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Is AVR-48 The First Mega Blockbuster Drug?

· Science

Is AVR-48 The First Mega Blockbuster Drug?

A First-In-Class Small Molecule Immunotherapy that Prevents and Treats a Range of Acute and Chronic Inflammatory Diseases

A Blockbuster drug is defined as one that achieves $1B in annual sales or more. Today, the best-selling drug on the market is Comirnaty, the Pfizer/BioNTech Covid Vaccine which is projected to hit $55B in revenue by 2027*. So, what do you call a drug with the potential to generate $100B in sales?

AyuVis is developing a new class of drugs with broad-based applications in the treatment of some of the most common and debilitating diseases. The initial list includes Sepsis, Renal Disease, Bronchopulmonary Dysplasia (BPD), Ventilator Associated Pneumonia (VAP), Acute Respiratory Distress Syndrome (ARDS), ocular, and dermatology applications.

Ayuvis’ compound is a first-in-class, small molecule immunotherapy. 

This single compound is an immunotherapy modulating the immune system which is also an anti-inflammatory and anti-microbial therapy. 

In preclinical animal models the compound has demonstrated high efficacy in reducing inflammation and lung tissue damage while fighting infection. Because of this, the compound also has the unique ability to treat multiple diseases in multiple organs including lungs, liver, kidneys, blood, eyes, and skin*. 

The FDA has granted AyuVis Orphan Drug and Rare Pediatric Drug Designations for the first AyuVis compound, AVR-48, to prevent BPD in at-risk preterm infants which will fast-track clinical trials. 

The company is also preparing IND-enabling studies for pulmonary applications including VAP and ARDS. The total global market opportunity for just these three diseases is $35B. 

Bronchopulmonary dysplasia is caused by the use of supplemental oxygen and mechanical ventilation and often develops in preterm infants first diagnosed with respiratory distress syndrome. It is the most common cause of death and lung injury in premature infants with approximately 60,000 babies at risk of developing BPD in the United States each year. 

It affects between 20 and 25% of all infants born before 28 weeks of gestational age, resulting in 10,000 to 15,000 BPD cases per year in the United States and a much higher number globally. 

There are no FDA approved therapies currently available for BPD and 9% of babies who contract BPD die from it. In addition to the human costs, the financial impact for each patient with BPD is more than $200,000 in just the first year, and doubles with other complications like pulmonary hypertension.

In preclinical tests, AVR-48 therapy restored lung structure and function in a BPD lamb model. It significantly improved lung maturation while reducing respiratory severity. 

The pre-IND meeting with the FDA was completed in June 2019 and all the recommended studies to file an investigational new drug application (IND) have been completed. This includes efficacy, dose, and formulation established in both small and large animal models of BPD. Immunomodulatory efficacy was tested in human whole blood and cord blood. 

Major GLP safety pharmacology and toxicity studies have been completed in rats, dogs and lambs, preparing AVR-48 to begin clinical trials in healthy adult volunteers later this year.

While BPD is the lead indication and these initial studies are targeted at neonates or preterm low birth weight infants, AVR-48 has applications in adult and pediatric diseases as well. AyuVis compounds modulate the innate immune system to treat both inflammation and infection. 

The company has identified additional compounds to expand the pipeline to include bacterial pneumonia, complicated intra-abdominal infection (cIAI), necrotizing colitis (NEC), acute kidney injury, systemic inflammatory response syndrome, fibrosis, and ocular diseases including retinitis of prematurity. 

They have been evaluated in several preclinical disease models, using a variety of formulations and delivery routes, with positive therapeutic outcomes. 

Selman Waksman, who was awarded the Nobel Prize in Medicine for developing 22 antibiotics—most notably Streptomycin

AyuVis compounds are unique thanks to their triple action immunomodulation, anti-inflammatory and anti-microbial activities. Their ability to bind to toll-like receptor 4 (TLR4) and scavenger receptor CD163 provides that bioactivity. 

Thus by increasing IL-10 and suppressing multiple inflammatory cytokines the molecule is more anti-inflammatory. However, the compounds are also formulated to modulate macrophages to be more phagocytic and kill bacteria which is antimicrobial. This flexibility and efficacy offer the potential to treat a number of indications that when added together, the global market opportunity exceeds $100B annually.

              A cluster of Escherichia coli bacteria magnified 10,000 times

 - Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis, PMID: 30814582. 

   Journal of Pediatric Intensive Care, 

2020 - Chitin Analog AVR-25 Prevents Experimental BPD, PMID: 32685255 

  1. Intl. Journal of Molecular Science, 2021 

Small Immunomodulatory Molecules as Potential Therapeutics…of ALI/ARDS, PMID: 33806560 Intl. Journal of Molecular Science, 2021 Chitin-Derived AVR-48 Prevents Experimental BPD &…Pulmonary Hypertension in…Mice, IJMS:22168547


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