Missione 4 — Istruzione e Ricerca | PNRR per la M4C2 Investimento 1.5
Codice identificativo: ECS_00000041 | CUP: H33C22000430006

Innovative Therapeutic Approaches: New Chemical Entities, Biologics and Drugs Delivery

SPOKE 8 — PNRR MISSIONE 4

Specialization Area/Technological Focus

UNIURB is located in the north-west of the Marche Region, specifically in the Pesaro e Urbino Province. As such, it plays a crucial role in both defining and implementing the Smart Specialisation Strategy (S3) of the Marche Region. Currently, we find ourselves in a “transition” phase since the previous seven-year period, which encompassed the previous S3 Strategy, ended over a year ago. This period spanned from 2014 to 2020. On the other hand, while a new seven-year period has begun (2021-2027), the new S3 Strategy has not yet been adopted. Since the beginning of 2021, the Marche Region has initiated consultation phases involving all stakeholders interested in the objectives and goals of the S3. At present, the themes for the S3 2021-2027 have already been identified, and one of the key focuses of the regional S3 2021-2027 will be “Health products and services.”

UNIURB, recognized as a center of high competence and expertise in Biology, Pharmaceutical Science, Personalized Medicine, Diagnosis, and related fields, hosted a round table dedicated to this S3 theme. In close proximity to the university, numerous spinoffs and private companies, including both SMEs and larger enterprises, are engaged in this sector at an exceptional level of excellence. These companies collectively employ a significant workforce of about 5,400 people. In other words, the “Health” sector is a driving force for the Marche Region and will continue to play a prominent role in the forthcoming regional S3 Strategy.

The identified “innovation lines” within the “Health products and services” theme for the S3 2021-2027 include:

    • Innovative therapeutic approaches
    • e-Health
    • Innovative approaches for elderly care and localized medicine
    • Innovative diagnostics

The Spoke led by UNIURB will implement actions aligned with the objectives of the regional S3 Strategy, thereby contributing to its realization during the 36-month program duration. It is worth noting that regional actors, such as companies, research centers, and universities, have already established a collaborative approach towards common goals. This collaborative spirit has yielded significant advantages in terms of innovation and the impact of research and development investments in the Marche Region. Two ongoing examples of such collaborations involving UNIURB are the “Collaborative Research Platform in Personalized Medicine: Drugs, Diagnostics, and New Therapeutic Approaches – MARCHE BIOBANK” and the “Marche Applied Research Laboratory for Innovative Composites – MARLIC.” These platforms aim to strengthen the implementation of the regional S3 2014-2020 by focusing on two thematic areas: 1. “Personalized Medicine, Drugs, and New Therapeutic Approaches” and 2. “Eco-sustainability of Products and Processes for New Materials and Demanufacturing.” These joint collaborations between universities, private companies, and research centers aim to establish Marche Region as a leader in these specific sectors and contexts, thereby generating positive economic and scientific impacts within the region.

The research program of the UNIURB Spoke is structured around four main research topics, each encompassing a range of initiatives, from theoretical research and training to technology transfer and dissemination. The research topics are as follows:

    • Development of a third-party-accessible, enabling platform for efficient preclinical drug discovery (WP1)
    • Innovative biologics for the treatment of unmet medical needs in rare metabolic disorders and oncology (WP2)
    • Advanced drug delivery systems and in vivo theranostic tools for personalized medicine (WP3)
    • Economic assessment, dissemination, and technology transfer (WP4).

INVOLVED PERSON

Università di Urbino Carlo Bo

Università "G. d'Annunzio" Chieti – Pescara

Università di Perugia

Meccano

CosMob

RESEARCH TOPIC

Work package

Objectives of research

Objectives of each research topic are briefly described in the following:

Development of a third party-accessible, enabling platform for efficient preclinical drug discovery (WP1)

