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Preclinical toxicology and pharmacology evaluation of a newTNFR2 antagonistic monoclonal antibody for CTCL therapy

新型TNFR2拮抗单克隆抗体用于CTCL治疗的临床前毒理学和药理学评价

基本信息

批准号：
10323802
负责人：
Kenneth Olivier
金额：
$ 39.8万
依托单位：
BOSTON IMMUNE TECHNOLOGIES AND THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323802
关键词：
Antibodies Autoimmunity Benchmarking Binding Boston Cancer Patient Cancerous Capital Cells Clinical Clinical Trials Colon Carcinoma Cutaneous T-cell lymphoma Cyclic GMP Data Development Dose Drug Kinetics Effector Cell Evaluation Formulation Frequencies Funding Future Growth Guidelines Health Health Care Costs Health Expenditures Human Immune Immune system Immunooncology In Vitro International Investigational Drugs Investigational New Drug Application Macaca fascicularis Malignant Neoplasms Malignant neoplasm of ovary Mediating Molecular Target Monoclonal Antibodies Mus New Drug Approvals Oncogenes Oncogenic Patients Pharmacologic Substance Pharmacology Pharmacology and Toxicology Phase Process Production Productivity Receptors, Tumor Necrosis Factor, Type II Regulatory Affairs Regulatory T-Lymphocyte Resistance Running Safety Sampling Secure Seeds Signal Transduction Small Business Innovation Research Grant Societies Surface Technology Testing Therapeutic Time Tissues Toxic effect Toxicology Validation antitumor effect base cGMP production cancer cell cancer therapy design dimer in vitro activity in vivo innovation interest large scale production novel strategies novel therapeutic intervention novel therapeutics overexpression pre-clinical prevent programmed cell death protein 1 programs receptor research clinical testing selective expression targeted cancer therapy targeted treatment therapeutic target therapy outcome tool tumor tumor microenvironment tumor necrosis factor receptor binding

项目摘要

PROJECT SUMMARY Cancer has killed over 600,000 people in US in 2020. The cost for healthcare and society is unbearable: because of cancer, $180B healthcare expenditure and $134B lost productivity are recorded every year. This is happening despite recent advancements in therapy and the emergence of an ever expanding array of new therapeutics for the over 1.8M new cancer patients every year. Indeed, because of the multitude and redundancy of mechanisms contributing to cancer growth, therapies are often ineffective. Several components should be targeted at the same time in order to maximize therapy outcome. However, this is particular hard to attain because of 1) the striking variability among cancers and the limited number of cancer specific targets 2) the ability of cancer cells to orchestrate a microenvironment of healthy tissue and cells around them, that promote cancer growth and therapy resistance. Boston Immune Technologies and Therapeutics (BITT) is developing BITT-1492, able to target both cancer cells and their microenvironment. BITT-1492 is an antagonist antibody against TNFR2 – a receptor highly expressed in cancer tissue and immune suppressive cells in the microenvironment, where it mediates pro-survival signaling. Thanks to BITT’s proprietary antibody design platform, BITT-1492 is the first and only antibody able to dominantly shut down TNFR2 signaling. Due to selective expression and key role of TNFR2 for a variety of cancers and tumor microenvironment cells, BITT-1492 will find application in the therapy of several cancers, starting with Cutaneous T cell Lymphoma (CTCL), where TNFR2 is known to act as an extremely potent oncogene. BITT has already completed extensive pre-clinical validation for BITT-1492, demonstrating potent activity in CTCL, colon and ovarian cancers. In the proposed Fast-Track project, BITT will complete a pre-clinical toxicology and pharmacology assessment of BITT-1492 to obtain relevant data for an Investigational New Drug (IND) application. This will be accomplished by performing, in line with ICH guidelines, an exploratory small-scale toxicology study to be carried out in Phase I, that will demonstrate the safety of use of BITT-1492 for a wider IND-enabling toxicology and pharmacokinetic studies in Phase II. As part of the PhaseII BITT will also test the suitability of BITT-1492 production process for cGMP standard compliance. At the end of the SBIR project, BITT will be ready to advance BITT-1492 to clinical testing for which a combination of Venture Capital seed funds and SBIR PhaseIIb are expected to be leveraged. The successful completion of this project and initial clinical testing evidence will help to secure the already expressed interest of pharmaceutical companies with whom BITT will engage to complete late-stage clinical testing and launch BITT-1492 into international markets.

项目总结