Basilea plans progression of oncology candidate lisavanbulin to targeted, biomarker-driven phase 2 study

• Confirmed signals of efficacy with profound responses in two patients with glioblastoma across two different clinical studies
• Manageable, well-characterized safety profile
• Plan to proceed with targeted, biomarker-driven oral expansion study in mid-2020

Basel, Switzerland, December 16, 2019 – Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today that it plans to advance the clinical development of its novel tumor checkpoint controller lisavanbulin (BAL101553) by focusing on a targeted, biomarker-driven approach based on the initial results from the two recent phase 1/2 clinical studies.

The phase 1 study (NCT02490800) with daily oral lisavanbulin with recurrent glioblastoma (GBM), or high grade glioma, was completed in August 2019. Basilea has now also completed an interim data review of the ongoing open-label phase 2a expansion study using weekly 48-hour intravenous (i.v.) administration in twelve patients with recurrent GBM and nine patients with platinum-resistant ovarian cancer (NCT02895360).

Glioblastoma is the most common type of primary brain cancer and one of the most lethal types of cancer.¹

Across the two studies, profound objective responses, with more than 80% reduction of the GBM tumor area, were observed in two patients with glioblastoma, who continue to remain on treatment with lisavanbulin. In the ovarian cancer group, four patients showed reduction in target lesion size but did not meet the formal response criteria of the study protocol. The safety profile observed with daily oral or weekly 48-hour i.v. lisavanbulin was consistent with previous studies. Basilea plans to submit the data for presentation at upcoming scientific conferences.

Dr. Marc Engelhardt, Basilea’s Chief Medical Officer, said: “We have observed clinical activity of lisavanbulin in recurrent glioblastoma, with profound clinical responses seen in a subset of patients. Based on this observation, we are investigating a panel of biomarkers, including end-binding protein 1, EB1, which could be useful for identifying cancer patients that may benefit most from the treatment with lisavanbulin. This allows us to take a targeted approach for advancing the clinical development of lisavanbulin, moving from the evaluation of an unselected patient population to a biomarker-driven phase 2 study in recurrent glioblastoma and potentially additional tumor types. Additionally, we currently intend to focus on the oral formulation in the next stage of clinical development of lisavanbulin given the consistent outcome observed with both formulations.”

There will be no additional patients enrolled in the weekly 48-hour i.v. infusion study. All ongoing patients will remain on treatment as long as they continue to benefit from treatment.

EB1 was previously identified by Basilea as a potential response-predictive biomarker for lisavanbulin, based on comprehensive preclinical studies in glioblastoma models. Initial clinical evidence was then provided in August 2019, when Basilea announced the completion of patient enrolment into the phase 1 study with daily oral lisavanbulin in recurrent glioblastoma or high-grade glioma.² One glioblastoma patient in that study, whose tumor tissue was strongly positive for EB1, was reported as an exceptional long-lasting responder.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 and a reduced sensitivity to chemotherapy with the standard-of-care drug temozolomide.⁴

About lisavanbulin (BAL101553)

Basilea's oncology drug candidate lisavanbulin (BAL101553, the prodrug of BAL27862)⁵ is being developed as a potential therapy for diverse cancers.^2, 4, 6 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.^{7, 8, 9} Lisavanbulin efficiently distributes to the brain, with anticancer activity in glioblastoma models.^10, 11, 12 In preclinical studies, end-binding protein 1 (EB1) was identified as a potential response-predictive biomarker in glioblastoma models.¹² The active moiety BAL27862 binds to the colchicine site of tubulin, with distinct effects on microtubule organization,¹³ resulting in the activation of the "spindle assembly checkpoint" which promotes tumor cell death.¹⁴

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.

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 +41 61 606 1102 media_relations@basilea.com investor_relations@basilea.com

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

References

1    B. M. Alexander, T. F. Cloughesy. Adult Glioblastoma. Journal of Clinical Oncology 2017 (35), 2402-2409

2    ClinicalTrials.gov identifier: NCT02490800

3    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

4    ClinicalTrials.gov identifier: NCT03250299

5    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)

6    ClinicalTrials.gov identifier: NCT02895360

7    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

8    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)

9    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)

10  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)

11  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)

12  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

13  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

14  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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