Basilea reports new prevalence data for EB1, a potential response-predictive biomarker for lisavanbulin in glioblastoma and other tumor types, at ASCO Annual Meeting

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

The following posters are presented at the 2021 ASCO Annual Meeting:
Abstract #	Title
3118	Expression of end-binding protein 1 (EB1), a potential response-predictive biomarker for lisavanbulin, in glioblastoma and various other solid tumor types Authors: Magdalena Skowronska, Crescens Tiu, Alexandar Tzankov, Fatima König, Joanne Lewis, Igor Vivanco, Malte Kleinschmidt, Kirk Beebe, Stephanie Anderson, Felix Bachmann, Marc Engelhardt, Heidi A. Lane, Thomas Kaindl, Alexandru C Stan, Elizabeth Ruth Plummer, T. R. Jeffry Evans, Inti Zlobec, Juanita Suzanne Lopez
TPS2068	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 Authors: Crescens Tiu, Sarah Derby, Noor Md. Haris, Liam Welsh, Anna Stansfeld, Thomas Hundsberger, Patrick Roth, Fatima König, Joel Robert Eisner, Malte Kleinschmidt, Stephanie Anderson, Felix Bachmann, Heidi A. Lane, Marc Engelhardt, Thomas Kaindl, Karine Litherland, Alexandru C. Stan, T. R. Jeffry Evans, Elizabeth Ruth Plummer, Juanita Suzanne Lopez

For further information, please visit https://conferences.asco.org/am/abstracts-posters

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, 11
Lisavanbulin 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:

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 www.basilea.com.

References

1. A. Nehlig, A. Molina, S. Rodrigues-Ferreira et al. Regulation of end-binding protein EB1 in the control of microtubule dynamics. Cellular and Molecular Life Sciences 2017 (74), 2381-2393
2. 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
3. ClinicalTrials.gov identifier: NCT02490800. Phase 1 results: 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. 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. J Clin Oncol 39, 2021 (suppl 15; abstr 3118)
5. C. Tiu, S. Derby, N. 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. J Clin Oncol 39, 2021 (suppl 15; abstr TPS2068)
6. 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)
7. ClinicalTrials.gov identifier: NCT03250299
8. ClinicalTrials.gov identifier: NCT02895360
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, 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)
11. 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)
12. 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)
13. 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)
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. American Association for Cancer Research (AACR) annual meeting 2015, abstract 3789; Cancer Research 2015, 75 (15 supplement)
    
    

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