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Our Science

“By naturally modulating a common and key pathway used to initiate inflammation, AMTX-100 has the ability to provide broad therapeutic activity without affecting important housekeeping genes essential for cell growth and viability, drastically minimizing side-effects and safety concerns seen with many small molecule and biologic anti-inflammatory drugs.”

Matthew A. Gonda, Ph.D, Amytrx CEO

Targeting Inflammation

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.

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Therapeutic Areas

Rheumatoid Arthritis

Psoriatic Arthritis

Therapeutic Areas

Parkinson’s

 MS

 Stroke

 ALS

 Alzheimer’s

Therapeutic Areas

Wet AMD

Uveitis

Conjunctivitis

Diabetic Retinopathy, Sjögren’s

Therapeutic Areas

Chronic Sinusitis

Allergies

Acne

Rosacea

Herpes

Therapeutic Areas

Acute Pneumonia

Asthma

COPD

COVID-19

Therapeutic Areas

NASH

Diabetes

Hypercholesteremia

Atherosclerosis

Heart Attacks

Therapeutic Areas

Lupus

Psoriasis

Eczema

Shingles

Therapeutic Areas

IBD

Crohn’s Disease

Pancreatitis

Other Autoimmune Disorders

AMTX-100 : A Novel Therapeutic Solution

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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.

Proinflammatory insults can stimulate cytoplasmic and genomic responses in immune and non-immune cells. Genomic responses depend on translocation of transcription factors (TF) from the cytoplasm to the nucleus to switch on genes to produce RNA gene transcripts that are translated in the cytoplasm into proinflammatory gene products that are subsequently secreted.

 

Large proinflammatory TF are also known as stress responsive transcription factors (SRTF), such as NFAT, NF-κB, c-rel, Rel A, Rel B, AP-1, NRF-2 and STAT1. The larger size of the SRTF excludes them from freely entering the nucleus through nuclear pores. Nuclear transport of SRTF requires the assistance of importins, specifically, the adaptor protein, importin-α5 (Impα) complexed with importin-β1 (Impβ). There is another class of larger TF involved in metabolic syndrome that include carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) that requires only Impβ for nuclear translocation (not shown).

AMTX-100 is a bioactive decoy containing both a cell-penetrating domain and the nuclear localization sequence (NLS) of the stress responsive transcription factor (SRTF) NF-kB that is capable of modulating the inflammatory response by competing with the NLS binding domain on fully functional NF-κB and other monopartite and bipartite NLS containing  SRTF like AP-1, NFAT, NRF-2 and STAT1, for their docking site on the Impα adaptor protein complexed to Impβ.

 

This competition between the NLS’s of AMTX-100 and SRTF for their cognitive binding site on Impα dilutes pro-inflammatory effects of SRTF upstream of DNA activation by modulating the amount of functional SRTF that enter the nucleus and stimulate promotors on inflammatory genes. This reduces initiation of transcriptional and translational processes resulting in reduced production of proinflammatory cytokines, chemokines and growth factors. Similarly (not shown), AMTX-100 also contains a second TF binding domain in the cell-penetrating sequences that binds Impβ and competes with transport of the fully functional TFs, SREBP and ChREBP, involved in activating genes responsible for overproduction and secretion of cholesterol, triglyceride and fatty acids observed in metabolic syndrome.

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Commercialization Advantages of 

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Excellent systemic and topical safety profile in preclinical studies

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Strong composition of matter and utility position 

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Broad application across a range of inflammatory diseases

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Collaborative opportunities for stand-alone or combination treatment

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Versatile and stable product formulations 

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Scalable manufacturing and favorable cost of goods