BBI-355 / Boundless Bio - LARVOL DELTA

Discovery of BBI-355, a Potent, Selective, and Orally Available Checkpoint Kinase 1 Inhibitor for the Treatment of Extrachromosomal DNA Oncogene-Amplified Cancers. (PubMed, J Med Chem) - "BBI-355 demonstrates strong antitumor activity when dosed orally in mouse xenograft models, achieving regressions both as a single agent and in combination with targeted therapies. BBI-355 also displays favorable ADMET and PK properties and has been advanced to a clinical trial for patients with oncogene amplified cancers."

Journal • Oncology • CHEK1

POTENTIATE: Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), and the RNR Inhibitor BBI-825, in Subjects With Tumors With Oncogene Amplifications (clinicaltrials.gov) - P1 | N=85 | Terminated | Sponsor: Boundless Bio, Inc. | Trial completion date: Mar 2027 ➔ Mar 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

First-in-human • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Leiomyosarcoma • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

Preclinical and clinical pharmacodynamic characterization of BBI-355, a novel, orally bioavailable, and selective CHK1 inhibitor being evaluated in the first-in-human Phase 1/2 POTENTIATE clinical trial of patients with cancer harboring oncogene amplifications (AACR 2024) - P1 | "Finally, and for the first time, PD activity of a CHK1 inhibitor in humans was demonstrated by increased pCHK1-S345 expression by immunohistochemistry in skin biopsies from patients enrolled on the POTENTIATE study and treated with BBI-355. In conclusion, pCHK1-S345 is a useful PD biomarker for confirming clinical on-target activity of BBI-355 and may be useful to inform the pharmacologically active range of BBI-355 to support clinical development."

First-in-human • P1/2 data • PK/PD data • Preclinical • Oncology • Solid Tumor

Oral CHK1 inhibitor BBI-355 allows flexibility of dose and schedule with demonstration of monotherapy and combinational antitumor activity in extrachromosomal DNA (ecDNA) driven preclinical models (AACR 2024) - P1 | "Oral dosing of BBI-355 provides dose/schedule flexibility to attempt to optimize antitumor activity with a tolerable safety profile in patients with highly aggressive cancers and significant unmet need. The POTENTIATE clinical trial is open and currently enrolling."

First-in-human • Monotherapy • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Sarcoma • Solid Tumor • CHEK1 • EGFR • FGFR2

POTENTIATE clinical trial of BBI-355 and BBI-825 (The Manila Times) - "In January 2026, Boundless announced its intention to cease enrollment in the Phase 1/2 POTENTIATE trial evaluating the combination of BBI-355 and BBI-825 based on market considerations, available clinical data, and prioritization of its BBI-940 program."

Enrollment closed • Pipeline update • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • High Grade Serous Ovarian Cancer • Leiomyosarcoma • Pancreatic Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature. (PubMed, Int J Mol Sci) - "Preclinical studies demonstrate that ATR inhibition disrupts replication stress tolerance, impairs homologous recombination, and disables checkpoint control, enhancing cytotoxicity from standard therapies including gemcitabine, FOLFIRINOX, fluoropyrimidines, and radiotherapy...Early-phase clinical trials of ATR inhibitors (ART0380, AZD6738, BBI-355) alone or in combination show promising safety, tolerability, and preliminary efficacy. In this review, we summarize current literature on targeting the ATM-CHK2 and ATR-CHK1 pathways in PC, highlighting preclinical evidence, clinical developments, and strategies for biomarker-driven, precision oncology approaches."

Journal • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ARID1A • CHEK1 • CHEK2

POTENTIATE: Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), and the RNR Inhibitor BBI-825, in Subjects With Tumors With Oncogene Amplifications (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Boundless Bio | Recruiting ➔ Active, not recruiting | N=127 ➔ 85

Enrollment change • Enrollment closed • First-in-human • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Leiomyosarcoma • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

POTENTIATE clinical trial of BBI-355 and BBI-825 (GlobeNewswire) - "The combination arm of the Phase 1/2 POTENTIATE trial evaluating BBI-355 and BBI-825 in oncogene-amplified cancers is actively enrolling. The Company expects to deliver initial proof-of-concept clinical data within its existing cash runway timeline."

Enrollment status • P1 data • Cervical Squamous Cell Carcinoma • Estrogen Receptor Positive Breast Cancer • High Grade Serous Ovarian Cancer • Leiomyosarcoma • Lung Non-Small Cell Squamous Cancer • Non-melanoma Skin Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

Synergistic oral combination of selective RNR inhibitor BBI-825 with selective CHK1 inhibitor BBI-355 targets unique dependencies of oncogene amplified cancers (AACR-NCI-EORTC 2025) - P1 | "Enrollment of dose escalation cohorts for this study is ongoing. Taken together, our data suggests that highly selective inhibition of RNR and CHK1 using BBI-825 and BBI-355, respectively, may synergistically exploit a unique vulnerability of certain oncogene and resistance gene amplified cancers with the potential to address a significant area of unmet need."

