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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - denovoSkin (Personalized, bio-engineered skin grafts for the permanent treatment of skin defects.)

Teaser

Summary

Skin is a humanÂ´s largest organ. Human skin is frequently damaged resulting in the loss of its integrity and physiological balance, which may result in significant disability and infections. The skinâ€™s natural restorative capacity is sufficient to heal itself when injured superficially (epidermis). Yet human skin cannot heal itself without medical intervention when wounds are too deep and damage the dermis. Deep partial (partial living dermis left) and full-thickness skin (no living dermis left) wounds are still a significant challenge to clinicians. Standard of care for the treatment of deep partial and full thickness skin wounds is split-thickness skin autografting. Split-thickness skin grafts (STSG) are thin but transplanted on deep wounds, thus the body creates scar tissue to fill up the gap and induces contraction to try and reduce the wound volume.

Unfortunately, too often, standard of care leaves patients with scars. STSG is composed of the epidermis but only remnants of the dermis. After transplantation, this lack of dermis induces the human body to react by quickly creating scar tissue (to fill up the gap), and by activating contraction (to reduce the wound area). Contraction leads to deformity and is characterized by skin constriction that results in scarring and functional limitation.

Furthermore, donor shortage is the biggest limitation in skin substitutes nowadays in the treatment of large skin wounds that require surgical intervention. To try to overcome donor site shortage, STSG can be meshed, but only up to 9x its size. Also, it can be repeatedly taken from the same site, but with long waiting intervals in between the harvestings, high distress for the patient and the unsatisfying final outcome that also results in scarring on the donor site area.

Being the outermost organ, skin health also entails social and behavioural impacts on individuals. Patients with conditions such as scarring frequently face psychologic challenges which, in turn, impact their social functioning and the kind of life that they lead. Patients may experience fearful anticipation of interaction with others, and develop avoidance-coping mechanisms. This may prevent them from partaking partially, or fully, in social and recreational activities or employment. Ultimately, visible symptoms may change how patients see themselves and how they perceive their future.

While the culturing of autologous epidermal sheets has been achieved, the real clinical challenge is creating a personalized, safe graft with a dermo-epidermal biological structure, in a relatively short time that minimally scars after transplantation that growth with the patient. denovoSkinâ„¢, possesses all the right features to target these medical needs. It is dermo-epidermal, meaning that the resulting graft is composed of both the dermal and epidermal layers, therefore the body will have little means of inducing contraction and scar tissue formation after transplantation. To produce denovoSkinâ„¢ a very small (at least 2cm2) skin biopsy is needed to produce high amounts of skin grafts and its single harvest causes minimal distress to the patient. It can also be produced in a relatively short-time and reduces or even avoids the need for further corrective interventions being a more cost-effective solution.

Throughout the Feasibility Study, CUTISS reviewed its progress to date and defined a sound development plan based on the remaining activities to be executed for denovoSkinâ„¢Â´s development. denovoSkinâ„¢ is at a mature stage of development and the steps planned regard the clinical validation of the product and its industrialization. The key objectives of denovoSkinâ„¢Â´s development are now to get the Orphan and Reconstructive Market Authorisation and to automate its production process to be at the forefront of the European Tissue Engineering Market.

Work performed

CUTISS evaluated in detail the current stage of development and given successful results from the Phase I clinical the Orphan Drug Designation (ODD) was granted. denovoSkinÂ´s ODD condition means that it is necessary to perform an additional clinical trial to get the Orphan Market Authorisation (burns). This Phase II clinical trials has already started and were defined with the key objective of validate denovoSkinÂ´s safety for human use, effectiveness in wound healing and cost savings in the long term.

CUTISS also found that production automation is key for its company business success. An automation project will create a standardised GMP-in-a-box production process that can be replicated anywhere, facilitating a global reach while ensuring denovoSkinÂ´s quality. An automated process will also allow to cut production costs due to less manpower and reduction of in process controls. Production efficiency will be also improved thanks to less variability and more robustness. Eventually, this production process will also serve to produce other products the company is already developing.

CUTISS analysed in detail the go-to-market strategy to define the approach for accelerated and effective market uptake. It was concluded that initially, denovoSkinâ„¢ will be targeted at private hospitals whilst large-scale validation trials are carried out to achieve reimbursement eligibility. CUTISS will undertake a reimbursement study to expand their knowledge on the regulations in each country and select the most cost-effective approach. Once reimbursement is approved, CUTISS expects a much wider market uptake as public hospitals also offer the solution.

denovoSkinâ„¢ project is fully aligned with CUTISS strategy to validate and maximize its potential for commercially favourable uses. With promising growth projections and considering the overall results of the Phase 1 assessment, CUTISS have concluded that it will be worthwhile to follow-up with the implementation of the development and commercialization plan. Following these carefully assessed considerations, CUTISS have evaluated that, SME Instrument Phase 2 funding can provide sufficient resources to carry out the automation project, co-funded by the financial and operational capacity of the company. This will allow the implementation activities to be performed in the most suitable conditions and will result in a faster market entry.

Final results

denovoSkinâ„¢ ensures that reimbursement policies are effective since based on a proven overall reduction in medical expenses and also brings great benefits to all the stakeholders involved in the value chain, from Medical facilities to patients, including surgeons. It is the first autologous, dermo-epidermal skin graft on the market. With transplantation now a commonplace technique, one of the main factors limiting the number of transplants is the shortage of donors. denovoSkinâ„¢ can be enlarged dozens of times the size of the biopsy needed for the bioengineering in a relatively short time. This is of great benefit for patients with large burns as well as other large skin defects who normally undergo multiple surgeries. denovoSkinâ„¢ also contains both dermis and epidermis, thus, leading to significantly better functional and aesthetical outcomes. It is a personalized, permanent and safe treatment grown from autologous skin grafts, thus also avoiding risks of transmission of diseases such as HIV, Hepatitis, fungi or parasites as it occurs with tissues that are acquired through cross-border exchanges, and originated from living or deceased donors.