Advance Partnerships

ADVANCE PARTNERSHIPS - The ecosystem for Pharma, Biotech, MedTECH and Cosmetics Companies  looking for latest discoveries & scientific collaboration in Drug Discovery & Therapeutic candidates, Diagnostics, R&D technologies &  MedTECH; and for Hospitals, Academic Centers, Universities and Scientific Institutes interested in Industry partners for their healthcare discoveries & expertise

Our experimental data show that, following treatment of SCs with chemotherapeutic drugs, it was possible to observe a significant reduction in hydroxymethylcytosine and a significant reduction in the gene expression of GDNF and of the GDNF protein compared to untreated SCs. Furthermore, a protective effect of EPA was demonstrated at a concentration of 100 μM on SCs treated at the highest dose of cisplatin (3.33 μM). This effect was demonstrated both in terms of gene and protein expression of Sertolian GDNF, and in terms of gene expression and secretion of AMH and inhibin B as specific markers of Sertolian functionality. In particular, Sertolian GDNF was surprisingly recovered compared to the control group and AMH and inhibin B reached values comparable to those of the control group. Current phase & next steps We have completed in vitro PC testing and are ready for in-vivo PC phase. Here at University of

This invention relates to the use of anakinra to produce an inhalable dry powder for the treatment of pathological inflammation in patients with cystic fibrosis (CF). Persistent inflammation and infection lead to permanent structural damage of the CF airways, impaired lung function, and eventually to respiratory failure and death. Recent studies have suggested a link between neutrophilic inflammation, mucus obstruction and the IL-1R signalling pathway. Therefore, targeting IL-1R signalling could be an effective strategy to prevent structural lung damage. Such conditions could be efficiently rescued by anakinra, a recombinant non-glycosylated form of the endogenous IL-1R antagonist. Anakinra (Kineret®) is administered subcutaneously for the treatment of rheumatoid arthritis, cryopyrin-associated periodic syndromes, and the systemic-onset juvenile idiopathic arthritis. Owing to low compliance and side effects, the current form is not suitable for chronic treatments, such as in CF. Therefore, turning anakinra into an inhalable dry powder can enhance efficacy, stability, and compliance, reduce side effects allowing repurposing of the drug in CF therapy. TECHNOLOGY/INVENTION An inhalable dry powder of anakinra was successfully developed to meet the specific needs of lung drug delivery. The new formulation was investigated in vitro for aerodynamic performances and activity and in vivo for its pharmacological profile, including the pharmacokinetics, treatment schedule, antimicrobial and anti-inflammatory activity and systemic toxicity. The protein was structurally preserved inside the formulation and retained its pharmacological activity in vitro immediately after preparation and over time when stored at ambient conditions. Anakinra when delivered to the lungs showed an improved and extended therapeutic efficacy in CF models in vivo as well as higher potency compared to systemic delivery. Peripheral side effects were significantly reduced and correlated with lower serum levels compared to systemic treatment.

The invention relates to oxysterol derivatives PFM037 and PFM046, able to act as antagonists of the Liver X Receptors (LXRs) which can be used alone or in combination with other anti cancer therapies, such as the immune checkpoint inhibitors (CI) or T cell adoptive therapy to treat different cancers, including melanoma, Hodgkin lymphoma, renal, lung, bladder and head and neck cancers. The inventors found that SULT2B1b system manipulation favours the differentiation of Ly6C+ monocytes into Mono-DCs. This pathway is associated with lipidome reprogramming characterized by reduced levels of cellular cholesterol/cholesterol derivatives and glycerophospholipids, and increased levels of polyunsaturated fatty acid precursors of lipid mediators endowed with pro-inflammatory activity. This lipidomic profile was also detected in tumours from mice treated with the new synthetic compounds PFM037 and PFM046, structurally and functionally related to SULT2B1b-derived products. PFM037 contributes to monocyte differentiation and induces effective antitumor responses by interfering with LXR signalling. Moreover, it increases the efficacy of ICIs and T cell adoptive therapy. Finally, by interrogating available scRNA-seq datasets

