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2024 AACR | Abbisko Therapeutics Presented 3 Pre-clinical Research Results with Oral and Poster Presentations

Apr 10,2024
By Abbisko
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10 April 2024, Shanghai – Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics) announced that it has presented the pre-clinical combination study results of its highly selective FGFR4 inhibitor Irpagratinib (ABSK011) with oral presentation during AACR 2024. In addition, Abbisko has also presented pre-clinical data of its innovative CSF-1R inhibitor pimicotinib(ABSK021)and oral small molecule PD-L1 inhibitor by posters. As one of the most prestigious oncology conferences in the world, this AACR conference was held in San Diego, USA from April 5 to 10, 2024.

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Abbisko presentations in the 2024 AACR:

Title: Selective FGFR4 inhibitor Irpagratinib (ABSK011) exhibits broad synergistic and combinatory anti-tumor effects with other therapeutic agents in preclinical HCC models

Oral presentation number:1228

Session: Novel Antitumor Agents 1

Session date and time: 7 April, 2024, 3:05-3:20 PM (PT)

Introductions:

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking as the sixth most prevalent cancer and the third leading cause of death worldwide. Deregulation of FGF19-FGFR4 signaling accounts for roughly 30% of HCC and plays a pivotal role in driving HCC tumorigenesis. Irpagratinib (ABSK011) is a highly potent and selective FGFR4 inhibitor, with the potential to become a first-in-class or best-in-class FGFR4 inhibitor. It showed promising anti-tumor activity in an ongoing phase Ib clinical study, with an ORR of 40.7% observed in FGF19 overexpressed late line HCC patients in cohorts treated with BID regimens. To further expand the therapeutic potential of Irpagratinib, Abbisko carried out an array of preclinical translational studies, exploring the efficacy and mechanisms of combination treatments.

Conclusion:

In summary, these findings collectively illustrate very broad synergistic anti-tumor effects of Irpagratinib when combined with various other therapeutic agents. These results may pave the road for potential novel combinatory therapeutic strategies that could expand the utility of Irpagratinib and provide innovative and more effective therapies to HCC patients.

Title: CSF-1R inhibition with Pimicotinib (ABSK021) enhanced anti-tumor efficacy of KRASG12C inhibitors in preclinical non-small cell lung cancer mouse models

Session: Late-Breaking Research: Immunology 1

Session Date and Time: Sunday Apr 7, 2024 1:30 PM - 5:00 PM (PT)

Location: Poster Section 54

Poster Board Number: 13

Poster Number: LB077

Introductions:

KRASG12C is a common oncogenic driver in human cancers, particularly in KRAS-mutant non-small lung cancer (NSCLC). Tumor associated macrophages (TAMs) are enriched in KRAS-driven transgenic lung cancer models, and their depletion significant reduces tumor burden and improves survival. Sotorasib (AMG510), the first KRASG12C inhibitor approved by FDA, has been found to increase macrophage levels in mouse model. CSF-1R inhibition depletes TAMs and reprograms tumor microenvironment (TME). Therefore, the combination of KRASG12C and CSF-1R inhibitors may synergize to enhance anti-tumor efficacy. Pimicotinib (ABSK021) is a potential best-in-class small molecule inhibitor of CSF-1R in clinical development of multiple indications. Here, Abbisko conducted preclinical translational studies to explore the combined effects of KRASG12C and CSF-1R inhibitors.

Conclusion:

For the first time, we demonstrate that the combined inhibition of KRASG12C and CSF-1R leads to superior therapeutic efficacy in preclinical NSCLC mouse models. These results suggest a potential novel therapeutic regimen that could yield improved clinical benefit to patients.

Title: Cellular characterization of small molecule PD-L1 inhibitors reveal their novel mechanisms of action

Session Category: Experimental and Molecular Therapeutics

Session Date and Time: Monday Apr 8, 2024 9:00 AM - 12:30 PM (PT)

Location: Poster Section 27

Poster Board Number: 22

Poster Number: 2039

Introductions:

Immune checkpoint , including PD-1/L1, are key regulators of immune response and promising targets in cancer immunotherapy. Like anti-PD-1/L1 antibodies, small molecule PD-L1 inhibitors that have been discovered by us and others could also efficiently block PD-1 and PD-L1 interaction and exhibit anti-tumor efficacy in preclinical and clinically settings. In this study, we explore the cellular mechanism of small molecule PD-L1 inhibitors, unveiling their novel mechanisms of action in the regulation of PD-L1 and its functions.

Conclusion:

Taken together, these results for the first time revealed the distinctive mechanisms of our small molecule PD-L1 inhibitors. With their multi-layer inhibitory effects stemming from various mechanisms, small molecule PD-L1 inhibitors may offer potentially improved activities and an alternative therapeutic treatment for the cancer patients.


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