Avanbulin

Potential to add third clinical-stage program to oncology pipeline Progressing patient enrolment towards interim analyses in lisavanbulin phase 2 study and in patient cohorts in FIDES-01 and FIDES-02 studies with derazantinib Basel, Switzerland, November 16, 2021 Basilea Pharmaceutica Ltd. (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with cancer and infectious diseases, announced today that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA), to start clinical studies with the company’s novel drug candidate BAL0891 in cancer therapy. BAL0891 is a potential first-in-class small-molecule kinase inhibitor. If the IND is granted, Basilea plans to initiate a phase 1 study in patients with advanced solid tumors in the first quarter of 2022. Dr. Laurenz Kellenberger, Chief Scientific Officer said: “We are very pleased with the progress made in the project. Submitting this IND is an important regulatory milestone for Basilea as we are moving closer to adding BAL0891 as the third oncology drug candidate to our clinical pipeline.” The two oncology drug candidates already in clinical development are derazantinib, an inhibitor of the fibroblast growth factor receptor (FGFR) family of kinases, which is currently in clinical studies for the treatment of bile duct (iCCA), urothelial and gastric cancers (the FIDES studies), and lisavanbulin, a tumor checkpoint controller, currently in clinical studies with patients with glioblastoma, the most aggressive primary brain cancer. Dr. Marc Engelhardt, Chief Medical Officer, said: “We are expecting to complete enrolment of the number of patients required to support interim analyses in three oncology studies around year-end. This is the phase 2 study with lisavanbulin in glioblastoma patients whose tumors tested positive on the potentially response-predictive biomarker EB1. For derazantinib, this is the cohort of patients with urothelial cancer refractory to prior FGFR inhibitors in the FIDES-02 study and the cohort of patients with intrahepatic cholangiocarcinoma, or iCCA, with non-fusion FGFR2 genetic aberrations in the FIDES-01 study. With enrolment progressing, we now have more visibility on the timelines and expect that interim data read-outs will become available over the course of the first half of 2022.“ About BAL0891 BAL0891 is a potential first-in-class small-molecule kinase inhibitor, which was in-licensed in 2018. The compound has shown anti-proliferative activity across diverse tumor cell lines in vitro and efficacy in in-vivo models of human cancers. Basilea has filed an Investigational New Drug application to the U.S. Food and Drug Administration, with the goal to initiate first-in-human clinical studies in the first quarter of 2022. About derazantinib Derazantinib is an investigational orally administered small-molecule FGFR 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 pro a previous 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 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.9 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.10 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 has in-licensed derazantinib from ArQule Inc., a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A. About lisavanbulin Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)12 is currently being developed as a potential therapy for glioblastoma.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 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models and strong EB1-positivity was shown in about 5% of tissue samples from glioblastoma patients.21, 22 The strongest expression of EB1 in non-glioblastoma tumors was detected in tissue samples from medulloblastomas and neuroblastomas, which are cancers that occur predominantly in the pediatric population. EB1-positive staining was also found in tissue samples from metastatic melanoma (skin cancer). Other tumors expressing slightly lower levels of EB1 staining include non-small cell lung cancer, colorectal cancer and triple-negative breast cancer.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 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 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 lisavanbulin and their 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 . References 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 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 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 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 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 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 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 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 FIDES-01: ClinicalTrials.gov identifier: NCT03230318 FIDES-02: ClinicalTrials.gov identifier: NCT04045613 FIDES-03: ClinicalTrials.gov identifier: NCT04604132 J. Pohlmann, F. Bachmann, A. Schmitt-Hoffmann et al. BAL101553: An optimized prodrug of the microtubule destabilizer