Hearty Start-ups

 

Cardiovascular diseases are in the sights of three medical technology start-ups from Tyrol. And they are relying on their scientific expertise, the perfect environment of the location and targeted local support.


"I started at Ergospect in 2007 – in an empty office, just me and one unsellable prototype," Thomas Hugl looks back, laughing. The business economist had been brought on board Ergospect by the radiologist Michael Schocke and the surgeon Andreas Greiner. The two doctors at the Medical University of Innsbruck had started to develop an exposure device compatible with magnetic resonance for the lower legs in order to be able to diagnose metabolic diseases in the calf muscles several years beforehand. The finished prototype gave them the motivation to market it through their own company. In 2005 their start-up team was admitted to CAST – Center for Academic Spin-offs Tirol, in 2006 they came in first place at adventure X, the business plan competition in Tirol, then in 2008 they founded their company. A road financed by equity and funding – namely the PreSeed and Seed programme of Austria Wirtschaftsservice GmbH (aws) – until 2010. The start-up had in the meantime come up with some strong products (devices for lower legs, thighs, buttocks), the subsequent desire to expand their portfolio became a labour of love.

Cardiovascular diseases are the most common cause of death in western industrial countries and the largest cost driver in healthcare – and accounted for 42.3 per cent of all deaths in Austria in 2014. Therefore, the international research community has been concentrating on innovative early detection methods and therapies. Even three medical technology start-ups in Tirol have got involved. While Ergospect with its Diagnostic Pedal Cardio – an ergometer, which can provide early detection of coronary heart disease by simulating stress situations in a magnetic resonance tomograph (MRT) – is already on the market, the team at AFreeze wants to treat atrial fibrillation caused by atrophia of the affected heart tissue by using cold temperatures. And the young entrepreneur Johannes Holfeld is focusing on shock waves in order to regenerate chronically undersupplied heart muscle tissue after a heart attack.

"We don't produce screwdrivers, these are highly technical devices," Hugl emphasises, therefore, development, production and mandatory guidelines are time-consuming and, therefore, the path to market entry is costly. For their "heart idea", the Ergospect team received funding of 600,000 euro from the K-Regio initiative of the state of Tirol (half of it came from the European Regional Development Fund) from 2011 to 2014. The consortium included Infpro IT Solutions from Innsbruck and the University Clinics for Radiology

and Cardiology. The starting point was the idea to combine the stress ECG with MRT. One option was to use medication to create stress," Hugl explains, but that would not have been the best solution. The Ergospect team fell back on its fibre optic experience with strain gauges: the patient, i.e. their upper body, is fixed onto the MR stretcher and slid into the MRT up to their hips. The feet go in two "special shoes" on the Diagnostic Pedal Cardio, which the patient uses to push and pull at the same time – the resistance is controlled by the software they developed themselves. "The movement occurs in the lower part of the body, the upper body remains still. As soon as the desired stress level is reached, sectional images are produced," the managing director of Ergospect explains. High resolution sectional images without errors as there is no magnetic field interference of the tomograph thanks to the metal-free ergometer device. They needed a year for the prototype, years two and three were earmarked for a trial, they have been ready to go into production since 2014. The first models have already been delivered, are now located in Japan, Europe and the USA. The feedback, Hugl says, has been very positive.

Ergospect is one of those innovative start-ups, which alongside the traditional Tirolean industry giants in the pharmaceuticals sector – Sandoz, Gebro Pharma and Montavit – as well as MED-EL (global leader for implantable hearing solutions) has brought life into the Tirolean life science and medical technology scene: Biocrates is specialised in analysing metabolic processes; Ionicon produces solutions for trace gas analysis; the Oxygraph-2k from Oroboros Instruments is the leading system for measuring cell respiration; Innovacell is developing personalised cell therapy for treating stress incontinence; and iSYS is focusing on robotic positioning systems for interventional radiology.

According to Florian Becke they bring added value to Tirol that cannot be underestimated. "Modern universities need to have companies in their vicinity with technologies that come from the universities themselves. That is one aspect that makes a scientific location attractive," the managing director of the CAST start-up centre is convinced of this. The environment in numbers: 50 Tirolean life science companies (without research institutes and hospitals) with 5300 employees achieving a turnover of about 1.5 billion euros. A location quality that Hugl also appreciates, "The relatively small and manageable size is an advantage. You get to know the others in the Life Sciences Cluster Tirol and exchange views. The hospital and universities we work closely with are also important for the location. For a new feature that our Diagnostic Pedal Cardio will control via pulse frequency we are

cooperating with the Private University UMIT in Tirol." Becke has also noticed that the universities have changed. On the one hand, they have increasingly been working with industrial companies in order to use their expertise, market knowledge and detailed knowledge for the academic environment, on the other hand researchers have increasingly been thinking about, "bringing their results independently onto the market." Just like Johannes Holfeld whose start-up is one of the latest CAST teams.,

Holfeld, a heart surgeon has been focusing on shock waves ever since his dissertation. In medicine, the physical phenomenon was first used more than 30 years ago to destroy kidney stones. "A German urologist noticed on X-ray images that the bone had become thicker on places on the pelvic bone where shock waves had been directed towards the ureter," the employee at the University Hospital for Cardiac Surgery in Innsbruck explains. The realisation that shock waves can also stimulate regeneration meant they could be used for treating wound and bone healing deficits as well as tendon insertion disorders. But Holfeld has another goal – the heart, or more specifically, the parts around the dead, irreparable tissue of the infarct scar.

