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AVM
platform
technologies
01 Control of stem cell
bio-distribution
• Competitive Advantages
More potent than chemoattractants
• Enforceable Intellectual Property
• Internal Clinical Development Strategy
Select indication JP/US/EU/UAE
• Business Model : Broad Licensing
Opportunities
02 fullyhuman biologics
manufacturing cell line
• Competitive Advantages
Ethical cell line/personalized medicine
• Enforceable Intellectual Property
Allowed US claims
• Leverages Past Investments in Induced
Pluripotent Stem Cells (iPS cells)
• Business Model : Broad Licensing
Opportunities
First in class best in class

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Stem cells home first to the spleen
Commercial logisticsoptimal fora drug
rather than astem cell product
Business Model based on AVM Clinicaldevelopment
as well as out-licensingdeals
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AVM’s Unique Approach to Regenerative Medicine:
Lessons learned from bone marrow transplant
University of WA Hematology and Amgen Experience

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$7.4 billion
Estimated Sales of G-CSF Products (2014)
)
Example of commercial logistics:
Source: Company Annual Reports and Generics and Biosimilars Initiative
Bioactivity Modulating Drugs vs. Stem Cell Products
A single company
(Amgen) sells $5.8B
in products that
modulate HSC
bioactivity
Over 100 US cancer
centers harvest and
process stem cells for
transplant

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Stem Cells
First home to
the spleen
• Transplanted BM cells
homed to spleen are visible
by eye within 10 days.
• Each colony contains an
excess of 10M cells.
• The # injected is linearly
related to the # spleen
colonies.

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Acute BM & Spleen stem cell homing
Secondary transplant of spleen recovered
cells engrafted neutrophils 13 days faster
than primary or secondary BM transplant
Cells recovered from the spleen engraft
faster than bone marrow recovered cells

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7 AVM Biotechnology LLC.
Bone Marrow Transplant was predictive of the
spleen’s role in regenerative medicine
Stem cells injected into
heart via catheter
Stem cells exit from the heart and
accumulate in the spleen (red - viable)
and liver (yellow –not viable)
Scale: red highest, purple lowest
Source: Hofmann et al. Circulation 2005
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• Treatment of ischemic stroke
patient with autologous bone
marrow mononuclear cells (BMC)
• Direct injection to middle cerebral
artery (MCA) – majority of stem
cells migrate to the spleen
• Stem cell sequestration in the
spleen is a general phenomenon of
stem cells and has been observed
in multiple diseases
Source: Barbosa da Fonseca et al. Circulation 2010
Bone Marrow Transplant was predictive of the
spleen’s role in regenerative medicine ( Cont.)
brain
spleen
liver

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THE SPLEEN &
secondary lymphatics
A Stem Cell “Control Center”
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Germinal Center decreasing after AugmenStemTM treatment,
with AugmenStemTM given on day 0
G-CSF only
Chemo and radiation recovery
G-CSF mobilization must first saturate the splenic
niches before circulating stem cells can be found.
Therefore, 5 to 14 days of G-CSF are required and
splenomegaly is a dangerous side-effect.
AugmenStemTM blocks the splenic accumulation,
reducing the needed days of G-CSF and
preventing splenomegaly.
Regenerative medicine
Human clinical trials demonstrate
that stem cells escape from locally
treated tissues ( heart, brain) and
the sequester in spleen.
AugmenStemTM blocks this,
keeping stem cells in the
circulation to be chemo-attracted
into damaged tissue.
Germinal center lymphomas
Lymphomas can hide in the spleen and
germinal centers. AugmenStemTM
eliminates germinal centers and forces
cancer cells into the blood where
chemotherapy can kill them.
Bone marrow transplant
Transplanted cells first home to the
spleen and form huge colonies
visible to the eye (white nodules in
the picture above). From there, stem
cells repopulate the bone marrow.
AugmenStem Effect
THE Spleen
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AugmenStem™ MOA (splenectomy) delivers over 200% more BM stem cells and improves liver function in mice and humans
Independentproof of concept
independentinvestigatoriwamotoet al.
Mouse
Conclusion: Splenectomy significantly improved prognosis in
liver failure patients compared to stem cells alone and restored
serum albumin levels (a marker of fibrosis) to almost normal.
Human
Liver fibrosis
improved
(albumin
went up)
Prognosis
improved (Child-
Pugh Score
went down)
Liver function
improved (Vit K
dependent Pro-
thrombin time
went down)
Fibrotic area reduced 85% when splenectomy was combined with stem cell infusion
Splenectomy: Over 200% more stem cells delivered to the liver
Red arrows identify stem cells targeted to the
liver (excerpt from Fig.2)
CCl4 = Carbon tetrachloride (induces liver toxicity)
CCl4
with spleen
CCl4
no spleen
CCl4
with spleen
+ BM stem cells
CCl4
no spleen
+ BM stem cells
Brownish purple color indicates fibrosis (excerpt from Fig. 3)
CCl4
with spleen
CCl4
no spleen
CCl4
with spleen
+ BM stem cells
CCl4
no spleen
+ BM stem cells

