Nuroflux

Acute ischemic stroke results from sudden blockage of blood flow in the brain and accounts for 87% of all stroke cases. It is a critical illness with high risks of death and disability. It is estimated that more than 795,000 United States residents suffer from a stroke annually, with 30% of these occurring in individuals of working age. Globally, it is estimated that 15 million people suffer a stroke, with a 33% mortality rate and another 33% being left permanently disabled. Accounting for direct financial cost and losses in wellbeing, stroke-related costs in the United States amounted to $US53 billion in 2018.

Neuroimaging is the standard method to diagnose stroke, and is performed as soon as possible following symptom onset to determine a patient’s eligibility for reperfusion therapy with lytic drugs or endovascular mechanical clot retrieval. In the acute phase, patients are also at high-risk of early neurological deterioration, which occurs in up to 40% of all acute ischaemic stroke patients. Standard of care involves repeat brain imaging at 24-hour intervals. In the absence of mechanisms to monitor objective markers of stroke progression (such as brain activity and blood flow), patient outcomes during this 24-hour timeframe are determined by routine nursing assessments. These are subjective, intensive (e.g. every 15 minutes for the first two hours), operationally burdensome, distressing for patients and ineffective in sedated or unconscious patients. There is currently no objective, long-term mechanism available for the monitoring of these key physiological parameters to indicate patient status (e.g. treatment response, deterioration).

Nuroflux have developed a safe, low-cost, comfortable, non-invasive, wearable device that utilises a multi-modal system (combining ECG and EEG inputs) to provide simultaneous and continuous monitoring of blood flow and electrical activity in the brain. This provides an opportunity for routine monitoring of patients with acute ischaemic stroke in low resource environments; to confirm locality and severity of stroke events, allow for rapid detection and intervention, as well as facilitate follow-on treatment of complications; to ultimately improve patient outcomes. 

A prototype device was implemented in a validation study (see below for link) to assess the feasibility of nuroflux’s proprietary method and measure – Electrical Brain Perfusion Index (EBPi) – to monitor changes in brain blood flow in 20 healthy volunteers who completed standard tasks: breath holding, hyperventilation, verbal fluency cognitive task, and aerobic exercise. EBPi was compared to transcranial Doppler ultrasound measures of cerebral blood flow (the current gold standard) captured pre- and post-task, and post-recovery. EBPi showed similar changes and significant positive correlation with transcranial Doppler ultrasound (r=0.27, p<0.01), providing proof-of-concept and validity of the method to continuously monitor cerebral blood flow as well as capture previously reported changes in EEG. 

In a second validation study, EBPi is being retrospectively implemented using clinical ECG/EEG data in ~20 subjects from Westmead Hospital to determine the degree of correlation between EBPi and cerebral blood flow during seizures. Increases in brain blood flow are expected to be highest at scalp electrodes adjacent to seizure location. This highlights the versatility of our device's application to a range of disease indications and the provision of multiple value propositions.

A clinical safety study in a cohort of stroke patients (18 in total) has demonstrated safety of the device and integration into clinical workflows with minimal disruption.

A clinical efficacy study (50-patient, single site) has recently enrolled its first anterior-circulation stroke patient and is aiming to ascertain whether the device can identify stroke location and severity, monitor patient response to treatment and detect secondary deterioration.

We envisage that EBPi data will be displayed in real-time for healthcare staff to observe, and to inform their decision-making. Alert algorithms will sound upon detection of favorable or unfavorable measures of brain activity and blood flow (i.e. sudden restriction in latter may indicate recurrent stroke). 

It is anticipated, in low resource settings where brain scanning technologies are not available, that the nuroflux device can provide the first objective clinical measurement to inform stroke patient management. Coupled with the fact that the standard of care treatment, tPA, is relatively inexpensive ($AU55.61 per patient), our innovation represents a real opportunity to revolutionise stroke patient management and outcomes in low- to middle-income nations.

The following stakeholder groups stand to benefit from deployment of our medical device solution:

1) Stroke patients and their families. In addition to the global metrics supplied above, in 2020, Australia alone witnessed 27,500 individuals suffer a stroke, making the collective total of 450,000 survivors living in the community. Approximately 30% of stroke events occur in individuals of working age. In addition to the patient detriment, per annum, stroke is estimated to cost $6.2 billion in direct financial costs and a further $26.0 billion in wellbeing loss and early mortality (Deloitte, 2020a).

Real-time detection of deterioration will allow: 1) faster intervention, 2) reduced brain damage and need for intensive rehabilitation, and 3) reduced number of CT scans and radiation exposure if available; to improve patient quality of life. Susceptible patients being monitored continuously will provide peace of mind, knowing that treatment outcomes and/or further deterioration will be rapidly and accurately detected.

