TFF Pharmaceuticals Announces Inhaled Niclosamide Significantly Inhibits Viral Replication of the Omicron Variant of SARS-CoV-2

Inhaled Niclosamide Demonstrates Potent Activity Against Omicron Variant

Dosing of Inhaled Niclosamide Estimated to Produce Concentrations in Excess of Effective Dose

Expecting to Complete Phase 1 Safety and Pharmacokinetic Data of Inhaled Niclosamide by End of 1Q’22

AUSTIN, Texas, Feb. 24, 2022 (GLOBE NEWSWIRE) — TFF Pharmaceuticals, Inc. (NASDAQ: TFFP), a clinical-stage biopharmaceutical company focused on developing and commercializing innovative drug products based on its patented Thin Film Freezing (TFF) technology platform, today announced that results from its recently completed in vitro neutralization and viral replication assays indicate that the Company’s inhaled niclosamide product candidate completely inhibits viral replication of both the Delta and Omicron variants of SARS-CoV-2.

Compared to data from previously published studies, the results demonstrate that inhaled niclosamide appears to be the most potent inhibitor of SARS-CoV-2 replication, including the Omicron variant. More specifically, nirmatrelvir and molnupiravir each showed complete inhibition of the Omicron variant at 2.5 μM.¹ In the studies announced today by TFF Pharmaceuticals, inhaled niclosamide demonstrated complete inhibition of Omicron at only 1μM. Results from these studies also confirm previous findings² which validated the potent antiviral efficacy of niclosamide in a human airway model.

In a Phase 1 study, TFF Pharmaceuticals has already demonstrated that a 6 mg BID dosing of inhaled niclosamide is well tolerated. Importantly, the 6 mg dose level is estimated to produce a concentration of >100 μM in the epithelial lining fluid in the lung following delivery as a dry powder.

“The data demonstrating that niclosamide inhibits viral replication of the Omicron variant is proof of concept for the activity of the drug against SARS-CoV-2,” said Dr. Michael Saag, Professor of Medicine at UAB School of Medicine and Member of the TFF Pharmaceuticals Scientific Advisory Board. “Niclosamide’s mechanism of action, which inhibits human pathways involved in viral replication, restricts development of mutations in the viral genome. This results in much less opportunity for the emergence of resistance to drugs that target the virus. These exciting results further validate the approach that TFF is pursuing for treatment of respiratory infections by delivering a host-directed antiviral directly to the lung using a dry powder inhaler device. Additionally, the TFF niclosamide powder is temperature stable, enabling broad accessibility around the globe.”

“These supportive data increase our confidence that inhaled niclosamide could become an important new therapeutic to combat COVID-19 infection,” said Glenn Mattes, CEO of TFF Pharmaceuticals. “Inhaled niclosamide’s demonstrable potency at such low concentrations should enable us to deliver reduced doses of the drug directly to the lung without compromising antirviral activity, thereby conferring a major potential advantage with respect to safety and tolerability. As more pathogenic variants of the SARS-CoV-2 virus emerge, it is essential that potent antiviral therapies are available to help significantly reduce the morbidity and mortality associated with this infection, particularly in the most vulnerable populations who suffer from cardiopulmonary deficiencies.”

As noted earlier in the year, TFF Pharmaceuticals has completed enrollment in the Phase 1 study of its inhaled formulation of niclosamide for the treatment of COVID-19 and expects to release safety and pharmacokinetic data for the trial by the end of 1Q’22.

“We are encouraged by the news from TFF that niclosamide neutralizes the Omicron variant,” stated Rasmus Toft-Kehler, Ph.D., Chief Operating Officer and Co-Founder of UNION Therapeutics. “The ability to deliver this antiviral directly to the site of infection with a simple at-home pocket-sized inhaler could be a game changer in the fight against COVID-19.”

Originally approved as an oral anthelmintic drug by the U.S. Food and Drug Administration in 1982, niclosamide was recently shown to exhibit potent antiviral activity against SARS-CoV-2 but has limited water solubility as well as low absorption and bioavailability when administered orally. TFF Pharmaceuticals intends to utilize its Thin Film Freezing technology to produce an inhaled formulation of niclosamide to target the lungs directly where SARS-CoV-2 infection occurs, avoiding gastrointestinal side effects and overcoming the bioavailability limitations of systemic administration. TFF previously completed a preclinical in vivo efficacy study that showed a seven-fold reduction in lung viral load in a hamster model when dry powder niclosamide was administered 24 hours after inoculation with SARS-CoV-2 when the disease was already severe.

