Rectify Pharmaceuticals is advancing a potential new treatment approach for primary sclerosing cholangitis (PSC), unveiling new discovery data for its lead clinical candidate, RTY-406, at the American Chemical Society Fall 2026 Meeting in Chicago.

 

The oral, once-daily investigational therapy is designed to target two key proteins involved in bile composition and flow — ABCB4 and BSEP — with the aim of addressing underlying drivers of PSC rather than simply treating its symptoms.

 

Rectify presented the discovery and characterization of RTY-406 during the Division of Medicinal Chemistry’s First Time Disclosures session. The presentation, titled “Discovery of RTY-406: A Positive Functional Modulator of ABCB4 and BSEP as a Disease-Modifying Therapy for the Treatment of Primary Sclerosing Cholangitis,” was delivered by Nate Fuller, the company’s vice president of chemistry.

 

“The data presented at ACS demonstrate that RTY-406 represents an entirely novel approach for the treatment of primary sclerosing cholangitis with pipeline-in-a-pill potential across multiple hepatobiliary diseases” said Rajesh Devraj, President and Chief Executive Officer of Rectify Pharmaceuticals. 

 

“By modulating ABCB4 and BSEP to restore normal bile composition and flow, we are directly addressing key pathophysiologic drivers of hepatobiliary disease. The meaningful improvements observed in bile composition, inflammation and fibrosis in an in vivo model give us confidence in this approach and its potential to become the first disease modifying therapy for PSC.”

 

According to the company, its Positive Functional Modulator (PFM) platform generated a series of compounds capable of simultaneously modulating ABCB4 and BSEP. Rectify said rapid optimization produced candidates with greater potency and improved drug-like properties.

 

High-resolution cryo-electron microscopy structures further confirmed that the compounds directly bind to the target proteins to alter their function, the company said.

 

RTY-406 emerged as a potent dual PFM with what Rectify described as an excellent pharmacokinetic profile. In a mouse model of PSC, treatment produced several potentially important changes:

 

Modulation of ABCB4 and BSEP activity.

Dose-dependent reductions in alkaline phosphatase (ALP) and cholesterol crystals, both associated with PSC progression.

Dose-dependent improvements in markers of ductular reaction, inflammation and fibrosis.

 

The findings suggest the compound could potentially affect multiple biological processes linked to PSC, including abnormal bile composition, impaired bile flow, inflammation and fibrosis.

 

RTY-406 is now being evaluated in a Phase 1 clinical study, marking a transition for Rectify from discovery-stage research into clinical development.

 

The company describes RTY-406 as an orally administered, once-daily ABCB4/BSEP dual-targeted PFM. Its proposed mechanism is intended to address two core pathophysiological drivers of PSC: abnormal bile composition and reduced bile flow.