INB03 / Xencor, INmune Bio - LARVOL DELTA

Soluble TNF blockade enhances trastuzumab-deruxtecan innate antitumor immune response and type-I IFN signalling in HER2-positive breast cancer (AACR 2025) - "Blocking sTNF with INB03 (DN), a dominant-negative molecule, sensitized tumors to therapy and improved the antitumoral immune response. Adding DN allows to de-escalate T-DXd dose without impairing the antitumor effect. Neutralizing sTNF could improve the outcome of patients treated with T-DXd by enhancing the antitumor immune response."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • ISG15

MUC4 downregulation by TNF blockade enhances trastuzumab deruxtecan antitumor effect in a HER2-positive breast cancer model (SABCS 2024) - "In addition, we have shown that TNF induces MUC4 expression and that soluble TNF (sTNF) neutralization with a dominant negative protein to TNF, INB03 (DN), downregulates MUC4 and overcomes trastuzumab resistance in preclinical models. As bioavailability of anti-cancer drugs can be affected by the TME, we propose that MUC4 would be a suitable biomarker to evaluate T-DXd resistance in HER2+ breast cancer, Therefore, addition of sTNF blocking agents would be an option to reinstate tumor sensitivity to T-DXd. In addition, dose reduction of T-DXd in combination with DN could be a feasible therapeutic option to reduce adverse effects."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC4

Muc4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy (AACR 2024) - "We have demonstrated that TNF induces trastuzumab resistance through mucin 4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer...TNF blockade was achieved with etanercept (E), which blocks the soluble (sTNF) and transmembrane isoform of TNF, or with the dominant negative protein INB03 (DN) which neutralizes only sTNF...MUC4 is associated with poorly-infiltrated TNBC, and sTNF blockade downregulates its expression decreasing MTS when combined with anti-PD-1. We propose the TNF as a new target for the treatment of TNBC, and MUC4 as a predictive biomarker to guide a combined treatment of TNF blockers with immunotherapy."

Biomarker • Combination therapy • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2 • KRT5 • MUC4 • PD-L1

INB03: a new immune checkpoint inhibitor that reprograms macrophage polarization, boosts ADCP and reverts T-cell exhaustion markers (AACR 2024) - "Trastuzumab resistance is an important clinical issue in HER2+ breast cancer (BC), and few actionable targets are available. INB03 can tailor the tumor microenvironment by promoting Mϕ ADCP against tumor cells and by acting as an ICP inhibitor for CD8+ T cells, possibly relieving their exhaustion. HER2+MUC4+ BC patients could benefit from the administration of INB03 to boost targeted therapy efficacy and overcome tumor-induced macrophage and T-cell immune escape."

Checkpoint inhibition • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • CD8 • CD86 • CSF1 • HAVCR2 • IFNG • IL10 • IL4 • LAG3 • MRC1 • MUC4 • PD-1 • PD-L1 • SIRPA • TIGIT • VTCN1

INmune Bio Inc. Presents Data on INB03’s Role as an Immune Check Point Modulator in the Treatment of High-Risk Breast Cancer at AACR 2024 (GlobeNewswire) - “In human TNBC cell lines, INB03 decreased the expression mesenchymal markers of invasive capacity, MUC4, SNAIL and Vimectin, and decreased activity in an invasion assay….In a murine LMM3 model, treatment with the combination of INB03 and anti-PD1 checkpoint antibodies dramatically decreased lung metastasis with no animals receiving combination therapy having >3 lesions compared to 40% of control animals.”

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

INmune Bio Inc. Presents Data on INB03’s Role as an Immune Check Point Modulator in the Treatment of High-Risk Breast Cancer at AACR 2024 (GlobeNewswire) - "The poster, titled, 'INB03: a new immune checkpoint inhibitor that reprograms macrophage polarization, boosts ADCP and reverts T-cell exhaustion markers' outlines the use of human macrophages and T cells in a MUC4+HER2+ syngeneic breast cancer model to demonstrate that the combination of INB03 with an anti-HER2 antibody 4D5 has five distinct effects on the tumor biology, which results in decreased tumor growth (p<0.001)....In the study, the increase in T cell infiltrate did not occur unless both anti-HER2 and INB03 immunotherapy were used in combination. Decreases in T cell and macrophage immune checkpoint proteins were caused by INB03."

Preclinical • Breast Cancer • Oncology • Solid Tumor

INB03: In-Booth Education: "Ask the Expert" - In Booth Demonstration of 3M™ Prevena™ Therapy Dressing (AAOS 2024) - "Presented by 3M Health CareStop by the 3M Health Care Booth to learn more about 3M™ Prevena™ Therapy and watch live as Dr.Michael Gardner (Chief, Orthopaedic Trauma Surgery; Stanford School of Medicine) demonstrates his besttips and tricks for optimal application of various Prevena Dressings on a live model."

