemoglobin. Inhibiting DNMT1, thereby increasing fetal hemoglobin, should improve outcomes.

Decitabine inhibits DNMT1. The snag is another enzyme in the body quickly inactivates the drug. To get around the problem, researchers combined decitabine with tetrahydrouridine, a CDA inhibitor that keeps decitabine levels high enough for the drug to take effect.

Novo, in collaboration with EpiDestiny, will now find out whether the idea holds up to scrutiny in more rigorous clinical trials. The success of EPI01 would deliver a boost to Novo’s rare blood disorder unit, which risks seeing sales slide as competition in the hemophilia market heats up. With Novo’s diabetes franchise also under pressure, management has tasked the business development team with buying in blood disorder assets, leading to the failed Ablynx bid and now the EpiDestiny deal.