BrainCool has developed products for early and rapid cooling (hypothermia) with controlled temperature regulation of various disease conditions.
RhinoChill System and BrainCool System (marketed as IQool System in the USA) is used for the treatment of stroke and sudden cardiac arrest. With the portable rapid cooling system RhinoChill, early and rapid cooling is first achieved, which is then followed by continuous cooling with the BrainCool System. The company has also developed the product Coral System which is intended for the treatment of oral mucositis, a serious side effect of chemotherapy that affects the lining of the mouth
EU-funded stroke study
In stroke, a blood clot blocks blood flow in the brain. Today, the most effective treatment is to mechanically remove the clot using a catheter (thrombectomy). However, permanent damage can still occur after blood flow returns to the brain – so-called reperfusion injury. With BrainCool's products, the brain's temperature is quickly cooled before reperfusion begins, in order to reduce this long-term damage.
Two years ago, BrainCool initiated a clinical development program together with the University Hospital of Freiburg, sponsored with 3 million euros from the EU. The aim of the studies, Cottis 1 and Cottis 2 (“Combination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke”), is to measure clinical benefits of combining the BrainCell concept with thrombectomy, compared to today's standard treatment.
Doubled number of survivors
Results from the first study, Cottis 1, were presented in October 2022. The treatment resulted in a doubling of the number of patients surviving with good neurological function already at hospital discharge and even stronger results were seen after 3 months. However, the study was not designed to measure survival but was a preparation (safety and feasibility) for the larger upcoming randomized clinical trial, Cottis 2, which has now been initiated. Cottis 2 will include 400 patients and is led by the University Hospital in Freiburg, Germany.
Comments from the CEO
BioStock contacted BrainCool's CEO Martin Waleij to learn more about the study that began at the end of last week after approval from the German Medicines Agency (BfArM).
Martin, you had hoped that the study would have started already in the fall, what is your comment on that and what is the timetable for the study?
– There are two basic reasons, the first is that we have also agreed the study with the American FDA, which recommended introducing ongoing reporting of SAEs (severe adverse events) per quarter, which prompted a change that BfArM also found positive. However, each change leads to a potential response time of 3 months from the authority.
– Ironically, the extremely strong results were obtained both in the feasibility study Cottis 1, which was published at the end of August, and in a so-called shift analysis of the data in Cottis 1 – which was requested by the FDA – where the 22 patients from Cottis 1 were compared with a historical control of 44 patients of the same age/gender and brain damage). The BBfArM has introduced and recommended a number of reinforcements to the statistical model. The reason for this was to ensure that the results cannot be questioned in the event of a positive outcome, since a positive study has the potential to significantly change the care of stroke patients and lead to a new stroke treatment.
– Both points will benefit the time for market approval after the study is completed and ensure that the study rests on a very solid foundation in the event of a positive outcome.
– Formally, the University Hospital of Freiburg is the sponsor of the study, and updates to the timetable must be coordinated with the EU. So any updated timetable will be communicated by BrainCool through a press release.
How is the patient group treated today and how does your technology add potential value in combination with current treatment guidelines?
– Today's standard treatment consists of thrombectomy and thrombolysis (clot-dissolving drugs), which is compared to this plus our cooling concept with early cooling before reperfusion has started (RhinoChill) and controlled cooling and warming with the BrainCool System.
Are there any competing studies aimed at the target group?
– Time and timing undoubtedly speak for BrainCool. Two pharma projects in neuroprotection in stroke have shown completely neutral results (and even worse results than thrombectomy alone). One was presented at World Stroke in October 2022 and on January XNUMXth an evaluation of infusion of thrombolysis in combination with thrombectomy was published, which have thus shown no effect whatsoever compared to today's standard treatment.
– The biotech company NoNO inc presented its ESCAPE NEXT study, a study of 850 patients conducted at 77 sites in North America, Europe, Singapore and Australia, with the candidate Nerinitide, which was evaluated in combination with thrombectomy/thrombolysis against today's standard of care. The study showed neutral results and is likely to face closure, not only because of the company name itself.
– On January 4, a publication was presented evaluating infusion of thrombolytic drugs against standard treatment, which also showed completely neutral results.
– What then remains as the most promising candidate for neuroprotection? Well, cooling. In addition to our project, there has also been a project with the product Thermoguard (the clinical study Reclaim 1/2) in the USA which has reportedly been stopped prematurely and closed due to lack of results, which is also confirmed by projects in China in collaboration with Wallaby Medical.
– In summary, BrainCool is in an exceptional situation, where within the cooling segment we have a unique ultra-early cooling treatment with a possible exclusivity in a multi-billion market if the Cottis 2 study turns out well.
What benefits do you see for BrainCool as a medtech company from participating in clinical studies where it is much more common for traditional drug therapy to be in focus?
– The vision with BrainCool is clear, we will develop products for patients with fewer side effects, at lower cost (development and clinical), with the same or higher added value than pharmaceutical products. Our stroke project benefits from the fact that thrombectomy has paved the way for a high level of reimbursement. In the case of Cooral, it is obvious – why use a drug to treat a problem generated by another drug?
– It is challenging to tackle the pharmaceutical industry as a medical technology company, but you should take into account that through our EU grant we basically have all the stakeholders in German stroke care behind us. And that without paying any of them, but they are running the project with a single purpose – to improve care for stroke patients.
Both you and Professor Jürgen Bardutzky, clinical trial leader at the University Hospital in Freiburg, highlight that a positive outcome of the study could mean a paradigm shift in stroke care. Can you elaborate on that?
– A positive outcome of the Cottis 2 study will simply create an enormous social impact on patients and families, which is actually the foundation of the medical device industry. The focus now is on conducting the clinical study and although our project rests on a solid foundation, we will have to await the results of the Cottis 2 study.
Finally, what does the path to the market look like and the possibility of obtaining insurance reimbursement for the treatment?
– We see several opportunities to obtain fast track reimbursement in both the USA and Germany. But France has also created similar systems. Reimbursement is complex but we aim to show the same added value as thrombectomy and there the public insurance system Medicare is 11 kUSD for the one-time treatment but also 27 – 39 kUSD for the cost within the hospital (resources, care days) and for the purchase of capital (system). Our value will be derived from the results of the study of course, but it is obvious that this is a huge opportunity for BrainCool on a completely different level than today's bread and butter with the BrainCool System.
– We have not come up with a sales strategy, but there are some clear potential sales channels:
* Expand collaboration with ZOLL in the area, we will be the only option.
* Collaboration with companies in thrombectomy, e.g. Medtronic, Stryker, J&J, Wallay Medical. There are different options, an exclusive partner or why not non-exclusive agreements with several companies (for example Cellavision during their build-up phase).
– You can take on any market with direct sales, e.g. Germany. We already have close cooperation with the entire German intensive care in the area. Suppose that 20 patients per year are treated in Germany, with a value per treatment of EUR 000. In Germany, it is possible to set up a direct sales organization of only 5-000 employees and still serve the market. These are the same hospitals that we address with the BrainCool System and through our EU program we are already working with the customers. How quickly do you reach 4 percent of the market? With a direct sales approach in Germany, if only 5-20 new employees you will quickly be able to take 3 percent of the potential market, that would mean annual sales of SEK 4 million and since the area fits well into our current organization, sales and other costs can be as low as 20-200 percent of sales. Which would generate an increased profit of over SEK 10 million annually. As mentioned, this should not be interpreted as a sales estimate but more as a discussion of possible paths forward. But of course, we are already working on different options in parallel with the clinical study and regulatory and reimbursement preparations.