Basilea presents preclinical data on synergy between drazantinib and paclitaxel in gastric tumor models at ANE conference

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Basel, Switzerland, October 11, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) today announced the presentation of data from preclinical studies demonstrating synergistic anti-tumor effects in a number of gastric cancer models for the fibroblast growth factor receptor (FGFR) inhibitor combination of Basilea, derrazantinib, with paclitaxel chemotherapy. The data was presented at the AACR-NCI-EORTC (ANE) International Virtual Conference on Molecular Targets and Cancer Therapeutics, held October 7-10, 2021, and provides further support for the potential role derrazantinib in the treatment of patients. with gastric cancer, which is currently being explored in the FIDES-03 study.1

In preclinical studies, synergistic antitumor effects have been reported in a number of gastric cancer models, including in vivo tumor models with different FGFR aberrations. Complete tumor regression was observed in most cases in models with FGFR2 fusions. In addition, higher levels of immunosuppressive macrophages associated with tumors of the M2 phenotype (M2-TAM) have been shown to be associated with a deeper response to the combination of drazantinib and paclitaxel. Drazantinib inhibits the colony stimulating factor 1 receptor (CSF1R), which plays an important role in the formation and function of M2-TAM. Therefore, tumors with higher levels of M2-TAM may be more sensitive to drazantinib.

Dr. Laurenz Kellenberger, Scientific Director, said: “These new combination therapy data build on previous preclinical studies which have shown significant activity of derazantinib as monotherapy in gastric cancer models. The synergistic effect between drazantinib and paclitaxel is particularly encouraging as we explore drazantinib alone and in combination, including paclitaxel, in our phase 1/2 FIDES-03 clinical study in patients with gastric cancer.

Gastric cancer is the fifth most common cancer in the world and the third most deadly type of cancer.2 Median survival rarely exceeds twelve months and five-year survival is less than 10%.3 Basilea estimates that there are around 190,000 new cases of gastric cancer per year in total in the 5 main EU countries, Japan and the United States. FGFR genetic aberrations have been observed in approximately 10% of gastric cancers.4

Derazantinib ePoster presented at AACR-NCI-EORTC conference

Presentation #

Authors / Title

P238

P. McSheehy, M. El-Shemerly, F. Bachmann, L. Kellenberger, H. Lane

Drazantinib, a fibroblast growth factor 1-3 receptor inhibitor, acts synergistically with paclitaxel in preclinical gastric tumor models.

For more information, please visit aacr.org/meeting/aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics/.

About derazantinib

Drazantinib is an investigational small molecule FGFR inhibitor administered orally with strong activity against FGFR1, 2 and 3.5 FGFR kinases are key drivers of cell proliferation, differentiation and migration. Genetic aberrations of FGFR, for example gene fusions, mutations or amplifications, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial, breast, gastric and pulmonary cancers.6 In these cancers, the genetic aberrations of FGFR are in the range of 5 to 30%.7
Drazantinib also inhibits colony stimulating factor 1 receptor kinase (CSF1R).5, 8 CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages and has therefore been identified as a potential target for anticancer drugs.9 Preclinical data have shown that depletion of tumor macrophages by blocking CSF1R makes tumors more responsive to T-cell checkpoint immunotherapy, including approaches targeting PD-L1 / PD-1.ten, 11
Drazantinib demonstrated antitumor activity and a manageable safety profile in a previous phase 1/2 biomarker-based study in iCCA patients,12 and received orphan drug designation in the US and EU for iCCA. Basilea is currently conducting three clinical studies with drazantinib. The first study, FIDES-01, is a phase 2 study in patients with inoperable or advanced iCCA. It includes a cohort of patients with FGFR2 gene fusions and another cohort of patients with mutations or amplifications.13 The second study, FIDES-02, is a phase 1/2 study evaluating derazantinib alone and in combination with Roche’s PD-L1 checkpoint inhibitor, aezolizumab, in patients with urothelial cancer advanced, including metastatic or surgically recurrent unresectable disease, expressing genetic FGFR aberrations.14 The third study, FIDES-03, is a phase 1/2 study evaluating drazantinib alone and in combination with Lilly’s anti-VEGFR2 antibody, ramucirumab and paclitaxel, or with atezolizumab, a checkpoint inhibitor. Roche’s PD-L1 in patients with advanced gastric cancer with FGFR genetic aberrations.1 Basilea holds a license for derrazantinib from ArQule Inc., a wholly owned subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

