ABLi Therapeutics reported Phase 2 data showing risvodetinib reduced phosphorylated alpha-synuclein and neuroinflammation biomarkers in early untreated Parkinson’s disease, supporting its disease-modifying potential.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
ABLi Therapeutics has reported new biomarker findings from its Phase 2 201 Trial (NCT05424276) showing that risvodetinib produced coordinated changes across multiple tissue, blood, and cerebrospinal fluid (CSF) biomarkers linked to neurodegeneration and neuroinflammation in patients with early, untreated Parkinson’s disease (PD). The results support the drug’s proposed disease-modifying potential and will inform upcoming late-stage clinical development.
ABLi completed an extensive biomarker analysis involving approximately 7,300 individual measurements collected from up to 80 participants enrolled in the Phase 2 201 Trial. The study evaluated 11 biomarkers reflecting key biological processes involved in Parkinson’s disease, including c-Abl kinase activity, alpha-synuclein pathology, neuroinflammation, neuronal degeneration, and mitochondrial health.
Biomarker Findings Support Disease-Modifying Activity
The biomarker analysis demonstrated consistent biological responses across multiple doses of risvodetinib administered once daily for 12 weeks.
All three evaluated doses (50 mg, 100 mg, and 200 mg) inhibited the therapeutic target, c-Abl kinase. Treatment also reduced neuroinflammatory activity, with suppression of the NLRP3 inflammasome and the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) to levels below baseline.
The strongest effects on phosphorylated alpha-synuclein, a modified form of alpha-synuclein widely considered a central driver of Parkinson’s disease pathology, were observed with the 100 mg and 200 mg doses in cerebrospinal fluid. All three dose levels also reduced phosphorylated alpha-synuclein concentrations in blood, supporting systemic biological activity.
According to the company, these findings indicate that risvodetinib influences multiple interconnected pathways involved in Parkinson’s disease progression rather than targeting a single biomarker.
Building on Earlier Clinical Results
The biomarker program expands on earlier findings from the Phase 2 201 Trial, which previously showed reductions in alpha-synuclein aggregates in skin biopsy samples from 36 participants. Those data formed part of the scientific foundation for ABLi’s launch in 2025.
For the current analysis, investigators incorporated longitudinal blood samples from 80 participants and cerebrospinal fluid samples from six participants collected at baseline and after 12 weeks of treatment. The integrated dataset enabled assessment of biological changes across peripheral tissues and the central nervous system.
Risvodetinib previously became the first investigational monotherapy to improve quality of life in a randomized, placebo-controlled trial of untreated Parkinson’s disease while also reducing underlying synuclein aggregate pathology.
Executive Perspective
Chairman and Chief Executive Officer Dr. Milton Werner said the biomarker analysis provides new insight into both Parkinson’s disease biology and patient response to treatment. He noted that coordinated improvements across tissue, blood, and cerebrospinal fluid biomarkers, including substantial reductions in phosphorylated alpha-synuclein, suggest reversal of key biological processes underlying disease progression during 12 weeks of therapy.
The company believes this coordinated biomarker responses represent the biological profile expected from a disease-modifying therapy, although confirmation will require larger, longer-term clinical studies.
Path Forward for Clinical Development
ABLi plans to use these biomarkers to support patient selection, disease monitoring, and outcome assessment in its upcoming BASE, ABILITY, and CAMPD clinical trials. The late-stage CAMPD study will also evaluate relationships between biomarker changes and clinical outcomes to determine whether biological improvements translate into sustained patient benefit.
The company expects to discuss the new biomarker dataset with the U.S. Food and Drug Administration during a scheduled meeting in August 2026 as it advances the clinical development of risvodetinib.
Risvodetinib is an oral, selective small-molecule inhibitor of non-receptor c-Abl kinases. Unlike currently approved Parkinson’s disease therapies that primarily manage symptoms, the investigational therapy is being developed to slow or alter the biological processes responsible for disease progression. The program is supported by intellectual property protection extending beyond 2036.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.