Moreover, is there room for one more?
How many blockbuster drugs are there? A Blockbuster drug’s definition is achieving $1B in annual sales or more. Today, the best-selling drug on the market is Comirnaty, the Pfizer/BioNTech Covid Vaccine with projections of hitting $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 begins due to the use of supplemental oxygen and mechanical ventilation. In addition, often develops in preterm infants first diagnosed with respiratory distress syndrome. Moreover, 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.
A chest radiograph of bronchopulmonary dysplasia.
Currently, the FDA hasn’t approved a therapy available for BPD. Furthermore, 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 completed in June 2019. Along with all of the recommended studies to file an investigational new drug application (IND). This includes efficacy, dose, and formulation established in both small and large animal models of BPD. Immunomodulatory efficacy tests took place in human whole blood and cord blood.
Major GLP safety pharmacology and toxicity studies occurred 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 target 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.
Already evaluated in several preclinical disease models, using a variety of formulations and delivery routes, with positive therapeutic outcomes.
Selman Waksman, Nobel Prize in Medicine for developing 22 antibiotics—most notably Streptomycin
In conclusion, AyuVis compounds are unique thanks to their triple action immunomodulation, anti-inflammatory and anti-microbial activities.
Furthermore, their ability to bind to toll-like receptor 4 (TLR4) and scavenger receptor CD163 provides that bioactivity.
Moreover, by increasing IL-10 and suppressing multiple inflammatory cytokines the molecule is more anti-inflammatory. However, the compounds have a formulation to modulate macrophages to be more phagocytic and kill bacteria which is antimicrobial. Lastly, 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
How many blockbuster drugs are there?
- Nature Science Report, 2019
– 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
- 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