October 30, 2019

Basilea reports positive preclinical data on oncology drug candidates derazantinib and lisavanbulin at AACR-NCI-EORTC conference




  • Late-breaking abstract on mode of action and potential response biomarkers for FGFR/CSF1R kinase inhibitor derazantinib
  • Survival advantage with monotherapy and standard-of-care combinations with tumor checkpoint controller lisavanbulin in glioblastoma models

Basel, Switzerland, October 30, 2019 – Basilea Pharmaceutica Ltd. (SIX: BSLN) reported today presentations of supporting preclinical data, on its clinical stage oncology drug candidates derazantinib and lisavanbulin (BAL101553), at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, USA, on October 29, 2019.

In a late-breaking abstract, novel preclinical data were presented demonstrating that derazantinib has equipotent inhibitory activity against fibroblast growth factor receptor kinases (FGFR1, 2 and 3) and the colony-stimulating factor 1 receptor (CSF1R) kinase. Structural analyses and in-cell inhibition of CSF1R activity in isolated macrophages, performed in collaboration with Dr. Paul Walker (University of Geneva), further supported CSF1R as an additional cancer target for derazantinib. As CSF1R inhibition plays a role in restoring T cell activity, thus promoting a tumoricidal immune environment, these observations support the rationale for derazantinib combination strategies with immune modulators. Furthermore, data from detailed derazantinib activity screens across a panel of urothelial cancer models were presented, providing evidence for potential response biomarkers beyond FGFR genetic aberrations that could facilitate patient selection.

Dr. Marc Engelhardt, Basilea’s Chief Medical Officer, said: “These late-breaking derazantinib data may have important clinical implications. The data support the activity of derazantinib in urothelial cancer models with genetic FGFR aberrations and highlight the dual targeting of derazantinib through FGFR and CSF1R kinase inhibition. The activity of derazantinib against CSF1R may increase the susceptibility of cancers to immunotherapy when derazantinib is combined with PD-1/PD-L1 inhibitors.”

Basilea is currently exploring derazantinib as monotherapy and in combination with Roche’s PD-L1 inhibitor atezolizumab (Tecentriq®) in a multicohort phase 1/2 study in patients with advanced urothelial cancer.1

A second abstract presented data obtained in collaboration with Dr. Jann Sarkaria (Mayo Clinic, Rochester), demonstrating significant survival benefits in patient-derived glioblastoma models after treatment with the microtubule-targeting tumor checkpoint controller lisavanbulin (BAL101553) as monotherapy or in combination with radiotherapy and/or standard-of-care chemotherapy, including the ‘Stupp’ regimen.2 Survival benefits conferred by lisavanbulin and radiotherapy combinations improved when lisavanbulin dosing continued after the radiation window, suggesting a benefit of prolonged lisavanbulin dosing.

Lisavanbulin is currently being evaluated as monotherapy in a phase 2a study in Switzerland in patients with recurrent glioblastoma and platinum-resistant ovarian cancer patients using a weekly 48-hour infusion.3 In the U.S., a phase 1 study is being conducted in collaboration with the Adult Brain Tumor Consortium (ABTC), in which oral lisavanbulin is evaluated in combination with radiotherapy in patients with newly diagnosed glioblastoma who have a reduced sensitivity to chemotherapy with the standard-of-care drug temozolomide.4 Patient recruitment into a further phase 1 study in recurrent glioblastoma or high-grade glioma with the oral formulation has just been completed with the determination of the maximum tolerated dose.5 In this study, daily oral lisavanbulin showed clinical antitumor activity, including one exceptional, long-lasting responder with an approximate 70% tumor area reduction.6

Derazantinib late-breaking abstract at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics
  • Derazantinib (DZB): A dual FGFR/CSF1R-inhibitor active in PDX-models of urothelial cancer – Paul McSheehy, Felix Bachmann, Nicole Forster-Gross, Marc Lecoultre, Mahmoud E. Shemerly, Mila Roceri, Stefan Reinelt, Laurenz Kellenberger, Paul R. Walker, Heidi Lane; abstract LB-C12.