The Phase 1 trial consisted of a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) phase. The SAD phase of the trial consisted of single inhalation doses of 0.5, 2.0, and 6.0 mg in three cohorts of healthy volunteers, including six volunteers that will receive active drug and two that will receive placebo, while the MAD phase consisted of doses of 3.0 and 6.0 mg administered twice per day (BID) for 4.5 days (9 total doses). The Safety Management Committee expressed no questions or concerns about safety and has recommended the 6.0 mg BID (12 mg total daily dose) as safe for progression into Phase 2 testing.

UNION Therapeutics A/S has an option to exclusively license the dry powder formulation of niclosamide in which case it would take over responsibility for development.

¹https://www.nature.com/articles/s41422-022-00618-w
²https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260958

About TFF Pharmaceuticals’ Thin Film Freezing Technology Platform
TFF Pharmaceuticals’ Thin Film Freezing (TFF) platform was designed to improve the solubility and absorption of poorly water-soluble drugs and is particularly suited to generate dry powder particles with properties targeted for inhalation delivery, especially to the deep lung, an area of extreme interest in respiratory medicine. The TFF process results in a “Brittle Matrix Particle,” which possesses low bulk density, high surface area, and typically an amorphous morphology, allowing the particles to supersaturate when contacting the target site, such as lung tissue. Based upon laboratory experiments the aerodynamic properties of the particles are such that the portion of a drug deposited to the deep lung has the potential to reach as high as 75 percent.

About TFF Pharmaceuticals
TFF Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative drug products based on its patented Thin Film Freezing, or TFF, technology platform. Early testing confirms that the TFF platform can significantly improve the solubility and absorption of poorly water-soluble drugs, a class of drugs that comprises approximately one-third of the major pharmaceuticals worldwide, thereby improving their pharmacokinetics. TFF Pharmaceuticals has two lead drug candidates: Voriconazole Inhalation Powder and Tacrolimus Inhalation Powder. The Company plans to add to this pipeline by collaborating with large pharmaceutical partners. The TFF Platform is protected by 42 patents issued or pending in the US and internationally. To learn more about TFF Pharmaceuticals and its product candidates, visit the Company’s website at https://tffpharma.com.

About UNION Therapeutics A/S 
UNION Therapeutics is a privately-held, multi-asset, clinical stage, biotechnology company focused on immunology and infectious diseases. The company is currently working with two complementary chemistry classes, spanning immunology and microbiology with six programs in clinical development. UNION is headquartered in Hellerup, Denmark, and led by an international team combining biotech entrepreneurs and senior pharma executives, with a track record of developing and launching more than fifteen marketed drugs. Read more at www.uniontherapeutics.com.

SAFE HARBOR
This press release contains forward-looking statements regarding TFF Pharmaceuticals, Inc., including the benefits of the Company’s TFF platform and its dry powder versions of niclosamide, and the Company’s plans to add to its existing pipeline of product candidates. Those forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause actual results to differ materially. Among those factors are: (i) the risk that the Company may not be able to successfully conclude clinical testing or obtain pre-market approval of its dry powder version of niclosamide, (ii) assuming that the Company is successful in its clinical testing of niclosamide, that the Company will be able to enter into a licensing arrangement with UNION on terms favorable to the Company, if at all, (iii) no drug product incorporating the TFF platform has received FDA pre-market approval or otherwise been incorporated into a commercial drug product, (iv) the Company has no current agreements or understandings with any large pharmaceutical companies for the development of a drug product incorporating the TFF Platform, (v) the risk that the Company will not be able to conclude a long-term commercial agreement with any third-party, and (vi) those other risks disclosed in the section “Risk Factors” included in the Company’s 2020 Annual Report on Form 10-K filed with the SEC on March 10, 2021. TFF Pharmaceuticals cautions readers not to place undue reliance on any forward-looking statements. TFF Pharmaceuticals does not undertake, and specifically disclaims, any obligation to update or revise such statements to reflect new circumstances or unanticipated events as they occur, except as required by law.

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