Production of pilot batches in GLP and non-clinical studies of a new PEG conjugated Asparaginase for the treatment of neoplasias

• Grant number: 23/13176-1
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Renata Bannitz Fernandes
• Grantee: Renata Bannitz Fernandes
• Company: Biobreyer Pesquisa e Desenvolvimento Científico Ltda
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais ; Atividades profissionais, científicas e técnicas não especificadas anteriormente
• City: Santos
• Associated researchers: Adalberto Pessoa Junior ; Carlota de Oliveira Rangel Yagui ; Eduardo Magalhães Rego ; Gisele Monteiro ; Marcos Antonio de Oliveira
• Associated scholarship(s): 24/02493-9 - Production of pilot batches in GLP and non-clinical studies of a new PEG conjugated Asparaginase for the treatment of neoplasias., BP.TT; 24/01762-6 - Production of pilot batches in GLP and non-clinical studies of a new PEG conjugated Asparaginase for the treatment of neoplasias, BP.PIPE

Abstract

The global pharmaceutical market generates approximately $1 trillion annually, with an estimated target of reaching $1.5 trillion by 2023. Among pharmaceutical products, significant attention is given to those produced through biotechnological routes, primarily represented by medications used in the treatment of cancer, Alzheimer's disease, cardiovascular diseases, among others. In Brazil, there is a significant shortage in the production of biopharmaceuticals, and according to the Index of the Brazilian Association of the Pharmaceutical and Pharmaceutical Inputs Industry (Abiquifi), the Ministry of Health spent R$3 billion in 2016 on this type of medication. Biopharmaceuticals account for only 10% of the quantity of medications acquired by the federal government but consume 60% of the budget allocated for medication purchases. Among biopharmaceuticals, particular emphasis is placed on the enzyme asparaginase (ASNase), widely used in the treatment of lymphatic system cancers, especially Acute Lymphoblastic Leukemia (ALL), since the 1980s. The administration of ASNase can lead to various adverse effects in patients, including toxic effects and immune responses that can result in anaphylactic shocks. In these cases, it is possible to continue treatment with other formulations of asparaginase; however, adverse reactions still occur in many patients, and most countries do not provide all formulations for treatment due to their high cost and lack of registration with regulatory agencies. Therefore, the search for new sources of ASNase and new variants of enzymes already used as medications is the focus of numerous research efforts worldwide. In addition to the problems mentioned, supply crises of these medications have been frequent in various countries, including Brazil. In 2017, there was a significant crisis in the country, compromising the treatment of hundreds of patients (both pediatric and adult), first due to its unavailability, followed by the low quality of urgently imported medication. Thus, our main goal is to develop a national technology for the production of asparaginase and achieve Brazil's independence in producing this biopharmaceutical. To do so, we have secured public funding from FAPESP and CNPq over the past 5 years. With FAPESP resources (PIPE Phase 1 #2017/08591-9 and PIPE Phase 2 #2019/12401-6, already completed), we have made improvements to the molecule through site-specific pegylation (patent application deposited under number BR 10 2023 006797 2), process enhancements, aiming for industrial-scale production of the biopharmaceutical, and conducted exploratory non-clinical studies compared to the reference medication. The CNPq funding is exclusively used for specialized labor payments through the RHAE program (Process 424164/2021-3, ongoing). Success in developing these stages leads us to the next step in technology development, where pilot batch productions will be conducted under Good Laboratory Practice (GLP) conditions, comprehensive non-clinical studies will be performed, medication stability testing will be conducted, and clinical study plans will be developed. By the end of the project, we hope to have established all the conditions for 100% national production of the innovative asparaginase, with validations of all non-clinical tests with ANVISA (Brazil's regulatory agency) and the complete design of the clinical study. Finally, we will seek and negotiate with investors and the government to secure investment for the clinical study and regulatory phases. (AU)