Innovent's IBI343: A Breakthrough in Advanced Pancreatic Cancer Therapy

Innovent Biologics, Inc. (HKEX: 01801), a world-class biopharmaceutical company, has received a significant boost with the National Medical Products Administration (NMPA) of China granting Breakthrough Therapy Designation (BTD) for its investigational drug, IBI343. This monoclonal antibody-drug conjugate (ADC) is designed to treat advanced gastric/gastro-oesophageal junction adenocarcinoma (GC) in patients who have progressed after at least two lines of prior systematic treatments. The BTD is based on promising data from an ongoing Phase 1 study (NCT05458219), which demonstrated favorable safety and tolerability, along with encouraging antitumor activity in advanced GC patients.

IBI343 is an antibody-drug conjugate composed of an anti-claudin18.2 antibody and a cytotoxic drug, exatecan. As a topoisomerase I inhibitor, exatecan effectively kills tumor cells by inhibiting DNA synthesis. Binding of IBI343 to claudin18.2-expressing tumor cells results in claudin18.2-dependent internalization of IBI343. Degradation of the cleavable linker releases the drug, causing DNA damage and leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343.

The BTD for IBI343 is a testament to the drug's potential in treating advanced GC, a disease with a poor prognosis and limited treatment options. The 5-year survival rate of patients with metastatic gastric cancer is less than 5%, and China and Japan are countries with the highest incidence of gastric cancer. Currently, chemotherapy combinations of fluoropyrimidine and platinum, and immune checkpoint inhibitor therapy are the standard-of-care treatments for patients with advanced metastatic GC. However, systemic therapy has limited efficacy in advanced gastric cancer, particularly in patients who have progressed after two or more lines of prior therapy.

Innovent is preparing to initiate a registrational Phase 3 multi-regional clinical trial (MRCT) of IBI343 in patients with claudin18.2-positive, HER2-negative GC (G-HOPE-001, NCT06238843). The company is confident that IBI343's unique Fc-silent antibody design, stable linker, and potent TOPO1i payload will continue to demonstrate encouraging efficacy and a favorable safety profile in the treatment of advanced pancreatic cancer.

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify IBI343 to receive status for rapid review by the CDE but also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace.

In conclusion, Innovent's IBI343 has shown great promise in the treatment of advanced GC, with a favorable safety profile and encouraging antitumor activity. The NMPA's BTD for IBI343 is a significant milestone in the drug's development and highlights its potential in addressing the unmet clinical need in this difficult-to-treat cancer. As Innovent continues to advance IBI343's clinical programs, it is poised to bring breakthrough treatments to patients worldwide.