Anterior Segment Company Showcase - Mati Therapeutics at OIS@AAO 2016. Presenter: Bob Butchofsky, Founder & CEO Powered by: Healthegy For more ophthalmology innovation Visit us at www.ois.net

1. Sustained Drug Delivery for Ophthalmology
Bob Butchofsky, CEO, Mati Therapeutics Inc.
Punctal Plug Delivery System
BButchofsky@MatiTherapeutics.com
CMuller@MatiTherapeutics.com

2. Evolute® Punctal Plug Delivery System
Consistent efficacy and
therapy control delivered
easily and comfortably

3. 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

4. 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

5. Easy Delivery & High Tolerability
Stable, Familiar Placement
Tolerable Position
Invisible

6. 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

7. Evolute®: Familiar, Precise Insertion

8. Evolute® Tearing & Comfort Scores
18.9
23 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
VASscoring,0=noresponse,100=intolerable

9. 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

10. 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

11. 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
Delivery(μg/day)
Day
NSAID Minimum Target μg for Delivery

12. NSAID: Aqueous Humor Concentrations of Amfenac*
0
5
10
15
20
25
2 3 4 7 8 9 10 11 15
AqueousConcentration(nM)
Day
NSAID Targeted IC50
*Approximation

13. Evolute® Steroid Elution Rate for Difluprednate
0
2
4
6
8
10
12
2 3 4 8 9 11 14
ElutionRate(µg/day)
Day
Evolute Targeted Elution

14. 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

15. 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
ChangeinIOP(mmHg)
Day
Animal model confirms greater efficacy of T-Evolute®

16. 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
ChangeinIOP(mmHg)
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®

17. 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

18. Evolute® Punctal Plug Delivery System
Consistent efficacy and
therapy control delivered
easily and comfortably