[SITC 2024] LigaChem Biosciences presents STING agonist preclinical data
HOUSTON, TX. -- By Lee Han-soo/Korea Biomedical Review correspondent -- LigaChem Biosciences presented encouraging preclinical data for its novel cancer immunotherapy candidate LCB39, a STING (Stimulator of Interferon Gene) agonist, in a poster presentation at the 39th Society for Immunotherapy of Cancer (SITC) conference held in Houston, Texas from Nov. 6-10.
LCB39 targets the cGAS-STING pathway, which plays a crucial role in activating innate immunity by detecting cytosolic DNA from pathogens or host cell DNA in conditions such as cancer. While STING agonists have shown promising results in preclinical tumor control through Type I IFN responses, their clinical success has been limited by bioavailability issues and difficulties achieving effective doses within tolerable limits.
The company’s CTO Chung Chul-woong met with Korea Biomedical Review in front of the company’s poster study during the event and highlighted several key advantages of LCB39 over existing STING agonists.
"While previous STING agonists have shown high potency at 0.7 nanomoles, they've faced significant safety challenges," Chung said. “LCB39 achieves activation at 273 nanomoles, demonstrating a deliberately moderated potency that contributes to a better safety profile.”
According to preclinical studies, LCB39 was specifically designed with lower cellular permeability while maintaining direct STING binding potency to improve systemic tolerability. Compared to competing compounds like diABZi, GSK#3, or XMT-1616, LCB39 showed approximately 100-fold lower THP-1 reporter activity with about 5-fold lower direct binding potency.
The research team observed minimal accumulation in the liver and plasma, with high concentration specifically in tumor tissues.
In preclinical studies, LCB39 showed impressive results across multiple cancer models, including colorectal cancer, lung cancer, and breast cancer. Particularly noteworthy was its effectiveness in "cold tumors" - cancers typically resistant to immunotherapy - especially when combined with PD-1 antibodies, leading to complete regression in some cases.
"When MD Anderson researchers saw the complete regression in these models, they were quite surprised," Chung remarked. The team's analysis of tumor tissues revealed increased activation of immune cell markers and favorable changes in macrophage populations, suggesting the creation of an environment conducive to fighting cancer.
Addressing safety concerns that have plagued previous STING agonists, Chung emphasized that LCB39 shows significantly better toxicity profiles in human PBMC and hematopoietic stem cells compared to competitors, demonstrating a 2.5-fold better safety margin.
Looking ahead, LigaChem Biosciences plans to initiate global clinical trials in the first half of 2026.
"We're taking a careful approach, particularly given the stringent requirements for small molecule development in immunotherapy," Chung said.
He also indicated that the company is already in discussions with experienced clinicians, particularly in Texas's prominent cancer centers, who have expressed strong interest in participating in future trials.
While keeping most data confidential for competitive reasons, Chung mentioned that independent validation studies by external researchers have yielded even more promising results in challenging models, with plans to publish comprehensive findings in conjunction with the clinical trial initiation.
Chung concluded that the company anticipates pursuing partnership opportunities for combination therapy development, acknowledging the complexity and scale of clinical trials required for combination approaches in immunotherapy.