CBL0137 / Incuron, Statera BioPharma, Children's Oncology Group - LARVOL DELTA

Chromatin remodeling with combined FACT and BET inhibition disrupts oncogenic transcription in Diffuse Midline Glioma (SNO 2025) - "In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures...Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting using Xenium spatial profiling with a 5000 gene panel. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor."

Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • BRD4 • MDM4 • PDGFRA • SOX2

Chromatin remodeling with combined FACT and BET inhibition disrupts oncogenic transcription in Diffuse Midline Glioma (WFNOS 2025) - "In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures...Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting using Xenium spatial profiling with a 5000 gene panel. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor."

Brain Cancer • Diffuse Midline Glioma • Solid Tumor • BRD4 • MDM4 • PDGFRA • SOX2

Novel therapeutic development for aggressive variant prostate cancer (PCF 2025) - "Currently, in vivo cisplatin optimization and CBL0137–cisplatin combination therapy preclinical studies are being conducted. Funding Acknowledgement This research was supported by the U.S. Department of Defense CDMRP Prostate Cancer Research Program Idea Development Award (Number W81XWH-22-1-0571) and a PA Research Foundation Translational Research Innovation Award. Conflicts of Interest Disclosure Statement None to declare"

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

CBL0137 as a promising therapeutic strategy for anaplastic, treatment-emergent neuroendocrine prostate cancer (AACR-NCI-EORTC 2025) - "Therefore, this study aims to assess the effect of CBL0137 as a novel targeted treatment for tNEPC, both as a monotherapy and as a co-therapy alongside the standard platinum-based chemotherapy, cisplatin and characterise the molecular consequences of CBL0137 by multi-omic profiling. The co-treatment consistently outperformed either drug alone, highlighting its potential as a more effective strategy for aggressive NEPC. Ongoing multi-omic profiling will further unravel the molecular consequences of CBL0137 treatment and support the development of improved therapeutic approaches for patients with anaplastic and treatment-resistant prostate cancer phenotypes."

Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • CDKN1A

PEPN2111: CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=63 | Recruiting | Sponsor: Children's Oncology Group | N=95 ➔ 63

Enrollment change • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • AFP

A phase 1 study of intra-arterial CBL0137 in extremity melanomas and sarcomas. (PubMed, Surg Oncol) - "The historic restrictions of standard regional therapies may be overcome with IA CBL0137, and this treatment is potentially applicable to a wide range of cancers beyond the extremities."

Journal • P1 data • Melanoma • Oncology • Sarcoma • Solid Tumor

A phase 1 trial of the FACT inhibitor CBL0137 in pediatric patients with relapsed or refractory solid and CNS tumors: A report from the Children's Oncology Group study PEPN2111. (ASCO 2025) - P1/2 | "The RP2D and MTD of CBL0137 in children and adolescents with solid or CNS tumors is 400mg/m2 IV weekly on Days 1 and 8 of 21-day cycles. CBL0137 leads to immune activation, with cytokine elevation and the possibility of CRS, an unexpected toxicity not previously reported in adults. A Phase 2 cohort in patients with Diffuse Midline Glioma is ongoing and includes further assessment of immune activation."

Clinical • P1 data • Anemia • Anorexia • Brain Cancer • Burkitt Lymphoma • CNS Tumor • Diffuse Midline Glioma • Ependymoma • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Hypotension • Lymphoma • Neuroblastoma • Neutropenia • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Thrombocytopenia • IL10 • IL1R1

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026 | Suspended ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases. (PubMed, Cancers (Basel)) - "Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy."

Journal • Breast Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: Fox Chase Cancer Center | Trial completion date: Sep 2024 ➔ Sep 2025 | Recruiting ➔ Suspended | Trial primary completion date: Mar 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Trial suspension • Melanoma • Oncology • Solid Tumor

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=95 | Recruiting | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Recruiting | N=38 ➔ 95

Enrollment change • Enrollment open • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial primary completion date: Nov 2024 ➔ Mar 2024

Combination therapy • Metastases • Trial primary completion date • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Suspended ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: Fox Chase Cancer Center | Not yet recruiting ➔ Suspended | Trial primary completion date: Mar 2024 ➔ Nov 2024

Combination therapy • Trial primary completion date • Trial suspension • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Fox Chase Cancer Center

Combination therapy • New P1 trial • Immune Modulation • Melanoma • Oncology • Solid Tumor

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=38 | Active, not recruiting | Sponsor: Children's Oncology Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: Children's Oncology Group | Not yet recruiting ➔ Recruiting | Trial primary completion date: Feb 2026 ➔ Dec 2026

Enrollment open • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=38; Not yet recruiting; Sponsor: Children's Oncology Group; Trial primary completion date: Dec 2026 ➔ Feb 2026

Clinical • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=38; Not yet recruiting; Sponsor: Children's Oncology Group; Initiation date: Sep 2021 ➔ Dec 2021

Clinical • Trial initiation date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

[VIRTUAL] Results of a completed phase I trial of CBL0137 administered intravenously (IV) to patients (Pts) with advanced solid tumors. (ASCO 2020) - P1 | "Nausea and vomiting were successfully prevented with dexamethasone/serotonin antagonists. CBL0137 administered IV was generally well tolerated with manageable toxicities The MTD and RP2D were estimated at 540 mg/m2 due to myelosuppressive DLTs. PK were predictable. Preliminary evidence of antitumor activity supports Phase 2 testing."

Clinical • P1 data • Brain Cancer • Cardiovascular • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Gynecologic Cancers • Hematological Disorders • Hepatocellular Cancer • Liver Cancer • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia • Thrombosis • Uterine Cancer • Venous Thromboembolism

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=4; Not yet recruiting; Sponsor: Children's Oncology Group

Clinical • New P1/2 trial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

Stimulation of an anti-tumor immune response with "chromatin-damaging" therapy. (PubMed, Cancer Immunol Immunother) - "CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-γ-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. Our collective data underscores a previously unrecognized role for both innate and adaptive immunity in the anti-tumor activity of curaxins."

Journal • Oncology

Targeting histone chaperone FACT complex sensitizes medulloblastoma cells to chemo and radiation therapy (AACR 2018) - "Of importance, downregulation of APE1 levels or inhibition of FACT with CBL0137/curaxin sensitizes a panel of highly aggressive MB cell lines to cisplatin and alkylating drug temozolomide.Together, our study suggest that co-suppression of both BER and NER pathways via targeting FACT complex can greatly sensitize MB tumors to chemo and radiation therapy. A major implication of our studies is that combination of curaxin with low dose of cisplatin may have considerable therapeutic potential to improve efficacy and reduce cytotoxic side effects of cisplatin to MB patients."

Neuroendocrine Tumor

Study of IV CBL0137 in Previously Treated Hematological Subjects (clinicaltrials.gov) - P1; N=5; Terminated; Sponsor: Incuron; N=230 ➔ 5; Suspended ➔ Terminated; Business reasons

Clinical • Enrollment change • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Oncology

CBL0137 increases the targeting efficacy of Rovalpituzumab tesirine against tumour-initiating cells in small cell lung cancer. (PubMed, Br J Cancer) - "Therefore, we investigated the potential effect of combining Rova-T and CBL in SCLC to eradicate TICs more effectively. Our preclinical studies report a novel and highly translatable therapeutic strategy of dual targeting TICs using Rova-T in combination with CBL to potentially increase survival of SCLC patients."

Clinical • Journal • Lung Cancer • Movement Disorders • Oncology • Small Cell Lung Cancer • Solid Tumor