Late-breaking abstract • Oncology

Boundless Bio Announces Upcoming Presentation at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire)

Clinical data • Oncology

Upcoming Milestones (The Manila Times) - "The BBI-355/BBI-825 combination arm of the POTENTIATE trial is open for enrollment."

Trial status • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • High Grade Serous Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

POTENTIATE: Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), and the RNR Inhibitor BBI-825, in Subjects With Tumors With Oncogene Amplifications (clinicaltrials.gov) - P1 | N=127 | Recruiting | Sponsor: Boundless Bio | Trial completion date: Sep 2027 ➔ Mar 2027

Trial completion date • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leiomyosarcoma • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

Boundless Bio Announces Portfolio Prioritization and Runway Extension (GlobeNewswire) - "Executive Summary: Discontinuing current monotherapy and combination arms of BBI-355 in POTENTIATE clinical trial; Plans to evaluate BBI-355 and BBI-825 as a combination therapy in the POTENTIATE clinical trial, targeting initiation in the second half of 2025."

Trial status • Solid Tumor

Boundless Bio Reports First Quarter 2025 Financial Results and Business Highlights (GlobeNewswire) - "Enrollment is ongoing in the Phase 1/2 POTENTIATE trial. Preliminary clinical proof-of-concept safety and antitumor activity data are expected in the second half of 2025."

P1/2 data • Trial status • Oncology • Solid Tumor

Boundless Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Business Highlights (GlobeNewswire) - "BBI-355: Enrollment in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a monotherapy and combination agent in patients with locally advanced or metastatic solid tumors with oncogene amplifications is ongoing; Boundless expects to report preliminary clinical proof-of-concept safety and antitumor activity data in the second half of 2025."

P1/2 data • Trial status • Solid Tumor

Clinical Studies Conducted at Florida Cancer Specialists & Research Institute Expanding Treatment Options and Improving Outcomes for Patients with Gastrointestinal and Genitourinary Cancers (PRNewswire) - "Clinical research conducted at Florida Cancer Specialists & Research Institute, LLC (FCS) is expanding treatment options and contributing to improved outcomes for patients diagnosed with gastrointestinal and genitourinary cancers. FCS research study results are featured at two global gatherings sponsored by the American Society of Clinical Oncology (ASCO)....At the ASCO 2025 Genitourinary Cancers Symposium, Cesar Augusto Perez, MD, as first author, will present results of a Phase I dose-escalation study of the next-generation nectin-4 targeting antibody–drug conjugate CRB-701 (SYS6002) in US and UK patients with urothelial cancer and other solid tumors."

Clinical data • P1 data • Preclinical • Colorectal Cancer • Gastric Cancer • Urothelial Cancer

Preclinical and phase 1/2 data of the CHK1 inhibitor BBI-355 in development for esophageal and gastric cancers (EGC) with EGFR or FGFR2 amplifications. (ASCO-GI 2025) - P1 | "The first ecDNA directed therapy, BBI-355, demonstrated significant synergistic anti-tumor activity in combination with targeted therapies in multiple ecDNA+ oncogene amplified EGC models. BBI-355 alone and in combination with erlotinib/futibatinib was well tolerated. Clinical testing in patients with EGFR and FGFR2 oncogene amplifications is ongoing with a strong rational for EGC."

P1/2 data • Preclinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • FGFR1 • FGFR2

Analytical validation of an NGS panel-based ecDNA detection device for use as a clinical trial assay for the POTENTIATE clinical study of the novel CHK1 inhibitor, BBI-355 (ESMO 2024) - P1 | "We developed and validated a novel CTA to detect ecDNA using routine clinical NGS panel data. This CTA will be used to facilitate patient enrollment in Part 3 of the precision medicine POTENTIATE study of BBI-355."

Clinical • Next-generation sequencing • Oncology

Analytical validation of an NGS panel-based ecDNA detection device for use as a clinical trial assay for the POTENTIATE clinical study of the novel CHK1 inhibitor, BBI-355 (PRNewswire) - "This poster presentation will focus on the analytical validation of a next-generation sequencing (NGS) panel-based extrachromosomal DNA (ecDNA) detection device. This innovative device has been developed as a clinical trial assay for Boundless Bio's ongoing, first-in-human POTENTIATE Phase 1/2 clinical study of its lead ecDNA-directed therapy (ecDTx), BBI-355."