2) Stroke clinicians and nurses. Specialists in neurology are responsible for the treatment and management of patients.

Access to objective and actionable clinical data will improve treatment management, and reduce the need for subjective observations. The burden of performing subjective clinical neurological assessments on patients (especially during the night) to determine patient progression will be significantly reduced.

3) Hospitals. Responsible for providing the resources and environment to treat severe ailments (including stroke). Our device will translate into better quality service and improved patient outcomes. This, and improved clinical staff efficiency, resulting in rapid intervention in deterioration events, will result in shorter hospital stay times and higher patient throughput.

4) Paramedics and general practice healthcare professionals. Typically the first-line response in the community, and often triage patients to hospital if required (e.g. in the event of a suspected stroke).

Our device will aid stroke diagnosis and triage of patients to most appropriate hospital, or allow for treatment on-site in the absence of resources. Provision of objective clinical information in an otherwise blind situation will assist decision-making dramatically.

5) Governments. Provide funding and overarching governance to the public health care system. Any cost-effective mechanisms with which to improve patient outcomes and reduce financial burden will be viewed favorably.

Dr. David Cardoso is a medical scientist by training, having undertaken a research doctorate at University of Sydney and Children’s Medical Research Institute investigating the development of novel drug candidates for epilepsy, where two compounds discovered formed pipelines for a spin-out sponsored by Takeda Pharmaceuticals. Following graduation, he shifted focus toward the business world, holding project management and commercialisation positions with the medical research ecosystem, all while studying an MBA. As the Co-Founder of Nuroflux, he is responsible for operations, legal, business development, commercial and scientific strategy, and funding acquisition (grants and investment) globally. He is from a socioeconomically disadvantaged background (having been born and raised well below the Australian poverty line), and actively mentors for entrepreneurship accelerators aimed at traditionally underserved populations (e.g. Remarkable, disability technology; Catalysr, first-generation immigrants). This provides a unique perspective and motivation towards leveraging entrepreneurship for the betterment of the human condition, especially with respect to underserved communities. Given his physical presence in Cambridge, Massachusetts, and track record of success in scientific project development and execution, he has been identified as the Team Lead for this application.

Dr. Samuel van Bohemen developed the proprietary technology and algorithms underpinning the Nuroflux value proposition during his PhD (Biomedical Engineering) at the University of Sydney, as well as having received First-Class Honours in Neuroscience from the University of Otago. Since graduation, he has been working diligently to facilitate the technical and clinical development of the Nuroflux device.

Strategic Partnership with The George Institute for Global Health: A close collaboration between the two organisations has facilitated: the acquisition of clinical efficacy evidence for the Nuroflux device, attainment of meaningful clinical advisory in stroke (and other neurological disorder) patient management, as well as how best to deploy the solution in underserved communities.

Nuroflux has developed a first-generation device that is currently the subject of a clinical efficacy study in a 50-patient, single-site study at Royal Prince Alfred Hospital - metrics pertaining to sensitivity and specificity of stroke location and severity, patient response to treatment and secondary deterioration events are anticipated to be elucidated following completion. To facilitate clinical and scientific development, Nuroflux has raised approximately $US300,000 in equity financing to date.

As an early-stage company led by first-time entrepreneurs, Nuroflux is actively seeking to build meaningful networks in the social impact domain. The Solve program provides a unique opportunity to receive broad-ranging guidance and mentorship across a myriad of domains; to facilitate the corporate vision of Nuroflux - to provide objective and continuous monitoring of patients suffering from neurological disorders at-scale.

Nuroflux has one intellectual property position assigned – a method/apparatus for detecting blood flow change in the brain of a subject (WO 2021/077154 A1). Reference: https://patentscope.wipo.int/s...

The patent has broad claims, has received a clear international preliminary report on patentability, and is currently undergoing National Phase filing, with prosecution ongoing in Australia, United States, European Union, Japan, South Korea, China and India. Further to this, an internal freedom-to-operate search has been conducted with respect to both the claims and anticipated device form factor, with no concerns identified.

Described extensively within the solution overview, the Nuroflux technology represents the first tangible opportunity to provide objective monitoring of patients with neurological disorders (including stroke), across a range of clinical settings (including hospitals and community clinics), as well as geographies (especially low-resources environments). As such, it is expected to heavily influence current clinical workflows in all these communities, for the betterment of the human condition.

