BOSTON, Mass., March 8, 2024— WaveBreak announced today the presentation of new preclinical data for WTX-607, the company’s first-in-class small-molecule inhibitor of α-synuclein oligomer generation, demonstrating efficacy for targeting and inhibiting the source mechanisms underlying the formation of α-synuclein oligomers and aggregates with high precision and specificity in cell and mouse models of Parkinson’s disease (PD) and Lewy body dementia (LBD). Oligomeric forms of the protein, α-synuclein, form aggregates known as Lewy bodies that underlie the onset and progression of synucleinopathy diseases such as PD and LBD. WaveBreak’s clinical candidate, WTX-607, disrupts these mechanisms with precision and is a potential disease-modifying therapeutic. The data will be presented in a poster presentation on March 8 and 9 at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD 2024) taking place from March 5–9 in Lisbon, Portugal.

“More than 1 million people in the U.S. are living with Parkinson’s disease, and 1.4 million people are affected by Lewy Body Dementia, and there are no approved drugs to slow or stop the progression of these devastating neurodegenerative diseases,” said Bart Henderson, CEO of WaveBreak. “We are excited about the promising preclinical data for WTX-607 demonstrating inhibition of α-synuclein oligomer generation and aggregation that is at the core of both these diseases. We have recently completed pre-IND development for WTX-607, and we are now preparing to initiate a biomarker-driven Phase 1 clinical development program.”

Highlights of the presentation follow, and the poster is available on WaveBreak’s website:

Poster #0528 (Shift 2, March 8–9): “Small molecule inhibitors for precise inhibition of α-synuclein oligomer generation in Parkinson’s disease”
Presenter: Kelvin Luk

Summary and key findings:
WTX-607, WaveBreak’s lead small-molecule clinical candidate for the treatment of Parkinson’s disease (PD) and Lewy body dementia (LBD), inhibits the source of α-synuclein oligomer and aggregate generation in mouse models of synucleinopathies, including PD and LBD, demonstrating the potential for clinical development as a disease-modifying therapeutic for these indications. Specifically, WTX-607:

  • Exhibits dual pharmacology and excellent PK properties, precisely inhibiting the molecular mechanisms at the source of α-synuclein oligomer formation—WTX-607 inhibited the primary nucleation process by 93% and the secondary nucleation process by 95%, with high specificity for α-synuclein, and showing no inhibition in tau and Aβ42 amyloid aggregation assays.
  • Delivers efficacy in the gold-standard M83 transgenic mouse model (which expresses aggregation-prone human A53T mutant, seeded with human fibrils), significantly reducing α-synuclein oligomers by at least 35%.
  • Significantly reduces pS129 α-synuclein aggregate levels in the line 61 transgenic mouse model, which overexpresses human α-synuclein, by 50%-75% in the cortex and hippocampus, respectively.

WaveBreak Technology Platform
The relatively recent understanding that oligomers resulting from errant protein folding are the toxic entities directly responsible for neurotoxicity in Parkinson’s disease, Alzheimer’s disease, and ALS has defined a new approach to treating a central molecular cause of neurodegeneration. Yet characterizing and suppressing these fleeting protein intermediates is one of the most challenging problems in drug discovery for scientists working with protein assembly reactions: Because these protein forms are highly transient, they cannot simply be put in a bottle and analyzed in isolation, which makes them difficult to target using conventional single-target drug discovery approaches. Targeting the complex, highly interconnected network of interactions that lead to oligomer formation in neurodegenerative diseases requires a fundamentally different approach to measure, assay, and analyze the proteins during their evolving assembly and disassembly process, from their formation to their disappearance. WaveBreak’s technology platform enables analysis of the inhibition of the source mechanisms that produce oligomer intermediates in complex disease processes. We are leveraging this approach to discover and develop small-molecule therapeutics that inhibit oligomer generation at the source of these protein aggregation assembly pathways with specificity and precision.

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 and non-motor symptoms. The therapeutics available today treat a subset of PD symptoms, and there are currently no treatments available that are disease-modifying and slow the 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, and there are currently no treatments available that are disease-modifying and slow the progression of LBD.

About WaveBreak
WaveBreak is a biopharmaceutical company transforming drug discovery for neurodegenerative diseases, targeting the fleeting protein intermediates central to many disease pathways that are beyond the reach of conventional drug discovery approaches. We have built a unique drug discovery platform to target the transient protein intermediates—the oligomers—in these disease pathways, to interrupt the molecular mechanisms that are the source of oligomer generation with small-molecule therapeutics. We are focusing this platform first on some of the greatest unmet medical needs of our time: Parkinson’s disease, Lewy body dementia, Alzheimer’s disease, and ALS. For more information, please visit:

Mary Moynihan
M2Friend Biocommunications
+1 (802) 951-9600

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