Basel, Switzerland, June 3, 2019 – Basilea Pharmaceutica Ltd. (SIX: BSLN) reported today the phase 1 data from an ongoing study with the oral formulation of its novel tumor checkpoint controller, BAL101553, in brain cancer patients with progressive or recurrent glioblastoma, or high-grade glioma. The data were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, USA, on June 2nd, 2019.

Results were based on 25 patients dosed in an open-label phase 1 study to explore once-daily oral BAL101553 as a single agent in patients with recurrent glioblastoma, the most common and aggressive primary brain tumor,1 and patients with high-grade gliomas. BAL101553 was well tolerated and showed clinical activity, with a long-lasting confirmed partial response in one patient whose glioblastoma had been rapidly progressing on two lines of prior therapy. Tumor tissue analyses showed strong expression of the microtubule plus-end binding protein 1 (EB1), which has previously been identified as a potential predictive biomarker of tumor response to BAL101553 in preclinical glioblastoma models.2 In addition, five further patients experienced stable disease as a best response.

In preclinical models, BAL101553 has been shown to cross the blood-brain barrier3 with antitumor activity in a panel of brain cancer models.3, 4

Dr. Marc Engelhardt, Basilea’s Chief Medical Officer, said: “The safety profile of oral BAL101553 and the signals of clinical activity in glioblastoma patients whose cancer progressed after prior therapy are encouraging. We continue to escalate the dose in the ongoing phase 1 study with the goal to establish a maximum tolerated dose for the oral formulation in glioblastoma, while also exploring whether EB1, or other biomarkers, may have clinical utility for patient stratification."

Basilea anticipates that the study will reach its primary goal, the definition of a maximum tolerated dose, in 2019. Two additional clinical studies with BAL101553 are ongoing: a phase 1 study in combination with standard radiotherapy in newly diagnosed glioblastoma, conducted in collaboration with the Adult Brain Tumor Consortium (ABTC) in the U.S., and a phase 2a expansion study, in which BAL101553 is administered as a weekly 48-hour intravenous (i.v.) infusion in patients with recurrent glioblastoma and in patients with platinum-resistant or refractory ovarian cancer.5, 6

For derazantinib, Basilea's most advanced oncology drug candidate, data from a post-hoc analysis from a previously completed non-comparative phase 2a study7 were published in abstract form. The results from this analysis indicated that the antitumor efficacy of derazantinib in patients with intrahepatic cholangiocarcinoma (iCCA), a form of biliary duct cancer, with FGFR2 gene fusions who received derazantinib in a post-second line setting was similar compared to patients who received derazantinib as first or second-line treatment. This suggests that derazantinib could be an effective treatment option at both early and later stages of the disease.

For further information, please visit meetings.asco.org/am.

About BAL101553
Basilea's oncology drug candidate BAL101553 (the prodrug of BAL27862)8 is being developed as a potential therapy for diverse cancers. The drug candidate is currently in phase 1/2a clinical evaluation. In Switzerland, a phase 2a expansion study is exploring the drug in recurrent glioblastoma and platinum-resistant ovarian cancer patients using weekly 48-hour infusion. In the UK, a phase 1 dose escalation with daily oral administration is ongoing in patients with progressive or recurrent glioblastoma or high-grade glioma. In the U.S., a phase 1 study is being conducted in collaboration with the Adult Brain Tumor Consortium (ABTC), in which BAL101553 is explored in combination with radiotherapy in patients with newly diagnosed glioblastoma who have a reduced sensitivity to chemotherapy with the standard-of-are drug temozolomide. In preclinical studies, BAL101553 demonstrated in-vitro and in-vivo activity against diverse treatment-resistant cancer models, including tumors refractory to conventional approved therapeutics and radiotherapy.9, 10, 11 BAL101553 efficiently distributes to the brain, with anticancer activity in glioblastoma models.2, 3, 4 The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,12 resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.13

About derazantinib
Derazantinib (BAL087, formerly ARQ 087) is an investigational orally administered small molecule panFGFR kinase inhibitor with strong activity against FGFR1, 2, and 3. FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR gene alterations, e.g. rearrangements, amplification or mutations, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial, breast, gastric and lung cancers.14 In these cancers, FGFR gene alterations are found in a range of 5% to 30%.15 Basilea in-licensed derazantinib from ArQule Inc. in April 2018. 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,7 and has received U.S. and EU orphan drug designation for iCCA.

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 anti-infectives. 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      B. M. Alexander, T. F. Cloughesy. Adult Glioblastoma. Journal of Clinical Oncology 2017 (35), 2402-2409
2      R. Bergès 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
3      A. Schmitt-Hoffmann 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)
4      A. C. Mladek 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
5      ClinicalTrials.gov Identifier: NCT0325029
6      ClinicalTrials.gov Identifier: NCT02895360
7      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
8      J. Pohlmann 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)
9      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
10    G. E. Duran 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
11    F. Bachmann 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
12    A. E. Prota 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
13    F. Bachmann et al. BAL101553 (prodrug of BAL27862): the spindle assembly checkpoint is required for anticancer activity. American Association for Cancer Research (AACR) annual meeting 2015, abstract 3789
14    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
15    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

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