Basilea announces data presentations at ESMO Virtual Congress 2020

Basel, Switzerland, July 28, 2020

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that three abstracts featuring preclinical and clinical data on its fibroblast growth factor receptor (FGFR) kinase inhibitor derazantinib and its tumor checkpoint controller lisavanbulin are going to be presented as e-posters at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which is taking place from 19-21 September, 2020.

Dr. Marc Engelhardt, Chief Medical Officer, said: “The preclinical derazantinib data may provide an explanation for differences in reported adverse event profiles between various FGFR kinase inhibitors. Furthermore, derazantinib shows promising efficacy in patient-derived tumor models with gene aberrations in FGFR1-3. The data which will be presented at ESMO are part of our broad preclinical and clinical program focused on generating further scientific evidence for the differentiation of derazantinib, in order to explore its full therapeutic potential in FGFR-driven tumors.”

He continued: “We are also pleased that the full data from the phase 1 study with oral lisavanbulin in patients with recurrent glioblastoma will be presented at ESMO. As previously reported, we observed clinical benefit in a subset of patients in the study. In particular, one patient shows an exceptional long-lasting response and the brain tumor tissue of this patient is strongly positive for EB1, a potential response-predictive biomarker. Based on the results from this and other clinical and preclinical studies, we are currently preparing the start of a biomarker-driven phase 2 study in patients with recurrent glioblastoma and subsequently potential additional tumor types.”

For further information, please visit https://www.esmo.org/meetings/esmo-virtual-congress-2020

About derazantinib

Derazantinib is an investigational orally administered small-molecule FGFR kinase inhibitor with strong activity against FGFR1, 2, and 3.¹ FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR genetic aberrations, e.g. gene fusions, mutations or amplifications, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial, breast, gastric and lung cancers.² In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.³ Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).^{1, 4} CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages and therefore has been identified as a potential target for anti-cancer drugs.⁵ Pre-clinical data has shown that tumor macrophage depletion through CSF1R blockade renders tumors more responsive to T-cell checkpoint immunotherapy, including approaches targeting PD-L1/PD-1.^6, 7
Derazantinib has demonstrated antitumor activity and a manageable safety profile in previous clinical studies, including a biomarker-driven phase 1/2 study in iCCA patients,⁸ and has received U.S. and EU orphan drug designation for iCCA. Basilea is currently conducting two clinical studies with derazantinib. The first study, FIDES-01, is a registrational phase 2 study in patients with inoperable or advanced iCCA. It comprises one cohort of patients with FGFR2 gene fusions and another cohort of patients with mutations or amplifications.⁹ The second study, FIDES-02, is a phase 1/2 study evaluating derazantinib alone and in combination with Roche's PD-L1-blocking immune-checkpoint inhibitor atezolizumab (Tecentriq^®)¹⁰ in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.¹¹
Basilea in-licensed derazantinib from ArQule Inc, a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About lisavanbulin (BAL101553)

Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)¹² is being developed as a potential therapy for diverse cancers.^13, 14, 15 In preclinical studies, lisavanbulin demonstrated in-vitro and in-vivo activity against diverse treatment-resistant cancer models, including tumors refractory to conventional approved therapeutics and radiotherapy.^{16, 17, 18} Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.^19, 20, 21 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.²¹ The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,²² resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.²³

About Basilea

Basilea Pharmaceutica Ltd. is a commercial-stage biopharmaceutical company, focused on the development of products that address the medical challenges in the therapeutic areas of oncology and infectious diseases. With two commercialized drugs, the company is committed to discovering, developing and commercializing innovative pharmaceutical products to meet the medical needs of patients with serious and life-threatening conditions. Basilea Pharmaceutica Ltd. is headquartered in Basel, Switzerland and listed on the SIX Swiss Exchange (SIX: BSLN). Additional information can be found at Basilea's website www.basilea.com.

