Periodic Reporting for period 1 - SupraCarrier (Supramolecular hydrogels as local controlled drug delivery carriers)
Berichtszeitraum: 2017-02-01 bis 2018-07-31
The ERC-2016-PoC project SupraCarrier explored the technical and commercial feasibility of a hydrogel-based drug-depot for the local controlled release of an anti-cancer drug. Business development was supported by participation of the research team in the Venture Challenge Business Incubator program of the Top Sector Life Sciences (Health Holland) to further reinforce the commercial feasibility.
The goal of this ERC PoC study was to:
1) Validate the commercial feasibility of the hydrogel; a fast pH-switchable, self-healing, injectable supramolecular hydrogel, for the sustained release of an anticancer drug in combination with intraperitoneal administration for potential treatment of peritoneal malignancies.
2) Conduct a market analysis to prioritize the clinical indications where this system can be deployed.
3) Evaluate and strengthen the IP position.
4) Establish a preclinical proof of concept of using the UPy-hydrogel for local and sustained release of an anti-cancer drug for the treatment of peritoneal malignancies.
Results
In order to enable effective local intraperitoneal chemotherapy, a lead formulation of the hydrogel carrier and chemotherapeutic agent has been identified and developed. Mitomycin C was identified as the optimal drug candidate for the treatment of peritoneal malignancies. In order to improve the retention of the drug within the hydrogel and to enable a sustained release, several conjugation strategies were explored. Conjugation of mitomycin C to cholesterol resulted in an effective MMC-conjugate (c-MMC) candidate. As demonstrated by in vitro experiments, the optimized c-MMC exhibits a preserved cytotoxic effect and is released in a sustained manner from the hydrogel depot. The combination of a controlled release of the drug on one hand, and a preserved potency on the other hand, enables a sustained therapeutic effect, which is essential for improving current intraperitoneal chemotherapy. Thereby, our tunable drug delivery system has the potential to revolutionize the treatment of patients suffering from peritoneal cancer.
In view of exploring the commercial feasibility of the proposed technology, different commercialization pathways were investigated. Aided by the business incubator program the Venture Challenge, further development and ultimately commercial exploitation in the form of a startup was chosen. The business case for such a venture is further supported by a market analysis identifying a clear unmet clinical need and a strong problem-solution fit of the proposition. Intellectual property rights are currently in the process of being secured. Two patent applications have been filed to protect the technology for controlled drug delivery, which are made available by the TU/e for licensing. Complementary IP is owned by SupraPolix, and access to their portfolio of materials is part of ongoing negotiations. For material development and preclinical evaluation, strategic partnerships have been engaged with industrial and academic partners.
Next steps
Further development of the proposed technology requires evaluation of safety and effectiveness in a relevant preclinical disease model. A research agreement is in place with our partner MUMC to conduct the preclinical evaluation and to arrive at a proof-of-concept. After establishing feasibility in vivo, a full safety and effectiveness assessment is required for the optimized formulation, in compliance with the applicable regulatory demands.
Secondly, in view of production at commercially attractive scale and costs, standardization of processes for manufacturing of quality compliant, clinical grade (GMP) components of the intended product is a necessity. Companies specialized in scale-up of active pharmaceutical ingredients will be identified to assist in the production of GMP-compliant materials. Within the scope of the next phase, the team will engage with partners and third-party manufacturers to enable optimization of the synthetic routes for production of the hydrogelators and the conjugated mitomycin C.
Conclusion
Upon completion of this PoC project the team concluded that a viable business case is in place to support the incorporation of a startup company that will commercially develop and exploit the proposed technology and make this innovative therapy available to patients with peritoneal cancer. The startup under incorporation is currently preparing to attract early stage funding and applied for the NWO Take-Off 2 program. With the support of this additional funding the required preclinical studies can be done and the business case is strengthened to become investor ready and continue to build the startup.
Additionally, to streamline preclinical and ultimately clinical development, a sound regulatory strategy will be designed. To this end the team will seek the support of consultancy firms specialized in regulatory affairs and pharmaceutical development.
The goal of this ERC PoC study was to:
1) Validate the commercial feasibility of the hydrogel; a fast pH-switchable, self-healing, injectable supramolecular hydrogel, for the sustained release of an anticancer drug in combination with intraperitoneal administration for potential treatment of peritoneal malignancies.
2) Conduct a market analysis to prioritize the clinical indications where this system can be deployed.
3) Evaluate and strengthen the IP position.
4) Establish a preclinical proof of concept of using the UPy-hydrogel for local and sustained release of an anti-cancer drug for the treatment of peritoneal malignancies.
Results
In order to enable effective local intraperitoneal chemotherapy, a lead formulation of the hydrogel carrier and chemotherapeutic agent has been identified and developed. Mitomycin C was identified as the optimal drug candidate for the treatment of peritoneal malignancies. In order to improve the retention of the drug within the hydrogel and to enable a sustained release, several conjugation strategies were explored. Conjugation of mitomycin C to cholesterol resulted in an effective MMC-conjugate (c-MMC) candidate. As demonstrated by in vitro experiments, the optimized c-MMC exhibits a preserved cytotoxic effect and is released in a sustained manner from the hydrogel depot. The combination of a controlled release of the drug on one hand, and a preserved potency on the other hand, enables a sustained therapeutic effect, which is essential for improving current intraperitoneal chemotherapy. Thereby, our tunable drug delivery system has the potential to revolutionize the treatment of patients suffering from peritoneal cancer.
In view of exploring the commercial feasibility of the proposed technology, different commercialization pathways were investigated. Aided by the business incubator program the Venture Challenge, further development and ultimately commercial exploitation in the form of a startup was chosen. The business case for such a venture is further supported by a market analysis identifying a clear unmet clinical need and a strong problem-solution fit of the proposition. Intellectual property rights are currently in the process of being secured. Two patent applications have been filed to protect the technology for controlled drug delivery, which are made available by the TU/e for licensing. Complementary IP is owned by SupraPolix, and access to their portfolio of materials is part of ongoing negotiations. For material development and preclinical evaluation, strategic partnerships have been engaged with industrial and academic partners.
Next steps
Further development of the proposed technology requires evaluation of safety and effectiveness in a relevant preclinical disease model. A research agreement is in place with our partner MUMC to conduct the preclinical evaluation and to arrive at a proof-of-concept. After establishing feasibility in vivo, a full safety and effectiveness assessment is required for the optimized formulation, in compliance with the applicable regulatory demands.
Secondly, in view of production at commercially attractive scale and costs, standardization of processes for manufacturing of quality compliant, clinical grade (GMP) components of the intended product is a necessity. Companies specialized in scale-up of active pharmaceutical ingredients will be identified to assist in the production of GMP-compliant materials. Within the scope of the next phase, the team will engage with partners and third-party manufacturers to enable optimization of the synthetic routes for production of the hydrogelators and the conjugated mitomycin C.
Conclusion
Upon completion of this PoC project the team concluded that a viable business case is in place to support the incorporation of a startup company that will commercially develop and exploit the proposed technology and make this innovative therapy available to patients with peritoneal cancer. The startup under incorporation is currently preparing to attract early stage funding and applied for the NWO Take-Off 2 program. With the support of this additional funding the required preclinical studies can be done and the business case is strengthened to become investor ready and continue to build the startup.
Additionally, to streamline preclinical and ultimately clinical development, a sound regulatory strategy will be designed. To this end the team will seek the support of consultancy firms specialized in regulatory affairs and pharmaceutical development.