Clinical applications for CDK4/6 inhibitors of Jiahe Bio1 new drug were accepted by CDE

On December 28th, a clinical trial application for the new class 1 drug, lerociclib, was accepted by CDE.
to be developed for the treatment of HR-/HER2-metastasis breast cancer.
Lerociclib is a potential "best-in-class" oral CDK 4/6 (cell cycle protein-dependent kinase 4/6) inhibitor developed by G1 Therapeutics.
June this year, Jia and Bio reached an exclusive licensing agreement with G1 Therapeutics, acquiring exclusive development and commercial rights in the Asia Pacific region ,lerociclib, excluding Japan.
a completed treatment of ER-plus, HER2-Breast Cancer preliminary clinical results showed that lerociclib was significantly effective and had better tolerance.
adverse reactions such as neurotic cell reduction are light, and neutral granulocyte reduction is one of the main toxicity of CDK4/6 inhibitors.
Lerociclib is currently conducting two Phase I/II clinical studies worldwide for the treatment of breast and non-small cell lung cancer.
and Bio plan to submit a listing application to the NMPA for the lerociclib 2-line treatment HR plus/HER2-mRC by 2023.
is expected to become the fifth CDK4/6 inhibitor to be listed in China.
breast cancer is one of the most common malignant tumors in women 40 years.
statistics, about 169,000 women are diagnosed with breast cancer in China every year, and 45,000 women die of breast cancer every year.
the basic mechanism of CDK4/6 inhibitors to treat breast cancer The proliferation process of normal cells is closely regulated by a range of cell cycle proteins and cell cycle protein-dependent kinases (Cyclin-Dependent Kinases, CDK).
cycle refers to the process by which a single mother cell divides into a new generation of child cells, including G1, S, G2, and M.
G1-S, S-G2 and G2-M are the three key checkpoints to regulate cell cycles.
the main molecules involved in cell cycle regulation include cyclin, cyclin-dependent protein dependence kinase (Cyclin-dependentkinases, CDKs) and CDK inhibitors (cyclin-dependentkinases inhibitors, CKIs).
CDKs are the center of cell cycle regulation.
cycle protein activates the CDK, while CKIs can inactivate the CDK.
CDK binds to the corresponding cell cycle protein to promote the cell cycle forward by phosphorylation of various substrates, while KCKI binds to CDK to inhibit CDK kinase activity and hinder cell cycle forward.
cdK proteins are silk/suline kinases, and their subsypes play different functions by number.
, for example, CDK4/6 initiates the transcription of downstream molecules by catalysis leading to the phosphation of the Rb protein, which dissophases the transcription factor E2F of the binding of the RB protein.
CDK4/6 is the key regulatory factor for the cell cycle from G1 to S.
of the cell cycle is a major feature of tumor cells.
cycle proteins are often overactive in cancer cells, leading to uncontrolled proliferation.
cell cycle regulation-related gene mutations have been found in the vast majority of tumors.
, by inhibiting the function of cell cycle proteins, tumor cells, especially breast tumors, can be targeted to inhibit the growth of normal cells with less impact.
CDK4/6 inhibitors global market and the Chinese pattern so far, the world has 3 CDK4/6 inhibitors approved for market.
cdK4/6 inhibitor sales in 2019 totaled more than $6 billion, according to the company's annual report.
China currently has 1 CDK4/6 inhibitor approved for market, but more than a dozen CDK4/6 inhibitors are in the clinical stage, some of which have reached the late stage of clinical development.
Pfizer's Ibrance was approved in 2015 and is the world's first CDK4/6 selective inhibitor to be approved for listing.
Ibrance's adaptation in the United States has been proven to be a joint treatment of estrogen-positive, human skin growth factor-negative (ER-/HER2-) patients with post-menoptocratic advanced breast cancer as an initial endocrine therapy program for metastatic breast cancer.
's Kisqali was launched in March 2017 for breast cancer treatment.
The drug can be combined with aromatase inhibitors as an initial endocrine therapy option for post-menotinal estrogen-positive, human skin growth factor 2 negative (HR-/HER2-) advanced or metastatic breast cancer in female patients.
Verzenio was approved by the FDA in September 2017 for treatment of HR-positive, HER2-negative advanced or relapsed breast cancer.
Verzenio can be used alone to treat patients who are metastasis after chemotherapy/hormone therapy, or in combination with fullstrant to treat adult patients with HR-positive, HER2-negative advanced or metastasis breast cancer.
Verzenio is the FDA-approved third CDK4/6 inhibitor and the only CDK4/6 inhibitor approved for single-drug use.
In the Chinese market, Pfizer's Ppisi has been approved for listing, Lilly's Abersil is about to be approved, and Novart's Riposili is in Phase III clinical trials;