January 03, 2018

Basilea reports start of clinical phase 1 study in collaboration with the U.S. Adult Brain Tumor Consortium to explore BAL101553 in newly diagnosed glioblastoma




Basel, Switzerland, January 03, 2018 - Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today the initiation of a phase 1 study conducted under its clinical study agreement with the Adult Brain Tumor Consortium (ABTC) in the U.S. The first patient has been treated in this open-label dose-escalation study to determine the safety and tolerability of the oral formulation of Basilea's novel anticancer drug candidate BAL101553 in combination with standard radiation in patients with newly-diagnosed glioblastoma. Patients participating in the study have a reduced sensitivity to standard chemotherapy with temozolomide due to an unmethylated MGMT promoter.

Ronald Scott, Chief Executive Officer, commented, "Glioblastoma patients have limited therapeutic options and new treatment opportunities are urgently needed. This is especially the case for patients with reduced sensitivity to standard chemotherapy. We are very pleased that this clinical study which includes patients with reduced sensitivity to standard agents has commenced in collaboration with the ABTC."

Glioblastoma is the most common type of primary brain tumor and one of the most lethal types of cancer. MGMT promoter methylation status is an important molecular genetic biomarker in glioblastoma. Median survival of about 22 months from diagnosis has been reported for adult glioblastoma patients with a methylated MGMT promoter receiving standard-of-care chemotherapy/radiation combination treatment.1, 2 Patients with an unmethylated MGMT promoter receiving the same treatment have a worse prognosis and a reported median survival of only about 13 months.1 It is estimated that approximately 55% of newly diagnosed glioblastoma patients have an unmethylated MGMT promoter.1

The study is performed at member sites of the ABTC in the United States, coordinated by the Johns Hopkins University's School of Medicine. The ABTC is funded by the U.S. National Cancer Institute (NCI).

Update on ongoing phase 1 programs with BAL101553

Basilea is already conducting two further open-label phase 1/2a clinical studies to explore different dosing regimens of BAL101553 in patients with advanced solid tumors, one study with weekly 48-hour continuous infusion and the other with once-daily oral dosing. The oral study was amended in late 2016 to also enroll patients with recurrent or progressive glioblastoma. Phase 1 recruitment of patients in the solid tumor part of the oral study and the 48-hour continuous infusion study has been completed and the Maximum Tolerated Doses (MTDs) have been established. Dose-limiting adverse events observed in both studies included reversible hallucinations and reversible hyponatremia (low sodium levels). Basilea plans to present the phase 1 results at upcoming scientific conferences. Basilea expects to complete phase 1 patient recruitment into the separate glioblastoma arm of the oral study in the first half of 2018 and is finalizing its strategy for exploring specific patient populations in an expansion of the 48-hour continuous infusion phase 1/2a study.

About BAL101553

Basilea's oncology drug candidate BAL101553 (the prodrug of BAL27862)3 is being developed as a potential therapy for diverse cancers. The drug candidate is currently in phase 1/2a clinical evaluation. Two studies are conducted in patients with advanced solid tumors where BAL101553 is given orally or as a 48-hour continuous infusion. The oral study includes a separate glioblastoma (brain cancer) arm. An additional study is evaluating oral BAL101553 in combination with standard radiation in patients with newly-diagnosed glioblastoma. In preclinical studies, the drug candidate demonstrated in-vitro and in-vivo activity against diverse treatment-resistant cancer models, including tumors refractory to conventional approved therapeutics and radiotherapy.4, 5, 6 BAL101553 efficiently distributes to the brain, with anticancer activity in glioblastoma models.7, 8, 9 The active moiety BAL27862 binds the colchicine site of tubulin with distinct effects on microtubule organization,10 resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.11

About Basilea

Basilea Pharmaceutica Ltd. is a commercial stage biopharmaceutical company developing products that address the medical challenge of increasing resistance and non-response to current treatment options in the therapeutic areas of bacterial infections, fungal infections and cancer. 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 concerning Basilea Pharmaceutica Ltd. and its business. 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 M. E. Hegi et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine 2005 (352) 997-1003

2 R. Stupp et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 2005 (352), 987-996

3 J. Pohlmann 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)

4 A. Broggini-Tenzer et al. The novel microtubule-destabilizing drug BAL101553 (prodrug of BAL27862) sensitizes a treatment refractory tumor model to ionizing radiation. EORTC-NCI-AACR symposium 2014, abstract 202

5 G. E. Duran 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

6 F. Bachmann 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

7 R. Bergès 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

8 A. Schmitt-Hoffmann 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)

9 A. C. Mladek 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

10 A. E. Prota 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

11 F. Bachmann et al. BAL101553 (prodrug of BAL27862): the spindle assembly checkpoint is required for anticancer activity. American Association for Cancer Research (AACR) annual meeting 2015, abstract 3789