Basilea presents full safety and efficacy data set on derazantinib in patients with FGFR2 fusion-positive iCCA at ESMO congress

 –      Progression-free survival (PFS) of derazantinib monotherapy
increased to eight months

Basel, Switzerland, September 17, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today the reporting of the updated efficacy and safety results from cohort 1 of the phase 2 study FIDES-01, which evaluated its fibroblast growth factor receptor (FGFR) inhibitor, derazantinib, in patients with FGFR2 fusion-positive advanced or metastatic intrahepatic cholangiocarcinoma (iCCA), a type of bile duct cancer, at the Congress of the European Society for Medical Oncology (ESMO), taking place as a virtual meeting from 16 to 21 September 2021.

Patients with advanced iCCA have a poor prognosis. With the current chemotherapy standard-of-care, the median overall survival is less than one year.¹

Cohort 1 of FIDES-01 enrolled 103 iCCA patients with confirmed FGFR2 fusions.² Since the reporting of first topline results in early February 2021, more patient follow-up data has been obtained, showing improvements in efficacy outcomes over time. At the cut-off date in early August, for the data presented at the ESMO congress, the disease control rate (DCR) was 75.7%, including 22 patients with a partial response as the best objective response, corresponding to an objective response rate (ORR) of 21.4%. Importantly, the progression-free survival (PFS) further increased to 8.0 months (previously: 7.8 months). The time to progression (TTP) with derazantinib was 8.1 months and thus markedly longer when compared to a TTP of only 4.5 months with the previous anti-cancer treatment the patients had received prior to entering the study.
Median overall survival was 15.9 months, with follow-up ongoing. As reported at ESMO, derazantinib had a notably well manageable adverse event profile, with a low incidence of class effects such as nail toxicities, stomatitis, hand-foot syndrome and retinal effects.

Dr. Marc Engelhardt, Chief Medical Officer, said: “The further improved efficacy data and confirmed good safety and tolerability profile presented at ESMO are very encouraging and further strengthen the evidence for the efficacy of derazantinib and its differentiation in iCCA to other FGFR inhibitors from a safety perspective.”

Derazantinib ePoster at ESMO Congress 2021, published on September 16

–

Derazantinib for patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements: Primary results from the Phase 2 study FIDES-01 – M. Droz dit Busset, W. L. Shaib, K. Mody, N. Personeni, N. Damjanov, W. P. Harris, F. Bergamo, G. Brandi, G. Masi, T. Halfdanarson, V. Tam, L. W. Goff, J. Knox, A. Hollebecque, T. Macarulla Mercade, F. Cantero, M. Saulay, S. Braun, M. Javle, M. Borad; abstract 47P

For further information please visit esmo.org/meetings/esmo-congress-2021.

About derazantinib

Derazantinib is an investigational orally administered small-molecule FGFR inhibitor with strong activity against FGFR1, 2, and 3.³ 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.⁴ In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.⁵
Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).^{3, 6} 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.⁷ 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.^8, 9
Derazantinib has demonstrated antitumor activity and a manageable safety profile in a previous biomarker-driven phase 1/2 study in iCCA patients,¹⁰ and has received U.S. and EU orphan drug designation for iCCA. Basilea is currently conducting three clinical studies with derazantinib. The first study, FIDES-01, is a 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.² The second study, FIDES-02, is a phase 1/2 study evaluating derazantinib alone and in combination with Roche's PD-L1 checkpoint inhibitor, atezolizumab, in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.¹¹ The third study, FIDES-03, is a phase 1/2 study evaluating derazantinib alone and in combination with Lilly’s anti-VEGFR2 antibody ramucirumab and paclitaxel, or with Roche’s PD-L1 checkpoint inhibitor atezolizumab, in patients with advanced gastric cancer with FGFR genetic aberrations.¹² Basilea has in-licensed derazantinib from ArQule Inc., a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About intrahepatic cholangiocarcinoma

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 is a commercial-stage biopharmaceutical company founded in 2000 and headquartered 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 assets in both cancer and infectious diseases in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit 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 use is investigational and has 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.

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. S. Rizvi, S. A. Khan, C. L. Hallemeier et al. Cholangiocarcinoma — evolving concepts and therapeutic strategies. Nature reviews Clinical oncology. 2018 (15), 95-111
2. FIDES-01: ClinicalTrials.gov identifier: NCT03230318.
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. FIDES-02: ClinicalTrials.gov identifier: NCT04045613
12. FIDES-03: ClinicalTrials.gov identifier: NCT04604132
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. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncology 2021 (22):690-701

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