The goal of WP1 is to enable the delivery of optimised leads at an accelerated pace. This key objective will be achieved by means of interconnected tasks: a) setting up a purposely conceived platform for the identification of new leads through a virtuous design-synthesis-test cycle. Efficiency (i.e., we do not aim at synthesising/testing many compounds, we aim at working with only the right ones) will be guaranteed by state-of-the-art physics- and AI-based simulative tools including virtual screening of ultra-large libraries, advanced synthetic paradigms such as flow technology and automation, assays in multiple cell lines and in organoid models, and lipidomics-based predictions of hepatotoxycology; b) adopting the now established multitarget-directed ligand approach, that is rationally engineering activity at multiple targets, as a way to rapidly exploit actionable knowledge coming from genomic and electronic medical records analysis; and c) leveraging our knowledge of specific metabolic pathways and pathologies (e.g., oxidative stress in cancer, nicotine addiction, etc.) to streamline the identification of new compounds. Hence, WP1 will not only generate value through new molecules but will also contribute to validate and de-risk new targets and target combinations. There is clear potential for synergy with the activities carried out in WP2 (e.g., drug-antibodies conjugates) and WP3 (drug delivery). Overall, the value of this endeavour is two-fold: on the one hand, generating IP through novel molecules, with the possibility of incorporating spinoffs, attracting investments and out licensing patents; on the other hand, to foster partnerships with commercial entities interested in using our platform to develop their projects.

Innovative biologics for the treatment of unmet medical needs in rare metabolic disorders and oncology (WP2)

The main objective of WP 2 is the development of innovative biologics for the treatment of unmet medical needs in rare metabolic disorders and oncology taking advantage from an already established public-private regional initiative involving 10 small and large companies and three universities and several patients’ organisations. The implementation proposed in this WP will exploit the results already obtained, the infrastructures activated, and the knowledge gained for an integrated action that will benefit patients, companies and contribute to promoting further entrepreneurial activities. The WP will be organised around 3 platforms a) metabolic rare diseases. Synthetic biology for the development of new recombinant enzymes or modmRNA to be administered to patients in need; b) human antibodies and fragment derivatives to be used in oncology; c) cell-based delivery systems for in vivo delivery of biologics. These platforms will be integrated with WP1 and WP3 activities and the results made available to the project partners. As explained in WP4 the results, products and knowledge will be exploited by the newly founded start-up. IP generated by the project will be protected according to the rules of participating institutions.

Advanced drug delivery systems and in vivo theranostic tools for personalised medicine (WP3)

The main goal of the WP3 is the design of innovative strategies to reach patient-centred therapies personalised on specific patient needs in terms of efficacy, accuracy, safety, and/or compliance of diagnosis and treatment of diseases. To this end, three specific objectives will be pursued: i) development of personalised pharmaceutical dosage forms by additive manufacturing technologies; ii) engineering bioinspired and biomimetic nanomedicines for precise drug delivery, and iii) optimization of innovative methods to screen tissues and organs based on drug loaded iron oxide nanoparticles (SPION), embedded into red blood cells that can be magnetically guided and traced by Magnetic Resonance Imaging (MRI) and magnetic particle imaging (MPI ).

Economic assessment, Dissemination and technology transfer (WP4)

WP4 main objective will be the evaluation of the economic equilibrium linked to the development of new drugs and therapeutic approaches in relation to the relationship between investment, industrialisation and commercialisation costs, on the one hand, and economic benefits (in terms of savings for health systems or income that can be generated for businesses), on the other hand; WP4 will also study the definition of communication policies and promotion of the innovative solutions identified, and the development of business models that can give life to innovative spin-offs and start-ups. Another main objective will be the Technology Transfer referred to the health and life sciences sector, with particular attention to new services, new products, new financing methods and the management of intellectual property.

