A Guide to Investing/Buying "Perfect Exosomes"

The Crowley Center for Regenerative Biotherapeutics, LLC, (dba ATVentureCenter.com) headquartered in Rochester, NY has been investing in a wide range of regenerative medical and biotherapeutic technologies since November 2017. In fact, today is our 7th anniversary.

Over these past seven years as both researchers, investors and venture builders, we have focused most of our investments upon a single source of human umbilical cord tissue for all our investments called "Wharton's jelly."

We it is fair to say that we are perhaps one of the leading independent commercial sources of information about Wharton's jelly advanced technology biotherapeutics product led by a top tier research and development team led by Dr. Michael Heke our CSO and Dr. Carla Mazzeo our Director of Research & Development. Our clinical laboratory team in the best team in the industry.

Our team of scientists provides us with the information we need to make investments, and build ventures, in this fast-growing field of regenerative biotherapeutics.

Of the various categories of regenerative biotherapeutics, the science of Exosomes is, in our view, the fastest growing and most exciting areas of therapeutic investment.

Based upon our many years of investing in this sector, we have chosen to invest only in Wharton's Jelly exosome regenerative biotherapeutics. Here is a small bit of information about this incredible source of Wharton's jelly regenerative biotherapeutics

Wharton's jelly is a gelatinous tissue found in the umbilical cord that protects and supports the umbilical vessels during fetal development:?

• What it is: A mucous connective tissue that contains fibroblasts, macrophages, and mesenchymal stromal cells (MSCs)
• What it does: Cushions and protects the umbilical vessels from compression, torsion, and bending. It also is the underlying tissue source for Wharton's Jelly MSC derived Exosomes.
• What it's made of: Primarily composed of hyaluronic acid and chondroitin sulfate, and also contains collagen and sulfated proteoglycan. It is also abundant in MSCs that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. T.
• Research: Wharton's jelly is a richest source of MSCs (the "Gold Standard" of MSCs), which have been extensively studied for their potential to treat a variety of medical condition and as the source for exosomes that also have tremendous potential to not only treat a wide variety of medical conditions, but also, as a way to potentially de-age skin and regrow hair.

Given the wide range of exosome investment opportunities, we thought that we would share a bit of our research findings that have driven our three most recent investments.

We have been presented multiple investment opportunities in the Exosome segment over the past several months that required us to do some significant additional due diligence before making our investment decisions.

Exosomes are tiny (nano-scale) extra-cellular lipid barrier sacs that carry a cargo of proteins, mRNA, and RNA from one cell to another. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. They are released by most cells, including MSCs, and can also be found in bodily fluids like blood, urine, and breast milk. The efficacy, value and potency of the Exosome is determined by the cell of origin source of the exosome. Our research has demonstrated that the very best source of Exosomes are those derived from Wharton's jelly MSC growth media.

The underlying investment decision in the current fast changing and competitive exosome field, and potential client questions about how to compare one exosome product from another, has caused us to do a much deeper dive into the Science of Exosomes.

Our Director of R&D, Dr. Carla Mazzeo, PhD has just recently completed a Transmission Electron Microscopy (TEM) study comparing exosomes that have been either Lyophilized or Non-Lyophilized exosomes that are distributed in vials containing a saline solution. The decision to Lyophilize exosomes has been entirely driven by the manufacturer's effort to provide users with a shelf-stable version of exosomes. Non-Lyophilized exosomes are shipped frozen (usually in a cold pack or dry-ice. Although exosomes are quite hardy they typically only are shelf stable for up to 30 days and are thereafter must be kept stable in either a refrigerator or a freezer.

Clearly, if Lyophilization of exosomes effectively kept the product shelf stable, of course requiring reconstitution, this manufacturing process would have a strategic advantage over exosome products shipped in saline. either being cold-packed or frozen,

Due to the nano-scale of exosomes, the only scientific evaluation method to finally determine whether or not Lyophilization left the exosome undamaged and fully biologically active was to review these products under a triple blind study of these two types of exosome product storage methods under a Transmission Electron Microscope. This study analyzed two different exosome preservation methods: Lyophilization and Saline. The analysis was conducted on three exosome samples, two lyophilized and one preserved in saline. These samples differed not only in the type of producer or secretory stem cells used but also in the number of expansion passages the stem cells underwent during the exosome production process.

This study and the preparation of the comparison report, that we requested of Dr. Mazzeo. was performed by her at the Harvard University Transmission Electron Microscopy (TEM) laboratory. The TEM imaging was conducted in collaboration with Dr. Maria Ericsson at Harvard University. This comparative study of exosome conservation methods between key industry competitors was carried out at both Boston University and Harvard University.

Dr. Mazzeo holds a PhD specializing in the Biogenesis of Exosomes and brings 20 years of research experience in the field working across various countries. She has authored over 30 peer-reviewed articles in prestigious scientific journals, including Nature, JACI, Science, and Cell. Dr. Mazzeo also established the first Core Facility for Extracellular Vesicle Research at Boston University (BU) and continues to actively collaborate within BU's scientific community.

Special acknowledgment goes to Dr. Francesca Seta and Dr. Gerald Denis and Carmen Elena Venegas from Boston University, and Anja Nordstrom from Harvard University, for their valuable contributions to this study.

The TEM image included above is an image of what Dr. Carla referred to as a "Perfect Exosome" manufactured by Regenerelle, LLC (RegenerelleStemCells.com) at their clean lab located in suburban Rochester, NY. Both Regenerelle, and its topical exosome cosmetic subsidiary, Resilielle Cosmetics, LLC (Resilielle.com ) distribute their WJ-MSC exosome products.

Although we had hoped that future Crowley Center strategic investments in exosomes for both medical and aesthetics purposes could take advantage of the long shelf life of Lyophilized exosomes, Dr. Mazzeo's research highlighted the apparent detrimental impact of lyophilization on exosome integrity by comparing TEM images of saline-preserved and lyophilized exosomes reconstituted in PBS or serum.

We have, therefor, elected to continue to support our existing investments in WJ-MSC exosomes using saline as manufactured by Regenerelle, LLC; rather than move to Lyophilization. We have also decided to make three new exosome investments based upon the findings of this study.

We expect that this comparison study will published and be made available to third-parties within the next 30-60 days.