Texas A&M Discovered Inhaled Therapeutic Targeting COVID-19: A Possible Blockbuster?

Texas A&M University Health Science (Texas A&M Health) and the University of Texas MD Anderson Cancer Center report progress on a recent Phase 2 clinical trial testing PUL-042. PUL-042 is an inhaled therapeutic that might provide broad protection against several life-threatening respiratory infections. The two organizations collaborated with the study sponsor, Houston-based biotechnology company Pulmotect, Inc. to perform the trial. Results show that the investigational product shows promising efficacy targeting COVID-19.

TrialSite offers a brief breakdown of the updates of this promising nasal therapy for SARS-COV-2, the virus behind COVID-19. Recently, Lindsey Hendrix writing for Texas A&M University Health Science Center, shared promising updates.

What is the company’s hypothesis?

The inhaled version of an investigational product called PUL-042 stimulates the innate immune system of the lungs, protecting against a wide variety of respiratory pathogens. The scientists behind it think PUL-042 could be directed against all existing and future variants of the COVID-19 virus, as well as future pandemics. Based on the promising results from this trial and remarkable activity in pre-clinical models, PUL-042 also has potential for use in other patient populations.

What is PUL-042

Pulmotect’s lead investigational product, PUL-042 is a clinical-stage inhaled therapeutic that stimulates the innate immune system in the lungs to provide immediate and effective protection in animal models against all major classes of pathogens, the company reports on its website.

The company positions the drug as a first in its class, a synergistic combination of two toll-like receptor agonists. The therapy triggers the innate immune system of the surface of the lungs to inhibit and kill a wide range of respiratory pathogens.

What is the science behind targeted therapy?

Pulmotect describes on its website that when microbes (including viruses) land on the epithelial cells of the lung lining, they are destroyed on-contact by antimicrobial peptides and reactive oxygen species (ROS), which are released by epithelial cells. 

Activation of the innate immune system also triggers a response from the adaptive immune system. In preclinical models, the company reports that PUL-042 demonstrates protection against a broad range of respiratory pathogens in preclinical models, including the coronaviruses that cause MERS and SARS. 

With robust pre-clinical protection shown against multiple pathogens even in models with immunocompromised animals and favorable tolerability demonstrated in clinical trials to date, PUL-042 could offer a broad-spectrum therapy for responding to epidemics and pandemics including current and future SARS-CoV-2 variants and it has potential use for multiple other indications.  

So, to summarize, the innate immune system represents the human body’s first line of defense against invading pathogens. When germs and foreign substances enter the body, the innate immune system responds quickly to fight them off. PUL-042, the first drug in its class, is composed of two small synthetic molecules and works by stimulating specific innate immune receptors in the lung lining within minutes. Protection only lasts for about three to five days, but it can be repeatedly administered once every few days.

A Texas A&M discovery

PUL-042 was discovered by Magnus Hӧӧk, a distinguished professor at the Texas A&M Health Institute of Biosciences and Technology, and Dr. Burton Dickey, chair of the pulmonary department at MD Anderson Cancer Center.

“The lungs are the point of entry for many viruses and bacteria. By activating the innate immune defense of the lungs, PUL-042 can provide effective protection against a wide range of deadly pathogens,” Hӧӧk said. “We believe that if we had this therapy available in December of 2019, we could have prevented the COVID-19 pandemic and avoided the 6 million lives lost.”

What are the results from recent Phase 2 clinical trial?

Results from a recent phase 2 clinical trial conducted through Houston-based biotechnology company Pulmotect, Inc. showed that it may be an effective treatment for COVID-19 and other respiratory illnesses.

Patients in the trial treated with inhaled PUL-042 showed improvement in cough and shortness of breath more quickly than those who received a placebo treatment. According to this venture founded in 2007, participants in this study experienced fewer hospitalizations and intensive care admissions.

The study randomized 101 patients with early diseases in the United States. The sponsor reported the investigational product was “well tolerated when administered as a single dose on Day 1, Day 3, and Day 6 of the trial with 28 days of patient follow up.”

In a recent press release, the company shared that two of the study patients were hospitalized with deterioration from pre-treatment of two or more points on the Ordinal Scale for Clinical Improvement. A total of three (3) patients were hospitalized due to progressing COVID-19, two in the placebo group—both required intensive care treatment for 5 days and 9 days, and one patient in the study drug group was hospitalized for four days. They did not require intensive care.

Note this data is not peer-reviewed yet, so cannot be cited as a certainty.

Clinical Trials Attracts DoD Funding

The Food and Drug Administration approved Pulmotect to begin two human clinical trials of PUL-042 last year, one focused on protection and another on treatment for COVID-19. Funding support for the trials was provided by the U.S. Department of Defense.

The company announced back in January 2021 that it received $6 million to conduct two clinical trials.

Broad Antiviral Applicability?

According to Dr. Colin Broom, CEO of  Pulmotect “We have not found a virus PUL-042 cannot work against in the lungs, in animal studies.” Broom continued “As an easily administered inhaled therapy, PUL-042 could have value in reducing the impact of COVID-19 irrespective of the development of further variants. It also has potential utility for other patient populations which we plan to explore, including immunosuppressed cancer patients.”

The Sponsor

Houston-based Pulmotect was founded by Hӧӧk and colleagues at Texas A&M to commercialize this intellectual property. The biopharma develops products that boost the innate immune system to protect against a wide range of lung infections.

Formed in 2007, according to Crunchbase, Pulmotect has raised at least $28.4 million.

About Texas A&M Health Center

Part of Texas A&M University, Texas A&M Health Center offers health professions research and education in a range of categories from biomedical sciences to medicine and dentistry, and pharmacy. The academic medical center was established in 1999 as an independent institution of the Texas A&M University System—receiving accreditation in December 2002.

The center includes the Institute of Biosciences and Technology at Houston. Texas A&M offers extensive research capability.