Work Plan, Feasibility, Monitoring

Capacity

All the listed activities will be carried on by the researchers of UNIURB belonging to different departments and research groups, with the integration of new researchers and PhD students funded by the project.. Also qualified staff of affiliated companies will collaborate on the project, especially for the technology transfer part. WP1 builds on UniUrb’s long-standing tradition in drug discovery, with several compounds conceived in Urbino later advancing to clinical trials (e.g., URB597) and is made possible by a multidisciplinary environment, with several research groups actively working in linked areas of interest in drug discovery, ranging from advanced mass spectrometry, medicinal chemistry, and pharmacology. WP2 will be based on the expertise and already established network of scientists with more than 15 patents and entrepreneurs that were involved in launching several start-ups. The expertise include biochemists, molecular biology researchers, biotechnology competences, regulatory expertise. In addition, the group is able to manage all activities related to upstream and downstream processes in the production of biologics. Monoclonal Ab obtained via traditional approaches and phage display libraries are part of the competences of the team. WP3 will be led by the pharmaceutical technology research group. Their expertises on innovative formulations development (e.g. 3D printing) and nano drug delivery systems manufacturing (e.g. microfluidics) will be joined by a multidisciplinary team, composed of researchers working in the biochemistry and inorganic chemistry fields. The later groups possess specific skills on exosomes isolation and characterization, red blood cells loading and SPION applications in vivo, together with synthesis and optimization abilities of imaging markers useful for diagnostic purposes. Advanced technical characterizations (e.g. flow cytometry and confocal analyses) and in vitro assays biological assessment are also present. The development of WP 4 will be managed by UNIURB which has internally qualified skills in business management, budgeting, marketing, communication, technology transfer, legal issues. This will allow optimal planning and management of all the activities planned within this WP. The working group will interact with the researchers involved in the research project for defining timing and content of the activities.

Monitoring and evaluation

Quality planning through the implementation of quality assurance procedures with particular focus on monitoring review activities built into the work programme and submitting quality review reports. A quality plan within the Project Quality Handbook will specify the quality procedures, internal and external peer reviews, control, monitoring and reporting activities to be implemented in the project to ensure that satisfactory quality standards are met. This activity will cover also the risk management, setting up a framework for risk identification, team discussion and approval of contingency plans to tackle the most severe risks. The qualitative evolution of the activities of the projects will be carried on during the monthy meeting of the scientific council of the spoke. At the end of the meeting a detailed report will be prepared where, for every project, the evolution status will be evaluated against the project Gantt. The quantitative evaluation will be performed by comparing the status of the single project versus the reach of the declared milestones and the expected targets. Corrective measures, if necessary, will be proposed by the project leader and approved by the scientific council of the spoke. Ex-post evaluation of each and any of the projects will be performed within 3 months after the end of the projects and, again, after 12 months, to compare the expected outcomes with the actual ones. A detailed ex-post evaluation report will be produced under the coordination of the Spoke coordinator.

Impact

Economic Impact

In line with the tenets of open innovation, we envision a bi-directional flow of people and ideas between UniUrb and companies, that is made possible by an agile and externally accessible platform for lead identification and optimisation. Encompassing advanced computational methods, synthetic chemistry skills and sound knowledge in key therapeutic areas, the platform generates value through:

i) unique know-how, made available to both big players and local SMEs, limiting the need for massive infrastructural investments (for example, for high-throughput wet screening), shortening time to market, and, thus, with clear potential for attracting extramural funds and partnerships.

ii) composition of matter patents, claiming in house generated compounds active in key therapeutic areas such as oncology. This IP is instrumental to incorporate spin-offs and attract investments within the emerging framework of portfolio-companies.

This spoke aims to support the National Health Service to increase the awareness of all interested parties regarding innovation based on omics sciences and its effects on the health of individuals and populations with the aim of: transferring genomic knowledge to the practice of health services, in a patient-centred approach; increase the effectiveness of the prevention, diagnosis and treatment of diseases, taking into account individual differences in genetic heritage, lifestyles and environment and provide professionals with the necessary resources to personalise interventions.

The thematic area of this project concerns personalised medicine and the development of new drugs and / or therapeutic approaches for the treatment and management of chronic diseases, oncological diseases with high medical needs and rare diseases. The technological megatrends of the thematic area provide for the development of highthroughput methods in the field of omics sciences and diagnostics useful for patient stratification and therapy personalisation for customised medicine; Big data management; the development of innovative and customisable formulations that also use 3D printing; in the treatment of rare diseases a trend is represented by the repositioning of drugs and active ingredients already approved; in the oncology field, the development of targeted drugs and especially biological drugs associated with companion diagnostics; in the prevention of chronic diseases the use of nutraceutical approaches that are accompanied by nutrigenetic and nutrigenomic information.

Social Impact

The National Health System expresses a strong need to implement personalised medicine and to have innovative diagnostic and therapy activities as evidenced by the numerous adhesions of patient organisations, in particular in the area of rare diseases and oncology. The proposed spoke intends to start a path that it has as an aim to provide answers to these medical needs.