Lisavanbulin (BAL101553) abstract at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics
  • Modeling the clinical paradigm of lisavanbulin (BAL101553) deployment in patient-derived xenografts (PDX) of glioblastoma (GBM) – Danielle M. Burgenske, Ann C. Mladek, Jenny L. Pokorny, Heidi A. Lane, Felix Bachmann, Rachael A. Vaubel, Mark A. Schroeder, Katrina K. Bakken, Lihong He, Zeng Hu, Brett L. Carlson, Surabhi Talele, Gautham Gampa, Matthew L. Kosel, Paul A. Decker, Jeanette E. Eckel-Passow, William F. Elmquist, Jann N. Sarkaria; abstract C096

For further information, please visit www.aacr.org.

About derazantinib

Derazantinib (formerly ARQ 087) is an investigational orally administered small-molecule panFGFR kinase inhibitor with strong activity against FGFR1, 2, and 3.7 FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR genetic aberrations, e.g. gene fusions, mutations or amplifications, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial, breast, gastric and lung cancers.8 In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.9
Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).7 CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages and therefore has been identified as a potential target for anti-cancer drugs.10 Pre-clinical data has shown that tumor macrophage depletion through CSF1R blockade renders tumors more responsive to T-cell checkpoint immunotherapy, including approaches targeting PD-L1/PD-1.11, 12
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,13 and has received U.S. and EU orphan drug designation for iCCA. Basilea is currently conducting two clinical studies with derazantinib. The first study, FIDES-01, is a registrational phase 2 study in patients with iCCA with FGFR2 gene fusions or mutations and amplifications.14 The second study, FIDES-02, is a phase 1/2 study evaluating derazantinib alone and in combination with Roche's PD-L1-blocking immune-checkpoint inhibitor atezolizumab (Tecentriq®) in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.1 Basilea in-licensed derazantinib from ArQule Inc.

About lisavanbulin (BAL101553)

Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)15 is being developed as a potential therapy for diverse cancers. It is currently evaluated in clinical phase 1 and 2a studies with glioblastoma and ovarian cancer patients.3, 4, 5 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.16, 17, 18 Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.19, 20, 21 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.21 The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,22 resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.23

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.


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
+41 61 606 1102

This press release can be downloaded from www.basilea.com.


1    ClinicalTrials.gov identifier: NCT04045613. Tecentriq® is a registered trademark of Hoffmann-La Roche Ltd.

2    R. Stupp, W. P. Mason, M. J. van den Bent et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 2005 (352), 987-996

3    ClinicalTrials.gov identifier: NCT02895360

4    ClinicalTrials.gov identifier: NCT03250299

5    ClinicalTrials.gov identifier: NCT02490800

6    J. S. Lopez, R. S. 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. American Society of Clinical Oncology (ASCO) annual meeting 2019, abstract 2025; Journal of Clinical Oncology 2019, 37 (15 supplement), 2025

7    T. G. Hall, Y. Yu, S. Eathiraj et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS ONE 2016, 11 (9), e0162594

8    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

9    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

10  M. A. Cannarile, M. Weisser, W. Jacob et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. Journal for ImmunoTherapy of Cancer 2017, 5:53

11  Y. Zhu, B. L. Knolhoff, M. A. Meyer et al. CSF1/CSF1R Blockade reprograms tumor-infiltrating macrophages and improves response to T cell checkpoint immunotherapy in pancreatic cancer models. Cancer Research 2014 (74), 5057-5069

12  E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment. Proceedings of the National Academy of Science of the United States of America 2018 (115), E4041-E4050         

13  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. ClinicalTrials.gov identifier: NCT01752920

14  ClinicalTrials.gov identifier: NCT03230318

15  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)

16  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

17  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)

18  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)

19  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)

20  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)

21  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

22  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

23  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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