Activated 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
VE-PTP is a critical down regulator of Tie2 activity
Blood vessel lumen
Intracellular Space
AKB-9778 mechanism of action
• Small molecule inhibitor of VE-PTP
• Activates Tie2
• Administered via subcutaneous injection
Targeting VE-PTP is the optimal approach to activating Tie2
TIME-2 study design
Observation
N=1441:1:1
D84 D140D28 D56 D112D00.3 mg ranibizumab
Placebo SC BID
15 mg AKB-9778 SC BID
Sham injection
Active Treatment
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
Change in central subfield thickness
Month 1 Month2 Month 3
-170
-120
-70
-20-10 -8
60
-91 -102 -110-106
-146 -164
AKB-9778 (N=46) RBZ (N=47) AKB-9778 + RBZ (N=48)
Chan
ge in
CST
(µm
)
p = 0.008*p = 0.02*
*ANCOVA w/ baseline CST as covariate
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
Series1
-700
-600
-500
-400
-300
-200
-100
0
100
200
AKB-9778 + RBZ (N=48)
RBZ (N=47)
Chan
ge in
CST
at 3
Mon
ths (
µm)
Per patient change in CST at 3 months
Visual acuity at 3 months
AKB-9778 (N=46)
RBZ(N=47)
AKB-9778 + RBZ(N=48)
Mean Δ from BL, letters 1.5 5.7 6.3≥ 2-lines, % 8.7 29.8 35.4≥ 3-lines, % 4.3 17.0 20.8
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
TIME-2 DRSS analysis
• Pre-specified, planned analysis comparing:– Study eyes: Treatment groups
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
TIME-2 DRSS analysis
• Pre-specified, planned analysis comparing:– Study eyes: Treatment groups– Non-study fellow eyes: Subcutaneous AKB-9778 treated and
placebo treated
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
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)
AKB-9778 has the ability to impact diabetic retinopathy severity bilaterally, without anti-VEGF therapy
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
Ocular and non-ocular adverse events were similar between groups
AKB-9778 (N=48)
RBZ(N=47)
AKB-9778 + RBZ
(N=49)Number of Ocular AEs 17 45 48Subjects w/ Ocular AEs, n (%) 10 (20.8) 19 (40.4) 23 (46.9)Number of Non-Ocular AEs 76 89 108Subjects w/ Non-Ocular AEs, n (%) 28 (58.3) 30 (63.8) 33 (67.3)Number of Serious AEs 2 0 2Subjects w/ Serious AEs, n (%) 2 (4.2) 0 2 (4.1)Number of Severe AEs 1 10 4Subjects w/ Severe AEs 1 (2.1) 5 (10.6) 3 (6.1)
Campochiaro P, et al. Ophthalmology. 2016; 123: 1722-1730,
Summary
• TIME-2 provides proof-of-concept for treatment of diabetic eye disease, both DME and DR, by activation of Tie2 with AKB-9778
• AKB-9778 alone and in combination with an anti-VEGF agent was well tolerated
• TIME-2 results support future development of AKB-9778
‒ in combination with anti-VEGF therapy for the treatment of DME
Summary
• TIME-2 provides proof-of-concept for treatment of diabetic eye disease, both DME and DR, by activation of Tie2 with AKB-9778
• AKB-9778 alone and in combination with an anti-VEGF agent was well tolerated
• TIME-2 results support future development of AKB-9778
‒ in combination with anti-VEGF therapy for the treatment of DME
‒ as monotherapy for the treatment of DR
• No approved treatments
• Diabetic eye disease is a global epidemic
• Targets a profound vascular stabilization mechanism with proven POC
• SC injection format addresses sustainability and access to care issues
• Treats both eyes (70% of patients have bilateral DR)
• Less invasive mode of delivery more acceptable to less symptomatic patients
AKB-9778 is ideally positioned to be the market leader in the treatment of NPDR without DME
Confidential
• 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 in combo
with anti-VEGF therapy– Initial indications: wAMD
and DME
ARP-1536: An alternative approach to targeting VE-PTP
Thank You