The ability to provide diagnostic and therapeutic answers represents a real engine for the development of an entire thematic area. In our Region we have met little known but highly innovative realities with core business in other areas but with the propensity to expand their business areas also in the health sector.

Some examples are those of a company that does 3D printing in the automotive area that is venturing into the production of cell culture printing to be used in the creation of cell therapies. Or of companies operating in the ICT area with interests in developing AI approaches to collect data from biological samples.

In practice, even if the biomedical industry, diagnostics and pharmaceuticals in the Region does not have a marked visibility, it is growing more than any other sector and is already increasing employment more than other sectors. The possibility of creating a platform of knowledge and services will contribute to the development of this thematic area.

The related activities deriving from the planned workplan will increase the direct employment of 40-50 highly qualified personnel over the three-year period. First of all, it will be the companies that will use the technological solutions offered by the platform for the development of their current products but also for future new products.

In addition, the companies of the health service will be indirectly responsible, being able to use the service of characterization of biological samples (second level characterization) within the spoke/hub without outsourcing these activities. The platform will have a detailed staff training program. In fact, training activities are planned in the field of production standards (GMP), in the context of analytical laboratory activities (GLP) and in the production and implementation of diagnostics (IVD).

Link with other actions

The Spoke leaded by UNIURB and the proposed activities are not extraneous to the national and regional programmes currently in force; in fact, they are in line and fit with the context in which the project will be realised and therefore are complementary and take advantage from other project and/or Programmes currently on-going. First of all, Spoke’s activities are aligned with the MARCHE BIOBANK Collaborative Platform objectives. This project was set up in Marche Region a couple of years ago and it is leaded by Diatheva Srl – former Spin-off of the University of Urbino founded in 2002 (twenty years ago).

In more detail, MARCHE BIOBANK intends to provide a response to the medical needs expressed by the territory in agreement with the priorities of the National Research Program 2015-2020 (that was ruling when the project was approved for funding). The area of Personalized Medicine is implemented by a regional network of 10 companies (two large: Angelini Pharma and Diatheva (SOL Group) and 8 SMEs: Diatech Pharmacogenetics, BiMind, Gluos, Mivell, PharmaProgress, Prosilas, Prosopika and Recusol) together with three public research organisms (University of Urbino, University of Camerino and Politecnico of Marche (Ancona)) and the regional foundation “Fondazione Cluster Marche”. It has to be underlined that all 3 University will be partners of this project proposal and collaborations with the above-mentioned companies will be defined and launched for the realisation of the Spoke’s activities.

The key priority of MARCHE BIOBANK is the implementation of a non-for-profit biobank that will be realised in the contest of the “Azienda Ospedaliero-Universitaria of Ancona” which will provide the land to be used for the new criobank. Four main activities are under implementation:

1. The implementation of a criobank (Marche BioBank) dedicated to the collection, characterization and distribution of samples donated mainly by patients with rare diseases, pediatric, and with oncological malignancies. The associate laboratory will be part of the biobank for the management of the samples and the preliminary characterization.

2. Three specific research projects (one in the area of oncology, one in the area of rare diseases and one in the area of chronic and debilitation conditions) are on-going.

3. A technology transfer program that involves all participants (public and private) where the large entities are supporting initiatives to facilitate the industrialization of research products from the partners and the Universities are supporting their TTO the SMEs by IP evaluation, networking and organization of training events.

4. Public engagement, communication and valorization of the platform. These activities are managed by the Fondazione Cluster Marche and involve not only Marche Region area but the whole national and European contest.

Potential technical and scientific collaborations, to be established between MARCHE BIOBANK partnership and the University of Urbino Spoke, could be reinforced both by common technology transfer actions as well as by joint communication and disseminations actions.

This project will be also supported by the National Technological Cluster “Life Sciences” founded by the Ministry of Education, University and Research and whose aims are to promote the dialogue between Universities, Public Research entities and Companies as well as between central and local territories for accelerating innovation processes and increase the industrial competitiveness of our Country.

Furthermore, Spoke’s activities are in line with the National Research Programme 2021-2027 considering that “Health” is one of the identified six “R&D Big Fields” and that three out of four selected intervention areas refer to “Biotechnology”, “Pharmaceutical Technology” and “Technology for Health”.