Boston, Mass. – August 27, 2026
Rectify Pharmaceuticals presented the discovery and characterization of RTY-406, an oral, once-daily investigational therapy targeting primary sclerosing cholangitis (PSC), at the American Chemical Society Fall 2026 Meeting in Chicago. RTY-406 is a novel ABCB4/BSEP dual-targeted Positive Functional Modulator (PFM) designed to restore membrane protein function and address key drivers of abnormal bile composition and impaired bile flow. For cGxP.wire, the key development is the public disclosure of RTY-406’s discovery and preclinical characterization, including structural evidence of direct target binding and activity across disease-relevant endpoints in a mouse model of PSC. RTY-406 is already being evaluated in a Phase 1 clinical study, moving the program beyond discovery-stage development.
Rectify Presents RTY-406 Discovery at ACS
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 during the ACS MEDI First Time Disclosures session. Rectify described the application of its PFM platform to identify dual ABCB4/BSEP modulators, followed by optimization to improve potency and drug-like properties. High-resolution cryo-electron microscopy structures provided evidence that the compounds directly bind to the target proteins and modulate their function. The optimization process ultimately produced RTY-406, which the company characterized as a potent dual PFM with a favorable pharmacokinetic profile. The disclosure provides a scientific rationale for advancing RTY-406 into clinical development, although the available evidence remains primarily preclinical and early clinical safety and efficacy data have not yet established whether the mechanism will translate into meaningful benefit for PSC patients.
RTY-406 Targets Key PSC Disease Mechanisms
RTY-406 is designed to simultaneously modulate ABCB4 and BSEP, two membrane proteins involved in bile physiology. Rectify’s approach is intended to address abnormal bile composition and reduced bile flow, which the company identifies as key pathophysiological drivers of PSC. In a mouse model of PSC, RTY-406 produced dose-dependent reductions in alkaline phosphatase (ALP) and cholesterol crystals, alongside improvements in markers associated with ductular reaction, inflammation and fibrosis. The dual-target mechanism is intended to provide broader disease modification than approaches directed toward a single downstream symptom or pathway. However, improvements in animal biomarkers and pathology do not establish clinical efficacy in humans, making the ongoing Phase 1 study an important next step for determining safety, tolerability, pharmacokinetics and the feasibility of translating the mechanism into patients.
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RTY-406 Advances Toward Clinical Development
RTY-406 is currently being evaluated in a Phase 1 clinical study, marking the transition of Rectify’s PSC program from preclinical discovery into human testing. The company’s longer-term objective is to develop RTY-406 as a potential disease-modifying therapy for PSC and potentially expand its use across other hepatobiliary diseases. Rectify describes the asset as having “pipeline-in-a-pill” potential because the ABCB4/BSEP mechanism could potentially be relevant across multiple diseases involving hepatobiliary dysfunction. The immediate development priority, however, is establishing clinical proof-of-concept. The ACS presentation strengthens the mechanistic and preclinical case for RTY-406, but Phase 1 results and subsequent controlled clinical studies will determine whether the promising preclinical profile translates into a meaningful therapeutic effect in PSC.
Source: Rectify Pharmaceuticals, press relese
