项Research background
发布者：医工融合 发布时间：2024-01-17
Research background
Breast cancer is the most common malignant tumor in women, breast cancer has replaced lung cancer to become the world's largest cancer in 2020, but overall, the prognosis of breast cancer is better than most other malignant tumors, with a five-year survival rate of about 83.2%. However, triple-negative breast cancer is the type with a relatively poor prognosis, and triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which accounts for 15% to 25%. At present, chemotherapy drugs for the treatment of triple negative subbreast cancer have poor efficacy, or no definite clinical benefit, or no significant improvement in median overall survival, which is far from meeting the clinical needs of patients.
Project introduction
01
Product introduction
The ADC anticancer drug developed by a pharmaceutical company showed excellent anti-tumor effect in multiple solid tumor models. The team's original ROR1-targeting camptothecin based ADC drug for the treatment of malignant tumors has completed the identification of preclinical candidate compounds. They screen out antibodies with high specificity and high affinity, improve the bioavailability of drugs by increasing the hydrophilicity of the linker, and achieve directional coupling between the antibody and the linker. This preclinical candidate compound has shown excellent anti-tumor effect in vitro and in mouse models of triple negative breast cancer, with high inhibitory effect and high killing activity, which is superior to similar foreign products, and is expected to be used in clinical practice.
02
Technical introduction
Antibody-drug Conjugates (ADCs) are "biological missiles" that combine cytotoxic drugs (payloads) with Antibody drugs through linkers. After the ADC drug enters the bloodstream, its antibody portion recognizes and binds to the surface antigen of the target cell. After the ADC-antigen complex is internalized into the cell through endocytosis, the complex will be degraded by the lysosome, and the payload will be released, thereby destroying DNA or microtubules, or playing the role of topoisomerase /RNA polymerase inhibition, and eventually leading to cell death. This is a new generation of therapeutic drugs with precise and lethal properties. In summary, ADC is a new type of drug that combines antibodies with small molecular toxins, and has the advantages of strong targeting and few side effects.
ROR1, the ADC drug developed by the company, is a novel tumor treatment target with important potential for triple-negative breast cancer. The drug has a highly effective killing effect at the cell level in vitro, and can achieve cell killing in the IC range of 50 ~10nM at H226, SKOV3, MDA-MB-231, BXPC3, etc. All of them are significantly better than the positive control VLS-101 (the activity of tumor inhibition is several times to more than 10 times) and the main technical indicators are better than the international similar products.
Project schedule
Research stage
Target ROR1 has been confirmed, and the technology of monoclonal antibody discovery based on target structure design is mature. Camptothecin has been used in the clinical treatment of cancer for many years and has high cell-killing activity. At present, the pre-clinical candidate compounds have been identified, the pharmaceutical studies have been completed, the structure of the API has been confirmed, the key physicochemical properties of the API have been studied, the synthetic chemical reaction formula has been determined, and the refining method has been established.
Plan objective
1. November 2023 - February 2024 (4 months)
ADC toxicology studies were conducted.
2. March 2024 - October 2024 (8 months)
Carry out CMC process development of ADC.
3. November 2024 - December 2024 (2 months)
Carry out IND declaration.
Complete the IND application of ADC anticancer drug.
Financing plan
