Posterior Segment Company Showcase - Aerpio at OIS@AAO 2016. Presenter: Joseph Gardner, President & CEO Powered by: Healthegy For more ophthalmology innovation Visit us at www.ois.net

2. Aerpio Therapeutics
• Private biotech advancing first in class ophthalmology
products
– AKB-9778
• Novel small molecule that activates Tie2
• Targeting non-proliferative diabetic retinopathy
• Administered via subcutaneous injection
• Phase 2 study in diabetic eye disease completed
– ARP-1536
• Novel monoclonal antibody that activates Tie2
• Targeting wAMD and DME
• Administered via intravitreal injection
• Entering clinic in Q1 2018

3. • Tie2 is a pivotal target for stabilizing
vasculature in multiple retinopathies
• Pipeline provides proprietary
products to 2034 and beyond,
including small molecule, MAb and
MAb co-formulations
• Company holds all global IP
Advancing first-in-class treatments for the eye

4. Active Tie2 is essential for vascular stability
• Transmembrane tyrosine kinase receptor located
almost exclusively on endothelial cells
• Active Tie2 is essential for vascular stability by
inhibiting permeability, blood retinal barrier
breakdown and inflammation
Blood vessel lumen
Intracellular Space

5. Tie2 is regulated by a few factors
Active Tie2
VE-PTP
Inactive Tie2
Ang2Ang1
PP
PP
Quiescent, Stable Vasculature Destabilized Vasculature

6. AKB-9778 inhibits VE-PTP, the most critical
negative regulator of Tie2
PP
AKB-9778
Blood vessel lumen
Intracellular space
VE-PTP

7. TIME-2 diabetic retinopathy severity score
analysis
• Pre-specified, planned analysis comparing:
• Images read by Digital Angiography Reading Center (DARC)
Study eyes by treatment group Fellow eyes by AKB-9778 exposure

8. AKB-9778 has the ability to improve underlying
diabetic retinopathy severity bilaterally, without
anti-VEGF therapy
10 8.8
11.4
0
5
10
15
Study Eye
%ofpatients
AKB-9778 (N=40)
RBZ (N=34)
AKB-9778 + RBZ (N=44)
Percentage of Patients with a ≥ 2-Step Improvement in DRSS from Baseline
4.2
11.4
Fellow Eye
Placebo Arm (N=24)
AKB-9778 Arms (N=70)

9. DR without DME represents that next major
growth opportunity in the treatment of retinopathy

10. • Targets an important vascular stabilization mechanism with proven
POC in randomized, placebo-controlled Phase 2 setting
• SC injection format addresses treatment and visit burden by
allowing for at home treatment
• Effective therapy that treats both eyes with a less invasive mode of
delivery more acceptable to patients with asymptomatic/minimally
symptomatic disease
AKB-9778 addresses the major unmet medical
needs for patients with NPDR

11. • Targets the extracellular
domain of VE-PTP
• Pre-clinical studies have
established biologic activity
similar to AKB-9778
• Provides additional options:
– Intravitreal dosing
– Stand alone therapy
– Single syringe w/ anti-
VEGF therapy
ARP-1536: An alternative approach to
targeting VE-PTP

12. IVT combinations of anti-VEGF/Tie2 targeted
therapies are major development programs
in wAMD & DME

13. P
Anti-Ang2
Antibodies
Ang2
Blood vessel lumen
Intracellular space
Ang1
P
VE-PTP
Inhibiting Ang2 does not address VE-PTP, the
most downstream inhibitor of Tie2

14. ARP-1536 inhibits VE-PTP, the most downstream
and critical negative regulator of Tie2
P
Anti-Ang2
Antibodies
Ang2
Blood vessel lumen
Intracellular space
Ang1
P
VE-PTP
ARP-1536

15. • Targets a profound vascular stabilization mechanism
• Published data demonstrating the ability to activate Tie2 irrespective
of Ang1 or Ang2 levels
• Ability to be administered alone with choice of anti-VEGF therapy or
as a single injection in a fixed dose combination with anti-VEGF
therapy
ARP-1536 has the potential to be the best-in-class
intravitreally administered Tie2 activating agent

16. Thank You