BUSINESS, CONSUMER SERVICES, AND HOUSING AGENCY EDMUND G. BROWN JR., GOVERNOR

STATE BOARD OF OPTOMETRY 2450 DEL PASO ROAD, SUITE 105, SACRAMENTO, CA 95834 P (916) 575-7170 F (916) 575-7292 www.optometry .ca.gov

Continuing Education Course Approval Checklist

Title: Safety and Efficacy of DARP in Patients with Neovascular AMD

Provider Name: Pacific Eye Associates c/o Cynthia Lieu

Completed Application Open to all optometrists? Yes No Maintain record agreement? Yes No

Detailed Course Description PowerPoint and/or other presentation materials Advertising (optional) CV for EACH course instructor License Verification for each course instructor

Disciplinary History? Yes No

www.optometry

--

BUSINESS, CONSUMER SERVICES, AND HOUSING AGENCY GOVERNOR EDMUND G. BROWN JR.

0 STATE BOARD OF OPTOMETRY 2450 DEL PASO ROAD, SUITE 105, SACRAMENTO, CA 95834 P (916) 575-7170 F (916) 575-7292 www.optometry.ca.gov

OPTOMETRY

CONTINUING EDUCATION COURSE APPROVAL

$50 Mandatory Fee ! APPLICATION

Pursuant to California Code of Regulations (CCR) 1536, the Board will approve continuing education (CE) courses after receiving the applicable fee, the requested information below and it has been determined that the course meets criteria specified in CCR 1536(9).

In addition to the information requested below, please attach a copy of the course schedule, a detailed course outline and presentation materials (e.g., PowerPoint presentation). Applications must be submitted 45 days prior to the course presentation date. Please type or print clearly. Course Title Course Presentation Date

Safety and Efficacy of DARPin in Patients with

Ne..ov (}.

1

J

BUSINESS, CONSUMER SERVICES, AND HOUSING AGENCY

,. ,ff\\... . STATE BOARD OF OPTOMETRY ,\ ~ ... 2450,DEl!J~AQ.i;{,OAD, SUITE 105, SACRAMENTO, CA 95834~---e ""''""'"'"""'""''" ::\7 P (916) 575-7170 F (916) 575-7292 WWW.optometry.ca.gov

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GOVERNOR EDMUND G. BROWN JR.

CONTINUINGEt.>'UCATION COURSE APPROVAL

I $50 Mandatory j ~~~LIC~:ION ~---- --PursuannoCalifomiaCoaeof Rego1aticfn!f{CCR)"-1536~the Boarc:i-wiu-approve continuing education-(CEtcourses after --~

receiving the applicable fee, the requested information below and it has been determined that the course meets criteria specified in CCR 1536(g).

In addition to the information requested below, please attach a copy of the course schedule and topical outline of the subject matter. Applications must be submitted 45 days prior to the course presentation date.

Please type or print clearly.

Course Title Course Presentation Date

Safety and Efficacy of DARPin in Patients with Neovascular AMO

@] []/@] []/[]@] [] [] Course Provider Contact Information

Provider Name

Ali Zaidi, MD A. '

(First) (Last) (Middle) Provider Mailing Address

2100 Webster St, #214 San Francisco 5 treet City State CA Zip 94115

Provider Email AddressAZAI D l@P AC IF ICEYE,COM

Will the proposed course be open to all California licensed optometrists? DYES l!!lNO

Do you agree to maintain and furnish to the Board and/or attending licensee such records of course content and attendance as the Board requires, for a period of at least three years l!!lYES ONO from the date of course presentation?

Course Instructor Information Please provide the information below and attach the curriculum vitae for each instructor or lecturer involved in the course. If th . t t . the course, p ease prov1"d the reques e t d . f f t heet f paper.ere are more ms rue ors 1n I e in orma 10n on a separa e s o

Instructor Name

Ali Zaidi, MD A. (First) (Last) (Middle)

License Number A 123024 License Type MD

Phone Number ( 415 ) 923-3007 E . Add AZAIDl@PACIFICEYE.COMma11 ress

I dee/ re under penalty ofperjury under the laws of the State of California that all the information submitted on this fi m-ant1J5n a'\Y accompanying attachments submitted is true and correct.

