Targeting the SARS-Cov2 spike protein, the mAb in question - AUG-3387 - was isolated from an asymptomatic patient and then identified through Augmenta’s platform in less than two weeks.
TFF said the plan is to develop AUG-3387 as an inhaled therapy for the treatment of COVID-19 disease in individuals already infected with SARS-CoV2 who are at high risk for severe disease but who have not yet been hospitalized, and for the prevention of SARS-CoV2 infection in individuals who are at high-risk for severe disease.
In in vitro preclinical testing, AUG-3387 effectively neutralized SARS-CoV2 and has demonstrated activity against all variant strains tested to date, including the major COVID-19 variants of concern, said TFF.
In November 2020, TFF and Augmenta announced the establishment of a joint development and collaboration agreement to develop novel commercial products incorporating Augmenta’s human-derived monoclonal antibodies (mAbs) for potential COVID-19 therapeutics. TFF also obtained the option to develop two additional Augmenta mAbs for indications other than COVID-19.
These antibodies will be developed utilizing TFF Pharmaceuticals’ Thin-Film Freezing (TFF) technology to manufacture dry powder formulations for inhalation delivery directly to the lungs of patients.
The agreement also includes the development of formulations suitable for parenteral administration, where the TFF dry powder formulations can be reconstituted, potentially mitigating the impacts of cold-chain storage and handling.
Advantages of inhaled therapy
Glenn Mattes, CEO of TFF Pharmaceuticals, told BioPharma-Reporter about the benefits of the inhaled form of monoclonal antibodies:
“The primary advantage of using an inhaled monoclonal antibody (mAb) for a respiratory virus is that you are delivering the neutralizing antibody directly to the site where the virus is replicating and requires binding of the antibody to neutralize its ability to infect new cells. When an antibody is administered systemically, a fraction of the total mAb delivered by IV or Subcutaneous injection reaches the lung and airways. Thus, by delivering the mAb directly to the lung, the amount needed for activity can also be reduced. Furthermore, since the dosing is done without injection, it can be provided for administration at home.
“TFF and Augmenta are confident that using TFF technology will improve both stability of the drug product and safety and efficacy profile by delivering directly to the lungs."
Distribution in developing countries
While current approved vaccines against COVID-19 have allowed for the protection of large portions of the world, distribution is limited in developing countries where cold chain storage is not readily available, he said.
“TFF allows for the development of therapies that are shelf stable, which will eliminate the need for cold-chain storage and broaden the opportunity for global access to COVID-19 therapies. Additionally, TFF formulations can be delivered via a pocket-sized breath actuated inhaler, which does not necessarily require health care professionals for administration.”
The compound will be developed broadly as a mAb therapeutic for all markets.
“By applying thin film freezing to the formulation of AUG-3387 it will enable a product that is not dependent on cold chain distribution and storage. Challenges with distributing vaccines in developing countries – including India, Thailand, Indonesia, Malaysia, Venezuela and countries across Africa – have led to rising cases, leaving the door open for continued virus replication and emerging variants. Through their ongoing collaboration, TFF and Augmenta are committed to enabling global access to therapies against COVID-19 and expect that this will be most needed in countries where extreme cold chain requirements are not feasible."
Human clinical trials
What are the next steps in terms of development of this therapy?
“TFF and Augmenta are continuing to monitor activity of AUG-3387 against emerging variants and will be completing in vivo preclinical efficacy studies in the coming weeks. In parallel, the companies will be scaling up manufacturing, completing toxicology studies and initiating human clinical trials of an inhaled dry powder formulation of AUG-3387 in the coming months," said Mattes.