China-based biopharma Innovent Biologics, Inc. (HKG: 1801) has announced receiving another Breakthrough Therapy Designation (BTD) from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for its IBI343. The latest designation was granted for the TOPO1i anti-CLDN18.2 antibody drug conjugate (ADC) as monotherapy for the treatment of CLDN18.2-positive advanced pancreatic ductal adenocarcinoma (PDAC) patients who have progressed after at least one line of prior systematic treatment.
IBI343: Mechanism of Action and Therapeutic Potential
IBI343 is an antibody-drug conjugate composed of an anti-CLDN18.2 antibody and a cytotoxic drug exatecan. The binding of IBI343 to CLDN18.2-expressing tumor cells results in CLDN18.2-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.” As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase I clinical studies, with its therapeutic potential currently being explored in tumor types such as gastric and pancreatic cancers.
Previous Regulatory Milestones
Previously, IBI343 was awarded BTD status in China in May of last year for its use as a monotherapy in patients with CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following two prior lines of systemic treatment. One month later, the drug earned Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy.
Strategic Implications
The receipt of another BTD for IBI343 highlights Innovent Biologics’ continued progress in developing innovative treatments for advanced cancers. This designation underscores the potential of IBI343 to address significant unmet medical needs in the treatment of CLDN18.2-positive PDAC. By leveraging the Fast Track and Breakthrough Therapy designations, Innovent is well-positioned to accelerate the development and regulatory approval of IBI343, potentially bringing a new treatment option to patients with this aggressive form of cancer.-Fineline Info & Tech
