WaveBreak Presents New Preclinical Data at MDS 2023 Demonstrating the Efficacy of its First-in-Class, Small-Molecule Inhibitors of Toxic Oligomers for Blocking Progression of Both α-Synuclein Oligomers and Aggregates in Models of Parkinson’s Disease

BOSTON, Mass., August 30, 2023— WaveBreak announced today the presentation of new preclinical data for its first-in-class, oral inhibitors of α-synuclein oligomer generation demonstrating efficacy for blocking the progression of both α-synuclein oligomers and aggregates in cell and mouse models of Parkinson’s disease. The data were presented in a poster presentation today at the MDS International Congress of Parkinson’s Disease and Movement Disorders® taking place August 27–31 in Copenhagen.

“We are excited by the findings from these latest studies, which used state-of-the art in vitro and in vivo models and analytical techniques to measure the ability of our small-molecule candidates to inhibit the production of α-synuclein oligomers and aggregates,” said John Thomson, Chief Scientific Officer of WaveBreak. “These data add to the growing body of preclinical evidence supporting the disease-modifying profile of WaveBreak’s small-molecule inhibitors, which interrupt the molecular mechanisms at the source of toxic oligomer formation with high precision and specificity.”

Highlights of the presentation follow, and the poster is available on WaveBreak’s website: https://wavebreaktx.com/our-science/publications

Poster #1461: “Small molecule inhibitors for precise inhibition of α-synuclein oligomer generation in Parkinson’s disease (PD)”
Presenter: Andrew Cridland

Summary and key findings:
A WaveBreak oral, small-molecule inhibitor of α-synuclein oligomer generation—WTX-A—demonstrated potent reduction of α-synuclein oligomers and aggregates in cell and mouse models of Parkinson’s disease. Specifically:

  • WTX-A inhibited 90% of both primary nucleation and secondary nucleation—the molecular mechanisms at the source of α-synuclein oligomer formation—with high specificity for α-synuclein, showing no inhibition in tau and Aβ42 amyloid aggregation assays.
  • WTX-A significantly reduced α-synuclein oligomer levels in a dose-dependent manner in iPSC-derived dopaminergic cells (seeded with human fibrils), in mouse primary neuron cells (seeded with murine fibrils), and in SNCA triplication iPSC-derived cortical neuron cells.
  • In the gold-standard M83 transgenic mouse model (expressing aggregation-prone human A53T mutant, seeded with human fibrils), WTX-A reduced α-synuclein aggregates by ~70%—substantively more than measured with a different first-generation WaveBreak small molecule.

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 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, Alzheimer’s disease, and ALS. For more information, please visit: www.wavebreaktx.com.

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

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