Basilea reported the new prevalence data of EB1 at the ASCO annual meeting. EB1 is a potential response predictive biomarker for Lisavanbulin in glioblastoma and other tumor types


Basel, Switzerland, June 7, 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 are being announced online at the American Society of Clinical Oncology (ASCO) annual meeting 2021 June 4th to 8th.

EB1 plays a key role in the regulation of microtubule dynamics during cell division, and has been shown to interact with microtubule targeting agents (such as lisavanbulin) to inhibit tumor growth.1 In the preclinical glioblastoma model, EB1 has been identified as the response prediction biomarker of Basilea’s tumor checkpoint controller lisavanbulin.2 In the previously reported phase 1 part of the ongoing phase 1/2 clinical study, long-term clinical benefit was observed in two patients with recurrent glioblastoma whose tumor tissue showed positive staining for EB1. Both patients have been in the study for more than 2 years.3

The assessment of the prevalence of EB1-positive or strong EB1 staining using immunohistochemical methods shown on ASCO is 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 medulloblastoma and neuroblastoma. These cancers mainly occur in the pediatric population.
EB1 positive staining was also found in tissue samples from metastatic melanoma (skin cancer). Other tumors that express slightly lower EB1 staining levels include non-small cell lung cancer, colorectal cancer, and triple negative breast cancer.4

Chief Medical Officer Dr. Marc Engelhardt commented: “We are very pleased that two EB1-positive recurrent glioblastoma patients have obtained long-term clinical benefit in our phase 1 study of lisavanbulin. We look forward to our mid-term results of the phase 2 study, Recruit EB1-positive patients with recurrent glioblastoma by the end of 2021. The new prevalence data provided on ASCO is consistent with our initial frequency estimate of EB1-positive glioblastoma. The clinical proof of concept is based on positive interim results Among the glioblastomas, it will support exploring options for EB1-positive patients based on other tumor types, such as melanoma, breast cancer, colorectal cancer, and lung cancer, or rare cancer types such as medulloblastoma or neuroblastoma .”

The second poster of the ASCO annual meeting showed the basic principles and research design of the ongoing Phase 2 study of risavanbulin EB1-positive recurrent glioblastoma patients.5

The following posters will be displayed at the 2021 ASCO Annual Meeting:
Abstract# title
3118 Expression of end-binding protein 1 (EB1), a potential response prediction biomarker for lisavanbulin, in glioblastoma and various other solid tumor types

Authors: Magdalena Skowronska, Crescens Tiu, Alexander Tzankov, Fatima König, Joanne Lewis, Igor Vivanco, Malte Kleinschmidt, Kirk Beebe, Stephanie Anderson, Felix Bachmann, Marc Engelhardt, Heidi A. Lane, Thomas Kaindl, Ruu C, Elizabeth, Ruu C, Elizabeth TR Jeffrey Evans, Intiz Lobek, Juanita Susanna Lopez

TPS2068 Potential utility of terminal binding protein 1 (EB1) as a biomarker for lisavanbulin response prediction: 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.hard Lane, Marc Engel Kaindl, Karine Litherland, Alexandru C. Stan, TR Jeffry Evans, Elizabeth Ruth Plummer, Juanita Suzanne Lopez

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

About Lisa Vanbrin (BAL101553)

Basilea’s tumor drug candidate Lisavanbrin (BAL101553, a prodrug of BAL27862)6 It is being developed as a potential therapy for a variety of cancers.1, 7, 8 In preclinical studies, lisavanbulin has demonstrated in vitro and in vivo activity against multiple drug resistances
Cancer models, including tumors that do not respond to conventionally approved treatments and radiotherapy.9, 10, 11
Lisavanbulin is effectively distributed to the brain and has anticancer activity in a glioblastoma model.12, 13 In preclinical studies, terminal binding protein 1 (EB1) was identified as a potential response prediction biomarker in glioblastoma models.2 The active part BAL27862 binds to the colchicine site of tubulin and has a significant effect on the microtubule organization.14 This leads to the activation of the “spindle assembly checkpoint” and promotes tumor cell death.15

About Brasilia

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 cancer and infectious disease patients. 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 research using two targeted drug candidates to treat a range of cancers and have many preclinical assets for cancer and infectious diseases in our portfolio. Basilea is listed on six Swiss exchanges (six: BSLN). Please visit basilea.com.

Disclaimer

This communication expressly or implicitly contains certain forward-looking statements, such as “believes”, “assumptions”, “anticipates”, “forecasts”, “projects”, “may”, “may”, “may”, “will” or Similar statements of Basilea Pharmaceutica Ltd. and its business, including the progress, timing and completion of research, development, and clinical studies of product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which may result in Basilea Pharmaceutica Ltd.’s actual results, financial condition, performance or achievements and any future results, performance implied by such forward-looking statements or Or there is a major difference in achievement-a statement that seems. Basilea Pharmaceutica Ltd. will provide this communication on this date and does not undertake to update any forward-looking statements contained herein due to new information, future events or other reasons.

