Basilea reports derazantinib/PD-L1 checkpoint inhibitor combination results from dose-finding part of FIDES-02 study in patients with solid tumors at ASCO GU symposium

Basel, Switzerland, February 12, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that data on the safety, tolerability and preliminary efficacy of the fibroblast growth factor receptor (FGFR) inhibitor derazantinib in combination with the PD-L1 checkpoint inhibitor atezolizumab, in patients with advanced solid tumors from the phase 1b dose-finding cohort in the FIDES-02 study, were presented at the virtual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2021), held from February 11 to 13, 2021.¹

The derazantinib-atezolizumab combination was well tolerated and no dose-limiting toxicities were observed. The most commonly reported adverse events were fatigue/asthenia (weakness), nausea and diarrhea. The study demonstrated that derazantinib and atezolizumab can be safely combined at doses of 300 mg of daily oral derazantinib, which is the derazantinib monotherapy dose used in the phase 2 study FIDES-01, and 1200 mg atezolizumab, administered intravenously once every three weeks which was the maximum dose pre-specified in the protocol.²

Several patients are still receiving treatment with derazantinib and atezolizumab, including one patient with a bile duct cancer and FGFR2 gene fusion, who is ongoing in the study for more than nine months and was reported with a partial response with continued tumor shrinkage. The combination of derazantinib and atezolizumab is supported by preclinical data demonstrating derazantinib’s strong inhibition of colony-stimulating-factor-1-receptor kinase (CSF1R). CSF1R inhibition may revert tumor-induced immunosuppression and thereby enhance the response to immune-checkpoint inhibition.

Dr. Marc Engelhardt, Chief Medical Officer, said: “The recently announced clinical proof of concept for derazantinib as monotherapy in the FIDES-01 study in patients with FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma and the efficacy signal obtained in the group of patients with advanced solid tumors in the FIDES-02 study are encouraging. Considering the manageable safety and tolerability profile and the rapidly evolving treatment landscape in urothelial cancer in patients both with and without FGFR genetic aberrations, we additionally plan to amend the FIDES-02 study protocol to explore a higher dose of derazantinib in two cohorts of this study. These cohorts would explore whether dosing derazantinib at its previously established maximum tolerated daily dose, which is about 30% higher than the current phase 2 dose, may provide additional benefits in monotherapy and combination to patients with FGFR-positive urothelial cancer.“

The FIDES-02 study (Fibroblast growth factor Inhibition with DErazantinib in Solid tumors) is an ongoing multi-center, open-label phase 1/2 study evaluating once-daily orally administered derazantinib and atezolizumab in patients with inoperable or metastatic urothelial (bladder) cancer and confirmed FGFR genetic aberrations.

The following e-poster was presented at ASCO GU 2021:
Abstract #	Title
437	Derazantinib (DZB) in combination with atezolizumab (AZB) in patients with solid tumors: Results from the dose-finding phase Ib substudy of FIDES-02. Authors: Raghad Karim, Arvind Chaudhry, Anna Patrikidou, Alejandro Falcon Gonzalez, Fabricio Racca, Yohann Loriot, Damien Pouessel, Jean-Laurent Deville, Shinkyo Yoon, Hyo Jin Lee, Frederique Cantero, Michalina Marszewska, Mikael Saulay, Stephan Braun, Rodryg Ramlau

For further information, please visit https://meetings.asco.org/gu/virtual-program

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 initial 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 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.² Positive topline results for the FIDES-01 cohort with FGFR2 gene-fusion positive iCCA patients have just been reported. 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.¹ 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.¹¹ Basilea in-licensed derazantinib from ArQule Inc., a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

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.

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-02: ClinicalTrials.gov identifier: NCT04045613
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-03: ClinicalTrials.gov identifier: NCT04604132

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