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Envisia Therapeutics
Precisely Engineering the
Future of Ophthalmology™
April 2015
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
© ENVISIA Therapeutics– All Rights Reserved
2
Envisia Therapeutics Pipeline
2014
2015
2016
2017
2018
ENV515 (glaucoma)
Pre-clinical
Ph 2a
Ph 3
Ph 2b
ENV905 (post cataract inflammation)
Research
Pre-clinical
Ph 2
Ph 3
NDA
Partnership (back of the eye)
Research
Research Collaborations
Product Development
© ENVISIA Therapeutics– All Rights Reserved
3
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
© ENVISIA Therapeutics– All Rights Reserved
4
Precisely Engineered Ophthalmic Drug
Delivery Systems
Travoprost
Difluprednate
0.5 mm
High Concentration Bevacizumab
Particles
5 µm
Dexamethasone
0.5 mm
Bevacizumab Microparticles in a
Polymer Hydrogel
5 µm
0.5 mm
PEG Hydrogel/RNA Nanoparticles
1 µm
Versatile technology, compatible with a wide range of polymers, small
molecules and biologics
© ENVISIA Therapeutics– All Rights Reserved
5
Intracameral Biodegradable
Formulations
Glaucoma—ENV515
ENV515 Intracameral Extended-Release
•
•
•
•
•
•
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
Large
Small
Travoprost
Extended-release biodegradable travoprost formulation puts the treatment of
the disease in the hands of the doctor, not the patient
© ENVISIA Therapeutics– All Rights Reserved
7
8 Months of IOP Reduction in Hypertensive
Beagle Dogs
Baseline
Placebo
ENV515
ENV515
30% change
from baseline
32% reduction in baseline IOP over 8 months from single dose of ENV515
© ENVISIA Therapeutics– All Rights Reserved
8
Phase 2a Study Underway
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)
2. Masked ENV515 Dosing
Period
(4 weeks)
• 20 patients
enrolled
• All PGA therapy
discontinued
3. Safety Follow-up
Period
(2 weeks)
• All patients
• 4 ENV515 dose groups
(5 patients per dose group, 20 patients total)
IOP
IOP
Initiate PGA
washout
Dose ENV515
IOP
IOP
IOP
Recover ENV515 during cataract surgery
(PK in aqueous humor and travoprost
content in recovered ENV515)
© ENVISIA Therapeutics– All Rights Reserved
9
Subconjunctival Biodegradable
Formulations
Ocular Inflammation—ENV905
ENV905: Post Cataract Difluprednate XR
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
•
•
•
•
•
Target Product Profile
3-4 week control of inflammation
Lower drug exposure
Easy administration
Fully biodegradable
Excellent safety
Difluprednate
0.5 mm
XR steroid formulation puts control of inflammation in the hands of the doctor
© ENVISIA Therapeutics– All Rights Reserved
11
ENV905 is Efficacious for More than 3
Weeks in Rabbit Model of Inflammation
Placebo
ENV905 dosed at day 1, with
sustained efficacy over 3 weeks
Durezol
ENV905
ENV905 in subconjunctival
space immediately post-dose.
Single dose ENV905 is equivalent or superior to daily topical QID Durezol® in vivo
© ENVISIA Therapeutics– All Rights Reserved
12
Intravitreal Biodegradable
Drug Delivery
Back of Eye Diseases
Extended Release Formulation Strategies
Solid-state antibody
or small molecule
(0.1-5 mm)
Material design
High conc. mAb
Micronized API
Biodegradable
Thermoplastics
Degradable
Hydrogels
Microparticles
Rods
Extended release
depot
(10’smm-mm)
PRINT creates multiple kinds of patentable size/shape/polymer combinations
designed for multi-month delivery of biologics and small molecules
© ENVISIA Therapeutics– All Rights Reserved
14
In-vivo Efficacy & Safety Proof-of-Concept
Achieved
Retinal Leakage Scores (rabbits at 2 months)
Positive
control
2
Formulation G
3
Negative
control
R e t in a l L e a k a g e S c o r e
4
Formulation G
1
50
F o r m u la tio n G
G
.
rm
l
F
o
o
s
tr
o
n
P
o
C
o
g
tr
e
n
N
o
C
% B e v a R e le a s e d
l
a
6 Months in-vitro release
100
it
ti
iv
v
e
e
0
Pilot safety and tolerability in
nonhuman primate of vehicle and
bevacizumab formulation shows good
tolerability at 2 months
0
0
50
100
150
T im e ( D a y s )
Signed collaboration with market validating partner
Other discussions ongoing
Herlihy et al. 2014: ARVO Poster
© ENVISIA Therapeutics– All Rights Reserved
15
New Technology Development
Combination Products
Demonstrated extended release from two different
drugs in one release depot formulation
Drug B
Drug A
Polymer
100
D ru g A
Extended Release Combination Formulations
% D r u g r e le a s e d
80
D ru g B
60
40
20
0
0
50
T im e ( D a y s )
© ENVISIA Therapeutics– All Rights Reserved
100
17
Engineered Nanoparticles for Drug Delivery
900
M a r k e te d P r o d u c t
850
P 1 - a n io n ic
500
P 2 - c a tio n ic
P 3 - c a tio n ic
400
P 4 - c a tio n ic
300
200
100
in
m
0
6
0
m
in
0
3
r e l. m a s s d r u g in te a r s
Particles can be used to study
the effects of size, shape,
chemistry and modulus for
improving PK/PD properties
© ENVISIA Therapeutics– All Rights Reserved
18
THANK YOU
[email protected]