TFF Pharmaceuticals Provides Update on Clinical Development Programs

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 provided an update on the clinical development progress of its Voriconazole Inhalation Powder and Tacrolimus Inhalation Powder products.

Voriconazole Inhalation Powder

The Phase 1 clinical trial of Voriconazole Inhalation Powder for the treatment of invasive pulmonary aspergillosis (IPA), an inhaled dry powder version of voriconazole, has been successfully completed and comprehensive safety and pharmacokinetic data is now available following delivery of the clinical study report. Voriconazole is recommended as the first line treatment for IPA according to the Infectious Disease Society (IDSA) - Practice Guidelines for the Diagnosis and Management of Aspergillosis (2016), but voriconazole is also associated with significant drug-drug interactions and toxicities.

Through completion of the Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) cohorts, TFF demonstrated that doses of 10, 20, 40, and 80 mg could be delivered twice daily using a dry powder inhaler device with no significant adverse events. There was no evidence of treatment-related or dose-related trends in the reporting of treatment emergent adverse events, throughout the study. No subjects experienced any dose limiting toxicity events during the study.

“This Phase 1 clinical trial safety data has dramatically exceeded our expectations for Voriconazole Inhalation Powder,” stated Glenn Mattes President and CEO of TFF Pharmaceuticals, “The ability to reach blood levels greater than two-fold higher than those shown to clear complex IPA infections provides confidence that dosing patients with the 80 mg dose has a high probability of efficacy without adverse events, and could establish our product as the leading therapy for IPA.”

Voriconazole Inhalation Powder is being developed by TFF to treat IPA with the goal of enhancing efficacy through more efficient delivery of the drug to the lung relative to the oral or intravenous forms of Vfend^®, where blood levels can reach greater than 5,000 ng/mL in order to deliver sufficient voriconazole to the lung. However, drug levels greater than 5,000 ng/mL in the blood are associated with severe adverse events including liver kidney and visual toxicities.

Evaluation of the pharmacokinetic profile of the Voriconazole Inhalation Powder demonstrated that mean peak plasma voriconazole levels reached concentrations of 227 ng/mL following repeated dosing at 80 mg twice daily for 7 days, without any reports of adverse events.

“Now that we have the final data from this Phase I trial, we have confidently selected the 80 mg dose of Voriconazole Inhalation Powder for our upcoming pivotal trial, where we will be comparing it to the oral form of voriconazole,” said Mattes. “We expect to continue to see a more favorable adverse events profile in the inhalable arm, and equal to or greater efficacy when compared to oral voriconazole.”

“We’re excited for the future development of Voriconazole Inhalation Powder because we feel it can achieve our target product profile of having better efficacy than oral voriconazole by delivering a greater amount of drug directly to the site of the infection, and of having fewer adverse effects than voriconazole that is dosed systemically to achieve drug levels able to reach the lung,” said Mattes.

In addition to the release of the final data from the Phase 1 clinical trial, TFF is continuing to enroll asthma patients in a Phase 1b study to understand if the Voriconazole Inhalation Powder is likely to trigger bronchospasm in patients with hyperreactive airway disease. Other inhaled anti-infective drugs have demonstrated this effect and require pretreatment with a bronchodilator prior to dosing. TFF is completing this reactive airway study to guide the clinical practice in patients with hyperreactive airway diseases (Asthma and COPD). The data from this study and from the completed healthy normal Phase 1 study will lead to the initiation of a pivotal study of Voriconazole Inhalation Powder, which will begin enrolling patients later this year.

Tacrolimus Inhalation Powder

TFF Pharmaceuticals also reports that dosing of the Single Ascending Dose portion of the Phase 1 study of Tacrolimus Inhalation Powder has been successfully completed and the Multiple Ascending Dose portion is ongoing. The SAD portion of the study indicated that TFF’s Tacrolimus Inhalation Powder was able to reach therapeutic blood levels of 5-16 ng/mL in all patients from a single inhaled dose of 5 mg of Tacrolimus Inhalation Powder, without significant adverse events.

“The ability to efficiently reach therapeutic drug levels with our Tacrolimus Inhalation Powder following just a single dose without any significant adverse events is very significant and ahead of our expectations,” said Mattes. “Achieving therapeutic blood levels efficiently, with low doses of the inhaled powder, suggests that our product may have application beyond lung transplant, potentially in heart, kidney and liver transplant patients.”

In clinical practice, tacrolimus blood levels are monitored and controlled to achieve blood levels that are known to be associated with efficacious immunosuppression, while not elevating the blood concentration to levels associated with toxicities. For lung transplant patients, therapeutic drug monitoring (TDM) is used to achieve maintenance tacrolimus levels from 5-15 ng/mL after transplant to prevent acute allograft rejection¹. The Phase 1 study of Tacrolimus Inhalation Powder utilized TDM measurements to determine when a sufficient dose level had been reached.

“We look forward to the additional safety and pharmacokinetic data that will be produced during the dosing of the remaining MAD cohorts as we complete this study and prepare for pivotal trials of this promising therapy,” concluded Mattes. “We expect to have final safety data completed by the end of the second quarter of 2021, enabling us to move into the pivotal trial phase in the second half of the year.”

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 Tac-Lac 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.

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 voriconazole 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 versions of voriconazole or tacrolimus, (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, (iv) the risk that the Company will not be able to conclude a long-term commercial agreement with any third-party, and (v) those other risks disclosed in the section “Risk Factors” included in the Company’s 2019 Annual Report on Form 10-K filed with the SEC on March 26, 2020. 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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