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Sustained Drug Delivery for Ophthalmology
Bob Butchofsky, CEO, Mati Therapeutics Inc.
Punctal Plug Delivery System
Evolute® Punctal Plug Delivery System
Consistent efficacy and
therapy control delivered
easily and comfortably
Considerations For Sustained Ocular Drug Delivery
Ocular Therapeutix Allergan / ForSight Ring
Keys To Success
1. Easy to place and remove
2. Cosmetically invisible – easy to identify
3. Tolerable
4. Consistent, sustained efficacy
5. Use in multiple disease states
Evolute® Punctal Plug Delivery System
StableFit™ Design
Successful By Design
1. Easy to place and remove
2. Cosmetically invisible – easy to identify
3. Tolerable
4. Consistent, sustained efficacy
5. Use in multiple disease states
Targeted Delivery
Drug Core
Polymer Sleeve
Cyanoacrylate Film
Proven Sustained Elution
Excellent Plug Retention Rates Over 12 Weeks
Study Week 4 Week 8 Week 12
Glau 12 (n = 92) 98% 97% 96%
Glau 13 (n = 87) 98% 96% 92%
U.S. Phase II Multi-center Trials
Evolute® Tearing & Comfort Scores
18.923 21 19.6
18.9 20.7 20 19.3
0
10
20
30
40
50
60
70
80
90
100
Baseline Week 4 Week 8 Week 12
Tearing Comfort
VA
S s
co
rin
g, 0
= n
o r
es
po
ns
e, 10
0 =
in
tole
rab
le
Multiple Disease State Treatment Applications
Glaucoma
Prostaglandins
• Latanoprost
• Travoprost
• Bimatoprost
Beta-Blockers
• Timolol
• Betaxolol
• Levobunolol
Alpha Agonists
• Brimonidine
NCEs
• Rho Kinase Inhibitors
• Adenosine agonists
Allergy
Antihistamines / Mast Cell Stabilizers
• Olopatadine
• Levocabastine
• alcaftadine
Mast Cell Stabilizers
• Cromolyn
• Nedocromil
Anti-Inflammatory
Steroids
• Difluprednate
• Loteprednol
• Fluorometholone
Dexamethasone
• NSAIDs
• Nepafenac
• Bromfenac
Dry Eye
Immunosuppressants
• Cyclosporine
Integrin antagonist
• Lifitegrast
OTC Demulcents / Oils / Emulsions
Multiple compounds can be formulated with
Evolute® Punctal Plug Delivery System
Strong Intellectual Property Position
U.S. Patent, De Juan
“Use of ocular implants to deliver a therapeutic agent to the
eye, either placed through the punctum or between the sclera
and conjunctiva tissue layer.”
82 issued patents
91 pending applications
15 patent families
NSAID – Nepafenac Elution Rate
Initial burst is tunable to extend duration of action or power of initial dose
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
2 3 4 7 8 9 10 11 15
Deli
very
(μ
g/d
ay)
Day
NSAID Minimum Target μg for Delivery
NSAID: Aqueous Humor Concentrations of Amfenac*
0
5
10
15
20
25
2 3 4 7 8 9 10 11 15
Aq
ueo
us
C
on
ce
ntr
ati
on
(n
M)
Day
NSAID Targeted IC50
*Approximation
Evolute® Steroid Elution Rate for Difluprednate
0
2
4
6
8
10
12
2 3 4 8 9 11 14
Elu
tio
n R
ate
(µ
g/d
ay)
Day
Evolute Targeted Elution
Travoprost - Accelerated Screening Model for Elution Rates
0
2
4
6
8
10
12
14
1 2 4 7
µg
Day
T-Evolute L-Evolute
0
1
2
3
4
5
6
µg/day
T-Evolute L-Evolute
T-Evolute® over one week can elute
much higher concentration of drug
when compared to L-Evolute®
At two weeks, the T-Evolute® can
elute at 5 times the rate of the
L-Evolute®
µg
Animal IOP Model (Mean Time Points) -Travoprost
-8
-7
-6
-5
-4
-3
-2
-1
0
1 2 3 4 5 6 7
T-Evolute L-Evolute
Ch
an
ge i
n I
OP
(m
mH
g)
Day
Animal model confirms greater efficacy of T-Evolute®
Ph II U.S. Multi-center 12 Week Results:L-Evolute® with Previously Shown Elution Profile
-6.09
-5.35 -5.44
-5.07
-5.56
-4.88
-5.3
-5.06
-7
-6
-5
-4
-3
-2
-1
0
1 2 3 4 6 8 10 12
Ch
an
ge
in
IO
P (
mm
Hg
)
Week
*95% CI excludes 0, indicating a p-value of <.05
All IOP included, regardless of plug loss/removal
Development data to date shows the T-Evolute® should out perform
the L-Evolute® shown above in humans
L-Evolute®
Evolute® Punctal Plug Delivery System
Summary Of Benefits
• Wide range of compounds
• Flexible drug delivery profile
• Non-invasive approach
• Steady elution – unlike eye drops
• Comfortable + excellent retention
o 92% and 96% in last two clinical trials at 12 weeks
• Cosmetically invisible / easily identifiable
• Preservative free
• “Passive” system for patients / physician controls compliance
• Favorable reimbursement opportunity for MDs and ODs
• Strong IP protection
• Favorable COGs
Evolute® Punctal Plug Delivery System
Consistent efficacy and
therapy control delivered
easily and comfortably