BAL0891 / Basilea, Crossfire Oncology, SillaJen - LARVOL DELTA

Population Pharmacokinetic Modeling and Exposure–Safety Analysis of Neutropenia Incidence Using Data from a BAL0891 Dose-Escalation Trial (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Clinical • PK/PD data • Oncology

Bayesian benefit-risk dose optimisation of BAL0891, a first-in-class TTK/PLK1 inhibitor, plus paclitaxel: recommended phase 2 dose selection in metastatic urothelial carcinoma (TTK-CS-101) (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Metastases • P2 data • Oncology • Solid Tumor • Urothelial Cancer

Safety and efficacy of BAL0891 as monotherapy and in combination with paclitaxel in a phase I study of advanced solid tumors (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Oncology • Solid Tumor

SillaJen’s next-generation oncology pipeline candidate BAL0891 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML). (BigGo) - "BAL0891 is a first-in-class anti-cancer drug candidate that simultaneously targets TTK and PLK1, two key proteins involved in cancer cell division, and is currently in global Phase 1 clinical trials for both solid tumors and hematologic malignancies."

Orphan drug • Acute Myelogenous Leukemia

Safety and efficacy of BAL0891 as monotherapy and in combination with paclitaxel: Results from a phase I study in advanced solid tumors. (ASCO 2026) - P1 | "BAL0891 demonstrated a tolerable safety profile and consistent systemic exposure in heavily pretreated pts. These interim data support continued clinical evaluation of BAL0891 as monotherapy and in combination with paclitaxel. Clinical trial information:NCT05768932."

Clinical • Combination therapy • First-in-human • Metastases • Monotherapy • P1 data • Febrile Neutropenia • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor

Clinical pharmacokinetics and neutropenia-related pharmacodynamics of BAL0891 in patients with solid tumors. (ASCO 2026) - P1 | "In patients with solid tumors, BAL0891 demonstrated linear and dose-proportional pharmacokinetics. Model-based simulations predict that repeated dosing will result in consistent plasma exposure, with no evidence of clinically relevant inter-occasional variability. Model-based simulations did not predict substantial accumulation with weekly administration."

Clinical • PK/PD data • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

All Screens Lead to Polo-like kinase 1: A Central Node in Cancer Therapeutics and Resistance. (PubMed, Pharmacol Res) - "Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo- and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment."

Journal • Review • Oncology • PLK1

TTK/PLK1 dual antagonist BAL0891 synergizes with pembrolizumab in a vascularized 3D tumor microenvironment model (AACR 2025) - "Qureator's vascularized TME model provided a robust platform to evaluate the synergy between BAL0891 and pembrolizumab. The study demonstrated BAL0891's ability to reshape the tumor immune landscape and enhance the efficacy of the immune checkpoint inhibitor. These findings offer valuable insights into the MOA of BAL0891 within this highly representative tumor model, supporting its further clinical development in combination with checkpoint inhibitors."

Biomarker • IO biomarker • Tumor microenvironment • Breast Cancer • Colorectal Cancer • Gastric Cancer • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • PLK1

Dual TTK/PLK1 inhibition combined with G-CSF treatment synergistically suppresses metastatic progression in triple-negative breast cancer (AACR 2026) - "However, combined BAL0891 and G-CSF treatment further potentiated BAL0891-mediated suppression of migration and invasion in these cells. Taken together, these findings suggest that dual TTK/PLK1 inhibition in combination with G-CSF may represent a valuable therapeutic strategy to suppress metastatic TNBC while potentially reducing the risk of neutropenia."

Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CSF3R • VIM

Mutation-dependent sensitivity to the dual TTK/PLK1 inhibitor BAL0891 in patient-derived gastric cancer organoids (AACR 2026) - "BAL0891 effectively disrupts mitotic checkpoint signaling through simultaneous inhibition of TTK and PLK1. The therapeutic outcome is genotype-dependent: KRAS-mutant tumors exhibit TTK-driven SAC dependency and higher sensitivity, whereas PTEN, PIK3CA, and BRAF mutants show relative resistance due to compensatory survival signaling. These findings identify SAC dysregulation as a predictive biomarker for BAL0891 responsiveness in gastric cancer."

