Community Research and Development Information Service - CORDIS

H2020

tagMDR Report Summary

Project ID: 736516

Periodic Reporting for period 1 - tagMDR (Identification of Multidrug Resistance for Chemotherapy Guidance in Cancer Using a Lab-on-a-chip Platform)

Reporting period: 2016-08-01 to 2016-12-31

Summary of the context and overall objectives of the project

Globally, nearly 1 in 6 deaths is due to cancer. In 2012, there were an estimated 14.1 million new cancer cases worldwide. In the same year, 8.2 million people died from cancer and there were a further 32.5 million individuals living with cancer. The number of new cases is expected to rise by 70% over the next 2 decades. Therefore, cancer exacts a devastating economic burden on health systems around the world, which can be measured in Disability Adjusted Life years (DALYs). In 2013, cancer caused 196.3 million DALYs worldwide. In 2012 in the EU there were an estimated 2.635 million cancer cases with 1.206 million in women and 1.430 million in men. This figure rose by 30% since 1995. The estimated cancer mortality was 1.3 million deaths (570,300 for women, 726,500 for men) in 2013, which was 13 % higher than in 1995. Cancer deaths contribute a great deal to the loss of earning potential and production for the EU. In 2014, this figure stood at €48.6 billion.

Traditionally, cancer diagnosis requires surgical biopsies which are invasive as they require the extraction of tissue samples from the tumour. This process is also expensive, lengthy, painful, and carries significant risk of infection. There may be instances where the cells aren´t accessible due to the location of the tumour. Due to these limitations, in ~20%-50% of cases there is insufficient tumour material for conclusive analysis. Furthermore, result detection may miss distant heterogeneous tumour cells. In many cases, treatments kill the identified clone, the clones that are missed could continue to spread and lead to recurrence. Therefore, there is a huge opportunity for non-invasive techniques in biopsies.

tagCTC only involves blood draw. This process allows metastasis to be detected sooner and more accurately than traditional surgical biopsies. In addition, liquid biopsy has a high positive predictive value; thus a positive result from a validated liquid biopsy test could lead directly to a clinician’s confidence that a targeted therapy is likely to benefit the patient. The condition of patients can also be monitored better and more closely which has opened the door for more personalised and targeted treatments. The technology could potentially revolutionise cancer treatment and move care from “an educated guess,” to accurately identifying targeted treatment therapies and then monitoring tumour response in real-time. Furthermore, liquid biopsies could potentially detect early cancer as well as recurrence before significant tumour formation or metastasis, a substantial improvement to current care processes.

However, there are limitations with current CTC detection technologies. CellSearch® by Janssen is the only FDA approved device and is widely considered the gold standard. However, it is not the ideal technology: It is not label-free which has implications for downstream analysis, there is substantial cell loss during preparation which has implication for accurate diagnostics, it requires lengthy sample preparation, and can be quite costly – in the US it cost around USD150 to USD300 per test.

tagCTC will provide a cost-effective solution with better performance such as higher sensitivity; number of CTCs captured; purity of CTCs, label-free; minimal pre-processing required, and a shorter testing time. These improvements will undoubtedly lead to quicker mainstream adoption which will result in critical advancements in companion diagnostics, personalised and precision treatment such as in drug selection, more accurate diagnosis/screening device, and accelerated drug development. All of these will result in huge benefits for cancer patients across the EU.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Overall objective of feasibility study is to elaborate the 10-year business plan for tagMDR. Specific objectives are:
• Identifying the possible business partners and competitors
• Establishing partner network for the clinical data collection
• Handling the ethical issues, safety, and regulatory requirements
• Performing the freedom-to-operate analysis to secure the market position of tagMDR
• Elaborating the market segmentation map and business model

During internal discussions, and with our collaborators and key partners, the potential of targeting the CTC detection & enrichment was brought up as an alternative and possibly more attractive avenue. As such, an executive decision was made to include CTC in our feasibility study. As such, there was a period of groundwork to establish which application, MDR or CTC, was more feasible before committing to building a 10-year plan.

The additional steps were tech assessment and market analysis to understand if it was possible to adapt the technology we had built from MDR to CTC, and to understand which market had a larger opportunity as well as impact.

The tech assessment was conducted internally. We identified that our MEMS-based core technology could also be tailored for other cancer cell detection applications besides MDR. Following on the tech validation, we conducted a market study to validate which application was more feasible to pursue. The market study was done via a market survey in conjunction with Yole Développement – a marketing and strategy consultancy, in the major markets of EU and US. In total, 104 key personnel from 79 major stakeholders in the global oncology market were contacted. Most interviewees, 10 of 17 companies, signalled strong and immediate interest in tagCTC whereas there was no strong interest from any of the 17 companies interviewed for tagMDR.