The invention described herein relates to the use of OMEGA-3 polyunsaturated fatty acids (EPA) for the prevention and treatment of male infertility in prepubertal subjects undergoing chemotherapeutic and/or radiotherapeutic treatments for the treatment of neoplasms. Background The chemo- and radiotherapy treatments used in the cure of pre-pubertal subjects affected by neoplastic diseases and serious inflammatory diseases of autoimmune etiology, have high cytotoxicity capable of altering or completely compromising the male gonad, with consequent reduction or loss of endocrine function and fertility. In adult patients, preservation of semen before cancer treatment is currently the only method of preserving future male fertility. Obviously, this technique is not an option for pre-pubertal patients who do not yet produce mature spermatozoa that can be used for routine sperm cryopreservation. The Sertoli cells (SCs), the only somatic cell type in the seminiferous tubules, can be considered the real “director” of spermatogenesis. SCs growth factors, such as glial cell line-derived neurotrophic factor (GDNF), have been identified as the most important upstream factors that regulate spermatogonial stem cells (SSC) germ cell self-renewal and spermatocyte meiosis. DNA methylation, considered as one of the main epigenetic mechanisms, is already known to influence male fertility. It was demonstrated that eicosapentaenoic acid (EPA), a fatty acid with anti-cancer properties, is able to decrease DNA methylation levels through the activation of ten-eleven translocation enzymes proteins (TETs). We report the effects on porcine neonatal SCs “in vitro” of three different chemotherapeutic agents, cisplatin, 4- Hydroperoxycyclophosphamide (40HP) and doxorubicin, commonly administered to pre-pubertal candidates undergoing anti-cancer therapy, and the positive effects of EPA on these gonado-toxic compromised SCs.

The manufacturing method is a physical recovery process of phenolic substances from the olive mill waste waters (OMWW) resulting from the virgin olive oil mechanical extraction process. The phytocomplex recovered is composed of a pool of hydrophilic phenols namely 3,4-DHPEA-EDA (oleacein), p-HPEA-EDA (oleochantal), 3,4-DHPEA (hydroxytyrosol), pHPEA (tyrosol) and verbascoside. The biological activities characterising the phenolic fraction of olive, virgin olive oil and olive mill by-products are largely demonstrated and are mainly referred to the antioxidant, antimicrobial and antinflammatory properties of those molecules. More recently several beneficial effects have been demonstrated on skin damage and skin disorders control underlining the olive phytocomplexes usefulness as active ingredients in the formulation of creams and serums. Due to the technology of recovery and concentration the olive phytocomplex obtained from OMWW have a particular qualitative-quantitative phenolic profile containing high percentages of unhydrolysed oleacein and oleochantal and also significant amount of hydroxytyrosol and (according to the olive cultivar) verbascoside. The ingredients obtained by this production methods are superior to similar ingredients obtained by different methods, in fact the bioactive phytocomplex can be obtained, according to the partial purification and concentration/stabilization technologies, in different form and title in total phenols (TPC): i) powder with maltodextrins (TPC ≃ 3-6 %); ii) liquid concentrate (TPC ≃ 6-8 %); iii) liquid purified extract T(PC ≃ 65-75 %). Furthermore, the qualitative-quantitative composition of phenols is always known and given (by HPLC). This method is also both very eco-clean and socially responsible, as it utilises currently unused/unusable waste of olive oil production, by recovering active biophenols and by contributing to the waste management and sustainability of the olive oil value-chain

In our lab, we have found that Cx43 induces cellular senescence in BRAF-mutated tumour and enhances BRAF/MEK- induced senescence and sensitizes cancer senescent cells to cell death by apoptosis mediated by activation of Caspase 3. Reactivation of Cx43 avoids acquisition of drug resistance in tumour cells and more importantly, re-sensitized resistant tumour cells to BRAF/MEKi treatment by inducing cell death by apoptosis. These results have been demonstrated in vitro and in vivo, and have been safeguarded in a patent protection. --- Mutations of MAPK, for instance BRAF mutations, are detected in many types of cancer. BRAF is a potent oncogene that is activated in more than 8% of all cancer types. Approximately about 30 - 50 % of thyroid cancer, 3 % of non-small cell lung cancer (NSCLC), 5 % to 10 % of patients with metastatic colorectal cancer, 100 % of hairy cell leukaemia and more than 50 % of melanoma patients have a mutation of the proto-oncogene BRAF, that lead to a constitutive activation of the serine/threonine kinases of the MAPK cascade. Mutations in BRAF were initially described with V600E being the most common mutation. These mutations lead to constitutive activation of BRAF and RAS-RAF-MEK-ERK signalling cascade, which promotes cancer growth by enhancing cell proliferation and survival while inhibiting cell death by apoptosis. Following the discovery of V600E mutation..

