TOOsonix A/S is a focused ultrasound company based in Hørsholm, Denmark. Founded in 2017, its first device was recently released in the European Union for aesthetic applications, and dermatology studies are ongoing for treating skin cancer. We interviewed one of its founding directors, Torsten Bove, MS, to learn more.
How did you get involved in starting or joining the company?
Tomasz Zawada, PhD, and I met when we worked together at Meggit A/S, a focused ultrasound original equipment manufacturing company. After participating in many high-intensity focused ultrasound (HIFU) projects with both start-ups and established medical device manufacturers over the last decade, and subsequently supplying their customer-specific piezoelectric HIFU components, it was clear that nobody was specifically looking at HIFU devices operating at higher frequencies than a few megahertz.
At higher frequencies, HIFU lesion points are fundamentally very small and can therefore be positioned and confined very accurately in superficial tissue. It is therefore a technology that directly offers therapeutic solutions to an extremely broad and unaddressed range of dermatological indications. As we had specific knowledge and ideas on design and production of such high-frequency devices, we decided to break out from Meggitt and start our own venture in TOOsonix.
Tell us about your company structure: ownership, lead executives, and their roles.
TOOsonix is partly owned by Consolidated Holdings A/S – one of Denmark’s most successful investor groups. Consolidated Holdings has provided significant financial backing and management support for the development of TOOsonix. Tomasz and I comprise the daily management team. While we share a lot of roles, I am mostly involved in the clinical and regulatory work, while Tomasz has been the main person responsible for the hardware and software development.
With the operational experience from our previous positions, we have been able to design the product and build the company structure around a strategy of maximum outsourcing supported by flexible external consultancy services from the very beginning. At this stage, we just employ an acoustic engineer and an electronics and software engineer, while all other activities are handled by external resources.
In general, what is the current status of your company?
We have just released our first medical product. At the moment, it is indicated for a small range of aesthetic treatments, but we see these only as the first of many applications to come (see our recent press release). The technical requirements for the device (safety testing, etc.) follow the same harmonized medical standards regardless of indication, but clinical requirements for aesthetic indications are less challenging than those needed for treating conditions like skin cancers. So we started with aesthetic indications. Now that we have obtained safety approval, the next step is to conduct more clinical trials on the medical indications, where recently published results from experimental treatments are extremely positive.
How many years has your treatment platform been in development, and what are its origins? Does it have a name?
Our first clinical HIFU device operating at 20 MHz, System ONE-M, has been in development for three years. It provides a diverse range of noninvasive treatments, which initially will address unmet clinical needs for several conditions within the field of aesthetics. Due to its high frequency, the system provides unprecedented accurate thermal lesion points confined to the very outer layer of the human dermis and epidermis. It thereby mobilizes the immune system to regenerate and replace cells with unwanted content of pigments and/or structure. The transducers are interchangeable for providing four different focal depths that are needed to fully cover the dermatology field. A key feature of the system is that it provides real-time guidance from an integrated dermascope, where all targeted features in the skin are directly visible on a high-resolution color video-feed.
We also offer a very similar preclinical device called System ONE-R. This system was originally developed for internal research purposes, primarily for use in our [preclinical] safety studies. Due to its status as a research instrument, it can be offered in a broader range of frequencies from 10 – 30 MHz, and with a potential to tailor handpieces for highly specific purposes. It is therefore a unique tool for fundamental research and preclinical work on HIFU technology. A good example of its use is in small animal research. Normal HIFU systems optimized for human use create HIFU lesions that far exceed the target features observed in the much smaller mouse model. Going to smaller lesion sizes (e.g., by using a 20 MHz operating frequency) facilitates a sufficiently accurate and to-scale HIFU treatments that are easier and more realistic to scale-up as studies move forward to human models.
Both systems are released for sale in the CE-regulated areas, but not yet in any other region.
What are some of the technical challenges your group has to overcome to develop a fully noninvasive system?
We started with a design on a blank piece of paper. The biggest challenge was to pass the type test, which gives a wide range of hardcore safety requirements to the device. Our earliest prototype was far from approval in terms of safety regulations, so there was a challenge to meet each technical requirement, boundary, and guideline that leads to compliance with medical regulations. It is somewhat tedious work, but it is extremely important to meet each of the compliance requirements.
What challenges do you have to tackle moving forward?
Our challenges have really been the same as any startup company. The next goal is full market entry through achieving reimbursement and developing established sales channels. In contrast to other larger HIFU systems aimed at hospital treatments, we fortunately have the advantage of mainly addressing smaller private clinics outside the public sector or insurance systems. Nevertheless, building a sales network and widespread local presence is a very big challenge for a small company.
Tell us about your clinical studies and the results.
We recently completed two clinical studies.
