WaveBreak Presents Human Brain Tissue Data Demonstrating Binding and Efficacy of Small Molecule WTX-607 Against Alpha-Synuclein Aggregates for Parkinson's Disease and Lewy Body Dementia
— Treatment of Parkinson's and Lewy body patient brain tissue with WTX-607 demonstrated highly specific binding to aggregates within neurons in patients' brain tissue and potent inhibition of alpha-synuclein aggregation —
— New methods developed for ex vivo testing of therapeutic candidates in brain tissue of Parkinson's and Lewy body dementia patients, with predictive potential for progression to cognitive impairment —
— Human brain tissue results cap preclinical development program demonstrating potential of WTX-607 to both inhibit disease progression and restore cognitive function in patients with Parkinson's disease and Lewy body dementia —
BOSTON, Oct. 7, 2025 /PRNewswire/ -- WaveBreak announced today the presentation of human brain tissue data demonstrating that WTX-607, a first-in-class small molecule clinical candidate for the treatment of Parkinson's disease and Lewy body dementia, binds with high selectivity to aggregates within neurons in patients' brain tissue and substantively inhibits alpha-synuclein (α-synuclein) aggregation. WaveBreak presented the data today at the International Congress of Parkinson's Disease and Movement Disorders meeting in Honolulu.
"The data we are presenting in this study is the first that demonstrates small molecule target engagement and potency for inhibiting α-synuclein aggregation seeded from patient brain tissue at therapeutically relevant drug concentrations," said co-investigator Kelvin Luk, PhD, Associate Professor of Pathology and Laboratory Medicine at the Perelman School of Medicine, University of Pennsylvania and a Scientific Advisor of WaveBreak. "The methods we developed for this study for ex vivo testing of therapeutic drug candidates using brain tissue of Parkinson's and Lewy body dementia patients has unlocked the capability to assess on-target engagement and efficacy for inhibiting α-syn aggregation as well as α-synuclein kinetics, which has predictive potential for progression to cognitive impairment."
These human brain data for WTX-607 culminate a preclinical development program that has demonstrated WTX-607:
- Interrupts α-synuclein aggregation and oligomerization across multiple cell and mouse models
- Restores cognitive function along with a 59% reduction in α-synuclein aggregates in OVX transgenic mice with established aggregate pathology
- Has a wide therapeutic margin for the projected human dose of WTX-607
Highlights of the human brain tissue data presentation follow, and the presentation is available on WaveBreak's website: https://wavebreaktx.com/our-science/publications/
"Patient-derived α-synuclein seed amplification as a tool for evaluating small molecule aggregation inhibitors for Parkinson's disease and Lewy body dementia therapeutics"
Presenter: Kelvin Luk, PhD MTR
Session OPP71: Tuesday, October 7th, 12:30-1:30 pm HST
Summary and Key Findings:
To validate on-target engagement and dose-dependent inhibition of α-synuclein aggregation by WTX-607 with disease-relevant ⍺-synuclein aggregates, the investigators adapted an ex vivo seeding assay and used an in situ binding assay involving direct staining in patient brain sections. Specifically:
- The Luk Lab at the University of Pennsylvania adapted the Seed Amplification Assay (SAA) to detect α-synuclein aggregates from paraffin-fixed human brain tissue to directly test therapeutic candidates for efficacy inhibiting aggregation of the isoforms and polymorphs of α-synuclein responsible for pathogenesis in synucleinopathy patients. The α-syn SAA is validated as a diagnostic biomarker for Parkinson's disease and related Lewy body diseases. In addition, a growing body of evidence supports SAA as a prognostic biomarker to predict cognitive impairment in Parkinson's disease based on the kinetics of aggregation, with faster kinetics correlating with a faster rate of progression to cognitive impairment.
- To measure WTX-607 on-target engagement in human brain tissue, the Luk Lab applied the drug to patient brain slices and used click chemistry to attach a dye to measure binding to α-synuclein aggregates within the brain tissues and co-stained with pS129 antibody to assess co-localization with aggregates.