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Independentproof of concept
independentinvestigatortang et al.
AugmenStem™ MOA (splenectomy) delivers 135% more adipose-derived stem cells and improves liver function in rats
Conclusion: Splenectomy + stem cells significantly reduced
fibrosis (row B panel D and graph), and improved liver function
compared to stem cells alone.
Stem cell fluorescent intensity in the liver was significantly
greater in splenectomized rats 5 days after stem cell injection.

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Independentproof of concept
Conclusion: Splenectomy + stem cells significantly reduced
fibrosis (row B panel D and graph), and improved liver function
compared to stem cells alone.
Stem cell fluorescent intensity in the liver was significantly
greater in splenectomized rats 5 days after stem cell injection.

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How do we optimize stem cell delivery?
TERM HERE
Type the subtitle of your great here
Stem cell sequestration in spleen and
lymph nodes is a ubiquitous phenomenon.
It is independent of type of stem cell, route
of administration and disease. Moreover,
the sequestered cells are long-term and
viable cells.
AVM technologies control this by
blocking stem cell sequestration ,
enabling stem cells to remain
longer in circulation and home in
greater numbers to sites of injury
stem cells
Block binding
spleen
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Control
of stem cell
bio-distribution
platform 01 Rapid, high-affinity lymphatic sequestration of stem cells limits
outcomes for Regenerative Medicine, CAR-T Immunotherapy &
Cancer Treatment Recovery
Enforceable intellectual property
• Issued claims provide both freedom to
operate and exclusivity by encompassing all
molecules with AugmenStemTM’ s mechanism
of action
Competitive advantages
• AugmenStemTM , AVM lead compound, blocks the
body’s rapid high-affinity reservoirs for stem cells
and beats competitor’s less potent chemoattractant
approaches
• Only AugmenStemTM is broadly applicable to
multiple types of stem cells for regenerative
medicine, immunotherapy, lymphoma treatment
and recovery from chemotherapy or radiation Compelling reasons to license
AVM technology
AugmenStemTM
• Optimizes clinical effectiveness of varied stem
cells to improve functional clinical results
• Boosts efficacy of CAR-T Immunotherapy
• Maximizes lymphoma response to chemotherapy
• Distinguishes G-CSF product from competitors
Internal clinical development
strategy
• Target time to market: 3-4 years
• 2nd generation product in development
(antibody)
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Blockingstem cell bindingin spleen Increasingsystemic stem cell circulation
Increasing systemic stem cell circulation
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17. Safely Accelerating & enhancing G-CSF Mobilization
Whole Blood CFU Assay
AugmenStem ™ concomitantly
administered (1x 114.6 mg/kg = HED
9.3 mg/kg of Dexamethasone base
eq) with two doses of Neupogen®
(GCSF 250 µg/kg/day);
n=4 C57BL/6 mice per group;
sacrificed after 96 h
Complete Blood Count
AugmenStem ™ concomitantly
administered (1x 138.5 mg/kg = HED
11.3 mg/kg of Dexamethasone base
eq) with three doses of Neupogen®
(GCSF 250 µg/kg/day);
AugmenStem™ + GCSF: n=6;
GCSF: n=5 C57BL/6;
sacrificed after 72 h
[K/µl]
[/µl]
Augmenstemtm
will prevent enlarged
spleen & splenic rupture
0.000
0.100
0.200
0.300
0.400
0.500
hG-CSF (n=8)
Neupogen
AugmenStem™
(n=5)
AugmenStem ™ +
hG-CSF (n=9)
Spleen Weight per Body Weight

