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Basilea reports preclinical data on oncology drug candidates BAL0891


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Basilea reports preclinical data on oncology drug candidates BAL0891

Basilea Pharmaceutica Ltd a commercial-stage biopharmaceutical company committed to meeting the needs of patients with infectious diseases and cancer, reported today that promising preclinical data on the anti-cancer activity of its three oncology drug candidates, BAL0891, derazantinib and lisavanbulin, have been presented at the Annual Meeting of the American Association for Cancer Research (AACR) that took place April 8-13, 2022, in New Orleans, USA.

BAL0891 is a potential first-in-class mitotic checkpoint inhibitor (MCI) that drives aberrant tumor cell division leading to tumor cell death. A first poster showed in-vitro data on the activity of BAL0891 against its targets, threonine tyrosine kinase (TTK) and polo-like-kinase 1 (PLK1). The activity of BAL0891 led to a faster disruption of the mitotic spindle assembly check point (SAC) than TTK- and PLK1-specific inhibitors alone. This was associated with a broad anti-cancer effect across diverse tumor cell lines, including those derived from breast, gastric and colorectal cancer. Data presented on a second poster confirmed the good tolerability and potent single-agent anti-cancer activity of BAL0891 across a panel of patient-derived xenograft (PDX) in-vivo models of triple-negative breast cancer. Complete tumor regressions were observed in a significant number of PDX models and support the further development of BAL0891 for the potential treatment of human cancer. The data on both posters were generated in collaboration with the Dutch precision medicine company, NTRC B.V., from which Basilea in-licensed the drug candidate.

Dr. Laurenz Kellenberger, Chief Scientific Officer of Basilea, said: “The data presented at the AACR Annual Meeting confirm the differentiated profiles of our drug candidates. For BAL0891, the in-vitro an in-vivo data provide additional support for the novel mode of action of our compound and its potent single-agent activity. We are particularly pleased that BAL0891 shows convincing activity in models of human triple-negative breast cancer, a difficult-to-treat cancer with a high medical need.”

Further in-vitro and in-vivo data was also presented for derazantinib, a fibroblast growth factor receptor (FGFR) inhibitor, confirming similar sensitivity of FGFR1-3 and colony stimulating factor 1 receptor (CSF1R) to derazantinib. CSF1R plays an important role in the anti-tumor immune response to PD-L1 checkpoint inhibitors used for cancer therapy. In-vivo tumor models with high CSF1R levels were partially sensitive to derazantinib, but not to another FGFR inhibitor with no activity against CSF1R. The importance of the additional CSF1R inhibition was highlighted by data that showed a synergistic effect of the combination of derazantinib with a PD-L1 antibody in an immunologically competent breast cancer model. As compared to the single agents, this combination increased efficacy against the primary tumor, and liver and lung metastases. The combination also led to a more pronounced activation of the immune microenvironment in the primary tumor.

Finally, preclinical data were presented on avanbulin, the active moiety of Basilea’s tumor checkpoint controller lisavanbulin. In-vitro, avanbulin treatment was associated with high anti-tumor activity in models of diffuse large B cell lymphoma (DLBCL), supporting a potential application of lisavanbulin for the treatment of lymphoma patients. These data were generated in collaboration with Prof. Bertoni (Institute of Oncology Research, USI, Bellinzona, Switzerland).

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