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Increasing Returns in Drug
Discovery

    Harnessing the Power of CellsTM
                      Executive Overview
Focus:
Provide pre-clinical development tools and methods to enable successful
outcomes in early phase drug discovery. Failure is success when
determined early.*
*90% of lead candidates identified by current in vitro systems fail to become drugs
Value Summary:
 Physiologically relevant human stem-derived terminally differentiated
cells, cellular systems and primary cell lines

          Better in vitro screening of targets and molecules =
             Reduced animal model use
             Shorten development timeline
             Lower downstream costs




     *Expanding hN2 Primary Human Neurons stained with
     our chicken polyclonal antibody to Vimentin and DAPI
     (blue)
                                                            MSCGro™ Media vs Alternative

                                                                                           Executive Overview-V1-30-2013
Why Consider our Solutions
 Research proven solutions used by large Pharmas, Biotechs,
  Academic and Government Labs. 2500+ customers
    Publications/Testimonials

 Lower per well costs-we can aggressively discount cells and media

 Customer success focused
    Expert technical support
    Detailed protocols and methods
    Quick replacements and reorders
    Large expert resource network
        Published expert input
        Non confidential; customer feedback and data sharing
         through social media outlets and blogs


                                                Executive Overview-V2-30-2013
Applications
High throughput and high content screening
     Compound Testing
     Toxicology Studies
     Discovery
Cell expansion, differentiation and migration
studies

In Vivo cell Imaging




Images: To demonstrate the capabilities of the NIR-FLIVO® 747 apoptosis               Images: (A) UCB Derived hMSCs cultured using our low
tracer, adult wild-type Balb/c mice were either inoculated with HSV-1 virus,          Serum MSCGro media and then differentiated using our
which is known to induce apoptosis in the brain, or given a sham treatment.           Oetsogenic Differentiation Media.
Seven days after viral inoculation, the mice were injected intravenously with
either the NIR-FLIVO® 747apoptosis tracer (cat. KF17368), the NIR-FLIVO®
747 free dye (cat. KF17370, DyLight®747), or no reagent.                        Executive Overview-V3-03-2013
Cell Based Assays                                                                  FITC Labeled
                                                                                     hChondrocytes
   Tools Include:
 • Growth-
    Differentiation
    Factors
 • High-                                                                             FITC Labeled                   3-D Solutions
    Performance                                                                      hOsteoblasts
    Media                     Human Mesenchymal
 • Transfection               Stem Cells-Green
    Kits                      Fluorescent-Labeled

 • Markers
 • 3-D                                                                                hDopamingergic
    Fibers/ECMs                                                                       Neurons Derived
                                                                                      using hGNDF
                                                                                                                    Migration Assays
Coming soon!                                                                                                        Courtesy of Essen
SPIO-Labeled                                                                          hN2 Human Neurons             Biosciences
Cells for in-vivo                                                                     (mixed) stained with
Imaging                                                                               MAP-2 , Courtesy of
                                                                                      Dr. Gerry Shaw, UF
                              hNP1 Neural
                              Progenitors-100%
                              Confluency
        Testimonial: got 10 million cells total after extraction from the tissue. At Day 4 they all developed long axons. Thank you
        so much for the replacement." Dr. Lidia Gardner, University of Tennessee HSC.
                                                                                         Executive Overview-V3-03-2013
Example hNP1TM Neural Progenitors to Sensory Neurons: Xiufang Guo, Severo Spradling, Maria
Stancescu, Stephen Lambert, James J. Hickman. Derivation of sensory neurons and neural crest
stem cells from human neural progenitor hNP1. Biomaterials, In Press, Corrected Proof,Mar
2013.doi:10.1016/j.biomaterials.2013.02.061.