The present invention offers a novel strategy for the treatment of Rb-positive tumors, applicable both as monotherapy and in combination therapies with CDK4/6 inhibitors. This approach addresses innate and acquired resistance to CDK4/6 inhibitors, enhancing their efficacy in patients with Rb-positive tumors and reducing the likelihood of cancer relapse. Specifically, the findings demonstrate that restoring Cx43 in Rb-positive cancer cells induces proliferation arrest and triggers a senescent-like phenotype. Moreover, combining Cx43 with CDK4/6 inhibitors significantly enhances the efficacy of the senolytic drug Navitoclax. The use of nanovesicles to deliver Cx43 shows robust anti-tumor activity in Rb-positive cancer cells and improves the therapeutic outcomes of both CDK4/6 inhibitors and Navitoclax.This innovative approach highlights the potential of Cx43 restoration and targeted delivery systems as a promising advancement in Rb-positive tumor therapy.

Despite its widespread prevalence, current treatments for osteoarthritis (OA) often provide only limited relief from symptoms without addressing the underlying disease progression. Our proposed therapeutic strategy is set to transform the treatment of OA by using mRNA CONNEXIN43 activator . This method focuses on direct intra-articular administration. This innovative, 1st-in-class treatment (new target and new MOA) approach aims not only to halt the progression of OA and enhance tissue regeneration, but also to redefine the standard for complex aging-related diseases therapies. Background Osteoarthritis (OA), the most prevalent form of arthritis worldwide, affects millions of individuals, particularly among older populations. It is estimated that approximately 10% of men and 18% of women aged over 60 years suffer from symptomatic OA globally. This chronic condition significantly impacts quality of life, causing pain, stiffness, and reduced mobility. Current treatments for OA, primarily non steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, offer limited relief from symptoms without addressing the underlying causes and progression of the disease. Emerging therapies, including senotherapeutics targeting cellular senescence, hold promise for OA patients. Specifically, peptides that target Connexin43 (Cx43) show potential for improving OA management. INVENTION The present invention relates to senolytic agents comprising peptide fragments of Cx43, preferably the peptide fragments...

Background Triple Negative Breast Cancer (TNBC) is known for its aggressiveness, poor prognosis, and lack of effective targeted treatments. Recent advancements offer promise for TNBC with BRCA1/2 mutations, which struggle with DNA repair. Specifically, new PARP enzyme inhibitors (PARPi) exploit this repair deficiency to effectively target BRCA1/2-mutated cancer cells. The accumulation of DNA damage sensitizes tumor cells to subsequent immunotherapies, with ongoing trials exploring the combination of PARPi with immune checkpoint inhibitors, yielding encouraging outcomes. However, resistance is present in more than 70% of patients, emphasizing the need to explore new targets to develop new combined therapies in order to enhance efficacy and overcome resistance. 6.1.2025 2/4 www.advance-parnerships.com Our proposal centers on a proof of concept (TRL3/TRL4) involving the restoration of a new target, connexin43 (Cx43), in human TNBC BRCA1-mutated cells using cell-derived nanovesicles (EVs) for (mRNA and protein) delivery. Cx43 emerges as a strategic approach to treat TNBC and to enhance efficiency and overcome resistance to PARP inhibitors, addressing a significant and unmet clinical limitation. Moreover, our research demonstrates that restoring Cx43 in tumor cells triggers a more robust anti-tumor immune response. INVENTION DESCRIPTION Connexin 43 provides a reliable therapeutic strategy for improving sensitivity and reducing resistance to PARPi in BRCA1/2 mutated tumours. This reliable therapeutic strategy comprises the use of