2021-09-001 + 2019-05-003 - SYNUCLEINOPATHIES DIAGNOSIS2 - IN VITRO METHOD FOR THE DIAGNOSIS OF SYNUCLEINOPATHIES

SYNUCLEINOPATHIES DIAGNOSIS2

2021-09-001 + 2019-05-003

In vitro method for the specific diagnosis of synucleinopathies and/or for the differential diagnosis of synucleinopathies versus Alzheimer disease (AD). Determining miRNAs as promising biomarkers for the diagnosis of neurodegenerative diseases

Easily accessible and minimally invasive: from blood samples Quick, non-expensive and differential diagnosis of DLB vs AD Easy standardization and low-cost analysis Allows disease confirmation: high accuracy and less uncertainty Personalized diagnosis and treatment Shortens time to diagnosis Correct patient stratification for Clinical Trials

Our IVD asset is an accurate, non-expensive and widely available way to diagnose DLB. This ensures that all dementia patients will have access to an accurate diagnostic test (territorial equity). Moreover, a correct DLB diagnosis will improve the clinical management of these patients, helping clinicians to provide the most appropriate treatment for them. This will lead to fewer adverse events in true DLBs currently misdiagnosed as AD patients due to the treatment with neuroleptics that will in turn lead to cost-savings for the healthcare system. A prodromal DLB diagnosis will also enable patients to receive early disease-specific therapy, and to be included in clinical trials aiming at delaying or slowing down the disease. Thus, it will be beneficial both to patients and R&D companies. Lastly, but most important, a prodromal or early DLB diagnosis will provide relief for both clinicians and patients and their families by shortening time to diagnosis and removing uncertainty.

Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia after Alzheimer’s disease (AD) with an incidencearound 1/1,000 persons per year in the older population and is expected to increase due to the aging of the world population. Currently, DLB diagnostic relies on clinical criteria for the evaluation of patients, which shows low sensitivity, and the only available technique is an invasive radio-tracer-based, expensive and not widely accessible technology as it requires highly-advanced equipment. As a result, the clinical diagnosis of DLB can take to 3 years from the symptoms onset, and is very often misdiagnosed as AD and occasionally also as PD. Lewy-Dx offers a clinical test, based on platelet miRNAs, with high capacity to differentiate dementia with Lewy bodies from Alzheimer’s disease. With the implementation of Lewy-Dx in the clinical practice we aim to solve the current unmet need in DLB diagnosis and management by offering a DLB-specific, non-invasive and widely-accessible diagnostic test.

55000000

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The business model proposed for this project entails the creation of a spin-off to clinically validate the test and then licensing them out. This risk affordable strategy would provide a good balance between the overall investment and the return. Moreover, there are several companies that may be able to assist with the development of the IVD test such as Roche Diagnostics, Biokit-Werfen, Abbot and BioArctic AB, among others.

Currently, doctors diagnose DLB by ruling out other conditions that may cause similar signs and symptoms. Up to date there are no biomarkers or molecular diagnostic tools for either the diagnosis of DLB or its differential diagnosis versus AD.

Our market focuses on hospitals (with neurology service) and pharmaceutics

This year we will require an investment of approximately 320K €, where the main investment areas include research and development costs, personnel costs, and costs related to prototype design and development. In the following three years, the clinical trials will be started, sequentially but overlapping, for the DLB diagnostic asset to reach commercial stage in 2025. For the asset to reach the market, a further investment of 4.870.800 € will be needed. This investment will include the cost of the CRO and the clinical trials in the US and EU, patent and regulatory support, advisory board, value dossiers, and other costs related to personnel, sales and marketing, communications, and administration.

Collaboration, financing

In the following three years, the clinical trials will be started, sequentially but overlapping, for the DLB diagnostic asset to reach commercial stage in 2025. For the asset to reach the market, a further investment of 4.870.800 € will be needed. This investment will include the cost of the CRO and the clinical trials in the US and EU, patent and regulatory support, advisory board, value dossiers, and other costs related to personnel, sales and marketing, communications, and administration.

We propose the use of a disruptive diagnostic biomarker as an alternative to DATScan imaging. Our asset is an IVD test based on a 7-miRNA platelet signature that can be measured from a blood sample. Our test represents the first molecular tool, able to aid clinicians DLB diagnosis and assessment of its progression. Our IVD test provides an accurate DLB diagnosis through a minimally invasive, non-expensive, fast, and simple blood test. Our asset only requires a blood sample to be processed easily with basic laboratory equipment available in most hospitals. Therefore, the implementation of our asset in the clinical practice will substantially improve the diagnosis and speed-up the therapeutic management of patients suffering from DLB.

One entry barrier for our technology could be its dependency on one specific PCR platform. So far, the results have been obtained using miRCURY LNA miRNA PCR Panel from Qiagen. This is a very common platform at hospital diagnostic laboratories, but some hospitals may use other similar platforms. Regulatory environment and industrial scale-up are two additional entry barriers for the project. Regarding regulatory requirements, difficulties could be expected when trying to obtain the CE marking.

The project started in 2018 with the discovery and first validation of the biomarker signature. Since then, the development of the asset has included a preliminary study confirming the biomarker diagnostic potential. Moreover, preliminary business viability and asset opportunity validation have been assessed. The next technical and clinical steps while transferring the project to a spin-off will include: 1)Optimize the platelet obtenting and processing protocol; 2) Design and develop the IVD test prototype and 3) Design clinical trials to further validate our biomarker signature. Meanwhile, pre-marketing actions including business development plan, regulatory roadmap and commercial contacts will also be carried out. The spin-off will be created to further develop the technology into later TRL stages and we plan to transfer the technology from the spin-off to an IVD licensee within the next 5 years.

Patents IN VITRO METHOD FOR THE DIAGNOSIS OF SYNUCLEINOPATHIES Patent Prioritària Europea - EP18382540.5 - 19/07/2018 - Abandonada EuroPCT - PCT/EP2019/069570 - 19/07/2019: • EP19745075.2 Under examination 6th annuity 31/07/2024 • 17/260,882(US) Under examination, non-final office action 08/04/2024 METHOD FOR IN VITRO DIAGNOSIS OF DEMENTIA WITH LEWY BODIES USING ALPHASYNUCLEIN GENE TRANSCRIPTS Patent Prioritària Europea - EP15382241.6 - 08/05/2015 - Abandonada EuroPCT - PCT/EP2016/060177- 06/05/2016 EP3294903 B1 - 18/09/2019 9ª anualitat

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Patents: WO2020016437A1 ; PCT/EP2019/069570 - Date: Jan 23rd, 2020 Status: Granted URL: https://patents.google.com/patent/WO2020016437A1/en

In vitro method for the specific diagnosis of synucleinopathies and/or for the differential diagnosis of synucleinopathies versus Alzheimer disease (AD). Determining miRNAs as promising biomarkers for the diagnosis of neurodegenerative diseases