Crossbeta Biosciences

Crossbeta Biosciences

Crossbeta Biosciences is a Dutch biotech company spun-out from the Utrecht University Medical
Center. Our activities are focused on high impact diseases caused by misfolded proteins, such as
Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, ALS and Diabetes Type 2.
Based on Crossbeta’s proprietary technology, the company has three main programs:
• Development of drug discovery platforms for misfolded protein diseases
• Development of highly disease-specific antibodies and biomarker assays
• Drug development program for oral treatment of Alzheimer’s Disease
The basis for Crossbeta’s program portfolio is a strong technology platform centered around
a revolutionary stabilization technology, which solves the instability problems of oligomers.
Oligomers are nowadays considered as the toxic precursor of amyloid deposits, such as plaque,
and are responsible for the detrimental effects observed in the progression of misfolded protein
diseases. Crossbeta’s stable oligomers preserve their pathological properties and therefore are
a unique candidate for use as target in drug discovery programs and for the development of
biomarker assays which can be broadly applied, even before symptoms arise.

Misfolded protein diseases: treatment options and
biomarker requirements

Alzheimer’s and Parkinson’s disease as well as other misfolded protein diseases are found to be
related to toxic oligomers. At present, most of these diseases lack curative medication and are
becoming a healthcare problem with a huge social and economic impact.
A common feature of misfolded protein diseases is that it involves proteins that have a tendency
to stick together when they become redundant, ultimately resulting in insoluble aggregates, e.g. plaque in the brain of Alzheimer patients.
It was long thought that plaque was the cause of disease, but nowadays there is scientific insight that smaller assemblies, so-called oligomers, are responsible for the detrimental effects that occur in the disease process. Efforts to find a cure for these diseases are typically aimed at either preventing formation of misfolded proteins, inhibiting aggregation or enhancing removal of protein aggregates. Unfortunately, this
tends to go hand-in-hand with unacceptable side effects or simply lacks efficacy in humans.
Crossbeta’s technology offers a new and unique treatment option that involves targeted neutralization of the toxic oligomers.
In contrast to the traditional approach of receptor-targeting, the oligomer-targeted approach aims at neutralizing the toxic
oligomers and leaves the physiologically important function of the receptor and its downstream pathways unaltered.

Crossbeta drug discovery platforms

Crossbeta’s unique technology to stabilize oligomers has application for a whole spectrum of misfolded protein diseases, comprising Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, ALS and Diabetes type 2. Crossbeta already managed to stabilize oligomers of Aβ1-42, pGluAβ3-42, alphasynuclein and tau. High-throughput screening options can be made available at the partner’s facilities or at specialized contract research organizations. The stable oligomers also have utility for inducing pathologically relevant effects in in vitro assays and in vivo models for reliable and efficient evaluation and optimization of compounds.

Crossbeta’s antibodies and biomarker assays

Crossbeta’s stable oligomers have excellent utility for raising and selecting high affinity/high selectivity oligomer-specific antibodies ideally suited for the development of the required ultrasensitive biomarker assays. The combination with Crossbeta’s stable oligomers as calibrator and reference standard, with proven shelf-life in excess of 12 months, makes a complete set of key assay components. The Crossbeta biomarker assets provide a perfect fit with the emerging trend to move therapeutic intervention in Alzheimer’s and other degenerative diseases to early stages, where no clinical symptoms are apparent yet.

Crossbeta’s proprietary Alzheimer program

Crossbeta’s Alzheimer program and in particular Crossbeta’s compound CBB68 has already served the purpose as flagship by showing, via established proof of concept, that Crossbeta’s stable oligomer platforms can effectively identify novel drug compounds that neutralize oligomertoxicity. Crossbeta’s Alzheimer program is open for partnering. At present, the range of stable oligomers includes Aβ1-42, pGluAβ3-42, alpha-synuclein and tau, which allows Crossbeta to expand its own drug discovery portfolio across multiple indications.

 

 

Why has this clever approach devised by Crossbeta not been tried by others? The answer is that oligomers are highly instable,
making them ‘moving targets’ and very difficult to work with, let alone allowing to use them as target for drug discovery.
Crossbeta solved this problem. Crossbeta successfully managed to overcome the instability problem of oligomers by developing a revolutionary stabilization technology that preserves the pathological properties. Despite many attempts, so far no-one else has been successful in achieving this. The value of Crossbeta’s stabilized oligomers is underscored by the interest from industrial and academic parties.In Crossbeta’s Alzheimer program these unique and proprietary stabilized oligomers have been successfully applied for drug discovery of small molecules. Crossbeta has screened a 100,000 compounds and after subsequent MedChem optimization, resulting compound CBB68 was shown to be effective in an Alzheimer’s disease animal model, thus demonstrating proof of concept. The most effective way to treat Alzheimer’s and other degenerative diseases will likely demand to start intervention before clinical symptoms appear. This implies the need for reliable and affordable diagnostic tools to initiate and monitor treatment. Crossbeta has access to the key components needed for developing oligomer-specific biomarker assays: the stable oligomers enable to raise and optimize oligomer-specific antibodies and are ideally suited for use as reference standard. The above applications would not be feasible without Crossbeta’s stable, biopathologically functional oligomers.

 

Crossbeta Biosciences BV, Padualaan 8, 3584CH Utrecht
Tel.: +31 30 253 2483
http://www.crossbeta.com