For more information, please contact:

Peer Nils Schröder, PhD

Head of Corporate Communications and Investor Relations

phone +41 61 606 1102
e-mail [email protected]
[email protected]

This press release can be downloaded from the following URL www.basilea.com.

reference

  1. A. Nehlig, A. Molina, S. Rodrigues-Ferreira, etc. Regulation of end-binding protein EB1 in the control of microtubule dynamics. Cell and Molecular Life Sciences 2017 (74), 2381-2393
  2. R. Bergès, A. Tchoghandjian, S. Honoré, etc. The new tubulin-binding checkpoint activator BAL101553 inhibits EB1-dependent migration and invasion and promotes the differentiation of glioblastoma stem cell-like cells. Molecular Cancer Therapeutics 2016 (15), 2740-2749
  3. ClinicalTrials.gov identifier: NCT02490800. Results of the first stage: C. Tiu, A. Tzankov, R. Plummer, etc. The potential utility of terminal binding protein 1 (EB1) as a biomarker for lisavanbulin response prediction: the final result of a phase I study of lisavanbulin (BAL101553) in adult recurrent glioblastoma (GBM). Yearbook of Oncology 2020 (31) Supplement 4, S396-S408
  4. M. Skowronska, C. Tiu, A. Tzankov, etc. The expression of end-binding protein 1 (EB1), a potential biomarker for lisavanbulin response prediction, in glioblastoma and various other solid tumor types. J Clin Oncol, 39, 2021 (Supplement 15; Abstract 3118)
  5. C. Tiu, S. Derby, N. Haris, etc. Potential utility of terminal binding protein 1 (EB1) as a biomarker for lisavanbulin response prediction: a phase 2 study of lisavanbulin (BAL101553) in adult patients with recurrent glioblastoma. J Clin Oncol, 39, 2021 (Supplement 15; Abstract TPS2068)
  6. J. Pohlmann, F. Bachmann, A. Schmitt-Hoffmann, etc. BAL101553: an optimized prodrug of the microtubule destabilizer BAL27862, with excellent anti-tumor activity. American Association for Cancer Research (AACR) 2011 Annual Meeting, Abstract 1347; Cancer Research 2011, 71 (8 supplements)
  7. ClinicalTrials.gov identifier: NCT03250299
  8. ClinicalTrials.gov identifier: NCT02895360
  9. A. Sharmq, A. Broggini-Tenzer, V. Vuong, etc. A new type of microtubule targeting agent BAL101553 combined with radiotherapy to treat refractory tumor models. Radiotherapy Oncology 2017 (124), 433-438
  10. GE Duran, H. Lane, F. Bachmann, etc. In vitro activity of the new tubulin activator BAL27862 in MDR1(+) and MDR1(-) human breast and ovarian cancer variants, which were selected to be taxane resistant. American Association for Cancer Research (AACR) 2010 Annual Meeting, Abstract 4412; Cancer Research 2010, 70 (8 supplements)
  11. F. Bachmann, K. Burger, GE Duran, etc. BAL101553 (the prodrug of BAL27862): a unique microtubule destabilizer used alone or in combination with trastuzumab to treat refractory breast cancer. American Association for Cancer Research (AACR) 2014 Annual Meeting, Abstract 831; Cancer Research 2014, 74 (19 Supplement)
  12. A. Schmitt-Hoffmann, D. Klauer, K. Gebhardt, etc. BAL27862: A unique microtubule targeted drug with the potential to treat human brain tumors. AACR-NCI-EORTC Conference 2009, Abstract C233; Molecular Cancer Therapeutics 2009, 8 (12 supplement)
  13. AC Mladek, JL Pokorny, H. Lane, etc. The new tubulin combined with the “tumor checkpoint controller” BAL101553 has anti-cancer activity alone, and has anti-cancer activity in the combination therapy of xenografts derived from a group of GBM patients. American Association for Cancer Research (AACR) 2016 Annual Meeting, Abstract 4781; Cancer Research 2016, 76 (14 Supplements)
  14. AE Prota, F. Danel, F. Bachmann, etc. The new microtubule unstable drug BAL27862 binds to the colchicine site of tubulin and has a significant impact on the microtubule organization. Journal of Molecular Biology 2014 (426), 1848-1860
  15. F. Bachmann, K. Burger, H. Lane. BAL101553 (prodrug of BAL27862): Anticancer activity requires spindle assembly checkpoints. American Association for Cancer Research (AACR) 2015 Annual Meeting, Abstract 3789; Cancer Research 2015, 75 (15 supplement)

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