About Basilea

Basilea is a commercial-stage biopharmaceutical company founded in 2000 and based in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the medical needs of patients with cancer and infectious diseases. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of severe bacterial infections. We are conducting clinical studies with two targeted drug candidates for the treatment of a range of cancers and have a number of preclinical cancer and infectious disease actives in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com.

Disclaimer

This communication expressly or impliedly contains certain forward-looking statements, such as “believe”, “assume”, “expect”, “anticipate”, “plan”, “could”, “could”, “could”, “will” or similar phrases regarding Basilea Pharmaceutica Ltd. and its activities, including with respect to the advancement, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain risks, uncertainties and other known and unknown factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd. forward-looking statements. Basilea Pharmaceutica Ltd. is providing this communication as of that date and does not undertake to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Drazantinib and its use are investigational and have not been approved by any regulatory authority for any use. Efficacy and safety have not been established. The information presented should not be interpreted as a recommendation for use. The relevance of the results of the non-clinical / preclinical studies for humans is currently being evaluated.

For more information, please contact:

This press release can be downloaded from www.basilea.com.

The references

  1. FIDES-03: ClinicalTrials.gov identifier: NCT04604132

  2. F. M Johnston, M. Beckman. Updates on the management of gastric cancer. Current Oncology Reports 2019 (21), 67

  3. M. Orditura, G. Galizia, V. Sforza et al. Treatment of gastric cancer, World Journal of Gastroenterology 2014 (20), 1635-1649

  4. A. Bass, V. Thorsson, I. Shmulevich et al. Complete molecular characterization of gastric adenocarcinoma. Nature 2014 (513), 202-209

  5. TG Hall, Y. Yu, S. Eathiraj et al. Preclinical activity of ARQ 087, a new inhibitor targeting FGFR deregulation. PLoS ONE 2016, 11 (9), e0162594

  6. R. Porta, R. Borea, A. Coelho et al. FGFR, a promising drug target in cancer: molecular biology and new drugs. Critical reviews in oncology / hematology 2017 (113), 256-267

  7. T. Helsten, S. Elkin, E. Arthur et al. The FGFR landscape in cancer: Analysis of 4,853 tumors by next-generation sequencing. Clinical Cancer Research 2016 (22), 259-267

  8. P. McSheehy, F. Bachmann, N. Forster-Gross et al. Derazantinib (DZB): A dual FGFR / CSF1R inhibitor active in PDX models of urothelial cancer. Molecular Cancer Therapeutics 2019 (18), supplement 12, pp. LB-C12

  9. MA Cannarile, M. Weisser, W. Jacob et al. Colony stimulating factor 1 receptor (CSF1R) inhibitors for the treatment of cancer. Journal for ImmunoTherapy of Cancer 2017, 5:53

  10. Y. Zhu, BL Knolhoff, MA Meyer et al. CSF1 / CSF1R Blockade reprograms tumor infiltrating macrophages and improves response to T cell checkpoint immunotherapy in pancreatic cancer models. Cancer Research 2014 (74), 5057-5069

  11. E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages prevent CD8 T cells from reaching tumor cells and limit the effectiveness of anti-PD-1 treatment. Proceedings of the National Academy of Science of the United States of America 2018 (115), E4041-E4050

  12. V. Mazzaferro, BF El-Rayes, M. Droz dit Busset et al. Derazantinib (ARQ 087) in advanced or inoperable intrahepatic cholangiocarcinoma with FGFR2 gene fusion. British Journal of Cancer 2019 (120), 165-171. ClinicalTrials.gov ID: NCT01752920

  13. FIDES-01: ClinicalTrials.gov identifier: NCT03230318

  14. FIDES-02: ClinicalTrials.gov identifier: NCT04045613

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