Sustained Drug Delivery for Ophthalmology • Bob Butchofsky, CEO, Mati Therapeutics Inc. • Punctal Plug Delivery System [email protected] [email protected]
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
Evolute® Punctal Plug Delivery System
StableFit™ Design
Successful By Design1. 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 FilmProven Sustained Elution
3
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
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• Dexamethasone • Loteprednol• Fluorometholone
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
Mati Therapeutics Inc. N-Evolute® Phase II Trial
• Study Design• Double masked• Placebo controlled
• Nepafenac Evolute® Vs Placebo Evolute®
• Randomized 2 to 1 in favor of active• Post Operative Cataract Trial• End Points = Pain and Inflammation• Plugs Inserted 1-2 Days Pre-Op• 63 patients enrolled (42 N-Evolute® – 21 Placebo)
Mati Therapeutics Inc. N-Evolute Phase II Trial
• Balanced Baseline Demographics & Surgical Procedure• Age, Gender, Race• Cataract Grade, Incision Size, Ease of Cortex Removal• Plug Retention:
• After 215 Total Patient Visits Over 2 Weeks of Follow Up – one plug (N-Evolute®) was not present and positioned normally
Nepafenac Evolute® Phase II Results
*70%
38%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Day 3 Post Op
% of Patients with No PainDay 3 Post Op
N-Evolute Placebo Evolute
% o
f pat
ient
s
Confidential – Mati Therapeutics Inc.
(p value = 0.032)
Nepafenac Evolute® Phase II Results
*42%
0%0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
% of patients with no pain
% of Patients with No PainThroughout Entire Post-OP Trial Period
N-Evolute Placebo Evolute
% o
f pat
ient
s
Confidential – Mati Therapeutics Inc.
(p value = <0.001)
Nepafenac Evolute® Phase II Results
82%
63%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Day 3 Post Op
% of Patients with None or Trace
Anterior Chamber CellsDay 3 Post Op
N-Evolute Placebo Evolute
(p value = 0.148)
% o
f p
atie
nts
Confidential – Mati Therapeutics Inc.
Nepafenac Evolute® Phase II Results
*97%
69%
0%
20%
40%
60%
80%
100%
120%
Day 3 Post Op
% of Patients with None, Trace or Mild
Anterior Chamber CellsDay 3 Post Op
N-Evolute Placebo Evolute
% o
f pat
ient
s
Confidential – Mati Therapeutics Inc.
(p value = 0.006)
Nepafenac Evolute® Phase II Results
94%
75%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Day 3 Post Op
% of Patients with None or Trace
Anterior Chamber FlareDay 3 Post Op
N-Evolute Placebo Evolute
% o
f pat
ient
s
Confidential – Mati Therapeutics Inc.
(p value = 0.067)
Nepafenac Evolute® Phase II Results
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
Day 14 Post Op
Uncorrected Mean Visual Acuity
N-Evolute Placebo Evolute
*(20/32)
(20/50)
Confidential – Mati Therapeutics Inc.
Mea
n Vi
sual
Acu
ityLo
gMAR
valu
e(p value = 0.015)
Nepafenac Evolute® Phase II Results
*53%
14%
0%
10%
20%
30%
40%
50%
60%
Day 14 Post Op
Uncorrected Visual Acuity% of Patients 20/25 or better
N-Evolute Placebo Evolute
(p value = 0.001)
Confidential – Mati Therapeutics Inc.
Mea
n Vi
sual
Acu
ity
Nepafenac Evolute® Phase II Results
*65%
29%
0%
10%
20%
30%
40%
50%
60%
70%
Day 14 Post Op
Best-Corrected Visual Acuity% of Patients 20/20 or better
N-Evolute Placebo Evolute
Confidential – Mati Therapeutics Inc.
Mea
n Vi
sual
Acu
ity
(p value = 0.021)
Mati Therapeutics Inc. N-Evolute® Phase II Trial
• Adverse Events• Total of 14 Adverse Events Reported:
• 8 N-Evolute® (19%)• 6 Placebo (29%)
• No Serious AEs• No Unexpected AEs
Upcoming Milestones
• Initiation of Travoprost Phase II Study• Initiation of Dexamethasone Phase II Study• Complete formulation of Cyclosporine• Complete Manufacturing Scale Up – Start Phase III Study with Nepafenac• Complete formulation of olopatadine
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.”
114 issued patents (11 issued in 2018)
61 pending applications
17 patent families
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
– 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