RTY-406 demonstrates significant improvements in disease relevant endpoints in a mouse model of primary sclerosing cholangitis (PSC) and proof of mechanism in non-human primates
RTY-406 is in Phase 1 clinical development as a potential first-in-class disease-modifying therapy for PSC patients
Presentation from UMCG collaborators provides additional validation for modulating ABCB4 and BSEP to address the underlying biology of cholestatic liver diseases
BOSTON, May 27, 2026 (GLOBE NEWSWIRE) -- Rectify Pharmaceuticals, a biotechnology company advancing Positive Functional Modulators (PFMs), a novel class of oral small molecules designed to restore and enhance membrane protein function, today announced the presentation of new preclinical data at the European Association for the Study of the Liver (EASL) Congress 2026, taking place May 27-30, 2026, in Barcelona.
"Primary sclerosing cholangitis 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. "The preclinical translational data we are presenting at EASL, in mice and non-human primates, strengthens our confidence in RTY-406’s clinical translation and validates advancement to first-in-human studies. RTY-406 simultaneously enhances the function of ABCB4 and BSEP, directly targeting two core pathophysiological drivers of PSC: abnormal bile composition and impaired bile flow. RTY-406's dual-acting, differentiated mechanism has the potential to become a first-in-class disease-modifying therapy for PSC, and could have therapeutic benefit across multiple hepatobiliary indications.”
Key Findings:
Poster 1: RTY-406 is a dual-acting ABCB4/MDR3 and ABCB11/BSEP positive functional modulator that demonstrates efficacy in a model of Primary Sclerosing Cholangitis
In a mouse model of PSC, RTY-406 demonstrated:
- Reduced serum total bile acids, alkaline phosphatase (ALP), and hepatic taurocholic acid (TCA), demonstrating BSEP target engagement and a reduction in cholestasis
- Reduced expression of markers associated with ductular reaction, including Ck19 and Vcam
- Reduced expression of fibrosis-related genes, including Itgb6, Spp1, Timp-1, and Col1a1/2
- Reduced expression of pro-inflammatory mediators involved in immune cell recruitment, including Mcp-1 and Cxcl-1
Poster 2: RTY-406, a candidate drug for Primary Sclerosing Cholangitis (PSC), a dual-acting ABCB4/MDR3 and ABCB11/BSEP positive functional modulator, demonstrates proof of mechanism in non-human primates
In healthy cynomolgus primates RTY-406 administered once daily, demonstrated:
- Reduced serum alkaline phosphatase (ALP), consistent with decreased hepatic bile acid accumulation and increased BSEP activity
- 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 and BSEP activity
- 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
Pol Boudes, MD, Rectify’s Chief Medical Officer, added, “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 improves bile composition and bile flow while reducing markers associated with liver and bile duct injury, all without evidence of liver toxicity. These data provide a strong translational foundation as we advance RTY-406 in the clinic as a potential disease-modifying therapy for PSC.”
Additional data presented by Henkjan Verkade, MD, PhD and collaborators from University Medical Center Groningen in a poster titled, “Small molecule approach for increasing biliary phospholipid secretion in a mouse model for MDR3 deficiency (Progressive Familial Intrahepatic Cholestasis type 3, PFIC3)” demonstrated that Rectify’s ABCB4/BSEP dual targeted PFM increased biliary phospholipid secretion in a mouse model with residual phospholipid transport function, providing independent validation of Rectify's therapeutic strategy for treatment of PSC and other hepatobiliary diseases.
Rectify’s posters are available on the Publications page of the company’s website.
About RTY-406
RTY-406 is an orally administered ABCB4 and BSEP dual-targeted Positive Functional Modulator (PFM) in clinical development for primary sclerosing cholangitis (PSC). RTY-406’s dual acting mechanism-of-action uniquely targets abnormal bile composition and reduced bile flow, two core pathophysiological drivers of PSC. In a preclinical model of PSC, RTY-406 demonstrated efficacy across multiple disease-relevant endpoints, including inflammation, cholangitis, cholestasis, and fibrosis. RTY-406 has pipeline-in-a-pill potential across multiple hepatobiliary diseases and the opportunity to become a first-in-class disease-modifying therapy for PSC.
About Rectify Pharmaceuticals
Rectify is advancing Positive Functional Modulators (PFMs), a novel class of oral, small molecules that restore and enhance membrane protein function to address the underlying cause of serious diseases. Rectify’s PFMs have potential to modulate the activity of wild-type and mutated membrane-bound proteins, a historically difficult challenge with a small molecule approach. The Company’s breakthrough product platform enables efficient and rapid discovery of first- and best-in-class small molecule therapies with the potential to address membrane protein dysfunction for treatment of rare and common diseases, including liver, cardio-renal-metabolic, and neurodegenerative diseases. For more information, please visit www.rectifypharma.com or follow us on X and LinkedIn.
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