The outcome of our extensive technology and market analyses demonstrates that tagCTC holds significantly greater impact and has a more promising market opportunity. There was strong interest from multiple stakeholders who were already keenly aware of the value that tagCTC can bring – this indicates potentially minimal work and time to convert interested parties to paying customers. Furthermore, the market opportunity of the CTC detection/liquid biopsy is at least 10 times bigger than microfluidics market which tagMDR was targeting. Using 2015 estimates the liquid biopsy market was worth USD28.6 B in the US alone compared to USD3.1 B for the microfluidics market worldwide. We also conducted an examination of competing technologies and compared tagCTC.

During our market analysis we able to fulfil the following two objectives:

• Identifying the possible business partners and competitors
METU MEMS Centre – MEMS fabrication
Designnobis – Industrial & mechanical design
Mikro Tasarim Inc – ASIC design
Hacettepe University Hospital – Clinical studies
Yalçıner Patent Consultancy – Trademarking, IPR
AYS Consultancy – ISO certification & CE mark

• Establishing partner network for the clinical data collection
CHU Lyon (France)
IC-HCL (France)
Novelcheck (Germany)

• Handling the ethical issues, safety, and regulatory requirements
MikroBiyo has received ethical approval from Hacettepe University Hospital. We have identified with AYS Consultancy the necessary regulatory requirements which include ISO certification and CE marking for EU, and FDA approval for the eventual US market. In fact, MikroBiyo has started working on ISO 13485 & 9001. Additionally, MikroBiyo is aware of impending changes to medical device regulations which we will continue to monitor.

We also looked at potential market risks and identified contingencies to overcome these barriers, which includes: Low adoption from broader oncology market, High competition & Intellectual Property, Payment/Reimbursement, and Regulation.

• Performing the freedom-to-operate analysis to secure the market position of tagCTC (changed from tagMDR)
A freedom-to-operate analysis was conducted to ensure that there were no IP infringements in the EU and US markets. There were 3 similar patents, 2 have been granted in the US. However, these patents do not directly refer to the use of MEMS technology to detect, isolate, enumerate, and enrich CTCs, or a combination of size and immunoaffinity techniques. Therefore, the conclusion of the FTO analysis indicates that there are no public patents, which might prevent the patentability and commercial exploitation of the tagCTC in the EU and US. However, MikroBiyo will actively monitor the freedom to operate landscape in key markets - especially since liquid biopsies and CTC detection are currently and for the foreseeable future will be an intense field of research.

• Elaborating the market segmentation map and business model
The next was to develop the work programme to map out the work required to go-to-market by the end of the 3-year SME Instrument Phase II project period. We developed a total of 7 work packages: Project mgt; Optimisation & mfg of analysis unit prototype; Optimisation & integration of MEMS chip & hybrid device; Optimisation and manufacturing of disposable polymer cartridges; Clinical studies; Product certification; and commercialisation, and Communication, Dissemination, and Exploitation.

MikroBiyo expects the interest in tagCTC to stem from:
• Academic & research centres
• Reference laboratories
• Clinical end-users such as hospitals & clinics
• Diagnostic/biotechnology companies
• Pharmaceutical companies, especially those with companion diagnostic products
• Other research end users such as public health laboratories, pathology laboratories, and small molecular laboratories

We have also developed our business model which will occur over 3 phases over a 10-year period. The first phase will occur within the 3-year phase 2 funding period. The target market will be cancer research organisations: Academic & research centres and Reference laboratories in the EU. tagCTC will use the following strategy to secure its market position:

• Focus on translational research with key opinion leaders (KOLs) that include major EU, US and international cancer centres to develop clinical application, undertake patient studies, and gain support from KOLs.
• Obtain CE marking & ISO certification
• KOL reporting on clinical applications supported by pilot studies
• Transition KOLs to first customers
• Patient studies to support clinical applications
• FDA authorisation
• Go to market via commercial collaborations with major biotechnology and pharmaceutical companies
• Enter mass production and roll out of commercial sales channels

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

MikroBiyo will bring to market an innovative circulatory tumour cell detection and enrichment system called tagCTC. It will employ a unique hybrid approach that combines: size-based enrichment + antibody binding + impendimetric detection. At the core of MikroBiyo´s novel technique is a CTC hybrid chip which is comprised of a microelectromechanical systems (MEMS) chip and features 3 key technologies: (1) a hydrodynamic enrichment unit (HEU) which uses size-based separation via spiral channels to enrich the CTCs; (2) a CTC capture unit which uses antibody binding; and (3) an electronic counting unit using the impedance spectroscopy (IS) technique.

tagCTC will be a more cost-effective solution with better performance such as higher sensitivity; number of CTCs captured; purity of CTCs, label-free; minimal pre-processing required, and a shorter testing time. tagCTC will have tremendous utility in cancer research as it can aid researchers in deciphering the complex biology of cancer metastasis. Besides the applications in cancer research, the detection and analysis of CTCs has enormous potential in cancer screening for early detection diagnosis, cancer profiling, in the development of personalised treatment, monitoring of treatment, and assessing possible recurrence. Each of these possible applications have huge market valuations. In the US, early cancer screening has the largest estimated valuation at $15.0B, followed by recurrence monitoring at $6.9B; treatment monitoring at $5.0B; and therapy selection which is related to cancer profiling is estimated to be worth $1.7B.

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