HE ERC Proof of Concept Grant 2022-2024

Preclinical validation and market analysis of a microMESH implant for brain cancer eradication

Sommario: Despite tremendous progress in the treatment of several malignancies, glioblastoma continues to be the less curable form of any cancer with an overall average survival of 20 months from diagnosis. In this PoC, an interdisciplinary team of engineers, biotechnologists and technology-transfer experts will work to prove that a ground-breaking drug delivery implant – microMESH – can be engineered to deploy intracranially a chemo-immuno-combination therapy to eradicate glioblastoma and minimize its life-long complications. microMESH will be engineered to deliver chemotherapeutic drugs (taxanes) and monoclonal antibodies (anti-CD47), that normally would not cross the blood brain barrier, uniformly and deep in the tumor bed. microMESH will comprise two physically distinct compartments – a micrometric network of poly(lactic-co-glycolic acid) (PLGA) strands, carrying taxane molecules; a poly(vinyl alcohol) (PVA) microlayer, encapsulating anti-CD47. Upon deposition on the tumor mass, the PVA microlayer will dissolve in a few days releasing directly on the tumor margins anti-CD47 while the thin and flexible PLGA network will progressively conform to the surrounding surface, establishing an intimate interaction with the malignant cells, and release taxanes in a sustained fashion over several weeks. While taxanes will prevent the rapid proliferating glioblastoma cells from growing, anti-CD47 will stimulate the removal of cancer cells by resident and infiltrating immune cells. The success of this PoC will result in a preclinically validated microMESH for the treatment of newly diagnosed and recurrent glioblastoma. Upon subsequent completion of GLP toxicological and cGMP manufacturing studies, microMESH will advance to a Phase 1/2 trial expected to start as early as 2024. In this space, companies with validated Phase 1/2 assets have market capitals ranging from 50M to 400M€. A successful microMESH could lead to revenues of 10M €/year starting already in 2027.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Proof of Concept Grant 2019-2021

tPA-Nanoconstructs for Treating Acute Ischemic Stroke: a Technical and Commercial Analysis

Sommario: Acute ischemic strokes result from the occlusion of cerebral vessels by blood clots causing neurological complications, brain damage and death. Based on WHO reports, stroke affects 17M people per year worldwide, with 6M deaths and 5M survivors suffering long-lasting disabilities. Recent statistics estimate an EU direct healthcare cost for stroke of €20B and indirect costs, due to disabilities and lost productivity, of €25B. The two current treatments – thrombolysis and thrombectomy – come with limitations and considerable side effects. Thrombolysis can be safely administered only to a small cohort of patients (about 5%) whereas thrombectomy induces disabilities in 50% of the cases. Moved by the societal, economical, and emotional burden associated with stroke, this proposal aims at developing and validating more effective and less toxic therapies via the combination of the clinically approved molecule tPA and rationally-designed, discoidal polymeric nanoconstructs (DPNs). As compared to tPA, the proposed thrombolytic nano-agents (tPA-DPNs) are expected to provide faster blood clot dissolution; safer administration profile; longer blood circulation and stability. On the technical side, tPA-DPNs will be re designed to improve their biodegradation and excretion profiles; validated in FDA-recognized stroke models for neurotoxicity and therapeutic efficacy. On the commercial side, a patent portfolio covering the fabrication and utilization of tPA-DPNs will be secured, together with thorough market and business analyses. This will facilitate the interaction with pharmaceutical companies that are investing in the fast growing markets of high-tech drug delivery systems and stroke diagnostics and therapies. tPA-DPNs are expected to alleviate the economic burden on healthcare systems, increase the total sale of thrombolytic agents, revolutionize the medical protocols for stroke management, and diminish the societal and emotional impact of stroke.

Total budget: 125.620,99€

Total contribution: 125.620,99€

FP7 ERC - Consolidator Grant 2014-2020

Engineering Discoidal Polymeric Nanoconstructs for the Multi-Physics Treatment of Brain Tumors

Sommario: Despite significant advances in chemotherapy, the effective treatment of malignant masses via systemically injectable agents are still limited by insufficient accumulation at the biological target (<< 10% injected dose per gram tumor) and non-specific sequestration by the reticulo-endothelial system (tumor/liver < 0.1). The goal of this proposal is to engineer Discoidal Polymeric Nanoconstructs (DPNs) to preferentially target the malignant neovasculature for the delivery of imaging agents, controlled release of therapeutic molecules and thermal energy. The central hypothesis is that the size, shape, surface properties and stiffness (4S parameters) of the DPNs can be controlled during synthesis, and that therapeutic molecules (Temozolomide), Gd(DOTA) complexes and ultra-small Super-Paramagnetic Iron Oxide nanoparticles (USPIOs) can be efficiently incorporated within the DPN polymeric matrix. This will be achieved by pursuing 3 specific aims: i) synthesis and physico-chemical characterization of poly(lactic-co-glycolic acid)/poly(ethylene glycol) DPNs with multiple 4S combinations; ii) in-silico and in vitro rational selection of DPN configurations with preferential tumor deposition, low macrophage uptake and high loading; and iii) in-vivo testing of the DPN imaging and therapeutic performance in mice bearing Glioblastoma Multiforme (GBM). The innovation stays in i) using synergistically three different targeting strategies (rational selection of the 4S parameters; magnetic guidance via external magnets acting on the USPIOs; specific ligand-receptor recognition of the tumor neovasculature); ii) combining therapeutic and imaging molecules within the same nanoconstruct; and iii) employing synergistically different therapeutic approaches (molecular and thermal ablation therapies). This would allow us to support minimally invasive screening via clinical imaging and enhance therapeutic efficacy in GBM patients.

Total budget: 2.390.000,00€

Total contribution: 2.346.785,16€