Nuroflux is uniquely positioned to deliver an outsized positive impact – the low-cost and versatile nature of the device, coupled with strong leadership commitment and strategic partnership with well-aligned organisations such as The George Institute for Global Health, will facilitate its deployment across a range of clinical (in-hospital, ambulatory, community healthcare clinics and at-home), geographic (metropolitan, rural, remote, and underserved communities) and disease (stroke, traumatic brain injury) contexts. 

Best illustrated through a Theory of Change framework, the inputs are as follows: 1) poor access to stroke healthcare, exacerbated by low-resourced environments, represents a significant community challenge and priority, 2) relationships and coordination among Nuroflux, The George Institute for Global Health (track record of developing healthcare solutions for underserved communities) and hopefully, MIT Solve members and organisations, and 3) sufficient information and resources that will be strongly enabled through proposal funding, in-depth mentorship and successful execution. The outputs will include improved access to stroke healthcare services (evidence-based decision-making), and cost-effective healthcare delivery across the aforementioned contexts. The intermediate and long-term outcomes will include: 1) improved equity of healthcare access (reduction in avoidable stroke injury, hospitalisation, and death), 2) reduced social and economic cost of stroke occurrence (with improved health and productivity), and 3) improved knowledge, skills, and health literacy. The key assumptions include: 1) economic, political, and social environment that is conducive to device development, commercialisation, and implementation, 2) access to tPA therapeutic ($US36 per patient) and storage, and 3) healthcare staff available to interpret device results and administer appropriate treatment.

Nuroflux and its corporate objectives align exceptionally well with the Sustainable Development Goals and its targets, more specifically:

Goal 3: Good Health and Well-Being

“By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote...well-being”

“Achieve universal health coverage...and access to safe, effective, quality and affordable essential medicines...for all”

“Strengthen the capacity of all countries...for early warning, risk reduction and management of...global health risks”

Goal 8: Decent Work and Economic Growth

“Achieve higher levels of economic productivity through...technological upgrading and innovation”

“Promote development-oriented policies that support...entrepreneurship, creativity and innovation, and encourage the formalisation and growth of...enterprises”

Goal 9: Innovation, Industry and Infrastructure

“Develop quality...infrastructure...to support economic development and human well-being, with a focus on affordable and equitable access for all”

“Enhance scientific research, upgrade the technological capabilities of industrial sectors...,encouraging innovation and substantially increasing the number of research and development workers...and public and private research and development spending”

“Support...technology development, research and innovation in developing countries”

Goal 17: Partnerships for the Goals

“Enhance...regional and international cooperation on and access to science, technology and innovation and enhance knowledge sharing”

“Promote the development, transfer, dissemination and diffusion of...technologies to developing countries”

“Enhance the global partnership for sustainable development...that mobilize and share knowledge, expertise, technology and financial resources”

Measurements Toward the Achievement of Targets and Goals

1) Performance of clinical efficacy studies to establish meaningful device sensitivity and specificity across a range of disease states - ideally above 90% for both parameters.

2) Acquisition of philanthropic, non-dilutive grant and equity funding obtained to support corporate activities - likely several million prior to clinical use.

3) Strategic partnerships formed with healthcare networks and organisations (such as The George Institute for Global Health) for deployment of nuroflux device into low resource settings.

4) Regulatory approval of the device achieved through FDA, EMA, TGA and other bodies in countries where underserved communities persist.

5) Suitable reimbursement mechanisms identified from public and private sources.

The Nuroflux value proposition is largely dependent on a novel metric - electrocardiography blood perfusion index (EBPi). EBPi is computed using electrical signals generated by the beating heart (ECG signals) and leverages unique characteristics of blood. EBPi is based on the following theory: The ECG is the largest electrical signal produced by the body. As one of the most electrically conductive components in the body, blood provides a major pathway for the propagation of electrical signals (such as ECG). Given that a change in blood flow alters the electrical conductivity of the blood, we hypothesised that cerebral blood flow (CBF)-induced changes in tissue conductivity would alter the propagation of the ECG signal from the heart to the scalp, manifesting as a change in the amplitude of the ECG signal recorded across scalp electrodes, with respect to the same signal recorded across the chest. 

Accordingly, EBPi is hypothesised to increase with increased CBF and decrease with decreased CBF. EBPi is an innovative technology that is linked to both the heart and blood, and as such, provides an exciting mechanism with which to objectively and quantitatively monitor neurological and cardiovascular disorders in a continuous fashion.

The scientific basis for our technology has been described in the following work:

1) S. J. van Bohemen, J. M. Rogers, P. C. Boughton, J. L. Clarke, J. T. Valderrama, and A. Z. Kyme, "Continuous Non-invasive Estimates of Cerebral Blood Flow Using Electrocardiography Signals: A Feasibility Study," Biomedical Engineering Letters, 2023, doi: 10.1007/s13534-023-00265-z.

