BBI-825 / Boundless Bio - LARVOL DELTA

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

STARMAP: Study of the RNR Inhibitor BBI-825 in Subjects With Tumors With Resistance Gene Amplifications (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Boundless Bio | Active, not recruiting ➔ Completed

Trial completion • Solid Tumor

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

Oral and selective ribonucleotide reductase (RNR) inhibitor, BBI-825, suppresses acquired resistance to mutant-specific, pan, and multi-RAS targeting inhibitors (AACR 2025) - P1 | "In this preclinical study, we sought to understand whether BBI-825 broadly antagonizes acquired resistance to mutant-specific, pan, and multi-RAS inhibitors in a range of tumor models.We tested the ability of BBI-825 to prevent or delay development of acquired resistance to RAS targeting in a panel of KRASG12D/C/V driven tumor cell lines when used in combination with mutant specific KRASG12D (MRTX-1133, RMC-9805), KRASG12C (adagrasib, sotorasib), pan-KRAS (BI-2493), and multi-RAS (RMC-6236) inhibitors. Overall, we found that BBI-825 successfully antagonizes the development of acquired resistance to mutant-specific, pan, and multi-RAS inhibitors in a range of preclinical models. These findings support clinical investigation of BBI-825 in combination with mutant-specific, pan, and multi-RAS inhibitors to prevent or delay resistance and prolong duration of response."

Preclinical • Oncology • Solid Tumor • KRAS

STARMAP: Study of the RNR Inhibitor BBI-825 in Subjects with Tumors with Resistance Gene Amplifications (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Boundless Bio | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2027 ➔ Sep 2025 | Trial primary completion date: Feb 2027 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

WITHDRAWN: Phase 1/2 study data of the RNR inhibitor BBI-825 in development for the prevention and treatment of patients with colorectal cancer with BRAF V600E or KRAS G12C mutations and resistance gene amplifications. (ASCO-GI 2025) - P1 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT06299761"

Clinical • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS

Boundless Bio Provides Business Updates Focused on Key Value Drivers and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - P1/2 | N=42 | STARMAP (NCT06299761) | Sponsor: Boundless Bio | "Multiple dose levels have been completed in the single-agent, dose-escalation portion of the STARMAP clinical trial and, to date, BBI-825 has demonstrated oral bioavailability and has been generally well-tolerated. Initial clinical proof-of-concept data from the trial are expected in the second half of 2025."

P1/2 data • PK/PD data • Oncology • Solid Tumor

Boundless Bio Announces First Patient Dosed in First-in-Human Phase 1/2 Clinical Trial of BBI-825 in Cancer Patients with Resistance Gene Amplifications (Businesswire) - "Boundless Bio...today announced that the first patient has been dosed with BBI-825 in a first-in-human, Phase 1/2 clinical trial for patients with locally advanced or metastatic cancer with resistance gene amplifications (NCT06299761)....STARMAP ('Study Treating Acquired Resistance: MAPK Amplifications') is an open-label, non-randomized, three-part Phase 1/2 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamic biomarkers, preliminary antitumor activity, and identify the maximum tolerated dose and recommended Phase 2 dose (RP2D) of BBI 825 administered as a single agent or in combination with select targeted therapies..."

Trial status • Oncology • Solid Tumor

STARMAP: Study of the RNR Inhibitor BBI-825 in Subjects With Tumors With Resistance Gene Amplifications (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Boundless Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

STARMAP: Study of the RNR Inhibitor BBI-825 in Subjects With Tumors With Resistance Gene Amplifications (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Boundless Bio

Combination therapy • Metastases • New P1 trial • Oncology • Solid Tumor

Boundless Bio Presents Preclinical Data on the Discovery of its Second ecDNA-Directed Therapeutic Candidate, BBI-825, at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "Boundless Bio...will present preclinical data on its second ecDNA-directed therapy (ecDTx), BBI-825, as well as present additional research on the intrinsic genomic plasticity of cancer cells enabled by ecDNA at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....BBI-825 has demonstrated RNR inhibition in a host of tumor cell lines and tumor regressions in ecDNA-enabled preclinical cancer models and is currently being evaluated in Investigational New Drug (IND)-enabling studies....The second poster presentation extends the field’s understanding of ecDNA and its key role in enabling resistance to cancer therapy."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Boundless Bio Announces Upcoming Presentations at 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "Boundless Bio...announced two upcoming poster presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place from October 11-15, 2023, in Boston, MA."

Preclinical • Colorectal Cancer