Published in Scientific Reports, a Nature Portfolio journal, the study details dual acting small molecules that restore myelin, modulate inflammation, and improve visual pathway function in preclinical MS models.
OKLAHOMA CITY, Oct. 9, 2025 /PRNewswire/ -- Cadenza Bio, Inc. today announced that a collaborative study, "Chloroindazole based Estrogen Receptor β ligands with favorable pharmacokinetics promote functional remyelination and visual recovery," has been published in Scientific Reports (https://www.nature.com/articles/s41598-025-20254-9).
The work, authored by scientists from the University of California Riverside, University of Illinois Urbana-Champaign, The Scripps Research Institute, and Cadenza Bio, and supported by the National Multiple Sclerosis Society's Fast Forward commercial funding program, reports that two ERβ selective small molecules, K102 and K110, repair myelin and improve function in established mouse models of multiple sclerosis (MS), with pharmacokinetics suitable for oral dosing and central nervous system exposure.
While most current MS therapies focus on reducing inflammation, few address the critical need for myelin repair or provide meaningful recovery. New preclinical results demonstrate that Cadenza Bio's lead compounds, K102 and K110, deliver dual benefits, enhancing remyelination and modulating immune activity, with functional recovery observed in visual pathway measures routinely used in human MS studies.
"Our findings demonstrate that ERβ ligand treatment promotes neuroprotection and enhances visual pathway function, as assessed by non-invasive measures such as OCT, ERG, and VEP in a mouse model of MS," said Dr. Seema Tiwari-Woodruff, Corresponding Author and Scientific Founder of Cadenza Bio. "These measures are particularly valuable because they can also be applied non-invasively in patients, allowing direct translation into clinical trials."
Both compounds, K102 and K110, were well tolerated and highly selective for ERβ, with no ERα-linked safety concerns observed. In addition, K102 promoted oligodendrocyte maturation in human iPSC-derived cells, reinforcing translational relevance.
Study highlights (Preclinical)
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Dual Mechanism of Action: K102 and K110 demonstrated dual activity – enhancing remyelination while modulating immune responses.
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Signals of Repair: In two established MS models, treated animals showed evidence of repair, with increased myelin and oligodendrocytes (the cells that produce myelin).
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Functional Recovery in the Visual Pathway: Treated animals demonstrated improved functional outcomes in measures commonly used in MS clinics to assess eye health and brain signaling. Both K102 and K110 improved electroretinogram (ERG) results, while K102 also preserved retinal nerve fiber layer (RNFL) thickness and restored visual evoked potential (VEP) measures to baseline.
- Brain penetration with Oral Dosing: K102 and K110 achieved biologically relevant brain concentrations across species following oral administration, supporting their potential for CNS activity.
"These findings highlight a novel dual mechanism of action supported by functional endpoints and aligned with clinical measures, providing a strong foundation for advancing K102 and K110 into clinical development," said Dr. Carol Curtis, Co-Founder and CEO of Cadenza Bio. "We are committed to rapidly advancing these drug candidates with the goal of halting progression, promoting repair, and ultimately improving quality of life for patients with MS."
MS remains a devastating disease with few options that repair myelin or restore function, especially in progressive forms. ERβ is a promising target for its ability to promote remyelination, protect neurons, and modulate harmful immune responses. Cadenza Bio aims to deliver a first-in-class oral treatment that not only reduces inflammation but also repairs the protective covering on nerves to improve function. While the results documented in this manuscript are from preclinical studies, they provide a strong foundation for moving into Phase 1 clinical trials, and Cadenza is actively raising funds to make this next step possible.
About Cadenza Bio, Inc.
Cadenza Bio, Inc. is a biotechnology company dedicated to developing novel small-molecule drugs for demyelinating and inflammatory diseases. With a mission to break the cycle of disease, Cadenza Bio aims to not only alleviate symptoms but also halt disease progression, promote repair, and restore quality of life for patients. The company's drug pipeline reflects its commitment to advancing life-changing therapies in collaboration with leading researchers.
Cadenza Bio holds an exclusive license to technology developed through an academic research collaboration between Dr. John Katzenellenbogen of the University of Illinois Urbana-Champaign (UIUC) and Dr. Seema Tiwari-Woodruff of the University of California, Riverside (UCR).
For additional information, visit www.cadenza.bio.
Forward Looking Statements (Safe Harbor): This press release contains forward‑looking statements, including statements regarding the potential efficacy and future development of K102 and K110. These statements are based on current expectations and assumptions and involve risks and uncertainties that could cause actual outcomes to differ materially. Preclinical results may not be predictive of clinical outcomes. Cadenza Bio undertakes no obligation to update forward‑looking statements.
Reference:
Feri, M., Kim, S.H., Cardenas, F.D. et al. Chloroindazole based estrogen receptor β ligands with favorable pharmacokinetics promote functional remyelination and visual recovery. Sci Rep15, 35056 (2025). https://doi.org/10.1038/s41598-025-20254-9
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