B. M. Alexander, T. F. Cloughesy. Adult Glioblastoma. Journal of Clinical Oncology 2017 (35), 2402-2409 ClinicalTrials.gov identifier: NCT02490800; C. Tiu, S. Derby, N. Md. Haris et al. The potential utility of end-binding protein 1 (EB1) as response-predictive biomarker for lisavanbulin: A phase 2 study of lisavanbulin (BAL101553) in adult patients with recurrent glioblastoma. Journal of Clinical Oncology 2021, 39 (15 supplement, TPS2068) ClinicalTrials.gov identifier: NCT03250299 ClinicalTrials.gov identifier: NCT02895360 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 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. Cancer Research 2010, 70 (8 supplement), abstract 4412 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. Cancer Research 2014, 74 (19 supplement), abstract 831 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. Molecular Cancer Therapeutics 2009, 8 (12 supplement), C233 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. Cancer Research 2016, 76 (14 supplement), abstract 4781 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 M. Skowronska, C. Tiu, A. Tzankov et al. Expression of end-binding protein 1 (EB1), a potential response-predictive biomarker for lisavanbulin, in glioblastoma and various other solid tumor types. Journal of Clinical Oncology 2021, 39 (15 supplement, 3118) 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 F. Bachmann, K. Burger, H. Lane. BAL101553 (prodrug of BAL27862): the spindle assembly checkpoint is required for anticancer activity. Cancer Research 2015, 75 (15 supplement), abstract 3789 Attachment Press release (PDF)

Basel, Switzerland, June 07, 2021 Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that data on the prevalence of end-binding protein 1 (EB1) in glioblastoma and other tumor types is being presented at the American Society of Clinical Oncology (ASCO) Annual Meeting that takes place online from June 4 to 8, 2021. EB1 plays a pivotal role in the regulation of microtubule dynamics during cell division and has been shown to interact with microtubule-targeting agents, such as lisavanbulin, inhibiting tumor growth.1 EB1 has been identified as a response-predictive biomarker for Basilea’s tumor checkpoint controller lisavanbulin in pre-clinical glioblastoma models.2 In the previously reported phase 1 portion of the ongoing phase 1/2 clinical study, long-lasting clinical benefit was observed in two patients with recurrent glioblastoma whose tumor tissues show EB1-positive staining. Both patients are ongoing in the study for more than 2 years.3 The prevalence assessment of EB1-positivity or strong EB1-staining using immunohistochemistry methods presented at ASCO was based on 565 patient tissue samples from 14 different tumor types, including more than 100 glioblastoma samples. Approximately 5% of glioblastoma tissue samples were found to be EB1-positive. The strongest expression of EB1 in non-glioblastoma tumors was detected in tissue samples from medulloblastomas and neuroblastomas, which are cancers that occur predominantly in the pediatric population. EB1-positive staining was also found in tissue samples from metastatic melanoma (skin cancer). Other tumors expressing slightly lower levels of EB1 staining include non-small cell lung cancer, colorectal cancer and triple-negative breast cancer.4 Dr. Marc Engelhardt, Chief Medical Officer, commented: ”We are very pleased that two patients with EB1-positive recurrent glioblastoma have obtained long-lasting clinical benefit in our phase 1 study with lisavanbulin. We are looking forward to the interim results in our phase 2 study, which is enrolling patients with recurrent glioblastoma that is EB1-positive, towards the end of 2021. The new prevalence data presented at ASCO are consistent with our initial frequency estimates of EB1-positive glioblastoma. A clinical proof-of-concept in glioblastoma based on positive interim results would support exploring the selection of patients based on EB1-positivity in other tumor types as well, such as melanoma, breast, colorectal and lung cancers or rare cancer types such as medulloblastomas or neuroblastomas.” The rationale and study design of the ongoing phase 2 study with lisavanbulin in patients with EB1-positive recurrent glioblastoma is being presented in a second poster at the ASCO Annual meeting.5 For further information, please visit About lisavanbulin (BAL101553) Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)6 is being developed as a potential therapy for diverse cancers.1, 7, 8 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.9, 10, 11Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.12, 13 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.2 The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,14 resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.15 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. For further information, please contact: This press release can be downloaded from . References Attachment