Author: Ma, Seunghyun ; Ahmed, Salman ; Baek, Kyusuk ; Lee, Jae Jung ; Baek, Jihye ; Sathe, Aneesh ; Kang, MinKyung ; Donnelly, Delaney ; Park, Hyeon-geun ; Rajput, Bushra ; Yoo, Sanghee ; Kim, Yangji ; Shin, Yunha ; Wang, Junfeng ; Lee, Byungjun ; Liu, Tsung-Li

AbstractIntroduction:Dysregulation of cell cycle checkpoints in cancer cells drives uncontrolled proliferation and tumor progression. Threonine Tyrosine Kinase (TTK) and Polo-like Kinase 1 (PLK1) are key regulators of the spindle assembly checkpoint (SAC) during mitotic division. Their overexpression is linked to tumor aggressiveness and poor prognosis in multiple malignancies. BAL0891, a first-in-class dual TTK/PLK1 inhibitor disrupts SAC integrity, increases cytoplasmic DNA, activates the cGAS/STING pathway, induces senescence-associated secretory phenotypes (SASP), and elevates PD-L1 expression, suggesting potential for synergy with immune checkpoint inhibitors. To explore patient-specific responses and identify predictive biomarkers of sensitivity to BAL0891, we utilized 3D patient-derived organoid (PDO) models within a microphysiological system (MPS), offering physiologically relevant insights beyond traditional models.Methods:PDOs from renal cell carcinoma, triple-negative breast cancer, gastric cancer, and colorectal cancer were established in collaboration with Qureator. These PDOs were cultured in Qureator’s CurioChips, which incorporate hydrogel-based extracellular matrix (ECM) to mimic the tumor tissue. Following organoid stabilization, BAL0891 was administered and cytotoxicity was assessed through live/dead dye staining and organoid volume measurements. PD-L1 expression was analyzed via flow cytometry to evaluate the potential for combination therapy with anti-PD-L1/PD-1 inhibitors. Cytokine profiling was conducted using multiplex secretome analysis to assess changes in the co-cultures. Additionally, RNA sequencing was performed to identify gene expression signatures associated with sensitivity and resistance to BAL0891.Results:BAL0891 exhibited variable cytotoxicity across PDOs, with a subset demonstrating resistance. Responding PDOs showed SASP, confirmed by β-Galactosidase staining, increased PD-L1 expression, and distinct pro-inflammatory cytokine profiles compared to non-responders. Preliminary cytokine analyses indicates that BAL0891 reshapes the immune landscape in sensitive PDOs. Ongoing RNA sequencing analysis aims to identify gene clusters associated with sensitivity to BAL0891, offering potential biomarkers or therapeutic targets.Conclusion: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.Citation Format:Junfeng Wang, MinKyung Kang, Delaney Donnelly, Jihye Baek, Bushra Rajput, Byungjun Lee, Hyeon-geun Park, Yunha Shin, Tsung-Li Liu, Aneesh Sathe, Yangji Kim, Kyusuk Baek, Sanghee Yoo, Salman Ahmed, Jae Jung Lee, Seunghyun Ma. Profiling patient response to TTK/PLK1 dual antagonist BAL0891 using 3D patient-derived organoid model in a microphysiological system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3017.

21 Apr 2025·Cancer Research

Abstract 2164: BAL0891 as a dual kinase inhibitor inducing anti-tumor immunity: A promising partner for immune checkpoint inhibitors

