A matter vital to the heart

Xeltis has developed an artificial heart valve that stimulates the body to rebuild a replacement one of its own. The implant is gradually absorbed while the tissue is being restored. Millions of children worldwide can be helped with this natural approach. This innovative method allows for faster healing and reduces the number of further risky operations. The clinical study results are winning the confidence of heart surgeons worldwide and this company, with a second-seat in the Netherlands, plans to launch the product on the Swiss market in 2021.

As the father of three sons, Laurent Grandidier cares about children. "Helping them is our biggest motivation," says the CEO of Xeltis. The problem: many babies are born with a closed - or a missing - pulmonary heart valve. In young patients in the past it was common to replace it with a vein from the neck of a cow and then prevent any rejection of foreign tissue with medication. Biological heart valves, however, must often be renewed 5 to 15 years after the initial operation. "The symptoms and risks increase with every further open-heart surgery. This is horrifying and an enormous challenge for the children, their parents as well as every cardiac surgeon," says Grandidier.

Organism recreates itself automatically & correctly
In order to remedy the problem, Xeltis has developed an artificial heart valve that is very porous. The ingenious aspect of this method is that the patient's blood vessels regrow and fill in the open pores. This initiates a healing process which results in the implant being absorbed by the body - all in the absence of an immune response. This process can take months but in the end the patient has a new heart valve generated by its own resources. And that's not all: because it is stimulated by the implant, the body replicates the missing tissue according to its original function - including the right type, size and shape.

Stroke of luck with Eindhoven research company
Endogenous Tissue Restoration (ETR) was the breakthrough for Xeltis. The path to it, however, was not easy or straightforward: the University of Zurich spin-off has been researching new heart valve therapies since the year 2000. "In 2009/2010, we found that the body can best replace a heart valve using an implant devoid of living cells. Based on this insight we started searching for a suitable and malleable synthetic material, "says Grandidier. After several trials he discovered Martijn Cox and the QTIS/e company in the Dutch city of Eindhoven. It was a stroke of luck: Cox was working on the groundbreaking "supramolecular technology" at that time - but for completely different applications, for example, in the field of cosmetics. The two companies teamed up to develop this novel heart valve therapy approach.

Nobel Prize winning technology
Behind the «RestoreX» platform are two groundbreaking innovations: Firstly, the material used consists of supramolecular polymers developed by Nobel laureate Jean-Marie Lehn, a current advisor for Xeltis. Secondly, the company uses its patented electrospinning procedure for the production of heart valve components. The properties of the polymers are altered specifically in an electric field of tension until, for example, a micrometer thin and several kilometres long fibre is created to construct a heart valve.

Twelve successfully treated patients
Xeltis started with the first implantations in Budapest because early clinical trials were possible there, according to Grandidier. Twelve pulmonary valves have been successfully implanted in patients as part of feasibility studies in Europe and Asia. More tests / studies are currently running in the USA. Young patients aged 6 to 21 years are carefully selected by doctors according to their needs as well as a risk / benefit assessment. Grandidier recalls an eight-year-old he accompanied during the procedure: "The girl was already so weak that she could only reach the operating theatre by wheelchair. Two years after the procedure she's able lead to a nearly normal life again, "he says happily.

But the Xeltis platform is reaching further. The company is currently using the same principles to continue research into, among other things, the development of aortic valves for adults. In contrast to the flexible version needed for growing children, a stable solution is called for here. "One cannot conserve the animal tissue needed for a biological valve for long periods of time. In addition, there would not be enough animal material available for the demand worldwide," says Grandidier. Implanting artificial heart valves is not a good alternative as patients must take blood clotting inhibitors with strong side effects. Xeltis' new therapy approach eliminates these serious drawbacks as well. The preclinical studies also attest to the full functioning of the valves – already within 12 months after implantation.

Billion market for aortic valves
Scientists and surgeons worldwide are convinced by the results of the new therapeutic approach. Xeltis plans to introduce the pulmonary valve in the EU and Switzerland (under Professor Thierry Carrell in Bern's Inselspital) in 2021. There is a high demand: around 2% of the population in industrialised countries suffer from this form of cardiovascular disease. Grandidier estimates the market for pulmonary valves in Europe and the US to be $300-400 million per year. He even predicts the potential for aortic valves to be up to $5 billion worldwide - and the trend is increasing.

Saving millions in treatment costs
Using ETR can save millions in treatment costs over the lifetime of a patient. Each procedure costs close to CHF 100,000 and that's not taking into account the examinations and subsequent treatments for chronic inflammation, the medications, treatment materials, etc. The economic benefits of the new method could be enormous.

To advance the extensive research and costly testing and studies, Xeltis completed a Series C financing round of € 45 million in 2017. Another challenge, however, are the new EU regulations. To date their product's risk class III CE marking took two to three months, but under the Medical Device Regulation (MDR), Grandidier expects twice the time for approval in the future.

Grown from 5 to 55 employees
Xeltis is securely established today. Research is conducted in Zurich and Eindhoven is home to the production facilities. The plan is to continue to market and distribute the niche product without any extra external help. The company has grown from five to 55 positions since its founding and is expected to employ around 150 individuals by 2021. Thanks to their Scientific and Medical Advisory Boards it also cultivates and maintains a large network with hospitals and universities. Grandidier is also committed to supporting foundations for the treatment of affected children - another important matter of the heart.