PHP-303 is a novel neutrophil elastase (NE) inhibitor. NE is a major inflammatory factor involved in the progression of NASH and AATD. Inhibition of NE improves inflammatory response and, especially in NASH, insulin resistance.

Development Status

  • pH Pharma acquired PHP-303 from Bayer AG in March 2017. Prior to acquisition, Bayer AG had conducted clinical studies on bronchiectasis, evaluating human safety and target inhibition.
  • pH Pharma is developing PHP-303 as a novel therapy for NASH indication, having completed Phase 1b SAD/MAD studies (US) in 2019.
  • pH Pharma has expanded PHP-303 indication to include the genetic disease alpha-1 antitrypsin deficiency (AATD) and completed a Phase 2 clinical study in EU.

What is non-alcoholic steatohepatitis?

Non-alcoholic steatohepatitis (NASH) is a condition characterized by accumulation of fat, inflammation and injury in liver cells in people who consume little or no alcohol. NASH can lead to cirrhosis and liver cancer. Global NASH market is expected to reach US$ 37.1 Billion by 2030. Despite of growing treatment need there are no approved therapeutic for NASH.

NASH Market Forecast (USD, billions)


What is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency (AATD) is a genetic disease that causes a lack of the protein, alpha-1 antrypsin (A1AT) due to the inability to release and accumulate antiprotease from the liver.  The current AATD treatment market reaches over USD 1 billion, and it is expected to grow up to USD 1.8 billion.

AATD Market Forecast (USD, millions)

(Reference: DelveInsight)

What is acute respiratory distress syndrome?

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by severe inflammation in the lungs and has significant morbidity and mortality associated with this condition. Factors that can elicit ARDS include body trauma, inhalation of toxic substances, severe blood infection, and severe infection of the lungs (such as pneumonia). Recently, ARDS has been demonstrated as one of the most serious and lethal consequence of coronavirus disease (COVID-19) since the pandemic began in early 2020. Excessive neutrophil elastase (NE) has been implicated in severe COVID-19. Treatment of COVID-19 patients with PHP-303, a potential best-in-class NE inhibitor, could mitigate pulmonary complications and lung function impairment by neutralising the damaging effects of excess NE on lung connective tissue. pH Pharma was awarded US Department of Defense grant to develop PHP-303 for the treatment of COVID-19-Associated ARDS and Organ Damage. ARDS will continue to be an important life-threatening disease beyond the Covid-19 pandemic.

(Reviewed in Mediators of Inflammation: Borges et al., 2020)

Clinical Advisory Board

David Brenner


  • Vice Chancellor, Health Sciences and Dean of the School of Medicine, University of California
  • President-elect, Association of American Physicians (AAP)
  • Board Member, AlphaOne Foundation
  • Board Member, Alcoholic Beverage Medical Research Foundation
  • Member of American Society for Clinical Investigation (ASCI), American College of Physicians (ACP), American Gastroenterological Association (AGA), and American Clinical and Climatological Association (ACCA)

Jerrold Olefsky


  • Professor, Medicine, Division of Endocrinology and Metabolism, University of California, San Diego (UCSD)
  • Associate Dean, Scientific Affairs, UCSD School of Medicine
  • Member of Institute of Medicine and the American Academy of Arts and Sciences

Rohit Loomba


  • Professor, Medicine, Division of Gastroenterology, University of California, San Diego (UCSD)
  • Adjunct Professor, Division of Epidemiology, UCSD
  • Co-chair, Research Award Panel, American Liver Foundation (ALF)
  • Member, American Association for the Study of Liver Diseases (AASLD)
  • Founding Director, UCSD NAFLD Translational Research Unit

Brent Neuschwander-Tetri


  • Professor, Medicine, Division of Gastroenterology and Hepatology, Saint Louis University
  • Member, American Association for the Study of Liver Diseases (AASLD)