GF9 / SignaBlok - LARVOL DELTA

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

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

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

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