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AugmensteMtm
in tendon
injury repair
improvement in tendon
injury repair
Stem cells alone Stem cells + augmenstemTMDressage horse BB treated for
tendon injury. Notable recovery
at 1 month. Back to light work in
6 months

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AugmensteMtm
in
OSTEOARTHRITIS
IMPROVEMENT in SEVERELY ADVANCED
OSTEOARTHRITIS
Stem cells + augmenstemTMDressage horse Jigsaw R treated
for OA. Previously placed 7th in
The Riders Shoppe Six Year Old
Young Horse Qualifier
Stem cells alone

20. Equine safety and efficacy data summary
• Collaborations with Regeneus ( Australia) and Quipolly Equine Research Center/Central West Equine; Rood&Riddle, Lexington, KY
• AugmenStemTM was tested together with CryoShot® Equine , an allogeneic off-the-shelf cell products; culture expanded BM MSC.
Safety
Case # Gender/Age Condition Treatment Response Results
EQ-101 Mare/NA Old mare with OA in multiple joints; Pilot
study case
6 mg/kg of AugmenStem™ (IV) Well tolerated; no side effects
noted
No infections, no laminitis, no Cushing’s syndrome
EQ-102 Mare/NA Young mare race horse with OA in one joint;
Pilot study case
6 mg/kg of AugmenStem™ (IV) Well tolerated; no side effects
noted
No infections, no laminitis, liver enzymes tested
normal
EQ-104 Mare/8 Normal mare without OA 6 mg/kg of AugmenStem™ (IV) Well tolerated; no side effects
noted
High dose well tolerated
Safety and efficacy
Case # Gender/Age Condition Treatment Response Results
EQ-103 Mare/NA Normal mare with OA 3 mg/kg of AugmenStem™ (IV);
mesenchymal SC (IA)
Well tolerated; no side effects
noted
Improvement in treated joints
EQ-105 Gelding/35 OA; adv. deg. joint disease in the pasterns,
hocks and knees
6 mg/kg of AugmenStem™ (IV);
mesenchymal SC (IA)
Well tolerated; no side effects
noted
Less pain on flexion of carpi; Lameness in
fore/hindlimbs improved by 1 whole grade
EQ-106 Mare/6 Normal mare with OA 3 mg/kg of AugmenStem™ (IV);
mesenchymal SC (IA)
Well tolerated; no side effects
noted
Improvement in treated joints
EQ-107 Gelding/8 Normal mare with OA 3 mg/kg of AugmenStem™ (IV);
mesenchymal SC (IA)
Well tolerated; no side effects
noted
Improvement in treated joints
EQ-108 Gelding/14 Tendon injury (DDFT) Grade 3 3 mg/kg of AugmenStem™ (IV);
mesenchymal SC (IA)
Well tolerated; no side effects
noted
Remarkable improvement observed at 3 weeks;
back to light work in 6 months instead of 12
EQ-110 Mare/NA Normal mare without OA 3 mg/kg of AugmenStem™ (IV);
labeled mesenchymal SC (IA)
Well tolerated; no side effects
noted
Well tolerated
Rood &
Riddle
Mare/15 months OA;, congenital OCD 3 lesions, right hock, 3
prior surgeries (partial response)
3 mg/kg of AugmenStem™ (IV);
expanded autologous bone
marrow MSC (IA)
Well tolerated; no side effects
noted
Lameness gone in 2 weeks

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Licensing Opportunities:
Over 180 Potential Stem Cell Corporate Partners

22. OUR GAME-CHANGING TECHNOLOGIES
MAKE STEM CELLS WORK BETTER
Follow-on antibody product for
Regenerative Medicine Cancer Treatment Recovery
AugmenStemTM lead compound for
Regenerative Medicine
Immuno-Oncology
Cancer Treatment Recovery
Nuclear Disaster Rescue
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