Orthopedics

Blocking soluble TNF to Improve potency of trastuzumab deruxtecan by increasing internalization and antitumor innate immune response in a resistant HER2-positive breast cancer model (SABCS 2023) - "In preclinical models of de novo trastuzumab-resistant tumors, combination of a sTNF blocking agent INB03, (DN), with T-DXd decreases tumor growth compared to T-DXd alone...Methods Nude mice bearing HER2+MUC4+ JIMT-1 tumor, primary resistant to trastuzumab, pertuzumab and lapatinib, were treated with IgG 5 mg/kg, T-DXd 5 mg/kg (T-DXd 5), 2.5 mg/kg (T-DXd 2.5) or 1.25 mg/kg (T-DXd 1.25), DN 10 mg/kg or the combined therapies...Combination of DN with T-DXd in MUC4 expressing HER2+ BC improves response to T-DXd alone by increasing T-DXd internalization and improving anti-tumor innate immune responses in the TME without increasing toxicity. The results suggest this combination should be investigated in clinical trials in patients who have MUC4 expressing tumors when T-DXd is started or become resistant to T-DXd therapy."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC4

INmune Bio Inc. Demonstrates that INB03 Enhances the Uptake of Trastuzumab Deruxtecan in HER2+ Breast Cancer with MUC4 Expression in Poster Presented at San Antonio Breast Cancer Symposium (GlobeNewswire) - "INmune Bio, Inc...is presenting data on the use of INB03, a dominant-negative TNF inhibitor of soluble TNF (sTNF) in the treatment of high-risk MUC4 expressing HER2. Roxana Schillaci, Ph.D., of Instituto de Biología y Medicina Experimental in Buenos Aries, Argentina, will present her work at the 46th annual San Antonio Breast Cancer Symposium, which runs from December 5 to 9...The poster...shows that INB03 improves the potency of T-DXd in a model of immunotherapy resistant HER2+ breast cancer. INB03 decreases resistance to T-DXd therapy in three ways. INB03 decreases MUC4 expression on the surface of the breast cancer cells increasing the ability of the antibody to bind to the HER2 target on the cancer cell....The poster concludes that the combination of INB03 may allow for lower doses of T-DXd to be effective in women with MUC4 expressing HER2+ breast cancer and that addition of INB03 may improve the response to T-DXd in women with resistant HER2+ disease."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

INB03: a new immune checkpoint inhibitor that reprograms polarization and promotes ADCP in human macrophages (SITC 2023) - "Background Trastuzumab resistance is an important clinical issue and few actionable targets are available. INB03 can tailor the tumor microenvironment by acting as an ICP inhibitor and by promoting ADCP against tumor cells. HER2+MUC4+ BC patients could benefit from the administration of INB03 to boost targeted-therapy efficacy and overcome macrophage immune escape."

Checkpoint inhibition • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • CD14 • CD86 • CSF1 • IFNG • IL10 • IL4 • MRC1 • MUC4 • PD-1 • SIRPA • VTCN1

INmune Bio Inc. Presents Preclinical Data at SITC 2023 Showing INB03 is an Innate Immune Check Point Inhibitor that Downregulates SIRPα (GlobeNewswire) - "INmune Bio, Inc...is presenting data on the use of INB03, a dominant-negative inhibitor of soluble TNF in the treatment of high-risk MUC4 expressing HER2+ breast cancer. Roxana Schillaci Ph.D. of Instituto de Biología y Medicina Experimental in Buenos Aries, Argentina, will present her work at the 38th annual Society of Immunotherapy in San Diego, California which runs from November 1-4...The poster...shows that INB03 is an innate immune checkpoint inhibitor working through the SIRPα-CD47 pathway to promote ADCP...The research presented in the poster examines animal models and human macrophages....In mice with trastuzumab resistant breast cancer, INB03 treatment polarizes splenic and tumor-infiltrating macrophages to M1 type macrophages that phagocytize tumor cells and decreased immune checkpoint expression (PD-L1, TIM3, LAG3) in tumor-infiltrating CD8+ T cells."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

MINDFuL: Study to Assess the Efficacy of XPro1595 in Patients With Mild Alzheimer's Disease With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Jul 2025 ➔ Dec 2024 | Trial primary completion date: Jul 2025 ➔ Dec 2024

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Inflammation • Mental Retardation • Psychiatry

MINDFuL: Study to Assess the Efficacy of XPro1595 in Patients With Mild Alzheimer's Disease With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Jun 2024 ➔ Jul 2025 | Trial primary completion date: Jun 2024 ➔ Jul 2025

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Inflammation • Mental Retardation • Psychiatry

Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Inmune Bio, Inc. | N=60 ➔ 0 | Trial completion date: Jan 2023 ➔ Oct 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jan 2023 ➔ Oct 2023

Biomarker • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Mental Retardation • Psychiatry

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease (clinicaltrials.gov) - P2 | N=261 | Recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Dec 2025 ➔ May 2026 | Trial primary completion date: Dec 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry

New therapeutic approach for triple negative breast cancer: soluble TNFα blockade and MUC4 expression as a prognostic biomarker (AACR 2023) - "We have demonstrated that the proinflammatory cytokine TNFα induces trastuzumab resistance through Mucin4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer...TNFα blockade was achieved using etanercept (E), which blocks the soluble (sTNFα) and transmembrane isoforms of TNFα, or dominant negative protein INB03 (DN) which only neutralizes sTNFα...MUC4 is an independent biomarker of poor overall survival, it is associated with an increased risk of metastasis and immune desert tumors. We propose TNFα as a new target for the treatment of TNBC, and MUC4 as a predictive marker to guide a combined treatment of TNFα blockers with chemotherapy or immunotherapy."

