• Key oncology clinical studies with derazantinib and lisavanbulin remain on track
• FDA approves protocol amendment for the phase 3 ERADICATE bacteremia study with ceftobiprole to include a broader spectrum of severely ill patients
• No negative COVID-19 impact expected on global prescriptions of Cresemba^® and Zevtera^®
• Early R&D portfolio prioritization

Basel, Switzerland, May 28, 2020

Basilea Pharmaceutica Ltd. (SIX: BSLN) provided a general corporate update today. The company does not expect a material impact on the timelines of ongoing or planned oncology studies with the FGFR kinase inhibitor derazantinib and the planned phase 2a biomarker driven study with its tumor checkpoint controller, lisavanbulin, due to the coronavirus pandemic. The impact on the ongoing ceftobiprole phase 3 study remains limited, with patient enrolment timelines potentially extended by up to a quarter.

David Veitch, Chief Executive Officer of Basilea, said: “We have assessed the potential impact of the coronavirus pandemic on our business based on the information available to date. We are pleased to report that we do not currently anticipate an impact on our key oncology clinical studies with our most advanced compounds derazantinib and lisavanbulin. As the global healthcare community is prioritizing measures against coronavirus infections, we expect a limited impact of up to a quarter on the timelines for our ceftobiprole phase 3 study. As previously reported, we have no indication from our commercial partners of any negative impact on global prescriptions for both Cresemba and Zevtera, our two marketed brands. The continued strong market demand is also reflected in the 30 percent year-on-year growth in U.S. Cresemba sales as reported by our license partner Astellas, mid-May, with sales of 155 million U.S. dollars for the period April 2019 to March 2020.”

For Basilea’s antibiotic ceftobiprole, the U.S. Food & Drug Administration (FDA) has recently approved a protocol amendment for the phase 3 study ERADICATE, to progress the study to the pre-planned second cohort and extend the maximum treatment duration from four to up to six weeks. ERADICATE explores intravenous ceftobiprole for the treatment of patients with Staphylococcus aureus bacteremia (SAB), a type of bacterial bloodstream infection, in comparison to intravenous daptomycin, with or without intravenous aztreonam.^{1, 2} The overall target patient enrolment number in the study remains unchanged.

Dr. Marc Engelhardt, Chief Medical Officer of Basilea, said: “We are very satisfied that the study progresses as planned to its next stage. The possibility for an extended treatment duration is important as it enables us now to expand enrolment to patients with more difficult-to-treat infections, including those with complications such as osteomyelitis and epidural or cerebral abscess.”

In its continued effort to optimize resource allocation across its portfolio, Basilea has taken several decisions with respect to its earlier stage R&D portfolio. Basilea has prioritized two potential first-in-class oncology programs, these are expected to potentially enter pre-clinical, IND-enabling studies in the next 12 months. At the same time, it will discontinue the development of the panRAF/SRC kinase inhibitor BAL3833, which was developed by scientists at The Institute of Cancer Research (ICR) in London, funded by Cancer Research UK and the Wellcome Trust, and in-licensed by Basilea in 2015. In 2018, a first-in-human phase 1 dose-escalation study of BAL3833 was completed by the ICR in conjunction with The Christie and Royal Marsden NHS Foundation Trusts and The Cancer Research UK Manchester Institute at The University of Manchester. Basilea had been conducting pre-clinical activities to explore alternative formulations of BAL3833. In addition, it has decided to discontinue one other, externally sourced, pre-clinical oncology project.

About derazantinib

Derazantinib is an investigational orally administered small-molecule FGFR kinase 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 previous clinical studies, including a 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 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.¹¹ 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^®) in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.¹² 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)¹³ is being developed as a potential therapy for diverse cancers.^14, 15, 16 In pre-clinical studies, lisavanbulin demonstrated in-vitro and in-vivo activity against diverse treatment-resistant cancer models, including tumors refractory to conventional approved therapeutics and radiotherapy.^{17, 18, 19} Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.^20, 21, 22 In pre-clinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.²² The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,²³ resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.²⁴

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.

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

References

1. ClinicalTrials.gov identifier: NCT03138733. The ceftobiprole phase 3 program is funded in part (up to USD 128 million, which is approximately 70% of the total estimated program costs) with federal funds from the U.S. Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201600002C.
2. K. Hamed, M. Engelhardt, M. E. Jones et al. Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiology 2020 (15), 35-48
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. ClinicalTrials.gov identifier: NCT03230318
12. ClinicalTrials.gov identifier: NCT04045613. Tecentriq^® is a registered trademark of Hoffmann-La Roche Ltd.
13. 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)
14. ClinicalTrials.gov identifier: NCT02490800
15. ClinicalTrials.gov identifier: NCT03250299
16. ClinicalTrials.gov identifier: NCT02895360
17. 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
18. 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)
19. 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)
20. 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)
21. 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)
22. 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
23. 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
24. 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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