AUR300 / Riptide Biosci, Aurinia Pharma - LARVOL DELTA

PET Imaging of CD206 Macrophages in Bleomycin Induced Lung Injury Mouse Model (SNMMI 2025) - "Purpose/Background: Idiopathic Pulmonary Fibrosis (IPF) is a severe, age-related pulmonary condition of unknown etiologies. Both linear and cyclic [68Ga]Ga-RP832c were prepared in radiochemical yields of >99%. The 4h % intact for stability of linear form was 88.3±2.1 in PBS (pH7) and 67.3±1.2 in mouse serum, 90.3±1.5 in PBS (pH7) and 69.7±3.2 for the cyclic form. Both linear and cyclic forms revealed a significantly higher lung uptake in BLM."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • MRC1

PET Imaging of CD206 Macrophages in Bleomycin-Induced Lung Injury Mouse Model. (PubMed, Pharmaceutics) - "Background/Objectives: The identification of inflammatory mediators and the involvement of CD206 macrophages in anti-inflammatory responses, along with the synthesis of fibrotic mediators, are crucial for the diagnosis and treatment of Idiopathic Pulmonary Fibrosis (IPF). In contrast, the healthy mice exhibited no detectable CD206 staining, lower PET signals, and reduced radiopharmaceutical accumulation in lung tissues at the same timepoint. These findings suggest that both linear and cyclic [68Ga]Ga-RP832c may function as promising PET imaging agents for CD206 macrophages, and thereby a strategy to non-invasively explore the role of macrophages during fibrogenesis."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • MRC1

Compartmental Modeling for Dual-Tracer [18F]F-FDG and [68Ga]68-RP832c PET Signal Separation: Applications in Preclinical Breast Cancer (SNMMI 2024) - "Compartment modeling can be used to reliably separate single scan dual-tracer TACs to create single-tracer TACs. Single-tracer TACs can then be used to measure various co-registered biological metrics that give insight into tumor heterogeneity and treatment response. Furthermore, this method of separating overlapping tracer signals from dual-tracer PET is shown to be accurate and consistent between pre-clinical imaging scans."

Preclinical • Breast Cancer • Oncology • Solid Tumor

Systemic Sclerosis Macrophages Stimulate Calcinosis in Adipose Derived Mesenchymal Stem Cells via the Activin a Pathway (ACR Convergence 2023) - "Calcinosis occurs in both diffuse and limited SSc subsets and across autoantibody subgroups and was associated with digital ulceration.Elevated plasma levels of Activin A, most notable in anti-Scl70 subgroup, is consistent with systemic upregulation of the Activin A pathway in SSc.Activated macrophages from SSc patients are a potential source of Activin A capable of stimulating MSCs via an osteogenic/calcinosis model.The AUR300 and SB431542 compounds as studied represent potential therapeutic inhibitors of this severe and currently resistant complication of SSc. Figure 1 Role of activin A/ALK5 pathway in SSc macrophages induced calcinosis. (A) Plasma levels of Activin A are raised in diffuse SSc anti-Scl70 (ATA) group."

Fibrosis • Immunology • Metabolic Disorders • Mood Disorders • Scleroderma • Systemic Sclerosis • TGFBR1

Reversal of the Activation State of Pro-fibrotic CD206 Positive Macrophages by Therapeutic Peptide AUR300 in Systemic Sclerosis (ACR Convergence 2023) - " Suction blister fluid-derived cells from lesional skin were profiled by 10X RNAseq matched to AKOYA antibody staining to characterise the tissue resident immune cells, including the CD206 positive macrophages of interest (n=12 SSc patients and controls).Tissue culture modelling with patients' blood monocyte-derived macrophages and disease fibroblasts (n=6 SSc cell lines), as well as bleomycin induced lung fibrosis as a model of organ involvement, were used to determine efficacy and mechanism of action of the therapeutic AUR300 peptide.Soluble CD206 (sCD206) (n=140 SSc and n=80 healthy control (HC) plasma samples) and cellular CD206 (n=17 SSc, n=9 HC macrophage lines) were investigated as potential biomarkers of SSc disease activity. In disease tissue, CD206 positive macrophages represent a spectrum of activation states, from pro-resolving MERTK IL-10 expressing cells, to pathogenic cells releasing profibrotic cytokines and growth factors in activating..."

