MBQ-167 / MBQ Pharma - LARVOL DELTA

First-in-class Rac/Cdc42 inhibitor MBQ-167 in patients with metastatic breast cancer (MBC): safety and preliminary efficacy (ESMO 2026) - No abstract available

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor

MBQ-ABC001: A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: MBQ Pharma | Trial completion date: Oct 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Dec 2026

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Oncology • Solid Tumor

Rac/Cdc42 inhibitors target pancreatic cancer cells and macrophages in the tumor microenvironment. (PubMed, Cancer Treat Res Commun) - "In Transwell co-culture, MBQ-167 and MBQ 168 decreased pancreatic cancer cell migration and reduced inflammatory mediators such as Interleukin-6 (IL-6), Chinase-3-like protein 1 (CHI3L1) and S100A8/A9 (calprotectin). Therefore, MBQ-167 and MBQ-168 are potential PDAC therapeutics by targeting both pancreatic cancer cells and macrophages in the TME."

Biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CHI3L1 • IL6 • S100A8

Novel Ect2-Rac inhibitor CPV-337 in breast and pancreatic cancer (AACR 2026) - "We developed the clinical-stage compound MBQ-167, a Rac and Cdc42 inhibitor, as a metastasis inhibitor...Ongoing studies are evaluating the inhibitory mechanism of CPV-337 and its specificity using CRISPR-Cas9 Rac-1 knockout breast cancer cells. In conclusion, CPV-337 is a promising anti breast and pancreatic cancer drug with a unique and specific mechanism of inhibition."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ECT2 • HER-2 • RAC1

Potential of Rac and Cdc42 inhibitors as pancreatic cancer therapeutics (AACR 2026) - "MBQ-167 treatment decreased tumor growth and increased survival compared to vehicle treatments. In conclusion, MBQ-167 and MBQ-168 pose as potential therapeutics for PDAC due to their ability to target both pancreatic and macrophage-like cells."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CHI3L1 • IL6 • KRAS • S100A8 • S100A9

Mechanisms by which the Rac & Cdc42 inhibitor MBQ-167 overcomes the adverse effects of paclitaxel in TNBC (AACR 2024) - "MBQ-167, but not PXL, reduced LPS-induced (i.e., TLR4-regulated) NfkB translocation to the nucleus, with a similar effect as the combination. Therefore, MBQ-167 may prevent PXL-induced metastasis by partially inhibiting the NF-kB pathway in TNBC tumors and reducing inflammation and immunosuppression from M1 and M2 macrophages in vivo."

Adverse events • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MRC1

Pharmacodynamic biomarkers for Rac and Cdc42 inhibitor efficacy (AACR 2024) - "These results demonstrate the potential of p-PAK and YKL-40/CHI3L1 from blood as biomarkers for Rac/Cdc42 inhibitor efficacy. This study impacts pharmacodynamic biomarker design for the planned Phase 2 clinical trials for MBQ-167 in breast and pancreatic cancer."

Biomarker • Clinical • PK/PD data • Breast Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CHI3L1 • IL6

Screening of Rac1 and Cdc42 inhibitors as anti-metastatic compounds (AACR 2024) - "Therefore, CPV-337 may have cytotoxic effects on breast cancer. We are continuing to screen the library of MBQ-167 derivatives in breast, pancreatic, lung, and prostate cancer cell lines."

Metastases • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • RAC1

Characterization of the Rac inhibitor CPV-337 in metastatic breast cancer (AACR 2025) - P1 | "Our lead compound MBQ-167, a dual Rac/Cdc42 inhibitor (IC50 of ~100nM; GI50 of 130nM), is currently in Phase I clinical trials for advanced triple-negative breast cancer (NCT06075810)...Interestingly, a significant increase in M1 anti-tumorigenic macrophages was observed in splenocytes of mice treated with CPV-337, implicating CPV-337 in the anticancer immune response. Further evaluation of CPV-337's inhibitory mechanism, toxicity, bioavailability, and Rac/Cdc42 regulated processes in the tumor microenvironment are warranted to translate this promising anticancer compound to the clinic."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • HER-2

Characterization of the RAC1/CDC42 inhibitor MBQ-167 to assess its utility as a tool for interrogating Rho GTPase biology (AACR 2025) - "Simulations helped understanding that MBQ-167 is not a specific inhibitor and therefore not adequate as a tool for interrogating the biology of interest. Further studies are needed to find additional inhibitors against RAC/CDC42 and to understand the effects of MBQ-167 on cancer cells and as a clinical asset tested in Phase I clinical trials as a single agent against advanced breast cancer."

