Lisata Therapeutics Inc (NASDAQ:LSTA) chief medical officer Kristen Buck talked with Proactive about encouraging preclinical results for their drug candidate, certepetide, in treating intrahepatic cholangiocarcinoma, otherwise known as bile duct cancer. Preclinical results support certepetide's potential to enhance chemotherapy and immunotherapy, which is expected to translate into improved patient survival.
Proactive: Lisata has announced encouraging preclinical results for your drug candidate, certepetide, in intrahepatic cholangiocarcinoma. Can you tell us more about the study and what the results reveal?
Kristen Buck: This is a very important pre-clinical study conducted in a mouse model with orthotopically implanted cholangiocarcinoma, also known as bile duct cancer. The study divided the mice into four treatment groups: a control group, a group that received only certepetide, a group treated with gemcitabine, cisplatin, and anti-PD-1 immunotherapy, and a fourth group that received certepetide along with gemcitabine, cisplatin, and anti-PD-1. The mice were imaged sequentially and longitudinally to observe how well certepetide assisted the effect of the chemotherapy and immunotherapy.
The study demonstrated that combining certepetide with standard care chemotherapy and immunotherapy prolonged the mice's survival, reduced metastases to their lungs, and decreased comorbidities such as ascites in their abdomen.
With cholangiocarcinoma being difficult to treat, is certepetide then a good candidate to help treat cancer patients?
Certepetide specifically targets two receptors that are upregulated on solid tumors, including cholangiocarcinoma, which also features a dense fibrotic stromal barrier. This barrier traditionally inhibits the effectiveness of chemotherapy and immunotherapy.
Certepetide is particularly effective in cholangiocarcinoma because it not only binds to these upregulated receptors but also transforms the stroma from a barrier into a conduit, facilitating the delivery of chemotherapies. Previous approaches involved high doses of chemotherapy or immunotherapy, resulting in significant off-target side effects. However, certepetide truly enhances the ability to get drugs into this very difficult to treat tumor.
These results were presented at the Cholangiocarcinoma Foundation annual conference. What do you do next with the results? What are the next steps?
We're enthusiastic about these results because they align with our ongoing Phase 2a study, known as the BOLSTER trial, which evaluates certepetide in human cholangiocarcinoma, particularly in the first-line setting. This study combines certepetide with the standard gemcitabine/cisplatin and durvalumab regimen, comparing it against a control arm using only gemcitabine/cisplatin and durvalumab.
Due to strong investigator interest, we've expanded the trial to include a second cohort for second-line treatment, pairing certepetide with FOLFOX against a FOLFOX-only control arm. These preclinical findings support our belief that certepetide can selectively target tumors, enhance chemotherapy penetration, and modify the hostile tumor microenvironment. This approach aims to decrease T regulatory cells and boost cytotoxic T-cells, potentially improving patient outcomes through enhanced survival with combined chemotherapy and immunotherapy.
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