Inflammation mobilizes the innate and adaptive immune systems to respond to and contain pathogens or injuries, playing a critical role in sustaining human health and vitality.
But when inflammation is uncontrolled—causing systemic or local dysregulation and imbalance of the immune system—it can lead to a range of chronic diseases. Much of the therapeutic focus on chronic inflammatory diseases has centered on approaches that inhibit inflammatory responses extracellularly or block a single proinflammatory pathway intracellularly, all of which can lead to serious side-effects and other significant challenges regarding efficacy and patient safety.
An optimal therapeutic solution would modulate, but not inhibit, inflammatory responses using a system of regulation naturally occurring in cells of the body to broadly attenuate stimulation of inflammatory or metabolic pathways. Such a solution would offer a safer and more effective approach to restoring immune and metabolic balance.
AMTX-100 : A Novel Therapeutic Solution
Resolution of inflammatory diseases involves an active process of reprogramming cells using mechanisms that limit inflammation to restore immune balance. AMTX-100 is a breakthrough therapeutic approach focused on reprogramming immune cell genomes. The peptide provides very efficient anti-inflammatory activity in that it can modulate at least 8 activators of inflammation intracellularly.
AMTX-100 is bioengineered from amino acid sequences of human fibroblast growth factor-4 (FGF-4) and the nuclear localization sequence (NLS) of NF-kB, the master regulator of inflammation, by eliminating NF-kB transcriptional activation functions. AMTX-100 penetrates cells, without the need for a receptor, and actively competes with the natural binding of transcription factors (TFs) with an NLS to their docking site on importins used to transport TFs from the cytoplasm to the nucleus.
Pre-clinical animal studies have demonstrated the successful therapeutic benefit of AMTX-100 in a range of disorders where inflammation or metabolic stressors form the underlying basis of the condition, highlighting the therapeutic potential of AMTX-100 across a range of inflammatory diseases where significant medical need remains.
How it Works
AMTX-100 is a first-in-class, cell-penetrating, anti-inflammatory peptide with a novel mechanism of action that leverages the tight cellular control required for nuclear transport of large stress response transcription factors (SRTFs) involved in inflammation and transcription factors (TFs) involved in metabolic syndrome through their obligatory use of importins.
When introduced into the body, AMTX-100 is rapidly and broadly distributed entering immune cells where it competes as a decoy with large stress responsive TFs involved in inflammation and TFs involved in metabolic syndrome for their nuclear transporters—the adaptor molecule Importin α (Impα) complexed to importin β (Impβ) (Impα/Impβ) or Impβ alone, respectively—without affecting smaller housekeeping TFs. This competition for the NLS docking site on Impα for SRTFs or Impβ for TFs involved in metabolic stress modulates, but does not completely inhibit, TF trafficking into the nucleus which leads to attenuation of inflammatory or metabolic gene transcription.
Commercialization Advantages of
Excellent systemic and topical safety profile in preclinical studies
Strong composition of matter and utility position
Broad application across a range of inflammatory diseases
Collaborative opportunities for stand-alone or combination treatment
Versatile and stable product formulations
Scalable manufacturing and favorable cost of goods