ABLi Therapeutics has reported coordinated changes across 11 biomarkers linked to neurodegeneration and neuroinflammation following 12 weeks of treatment with risvodetinib in people with early, untreated Parkinson’s disease.

The biotechnology company said the findings from its Phase 2 201 Trial provide evidence that risvodetinib may affect multiple biological processes associated with Parkinson’s disease pathology, including phosphorylated alpha-synuclein, c-Abl kinase activity and neuroinflammation.

The analysis included 7,300 individual biomarker measurements from up to 80 participants, using tissue, blood and cerebrospinal fluid samples collected at baseline and after 12 weeks of once-daily treatment.

ABLi said the findings support further investigation of risvodetinib as a potential disease-modifying treatment for Parkinson’s disease. However, the company has not yet demonstrated that the biomarker changes translate into a slowing of disease progression or improved long-term clinical outcomes.

Risvodetinib targets Parkinson’s disease biology

Parkinson’s disease is associated with progressive loss of neurons and a range of biological processes, including the accumulation of abnormal alpha-synuclein and neuroinflammation.

Current treatments are primarily focused on managing symptoms, while the development of therapies capable of slowing or stopping the underlying progression of Parkinson’s remains a major area of research.

Risvodetinib is an oral, once-daily small-molecule inhibitor of c-Abl kinases, which are enzymes that ABLi believes play a role in the biological processes involved in Parkinson’s disease.

The latest analysis was designed to assess whether treatment affected a broader range of biological markers associated with the disease.

ABLi said the 11 biomarkers examined reflected processes including neuronal degeneration, mitochondrial health and neuroinflammation.

Milton Werner, chairman and chief executive of ABLi Therapeutics, said: “The analysis of tissue, blood and spinal fluid measures from participants in the 201 Trial has revealed surprising information, both about the underlying processes of disease and how patients respond to risvodetinib treatment.”

The company said the analysis showed that all three risvodetinib doses studied — 50 mg, 100 mg and 200 mg once daily — inhibited the target c-Abl kinase.

Biomarkers linked to alpha-synuclein and inflammation respond to treatment

The analysis also found dose-dependent changes in phosphorylated alpha-synuclein biomarkers.

According to ABLi, the 100 mg and 200 mg doses substantially reduced phosphorylated alpha-synuclein biomarkers in cerebrospinal fluid, while all three doses reduced phosphorylated alpha-synuclein levels measured in blood.

Alpha-synuclein is a protein strongly associated with Parkinson’s disease, and abnormal forms of the protein are a key feature of the disease’s pathology.

ABLi said the findings support further evaluation of the 100 mg and 200 mg doses in upcoming clinical studies, including the BASE, ABILITY and CAMPD trials.

The company also reported changes in biomarkers associated with neuroinflammation.

Treatment with 50 mg, 100 mg and 200 mg risvodetinib was associated with suppression of NLRP3 and the pro-inflammatory cytokines IL-1β and IL-18, with levels reported to fall below baseline.

The findings suggest that risvodetinib may affect inflammatory pathways associated with Parkinson’s disease, although further research will be needed to establish whether these biomarker changes result in meaningful clinical benefits for patients.

The study included longitudinal blood samples from 80 participants and cerebrospinal fluid samples from six participants, collected at baseline and following the 12-week treatment period.

The difference in sample numbers is relevant when interpreting the findings, particularly those involving cerebrospinal fluid biomarkers.

Further trials will assess clinical relevance

ABLi said the biomarker findings will inform the development of its late-stage CAMPD trial, which is planned to investigate relationships between biomarkers of disease biology and clinical outcomes.

The company is also exploring the potential use of the biomarkers as diagnostic and prognostic tools.

The next stage of development will be important in determining whether the biological changes observed with risvodetinib are associated with measurable effects on Parkinson’s disease progression and patient outcomes.

Werner said: “The outcomes indicate that the biological cascade of disease is reflected by these biomarkers and is substantially reversed in 12-weeks of once daily treatment with risvodetinib, including substantial reduction in phosphorylated alpha-synuclein, believed to be the causative agent of human PD.”

The company describes these findings as evidence of disease modification, but the current biomarker analysis does not by itself establish that risvodetinib slows or stops the clinical progression of Parkinson’s disease.

The relationship between changes in biomarkers and clinical outcomes will therefore be an important focus of future studies.

ABLi said the new data and other findings are due to be discussed with the FDA in August 2026.

The company is positioning risvodetinib as a potential disease-modifying therapy for Parkinson’s disease, with its development programme focused on targeting biological mechanisms that may contribute to disease initiation and progression.

If future trials demonstrate that the biomarker changes observed in the 201 Trial correlate with slower disease progression or improved clinical outcomes, the findings could strengthen the case for risvodetinib as a potential disease-modifying approach.

For now, the results provide evidence that treatment with risvodetinib is associated with coordinated changes across multiple biological markers linked to Parkinson’s disease, offering further data to guide the drug’s ongoing clinical development.