1 . , l_.,. & b I,~ It~ Signa ure of Course Provider Date

Form CE-01, Rev. 2/16 2

mailto:AZAIDl@PACIFICEYE.COMhttp:WWW.optometry.ca.gov

Course outline:

Introducing a new treatment option for wet age-related macular degeneration: Abicipar pegol

--Review present treatment --Present the Abicipar molecule --Review phase I and II clinical trial results --Introduce the phase III clinical trial --Review inclusion and exclusion criteria

Course summary:

This presentation will provide an overview of the wet AMD treatment options. It is important to know the limitations of the current drug treatments. We will review a new drug: Abicipar pegol. This drug has shown promising results in phase I and II clinical trials and now a phase III clinical trial is ongoing. Optometrists can identify patients who are candidates for this new therapy and refer them to appropriate places.

3

25/07/2016

1

DARPins A Potential New Generation of Protein Therapeutics

Abicipar Pegol Recombinant protein of the designed ankyrin repeat protein (DARPin) family

Small molecular weight (34 kDa)1

Highly potent antagonist to VEGF-A isoforms2

1. Data on file. 2. Souied et al, AJO. 2014

2

Safety and Efficacy of DARPin(abicipar

pegol) in Patients with

Neovascular AMD

DARPin Abicipar Pegol

The Class The Compound

4

-

25/07/2016

DARPin (Designed Ankyrin Repeat Proteins)

Abicipar s higher binding affinity1 and longer vitreous half life

compared to published data for ranibizumab may produce a longer

dosing interval

Characteristics Abicipar2 Ranibizumab

Molecular weight 34 kDa 48 kDa

Binding affinity (Kd) 0.4 pM 42.5 pM

Half-life (t ) 4-7 days 3 days3

3 1. Data on file, Allergan, Inc.; 2. Data on file, Allergan, Inc.; 3. Ophthalmology. 2007

Nonclinical Efficacy: Inhibition of Vascular Leakage

In a rabbit model of VEGF-induced vasculopathy, an

equimolar dose of abicipar provided superior duration

of action compared to ranibizumab (at 4 weeks)

Vehicle

Ranibizumab

Abicipar

Abicipar may be efficacious in treating patients with neovascular AMD

4

5 2

25/07/2016

PHASE 2 CLINICAL STUDIES IN

ABICIPAR PEGOL FOR NEOVASCULAR AMD

Phase 1 study of abicipar pegol in neovascular AMD conducted by Molecular Partners (Study MP0112 CP01)

REACH: A Phase 2 Study in Neovascular AMD (nAMD)

Study Country Population Objective

150998-001* Global**

Stage 1 Advanced disease

N = 24 Evaluate safety

Stage 2 Treatment-naive

N = 183 Evaluate effect of single dose

Stage 3 Treatment-naive

N = 64

Evaluate effect of repeat

dosing

6

* NCT01397409 **US, Australia, Austria, Switzerland, France, Germany, Israel, Italy

6 3

Stable vision s def ned as < 15 letter oss n ETDRS BCVA

= =

=

-

-

i i - l i

25/07/2016

Completed Phase 2a Clinical Study

NCT01397409* (REACH)

Stage 3, 64 patients received 2mg (N 23), 1mg (N 25)

or ranibizumab (N 16) and followed for 20 weeks

IVT injections at Day 1, weeks 4 and 8 (abicipar) and

also weeks 12 and 16 (ranibizumab only)

Abicipar Pegol 2mg BCVA Letter Gain

Abicipar Pegol 1mg BCVA Letter Gain

Ranibizumab BCVA Letter Gain

Week 16 8.2 6.3 5.3

Week 20 9.0 7.1 4.7

7 * Clinicaltrials.gov and press release (30Jun2014, Allergan)

REACH Stage 3 Effect of Repeat Dosing

Objective: To assess the safety and treatment effects of 3 doses of abicipar every 4 weeks in treatment nave patients with nAMD

Primary Endpoint: Mean change in ETDRS BCVA

Key Additional Efficacy Endpoints: Proportion of patients with 15 letter gain, proportion of patients with stable vision*, change in CRT from baseline

