June 12, 2017
Basilea announces clinical study agreement with Adult Brain Tumor Consortium to explore BAL101553 in newly diagnosed glioblastoma
- The Adult Brain Tumor Consortium (ABTC) is designed to develop more effective treatments for malignant brain tumors. It is funded by the US National Cancer Institute (NCI).
- The ABTC will conduct a clinical phase 1 study to determine the safety and tolerability of Basilea's novel tumor checkpoint controller BAL101553 in newly diagnosed glioblastoma patients.
Basel, Switzerland, June 12, 2017 - Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that it has entered into a clinical study agreement with the Adult Brain Tumor Consortium (ABTC). The consortium will conduct a clinical phase 1 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 who have a reduced sensitivity to standard chemotherapy due to an unmethylated MGMT promoter. MGMT promoter methylation status is an important molecular genetic biomarker in glioblastoma.
Prof. Achim Kaufhold, Chief Medical Officer of Basilea, said: "There is a critical medical need for new agents in the treatment of patients with glioblastoma with an unmethylated MGMT promoter. Today these patients have fewer therapeutic options than those with a methylated MGMT promoter and a worse disease prognosis. We are very pleased to be working with the ABTC to potentially provide an urgently needed new treatment modality for fighting brain cancer in this patient group."
The ABTC is designed to develop more effective treatments for malignant brain tumors. It has 11 brain tumor centers at leading universities across the United States. It is funded by the US National Cancer Institute (NCI).
Glioblastoma is the most common primary brain tumor and one of the most lethal types of cancer. The incidence of glioblastoma is approximately 3 patients per 100,000 in the United States.1 Median survival of about 15 months from diagnosis has been reported for adult glioblastoma patients receiving standard-of-care treatment,2 with a 5-year survival rate of 5%.1 It is estimated that approximately 55% of newly diagnosed glioblastoma patients have an unmethylated MGMT promoter, and these patients have a worse prognosis than those with a methylated MGMT promoter.3
The dose escalation phase 1 study will be conducted at ABTC member sites in the United States, coordinated by the Johns Hopkins University's School of Medicine. The majority of the study costs will be borne by the ABTC. The study is anticipated to start in the third quarter of 2017.
Basilea's small molecule oncology drug candidate BAL101553 (the prodrug of BAL27862)4 is being developed as a potential therapy for diverse cancers. BAL101553 is currently undergoing clinical phase 1/2a evaluation in patients with advanced solid tumors or glioblastoma (brain cancer). 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.5, 6, 7 BAL101553 efficiently distributes to the brain, with anticancer activity in glioblastoma models.8, 9, 10 The active moiety BAL27862 binds the colchicine site of tubulin with distinct effects on microtubule organization,11 resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.12
Basilea Pharmaceutica Ltd. is a 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 uses the integrated research, development and commercial operations of its subsidiary Basilea Pharmaceutica International Ltd. to discover, develop and commercialize 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.
The Adult Brain Tumor Consortium (ABTC) is a multi-institutional consortium, consisting of investigators at renowned institutions across the United States. It is funded by the US National Cancer Institute (NCI). The consortium performs innovative, multidisciplinary phase 1 - 2 clinical trials that focus predominantly on adult patients with grade IV gliomas (glioblastoma multiforme). The ABTC has demonstrated that clinical trials are not only possible in this challenging tumor type, but represent the best hope for making further progress against this devastating disease. For more information visit www.abtconsortium.org.
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 Q. T. Ostrom et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro-Oncology 2014 (16, Suppl 4), iv1-iv63
2 R. Stupp et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 2005 (352), 987-996
3 M. E. Hegi et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine 2005 (352) 997-1003
4 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
5 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)
6 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
7 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)
8 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
9 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
10 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
11 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
12 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