Breast Cancer • Oncology • Solid Tumor • AURKA • CDK1 • MAPK14 • PLK1 • PLK2 • RAC1

M6 metabolite contributes to the efficacy of the Rac/Cdc42 inhibitor MBQ-167 in metastatic breast cancer. (PubMed, Mol Cancer Ther) - "In vivo studies with immunocompromised mice bearing HER2-BM tumors demonstrated that M6 inhibits tumor growth and metastasis to the lungs, livers, and kidneys by ~90%, comparable to MBQ-167. These findings suggest that M6 exhibits potent anticancer properties both in vitro and in vivo, potentially contributing to the sustained efficacy of MBQ-167 in metastatic breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • RAC1

Pharmacokinetic Evaluation of MBQ-167 a Dual Rac/Cdc42 Inhibitor in Advanced Breast Cancer Patients (SABCS 2025) - P1 | "The observed pharmacokinetics support continued clinical development and provided essential dosing guidance for Phase 2 trials. Further analyses with additional cohorts will be presented up to 400 mg BID."

Clinical • Metastases • PK/PD data • Breast Cancer • Oncology • Solid Tumor • CDC42

Rac/cdc42 inhibitor mbq-167 modulates the breast tumor immune microenvironment (SABCS 2025) - "In conclusion, the Rac/Cdc42 inhibitor MBQ-167 targets metastatic BC cells and immunosuppressive inflammatory cells in the BC TME and is a viable TNBC therapeutic. Funded by DoD/BCRP HT94252310166, BC220526 and HT94252410094, BC230070."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • CHI3L1 • GZMB • HER-2 • IL6 • S100A8 • S100A9

Rac/cdc42 inhibitor MBQ-167 in the estrogen receptor positive breast cancer tumor microenvironment (SABCS 2025) - P1 | "In conclusion, MBQ-167 reduces active p-PAK levels in ER+ breast cancer, and p-PAK levels can be used to demonstrate target engagement for the Rac/Cdc42 inhibitor MBQ-167 in ER+ breast cancer. These results inform the dynamics of Rac/Cdc42 inhibitor therapy in breast cancer patients and forward Phase 2 trials for this novel therapeutic in all breast cancer patients regardless of the clinical subtype."

Biomarker • Tumor microenvironment • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Systematic Evaluation of GAPs and Gefs Identifies ARHGAP45 As a Targetable Leukemia-Specific Dependency (ASH 2024) - "Pharmacological inhibition of CDC42 with the CDC42/Rac1 inhibitor MBQ-167 further enhanced survival following ARHGAP45 KO in AML models...We find that ARHGAP45 is a bona fide GAP for RhoA that is selectively required in AML cells but dispensable in normal hematopoietic cells. Furthermore, we propose a novel immunotherapeutic strategy to target AML by augmenting new and existing TCR-T therapies against ARHGAP45-derived antigens."

IO biomarker • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Solid Tumor • CD34 • HLA-A • RHOA

A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: MBQ Pharma | Trial completion date: Oct 2024 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

M6 metabolite enhances the efficacy of the Rac/Cdc42 inhibitor MBQ-167 in metastatic advanced breast cancer (SABCS 2024) - P1 | "Therefore, M6 is expected to significantly contribute to the duration and intensity of MBQ-167 efficacy in metastatic advanced breast cancer. This study was supported by the US Army Breast Cancer Research Program (BCRP) W81XWH2010041 and HT9425-23-1-0166 (to SD) and HT9425-23-1-0381 (to JFRO)."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CASP7 • CDC42 • HER-2