Author: Ma, Seunghyun ; Yoo, Sanghee ; Kang, MinKyung

AbstractBAL0891 is a first-in-class dual inhibitor targeting threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1). These kinases collaborate to activate the mitotic spindle assembly checkpoint (SAC) at the kinetochore, ensuring proper chromosome alignment and segregation prior to mitotic exit. Dual inhibition of TTK and PLK1 by BAL0891 rapidly disrupts the SAC, leaving tumor cells insufficient time for proper chromosome segregation, thereby exerting potent anti-cancer effects. Recent studies have underscored the potential of cell cycle inhibitors, including TTK and PLK1 inhibitors, as therapeutic partners for immune checkpoint inhibitors in various cancers. Given these findings, we investigated whether BAL0891 induces anti-cancer immune responses and evaluated its potential for combination therapy with immune checkpoint inhibitors.Our results demonstrate that BAL0891 induces aberrant cell cycle progression in cancer cells, leading to elevated levels of cytosolic DNA, a well-known activator of the cGAS/STING signaling pathway. Activation of this pathway by BAL0891 promotes cellular senescence and enhances anti-tumor immunity through the secretion of pro-inflammatory cytokines and chemokines. Notably, BAL0891 treatment increases pro-inflammatory factors such as IFNβ1, CXCL10, and CXCL11. Among these, IFNβ1 plays a pivotal role in upregulating PD-L1 expression on cancer cells, potentially enhancing the efficacy of immune checkpoint inhibitors like anti-PD-1/PD-L1 agents. Furthermore, CXCL10 and CXCL11 contribute to recruiting immune cells to the tumor microenvironment, further amplifying immune responses. In an in vivo syngeneic mouse model, BAL0891 treatment increased the presence of CD4+ T cells, CD11c+ dendritic cells (DCs), and NK1.1+ NK/NKT cells, while reducing immunosuppressive populations such as regulatory T cells (CD25+ FoxP3+ CD4+) and myeloid-derived suppressor cells (Gr-1+ CD11b+) in tumors and tumor-draining lymph nodes. These results demonstrate BAL0891’s potential to reshape the tumor microenvironment in favor of anti-tumor immunity.This study highlights the potential of BAL0891 as a combination partner for immune checkpoint inhibitors in cancer therapy. 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.Citation Format:MinKyung Kang, Sanghee Yoo, Seunghyun Ma. BAL0891 as a dual kinase inhibitor inducing anti-tumor immunity: A promising partner for immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2164.

21 Apr 2025·Cancer Research

Abstract 2169: TTK/PLK1 dual antagonist BAL0891 synergizes with pembrolizumab in a vascularized 3D tumor microenvironment model

Author: Donnelly, Delaney ; Ma, Seunghyun ; Ahmed, Salman ; Lee, Jae Jung ; Baek, Kyusuk ; Liu, Tsung-Li ; Sathe, Aneesh ; Kang, MinKyung ; Park, Hyeon-geun ; Baek, Jihye ; Yoo, Sanghee ; Kim, Yangji ; Lee, Byungjun ; Rajput, Bushra ; Wang, Junfeng ; Shin, Yunha

AbstractIntroduction:BAL0891, a first-in-class dual TTK/PLK1 inhibitor, activates the cGAS/STING pathway and induces a senescence-associated secretory phenotype (SASP), resulting in increased PD-L1 expression and pro-inflammatory cytokine production in cancer cells. These changes enhance tumor susceptibility to immunotherapies. However, evaluating the synergy between BAL0891 and immune checkpoint inhibitors like pembrolizumab (PD-1 inhibitor) is challenging in traditional preclinical models, which lack human immune cells and key features of the tumor microenvironment. To address these limitations, Qureator’s advanced 3D tumor microenvironment (TME) model, incorporating perfusable vessels, human primary cells, and patient-derived organoids (PDOs) was utilized. This physiologically relevant system enabled a detailed investigation of BAL0891's mechanism of action (MOA) and its combination with pembrolizumab across multiple cancer types, aiming to guide clinical trial design and patient stratification.Methods:Vascularized TME models were developed by co-culturing endothelial cells, fibroblasts, and PDOs derived from renal cell carcinoma, triple-negative breast cancer, gastric cancer, and colorectal cancer within Qureator’s Microphysiological System (MPS). Following vasculature formation, models were primed with BAL0891 for two days and then treated with PBMCs and pembrolizumab or isotype control antibodies. Tumor growth, immune infiltration, and tumor cell killing were assessed via live cell imaging and immunofluorescence staining. Post-treatment immuno-profiling included flow cytometry to analyze macrophage polarization and T cell activation/exhaustion. Multiplex secretome analysis was performed to characterize chemokine and cytokine profiles associated with BAL0891 and the combination therapy.Results:BAL0891 priming sensitized a subset of PDOs to pembrolizumab, demonstrating synergistic anti-tumor activity in the vascularized TME model. Responsive PDOs exhibited significant organoid shrinkage, increased immune cell infiltration, enhanced T cell activation, and macrophage polarization towards an anti-tumoral phenotype. Cytokine and chemokine analysis revealed a shift to a pro-inflammatory microenvironment. Conversely, non-responders showed limited immune infiltration and minimal activation.Conclusion: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.Citation Format:Junfeng Wang, MinKyung Kang, Byungjun Lee, Delaney Donnelly, Jihye Baek, Bushra Rajput, Tsung-Li Liu, Hyeon-geun Park, Yunha Shin, Aneesh Sathe, Yangji Kim, Kyusuk Baek, Sanghee Yoo, Salman Ahmed, Jae Jung Lee, Seunghyun Ma. TTK/PLK1 dual antagonist BAL0891 synergizes with pembrolizumab in a vascularized 3D tumor microenvironment model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2169.