Fibrosis • Immunology • Inflammation • Respiratory Diseases • Scleroderma • Systemic Sclerosis • CD63 • CD68 • IL10 • IL6 • LAMP3 • MERTK • MRC1 • SIGLEC1

A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice. (PubMed, Cells) - "Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CXCL1 • IFNG • IL10 • IL6 • MMP13 • MRC1 • TGFB1 • TNFA

Immunosuppressive macrophage targeting as a therapeutic strategy for cutaneous T-cell lymphoma (ISID 2023) - "Our data suggest that both TLR4 inhibition and CD206 activation in the CTCL tumor microenvironment inhibit tumor growth by inducing a phenotypic shift from immunosuppressive M2-like to anti-tumor M1-like macrophages. Therefore, topical or systemic formulations of CD206 binding peptide, RP-832c, and small molecule TLR4 inhibitors present promising immunomodulatory therapeutic options in CTCL."

IO biomarker • Cutaneous T-cell Lymphoma • Hematological Malignancies • Immune Modulation • Immunology • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • MRC1 • TLR4

Evaluation of a CD206-Targeted Peptide for PET Imaging of Macrophages in Syngeneic Mouse Models of Cancer. (PubMed, Mol Pharm) - "In addition, it has shown inhibition in bleomycin-induced pulmonary fibrosis through interactions with CD206 macrophages. A significant correlation was found between the percentage of CD206 present in each tumor imaged with [Ga]RP832c and PET imaging mean standardized uptake values in a CT26 mouse model of cancer. The data shows that [Ga]RP832c represents a promising candidate for macrophage imaging in cancer and other diseases."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Melanoma • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • MRC1

Targeting Immunosuppressive Macrophages in the Cutaneous T-Cell Lymphoma Microenvironment (ASH 2022) - "Our data suggest that both TLR4 inhibition and CD206 activation in the CTCL tumor microenvironment inhibit tumor growth by inducing a phenotypic shift from immunosuppressive M2-like to anti-tumor M1-like macrophages. Therefore, topical or systemic formulations of CD206 binding peptide, RP-832c, and small molecule TLR4 inhibitors present promising immunomodulatory therapeutic options in CTCL. Figure 1: MBL2 cells were injected s.c. into flanks of C57BL/6 and TLR4-/- recipients (5 mice /grp.) and tumor volumes monitored overtime."

IO biomarker • Cutaneous T-cell Lymphoma • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • MRC1 • TLR4

Therapeutic Peptide Aur300 Targeting Cd206 Inhibits Macrophage-Dependent Inflammation, Fibrosis And Calcinosis In Scleroderma (IWSR 2022) - "These data support the notion that multiple aspects of SSc could be attributable to activated macrophages. By targeting these cells, therapeutic peptide AUR300 effectively inhibits multiple disease-relevant pathways resistant to current standard DMARDs."

Fibrosis • Immunology • Inflammation • Metabolic Disorders • Scleroderma • Systemic Sclerosis • CSF1 • IL6 • MRC1

Novel therapeutic peptides targeting CD206 modulate ATP-induced release of inflammatory and B cell activating factors in lupus macrophages (BSR 2022) - "These data confirm macrophages as a potential source of inflammatory mediators and B cell-activating factors in lupus. These properties are enhanced by exposure to an ATP-like stimulus. In particular, lupus but not control macrophages had the capacity to synthesis BAFF when exposed to the DAMP stimulus."

Immunology • Inflammatory Arthritis • Lupus • CD86 • CSF1 • IL10 • IL6 • MRC1

Evaluating Novel Therapeutic Peptide Rp832C Targeting Cd206 In Models Of Scleroderma Macrophage-Dependent Fibrosis And Inflammation (SSWC 2022) - No abstract available

Fibrosis • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • MRC1

Evaluating Novel Therapeutic Peptide Rp832C Targeting Cd206 In Models Of Scleroderma Macrophage-Dependent Fibrosis And Inflammation (SSWC 2022) - No abstract available

Fibrosis • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • MRC1