BOS172722 / Boston Pharma - LARVOL DELTA

Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies (clinicaltrials.gov) - P1; N=38; Completed; Sponsor: Boston Pharmaceuticals; Active, not recruiting ➔ Completed; N=68 ➔ 38

Enrollment change • Trial completion • Breast Cancer • Hematological Malignancies • Oncology • Triple Negative Breast Cancer

Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies (clinicaltrials.gov) - P1; N=68; Active, not recruiting; Sponsor: Boston Pharmaceuticals; Trial completion date: Dec 2020 ➔ Jun 2021; Trial primary completion date: Dec 2020 ➔ Jun 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • Hematological Malignancies • Oncology • Triple Negative Breast Cancer

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers. (PubMed, Mol Cancer Ther) - "This mechanistic synergy results in significant in vivo efficacy, with robust tumor regressions observed for the combination of BOS172722 and paclitaxel versus either agent alone in long-term efficacy studies in multiple human tumor xenograft TNBC models, including a patient-derived xenograft and a systemic metastasis model. The current target indication for BOS172722 is TNBC, based on their high sensitivity to MPS1 inhibition, the well-defined clinical patient population with high unmet need, and the synergy observed with paclitaxel."

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

Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies (clinicaltrials.gov) - P1; N=68; Active, not recruiting; Sponsor: Boston Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722). (PubMed, J Med Chem) - "Met ID studies suggested that the methyl group suppressed metabolism at the distant aniline portion of the molecule, likely by blocking the preferred pharmacophore through which P450 recognized the compound. This work ultimately led to the discovery of BOS172722 as a Phase 1 clinical candidate."

Clinical • Journal • P1 data

Discovery of orally available and potent MPS1(TTK) kinase inhibitors for anti-cancer drugs (AACR 2019) - "...Some of MPS1 inhibitors (NMS-P153, BOS-172722, CFI-402257, BAY-1217389, and BAY-1161909) are in clinical trials. These compounds are treated for solid tumors with or without Paclitaxel...The compounds selectively inhibit MPS1 based on kinase profiling and decrease phosphorylation of MPS1 and Phospho-HH3 signaling, effectively. Some of compounds were selected for further preclinical studies."

Study of Paclitaxel in Combination With BOS172722 in Patients With Advanced Nonhaematologic Malignancies (clinicaltrials.gov) - P1; N=68; Recruiting; Sponsor: Boston Pharmaceuticals; Trial completion date: Oct 2019 ➔ Dec 2020; Trial primary completion date: Apr 2019 ➔ Dec 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date