Burn, trauma, and plastic surgery patients and others needing skin autografts often have limited quantities of healthy tissue from which to take skin biopsies, and when skin grafts are transplanted, they often leave permanent, disfiguring, and painful scars. These problems motivated Cutiss to develop a manufacturing process to produce personalized, autologous, bioengineered human skin grafts. The process was manual at first, but now it has been translated into an automated, fully closed production technology.
“The product we developed—denovoSkin, currently completing Phase II trials—can be produced in large quantities from a small biopsy, so there’s no need to harvest lots of skin from healthy parts of the body,” Daniela Marino, PhD, co-founder and CEO of Cutiss, tells GEN. The technology uses a skin biopsy about three square centimeters in size to produce sheets of skin about 100 times as big in three to four weeks. Quantities can be increased either by starting with a larger sample or by extending the culture time.
Marino says that because denovoSkin has both epidermis and dermis, it can replace the patient’s skin at its full thickness. As a result, when denovoSkin is used, scarring is expected to be minimal.
An automated, modular process
“Skin is our largest organ, and some patients require a really large quantity of skin in a short time,” Marino observes. “So, you can imagine how challenging it is to scale up this approach.”
Traditionally, the cell isolation, expansion, and tissue formation steps of graft processing are performed manually using pipettes, plates, bottles, and so on. Cutiss, however, has automated those steps in a closed system composed of three modules: Semotiss, Quantum, and denovoCast.
Semotiss, the cell isolation module, can receive a biopsy and provide a single-cell suspension of epidermal and dermal cells as output. Those cells are transferred into Quantum, the cell expansion module. Then the cells are moved to denovoCast, the tissue formation module. It produces personalized skin grafts.
“It’s a fully closed system, but it is not intended to be fully automated,” Marino says. “There is no interaction between the external environment and the cells” even though the cells are transferred manually among the three modules. “Modularity allows for maximum flexibility during the process, to best adapt to patient needs and timing,” she adds.
denovoSkin lacks pigmentation, so it is colorless. “The cells that produce pigmentation—melanocytes—are very sensitive to expansion, and their culture process would need to be aligned with the other cells, increasing complexity and costs,” Marino points out. Therefore, Cutiss decided to develop ways to restore pigmentation in a second step, after transplantation.
In this step, the patient’s own melanocytes are transferred from a pigmented area to the colorless one, without undergoing expansion, to restore the patient’s own pigmentation. To do this, Cutiss has exclusively in-licensed VitiCell, a medical device developed by IBSA Pharma, to treat vitiligo and dyspigmented burn scars through autologous cell transfer. The device is approved in the European Union. Marino expects pigmentation treatments to begin in Europe in two to three years.
From bench scientist to entrepreneur
Marino founded Cutiss in 2017. “I was a researcher at Zurich University Children’s Hospital, and I was trying to bioengineer human skin in collaboration with the departments of burns and reconstructive plastic surgery,” she recalls. “I had wanted to be a scientist my whole life, and I didn’t expect to become an entrepreneur.”
“I started talking with people about the science and the possibility of forming a company. They were telling me that I had a simple way of explaining things, that I understood what I was doing, and that I had drive.” After hearing that repeatedly, she decided to take a risk and create the company.
“My first challenge was to transition from classical bench scientist to entrepreneur, and my second was creating a team,” she relates. “It was extremely fun and very challenging. Thanks to a very good Swiss ecosystem for startups, I could access help, including networking and coaching events.”
According to Marino, the challenges since then haven’t changed much—they’re just bigger. In addition, she notes that in tissue regeneration, a new field, it’s difficult to find people with the experience to take her clinical-stage company forward.
Global ambitions
“The product we are developing really can replace autografting—the current standard-of-care treatment—not only for severe burns patients but also for other reconstructive surgeries,” Marino asserts. She is optimistic that this potential can be realized and that denovoSkin will become accessible to patients throughout the world. “Our first manufacturing hub is in Switzerland,” she says. “We built it during the COVID-19 global pandemic.” The company plans to create additional hubs in the United States and then to expand into Latin America, Southeast Asia, and the Middle East.
The expansion plans makes sense because some 70% of burn accidents occur in middle income or developing countries. “We have a responsibility to take this product to a certain level of cost effectiveness that will allow us to reach out to global markets,” Marino declares.
From a COVID-19 low to an ISS high
Like many companies, Cutiss had its struggles during the COVID-19 pandemic. For example, the company had to accommodate social distancing regulations in its production facility. Also, as a clinical-stage life sciences company, Cutiss had to slow or halt clinical trials as patients deferred elective surgeries and as supply shortages beset the healthcare ecosystem.
Now that the pandemic is receding, Cutiss is advancing. This spring, the company received 2.5 million Swiss francs (about 2.79 million U.S. dollars) from Innosuisse, the Swiss Innovation Agency, to industrialize denovoCast. (Cutiss continues to actively seek investors.) In roughly the same timeframe, Cutiss had a research project on the International Space Station (ISS).
“Wound healing processes differ in space versus Earth,” Marino says. “Microgravity and radiation may influence cell growth and migration, as well as cells’ ability to produce extracellular matrices. Insights gained in space may lead to new therapeutic options on Earth, as well as for astronauts in space.”
In another recent development, Cutiss announced positive results from Phase I and II trials in Europe. “We are now in discussion with regulatory agencies to discuss the next steps, hoping we can provide this lifesaving technology to patients very soon,” Marino reports. “First discussions with the FDA have been initiated and will continue.”
Marino emphasizes that Cutiss is committed to ensuring its skin production method will be robust, cost effective, and accessible. “We have seen the challenges in cell therapy, for example, where very high prices limit the use of the technology,” she elaborates. “So, automation will be the game changer.”
