New Published Data Demonstrates Correlation Between Itch Cytokine Interleukin-31 Reduction and Pruritis Improvement in Primary Biliary Cholangitis in Phase 3 Post-Hoc Analysis of CymaBay's Seladelpar

-- First clinical trial in PBC to show coordinate reductions of IL-31, bile acids and pruritus --

NEWARK, Calif., Jan. 3, 2024 /PRNewswire/ -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on innovative therapies for patients with liver and other chronic diseases, today announced the first published findings demonstrating the impact of seladelpar on serum interleukin-31 (IL-31) levels and its correlation with pruritus improvement in people with primary biliary cholangitis (PBC). Seladelpar is a first-in-class oral, selective PPARδ agonist being investigated for the treatment of patients with PBC. The latest findings from a post-hoc analysis of the Phase 3 ENHANCE study, were published today in the open access journal Hepatology and are the first peer-reviewed published report of a correlation in decreases in IL-31, bile acids and pruritus symptoms in PBC following treatment with an investigational agent.

In a post-hoc analysis of the Phase 3 ENHANCE study, IL-31 serum levels were measured in people with PBC who received daily oral doses of seladelpar 5 mg (n=53), 10 mg (n=53) or placebo (n=55) for three months. IL-31 is a cytokine known to mediate pruritus and blocking IL-31 signaling can provide relief in pruritic skin diseases. Statistically significant dose-dependent decreases in IL-31 were observed with seladelpar 5 mg (-30%, p=0.0003) and 10 mg (-52%, p<0.0001) compared to placebo (+31%) in the study. IL-31 levels correlated with pruritus intensity using a numerical rating scale (NRS, 0-10; r=0.54, p<0.0001). Participants who experienced an improvement in pruritus (decrease in NRS of 2 or more) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (decrease in NRS of less than 2).

Baseline IL-31 levels also closely correlated with total (r=0.54, p<0.0001) and conjugated bile acids (up to 0.64, p<0.0001). Strong correlations were also observed between changes in IL-31 levels and changes in total bile acids (r=0.63, p<0.0001) and conjugated bile acids in the seladelpar 10 mg group.

"Pruritus is a debilitating symptom for many people living with PBC, yet the underlying mechanism of itch is not well understood," said Andreas Kremer MD, Ph.D., MHBA, Professor and Head of Hepatology, University Hospital Zurich and primary author of the study. "These latest data are critical in advancing our understanding of potential mediators of cholestatic itch and suggest that IL-31 may have a role in driving pruritis in people with PBC. While current treatments for cholestatic pruritus remain limited, these data can help inform potential novel therapeutic approaches."

About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the US). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP, ALT, and GGT, enzymes found primarily in the liver, as well as total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.

About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, or delpar, shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport.

For further information, the ENHANCE Post-Hoc Analysis can be accessed here:  Kremer, Andreas E.; Mayo, Marlyn J.; Hirschfield, Gideon M.; Levy, Cynthia; Bowlus, Christopher L.; Jones, David E.; Johnson, Jeff D.; McWherter, Charles A.; Choi, Yun-Jung. Seladelpar treatment reduces interleukin-31 and pruritus in patients with primary biliary cholangitis. Hepatology ():10.1097/HEP.0000000000000728, December 20, 2023. | DOI: 10.1097/HEP.0000000000000728

About CymaBay
CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need through a pipeline of innovative therapies. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (U.S. Food and Drug Administration), Priority Medicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class investigational treatment for people with PBC. Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families, and communities we serve. To learn more, visit www.cymabay.com and follow us on X (formerly Twitter) and LinkedIn.

Cautionary Statements
Any statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve pruritus, and the future development plans of CymaBay are forward-looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials; and effects observed in trials to date that may not be repeated in the future. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law.

For additional information about CymaBay visit www.cymabay.com.

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SOURCE CymaBay Therapeutics