Search for partnering and collaboration

Development of AvidinOX-targeted lung cancer therapy by aerosol. Lung cancer is the most common neoplasia and the leading cause of death from cancer across the world. Since the introduction of targeted therapies with tyrosine kinase inhibitors over 20 years ago, the treatment of NSCLC showed improvement. Nowadays, these therapies remain the gold standard for many patients, but they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits. Despite this, challenges remain, as not all patients respond favorably to ICIs, and resistance to therapy can develop over time leading to an average 5-year survival below 30%. Lung cancer, as well as lung metastases from distal tumors, are still conditions with a high medical need. Proposed technology is an unprecedented drug delivery platform based on AvidinOX® that is the oxidized derivative of avidin, the natural biotin binding protein. AvidinOX was surprisingly found to chemically react with tissue proteins upon contact, thus becoming a stable artificial receptor for biotin and biotin-linked drugs. A variety of preclinical data are reported in 19 peer reviewed papers. Dosimetry data from 17 patients injected with AvidinOX within inoperable tumor lesions and then intravenously with radiolabeled biotin, confirmed biotin uptake, in the AvidinOX-treated site, up to 15 days. Stable binding of AvidinOX to tissues is due to the formation of Schiff’s bases between the aldehydes, deriving from avidin sugar oxidation, and tissue protein amino groups. Investigation of the MoA indicates that AvidinOX-bound cetuximab, as well as panitumumab, pertuzumab, trastuzumab, lead to the arrest of trafficking of the targeted growth factor receptor, and this is associated to massive intracellular receptor degradation and finally to cell death. In pre-clinical models it was found that mice bearing human KRAS-mutated metastatic lung cancer, could be effectively treated with AvidinOX and mcg-doses of biotinylated cetuximab by aerosol. AvidinOX pre-targeting can turn non-effective doses of biotinylated monoclonal antibodies into highly cytotoxic treatment. Aerosol therapy with AvidinOX and biotinylated antibodies appears to be interesting because it is an original, non-competed technology, it would be easily deployed, it would give local efficacy without systemic exposure, it would be low cost (avidin from waste material of lysozyme process, mg-dose of monoclonal antibodies). The AvidinOX technology stemmed from the in vivo use of avidin and radiolabeled biotin to deliver radioactivity to tumor tissues (i.e. Pretargeted Antibody Guided RadioImmunoTherapy and Intraoperative Avidination Radionuclide Therapy). AvidinOX was discovered in the search for chemical modifications that would make avidin more stable in injected tissues aiming at improving dosimetry and anti-tumor efficacy. The company, where the invention was made, started clinical trials during a reorganization phase that ended up with a merging. The newly formed company decided to focus on different strategic fields. The inventor of the technology founded Kiran biotech Srl that acquired the AvidinOX patents and trademark. The intratumor injection of AvidinOX in 17 patients was found to be well tolerated. No immune-related effects were reported. The maximum tolerated dose of radioactive biotin was not reached. Aerosol therapy with AvidinOX and biotinylated antibodies appears to be interesting because is an original, non-competed technology, it is going to have good patient compliance and to exert local efficacy without systemic exposure and related side effects. Low cost (avidin produced from waste material of lysozyme process, mg-dose of monoclonal antibodies). It has the potential to became “Pipeline in a drug” by addressing new indications and by using novel monoclonal antibodies like our anti-HER3 and anti-PDL1. Kiran wishes to engage in strategic partnerships to: speed up the current research activities aiming at expanding the breadth of the IP protection through technical improvements in the AvidinOX production process; perform clinical trials with AvidinOX anti-HER3 and anti-PDL1 antibodies. Potential revenues are expected to be positively affected by:  Huge potential target population (>2.4 Millions/y new lung cancer cases plus patients with lung metastases from solid tumors; High selling price. As a reference, cetuximab, the most common benchmark of willingness-to-pay (WTP) threshold is $150,000 per quality-adjusted life-year (QALY); Low COGS (mg dose of cetuximab, waste material as AvidinOX origin). [COGS for one cycle AvidinOX + biotinylated antibody by aerosol is estimated to be<100 Euro]; No direct competition and potential add-on positioning.