Basilea initiates targeted biomarker-driven phase 2 study with lisavanbulin in patients with brain cancer

Basel, Switzerland, September 29, 2020

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that it has initiated a phase 2 expansion study with its tumor checkpoint controller, lisavanbulin, in patients with recurrent glioblastoma multiforme (GBM), whose tumor has tested positive for the potential response-predictive biomarker EB1 (end-binding protein 1).¹

Glioblastoma is the most common type of primary brain cancer and one of the most lethal types of cancer.² In the open-label study, patients will receive once daily oral lisavanbulin. To identify patients with EB1-positive glioblastoma, a tissue screening program has been implemented using a CE-marked immunohistochemistry clinical trial assay developed for the lisavanbulin program.

Dr. Marc Engelhardt, Chief Medical Officer, said: “The initiation of the phase 2 study is an important step for us to validate our hypothesis that lisavanbulin may be developed for a targeted patient population based on a patient-selection biomarker. We expect interim results in the first half of 2021 and the outcome of this study will define the next development steps for lisavanbulin, including potentially expanding into other tumor types using a biomarker-driven approach.”

EB1 was selected by Basilea as a potential response-predictive biomarker for lisavanbulin based on preclinical studies in glioblastoma models and initial clinical signals from earlier clinical studies. One glioblastoma patient in the phase 1 portion of the current study, whose tumor tissue was strongly positive for EB1, was reported as an exceptional long-lasting responder.³ This patient continues on treatment for more than two years now and shows a more than 80% area reduction of the brain tumor.

About lisavanbulin (BAL101553)

Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)⁴ is being developed as a potential therapy for diverse cancers.^1, 5, 6 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.^{7, 8, 9} Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.^10, 11, 12 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.¹² The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,¹³ resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.¹⁴

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 .

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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References

1. ClinicalTrials.gov identifier: NCT02490800
2. B. M. Alexander, T. F. Cloughesy. Adult Glioblastoma. Journal of Clinical Oncology 2017 (35), 2402-2409
3. J. S. Lopez, R. Kristeleit, R. Rulach et al. Phase 1/2a study of once daily oral BAL101553, a novel tumor checkpoint controller (TCC), in adult patients with progressive or recurrent glioblastoma (GBM) or high-grade glioma. Journal of Clinical Oncology 2019, 37, 15 supplement, 2025
4. 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)
5. ClinicalTrials.gov identifier: NCT03250299
6. ClinicalTrials.gov identifier: NCT02895360
7. 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
8. 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)
9. 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)
10. 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)
11. 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)
12. 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
13. 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
14. 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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