Many of us will remember that at the start of the pandemic, the breakthrough drugs that transformed the treatment of COVID-19 were hard to come by. The main reason was that these therapies, including mRNA vaccines and monoclonal antibodies, are “biobased” and often unstable at room temperature. Therefore, mRNA vaccines must be stored in ultra-cold freezers, sometimes discarded at the end of the day after reconstitution, and monoclonal antibodies require a hospital environment for administration and cannot be taken home.
Access to these therapies has improved since the start of the pandemic but remains a challenge. Limitations in the formulation of other biologics such as cell and gene therapies have also hampered innovation in these areas. Researchers in the laboratory of Dr. Robert O. (Bill) Williams III, Division Chief and Professor of Molecular Pharmacology and Drug Delivery at the University of Texas at the Austin College of Pharmacy, are advancing platform technology innovative form known as Thin Film Freezing, which could revolutionize the administration, distribution and access to vaccines and therapies.
Thin-film freezing technology, invented by Dr. Williams and his team and perfected by Fort Worth-based TFF Pharmaceuticals, is developed through a well-controlled process that involves rapid freezing and drying of powdered drugs. The technology is unique in that it can convert vaccines and other biologics, which are traditionally delivered in liquid form, into a powder that is more stable at room temperature, eliminating the need for ultra-cold refrigeration and making medicines more accessible globally. by overcoming the logistical challenges of distribution. The technology has broad applicability across all therapeutic areas, including great potential for treating infectious diseases like COVID-19.
Thin-film freezing formulations can be injected like today’s mRNA vaccines, but also have the advantage of being inhaled or administered intranasally, which does not require healthcare professionals to administer. administration. Intranasal formulations offer yet another advantage by directly targeting the mucosal system, harnessing the key mechanisms that trigger the immune defense at the gate where viruses enter the body to more quickly neutralize the virus at its source.
“Oral therapies for conditions aimed at the lungs and respiratory system, such as COVID, are an example of suboptimal drug delivery,” Dr. Williams explained. “The administration of these drugs in their oral form usually requires a large dose to reach the target tissues in the organs and can lead to serious side effects that are sometimes life-threatening. By directly targeting the site of need, our thin-film freezing formulations bypass toxicity and avoid drug interactions.
Dr. Williams and his lab have accumulated a large and growing body of research supporting thin-film freezing as a promising technology for converting vaccines and other treatments into inhaled and intranasal forms. Scientists have also published papers and articles that discuss how thin film freezing compares to other dry powder drug delivery techniques. Dr. Williams’ invention has shown significant benefits as a gentler process for sensitive modalities such as proteins, DNA, mRNA and other biologicals as well as small molecules.
Recent research published on the bioRxiv preprint server has shown how thin layer freezing can be used to develop dry powdered versions of plasmid DNA for optimized delivery to the lungs, while another paper has just been released. published in the International Journal of Pharmacy showed how the intermediate freezing rate of thin-layer freezing resulted in reduced protein denaturation compared to spray freeze-drying (SFD) and conventional freeze-drying. The minimal shear forces of the process also reduce the chances of protein degradation.
Dr. Williams and his team are even applying artificial intelligence and machine learning to improve the efficiency of developing product-specific dry powder formulations. In research presented at this year’s American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 meeting, researchers used a deep learning-based method to estimate aerosol performance based on the properties of the powder made by Thin Film Freezing, specifically using image analysis. The poster, along with another poster from Dr. Williams’ team demonstrating the successful application of thin-film freezing formulations to a number of biologic drugs, including anti-SARS-CoV-2 and anti-SARS-CoV-2 antibodies. -PD1, were selected as part of the “Special Poster Collections” during the meeting.
All of these findings are good news for the future of biologic drug development and could not only support the development of future COVID-19 therapies, but also treat future pathogens as they emerge. TFF Pharmaceuticals is applying this technology to a wide range of treatments, three of which are currently in clinical trials, including a dry powder version of niclosamide, a potent antiviral that has been shown to be effective against all COVID-19 variants tested to date. TFF inhaled niclosamide powder was well tolerated Phase 1 studies with reduced side effects compared to the oral form of treatment.
In addition to developing therapies in-house, TFF Pharmaceuticals works with numerous Big Pharma, academic and CDMO partners and recently opened a new factory in Austin, Texas – located not far from the laboratory of Dr. Williams – which provides additional space to facilitate the scale-up and manufacturing of dry powder materials, including for biologics, and to produce supplies for preclinical studies.
“We are excited to continue to see scientific advancements using the thin-film freezing technology platform for various modalities in the treatment landscape thanks to the innovative work of our collaborators at UT Austin,” commented the CEO of TFF, Glenn Mattes. “Bill and his team’s latest research continues to demonstrate the versatile applications of thin-layer freezing for the development and delivery of biologic drugs. We look forward to continuing our collaboration and sharing more data leveraging our platform in the years to come. »
Although we don’t know what future pandemics might look like, based on recent developments in COVID-19 treatment and the government’s call for alternative methods to vaccinate and treat contagious diseases, it is likely that therapies inhaled and intranasal will play a role. Thin-film freezing technology can better equip industry for future pandemic preparedness and other emerging pathogens or biological threats that may arise. More research from Dr. Williams’ lab will be available soon.