Basilea announces completion of patient enrolment into first cohort of phase 2 study FIDES-01 with derazantinib in bile duct cancer (iCCA)

Basel, Switzerland, July 20, 2020

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today the completion of patient enrolment into the first cohort of the phase 2 registrational study, FIDES-01, assessing the activity of the FGFR kinase inhibitor derazantinib in patients with intrahepatic cholangiocarcinoma (iCCA), a form of bile duct cancer. This first cohort enrolled patients with iCCA expressing fusions of the fibroblast growth factor receptor 2 (FGFR2) gene and reached its target enrolment of 100 patients.

The FIDES-01 (Fibroblast growth factor Inhibition with DErazantinib in Solid tumors)¹ study is a multi-center, open-label phase 2 registrational study of once-daily oral derazantinib for the treatment of patients with inoperable or advanced iCCA and FGFR2 gene fusions or FGFR2 gene mutations or amplifications. In January 2019, a pre-planned interim analysis of the FGFR2 gene fusion-positive cohort of the study showed promising efficacy in this patient population and also confirmed the safety profile and tolerability of derazantinib observed previously in the clinical program.^{2, 3}

Dr. Marc Engelhardt, Chief Medical Officer, said: “Topline data from the first FIDES-01 cohort of FGFR2 gene fusion-positive patients are expected to become available towards year-end. These data will be important to help define our regulatory strategy in iCCA. With the FIDES range of studies, FIDES-01, FIDES-02 and FIDES-03, our goal is to leverage the unique properties of derazantinib, for the benefit of patients with advanced FGFR-driven cancers in iCCA, urothelial and gastric cancer.”

Enrolment into the second cohort of FIDES-01 is ongoing. This cohort is assessing the activity of derazantinib in patients with FGFR2 gene mutations or amplifications, thus broadening the range of investigated FGFR2-driven tumors. Interim data from this second cohort are expected to become available in the second half of 2020. The results from the second cohort will support defining the full therapeutic potential of derazantinib in iCCA and potentially further strengthen the differentiation of derazantinib from other FGFR inhibitors. In addition, the clinical development program for derazantinib includes two further Phase 1b/2 studies, the ongoing FIDES-02 in patients with urothelial cancer and the planned FIDES-03, in patients with advanced gastric cancer, which is expected to start in Q3 2020.⁴

About derazantinib

Derazantinib is an investigational orally administered small-molecule FGFR kinase inhibitor with strong activity against FGFR1, 2, and 3.⁵ 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.⁶ In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.⁷
Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).^{5, 8} 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.⁹ 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.^10, 11
Derazantinib has demonstrated antitumor activity and a manageable safety profile in a previous biomarker-driven phase 1/2 study in iCCA patients,² 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.¹ 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^®)¹² in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.⁴
Basilea in-licensed derazantinib from ArQule Inc, a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About intrahepatic cholangiocarcinoma (iCCA)

Intrahepatic cholangiocarcinoma (iCCA) is a cancer originating from the biliary system. The age-adjusted incidence rate of iCCA in the United States has been increasing over the past decade and is currently estimated to be approximately 1.2 per 100,000.¹³ Patients are often diagnosed with advanced or metastatic disease that cannot be surgically removed. Current first-line standard of care is the chemotherapy combination of gemcitabine and platinum-derived agents. The prognosis for patients with advanced disease is poor, with a median survival of less than one year.¹⁴

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.

For further information, please contact:

Peer Nils Schröder, PhD Head of Corporate Communications & Investor Relations
Phone	+41 61 606 1102
E-mail	media_relations@basilea.com investor_relations@basilea.com

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

References

1. FIDES-01: ClinicalTrials.gov identifier: NCT03230318
2. 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
3. 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
4. FIDES-02: ClinicalTrials.gov identifier: NCT04045613.
5. 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
6. R. Porta, R. Borea, A. Coelho et al. FGFR a promising druggable 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), 12 supplement, pp. LB-C12
9. 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
10. 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
11. 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
12. Tecentriq^® is a registered trademark of Hoffmann-La Roche Ltd.
13. S. K. Saha, A. X. Zhu, C. S. Fuchs et al. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. The Oncologist 2016 (21), 594-599
14. A. Lamarca, D. H. Palmer, H. S. Wasa et al. ABC-06 | A randomised phase III, multi-centre, open-label study of Active Symptom Control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. Journal of Clinical Oncology 2019 (37), supplement, abstract 4003

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