Images: Phase contrast images of the cultures before and after the sensory neuron induction. A) hNP1 culture before sensory
induction. B) hNP1 culture 10 days after sensory induction. C) hNP1 culture 30 days after sensory induction. Neuronal clusters and
axonal bundles, which resemble rat DRG cell cultures, were typically observed. D) For comparison, an image of a rat embryonic DRG
cell culture at 7 DIV is provided.
                                                                                     Executive Overview-V3-03-2013
Key Product Category Links:
 Cell Based Assay-Cells, Media and 3-D Solutions, stem cell potency/toxicity

 Antibodies-Markers-internally developed markers for neuroscience, immune
  response, cancer, Autoimmune disease and stem cell research
 Apoptosis Research Reagents -includes: detection kits, antibodies and
  proteins

 Proteins Recombinant and natural proteins-includes a wide selection of cell
  growth factors.

 Transfection & Reagents-Gene Expression Analysis,
  engineered cell lines for custom applications




                                                     Executive Overview-V2-30-2013
Competitive advantages

 Human Stem cell-derived: less animal studies, highly reproducible, cost-
  effective, bulk cells/systems of in-vivo replicates as in-vitro, defined systems.
 Expertise in Stem Cell Differentiation: Substantial experience in differentiation,
  trans-differentiation and characterization
 NSC & MSC-derived cell systems: Neurons, DA and mixed, 5-HT, ACh, NE, GABA-
  nergic, etc. MSC-derived chondrocytes, osteoblasts and endothelial cells.
 IPSC-based cell-line generation platform: The classic four-gene method of
  Grudin and Yamanaka, the 2012 Nobel Prize winners, can be replaced by over-
  expression of Oct 3/4 only in adult stem cells & Vitro Biopharma has a
  proprietary position (with licensing opportunities). IPSCs platform provides
  capacity for any human cell lineage.
 Transfection Expertise: This allows us to provide custom engineered cell systems
  for HTP screening.
 Cell labeling: Stem cell/derivative labeling by fluorescent, magnetic and
  nanoparticle-based probes. Ideal for in-vivo imaging, HTP and marker analysis.
 Technical Support: Substantial technical support in all phases of projects.

                                                            Executive Overview-V2-30-2013
 Clear Understanding of where Neuromics/Vitro Biopharma
  could have a positive impact.
     More intense in vitro screening of compounds and targets.
     Better candidates for downstream processes.
     Tools for in vivo assays

 Propose solutions based on this understanding

 Follow up, tweak and improve

Pete Shuster
CEO and Owner
Direct Phone: 612-801-1007
pshuster@neuromics.com



                                                     Executive Overview-V2-30-2013

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Cell based assays presentation V2_03_2012