Testing the Rac/Cdc42 inhibitor MBQ-167 in ex vivo cultures of Hispanic TNBC tissue (SABCS 2024) - P1 | "The results of this study promise to directly address the dynamics of Rac/Cdc42 inhibitor therapy in Puerto Rican TNBC patients and forward Phase 2 trials for this novel therapeutic in advanced breast cancer patients. This study was supported by the US Army Breast Cancer Research Program (BCRP) HT9425-23-1-0166 (to SD), 5R25GM061151-21 (ATS), and NIH NCI 5R25CA240120-05 (MDT)."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Triple Negative Breast Cancer • HER-2

Synthesis of novel, covalent inhibitors of Rac/Cdc42 for the treatment of metastatic breast cancer (ACS-Fall 2024) - "Building on existing inhibitors EHop-016 andMBQ-167, recently CPV-337 was developed and found to be five times more potent than MBQ-167...This research is proposed to develop novel compounds with improved potency to address the urgent need for improved therapeutics for Stage IV breast cancer, focusing on disrupting metastasis at its initiation phase, invasion. Possible future works include exploring the in vivo efficacy and safety profiles of the optimized compounds in preclinical models."

Metastases • Breast Cancer • Oncology • Solid Tumor • CDC42 • RAC1

Novel inhibition of central carbon metabolism pathways by Rac and Cdc42 inhibitor MBQ-167 and paclitaxel. (PubMed, Mol Cancer Ther) - "Biochemical validation, by immunoblotting and metabolic Seahorse analysis, shows that combined MBQ-167 and paclitaxel reduces glycolysis. This study provides a strong rationale for the clinical testing of MBQ-167 in combination with paclitaxel as a potential therapeutic for TNBC and identifies a unique mechanism of action."

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

Efficacy and delivery strategies of the dual Rac/Cdc42 inhibitor MBQ-167 in HER2 overexpressing breast cancer. (PubMed, Transl Oncol) - "When MBQ-167 was targeted to mammary fatpad tumors established from HER2 overexpressing cells via immunoliposomes functionalized with trastuzumab, MBQ-167 and MBQ-167-loaded liposomes show equal efficacy in reducing the viability of trastuzumab-resistant cells, inhibiting tumor growth in mouse xenografts, and reducing metastasis to lungs and liver. This study demonstrates the efficacy of MBQ-167 as an alternative therapeutic in HER2 overexpressing cancers, delivered either in free form or in liposomes."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Implication of Rac1 GTPase in molecular and cellular mitochondrial functions. (PubMed, Life Sci) - "Inhibitors of Rac1 have been identified (NSC-23766, EHT-1864) and some are being developed for the treatment of cancer (MBQ-167) or central nervous system diseases (JK-50561). Their effects on mtRac1 warrant further investigations. An overview of mtRac1 is provided here."

Journal • Review • Oncology • BCL2 • RAC1

MBQ Pharma announces the First-in-Human Dose for Advanced Breast Cancer with the dual targeted Rac/Cdc42 inhibitor: MBQ-167 (Issuer Direct) - "MBQ Pharma...is thrilled to announce a significant milestone. We are proud to announce that we have dosed the first participant in our Phase 1 clinical trial of MBQ-167. MBQ-167 is the first-in-class drug as a dual inhibitor designed to target two GTPase proteins: Rac and Cdc42. Overexpression of these proteins in cancer cells are considered the primary drivers of solid tumor cancer spread and of cancer cells developing resistance to treatment. MBQ Pharma has successfully initiated this trial for patients who need additional options after all possible standard cancer therapies have been attempted....This Phase 1 clinical trial is an open-label, dose-escalation study aimed at establishing the maximum tolerated dose (MTD) of MBQ-167."

Trial status • Breast Cancer

A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: MBQ Pharma

Metastases • New P1 trial • Breast Cancer • Oncology • Solid Tumor

Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models. (PubMed, Front Oncol) - "This was confirmed from splenocytes treated with lipopolysaccharide (LPS) where EHop-016 or MBQ-167 reduced IL-6 secretion in response to LPS. Rac/Cdc42 inhibition induces an antitumor environment via inhibition of both metastatic cancer cells and immunosuppressive myeloid cells in the TME."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • IL6