Clinical • Gastric Cancer • Oncology • Solid Tumor • BRAF • KRAS • PIK3CA • PLK1 • PTEN • SMAD4 • TTK

The potential anti-cancer activity of dual TTK/PLK1 inhibitor, BAL0891, in bladder cancer (AACR 2024) - "Representative bladder cancer cell lines (253J, 253J-BV, J82, RT4, T24, J82, HT1197, and HT1376) were treated with the dual protein kinase inhibitors, BAL0891, in comparison with TTK inhibitor (BAY1217389) or PLK1 inhibitor (onvansertib). This is the first study to suggest the potent anti-cancer activity of BAL0891 in bladder cancer. BAL0891 effectively worked on bladder cancer by two tracks which not only induced G2/M arrest but also increased in polyploidy. Furthermore, BAL0891 in combination with CDK4/6 inhibitor promoted anti-cancer effects."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • TTK

Profiling patient response to TTK/PLK1 dual antagonist BAL0891 using 3D patient-derived organoid model in a microphysiological system (AACR 2025) - "This study highlights the value of PDO-based 3D MPS in evaluating patient-specific responses to BAL0891 and identifying predictive biomarkers. These findings establish a foundation for patient stratification and personalized treatment strategies in clinical trials combining BAL0891 with immune checkpoint inhibitors. Further analysis of gene signatures may provide insights into potential therapeutic targets and improve our understanding on the mechanism driving TTK/PLK1 inhibition and its combination with immunotherapy."

Clinical • IO biomarker • Breast Cancer • Colorectal Cancer • Gastric Cancer • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • PLK1

BAL0891 as a dual kinase inhibitor inducing anti-tumor immunity: A promising partner for immune checkpoint inhibitors (AACR 2025) - "By dual inhibition of TTK and PLK1, BAL0891 not only exerts potent anti-cancer activity but also enhances anti-tumor immunity through activation of the cGAS/STING pathway and modulation of the tumor microenvironment. These results support further investigation of BAL0891 in preclinical and clinical studies, particularly in combination immunotherapy strategies."

Checkpoint inhibition • IO biomarker • Oncology • CD4 • CXCL10 • CXCL11 • FOXP3 • IFNB1 • IL2RA • ITGAM • ITGAX

BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: SillaJen, Inc. | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Malignancies • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

SillaJen Unveils BAL0891 Combination Strategy at the US Society for Immuno-Oncology [Google translation] (HIT News) - "The company announced in its announcement that it quantitatively analyzed the immune activity of 'BAL0891' using a 3D tumor microenvironment (3D organoid) platform, and confirmed that 'BAL0891' induces immune cell infiltration into tumors, increases inflammatory cytokine secretion, and activates the cGAS–STING axis, an innate immune pathway, thereby enhancing the immune responsiveness of tumors."

Preclinical • Triple Negative Breast Cancer

The company also disclosed an outline of a Phase 1 clinical trial evaluating the combination of BAL0891 and Biwon Medicine's immune checkpoint inhibitor tislelizumab in patients with advanced solid tumors. [Google translation] (HIT News) - "This is a dose-escalation study conducted in a multicenter setting in the US and Korea with approximately 30 participants. The goal is to evaluate safety and tolerability and to derive the recommended primary dose (RP2D) and maximum tolerated dose (MTD)."

Clinical protocol • Solid Tumor

Optimizing Immunomodulation of BAL0891, a TTK/PLK1 dual Inhibitor, to Enhance Synergy with Immune Checkpoint Blockade Using a Biomimetic Tumor Microenvironment Platform and Pharmacometric Modeling (SITC 2025) - P1 | "PMx simulations indicated that optimal anti-tumor efficacy with an ICI could be achieved when the ICI was administered consistently 3-5 days after BAL0891 dosing, depending on the dose level.Conclusions By integrating advanced biomimetic and model-informed drug development technologies, our study successfully predicted optimal combination regimens for BAL0891 and an ICI.3 4 This approach effectively demonstrated the critical importance of precise dose timing and optimization to maximize immunomodulatory and direct anti-tumor effects. Our findings highlight the broad applicability of this integrative strategy for optimizing similar immunotherapy combination regimens in clinical practice.Trial Registration NCT05768932"

Biomarker • Checkpoint block • Checkpoint inhibition • Immunomodulating • IO biomarker • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IFNG • PD-L1 • PLK1

Phase 1 study of mitotic checkpoint inhibitor BAL0891 in combination with Tislelizumab (anti-PD-1 antibody) in patients with advanced solid tumors (SITC 2025) - "Background BAL0891 is a first-in-class small-molecule mitotic checkpoint inhibitor (MCI) that targets threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) to disrupt spindle assembly checkpoint (SAC) regulation and induce tumor cell death. Enrollment will begin at the end of 2025 in the United States and South Korea.TTK-CS-101 is now enrolling patients with advanced solid tumors to determine safety and maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BAL0891 monotherapy and combination with paclitaxel.Trial Registration NCT05768932Ethics Approval The study will be conducted in accordance with the Declaration of Helsinki and the International Council for Harmonization Good Clinical Practice guidelines. The study protocol will be reviewed and approved by an Institutional Review Board (IRB), and written informed consent will be obtained from all participants prior to enrollment."

