Periodic Reporting for period 1 - TRANSFORMER (Transforming bone cancer therapy with composite biomaterials encapsulating plasma-generated RONS)
Reporting period: 2022-11-01 to 2024-04-30
Osteosarcoma is a rare and aggressive primary bone cancer, predominantly affecting children and young adolescents. It constitutes less than 0.2% of all cancers and presents significant treatment challenges. Current therapeutic strategies involve extensive surgical removal of tumors, often requiring secondary reconstructive surgeries, and even limb amputations. This is paired with adjuvant chemotherapy, which can lead to severe side effects and long-term health issues. Moreover, recurrence rates are considerably high (30-50% of the patients with localized disease). The limited progress in osteosarcoma treatment over the past four decades underscores a critical unmet need for innovative therapies that are both effective and less harming for the patients.
Cold atmospheric plasma (CAP) gas consists on a partially ionized gas that has emerged as a promising tool in cancer treatment, due to its ability to kill cancer cells without harming healthy tissues. This selectivity is mainly attributed to the Reactive Oxygen and Nitrogen Species (RONS) generated during plasma treatments, which can induce cancer cell death at appropriate doses. In this context, different liquids can be treated with plasma (PTL, for plasma-treated liquids) to generate and store RONS in them, which can then be released to target cancer cells. Our previous work under the ERC Starting Grant ‘APACHE’ (ID 714793) demonstrated the anticancer properties of these PTL, particularly in osteosarcoma cells. We also found that these reactive species could be effectively encapsulated in hydrogels for localized delivery to the tumor site (PTH, for plasma-treated hydrogels).
The TRANSFORMER project, titled "Transforming bone cancer therapy with composite biomaterials encapsulating plasma-generated RONS”, aimed to advance these findings towards clinical application. The proposed solution encompasses a localized treatment using combinational therapies with these PTL or PTH to selectively target cancer cells, while enhancing bone tissue regeneration and/or avoiding recurrences. This innovative approach could provide significant benefits for both patients and healthcare providers by reducing side effects related to high chemotherapy doses, avoiding secondary reconstructive surgeries, and potentially improving long-term survival rates.
Cold atmospheric plasma (CAP) gas consists on a partially ionized gas that has emerged as a promising tool in cancer treatment, due to its ability to kill cancer cells without harming healthy tissues. This selectivity is mainly attributed to the Reactive Oxygen and Nitrogen Species (RONS) generated during plasma treatments, which can induce cancer cell death at appropriate doses. In this context, different liquids can be treated with plasma (PTL, for plasma-treated liquids) to generate and store RONS in them, which can then be released to target cancer cells. Our previous work under the ERC Starting Grant ‘APACHE’ (ID 714793) demonstrated the anticancer properties of these PTL, particularly in osteosarcoma cells. We also found that these reactive species could be effectively encapsulated in hydrogels for localized delivery to the tumor site (PTH, for plasma-treated hydrogels).
The TRANSFORMER project, titled "Transforming bone cancer therapy with composite biomaterials encapsulating plasma-generated RONS”, aimed to advance these findings towards clinical application. The proposed solution encompasses a localized treatment using combinational therapies with these PTL or PTH to selectively target cancer cells, while enhancing bone tissue regeneration and/or avoiding recurrences. This innovative approach could provide significant benefits for both patients and healthcare providers by reducing side effects related to high chemotherapy doses, avoiding secondary reconstructive surgeries, and potentially improving long-term survival rates.
The TRANSFORMER project was structured around two main goals: technical validation of the technology and assessment of its commercial viability. Both goals were successfully achieved. Below is a comprehensive summary of the technical validation:
Technical proof of concept in advanced preclinical models: Comprehensive studies were conducted to understand the physico-chemical properties of PTL and PTH, and the impact of plasma in their characteristics. Several in vitro biological studies were conducted to thoroughly analyze the effects of PTL and PTH on cancer cells compared to their impact on healthy tissues. Important findings in this section included the effects of ageing, dosage, and immunogenic response, among others. In vivo experiments using mouse models of osteosarcoma revealed that precise control of RONS concentrations is critical, and that the combinatorial strategy that we propose with our technology has been validated.
Overall, the development of these studies has significantly advanced our technology and set a promising trajectory for further research and eventual integration into clinical practice.
Technical proof of concept in advanced preclinical models: Comprehensive studies were conducted to understand the physico-chemical properties of PTL and PTH, and the impact of plasma in their characteristics. Several in vitro biological studies were conducted to thoroughly analyze the effects of PTL and PTH on cancer cells compared to their impact on healthy tissues. Important findings in this section included the effects of ageing, dosage, and immunogenic response, among others. In vivo experiments using mouse models of osteosarcoma revealed that precise control of RONS concentrations is critical, and that the combinatorial strategy that we propose with our technology has been validated.
Overall, the development of these studies has significantly advanced our technology and set a promising trajectory for further research and eventual integration into clinical practice.
