Sustained Drug Delivery for Ophthalmology• Bob Butchofsky, CEO, Mati Therapeutics Inc.

•Punctal Plug Delivery System

BButchofsky@MatiTherapeutics.com

CMuller@MatiTherapeutics.com

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