Biomarker • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2 • KRT5 • MUC4 • PD-L1 • VIM

Soluble TNFα blockade improves effectiveness of trastuzumab deruxtecan and boosts antitumor potential of macrophages in a HER2+ tumor model (AACR 2023) - "Here, we study whether sTNFα blockade with INB03 (DN) plays a role in regulation of innate immunity to enhance T-DXd antitumor effects in a multiple HER2-targeted therapy-resistant model. Nude mice bearing HER2+MUC4+ JIMT-1 tumor, primary resistant to trastuzumab, pertuzumab and lapatinib, were treated with IgG 5 mg/kg, T-DXd 5 mg/kg (T-DXd 5), 2.5 mg/kg (T-DXd 2.5) or 1.25 mg/kg (T-DXd 1.25), DN 10 mg/kg or the combined therapies...Adding DN allows to lower T-DXd doses to induce a reinforced antitumor innate immune response, reduced tumor cell mitosis and achieve similar tumor inhibition. Since sTNFα and MUC4 expression proved to be important variables in the response to T-DXd, neutralizing this cytokine may open new therapeutic strategies to treat patients with MUC4 expressing tumors or have progression on T-DXd therapy."

Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC4

INmune Bio, Inc. to Present Preclinical Data at the 2023 AACR Annual Meeting Showing Improved Outcomes in High-Risk Breast Cancer by Targeting MUC4 Expression with INB03 (GlobeNewswire) - "INmune Bio...is presenting data on the use of INB03, a dominant-negative TNF inhibitor of soluble TNF (sTNF) in the treatment of high-risk MUC4 expressing HER2+ and triple negative breast cancer....Two presentations show targeting high-risk MUC4 expressing HER2+ and Triple Negative Breast Cancer with INB03 reverses resistance mechanisms to immunotherapy."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

INmune Bio, Inc. Announces 2022 Results and Provides Business Update (BioSpace) - '"...Despite advances in the treatment of men with metastatic castration-resistant prostate cancer, the lethal form of the disease, median survival remains short and novel treatment approaches are urgently needed,” said Matt Rettig MD...who will be Principal Investigator (PI) of the INKmune trial..."

Media quote

Soluble TNFα blockade enhances trastuzumab deruxtecan antitumor effect in HER2-positive breast cancer model (SABCS 2022) - "In preclinical models of de novo trastuzumab-resistant tumors, we proved that administration of the sTNFα blocking agent INB03 (DN) together with trastuzumab inhibited tumor growth and induced an innate immune response in the tumor microenvironment (TME)...Methods JIMT-1 is a HER2- positive BC cell line resistant to trastuzumab, pertuzumab and lapatinib, which expresses MUC4...This finding highlights that sTNFα and MUC4 expression are important variables in the response to T-DXd. Neutralization of sTNFα may open new therapeutic strategies for treatment of patients who present with MUC4 expression or have progression on T-DXd therapy."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC4

INmune Bio, Inc. Announces 2022 Results and Provides Business Update (GlobeNewswire) - "In pre-clinical models, INB03™ DN-TNF reduces MUC4 expression to decrease resistance to immunotherapy. A pSar DN-TNF compound with new composition-of-matter IP is in animal testing and if positive, this unique DN-TNF drug will be moved into a strategic partnering program in oncology....Additional data will be presented at AACR in April 2023."

Preclinical • Oncology

MINDFuL: Study to Assess the Efficacy of XPro1595 in Patients With Mild Alzheimer's Disease With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Immunology • Inflammation • Mental Retardation • Psychiatry

INmune Bio, Inc. Reports Combination Therapy with INB03 Overcomes Resistance to Trastuzumab-Deruxtecan in MUC4 expressing HER2+ Breast Cancer (GlobeNewswire) - "INmune Bio...has been invited to present data on the combination of INB03™ and trastuzumab-deruxtecan (TDxd) for treatment of HER2 positive breast cancer....Using the well-established nude mouse model of HER2 resistance in mice with MUC4 expressing HER2+ breast cancer, JIMT-1 tumors exhibit decreased growth when treated with TDxd. The combination of TDxd with INB03™ improved anti-tumor immunology of the TME with fewer myeloid derived suppressor cells (MDSC) and more antitumor tumor macrophages, which further decreased tumor growth compared to TDxd alone."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease (clinicaltrials.gov) - P2 | N=261 | Recruiting | Sponsor: Inmune Bio, Inc.

New P2 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry

Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Inmune Bio, Inc. | Initiation date: May 2022 ➔ Sep 2022

Biomarker • Trial initiation date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Inflammation • Mental Retardation • Psychiatry