Checkpoint inhibition • Clinical • Combination therapy • Metastases • P1 data • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • PLK1

SillaJen advances BAL0891–tislelizumab combo trial in US after FDA IND amendment (Chosun Biz) - "SillaJen signed a strategic partnership agreement with BiOne Medicine in Jan. Under the agreement, the company will receive tislelizumab free of charge and conduct combination trials of BAL0891 in solid tumors, including triple-negative breast cancer and gastric cancer."

IND • Gastric Cancer • Solid Tumor • Triple Negative Breast Cancer

Two studies on SillaJen’s anticancer drug candidate BAL0891 accepted by the American Society for Immunotherapy of Cancer (The Bio) - "The research aimed to optimize immune modulation by BAL0891, a dual TTK/PLK1 inhibitor, and to evaluate its synergistic potential with immune checkpoint inhibitors (ICIs). The findings clearly demonstrated synergistic antitumor effects through simulation studies of the combined therapy and identified the optimal timing for co-administration of BAL0891 and ICIs....The second study will present a Phase 1 clinical trial evaluating the combination of BAL0891 with tislelizumab (anti-PD-1), an immune checkpoint inhibitor developed by the global pharmaceutical company BeOne Medicines, in patients with advanced solid tumors."

Preclinical • Trial status • Oncology • Solid Tumor

BAL0891, a Dual TTK/PLK1 Inhibitor, Exhibits Anti-Leukemic Activity as Mono-therapy and in Combination with Targeted Agents (ICBMT 2025) - "In summary, BAL0891 demonstrates strong anti-leukemic activity through mitotic checkpoint disruption, both as a single agent and in combination with venetoclax. These findings validate the translational relevance of BAL0891, especially in mitotic stress–sensitive AML models. This combinatorial approach underscores the therapeutic benefit of co-targeting mitotic stress and BCL-2 signaling."

Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • PLK1

Phase 1 Study of Mitotic Checkpoint Inhibitor BAL0891 as Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (SOHO 2025) - "In preclinical studies, BAL0891 showed significant anti-leukemic activity and confirmed tolerability as monotherapy and in combination with the BCL-2 inhibitor venetoclax in the MOLM14-Luc-Thy1.1 acute myeloid leukemia (AML) xenograft model. This study aims to evaluate the safety and tolerability of BAL0891 in patients with R/R AML. The findings will inform subsequent clinical development and therapeutic strategies in this high-risk patient population."

Checkpoint inhibition • Clinical • IO biomarker • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PLK1 • THY1

SillaJen Approves IND for Clinical Trial of BAL0891 and Tislelizumab Combination [Google translation] (Nate) - "Through this combined clinical trial, the two companies will focus on confirming the safety and optimal dosage of the combination therapy of BAL0891 and tislelizumab, evaluating the synergistic effect, and confirming the potential of BAL0891 as an optimal combination partner for immune checkpoint inhibitors."

New trial • Oncology

SillaJen applies for clinical approval for BAL0891-immune checkpoint inhibitor combination to the US FDA [Google translation] (Pharm News) - "SillaJen...announced on the previous day that it had applied for approval for a change in IND (clinical trial plan) for the combined use of anticancer drug BAL0891 and global pharmaceutical company Biwon Medicine (formerly Beigene)'s immune checkpoint inhibitor tislelizumab...This clinical trial is based on the strategic partnership with Biwon Medicine signed in January. According to the contract, SillaJen will receive tislelizumab free of charge from Biwon Medicine and conduct a combination clinical trial with BAL0891 for solid tumor patients in both the United States and Korea."

Clinical protocol • Acute Myelogenous Leukemia • Solid Tumor

ANTI-LEUKEMIC ACTIVITY OF MITOTIC CHECKPOINT INHIBITOR BAL0891 AS MONOTHERAPY AND IN COMBINATION WITH TARGETED AGENTS (EHA 2025) - "BAL0891 demonstrates potent anti-leukemia activity by inhibiting cell growth and inducing cell death through mitotic catastrophe in AML, both in vitro and in vivo. Notably, its efficacy is enhanced when combined with venetoclax. These findings position BAL0891 as a promising candidate for AML therapy and underscore the need for further investigation into its optimal clinical application, including studies using patient-derived samples and additional combination regimens."

Checkpoint inhibition • Combination therapy • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5