First Patient in Phase 1 Trial to be Dosed in November with Enrollment Completion Anticipated by Early Q1 2022
Preclinical Studies of Inhaled Dry Powder Formulation of Niclosamide Showed a Seven-Fold Reduction in Lung Viral Load in Hamsters When Administered 24 Hours After Inoculation with SARS-CoV-2
AUSTIN, Texas, Oct. 28, 2021 (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 it has received approval from Health Canada to begin a Phase 1 clinical trial of a dry powder formulation of niclosamide, an antiviral treatment with potential to address COVID-19 and other infectious diseases.
The Phase 1 study was cleared by Health Canada via a No Objection Letter (NOL) received on October 22, 2021. TFF Pharmaceuticals anticipates the first patient will be dosed in the study in November and that enrollment will be completed by early Q1 2022.
“Early on in the COVID-19 pandemic, niclosamide was identified as a highly promising option for treating severe COVID-19 because of its ability to inhibit cellular processes in the human cell that are required for SARS-CoV-2 replication, thereby inhibiting the production of new viral particles from infected cells,” said Glenn Mattes, CEO of TFF Pharmaceuticals. “Our inhaled niclosamide powder, developed via TFF’s unique Thin Film Freezing technology platform, has been shown to reduce COVID-19 viral load in vivo and offers both direct delivery to the site of infection in the lung and more convenient outpatient administration compared to the IV administered approved antibody COVID-19 treatments. We believe that our preclinical results for inhaled niclosamide will translate to positive outcomes in humans and look forward to initiating the study.”
First approved by the U.S. Food and Drug Administration for use in humans in 1982, niclosamide is an oral anthelmintic drug and is included in the World Health Organization's list of essential medicines1. It has been used to safely treat millions of patients and was recently shown to exhibit potent antiviral activity against SARS-CoV-22, but has limited water solubility as well as low absorption and oral bioavailability. TFF Pharmaceuticals’ Thin Film Freezing technology enables the development of a dry powder formulation of niclosamide that can be delivered directly to the site of viral replication within the lungs by inhalation and administered to patients in an outpatient setting using a standard dry powder inhaler.
“Inhaled niclosamide presents a potentially game-changing solution to addressing ongoing cases of COVID-19, combining a known potent antiviral against SARS-CoV-2 with TFF’s Thin Film Freezing technology to allow direct delivery to the lungs,” said Jay Peters, M.D., Chief of Pulmonary and Critical Care Medicine at the University of Texas Health Science Center at San Antonio and a member of TFF’s Scientific Advisory Board. “Inhaled niclosamide could also serve as an essential treatment for other infectious diseases that affect the lungs. I look forward to seeing the results of the upcoming clinical trial.”
In June 2021, the Company published in vivo pharmacokinetic data in hamsters and rats showing sufficient lung exposure to achieve an antiviral effect. An accompanying GLP inhalation toxicology study showed no toxicity from the inhaled formulation of niclosamide. Recently, the Company completed an 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.3
The Phase 1 study will consist of a Single Ascending Dose (SAD) phase with single inhalation doses of 0.5, 2, and 6 mg in three cohorts of healthy volunteers, including six volunteers that will receive active drug and two that will receive placebo; followed by a Multiple Ascending Dose (MAD) phase in which two cohorts of healthy volunteers will receive doses of 3 and 6 mg, respectively, every 12 hours (BID dosing) for five days. Following results from the Phase 1 trial, the next step will be to initiate a Phase 2/3 study in patients with COVID-19. Per an agreement initiated in August 2020, UNION Therapeutics A/S (UNION) has an option to exclusively license the dry powder formulation of niclosamide.
“We find the pre-clinical work by the TFF team encouraging and appreciate that Thin Film Freezing technology may offer an option to improve the delivery of niclosamide. The use of a dry powder inhaler could help to circumvent the poor oral bioavailability and significantly elevate the local exposure in lungs, the primary site of infection,” said Günter Ditzinger, Chief Technology Officer of UNION Therapeutics. “We are looking forward to the results of the Phase 1 program and continuing the partnership with TFF Pharmaceuticals.”
About UNION Therapeutics A/S
UNION therapeutics is a privately held, multi-asset, clinical stage, pharmaceutical company focused on immunology and infectious diseases. The company is currently working with two complementary chemistry classes, spanning immunology and microbiology with seven programs in clinical development. UNION is headquartered in Copenhagen, Denmark, and is led by an international team combining biotech entrepreneurs and senior pharma executives, with a collective track record of completing more than fifteen product approvals.
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.
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 Comnay 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.
President and CEO
TFF Pharmaceuticals, Inc.
Chief Financial Officer
TFF Pharmaceuticals, Inc.
Investor Relations Contact:
Corey Davis, Ph.D.
Source: TFF Pharmaceuticals, Inc.
WHO. World Health Organization; Geneva: 2007. The Selection and Use of Essential Medicines.
Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Sangeun Jeon, Meehyun Ko, Jihye Lee, Inhee Choi, Soo Young Byun, Soonju Park, David Shum, Seungtaek Kim. DOI: 10.1128/AAC.00819-20
Niclosamide inhalation powder made by thin-film freezing: Multi-dose tolerability and exposure in rats and pharmacokinetics in hamsters. Miguel O. Jara, Zachary N. Warnken, Sawittree Sahakijpijarn, Chaeho Moon, Esther Y. Maier, Dale J.Christensen, John J. Koleng, Jay I. Peters, Sarah D. Hackman Maier, Robert O. Williams III. DOI: 10.1016/j.ijpharm.2021.120701