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

• 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

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

Tie2 is regulated by a few factors

Active Tie2

VE-PTP

Inactive Tie2

Ang2Ang1

PP

PP

Quiescent, Stable Vasculature Destabilized Vasculature

AKB-9778 inhibits VE-PTP, the most critical negative regulator of Tie2

PP

AKB-9778

Blood vessel lumen

Intracellular space

VE-PTP

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

AKB-9778 has the ability to improve underlying diabetic retinopathy severity bilaterally, without anti-VEGF therapy

Study Eye 0

5

10

15

10 8.811.4

AKB-9778 (N=40) RBZ (N=34)

AKB-9778 + RBZ (N=44)

% o

f pati

ents

Percentage of Patients with a ≥ 2-Step Improvement in DRSS from Baseline

Fellow Eye

4.2

11.4

Placebo Arm (N=24)

AKB-9778 Arms (N=70)

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

• 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

• 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

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

YP

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

ARP-1536 inhibits VE-PTP, the most downstream and critical negative regulator of Tie2Y

P

Anti-Ang2 Antibodies

Ang2

Blood vessel lumen

Intracellular space

Ang1

P

VE-PTP

YARP-1536

• 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

Thank You