We are committed to original innovation in precision oncology therapeutics. With a forward-looking focus on the Ras-MAPK signaling pathway and synthetic lethality, we have built a globally competitive pipeline. We firmly believe that our pipeline will deliver more and better therapeutic options to cancer patients worldwide and help the Company achieve globally impactful commercial value.
RAS represents a family of proteins involved in signal transduction pathways that regulate critical cellular processes such as growth, proliferation, migration and survival, making it a significant target for drug discovery. RAS proteins function as molecular switches, cycling between active GTP-bound and inactive GDP-bound states during signal transduction. Mutations in the RAS genes or their regulators can cause RAS proteins to remain persistently active, resulting in continuous signaling to activate a number of downstream signaling pathways as well as aberrant cell growth, proliferation and survival, which may ultimately lead to a variety of types of cancer. Inhibiting RAS has emerged as a desirable treatment approach in the development of anti-tumour drugs.
Activation of the MAPK pathway is one of the key drivers of tumorigenesis and cancer progression, observed in approximately 30% of solid tumours, accounting for more than 5 million new patients worldwide annually. In face of prevalent drug resistance and limited efficacy in major indications including NSCLC, CRC and PDAC, we have built a differentiated pipeline covering the MAPK pathway, centered on our SHP2 inhibitor GH21 and ERK1/2 inhibitor GH55. Through rational combination strategies, our drug candidates can exert collaborative effects with approved EGFR inhibitors and antibody drugs, bringing longer survival and better quality of life to patients with refractory tumours, and unlocking substantial clinical and market value.
Source：CIC
Synthetic lethality refers to a biological phenomenon: a synthetic lethal interaction occurs between two genes when perturbation of either gene alone is viable, but perturbation of both genes simultaneously results in the loss of viability. Tumour cells arise from the accumulation of mutated or aberrantly expressed genes in normal cells.Hence, inhibitors that target synthetic lethal partners of mutated or aberrantly expressed genes in tumour cells can selectively kill cancer cells without compromising the survival of normal cells. Synthetic lethality provides a conceptual framework for tackling certain difficult-to-target genetic mutations, including loss-of-function mutations that are challenging for traditional targeted therapies, and a substantial proportion of gain-of-function mutations that currently lack effective targeted therapies.
As a well-researched and clinically validated mechanism, the feasibility of synthetic lethality has been confirmed by the success of PARP inhibitors. In 2024, the global aggregate annual sales of PARP inhibitors exceeded US$4.0 billion. It is predicted that the overall global market size of synthetic lethal drugs will reach US$11.4 billion by 2030.
Taking MTAP as an example, approximately 15% of patients with solid tumors have MTAP deletion; however, there are currently no approved drugs targeting MTAP deletion worldwide. Our drug candidates are expected to fill this market gap and bring new therapeutic options to patients.
Source：CIC
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Effective and Last Updated: April 15th 2021
