Rectify Pharma Announces Publication of BSEP Transporter Biophysical Characterization in Communications Biology

Key structural and mechanistic insights into BSEP transporter mutations that lead to improper protein folding and function

Findings have potentially broad-ranging clinical relevance for multiple hepatobiliary diseases including progressive familial intrahepatic cholestasis type 2 and primary sclerosis cholangitis

BOSTON, April 07, 2025 (GLOBE NEWSWIRE) — Rectify Pharmaceuticals, Inc. (“Rectify”), a biotechnology company pioneering positive functional modulators (PFMs) that restore and enhance membrane protein function, today announced the publication of foundational structural biology research in Communications Biology, a Nature portfolio journal. The publication, titled “A structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease,” provides critical insights into the mechanisms through which the most severe patient mutations drive cholestatic diseases such as progressive familial intrahepatic cholestasis type 2 (PFIC2).

“Patients with cholestatic diseases such as PFIC2 have few therapeutic options, and we are committed to addressing this unmet need by understanding key drivers of biliary pathophysiology,” said Rajesh Devraj, Ph.D., President and Chief Executive Officer of Rectify Pharmaceuticals. “For the first time, this study provides detailed structural and mechanistic insights into BSEP misfolding and informs our work developing positive functional modulators to correct membrane protein dysfunction. Understanding these aberrant folding mechanisms is essential for advancing novel disease-modifying small molecule candidates that can improve bile flow and composition.”

The study reveals that mutations in BSEP disrupt the NBD2-ICL2 protein region, a critical structural domain required for proper protein folding and function. This disruption results in structural instability and cellular degradation of the transporter, ultimately impairing its ability to regulate bile acid transport.

PFIC2 is a rare and severe genetic pediatric liver disease caused by mutations in BSEP, leading to bile acid accumulation, progressive bile duct obstruction, liver toxicity, and, ultimately, liver failure. There are currently no treatment options to alter the course of the disease beyond a liver transplant.

About Rectify Pharmaceuticals, Inc. (“Rectify”)
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. Rectify was founded and seeded by Atlas Venture who co-led the $100M Series A round with Omega Funds and were joined by Forbion and Longwood Fund.

For more information, please visit www.rectifypharma.com or follow us on X and LinkedIn.

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