The TRANSFORMER project has made significant progress in advancing plasma-based therapies, bringing them closer to a viable clinical solution. Our research has not only validated the technical feasibility of using plasma-treated liquids and hydrogels as delivery systems, but also advanced in the development of IP, regulatory and technology transfer strategies, along with market analysis and business plans, have been key for the effective advancement of the technology. In this regard, the objectives related to the assessment of the commercial viability have been accomplished and are the following:
1. Regulatory position and analysis: The regulatory landscape was evaluated to identify potential hurdles and ensure compliance with existing medical device regulations. A viability analysis and two regulatory pathways for our two patents were developed with the help of a specialized consultancy. This step was crucial to outline the pathway to clinical trials and adapt our strategy from early stages.
2. IP position and strategy: Our two patents (WO 2021/255179 and WO 2022/112206) are currently in National Phases. A detailed roadmap has been developed to highlight the next steps and required payments to secure the protection in the designated countries. A thorough analysis of the IP landscape has been performed, with a Freedom To Operate (FTO) search and an IP strategy to avoid infringements.
3. Market analysis: A detailed market analysis was conducted to understand the potential demand for our technology, identify key stakeholders, and evaluate the competitive landscape. This analysis helped in refining the value proposition and business model.
4. Technology transfer position and strategy: Several strategies have been studied for transferring the technology from the research phase to clinical application. This included identifying potential industry partners, exploring licensing opportunities, and planning for future collaborations.
The commercial need for such an innovation is evident across several dimensions. This disruptive technology has the potential to address the current unmet needs in osteosarcoma treatment, including high relapse rates, the necessity for high chemotherapy doses, and the frequency of secondary reconstructive surgeries. By providing a localized, less invasive treatment option, the physical and psychological burden on patients can be reduced, while providing more efficient treatment options for clinicians. The proposed solution also stands to redefine the economic landscape of cancer care through direct cost savings, enhanced patient outcomes leading to reduced indirect costs, and stimulate growth within the biotechnology and healthcare industries. Furthermore, the environmental impact of the technology can be seen as part of a broader movement towards more sustainable medical treatments, minimizing resource utilization, and reducing the chemical waste related to the current treatments.
Looking forward, several key steps are needed to ensure the successful uptake and commercialization of this technology. Further research and development will refine treatment protocols and confirm long-term safety and efficacy. Fundraising efforts will be essential for technological progress and exploitation. The creation of a spin-off company will facilitate market introduction and business operations. Ongoing stakeholder engagement will support the adoption and integration of the technology into clinical practice. Maintaining a robust intellectual property strategy will protect our technology in the designated countries and secure competitive advantage.
In conclusion, the TRANSFORMER project has laid a strong foundation for a novel, dual-function cancer therapy that promises significant benefits for patients and the healthcare system. By continuing to build on these achievements, more effective, less invasive treatments for osteosarcoma and potentially other cancer types can be developed, ultimately transforming the landscape of cancer care.
1. Regulatory position and analysis: The regulatory landscape was evaluated to identify potential hurdles and ensure compliance with existing medical device regulations. A viability analysis and two regulatory pathways for our two patents were developed with the help of a specialized consultancy. This step was crucial to outline the pathway to clinical trials and adapt our strategy from early stages.
2. IP position and strategy: Our two patents (WO 2021/255179 and WO 2022/112206) are currently in National Phases. A detailed roadmap has been developed to highlight the next steps and required payments to secure the protection in the designated countries. A thorough analysis of the IP landscape has been performed, with a Freedom To Operate (FTO) search and an IP strategy to avoid infringements.
3. Market analysis: A detailed market analysis was conducted to understand the potential demand for our technology, identify key stakeholders, and evaluate the competitive landscape. This analysis helped in refining the value proposition and business model.
4. Technology transfer position and strategy: Several strategies have been studied for transferring the technology from the research phase to clinical application. This included identifying potential industry partners, exploring licensing opportunities, and planning for future collaborations.
The commercial need for such an innovation is evident across several dimensions. This disruptive technology has the potential to address the current unmet needs in osteosarcoma treatment, including high relapse rates, the necessity for high chemotherapy doses, and the frequency of secondary reconstructive surgeries. By providing a localized, less invasive treatment option, the physical and psychological burden on patients can be reduced, while providing more efficient treatment options for clinicians. The proposed solution also stands to redefine the economic landscape of cancer care through direct cost savings, enhanced patient outcomes leading to reduced indirect costs, and stimulate growth within the biotechnology and healthcare industries. Furthermore, the environmental impact of the technology can be seen as part of a broader movement towards more sustainable medical treatments, minimizing resource utilization, and reducing the chemical waste related to the current treatments.
Looking forward, several key steps are needed to ensure the successful uptake and commercialization of this technology. Further research and development will refine treatment protocols and confirm long-term safety and efficacy. Fundraising efforts will be essential for technological progress and exploitation. The creation of a spin-off company will facilitate market introduction and business operations. Ongoing stakeholder engagement will support the adoption and integration of the technology into clinical practice. Maintaining a robust intellectual property strategy will protect our technology in the designated countries and secure competitive advantage.
In conclusion, the TRANSFORMER project has laid a strong foundation for a novel, dual-function cancer therapy that promises significant benefits for patients and the healthcare system. By continuing to build on these achievements, more effective, less invasive treatments for osteosarcoma and potentially other cancer types can be developed, ultimately transforming the landscape of cancer care.