The Company. Novel technologies for cell sorting. Stem Sel, a new firm for cellular biotechnologies

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1 The Company Stem Sel, a new firm for cellular biotechnologies Today cellular biotechnology can rely on a brand new Italian excellence: Stem Sel. We present an innovative and efficient method to select stem cells. We are a university spinoff founded November Our business then is at its startup phase. Its core activity bases on creating and developing novel, proprietary technologies to decline them into products able to select stem cells from adult tissues with the highest potential, also for future medical use. Our first product, the brand new device Celector, will significantly improve applications in the field of cellular biotechnologies targeted to stem cell therapies. Celector, the revolutionary idea Celector is our first product based on our proprietary methodology that isolates and sorts stem cells without immunotags. The novel methodology cellects cells due to their physical differences only. This absence of immunotags is the unique feature of celector and it avoids possible cell alteration, and it helps cells keeping their native, regenerative power. Novelty and unique features of Celector make Stem Sel a potential leader in the industry of technologies and tools for cell treatments. Celector aims to change the operational framework of stem cell characterization and production in R&D labs, cell banks, cell factories and, in the future, in clinics. Stem cells, a booming market Stem cell market is constantly expanding, also because of the progressive aging of population. Such an expansion comes together with the increasing incomes of the emerging economies (firstly, Asian countries). The use of stem cells is also increasingly requested by pharmaceutical industry to develop and test new pharmaceuticals. Recent surveys forecast cell market increasing, by 2018, of more than 25%, with a business worth 120 billion dollars. Within stem cell market, the market sector of technologies and tools for cell treatment is also rapidly increasing, and it is expected to reach in two years a global turnover of 2.5 billion dollars. Stem Sel is then well positioned in the global market and, if properly supported, it might soon reach a leading position.

2 Awards (2012) 1 st position at StartCup 2013, business plan competition won by Stem Sel between 52 projects, selected by investors and a committee of experts in high technology content companies. (2012) UK Trade Investment's UKIT Entrepreneur Award for business internationalization (2012) ItaliaCamp - Celector is winning idea of regional phase, and it was presented January 2014 to the Presidence of Governement Council at the event Your Idea for the Country. (2013) Intel Business Challenge's European phase. talked about Celector, at the Rizzoli Hospital, Bologna, Italy Laboratory of Biomechanics & Technological Innovation:..no one actually knows exactly what and how much you inject in cell treatments, while the quantity and quality of MSCs is a fundamental condition. It s essential that cells are not marked. Celector would have a decisive advantage compared to competitors.. Prometeo Laboratory:..using Celector the quality of cells results better than the ones obtained by reference techniques using tag or enzymes. When Celector will be available it will be very interesting tool for tissue banks... Ramses Laboratory: whoever does experiments in which cellular response is a very important element knows that it is essential to maintain cells intact. This is one of the main reasons for the interest in technologies for tag-less cell enrichment. Application of Celector to stem cells is significant because all others alternatives are based on immunomarking. Costs should be an additional advantage of using Celector... Team Founders: R&D: Prof. Pierluigi Reschiglian President/CEO Prof. Barbara Roda, Project Manager/CTO Prof. Andrea Zattoni, CFO Kristel Martinelli, Product Engineer Incubator (AlmaCube Ltd) Investors Martina di Venere, Product Manager Martina Rossi, Quality Engineer Pietro Matiazzi, Electronic Engineer Niccolò Dionisi, Software Engineer Current equity share

3 The Product: Celector Why Celector? Cells extracted from tissues are introduced in Celector to cellect (i.e. separate and isolate) stem cells from all other cells composing tissue, and sort "most potent" stem cells. Cellection is based on a proprietary, tag-less methodology that, compared to analog technologies, does not manipulate the cells at all. These cellected "super cells" can be further characterized, expanded, or committed to differentiation. This in view of their implantation in patients to reconstruct damaged tissue such as cartilage, tendons, bone, epithelium, blood and neurotissues. Celector will allow using your own cells to rebuild damaged tissues (autologous application without risk of rejection). No cell manipulation is key factor to pass regulatory restrictions while the tag-less methodology allows selection/sorting of stem cells for which there are not efficient technologies on the market. Fluorescence/magnetic-activated cell sorting (FACS/MACS) indeed manipulate cells using immunomarkers, which are often not available or highly specific to efficiently select highly potent stem cells such as mesenchymal stem cells (MSCs). Performance 1. Cell source e.g. umbilical cord (i.e. Whaton s jelly), dental pulp, peripheral blood mononuclear cells, platelets, leukemia/mammalian tumor lines, raw cellular samples as lipoaspirates, placenta, whole blood. 2. Number of sorted cells (current Lab version) 3. Fractionation time about 30 minutes 4. Cell purity high-yield removal of clusters, cellular debris and impurities from cell source 5. Cell isolation total separation of stem cells from differentiated cells present in the cell source 6. Stem cell sorting highest commitment of the cellected cells to differentiation in specialized cells (i.e. highest ability of stem cells to differentiate into specialized, also in case of stem cells already isolated by flask culture (which is the standard procedure to isolate pluripotent cells).

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5 Parts and operations 1 Autosampler, to automatically introduce cell samples to be cellected. 2,4 Pump, valves and capillaries made of biocompatible material for fluids control. 3 Fluid reservoirs. (a) Biocompatible fluid for the transport of cells; (b) Cleaning solution, (c) Coating solution (optional). 5 Cell fractionation device. Separation develops into capillary channel in which Earth gravity and hydrodynamic lift forces act on fluid-driven cells and separate them based on their morpho/biophysical differences. In this way different cells are swept down the channel at different velocities and they can be collected at different times. Single/Multi-channel configuration is possible based on cell production scale. Channels and the tubing sets can be disposable. 6 Optical detection system. Interfaced with the fraction collector to visualize and real-time count swept cells and trigger collection of selected cell subpopulations. 7 Fraction collector. Cell subpopulations are collected in tubes, flasks or well-plated for specifics uses. Lab - medical device - clinical Current Celector version is targeted to R&D labs ( Lab version). A Clinical/Medical Device version will be developed to scale up cell production and direct applications to patients. A. Lab Target: LABORATORIES FOR CELL QUALITY CONTROL 1. Research laboratories of public and private institutions 2. QC laboratories of biotech pharmaceutical industries, cell factories, cell banks, clinics. B. Medical device Target: CELL BANKS AND CELL FACTORIES 1. GMP-compliant, stem cell production C. Clinical Target: CLINICAL TRIALS IN HOSPITALS, AMBULATORIES AND CLINICS 1. Regenerative surgery 2. Cosmetic and reconstructive surgery

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