ABLi Therapeutics analyzed 7,300 biomarker measurements from up to 80 participants in its Phase II 201 trial and reports that once‑daily risvodetinib altered multiple PD‑related pathways after 12 weeks. All doses inhibited c‑Abl kinase; the 100 mg and 200 mg doses lowered phosphorylated alpha‑synuclein in CSF while all doses reduced the biomarker in blood. Risvodetinib also suppressed neuroinflammation markers (NLRP3, IL‑1beta, IL‑18). The company will advance 100 mg and 200 mg into follow‑on studies to link these biomarker changes to clinical outcomes.
ABLi: Risvodetinib Shows Promising Biomarker Changes Suggesting Potential Disease‑Modification in Parkinson’s
ABLi Therapeutics is exploring further biomarker use in the CAMPD trial to examine links to clinical outcomes in Parkinson’s disease. Credit: Jo Panuwat D / Shutterstock.com.
ABLi Therapeutics has released a comprehensive biomarker analysis from its Phase II 201 trial of risvodetinib in Parkinson's disease (PD), evaluating 7,300 individual measurements from up to 80 participants. The company reports that once‑daily risvodetinib produced consistent changes across multiple PD‑related pathways after 12 weeks of treatment.
Key Biomarker Findings
Target engagement: All three dose levels (50 mg, 100 mg and 200 mg once daily) inhibited cellular Abelson tyrosine kinase (c‑Abl), the drug's pharmacologic target.
Alpha‑synuclein: Levels of phosphorylated alpha‑synuclein—a form implicated in PD pathology—fell substantially. The 100 mg and 200 mg doses reduced phosphorylated alpha‑synuclein in cerebrospinal fluid (CSF), while all three doses reduced it in blood samples.
Neuroinflammation: Risvodetinib suppressed markers of neuroinflammation, including NOD‑like receptor family pyrin domain containing 3 (NLRP3) and the pro‑inflammatory cytokines interleukin‑1 beta (IL‑1beta) and IL‑18, driving them below baseline in trial participants.
Interpretation and Next Steps
ABLi interprets these changes as consistent with a reversal of several biological processes linked to PD and describes the pattern as compatible with potential disease‑modifying activity. The company plans to advance the 100 mg and 200 mg dose levels into upcoming studies BASE, ABILITY and CAMPD, with CAMPD specifically designed to explore how these biomarker changes relate to clinical outcomes in people with PD.
Dr Milton Werner, ABLi Chairman and CEO: 'The combined analysis of tissue, blood and cerebrospinal fluid from the 201 Trial revealed unexpected insights into disease biology and patient response. The biomarker shifts we observed after 12 weeks—particularly reductions in phosphorylated alpha‑synuclein and markers of neuroinflammation—are consistent with how true disease modification might appear, but will need confirmation in larger, outcome‑focused studies.'
About Risvodetinib
Risvodetinib is a selective, small‑molecule inhibitor of c‑Abl kinases formulated for once‑daily oral dosing and developed to target mechanisms believed to underlie Parkinson's disease.
Note of caution: While the biomarker profile is encouraging, clinical confirmation is required to determine whether these molecular changes translate into meaningful slowing of disease progression for patients with PD.
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