lisavanbulin (BAL101553) / Basilea - LARVOL DELTA

A phase 1/2a dose-finding study and biomarker assessment of oral lisavanbulin in patients with high-grade glioma or glioblastoma. (PubMed, Cell Rep Med) - P1/2 | "We present here the clinical and translational results from this trial, including a description of a response-predictive molecular signature that warrants further exploration in these tumor types of significant unmet need. The study is registered at ClinicalTrials.gov (NCT02490800)."

Biomarker • Journal • P1/2 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor

Lisavanbulin (BAL101553), a novel microtubule inhibitor, plus radiation in patients with newly diagnosed, MGMT promoter unmethylated glioblastoma. (PubMed, Neurooncol Adv) - "This multicenter phase 1 study sought to determine the MTD of oral Lisavanbulin in combination with standard RT (60 Gy/30 fractions) but without temozolomide in patients with newly diagnosed MGMT promoter unmethylated GBM (uGBM). Avanbulin exposures increased in a relatively dose-proportional manner with increasing oral dose of Lisavanbulin from 4 to 15 mg. Lisavanbulin in combination with RT was considered safe up to the highest predefined oral dose level of 15 mg daily."

Journal • Alzheimer's Disease • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • MGMT

Basilea partners oncology drug candidate lisavanbulin with Glioblastoma Foundation (GlobeNewswire) - "Basilea Pharmaceutica Ltd...announced today that it has entered into an asset purchase agreement with the Glioblastoma Foundation Inc., for Basilea’s oncology drug candidate lisavanbulin (BAL101553), which has been developed as a potential therapy for glioblastoma, the most common type of primary brain cancer...Under the terms of the agreement, Basilea sells and transfers all rights to lisavanbulin to the Glioblastoma Foundation for an undisclosed initial purchase price. In addition, Basilea will participate in future proceeds from any potential commercial partnerships at a fixed double-digit percentage. The Glioblastoma Foundation will continue the post-trial access program for patients from previous clinical studies to continue to receive lisavanbulin."

Licensing / partnership • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Effect of potassium fertilization on storage root number, yield, and appearance quality of sweet potato (Ipomoea batatas L.). (PubMed, Front Plant Sci) - "This promotes an increase in the number of storage roots and ultimately enhances both yield and appearance quality of sweet potato. The effect of potassium fertilizer on lignin metabolism in BJ553 roots was earlier and resulted in a greater increase in the SR number compared to YS25."

Journal

The microtubule-targeted agent lisavanbulin (BAL101553) shows anti-tumor activity in lymphoma models. (PubMed, Am J Cancer Res) - "Due to its unique binding to the colchicine site of tubulin, differently from other MTAs, avanbulin has previously shown activity in solid tumor cell lines. Half of the cell lines tested showed an induction of apoptosis already in the first 24 h of treatment, the other half in the first 48 h. EB1 showed expression in DLBCL clinical specimens, opening the possibility for a cohort of patients that could potentially benefit from treatment with lisavanbulin. These data show the basis for further preclinical and clinical evaluation of lisavanbulin in the lymphoma field."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Lisavanbulin (BAL101553), a novel, oral microtubule destabilizer plus radiation in patients with newly diagnosed, MGMT promoter unmethylated glioblastoma: A phase 1 Adult Brain Tumor Consortium study (ABTC1601). (ASCO 2023) - P1 | "It has promising antitumoral activity in orthotopic glioblastoma (GBM) models in combination with radiation (RT) ± temozolomide (TMZ), including in MGMT promoter unmethylated (uMGMT) tumors. The maximum studied safe dose for Lisavanbulin in combination with RT in newly diagnosed uMGMT GBM was determined at 15 mg daily during radiation. Overall, the safety of this combination was acceptable. Next steps in developing Lisavanbulin in newly diagnosed GBM include safety studies in combination with TMZ and of TMZ+RT in MGMT promoter methylated GBM prior to formally studying efficacy in a prospective randomized trial."

