About RSV

RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under one year of age in the U.S. and a significant cause of respiratory illness in older adults and immunocompromised individuals.

According to a study published in The Lancet, globally, there are an estimated 33 million cases of RSV annually in children less than 5 years of age, with about 3 million hospitalized and up to approximately 120,000 dying each year from complications associated with the infection.



About hMPV

Discovered in 2001, hMPV is in the same paramyxovirus family as RSV. It is the second most common cause of lower respiratory tract infection in children of less than five years of age (behind RSV) and is associated with greater than 20,000 hospitalizations in the U.S every year. It also presents a significant health challenge in the elderly and immunocompromised individuals with more than 100,000 hospitalizations annually.



About SARS-CoV-2

SARS-CoV-2, initially called 2019-nCoV, is a novel human coronavirus renamed after because of its significant homology to SARS-CoV. It is an enveloped, positive sense, single strand RNA virus with a genome size of almost 30KB, which encodes both structural proteins such as the spike glycoprotein responsible for interaction with cell receptor and viral entry and non-structural proteins such as 3C-like protease, papain-like protease and RNA-dependent RNA polymerase that are essential for viral replication.

Respiratory Syncytial Virus (RSV)

RSV is a virus that infects the lungs and represents a serious unmet medical need in infants and children, as well as immunocompromised individuals and the elderly. RSV is the most common cause of bronchiolitis and pneumonia in children under the age of one. In a large United States based study published in the New England Journal of Medicine, RSV infection in children was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of pediatric office visits for acute respiratory infections in a six month timeframe. Though a prophylactic monoclonal antibody-based treatment (palivizumab) is available for those considered at high risk for RSV infection, this study found that most young children affected by RSV infection were previously healthy, and thus would not normally be considered for prophylaxis. Currently, no safe and effective treatments exist for RSV infection.

Enanta is developing EDP-938, a potent non-fusion inhibitor of both RSV-A and RSV-B activity, as its first candidate for RSV. Top-line results of a Phase 2 challenge study of EDP-938 showed that EDP-938 achieved highly statistically significant (p<0.001) reduction in viral load and resolution of clinical symptoms compared to placebo. Preclinical data also demonstrated a rapid reduction in viral load, below the limits of detection in animals treated with EDP-938.

EDP-938, which has Fast Track Designation from the FDA, is being evaluated in a broad clinical development program, consisting of three trials. RSVP, a Phase 2b study in adult outpatients with community acquired RSV; RSVTx, a Phase 2b study in in adult hematopoietic cell transplant recipients; and RSVPEDs, a Phase 2 study in pediatric RSV patients, are all ongoing.

Enanta also has an ongoing RSV L-inhibitor discovery initiative that includes potent nanomolar leads active against both RSV-A and RSV-B. An RSV-L-inhibitor is not expected to have cross-resistance to other classes of inhibitors, and therefore can potentially be used alone or in combination with agents targeting other RSV mechanisms, such as EDP-938.


Human Metapneumovirus (hMPV)

hMPV is a significant cause of respiratory tract infections (RTIs), particularly in children, the elderly, and immunocompromised individuals. It is the second most common cause of lower respiratory tract infection in children of less than five years of age (behind RSV), associated with greater than 20,000 hospitalizations in the U.S every year. It also presents a significant health challenge in the elderly and immunocompromised individuals with more than 100,000 hospitalizations annually. Children hospitalized with hMPV infection, as compared to those without, are more likely to be diagnosed with pneumonia or asthma, to require supportive care, and to have longer stays in the intensive care unit. In adults, hMPV infection accounts for up to 13.2% of hospitalizations with acute RTIs, similar to those of RSV and influenza. In one prospective study, high morbidity rates were reported with hMPV infections in hematologic malignancy patients and hematopoietic cell transplant recipients developing lower RTIs (34%), and patients who progressed to lower RTIs experienced higher mortality rates (27%). Currently there is no vaccine or specific antiviral treatment available for hMPV thereby creating a significant unmet medical need.

Enanta has discovered a series of novel small molecular inhibitors of hMPV with nanomolar EC50 in vitro. These compounds are currently under lead optimization, with the goal of identifying a potential drug candidate for preclinical and clinical proof-of-concept studies.


SARS-CoV-2

The pandemic coronavirus disease COVID-19 is caused by the infection of a novel human coronavirus, severe acute respiratory syndrome-coronavirus (SARS-CoV-2). This is only the seventh known coronavirus that infects humans. Some of the previously identified strains such as HCoV-229E and HCoV-OC43 have been circulating in humans for years but usually cause only very mild symptoms. Two recent outbreaks with the highly pathogenic SARS-CoV and MERS-CoV were quickly suppressed through rigorous infection control.

In August 2021, Enanta announced that it had nominated EDP-235, its lead oral protease inhibitor specifically designed for the treatment of COVID-19. Enanta expects to initiate a Phase 1 single and multiple ascending dose study to evaluate the safety, tolerability, and pharmacokinetics of EDP-235 in healthy volunteers in early 2022.

EDP-235 potently and selectively inhibits SARS-CoV-2 replication in multiple cellular models, including primary human airway epithelial cells, with an EC90 of 33nM. EDP-235 retained activity against protease enzymes from currently circulating SARS-CoV-2 variants. Importantly, EDP-235 has excellent lung distribution preclinically and demonstrates properties supportive of once daily oral dosing. Furthermore, EDP-235 has shown activity against other coronaviruses, providing the opportunity to potentially treat other infections that may emerge in the future.

While vaccines and antibody therapeutics in development today target the viral spike protein, EDP-235 has been specifically designed to target conserved regions in the active site of a viral enzyme essential for SARS-CoV-2 replication. Thus, Enanta does not expect mutations in the spike protein to affect the activity of EDP-235 and is encouraged by the promising preclinical data generated to date.

For an overview of our research, including our licensed products, please see Our Pipeline.