First, our research team investigated whether focused ultrasound could effectively treat skin cancer and actinic keratosis (AK). The video at right demonstrates a similar procedure for AK. Eight patients with 215 lesions underwent up to three treatments on each lesion, using probes with different target depths. After three to six months, the patients with AK had a 97 percent cure rate with no scarring. The patients with basal cell carcinoma and Kaposi sarcoma experienced full healing that was confirmed histologically. While further studies are needed, these early results show AK and skin cancer as promising new applications for focused ultrasound. This work was published in Skin Research and Technology.
Additionally, we used focused ultrasound for ablative tattoo removal on particular problematic cases presented at the dermatology department at the University Hospital Bispebjerg in Copenhagen Denmark. After completing preclinical safety studies, our researchers tested whether focused ultrasound could remove ink from tattoos that did not respond to laser or dermatome shaving. Using 1.1- and 1.7-mm transducers, the tattoos were covered with synergistic “shoulder‐by‐shoulder” shots of focused ultrasound in 22 subjects with 67 tattoos. The treatment was effective, painless, and free of side effects, but it did not always remove enough ink to satisfy all of the aesthetic treatment goals. It was beneficial, however, for patients who have allergic reactions to tattoo ink. This study was also published in Skin Research and Technology.
We have additional publications posted on our website.
What are the benefits of your technology over companies?
Our system is more efficient, less painful, simpler, and quicker than current dermatology treatments such as laser or photodynamic therapy. For example, photodynamic therapy requires a pre-treatment followed by a long waiting period before the actual light therapy is administered. A treatment thereby lasts several hours with a very high pain level for the patient and a high cost to the clinic/hospital due to the time consumption. Our system provides at least the same results with a single five-minute treatment with much less pain for the patient and without any special pre- or post-treatment. So far, this has therefore been working very well.
Similarly, removal of a tattoos (or any other of the aesthetic indications) by laser takes anywhere from 4 to 15 treatment sessions. Each treatment is extremely painful for the patient and only efficient for certain colors/types. With HIFU, small tattoos in any color can be removed in a single treatment with significantly reduced pain and without generation of allergic side-effects. It is not a magic treatment for any and all tattoos (in particular not large areas), but it provides significant improvements and complementary options in special cases.
Our device therefore has the ability to become a standard in-office dermatology device for a very wide range of conditions. Clinicians should furthermore have the ability to provide follow-on treatments that are paid for out-of-pocket.
Have you learned any lessons for watching the experience of the other companies?
Yes. On the business side, we have worked very hard on designing a device that is easy to manufacture from standardized electronic processes. Outsourcing and scale-up will therefore be significantly easier than in many other known cases, where highly specialized and manual manufacturing processes are needed.
From the very beginning, we also decided to pursue a market model, wherein a part of the revenue stream comes from renewable handpieces. With this model we can keep the initial cost for the device reasonable low and also ensure that handpieces are always fully valid and in line with expected energy output.
We have therefore aimed at using the most successful and proven models from the fields of aesthetics and dermatology.
Do you partner with other companies?
Yes, we outsource our manufacturing, clinical work, and regulatory process. We have business partners for everything except the manufacturing of our transducers.
Is your system approved for commercial use in any markets? If so, how is it being used in these markets?
Europe is still operating with “the old” device directive. Under this legislation, our device falls under Class 1 for aesthetic applications. With the recently approved safety tests and clinical evaluations, we could therefore release our System ONE-M for sale in the CE-regulated region. Indicating the system for further medical conditions, such as actinic keratosis, basal cell carcinoma, etc., takes the device classification to Class 2, which requires approval from a notified body. We are currently working on this with our notified body.
Which health conditions or diseases will your technology be used for?
At the moment, System ONE-M is indicated for the aesthetic applications of tattoo removal, cherry angiomas, telangiectasia (spider veins), solar lentigines (liver spots), and fine-line wrinkles. We are currently working to expand this to also include medical dermatological indications such as actinic keratosis, basal cell carcinoma, and Kaposi sarcoma.
In total, we have identified more than 25 different aesthetic and medical dermatological indications, which can be targeted by the same system using one of the four standard HIFU focal depts offered for the System ONE-M. This is possible because the high frequency (20 MHz) HIFU creates small and highly accurately positioned focal points within the skin tissue. The operator can therefore selectively target very small and delicate features without inflicting damage to nearby areas, which would otherwise be the case if lower frequencies, and thereby a larger lesion size, was used.
System ONE-R utilizes the same principle and strategy, but it is aimed at fundamental research and early-stage use for general dermatology, cosmetology, dermato-oncology, small-animal model research, ultrasound-mediated drug delivery, fundamental HIFU research, and sonochemistry research.
How has the pandemic affected your company?
We had fortunately just finished type testing before all of the clinical trials stopped. This gave us documentation to work with from home. Our design, development, and regulatory processes have not yet been affected, but our clinical work has now stopped. It is difficult getting people getting back to the hospital, so enrollment will be slow.
Is there anything else we should know about your company?
We recommend working with the Focused Ultrasound Foundation. The team members have been helpful from the time that we started TOOsonix, and we are happy to participate in their programs (e.g., reimbursement education). They have not helped us with finding investment money because we have private investors in Denmark, but they help us with many other things.