Clinical • P1 data • Alzheimer's Disease • Brain Cancer • Cardiovascular • CNS Disorders • CNS Tumor • Cognitive Disorders • Epilepsy • Glioblastoma • Heart Failure • Hypertension • Oncology • Solid Tumor • IDH1 • MGMT

Lisavanbulin in patients with recurrent glioblastoma: Phase 2a results and a consolidated analysis of response-predictive biomarkers. (ASCO 2023) - P1/2 | "This Phase 2a study supports previous study results that lisavanbulin is associated with durable responses and clinical benefit in a subset of patients with GBM. RNA-seq analyses of GBM samples suggest further evaluation of the lisavanbulin predictive response signature. 1Lopez et al, JCO 2019;37,15 suppl, 2025."

Biomarker • Clinical • P2a data • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • Microtubule Associated Protein RP/EB Family Member 1

Evaluation of response-predictive biomarkers for lisavanbulin: A phase II study in patients with recurrent glioblastoma (ESMO-TAT 2023) - P1/2 | "Conclusions This phase 2a study supports previous study results that lisavanbulin is associated with durable responses and clinical benefit in a subset of patients with GBM. RNA-seq analyses of GBM samples suggest further evaluation of the lisavanbulin predictive response signature."

Biomarker • Clinical • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • Microtubule Associated Protein RP/EB Family Member 1

[VIRTUAL] Expression of end-binding protein 1 (EB1), a potential response-predictive biomarker for lisavanbulin, in glioblastoma and various other solid tumor types. (ASCO 2021) - P1/2 | "Strong EB1-positivity is infrequent but occurs in a variety of tumor types, with the strongest signals in medulloblastoma, neuroblastoma and GBM . A phase 2 study is ongoing to assess prospectively whether EB1 is a response-predictive biomarker for lisavanbulin in GBM."

Biomarker • Brain Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Lung Cancer • Medulloblastoma • Melanoma • Neuroblastoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study. (PubMed, Invest New Drugs) - P1/2 | "No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360."

Journal • P2a data • Brain Cancer • CNS Tumor • Glioblastoma • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

[PREPRINT] Assessment of lisavanbulin (BAL101553) as an anti-lymphoma agent (bioRxiv) - “Avanbulin showed a potent in vitro anti-lymphoma activity, which was mainly cytotoxic with potent and rapid apoptosis induction. Median IC50 was around 10nM in both activated B cell like (ABC) and germinal center B cell like (GCB) DLBCL. Half of the cell lines tested showed an induction of apoptosis already in the first 24h of treatment, the other half in the first 48h. EB1 showed expression in DLBCL clinical specimens, opening the possibility for a cohort of patients that could potentially benefit from treatment with lisavanbulin. These data show the basis for further preclinical and clinical evaluation of lisavanbulin in the lymphoma field.”

Preclinical • Preprint • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma (clinicaltrials.gov) - P1/2 | N=71 | Completed | Sponsor: Basilea Pharmaceutica | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

A phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of BAL101553, a novel tumor checkpoint controller (TCC), administered as 48-hour infusion in adult patients with advanced solid tumors. (ASCO 2017) - P1/2; "PK profiles are assessed during the first 2 cycles. Two dose cohorts (30 and 45 mg/m2) have completed without DLTs or signs of vascular toxicity."

P1 data • Biosimilar • Oncology

A phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of daily oral BAL101553, a novel tumor checkpoint controller (TCC) in adult patients with progressive or recurrent glioblastoma (GBM) or high-grade glioma. (ASCO 2017) - P1/2; "PD assessments include circulating tumor cells. PK profiles are assessed throughout the first two treatment cycles."

P1 data • Biosimilar • Oncology

Phase 1/2a trial of daily oral BAL101553, a novel tumor checkpoint controller (TCC), in advanced solid tumors. (ASCO 2017) - P1/2; "Daily oral BAL101553 enables higher weekly exposures of BAL27862 with lower Cmax levels compared with a 2-h weekly infusion, due to the absence of Cmax related vascular toxicity. Doses up to 16 mg QD are well tolerated. The MAD has been identified as 30 mg QD; definition of the MTD is ongoing."

