TFF Pharmaceuticals Announces Safety and Pharmacokinetic Data from Phase 1 Study of Niclosamide Inhalation Powder

Niclosamide Inhalation Powder Well Tolerated with No Serious Adverse Events Across All Subject Cohorts

Current Data Suggests Niclosamide Inhalation Powder is a Promising Antiviral Treatment to Combat COVID-19

FORT WORTH, Texas, April 19, 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 safety and pharmacokinetic (PK) data from its Phase 1 study of Niclosamide Inhalation Powder, which is being developed for the treatment of COVID-19.

“We are very pleased to announce these positive safety and PK data for our Niclosamide Inhalation Powder,” said Glenn Mattes, CEO of TFF Pharmaceuticals. “While vaccines have played a vital role in addressing the COVID-19 pandemic, highly potent and safe antiviral therapeutics are clearly needed to combat this persisting virus. Given niclosamide’s potent activity across multiple variants including Omicron and the ability of the inhaled formulation to more directly target the site of infection in the lungs, we believe the positive safety and pharmacokinetic data announced today help position our Niclosamide Inhalation Powder as a promising new treatment against COVID-19.”

“It is great to follow the progress and success of the TFF Niclosamide Inhalation Powder program,” stated Rasmus Toft-Kehler, Ph.D., Chief Operating Officer and Co-Founder of UNION Therapeutics. “The Phase 1 data coupled with the neutralizing effect of TFF Niclosamide Inhalation Powder against Omicron and other variants demonstrate that this TFF product candidate, when delivered directly to the site of infection with a simple at-home pocket-sized inhaler, has potential to become an essential product for patients and prescribers in the ongoing fight against COVID-19.”

The Company also announced that the study’s Safety Management Committee expressed no questions or concerns about safety and recommended a 6 mg BID (12 mg total daily dose) as safe for progression into Phase 2 testing. More details on the trial design, safety and PK data are included below.

TFF Pharmaceuticals believes the 6 mg dose level of Niclosamide Inhalation Powder is estimated to produce a concentration of >100 μM in the epithelial lining fluid in the lung following delivery as a dry powder, which would be considered highly potent with respect to inhibiting viral replication. A single administration of 6 mg of Niclosamide Inhalation Powder to the lungs provided equal mean maximum drug concentration (Cmax) in the blood as 100 mg delivered as a nebulized spray to the lungs and nasal cavity, as demonstrated in a recent publication.¹

“We found that TFF Pharmaceuticals’ Niclosamide Inhalation Powder was easy to administer and was well tolerated by participants in this Phase 1 study,” said Dr. Eric Sicard, Senior Principal Investigator at Altasciences Phase 1 Unit in Montreal, Quebec, Canada and Principal Investigator for the study. “Considering both niclosamide’s known potency and the safety of this inhalation powder formulation which showed no severe adverse events and no dose limiting toxicities, further clinical testing is clearly merited to determine if the inhaled formulation of niclosamide can be developed as a potential outpatient therapy for COVID-19 patients.”

In February, TFF Pharmaceuticals announced results from recently completed in vitro neutralization and viral replication assays demonstrating that Niclosamide Inhalation Powder completely inhibited viral replication of both the Delta and Omicron variants of SARS-CoV-2.

The results showed that inhaled niclosamide appears to be a more potent inhibitor of SARS-CoV-2 replication, including the Omicron variant. Inhaled niclosamide demonstrated complete inhibition of Omicron replication at only 1 μM, compared to nirmatrelvir and molnupiravir that each showed complete inhibition of the Omicron variant at 2.5 μM.²

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.

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 further development.

Trial design

The Phase 1 trial of Niclosamide Inhalation Powder 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, and 6 mg in three cohorts of healthy volunteers, with each cohort including six volunteers that received active drug and two volunteers that received placebo. The MAD phase consisted of doses of 3 and 6 mg administered twice per day (BID) in two cohorts of healthy volunteers, with each cohort also including six volunteers that received active drug and two volunteers that received placebo.

Safety data

Phase 1 study results show that Niclosamide Inhalation Powder was well tolerated with no dose limiting cough or irritation. In addition, no serious adverse events (SAEs) were reported across the three SAD and two MAD cohorts, which included 6 mg BID as the top dose. One subject experienced an FEV1 drop of approximately 20% that resolved after administration of a bronchodilator.

Pharmacokinetic data

• Niclosamide Inhalation Powder demonstrated a maximal level (Tmax) at the first time point post dose, 0.25 h, for the SAD and MAD cohorts on Day 1 and Day 5. 
• Niclosamide exposure increased with increasing dose and was generally dose proportional with the SAD cohort 0.5 mg dose exhibiting a mean maximum drug concentration (Cmax) of 5.72 ng/mL and the 6 mg dose exhibiting a Cmax of 73 ng/mL. 
• Exposures were slightly higher in the MAD cohorts but were still linear with the 3 mg BID group exhibiting a Cmax on Day 1 of 53.2 ng/mL and the 6 mg BID group exhibiting a Cmax of 112 ng/mL. 
• Total exposure over the dosing interval of 12 hours did not increase with repeat administration from Day 1 to Day 5. 
• The mean half-life of niclosamide after a single inhalation was generally slightly longer than 1 h and did not significantly change (increase or decrease) after repeat administration.

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 engaging patented rapid freezing technology to develop and transform medicines into potent dry powder formulations for better efficacy, safety and stability. The company’s versatile Thin Film Freezing (TFF) technology platform has broad applicability to convert any drug, including vaccines, small and large molecules and biologics, into an elegant dry powder highly advantageous for inhalation, with improved absorption so drugs can also be delivered to the eyes, nose and topically to the skin. TFF has two lead drug candidates in the clinic: Voriconazole Inhalation Powder and Tacrolimus Inhalation Powder, and continues to expand its pipeline by collaborating with a broad array of pharmaceutical companies, academic institutions and government partners to revolutionize healthcare around the globe. The TFF Platform is protected by 120+ patents issued or pending in the U.S. and internationally. To learn more about TFF Pharmaceuticals and its product candidates, visit the Company’s website at https://tffpharma.com.

SAFE HARBOR
This press release contains forward-looking statements regarding TFF Pharmaceuticals, Inc., including the expectations for its continued development of Niclosamide Inhalation Powder for the treatment of COVID-19 infection, Inhaled Tacrolimus and Voriconazole Powders and the benefits of the Company’s TFF platform 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 Inhaled Niclosamide Tacrolimus or Voriconazole Powders or any of its dry powder product candidates, (ii) no drug product incorporating the TFF platform has received FDA pre-market approval or otherwise been incorporated into a commercial drug product, (iii) 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 2021 Annual Report on Form 10-K filed with the SEC on March 24, 2022. 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.

¹https://www.sciencedirect.com/science/article/pii/S2666776221000612?via%3Dihub  

²https://www.nature.com/articles/s41422-022-00618-w   

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