Disclaimer

This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd. and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd. is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. Derazantinib and its uses are investigational and have not been approved by a regulatory authority for any use. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in nonclinical/preclinical studies to humans is currently being evaluated

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

References

1. T. G. Hall, Y. Yu, S. Eathiraj et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS ONE 2016, 11 (9), e0162594
2. R. Porta, R. Borea, A. Coelho et al. FGFR a promising druggable target in cancer: Molecular biology and new drugs. Critical K. P. Papadopoulos, B. F. El-Rayes, A. W. Tolcher et al. A phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours. British Journal of Cancer 2017 (117), 1592-1599. ClinicalTrials.gov identifier: NCT01752920
3. 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
4. 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), 12 supplement, pp. LB-C12
5. M. A. Cannarile, M. Weisser, W. Jacob et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. Journal for ImmunoTherapy of Cancer 2017, 5:53
6. Y. Zhu, B. L. Knolhoff, M. A. 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
7. E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment. Proceedings of the National Academy of Science of the United States of America 2018 (115), E4041-E4050
8. V. Mazzaferro, B. F. El-Rayes, M. Droz dit Busset et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. British Journal of Cancer 2019 (120), 165-171. ClinicalTrials.gov identifier: NCT01752920
9. FIDES-01: ClinicalTrials.gov identifier: NCT03230318
10. Tecentriq^® is a registered trademark of Hoffmann-La Roche Ltd.
11. FIDES-02: ClinicalTrials.gov identifier: NCT04045613.
12. J. Pohlmann, F. Bachmann, A. Schmitt-Hoffmann et al. BAL101553: An optimized prodrug of the microtubule destabilizer BAL27862 with superior antitumor activity. American Association for Cancer Research (AACR) annual meeting 2011, abstract 1347; Cancer Research 2011, 71 (8 supplement)
13. ClinicalTrials.gov identifier: NCT02490800
14. ClinicalTrials.gov identifier: NCT03250299
15. ClinicalTrials.gov identifier: NCT02895360
16. A. Sharmq, A. Broggini-Tenzer, V. Vuong et al. The novel microtubule targeting agent BAL101553 in combination with radiotherapy in treatment-refractory tumor models. Radiotherapy Oncology 2017 (124), 433-438
17. G. E. Duran, H. Lane, F. Bachmann et al. In vitro activity of the novel tubulin active agent BAL27862 in MDR1(+) and MDR1(-) human breast and ovarian cancer variants selected for resistance to taxanes. American Association for Cancer Research (AACR) annual meeting 2010, abstract 4412; Cancer Research 2010, 70 (8 supplement)
18. F. Bachmann, K. Burger, G. E. Duran et al. BAL101553 (prodrug of BAL27862): A unique microtubule destabilizer active against drug refractory breast cancers alone and in combination with trastuzumab. American Association for Cancer Research (AACR) annual meeting 2014, abstract 831; Cancer Research 2014, 74 (19 supplement)
19. A. Schmitt-Hoffmann, D. Klauer, K. Gebhardt et al. BAL27862: a unique microtubule-targeted agent with a potential for the treatment of human brain tumors. AACR-NCI-EORTC conference 2009, abstract C233; Molecular Cancer Therapeutics 2009, 8 (12 supplement)
20. A. C. Mladek, J. L. Pokorny, H. Lane et al. The novel tubulin-binding 'tumor checkpoint controller' BAL101553 has anti-cancer activity alone and in combination treatments across a panel of GBM patient-derived xenografts. American Association for Cancer Research (AACR) annual meeting 2016, abstract 4781; Cancer Research 2016, 76 (14 supplement)
21. R. Bergès, A. Tchoghandjian, S. Honoré et al. The novel tubulin-binding checkpoint activator BAL101553 inhibits EB1-dependent migration and invasion and promotes differentiation of glioblastoma stem-like cells. Molecular Cancer Therapeutics 2016 (15), 2740-2749
22. A. E. Prota, F. Danel, F. Bachmann et al. The novel microtubule-destabilizing drug BAL27862 binds to the colchicine site of tubulin with distinct effects on microtubule organization. Journal of Molecular Biology 2014 (426), 1848-1860
23. F. Bachmann, K. Burger, H. Lane. BAL101553 (prodrug of BAL27862): the spindle assembly checkpoint is required for anticancer activity. American Association for Cancer Research (AACR) annual meeting 2015, abstract 3789; Cancer Research 2015, 75 (15 supplement)

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