CUTISS’ CEO, Dr Daniela Marino explains how the company plans to provide safe, personalised tissue therapy for skin conditions worldwide.
Skin is the largest organ of the human body, composed mainly by an outer epidermis and an inner dermis. It is our interface to the outer world and its total loss is incompatible with life. In contrast to small skin lesion, if large proportions of epidermis and dermis are lost, the resulting full-thickness defects (FTSD) represent a significant, and sometimes unsolvable, problem for surgeons. The classical conditions that often lead to extended full thickness skin loss are burns, avulsion injuries, septic skin necroses, and iatrogenic skin defects.1
Today, FTSD are treated by means of skin autografting: a split-thickness skin graft (STSG) is harvested from a healthy donor site of the patient’s body and transplanted on the full-thickness wound. STSG, being composed of epidermis but only remnants of dermis, are thinner than the wounds, thus, after transplantation, scar tissue is deposited to fill up ‘the gap’ and contraction is promoted to try and reduce the wound volume. Clearly, during the acute phase, donor site shortage represents an unmet need that can be even lethal. In the mid-long term, scarring becomes the major issue. Scars are indeed not just disfiguring but also debilitating, highly discomforting; they can be painful and can impair mobility and growth and require corrective surgeries, intense homecare and psychosocial rehabilitation.1
denovoSkinTM a personalised bio-engineering dermo-epidermal skin grafts offers a solution to the lack of permanent skin coverageDenovoSkinTM, the Advanced Therapy Medicinal Product (ATMP) developed at CUTISS, is made of cells isolated from a stamp-sized patient’s split thickness biopsy and it comprises both an epidermal and a dermal components. DenovoSkinTM has received Orphan Drug Designation for the treatment of burns by Swissmedic, EMA and, FDA. After a successfully completed safety phase I clinical trial,2 it is now in Phase II efficacy trials in Europe (NCT03227146, NCT03229564, NCT03394612). In parallel, CUTISS’ research and development team is working on scale-up and automation of the manufacturing process.The ultimate goal is to position denovoSkinTM as the first-in-class automatically produced personalised tissue therapy that can treat patients in a safe, effective and accessible way.
The company: past and present
CUTISS is a spin-off of the University of Zurich (UZH), and was incorporated in March 2017. Until then, denovoSkinTM was developed at the Tissue Biology Research Unit (TBRU), a laboratory associated with the Department of Surgery of the University Children’s Hospital in Zurich, Switzerland, where close collaboration between researchers and surgeons was envisioned to be the ideal substrate to succeed. The message from the clinical team was clear: donor site shortage and scarring have often no solution. The mission for the scientists was clear: creating a real, innovative and effective alternative to autografting.
In 2011, the TBRU received an EU FP7 grant to translate denovoSkinTM from bench to clinic. At the same time, the UZH had opened state of the art GMP manufacturing boxes. Timing was perfect for the development of denovoskin. With the help of our partners in the collaborative EU project, and additional funds from UZH and private donors, denovoSkinTM was patented, translated into GMP and then tested for safety on 10 pediatric patients at the Kinderspital in Zurich. The clinical results gave very good ground for optimism and forced the team to think quickly about the future. There, the idea of CUTISS was born, with the vision of making denovoSkinTM accessible to patients in need worldwide. Indeed, every year, more than 50 million people worldwide could benefit from denovoSkinTM technology personalised tissue therapy.
2016, the startup incubator Wyss Zurich (www.wysszurich.uzh.ch/projects/wyss-zurich-projects/denovoskin/) decided to financially support the Phase II trials for denovoSkinTM. In July 2017, soon after incorporation, the newly funded UZH Life Science Fund, a joint venture of UZH Foundation and Novartis Venture Fund, injected a seed round of 1 Million CHF to launch the automation of production of denovoSkinTM.
The go to market strategy became clearer: denovoSkinTM must be proven to be effective on patients and Cutiss must develop its manufacturing process to produce and distribute at the large scale. Therefore, new challenges and activities were developed: process improvements such as automation of the production, GMP upgrade, regulatory and reimbursement roadmaps. In May 2018, CUTISS Ltd closed a Series A funding with 7.255.000 CHF (lead investor, Giammaria Giuliani, from Giuliani Pharma) and received a H2020 SME Instrument grant for €250,000. These finances will now take the company to the next level all the way forward to 2020.
CUTISS’ team is now composed of 17 people involved in the R&D, automation, production, and Clinical Trials of personalised tissue therapy – a very strong team that works in close relation with clinical, regulatory and engineering partners.
CUTISS Ltd has been awarded with prestigious prizes in Switzerland: the best pitch at the Swiss startup day in 2014, the TOP1 Swiss business plan 2015, the De Vigier prize in 2017, and is in the 2018 TOP5 Swiss startup and TOP1 Swiss biotech lists.
Present and future plans
Key issues around the scalability of current autologous therapies are that manufacturing processes require a significant amount of manual intervention, involving a highly trained workforce and dedicated cleanrooms, time consuming procedures and high investments. To address these issues, the automation of production (i.e. ‘GMP-in-a-box’) is part of the solution. A fully automated, closed system would provide robustness, safety and standardisation to deliver consistent product to surgeons and optimal treatment patient. This automation concept would change the business model from a classical, centralised production to a disruptive, decentralised manufacturing process available directly at point of care.
Automation would impact overall product safety, efficacy, and, pricing. We believe this would be an important step toward commercial success. In addition, a GMP-in-a-box approach would ensure replicability between different sites and enable a straightforward integration into data management systems, where manufacturing data from thousands of patients could be recorded, traced and, analysed. We strongly believe that all-in-one concepts have the potential to become the gold standard in autologous personalised tissue therapy manufacturing at point of care.
The automation project has been launched in 2017 and plans to achieve the very first Proof-of-Concept in the next two years. CUTISS is collaborating with international engineering companies to assure a successful completion of the project. Automation might project CUTISS into new dimensions, representing an incredible opportunity to launch a personalised tissue therapy production platform that could go beyond skin.
Furthermore, at CUTISS we are working on adding aesthetical and functional features to denovoSkinTM to reach a higher degree of personalisation with personalised tissue therapy and to provide patients with a graft that best resembles the rest of the skin on their body. To this extent, we are currently developing the manufacturing of pigmented skin. Indeed, this feature would provide an both aesthetic benefit but also UV light protection, significantly improving the quality of life of the patients.
1 Marino D., Reichmann E. , Meuli M. Skingineering. Eur J Pediatr Surg. 2014 Jun;24(3):205-13. doi: 10.1055/s-0034-1376315. Epub 2014 Jun 11
2 Meuli M. et al. A Cultured Autologous Dermo-Epidermal Skin Substitute for Full Thickness Skin Defects: ‘A Phase I, Open, Prospective Clinical Trial in Children’. Plastic and Reconstructive Surgery, Printing in process. October 2018
Dr Daniela Marino
+41 76 230 8046