Visit Schedule (week)

Abicipar 1 mg

Abicipar 2 mg

Ranibizumab 0.5 mg N

B 4 8 12 16 20

Primary endpoint

Active treatment

n=64 (3:3:2) Sham treatment

No treatment

Study was not powered to show statistically significant differences between treatment groups 8*

7 4

http:Clinicaltrials.gov

Abicipar 2.0 mg (n 23)

Abicipar 1.0 mg (n 25)

Ranibizumab 0.5 mg (n 1

25/07/2016

0

2

4

6

8

10

12

Baseline Week 1 Week 4 Week 8 Week 12 Week 16 Week 20

=

=

= 6)

BC

VA

Me

an

Ch

an

ge F

rom

Ba

se

lin

e(L

ett

ers

S

E)

mITT with LOCF

Assessment Visits (week)

REACH Stage 3 Mean Change in BCVA From Baseline

Abicipar 2.0 mg (n = 23)

Abicipar 1.0 mg (n = 25)

Ranibizumab 0.5 mg (n = 16)

9

REACH Stage 3 Mean Change in CRT From Baseline

-250

-200

-150

-100

-50

0

Abicipar 2.0 mg (n=23)

Abicipar 1.0 mg (n=25)

Ranibizumab 0.5 mg (n=16)

CR

T M

ea

n C

ha

ng

e (

m

SE

)

Week 1

Week 4

Week 8

Week 12

Week 16

Week 20

Baseline

10 mITT with LOCF

8 5

25/07/2016

REACH Stage 3

Ocular Adverse Events of Special Interest

Number of Patients with Event (%)

Adverse Event Abicipar 2 mg

(N = 23) Abicipar 1 mg

(N =25) Ranibizumab 0.5 mg

(N =16)

Vitreous Detachment 2 (8.7) 2 (8) 0

Eye Pain 2 (8.7) 1 (4) 1 (6.3)

Iritis 1 (4.3) 1 (4) 0

Choroiditis 1 (4.3) 0 0

Vitritis 0 1 (4) 0

Uveitis 0 1 (4) 0

Retinal haemorrhage 0 3 (12) 2 (12.5)

Macular Scar 0 0 2 (12.5)

No Serious Adverse Events were reported

11

REACH Stage 3 Summary

Visual acuity improvement was numerically greater than ranibizumab at Week 16 (8 weeks after the final abicipar injection)

This greater numerical difference between treatments was sustained at week 20, 12 weeks after the final abicipar injection

No serious adverse events were observed

Intraocular inflammation occurred in 2 patients treated with abicipar 2mg, 3 patients treated with abicipar 1 mg, none with ranibizumab

Data support current AMD clinical program

12

9 6

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25/07/2016

Ongoing Phase 2 Clinical Studies in nAMD*

Objective: To assess the safety and treatment effects of 3 doses of abicipar every 4 weeks in treatment naive patients with nAMD

Primary endpoint: Mean change from baseline ETDRS BCVA Secondary endpoints: CRT, vision gain

Abicipar 1 mg

Abicipar 2 mg

Ranibizumab 0.5 mg

Active treatment

Sham treatment

No treatment

B 4 8 12 16 20

Visit Schedule (week)

Primary endpoint

n=25 (2:2:1)

13 Clinicaltrials.gov NCT02181517 and NCT02181504

PHASE 3 CLINICAL STUDIES IN

ABICIPAR PEGOL FOR NEOVASCULAR AMD

Phase 1 study of abicipar pegol in neovascular AMD conducted by Molecular Partners (Study MP0112 CP01)

10 7

http:Clinicaltrials.gov

-

-- -

25/07/2016

Phase 3 Study Design

Objective: To assess the safety and efficacy of abicipar pegol compared with ranibizumab in treatment naive patients with neovascular AMD

Primary endpoint: Proportion of patients with stable vision*

Secondary endpoints: Mean change from baseline in ETDRS BCVA, mean change from baseline in CRT, proportion of patients with 15 letter gain, mean change from baseline in NEI VFQ 25 composite score

*Defined as a loss of fewer than 15 letters in ETDRS BCVA compared to baseline

Abicipar pegol 2 mg

Ranibizumab 0.5 mg

Sham treatment

No treatment

n = 900 (1:1:1)