P1 data • Oncology • Solid Tumor

SOPHiA GENETICS Announces Validation of Novel Clinical Trial Assay Together with Precision for Medicine at World Clinical Biomarkers & CDx 2024 (PRNewswire) - "SOPHiA GENETICS...announced an update from the Company's work with biopharma company Boundless Bio...The two companies collaborated with precision medicine clinical research organization (CRO) Precision for Medicine, which contributes its state-of-the-art, CAP-accredited, CLIA-certified laboratory services to Boundless Bio's POTENTIATE Phase 1/2 clinical trial by successfully validating a proprietary workflow to process patient samples...Precision is supporting the POTENTIATE clinical trial by adapting its diagnostic workflow to ensure a seamless connection with the SOPHiA DDM Platform. Results from testing of POTENTIATE trial participants' biopsy samples will be used to further analyze clinical activity of the investigational drug BBI-355 in specific patient populations....More information about this collaboration will be provided during the World Clinical Biomarkers & CDx event in Boston on September 5, 2024."

Diagnostic • Licensing / partnership • Trial status • Oncology • Solid Tumor

Boundless Bio Provides Business Updates Focused on Key Value Drivers and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - P1/2 | N=150 | POTENTIATE (NCT05827614) | Sponsor: Boundless Bio | "Enrollment is progressing in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a single agent and in combination with targeted therapies in patients with locally advanced or metastatic solid tumors with oncogene amplifications. To date, no new safety signals have been observed, and there has been no evidence of combinatorial toxicity in the dose escalation cohorts evaluating BBI-355 in combination with either the EGFR inhibitor erlotinib or the FGFR inhibitor futibatinib...Based on its current projections, the company now anticipates reporting initial clinical proof-of-concept data from POTENTIATE in the second half of 2025...ECHO was previously determined by the FDA to be a non-significant risk device for use as a clinical trial assay (CTA) in the BBI-355 POTENTIATE trial; ECHO has now been analytically validated and institutional review board (IRB)-approved for use as a CTA in the BBI-355..."

Diagnostic • Enrollment status • P1/2 data • Trial status • Oncology • Solid Tumor

Boundless Bio Reports First Quarter 2024 Financial Results and Corporate Highlights (Businesswire) - "Initiated dose escalation in Part 2 of the Phase 1/2 POTENTIATE trial, which evaluates BBI-355 in combination with the EGFR inhibitor erlotinib and BBI-355 in combination with the FGFR inhibitor futibatinib in patients with tumors harboring EGFR or FGFR oncogene amplifications, respectively, to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of each combination regimen....Research and development (R&D) expenses were $13.1 million for the first quarter of 2024, compared to $9.5 million for the same period in 2023. The increase in R&D expenses was primarily due to a $1.8 million increase in the direct program costs for BBI-355, BBI-825, and other development programs..."

Commercial • Trial status • Bladder Cancer • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Liposarcoma • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Boundless Bio Presents Preclinical and Clinical Pharmacodynamic Data on its Lead Extrachromosomal DNA (ecDNA)-Directed Therapy, BBI-355, at the American Association for Cancer Research Annual Meeting 2024 (Businesswire) - "Abstract Number: 613:...BBI-355 showed inhibition of CHK1 in a host of tumor cell lines and demonstrated in vivo single agent tumor growth inhibition, including complete tumor regressions, across a range of tumor models representing multiple different oncogene amplifications and tumor types. BBI-355 also demonstrated synergistic tumor growth inhibition, including durable regressions, when combined with targeted therapies across multiple oncogene amplified tumor models."

Preclinical • Oncology

Boundless Bio Presents Preclinical and Clinical Pharmacodynamic Data on its Lead Extrachromosomal DNA (ecDNA)-Directed Therapy, BBI-355, at the American Association for Cancer Research Annual Meeting 2024 (Businesswire) - "Number: 3631:...The findings showed that phosphorylated-CHK1 Ser345 (pCHK1-S345) is a useful pharmacodynamic (PD) biomarker for confirming clinical on-target activity of BBI-355 and could potentially inform the pharmacologically active range of BBI-355 in clinical development. In addition to preclinical data, increased pCHK1-S345 expression by immunohistochemistry in skin biopsies from patients treated with BBI-355 in the ongoing POTENTIATE clinical study were also observed, marking the first, real-time analysis of PD activity from a CHK1 inhibitor in humans."

Biomarker • Preclinical • Oncology

Boundless Bio Announces Multiple Upcoming Presentations at the American Association for Cancer Research Annual Meeting 2024 (Businesswire) - "Boundless Bio...announced multiple upcoming poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2024, which is being held April 5-10, 2024, in San Diego, CA."

Clinical • Preclinical • Oncology