2) S. J. van Bohemen, J. M. Rogers, A. Alavanja, A. Evans, N. Young, P. C. Boughton, J. T. Valderrama, A. Z. Kyme, "Safety, feasibility, and acceptability of a novel device to monitor ischaemic stroke patients," arXiv, 2024.

3) S. J. van Bohemen, J. O. Nardo, J. M. Rogers, E. Stephens, C. H. Wong, A. F. Bleasel, A. Z. Kyme, "Spatio-Temporal Correlation of Epileptic Seizures with The Electrocardiography Brain Perfusion Index," arXiv, 2024.

Dr. David Almeida Cardoso - 0.6 FTE. Responsible for commercial and operational development.

Dr. Samuel van Bohemen - 1.0 FTE. Responsible for scientific and clinical development.

The George Institute for Global Health - 2.0 FTE, shared across several employees (Prof. Craig Anderson, 0.2 FTE; A/Prof. Candice Delcourt, 0.2 FTE; Dr. Xiaoying Chen, 0.6 FTE and Mrs. Ava Khan, 1.0 FTE) who have been contracted to facilitate scientific and clinical development of Nuroflux.

Nuroflux Pty Ltd was incorporated in 2020, and have been seeking to commercialise the proprietary mechanism for continuous blood flow measurement since then.

Nuroflux remains steadfast in its commitment to the enhancement of diversity in its corporate workforce and the ecosystem more broadly – acknowledging that a highly demographically, experientially, and cognitively diverse team facilitate increased innovation and robustness of decision-making. Nuroflux has inherently global ambitions, evidenced through co-founders based in Australia and the United States, and a strong strategic partnership with The George Institute for Global Health (Australia, China, India, and United Kingdom sites) where, of the two total FTE equivalents contracted to support Nuroflux research-and-development, there is demographic [gender (75/25% female-to-male) and cultural background (75% foreign-born)] and experiential (professional stage, split between senior-, mid- and early-career) diversity. Further to this, the Team Leader of the current proposal is from a socioeconomically disadvantaged background, and actively mentors in accelerators aimed at traditionally underserved populations (e.g. Remarkable, disability technology; Catalysr, first-generation immigrants).

In close collaboration with the MIT Solve team, Nuroflux will seek to undertake initiatives to ensure maintenance and enhancement of diverse perspectives, including but not limited to: 1) fellowship, internship, and mentorship opportunities to facilitate the professional development of diverse early-stage talent from Australian and United States ecosystems (e.g. MLSC NextGen Fellowships and Internships), 2) support of entrepreneurship programs with diversity in their foundational values (e.g. Lever), and 3) formal development of diverse scientific and commercial advisory board.

Following approval for clinical use (anticipated in Q2 2028), our device will be sold directly to hospitals through 1) hardware (medical device, bespoke consumable accessories), 2) software (real-time data display and analytics), and 3) technical support (service maintenance contracts). Reduced length of hospital stays (real-time intervention improves patient outcomes), and productivity gains (reduced need for nurses to perform neurological assessments to ascertain patient status) will provide a compelling case to purchase the device. Within the USA, there are 2,446 stroke centres, and assuming ten devices sold at $5,000 for hardware (current cost-of-goods-sold of $1,200), $15,000 for annual software subscription and 50% market capture, this represents a commercial opportunity of $61,150,000 (one-off) and $183,450,000 (annualised recurring revenue). This will expand upon entry into different geographies, disease, clinical contexts, as well as acquisition of reimbursement.

For public reimbursement, subject to Congress approval of 'Ensuring Patient Access to Critical Breakthrough Products Act of 2023', a Breakthrough Device Designation will ensure our device is temporarily covered under Medicare during a four-year transitional period and facilitate engagement with the Centre for Medicare Services – health economics analysis pertaining quality-adjusted life years gained (reduced disability due to faster intervention leading to improved productivity), and cost to the healthcare system, will guide the process. K- and/or E-codes (covering durable medical equipment) will be pursued, allowing for device prescription to patients at high risk of neurological deterioration. For private reimbursement, the increase in quality-adjusted life years will lead to insurees filing fewer insurance claims to cover longitudinal care.

Prior to achievement of healthy revenues (described within business model above), Nuroflux research-and-development and corporate activities are anticipated to be funded through a mixture of philanthropic funding, non-dilutive grants and equity financing. To date, Nuroflux has received $US300,000 in early-stage equity financing, mainly from not-for-profit entities committed to service underserved communities at-scale (The George Institute for Global Health, and Cerebral Palsy Alliance).