"These tissue areas are chronically undersupplied and can no longer fulfil their function properly," the physician explains. As a consequence, the performance of the recovering patient decreases drastically, the undersupplied area, the "hibernating heart muscle," is, therefore, the goal of regenerative therapies. Stem cell and gene therapy, Holfeld says, have still not been able to find any broad clinical use despite intensive research. The shock wave therapy refined by himself and his colleagues has convinced him that they are on the right path.

Together with an industrial partner, Nonvasiv Medical GmbH from Constance, they developed a suitable small shock wave head that can stimulate the open heart with shock waves during heart bypass surgery. Holfeld was able to observe "infinitely impressive effects" in cell culture and animal models as well as in a first small clinical trial on patients. "We were able to prove the safety and feasibility. We were also able to clarify in our experimental trials how shock wave therapy works," the heart surgeon explains his research work. Shock waves cause small bubbles – filled with proteins, RNA and growth factors – on the cell surface, they then stimulate the Toll-like receptor 3 in the surrounding healthy cells. As part of the innate immune system it activates an endogenous self-healing programme that results in new blood vessels growing.

The next step now is a multi-centric trial with 200 patients – an expensive step. Holfeld estimates 5.5 to 6.5 million eures are needed

for the planned four years. Money that can only be generated by investors and also encouraged the university employees to found the start-up HeaRT – Heart Regeneration Technologies. He created a business plan for the adventure X competition, "valuable support came from CAST, the Standortagentur Tirol as well as the aws PreSeed funding grant." A package that, combined with scientific awards, is a great help in finding investors, "Funding from CAST and aws means that the concept is assessed by experts, a science prize that the research impresses professionals, adventure X that there is an evaluated business plan." The result - " we are in in-depth discussions at the moment with several investors." Holfeld's goal is market maturity in five years – " you then definitely need a big partner" – the economic concept is not only based on the console, but also on the shock wave head. "Because they are doing open-heart surgery, it is a disposable product that would cost between 3000 and 3500 euros." With 82,000 bypass surgeries carried out just in Germany and Austria every year, they will be tackling this market potential, which should not be underestimated, from 2020 onwards.

Becke also knows that this long-term approach is necessary. "You need special funding formats for technologies and business ideas that similar to life sciences themselves need a long time until they are ready for the market. You can get financial help in Tirol from CAST, in all of Austria from aws and the FFG, the Austrian Research Promotion Agency. You need equity quite early on when you have a financially intensive project." A fund portfolio that also took Gerald Fischer from his concept and computer model to the final trial phase.

"My great vision, even at school, was to always get something to work," Fischer says. Therefore, the interjection by the cardiologist Florian Hintringer that research projects and computer models for treating atrial fibrillations may all be well and good but you need instruments to treat patients, was a turning point. Atrial fibrillations are the most common and clinically most important cardiac arrhythmia, about one million people suffer from it in Germany. Atrial fibrillations are not life-threatening but increase the risk of having a stroke. Current pharmacological therapies or the atrophy (ablation) of parts of the left atrium using high frequency alternating current are not completely satisfactory.

Fischer and Hintringer are, however, pursuing a different approach. A catheter is guided into the left atrium in a stretched state via the groin and lower vena cava. The catheter opens

into a loop, which is pressed on to the atrium. Then a coolant is introduced into the catheter, which by quick-freezing at temperatures of minus 80 to 90 degrees creates a long, arch-shaped and reliable atrophy line along the loop, which like a dam prevents the electrical impulses from spreading.

They started their concept in a basement lab in 2005 and took part in adventure X. "We systemised our project, created project plans and timetables as well as a budget. It was a great help – even when we now know that the budget was too low and the schedules too tight," Fischer says, laughing. The CoolLoop concept and patent applications convinced CAST and aws. Thanks to their support, the company AFreeze was founded in 2008 – Fischer moved from UMIT to his own company. "On the one hand, we first had to learn our craft, on the other hand fulfil the strict regulatory requirements for medical products," Fischer recalls. The first successes alternated with phases, "where not enough headway was being made." At the end of 2010, AFreeze was able to land a K-Regio project. They carried on working with their Tirolean industrial partners Westcam-Fertigungstechnik and Micado CAD-Solutions as well as the cardiology department at Innsbruck and the UMIT Institute of Electrical and Bioengineering on CoolLoop and on developing another product independently – a cryo-tip catheter.

In 2012, AFreeze was finally able to start, having all the necessary permits and FFG support, a first trial on ten patients. "We were able to show that our method was safe and feasible," Fischer is proud, but also admits that they were somewhat naive in their approach, "We thought that if it was successful in the hospital then it would be a sure-fire success." It was difficult at this stage, just before its usage, to acquire public financial aid, "you need investors and venture capital."

Gertraud Unterrainer came as an additional managing director to AFreeze in 2012 and took on this task. AFreeze is now being financed by private investors, there are no key strategic partners, Unterrainer claims. The next trial started in Austria in 2014, Germany and Switzerland will be following soon. "100 patients are taking part, a follow-up is planned for one year," Fischer explains. 15 employees are employed by AFreeze today, but Fischer admits that ten years ago he didn't know what he was getting himself into. "Otherwise I wouldn't have had the guts. But when today I hear that a patient from our first trial is still free of complaints two and a half years later on, that may not be a quantifiable result but it gives me such a great feeling of achievement."

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