Envisia Therapeutics Company Presentation from OIS@ASCRS 2015

1. Envisia Therapeutics
Precisely Engineering the
Future of Ophthalmology™
April 2015

2. 2© ENVISIA Therapeutics– All Rights Reserved
Corporate Milestones
• Company formed in Nov 2013 as a spin out of Liquidia
Technologies--$25m in funding
• IND filed for ENV515, a 6 month biodegradable
formulation for glaucoma – Ph 2a underway
• Initiated development of ENV905, a biodegradable
formulation for post cataract inflammation (IND expected
2H’15)
• Developed XR formulations of biologics – assessing
several partnership opportunities
• Appointed Dr. Adrienne Graves and Dr. Gary Phillips to
Board of Directors

3. 3© ENVISIA Therapeutics– All Rights Reserved
Envisia Therapeutics Pipeline
Ph 2a
2014 2015 2016 2017 2018
Pre-clinical Ph 2b Ph 3
Research Pre-clinical Ph 2 Ph 3
ENV515 (glaucoma)
ENV905 (post cataract inflammation)
Research Research Collaborations Product Development
Partnership (back of the eye)
NDA

4. 4© ENVISIA Therapeutics– All Rights Reserved
PRINT® Technology Platform
• Engineering and production of <100 nm particles to
>1000 micron implants
• cGMP manufacturing with high batch-to-batch
reproducibility and dose uniformity
• Manufacturing scale capable of supporting commercial
demand
cGMP Manufacturing
Best in class control over particle size, shape and formulation

5. 5© ENVISIA Therapeutics– All Rights Reserved
5 µm
0.5 mm
Precisely Engineered Ophthalmic Drug
Delivery Systems
Versatile technology, compatible with a wide range of polymers, small
molecules and biologics
High Concentration Bevacizumab
Particles
Travoprost
PEG Hydrogel/RNA Nanoparticles
Difluprednate
Bevacizumab Microparticles in a
Polymer Hydrogel
1 µm
0.5 mm
5 µm
Dexamethasone
0.5 mm

6. Intracameral Biodegradable
Formulations
Glaucoma—ENV515

7. 7© ENVISIA Therapeutics– All Rights Reserved
ENV515 Intracameral Extended-Release
Large
Small
Target Product Profile
• 24/7 control of IOP (25-30% decrease)
• 6 month duration of action
• Less hyperemia than drops
• Easy administration
• Fully biodegradable
• Excellent safety
Extended-release biodegradable travoprost formulation puts the treatment of
the disease in the hands of the doctor, not the patient
Travoprost

8. 8© ENVISIA Therapeutics– All Rights Reserved
8 Months of IOP Reduction in Hypertensive
Beagle Dogs
Baseline
30% change
from baseline
ENV515
Placebo
ENV515
32% reduction in baseline IOP over 8 months from single dose of ENV515

9. 9© ENVISIA Therapeutics– All Rights Reserved
Phase 2a safety, efficacy, and ocular PK in glaucoma patients about to undergo cataract surgery:
20 patients, 4 weeks , 4 dose groups, TRAVATAN Z in non-study eye, IOP at several time points,
ocular PK in aqueous humor and travoprost content in ENV515 retrieved during cataract surgery
Phase 2a
1. PGA Washout
Period
(4 weeks)
• 20 patients
enrolled
• All PGA therapy
discontinued
2. Masked ENV515 Dosing
Period
(4 weeks)
3. Safety Follow-up
Period
(2 weeks)
• All patients
• 4 ENV515 dose groups
(5 patients per dose group, 20 patients total)
Dose ENV515
Recover ENV515 during cataract surgery
(PK in aqueous humor and travoprost
content in recovered ENV515)
IOP IOP IOP IOP IOP
Initiate PGA
washout
Phase 2a Study Underway

10. Subconjunctival Biodegradable
Formulations
Ocular Inflammation—ENV905

11. 11© ENVISIA Therapeutics– All Rights Reserved
ENV905: Post Cataract Difluprednate XR
Difluprednate
0.5 mm
Target Product Profile
• 3-4 week control of inflammation
• Lower drug exposure
• Easy administration
• Fully biodegradable
• Excellent safety
Current Situation
• Topical steroids are QID dosing
• Generics dominate, but branded products are competitive
• Need for improvement in overall efficiency of managing cataract
patients from beginning to end
XR steroid formulation puts control of inflammation in the hands of the doctor

12. 12© ENVISIA Therapeutics– All Rights Reserved
ENV905 is Efficacious for More than 3
Weeks in Rabbit Model of Inflammation
ENV905 in subconjunctival
space immediately post-dose.
ENV905 dosed at day 1, with
sustained efficacy over 3 weeksPlacebo
Durezol
ENV905
Single dose ENV905 is equivalent or superior to daily topical QID Durezol® in vivo

13. Intravitreal Biodegradable
Drug Delivery
Back of Eye Diseases

14. 14© ENVISIA Therapeutics– All Rights Reserved
Extended Release Formulation Strategies
Solid-state antibody
or small molecule
(0.1-5 mm)
Extended release
depot
(10’smm-mm)
Material design Biodegradable
Thermoplastics
Degradable
Hydrogels
PRINT creates multiple kinds of patentable size/shape/polymer combinations
designed for multi-month delivery of biologics and small molecules
RodsMicroparticles
High conc. mAb Micronized API

15. 15© ENVISIA Therapeutics– All Rights Reserved
N
e
g
a
tiv
e
C
o
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tro
l
P
o
s
itiv
e
C
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n
tro
l
F
o
rm
.
G
0
1
2
3
4
RetinalLeakageScore
In-vivo Efficacy & Safety Proof-of-Concept
Achieved
0 5 0 1 0 0 1 5 0
0
5 0
1 0 0
T im e (D a y s )
%BevaReleased
F o rm u la tio n G
Herlihy et al. 2014: ARVO Poster
Retinal Leakage Scores (rabbits at 2 months)
6 Months in-vitro release
Formulation G
Signed collaboration with market validating partner
Other discussions ongoing
Pilot safety and tolerability in
nonhuman primate of vehicle and
bevacizumab formulation shows good
tolerability at 2 months
Negative
control
Positive
control
FormulationG

16. New Technology Development

17. 17© ENVISIA Therapeutics– All Rights Reserved
Combination Products
Demonstrated extended release from two different
drugs in one release depot formulation
Extended Release Combination Formulations
Polymer
Drug A
Drug B
0 5 0 1 0 0
0
2 0
4 0
6 0
8 0
1 0 0
T im e (D a y s )
%Drugreleased
D ru g B
D ru g A

18. 18© ENVISIA Therapeutics– All Rights Reserved
3
0
m
in
6
0
m
in
0
1 0 0
2 0 0
3 0 0
4 0 0
5 0 0
8 5 0
9 0 0
rel.massdrugintears
M a rk e te d P ro d u c t
P 1 - a n io n ic
P 2 - c a tio n ic
P 3 - c a tio n ic
P 4 - c a tio n ic
Particles can be used to study
the effects of size, shape,
chemistry and modulus for
improving PK/PD properties
Engineered Nanoparticles for Drug Delivery

19. THANK YOU
ben.yerxa@envtx.com