Lazo Response to Weiss et al. (Re: DOI: 10.1089/scd.2020.0114)

We acknowledge the concerns raised by Drs. Weiss, Lim, Rohde, Witwer and Giebel regarding availability of ExoFlo characterization data to enable a deeper understanding of the extracellular vesicle product and the mechanism of action required to produce the results we observed in our severe COVID-19 patients. We again wish to state that the purpose of the initial paper was to report results and outcomes of our clinical study and not to provide an initial characterization of Direct Biologics' product. This study was performed independently of Direct Biologics and under our hospital's institutional review board (IRB) and data safety monitoring board (DSMB). We have communicated with the Direct Biologics scientific team regarding the authors interest for them to share the ISEV prescribed characterization data for an EV-based biologic. This was their reply.

“As we stated in our response to Lim et al, Direct Biologics understands well the importance of product characterization to achieve the requisite requirements for establishment of product identity, purity, strength, and safety. Prior to our IND submission we had undertaken extensive efforts to satisfy the US FDA's CMC submission requirements for the characterization of the protein, RNA, and EV content of ExoFlo, which included in-process as well as multiple lot, drug product characterizations. To do this we used multiple approaches and methods including both array and sequencing based ‘omics, nanoparticle tracking analysis, traditional transmission electron microscopy, fluorescent antibody based methods using NanoView nanoparticle analysis and STED microscopy to characterize EV tetraspanin content within the product as well as within the source cells from which the product is derived. The company is compiling this information to address academic interest in our product and aid in the understanding of how ExoFlo may be effective in treating COVID-19 patients with moderate and severe ARDS symptoms. Our current phase II, double blinded, placebo controlled trial (EXIT COVID-19) is designed to obtain the Level I evidence of efficacy to support a phase III trial in the near future. It is our hope that upon reviewing our future published characterization data, that new doors of collaboration will be opened to allow all of us to comprehend and bring to fruition the potential of secretome and exosome based therapeutics more fully to mitigate this SARS-CoV-2 pandemic and support future therapies.”