Lead Candidate

A New Frontier in Inflammatory, Metabolic & Infectious Disease

Chronic inflammation, neurodegeneration, metabolic dysfunction, and life‑threatening infections share a hidden driver: peptidoglycan (PGN) — a structurally conserved bacterial cell‑wall polymer that constantly sheds bioactive fragments known as muropeptides. These fragments activate powerful innate immune pathways including NOD1/2, PGRPs, and hexokinase, triggering systemic and CNS inflammation.

This biology is well‑established in peer‑reviewed literature, which shows muropeptides act as potent signaling molecules and immune activators.

In the CNS, the microglial receptor PGLYRP1 is now recognized as a key amplifier of neuroinflammation, with strong upregulation in human MS, EAE, LPS, and TBI models. Neutralizing PGLYRP1 profoundly reduces inflammatory cytokines and glial activation.

Longhorn’s platform directly targets this biology with first‑in‑class monoclonal antibodies that bind conserved PGN epitopes across Gram‑positive, Gram‑negative, and mycobacterial pathogens.

Our Pipeline

HE‑MD11 — Extended‑Half‑Life Anti‑PGN IgG (Chronic Disease)

HE‑MD11 is designed to function as a long‑acting PGN/muropeptide “sponge”, reducing activation of inflammatory pathways that drive:

• Metabolic inflammation & NASH

• Neuroinflammatory & neurodegenerative diseases

MD11, the parent antibody, demonstrates:

• High‑affinity binding to ultrapure PGN

• Broad reactivity with S. aureus, S. epidermidis, B. subtilis, GBS, mycobacteria, and E. coli PGN

• Strong opsonophagocytic killing (OPKA) across macrophages, granulocytes, and neutrophils (often 50–70% killing in U‑937 assays)

These data are supported by multiple conference posters and internal validation sets.

DRG-BD11 — IgM Anti‑PGN for ICU & High‑Risk Surgical Infection Prevention

Human IgM monoclonal DRG-BD11 binds ultrapure PGN and multiple live Gram‑positive bacteria, including M. smegmatis, S. epidermidis, and S. aureus.

Demonstrates significant OPKA (80%) against E. coli in U‑937 assays.

DRG-BD11 is engineered for rapid, high‑avidity bacterial neutralization—ideal for:

• ICU patients with ventilation, central lines, ECMO

• High‑risk cardiac, abdominal, transplant, trauma, or neurosurgical procedures

• Settings with MDR organisms where antibiotics fail

Longhorn is also developing monoclonal antibodies targeting LTA and LPS offering a comprehensive and innovative strategy for sepsis and inflammatory disease prevention and treatment. By neutralizing key toxins and enhancing bacterial clearance, this cocktail can significantly improve patient outcomes and reduce long-term disease and mortality.