The investigations demonstrated:
- Low nM concentrations of WTX-607 inhibited α-synuclein aggregation by ~90% in SAA reactions seeded with tissue-derived seeds from patients with Parkinson's disease, Lewy body dementia, or multiple system atrophy (n=10).
- Labeled WTX-607 demonstrated high levels of staining in brain tissue from patients with Lewy body dementia and Parkinson's disease (n=3) compared to healthy control subjects, with a high degree of overlap with pS129 α-synuclein aggregate labeling.
"Parkinson's disease and Lewy body dementia together affect more than 2.4 million people in the U.S., with significant unmet medical need," said Bart Henderson, CEO of WaveBreak. "These human data demonstrate that WTX-607 works within brain tissue at the site of disease pathogenesis and, in addition, stops α-synuclein aggregation with notable potency, at very low concentrations. Cumulatively, our preclinical results provide a strong foundation for the initiation of Phase 1 clinical trials that are designed not only to demonstrate safety of WTX-607 in patients with Parkinson's disease and Lewy body dementia, but also to establish biological activity at clinically relevant doses."
About WTX-607
WTX-607 is a first-in-class small molecule clinical candidate for the treatment of Parkinson's disease and Lewy body dementia that is designed to inhibit alpha-synuclein nucleation, the initiating step in the aggregation cascade that drives disease progression in synucleinopathies. By reducing the buildup of alpha-synuclein protein and oligomers in the brain, WTX-607 can potentially prevent further accumulation and spreading between cells, which may slow progression of the disease and also restore cognitive impairment by improving neuronal synaptic function.
About Parkinson's Disease
One million people in the U.S. and up to 10 million people worldwide are living with Parkinson's disease (PD). With nearly 90,000 people in the U.S. diagnosed each year, PD is the fastest-growing neurologic disease in the U.S. and is expected to affect 1.2 million people by 2030. The accumulation of aggregated α-synuclein protein in neurons is a hallmark of the disease, with progressive development of both motor symptoms and cognitive impairment. Approximately half of PD patients with normal cognition upon diagnosis will develop cognitive impairment within six years and advance to develop dementia within an additional five years. The therapeutics available today treat a subset of PD symptoms. There are no therapies that slow down or stop the clinical progression of PD.
About Lewy Body Dementia
Lewy body dementia (LBD) is the second-most-common neurodegenerative dementia in the U.S. and affects an estimated 1.4 million people. Clinical care in individuals with LBD is challenging due to complex motor, cognitive, behavioral, and autonomic symptoms. LBD is associated with higher healthcare costs, lower quality of life, and greater caregiver distress than Alzheimer's disease. The pathologic hallmark in LBD is the presence of α-synuclein–positive Lewy bodies and neurites in cortical, limbic, and brainstem regions. Lewy body formation and propagation is accompanied by progressive neurodegeneration, particularly affecting the dopaminergic and cholinergic neurons, leading to both motor and cognitive impairments. The therapeutics available today treat a subset of LBD symptoms, often with severe side effects. There are no therapies that slow down or stop the clinical progression of LBD.
About WaveBreak
WaveBreak is a biopharmaceutical company developing a new class of therapeutics for the treatment of neurodegenerative diseases that are beyond the reach of conventional drug discovery approaches. We are advancing small molecules that inhibit the disease-specific aggregation source mechanisms of neurodegenerative proteinopathies that are known biological drivers of Parkinson's disease, Lewy body dementia, and ALS. Our pipeline includes WTX-607, which is Phase-1 ready for the treatment of Parkinson's disease and Lewy body dementia, as well as the TDP-43 program focusing on small molecules for the treatment of ALS. For more information, please visit: www.WaveBreakTx.com.
Contact:
Mary Moynihan
M2Friend Biocommunications
+1 (802) 951-9600
mary@m2friend.com
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