News (Medical) associated with Qureator Inc.

01 Jun 2022

·www.biospace.com

Qureator Closes $15 Million in Series A Funding to Deliver Improved Disease Modeling and Drug Design Solutions

San Diego, CA, May 27, 2022 Qureator, a San Diego-based biotech company, is pleased to announce the closure of a $15M Series A funding round led by HG Initiative along with other VCs. Formerly known as Curiochips, Qureator’s focus is the creation of novel platforms and high-throughput disease models for drug discovery and precision medicine. The just-closed funding will help Qureator accelerate its research activities and expand into different disease areas. Animal studies have been used extensively over the years to model the effect of medicinal compounds on the human body. However, animal models often do not translate clinically although they add significant costs to the overall drug discovery process. Designed to recapitulate the complexity of tissue microenvironments, Qureator’s Microphysiological Systems (MPS) will be used to establish disease models that closely mimic the in-vivo environment. As such, these models promise to be much more predictive clinically. Qureator’s Curiochips Microfluidic Technology will be a gamechanger as it allows for: Investigation of the underlying biology of disease Establishment of disease models based on patient-derived samples Accurate prediction of clinical responses and patient stratification Target validation in 3D co-culture conditions High-throughput screening for new drugs or combo agents with existing drugs Identification of biomarkers to help with clinical studies Solutions created by Qureator have already made a significant impact in different fields including: Oncology: 3D co-culture models to mimic the complexity of the tumor microenvironment (TME) Vascular Biology: Ex-vivo vascular systems to mimic the dynamic processes of angiogenesis and vasculogenesis Blood-Brain-Barrier: 3D co-culture models to mimic the barrier integrity of epithelial and endothelial cells Others: 3D co-culture models to mimic the pathological conditions in tissues of interest Qureator CEO Kyu Baek studied Electrical Engineering and was extensively involved in biomedical engineering research during his Ph.D. Inspired by his wealth of industry experience and knowledge, he created a startup dedicated to transforming the lives of patients by discovering new drugs through engineering and physics. Discussing the significance of the successful Series A funding round, Kyu stated: “Qureator now has the financial means to forge ahead in using our cutting-edge MPS platform to establish predictive disease models that will enable the discovery of potent and efficacious new drugs. We aspire to help patients with currently unmet medical needs with drugs discovered with these innovative MPS-based models and assays.” To find out more, please visit or follow us on LinkedIn. About Qureator: Qureator Inc., a biotech company, focuses on developing high-throughput platforms for novel disease models in areas of high unmet medical needs. The company utilizes its unique Microphysiological Systems (MPS) known as Curiochips that enable our investigators to perform co-cultures with multiple cell types in 3D making possible high-throughput screenings for biomedical research and drug discovery. About HG Initiative: HGI is an impact business company that seeks to solve the problems facing humanity with sustainable and innovative business ideas. The company executes impact investments based on the four core values of 'data-centric, optimization, future preparedness, and inclusiveness'. Contact: Kyu Baek Chief Executive Officer kyu.baek@qureator.com

100 Deals associated with Qureator Inc.

100 Translational Medicine associated with Qureator Inc.

Corporation Tree

Boost your research with our corporation tree data.

view full example data

Pipeline

Pipeline Snapshot as of 16 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

Current Projects

Drug(Targets)	Indications	Global Highest Phase

BAL0891 ( PLK1 x TTK )	Triple Negative Breast Cancer More	Preclinical

Deal

Boost your decision using our deal data.

view full example data

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Profit

Explore the financial positions of over 360K organizations with Synapse.

view full example data

Grant & Funding(NIH)

Access more than 2 million grant and funding information to elevate your research journey.

view full example data

Investment

Gain insights on the latest company investments from start-ups to established corporations.

view full example data

Financing

Unearth financing trends to validate and advance investment opportunities.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis