Rectify Pharmaceuticals Reports Promising Preclinical Data for RTY-406 in Primary Sclerosing Cholangitis at EASL 2026
Key Insights
Rectify Pharmaceuticals (search) presented new preclinical data at EASL 2026 showing RTY-406 (search) significantly improved disease-relevant endpoints in a mouse model of primary sclerosing cholangitis (search) and demonstrated proof of mechanism in non-human primates.
RTY-406 (search) is a dual-acting ABCB4 (search)/BSEP (search) positive functional modulator that targets abnormal bile composition and impaired bile flow, two core pathophysiological drivers of PSC (search).
The drug candidate is currently in Phase 1 clinical development as a potential first-in-class disease-modifying therapy for PSC (search) patients, a devastating disease with no approved therapies addressing underlying biology.
Rectify Pharmaceuticals (search) announced promising preclinical data for RTY-406 (search), its clinical candidate for primary sclerosing cholangitis (search) (PSC (search)), at the European Association for the Study of the Liver (EASL) Congress 2026 in Barcelona. The biotechnology company presented evidence that RTY-406 demonstrated significant improvements in disease-relevant endpoints in both mouse models and non-human primates, supporting its advancement to first-in-human studies.
Novel Dual-Acting Mechanism Targets Core PSC Pathophysiology
RTY-406 (search) represents a novel class of oral small molecules called Positive Functional Modulators (PFMs) designed to restore and enhance membrane protein function. The drug candidate simultaneously enhances the function of ABCB4 (search) and BSEP (search), directly targeting two core pathophysiological drivers of PSC (search): abnormal bile composition and impaired bile flow.
"Primary sclerosing cholangitis (search) is a devastating disease for which there are no approved therapies that address the underlying biology driving disease progression," said Rajesh Devraj, PhD, President and Chief Executive Officer of Rectify Pharmaceuticals (search). "The preclinical translational data we are presenting at EASL, in mice and non-human primates, strengthens our confidence in RTY-406 (search)'s clinical translation and validates advancement to first-in-human studies."
Significant Efficacy Demonstrated in PSC Mouse Model
In a mouse model of PSC (search), RTY-406 (search) demonstrated comprehensive improvements across multiple disease markers. The treatment reduced serum total bile acids, alkaline phosphatase (ALP), and hepatic taurocholic acid (TCA), demonstrating BSEP (search) target engagement and a reduction in cholestasis (search). Additionally, RTY-406 reduced expression of markers associated with ductular reaction, including Ck19 and Vcam.
The drug candidate also showed anti-fibrotic effects, reducing expression of fibrosis (search)-related genes including Itgb6, Spp1, Timp-1, and Col1a1/2. Furthermore, RTY-406 (search) reduced expression of pro-inflammatory mediators involved in immune cell recruitment, including Mcp-1 and Cxcl-1.
Proof of Mechanism Confirmed in Non-Human Primates
In healthy cynomolgus primates, RTY-406 (search) administered once daily demonstrated proof of mechanism through several key findings. The treatment reduced serum alkaline phosphatase (ALP), consistent with decreased hepatic bile acid accumulation and increased BSEP (search) activity. RTY-406 also showed dose-dependent reduction in gamma-glutamyl transferase (GGT), a marker associated with cholangiocyte turnover, suggesting improved bile acid flow and enhanced bile composition resulting from increased ABCB4 (search) and BSEP activity.
Additionally, the treatment produced dose-dependent reduction in serum cholesterol, the principal substrate for de novo bile acid synthesis, consistent with increased bile acid synthesis and export from the liver.
Clinical Translation and Safety Profile
Pol Boudes, MD, Rectify's Chief Medical Officer, emphasized the consistency of findings across models. "What is encouraging about these results is the consistency of the findings across both disease models and non-human primates. We observed evidence that RTY-406 (search) improves bile composition and bile flow while reducing markers associated with liver and bile duct injury, all without evidence of liver toxicity."
RTY-406 (search) is currently in Phase 1 clinical development as a potential first-in-class disease-modifying therapy for PSC (search) patients. The drug candidate has pipeline-in-a-pill potential across multiple hepatobiliary diseases and represents an opportunity to become a first-in-class disease-modifying therapy for PSC.
Independent Validation from Academic Collaborators
Additional validation came from collaborators at University Medical Center Groningen, who presented data showing that Rectify's ABCB4 (search)/BSEP (search) dual targeted PFM increased biliary phospholipid secretion in a mouse model with residual phospholipid transport function. This independent research provides additional validation of Rectify's therapeutic strategy for treatment of PSC (search) and other hepatobiliary diseases.