Clinical • P1/2 data • Biliary Cancer • Biosimilar • Cardiovascular • Neuroendocrine Tumor • Pancreatic Cancer

Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1 | N=26 | Terminated | Sponsor: Basilea Pharmaceutica | Active, not recruiting ➔ Terminated; Due to the National Cancer Institute's (NCI)-mandated termination of the Adult Brain Tumor Consortium which was conducting the study

Combination therapy • Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma (clinicaltrials.gov) - P1/2 | N=71 | Active, not recruiting | Sponsor: Basilea Pharmaceutica | Recruiting ➔ Active, not recruiting | N=104 ➔ 71 | Trial completion date: Jun 2022 ➔ Sep 2022 | Trial primary completion date: Jun 2022 ➔ Sep 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Basilea reports progress on the implementation of its strategy to focus on anti-infectives (GlobeNewswire) - "Partnering discussions for the TTK/PLK1-inhibitor (BAL0891) and preclinical oncology assets are well advanced and expected to be concluded in H2 2022. In line with its strategic priorities and based on data from the ongoing open-label studies, Basilea has decided not to expand the studies for the tumor checkpoint controller lisavanbulin. Ongoing patients will be offered continued access to lisavanbulin, whilst partnering opportunities continue to be explored. With regard to the FGFR inhibitor derazantinib, the company has decided to terminate the license agreement and return the rights to Merck & Co, Inc. by the end of the year."

Licensing / partnership • Oncology

Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Basilea Pharmaceutica | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Avanbulin, the active moiety of the tumor checkpoint controller lisavanbulin (BAL101553), has anti-lymphoma activity (AACR 2022) - "MTAs are active agents for lymphoma patients, as exemplified by the inclusion of vincristine in the R-CHOP regimen, standard treatment for diffuse large B cell lymphoma (DLBCL). Our data demonstrate the high cytotoxic anti-lymphoma activity of avanbulin, suggesting a potential activity of its prodrug lisavanbulin in lymphoma patients."

IO biomarker • Brain Cancer • Diffuse Large B Cell Lymphoma • Glioblastoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BCL2 • MYC • MYD88 • TP53

Basilea reports preclinical data on oncology drug candidates BAL0891, derazantinib and lisavanbulin at AACR Annual Meeting (GlobeNewswire) - "...preclinical data were presented on avanbulin, the active moiety of Basilea’s tumor checkpoint controller lisavanbulin. In-vitro, avanbulin treatment was associated with high anti-tumor activity in models of diffuse large B cell lymphoma (DLBCL), supporting a potential application of lisavanbulin for the treatment of lymphoma patients."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Avanbulin, the active moiety of the tumor checkpoint controller lisavanbulin (BAL101553), has anti-lymphoma activity: one of our posters at the next #AACR22: ⁦@IOR_Bellinzona⁩ ⁦@USI_en⁩ ⁦@EnteOspedaliero⁩ ⁦⁦@CascioneLuciano⁩ https://t.co/6hIDPVVXij" (@frbertoni)

Hematological Malignancies • Lymphoma • Oncology

Basilea to become a leading anti-infectives company backed by strong financial results 2021 (GlobeNewswire) - "FGFR inhibitor derazantinib: Clinical proof-of-concept provided for FGFR2 fusion-positive bile duct cancer (iCCA)...FIDES-01 continues to enroll and topline results for cohort 2 are expected mid-2022. Ongoing biomarker-driven phase 2 study with lisavanbulin:...A phase 2 study, enrolling patients with recurrent glioblastoma, which have tested positive for the potential response-predictive biomarker, EB1 (end-binding protein 1), is expected to report interim results in the first half of 2022...BAL0891 added to oncology clinical pipeline...Preparations are ongoing to enable the start of a phase 1 study in patients with advanced solid tumors mid-2022."

Enrollment status • New P1 trial • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • CNS Tumor • Gastrointestinal Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Basilea Pharmaceutica; Trial primary completion date: Jun 2021 ➔ Apr 2022

Clinical • Combination therapy • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT • MRI • PCR

Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma (clinicaltrials.gov) - P1/2; N=104; Recruiting; Sponsor: Basilea Pharmaceutica; Trial completion date: Dec 2021 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • MRI