BAL0891 / Basilea, Crossfire Oncology, SillaJen - LARVOL DELTA

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

PHASE 1 STUDY OF MITOTIC CHECKPOINT INHIBITOR BAL0891 AS MONOTHERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2025) - "In preclinical studies, BAL0891 showed significant anti-leukemic activity and confirmed tolerability with no significant weight loss both as monotherapy and in combination with BCL-2 inhibitor venetoclax in the MOLM14-Luc-Thy1.1 AML xenograft model. The present trial will evaluate the safety and tolerability of the mitotic checkpoint inhibitor BAL0891 in patients with relapsed or refractory AML."

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

Shillajen's 'BAL0891', Targeting Blood Cancer… First Global Stage Release at EHA [Google translation] (HIT News) - "At this conference, Shillajen will present two cases: BAL0891's acute myeloid leukemia (AML) clinical trial overview (Trial in Progress) and AML preclinical results...The first adoption study is a phase 1 trial design for AML of BAL0891, which recently received clinical trial approval from the US Food and Drug Administration (FDA). This trial aims to evaluate the safety and tolerability of BAL0891 in patients with relapsed or refractory AML, and to derive the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)....The second is a preclinical result conducted by the research team of Professor Cho Byeong-sik at Seoul St. Mary’s Hospital of Catholic University of Korea, in which anticancer activity and survival extension effects were observed in AML cell lines and animal models through BAL0891 monotherapy and combination therapy with venetoclax."

Preclinical • Trial status • Acute Myelogenous Leukemia

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

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

SillaJen gains FDA OK to test leukemia drug, buys full rights for $2.4 mil (Korea Biomedical Review) - "SillaJen said it had acquired global rights to BAL0891 from the drug’s original developer, Crossfire Oncology, a Netherlands-based company specializing in kinase inhibitors, for 2 million Swiss francs, or about $2.4 million...The acquisition includes two patents tied to the compound’s structure and its potential use in identifying treatment-eligible patients. The company said the deal eliminates future royalty and milestone payments that would have otherwise been owed to Crossfire under a previous licensing agreement...In its announcement, the company said the expansion into blood cancer represents a broader strategy to diversify its pipeline beyond solid tumors. A company spokesperson said that BAL0891 may offer a potential new option for patients with few alternatives and that the company is positioning itself for future development in hematologic malignancies."

Commercial • Breast Cancer • Hematological Malignancies • Solid Tumor

SillaJen receives FDA approval for clinical trial changes to leukemia drug BAL0891 (Chosun Biz) - "SillaJen announced on the 21st that it has received approval from the U.S. Food and Drug Administration (FDA) for a change in its clinical trial plan to expand clinical trials of the anticancer drug BAL0891 for patients with acute myeloid leukemia. Acute myeloid leukemia is a type of blood cancer that has a high possibility of recurrence."

FDA approval • Acute Myelogenous Leukemia

SillaJen expands BAL0891 clinical program to AML with MD Anderson, Yale Cancer Center (Korea Biomedical Review) - "SillaJen...said it will expand its phase 1 clinical trial of its investigational cancer drug BAL0891 in acute myeloid leukemia (AML) with five U.S. institutions, including MD Anderson Cancer Center, Yale Cancer Center, and Montefiore Medical Cancer Center, and one Korean hospital - St. Mary’s Seoul Hospital. With the six additional hospitals, the total number of U.S. and Korean hospitals participating in the phase 1 clinical trial for BAL0891 in AML has risen to 13....The phase 1 trial will focus on evaluating the safety of BAL0891 monotherapy in patients with relapsed or refractory AML....SillaJen aims to initiate the AML clinical trial within the year. The company also plans to present some of its preclinical AML data at an international scientific conference in the first half of this year."

Preclinical • Trial status • Acute Myelogenous Leukemia

Sillajen partners with BeiGene for solid tumor combo therapy (Korea Biomedical Review) - "Sillajen said on Tuesday it signed a clinical drug supply agreement with BeiGene, a global biopharmaceutical company. Under this accord, BeiGene will provide Tevimbra (ingredient: tislelizumab), its PD-1 inhibitor, for use in combination clinical trials with BAL0891, Sillajen’s investigational drug currently under development for solid tumors in the U.S. and Korea....Sillajen is conducting a phase 1 trial to evaluate its safety and maximum tolerated dose in patients with solid tumors. The company is also planning additional studies for patients with acute myeloid leukemia (AML)."

Licensing / partnership • Solid Tumor

Shillazen, Anticancer Candidate 'BAL0891' FDA Phase 1 Clinical Trial IND Change Approval [Google translation] (eDaily) - "Shinlazen....announced on the 15th that the US Food and Drug Administration (FDA) approved a change to the Phase 1 clinical trial plan (IND) for BAL0891 as a monotherapy and combination therapy with chemotherapy for patients with advanced solid cancer."

IND • Solid Tumor

Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination. (PubMed, Front Oncol) - "Here we present the in vitro and in vivo characterization of a first in class, dual TTK/PLK1 inhibitor (BAL0891)...Anticancer activity was assessed in vitro using cell growth assays and efficacy was evaluated, alone and in combination with paclitaxel and carboplatin, using mouse models of triple negative breast cancer (TNBC)...Dual TTK/PLK1 inhibition represents a novel approach for the treatment of human cancer, including TNBC patients, with a potential for potent anticancer activity and a favorable therapeutic index. Moreover, combination approaches may provide an avenue to expand responsive patient populations."

Journal • Monotherapy • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

‘Pexa-Vec’ SillaJen, return of bio representative player?... Successful bequest of 100 billion won [Google translation] (Investing.com) - "Shinlazen, which narrowly escaped the crisis after going to the brink of delisting, is showing signs of recovery. It has also succeeded in securing R&D funds by raising paid-in capital of 100 billion won....Sillazen plans to invest nearly 90 billion won of the funds secured this time into R&D for PEXA-VEC, BAL0891, SJ-600 series. The remaining funds are expected to flow into the U.S. subsidiary Sillazen Bio. The plan is to get back on track by focusing resources on anti-cancer R&D, including kidney cancer and solid cancer."

Financing • Kidney Cancer • Oncology • Solid Tumor

SillaJen meets with partner Regeneron at Bio USA [Google translation] (HIT News) - "SillaJen...announced on the 11th that it discussed various cooperation plans with global pharmaceutical companies from each country at the 'Bio International Convention 2024 (hereinafter referred to as Bio USA)' held in San Diego, USA from the 3rd to the 6th...According to the company, this year's event schedule included various discussions on each pipeline (new drug candidate) that was more advanced than before. In the case of Pexa-Vec, which completed phase 2a kidney cancer treatment, a business meeting was held with partner Regeneron. Senior officials from both companies attended and discussed licensing out (L/O) and development expansion....Sillajen announced that in addition to Pexa-Vec, it also held meetings about BAL0891 and SJ-600 series, which Sillajen is developing." "

Clinical • Licensing / partnership • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

BAL0891 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=216 | Recruiting | Sponsor: SillaJen, Inc. | N=120 ➔ 216

Combination therapy • Enrollment change • Metastases • Monotherapy • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer