PharmaShots Interview: TFF Pharmaceuticals’s Glenn Mattes Shares Insights on the Thin Film Freezing Technology

In an interview with PharmaShots, Glenn Mattes, President, CEO, and Director at TFF Pharmaceuticals share his views on the thin film freezing technology for the development of vaccines and therapeutics against multiple infectious diseases including IPA

Shots:

The company focuses on developing and commercializing innovative drug products based on its patented TFF technology platform including the development of vaccines and therapeutics against multiple infectious diseases
TFF technology uses a rapid freezing process & is designed to effectively convert any therapy including vaccines, small molecules, and biologics into a fine dry powder with advantageous properties for inhalation
Voriconazole is used to treat fungal infections which are currently administered as an oral treatment and recommended as a 1L antifungal treatment for IPA

Tuba: Can you tell us about Invasive Pulmonary Aspergillosis (IPA)?

Glenn Mattes: Aspergillus is a type of fungus (mold) commonly found in the environment both indoors and outdoors. While the inhalation of Aspergillus spores does not normally cause sickness, people with weakened immune systems caused by chemotherapy, immunosuppressive drugs, and chronic lung disease are at higher risk of developing Aspergillosis infections.

Invasive pulmonary aspergillosis (IPA) can occur in patients with predisposing risk factors, including transplants, cancer, and viral infections. Pulmonary fungal infections, such as COVID-19 Associated Pulmonary Aspergillosis (CAPA), are also increasing due to the use of corticosteroids for the treatment of COVID-19, as corticosteroids predispose patients to Aspergillus infections.

Asthma patients, along with a portion of patients with Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disease (COPD), currently represent a proportion of people with IPA and Allergic Broncho Pulmonary Aspergillosis (ABPA) and other fungal infections due to impaired mucociliary clearance, which allows Aspergillus spores to become trapped and grow in the mucus that builds up in their lungs. ABPA can affect up to 15% of CF patients and 2.5% of asthma patients. Of the 4.8 million asthma patients who have ABPA, 400,000 are estimated to have chronic pulmonary aspergillosis.

Tuba: How is IPA classically treated?

Glenn Mattes: Voriconazole, which is used to treat a variety of fungal infections, is currently administered as an oral treatment and is recommended as the first-line antifungal treatment for IPA, according to the Infectious Disease Society (IDSA). However, orally administered voriconazole requires a high dosage to produce clinical benefits, resulting in an increased risk of severe adverse effects, such as liver damage and visual disturbances. Oral administration also causes drug levels of concomitant medications to be altered because voriconazole inhibits the enzymes that metabolize these other drugs. This creates a situation where drug levels of medications that are affected by voriconazole can cause additional toxicity.

Tuba: How can Thin Film Freezing (TFF) technology improve the treatment of IPA?

Glenn Mattes: TFF technology uses a rapid freezing process that is designed to effectively convert any therapy (including vaccines, small molecules, and biologics) into a fine dry powder with advantageous properties for inhalation.

TFF technology can convert voriconazole into an inhalable dry powder, which can be delivered directly to the lung where it is needed using a pocket-sized inhaler. This form of treatment bypasses the gut, potentially improving safety by reducing systemic toxicities, and may also lead to greater efficacy by reducing drug-drug interactions and administering at a lower dose than classic orally administered voriconazole.

Tuba: As the drugs will be directly delivered to the respiratory mucosal system of the lungs, tell us about their suitability to the patients.

Glenn Mattes: TFF’s Voriconazole Inhalation Powder (TFF VORI) delivers voriconazole directly to the respiratory tract, the site of infection, to yield faster onset of action at a reduced dose and through convenient administration. As noted above, patients with asthma and other lung conditions are at a higher risk for fungal infections and thus represent a significant portion of patients that may benefit from this treatment. Early evidence suggests that TFF’s treatment is well tolerated in asthma patients.

Tuba: Can you tell us about TFF’s clinical trials of TFF VORI, including the Phase 1b study which recently completed dosing?

Glenn Mattes: In November 2021, TFF completed dosing in a Phase 1b study of TFF VORI in mild to moderate asthma patients. Patients with asthma, and a portion of patients with cystic fibrosis and chronic obstructive pulmonary disease (COPD), are susceptible to IPA infections but also tend to have hyperreactive airways, which can trigger bronchospasm – in which the airways contract similar to an asthma attack – following administration of inhaled drugs by inhalation. As a result, many inhaled therapies, including approved antibacterial treatments, require bronchodilator pretreatment for safe administration in asthma patients or in people with CF and COPD. Initial data showed TFF VORI is well tolerated in asthma patients, supporting progress to a Phase 2 study including patients with asthma.

The completed Phase 1b trial is evaluating safety, pharmacokinetics, and induction of bronchospasm in cohorts of asthma patients receiving doses of 40 and 80 mg, respectively, twice daily for five days. In each cohort of eight patients, six subjects received treatment and two received placebo.

Previous topline results in healthy volunteers demonstrated that dosing of TFF VORI twice daily for seven days was well tolerated at doses up to 80 mg with no clinically significant adverse findings or changes in pulmonary function. We expect to report additional data from the study in the coming months and to initiate the Phase 2 trial in due course.

Tuba: What other indications and/or infectious diseases have TFF has been working on and exploring to assess Thin Film Freezing technology?

Glenn Mattes: TFF technology is being applied to the development of vaccines and therapeutics against multiple infectious diseases to transform medicines for better efficacy, safety, and stability. We are pursuing multiple clinical programs and partnerships with academic, pharma, and government organizations to reach this goal. Highlights of current programs include:

TFF is developing a shelf-stable treatment for COVID-19 in collaboration with Augmenta Bioworks. AUG-3387 is an inhalable monoclonal antibody treatment against COVID-19 that is effective against multiple variants of concern, including the Delta variant, and can be delivered directly to the lung where the virus replicates to neutralize infection. In October 2021, we published data showing the dry powder form of AUG-3387 successfully neutralized SARS-CoV-2 infection and reduced viral load in hamsters when treatment was initiated 24 hours after infection with SARS-CoV-2.
TFF is advancing a dry powder formulation of niclosamide, an oral anthelmintic drug that has shown potent antiviral activity against SARS-CoV-2, in partnership with UNION Therapeutics. In October 2021, we received approval from Health Canada to begin a Phase 1 clinical trial of a dry powder formulation of niclosamide, for which we began dosing in November.
TFF is developing an inhaled formulation of tacrolimus to improve immune rejection following lung transplant. Tacrolimus is the current standard of care for reducing immune rejection from an organ transplant, but high dosages of the oral formulation can cause severe toxicities including Acute Kidney Injury (AKI). Results from TFF’s completed Phase 1 study of Inhaled Tacrolimus Powder, first announced in September 2021, indicate that the inhaled formulation achieves the appropriate balance of local and systemic concentrations for immunosuppression at the site of a lung transplant at a low dose that minimizes the risk of kidney toxicity.
In addition to these programs, TFF is also collaborating with various academic institutions to develop TFF-formulated compounds that provide long-lasting protection against a wide variety of viruses, including an ongoing project to develop a dry powder universal influenza vaccine. TFF also has partnerships with government and military institutions to develop therapeutics and vaccines that can be transported and administered with ease for future pandemic preparedness.

References

Aspergillosis | Types of Fungal Diseases | Fungal Diseases | CDC
Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis–state of the art: Cystic Fibrosis Foundation Consensus Conferenceexternal icon. Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64.
Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults.external icon Med Mycol. 2013 May;51(4):361-70
Barnes, P. D., & Marr, K. A. (2006). Aspergillosis: spectrum of disease, diagnosis, and treatment. Infectious disease clinics of North America, 20(3), 545–vi. https://doi.org/10.1016/j.idc.2006.06.001
Singh, N., & Bhalodiya, N. H. (2005). Allergic fungal sinusitis (AFS)--earlier diagnosis and management. The Journal of laryngology and otology, 119(11), 875–881. https://doi.org/10.1258/002221505774783412

Source: Medical News Today

About Author: Glenn Mattes is the President, CEO, and Director of TFF Pharmaceuticals. He has more than 30 years of business leadership, global therapeutics development expertise, and executive management experience. He holds a BS from the City University of New York.