Impact case study database

Directly following the successful completion of the IXI project, a university spinout called IXICO Ltd. (literally the Company that came from IXI) was formed in 2004 by Derek Hill and David Hawkes from the School of Biomedical Engineering and Imaging Sciences at King’s together with partners at Imperial College [S1]. IXICO’s first employee, Thomas Hartkens, transitioned from being a postdoctoral researcher on the IXI project at King’s, bringing expertise and software know-how. He was instrumental in importing key elements of the project software, which were rapidly implemented within a bespoke ISO certified quality management system. A critical feature was companywide compliance by construction (i.e. from the ground upwards), with the relevant regulations in place for electronic record-keeping in clinical trials, most notably the USA Food and Drug Administration (FDA) title 21 of the Code of Federal Regulations; Electronic Records (21 CFR, Part 11) [S11]. This technological edge helped launch the company on its path to developing a thriving business offering medical image analysis for clinical trials and healthcare products for diagnosis of dementia. Jo Hajnal, who has been at King’s since April 2012, was on IXICO’s board, acting as a scientific advisor working with the company 1 day/week until October 2013. He provided expertise on medical image protocol design, data acquisition and image analysis, sustained by his ongoing research activities [R6, S1, S2 p.38].

The table below summarises the key impact metrics for the REF2021 reporting period [S1, S3, S8, S10].

Economic impact

In October 2013, IXICO was listed on AIM, London Stock Exchange's market for small and medium size growth companies, becoming IXICO Plc [S2]. In 2020, the company which employed 78 FTE staff members reported a full year revenue of GBP9,500,000, an order book of GBP21,700,000, and a four-year compound annual growth rate of 33% [S1].

“IXICO Technologies Limited was incorporated in 2004 and spun out of King’s (which remains a shareholder), building on the ‘IXI’ project. … We are very pleased to have achieved [in 2020] GBP1,300,000 [earnings before interest, tax, depreciation, and amortisation] EBITDA profitability, more than doubling our profitability in 2019 (which was GBP500,000) and outperforming the market expectations. GBP1,300,000 EBITDA represents 14% EBITDA margin and further reflects the strengthening of IXICO as a growth medical imaging technology company.” – CEO of IXICO [S1]

Impact on the neurological drug development industry and healthcare

A key benefit of IXICO’s medical image analysis products is that they provide more definitive results requiring smaller patient cohorts than other outcome measures [S1]. IXICO has worked with 9 of the top 15 pharmaceutical companies (including Pfizer, Bristol-Myers Squibb, Biogen and Eli Lilly) as well as with many speciality biotechnology companies [S1, S7b]. It has completed multiple clinical trials (phases 1–4) and is currently responsible for data acquisition and analysis of primary endpoints on 4 late-phase pivotal clinical trials [S1, see also patient numbers quoted above]. During the reporting period, the company has expanded both the neurological conditions that its technology can be applied to and has moved into healthcare, supporting both early diagnosis and disease monitoring.

The company now has active contracts focusing on Huntington’s Disease (HD) [S6c, S7a], Parkinson’s Disease (PD), Multiple Sclerosis and rare neurological disorders, as well as its historic strength in Alzheimer’s Disease (AD) [S6a, S6b]. For example, IXICO has won 11 clinical trial contracts in HD, including a GBP10,500,000 contract for a late-phase open label study in Huntington's disease with an estimated 1000 subjects in Europe, North America and Asia enrolled during the summer of 2020 [S6d]. An important function that IXICO has provided focuses on the need to enrich clinical trials with carefully profiled subjects. Since 2013, IXICO has provided safety and eligibility reports on over 20,000 subjects [S10].

Impact on health regulatory policy

IXICO’s image analysis and data management/curation technologies are playing a key role in a number of public-private consortia, that are gathering the evidence base needed for policy changes in relation to the assessment of key neurological diseases and development of new treatments for them [S9]. For example, IXICO played a leading role in the submission to European regulators to qualify low hippocampal volume as a biomarker that can provide more precise and effective assessment of patients to enrich trials of treatments for AD [S4]. This submission, which was supported by the US Food and Drug Administration (US FDA) [S5], incorporates key data obtained using a core IXICO image analysis technology.

IXICO’s role in some of the key consortia is as follows:

• The European Prevention of Alzheimer’s Dementia (EPAD) – “the largest ever public-private partnership in Alzheimer’s Disease research”, which has built an adaptive clinical trials platform to enable pharma companies to efficiently evaluate the safety and effectiveness of their medicines in patients prior to onset of symptoms by utilising adaptive clinical trial approaches. IXICO provided the technology to collect, manage, and analyse magnetic resonance imaging (MRI) scans (pan European register of 0.5m subjects, >1,500 subjects in database in 2020) [S7c].

“IXICO were a pivotal partner in the EPAD programme providing excellent service throughout the 6 years to our sites and central team. Not only did they provide valued operational support they also contributed in a crucial way to design aspects of EPAD in terms of data flows and imaging science. The data from EPAD will make a huge difference to our understanding of Alzheimer’s Disease in its early stages and IXICO has been pivotal in providing the best quality and relevant imaging data to that effort.” – Professor Craig Ritchie, EPAD Principal Investigator, Chair of the Psychiatry of Ageing and Director of the Centre for Dementia Prevention at the University of Edinburgh [S8 p. 16]

• Critical Path Institute initiatives: Huntington’s Disease Regulatory Science Consortium (HD-RSC), a global initiative aiming to improve the regulatory path for new HD therapies, and Critical Path for Parkinson’s (CPP) Disease, which brings together the world’s largest pharmaceutical companies advancing novel promising treatments for people living with Parkinson’s. IXICO is contributing towards FDA clearance of imaging biomarkers to support the development and approval of new medicines to treat HD and PD. Achieving regulatory approval for imaging biomarkers for these diseases is a critical step for conducting more efficient clinical trials using smaller cohorts and is therefore a gatekeeper for maximising societal impact.

In words of Diane Stephenson, Executive Director, Critical Path for Parkinson’s Consortium (‘CPP’), Critical Path Institute: “We are delighted to continue our collaboration with the IXICO team in two further Critical Path consortia, the Critical Path for Parkinson’s (‘CPP’) consortium and the HD Regulatory Science Consortium (‘HD-RSC’). In these consortia, our aims are to develop new, regulatory-endorsed drug development tools that will improve the clinical trial process and regulatory path for emerging therapies for HD and PD and ultimately de-risk the development of new treatments that are urgently needed. IXICO’s expertise in data analysis and regulatory qualification is supporting our efforts to develop the regulatory path to qualify new imaging and digital biomarkers for use in clinical trials.” [S10]

• Amyloid Imaging for Prevention of Alzheimer’s Dementia (AMYPAD) – IXICO provided the technology to collect, manage, and analyse MRI and positron emission tomography (PET) scans for evaluating the diagnostic value of amyloid imaging in Alzheimer’s Disease [S6e]. The project succeeded in recruiting 844 out of the planned 900 participants despite the negative impact of COVID-19. These studies are ongoing, but large cohort data is already available, providing a massive community resource [S7d).

The societal impact of IXICO’s work is significant. Its technology has been, and continues to be, helping large pharmaceutical companies develop treatments for neurological diseases with major unmet medical needs. IXICO has provided automated analysis of over 100,000 images as part of clinical trials, its technology is now enabling a new generation of clinical trials for neurodegenerative diseases such as Alzheimer’s Disease where patients early in their disease pathway can be identified and recruited for better understanding of pharmacological interventions and this has contributed to health policy and regulation.