GF9 / SignaBlok - LARVOL DELTA

TREM-1 inhibitor specificity and composition impact its therapeutic efficacy in experimental retinopathy of prematurity (ARVO 2026) - "Intolerance or lack of response to conventional therapies as well as serious side effects indicate an unmet need for novel treatment options. The findings of this study are anticipated to result in the development of novel mechanism-based systemic therapeutics that could substantially improve treatment of neovascular retinal diseases and decrease the nation's annual cost of eye and vision disorders currently exceeding $140 billion."

Clinical • Prematurity • Age-related Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinopathy of Prematurity

Specificity and timing of TREM-1 blockade initiation impact its therapeutic efficacy in cancer (AACR 2026) - "In summary, these findings for the first time demonstrate that both inhibitor specificity and timing of treatment initiation are crucial for therapeutic TREM-1 inhibition. This has significant implications for clinical strategies targeting TREM-1, particularly informing tailored treatment approaches for not only pancreatic cancer but also other hard-to-treat tumors."

Clinical • IO biomarker • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • PDX1 • TP53

TREM-1-mediated modulation of innate immune response in acute and chronic inflammation: Effect of treatment timing and cell specificity on outcome (IMMUNOLOGY 2026) - "In summary, this is the first direct evidence that pan-TREM-1 and macrophage-restricted TREM-1 blockades may differ in their therapeutic efficacy depending on the disease, timing of treatment initiation and the type and stage of inflammatory response."

Acute Lung Injury • Immunology • Infectious Disease • Inflammation • Pancreatic Cancer • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor

Timely resolution of TREM-1-mediated inflammation after chemotherapy improves complete response rate and survival in experimental pancreatic cancer (AACR 2025) - "To address the problem of multiplicity and promiscuity of natural TREM-1 ligands and reduce the risk of drug failure in clinical efficacy testing, we developed a first-in-class TREM-1 inhibitory peptide sequence GF9 that employs a novel, ligand-independent mechanism of action...This may have important clinical implications in the treatment of patients with not only PDAC, but also other inflammation-associated, hard-to-treat solid tumors. By supplementing current first-line cancer treatments (chemo- and immunotherapies, radiation and surgery), pharmacological interventions that timely resolve TREM-1-mediated inflammation may improve quality of life and extend survival of cancer patients."

Clinical • Late-breaking abstract • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • APOA1

Ligand-Independent TREM-1 Blockade Ameliorates Pulmonary Inflammation and Fibrosis (ATS 2025) - "Multiplicity and promiscuity of TREM-1 ligands significantly increase the risk of failure of traditional, ligand-dependent approaches to TREM-1 inhibition (e.g., anti-TREM-1 blocking antibodies and decoy peptides) in clinical efficacy testing. Despite promising preclinical data and safety in humans, the first clinical inhibitor of TREM-1, a decoy peptide LR12 (nangibotide), failed in phase IIb sepsis trial... Ligand-independent TREM-1 blockade for the first time has been shown to ameliorate pulmonary inflammation and fibrosis in animal models, warranting further development of a novel, first-in-class TREM-1 therapy for human ARDS and PF."

Acute Lung Injury • Acute Respiratory Distress Syndrome • Fibrosis • Immunology • Infectious Disease • Inflammation • Pneumonia • Septic Shock

Inhibiting Triggering Receptor Expressed on Myeloid Cells-1 signaling to ameliorate skin fibrosis. (PubMed, JCI Insight) - "Selective pharmacological TREM-1 blockade prevented and reversed skin fibrosis induced by bleomycin in mice and mitigated constitutive collagen synthesis and myofibroblast features in SSc fibroblasts in vitro. Our results implicate aberrantly activated TREM-1 signaling in SSc pathogenesis, identify a unique approach to TREM-1 blockade, and suggest a potential therapeutic benefit for TREM-1 inhibition."

Journal • Fibrosis • Immunology • Infectious Disease • Rheumatology • Scleroderma • Systemic Sclerosis • TGFB1

Inhibition of TREM-2 Markedly Suppresses Joint Inflammation and Damage in Experimental Arthritis. (PubMed, Int J Mol Sci) - "Previously, we demonstrated that TREM-1 blockade, using a ligand-independent TREM-1 inhibitory peptide sequence GF9 rationally designed by our signaling chain homooligomerization (SCHOOL) model of cell signaling, ameliorates collagen-induced arthritis (CIA) severity in mice. Here, we designed a TREM-2 inhibitory peptide sequence IA9 and tested it in the therapeutic CIA model, either as a free 9-mer peptide IA9, or as a part of a 31-mer peptide IA31 incorporated into lipopeptide complexes (IA31-LPC), for targeted delivery. We demonstrated that administration of IA9, but not a control peptide, after induction of arthritis diminished release of proinflammatory cytokines and dramatically suppressed joint inflammation and damage, suggesting that targeting TREM-2 may be a promising approach for the treatment of RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to Bordetella pertussis inflammatory pathology. (PubMed, Infect Immun) - "Interestingly, S1PR agonists dampen pulmonary inflammation and TREM-1 expression. Mice receiving TREM-1 inhibitors showed reduced pulmonary inflammation compared to controls indicating that TREM-1 promotes inflammatory pathology, but not bacterial control, during pertussis infection. This implicates TREM-1 as a potential therapeutic target for the treatment of pertussis."

Journal • Immunology • Infectious Disease • Inflammation • Pertussis • Pneumonia • Respiratory Diseases • CCL2 • TLR9 • TNFA