  • 1. Increasing Returns in Drug Discovery Harnessing the Power of CellsTM Executive Overview
  • 2. Focus: Provide pre-clinical development tools and methods to enable successful outcomes in early phase drug discovery. Failure is success when determined early.* *90% of lead candidates identified by current in vitro systems fail to become drugs Value Summary:  Physiologically relevant human stem-derived terminally differentiated cells, cellular systems and primary cell lines  Better in vitro screening of targets and molecules =  Reduced animal model use  Shorten development timeline  Lower downstream costs *Expanding hN2 Primary Human Neurons stained with our chicken polyclonal antibody to Vimentin and DAPI (blue) MSCGro™ Media vs Alternative Executive Overview-V1-30-2013
  • 3. Why Consider our Solutions  Research proven solutions used by large Pharmas, Biotechs, Academic and Government Labs. 2500+ customers  Publications/Testimonials  Lower per well costs-we can aggressively discount cells and media  Customer success focused  Expert technical support  Detailed protocols and methods  Quick replacements and reorders  Large expert resource network  Published expert input  Non confidential; customer feedback and data sharing through social media outlets and blogs Executive Overview-V2-30-2013
  • 4. Applications High throughput and high content screening  Compound Testing  Toxicology Studies  Discovery Cell expansion, differentiation and migration studies In Vivo cell Imaging Images: To demonstrate the capabilities of the NIR-FLIVO® 747 apoptosis Images: (A) UCB Derived hMSCs cultured using our low tracer, adult wild-type Balb/c mice were either inoculated with HSV-1 virus, Serum MSCGro media and then differentiated using our which is known to induce apoptosis in the brain, or given a sham treatment. Oetsogenic Differentiation Media. Seven days after viral inoculation, the mice were injected intravenously with either the NIR-FLIVO® 747apoptosis tracer (cat. KF17368), the NIR-FLIVO® 747 free dye (cat. KF17370, DyLight®747), or no reagent. Executive Overview-V3-03-2013
  • 5. Cell Based Assays FITC Labeled hChondrocytes Tools Include: • Growth- Differentiation Factors • High- FITC Labeled 3-D Solutions Performance hOsteoblasts Media Human Mesenchymal • Transfection Stem Cells-Green Kits Fluorescent-Labeled • Markers • 3-D hDopamingergic Fibers/ECMs Neurons Derived using hGNDF Migration Assays Coming soon! Courtesy of Essen SPIO-Labeled hN2 Human Neurons Biosciences Cells for in-vivo (mixed) stained with Imaging MAP-2 , Courtesy of Dr. Gerry Shaw, UF hNP1 Neural Progenitors-100% Confluency Testimonial: got 10 million cells total after extraction from the tissue. At Day 4 they all developed long axons. Thank you so much for the replacement." Dr. Lidia Gardner, University of Tennessee HSC. Executive Overview-V3-03-2013
  • 6. Example hNP1TM Neural Progenitors to Sensory Neurons: Xiufang Guo, Severo Spradling, Maria Stancescu, Stephen Lambert, James J. Hickman. Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1. Biomaterials, In Press, Corrected Proof,Mar 2013.doi:10.1016/j.biomaterials.2013.02.061. Images: Phase contrast images of the cultures before and after the sensory neuron induction. A) hNP1 culture before sensory induction. B) hNP1 culture 10 days after sensory induction. C) hNP1 culture 30 days after sensory induction. Neuronal clusters and axonal bundles, which resemble rat DRG cell cultures, were typically observed. D) For comparison, an image of a rat embryonic DRG cell culture at 7 DIV is provided. Executive Overview-V3-03-2013
  • 7. Key Product Category Links:  Cell Based Assay-Cells, Media and 3-D Solutions, stem cell potency/toxicity  Antibodies-Markers-internally developed markers for neuroscience, immune response, cancer, Autoimmune disease and stem cell research  Apoptosis Research Reagents -includes: detection kits, antibodies and proteins  Proteins Recombinant and natural proteins-includes a wide selection of cell growth factors.  Transfection & Reagents-Gene Expression Analysis, engineered cell lines for custom applications Executive Overview-V2-30-2013
  • 8. Competitive advantages  Human Stem cell-derived: less animal studies, highly reproducible, cost- effective, bulk cells/systems of in-vivo replicates as in-vitro, defined systems.  Expertise in Stem Cell Differentiation: Substantial experience in differentiation, trans-differentiation and characterization  NSC & MSC-derived cell systems: Neurons, DA and mixed, 5-HT, ACh, NE, GABA- nergic, etc. MSC-derived chondrocytes, osteoblasts and endothelial cells.  IPSC-based cell-line generation platform: The classic four-gene method of Grudin and Yamanaka, the 2012 Nobel Prize winners, can be replaced by over- expression of Oct 3/4 only in adult stem cells & Vitro Biopharma has a proprietary position (with licensing opportunities). IPSCs platform provides capacity for any human cell lineage.  Transfection Expertise: This allows us to provide custom engineered cell systems for HTP screening.  Cell labeling: Stem cell/derivative labeling by fluorescent, magnetic and nanoparticle-based probes. Ideal for in-vivo imaging, HTP and marker analysis.  Technical Support: Substantial technical support in all phases of projects. Executive Overview-V2-30-2013
  • 9.  Clear Understanding of where Neuromics/Vitro Biopharma could have a positive impact.  More intense in vitro screening of compounds and targets.  Better candidates for downstream processes.  Tools for in vivo assays  Propose solutions based on this understanding  Follow up, tweak and improve Pete Shuster CEO and Owner Direct Phone: 612-801-1007 pshuster@neuromics.com Executive Overview-V2-30-2013