Basilea announces U.S. FDA Orphan Drug Designation granted to lisavanbulin for the treatment of malignant glioma

Basel, Switzerland, July 29, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to Basilea’s tumor checkpoint controller, lisavanbulin, for the treatment of malignant glioma (brain cancer). This includes glioblastoma, the most common type of primary brain cancer and one of the most lethal types of cancer.¹ Orphan Drug Designation qualifies the sponsor of the drug for various incentives, including longer regulatory market exclusivity.

Dr. Marc Engelhardt, Chief Medical Officer, commented: “The Orphan Drug Designation of lisavanbulin by the U.S. FDA is an important milestone for the development of lisavanbulin. Glioblastoma is associated with a poor prognosis and there are only very limited therapeutic options available. Lisavanbulin, as a targeted treatment, could be a useful new approach to expand the treatment options for patients with this devastating disease.”

Basilea is currently conducting a phase 1/2 study in patients with recurrent glioblastoma, using end-binding protein 1 (EB1) for patient selection.² In the previously reported phase 1 part of the study, long-lasting clinical benefit was observed in two patients with recurrent glioblastoma whose tumor tissues showed EB1-positive staining.³ Interim results from the phase 2 part of the study are expected in the second half of 2021.

About lisavanbulin (BAL101553)

Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)⁴ is currently being developed as a potential therapy for glioblastoma.^2, 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 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.^12, 13 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.¹³ 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.

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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. 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)
3. C. Tiu, A. Tzankov, R. Plummer et al. The potential utility of end-binding protein 1 (EB1) as response-predictive biomarker for lisavanbulin: Final results from a phase I study of lisavanbulin (BAL101553) in adult patients with recurrent glioblastoma (GBM). Annals of Oncology 2020 (31) supplement 4, S396-S408
4. J. Pohlmann, F. Bachmann, A. Schmitt-Hoffmann et al. BAL101553: An optimized prodrug of the microtubule destabilizer BAL27862 with superior antitumor activity. Cancer Research 2011, 71 (8 supplement), abstract 1347
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. Cancer Research 2010, 70 (8 supplement), abstract 4412
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. Cancer Research 2014, 74 (19 supplement), abstract 831
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. Molecular Cancer Therapeutics 2009, 8 (12 supplement), C233
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. Cancer Research 2016, 76 (14 supplement), abstract 4781
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. 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)
14. 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
15. 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

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