BL 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100

2Q8

2Q12

RQ4

Week

Primary endpoint

15

Phase 3 Clinical Studies Key Inclusion Criteria

> 50 years of age

BCVA 73 and 24 letters (20/40 to 20/320 Snellen

equivalents, respectively) in the study eye

Presence of active subfoveal and/or juxtafoveal CNV

secondary to AMD with retinal fluid on OCT and/or

fluorescein leakage under the fovea in study eye

Area of CNV lesion, including both classic and occult

components, must be >50% of the total lesion area in

study eye

16

11 8

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25/07/2016

Phase 3 Clinical Studies Key Exclusion Criteria for the Study Eye

Previous use of verteporfin PDT or any ocular

antiangiogenic therapy (eg, aflibercept, bevacizumab,

ranibizumab, pegaptanib), approved or investigational,

for the treatment of neovascular AMD

Any prior or current systemic or ocular treatment

(including surgery) for neovascular AMD, approved or

investigational, except dietary supplements or vitamins

Prior use of ocular anti VEGF agents for neovascular

eye diseases other than AMD

17

THANK YOU

12 9

J_

Ali Zaidi, MD 2100 Webster Street, Suite 214, San Francisco CA 94115

Phone: 415-923-3007 E-Mail: azaidi@pacificeye.com

Work Experience

-~ - - ---Retina-surgeon, PacificEye-Associates;-San-Francisco;-CA--~------ - --------~ -- --Mar-2014-

Present

Retinal Surgeon, Retina-Macula Specialists, Tacoma, WA Jan 2014

Teacher, Casablanca American School, Morocco

College Coordinator, Woosh!, Palo Alto

Education

Board Certified, American Board of Ophthalmology

Retina surgery fellowship - Scheie Eye Institute, Philadelphia, PA

Ophthalmology residency - Scheie Eye Institute, Philadelphia, PA

Internship - Cambridge Hospital, Cambridge, MA

Medical School - University of California, San Francisco

Undergraduate - Stanford University, Stanford, CA

Publications

~~--~----

Aug 2011

Aug 2000 -June 2001

June 2000 - Sept 2000

June 2011

July 2009 - June 2011

July 2006 - June 2009

July 2005-July 2006

Sept 2001 -June 2005

Sept 1996 - June 2000

Wehrli, S Tawse, K, Zaidi, et al. A lack of delayed intraocular pressure elevation in patients treated with intravitreal injection of bevacizumab and ranibizumab. Retina 2012; 32(7): 1295-301.

Zaidi AA, Brucker AJ, Johnson MW. Diagnostic and therapeutic challenges: management of macular schisis. Retina 2011; 31(10): 2125-8.

Zaidi A, Ying GS, Kempen JK, et al. Hypopyon in patients with uveitis. Ophthalmology 201 O; 117; 366372.

Zaidi, A, Pistilli M, Brucker AJ. Letter to editor of BJO in response to "Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents" by Good et al. BJO Aug 2010.

Melese M, Alemayehu W, Zaidi A, et al. Comparison of annual and biannual mass antibiotic administration for elimination of infectious trachoma. JAMA 2008; 299(7):778-784.

Zaidi A, Brucker AJ. Management of diabetic macular edema: Are standards changing? Retinal physician. April 2010.

Zaidi A, Alvarado R, Irvine A. Pneumatic retinopexy: success rate and complications. Br J Ophthalmol 2006; 90:427-428.

13

mailto:azaidi@pacificeye.com

l I 'Page 2

i Zaidi A, McLeod s. Laser in situ keratomileusis in a i:>atient with i:>resumed central cloudy corneal I ---------

dystrophy of Francois. Am J Ophthalmol 2005; 139:376-377.

14

CE Course Provider Checklist Template (2)Safety and Efficacy of DARP in Patients with Neovascular AMDDr. Zaidi ChecklistSafety and Efficacy of DARP in Patients with Neovascular AMDSafety and Efficacy of DARP in Patients with Neovascular AMDzaidi_ceSafety and Efficacy of DARP in Patients with Neovascular AMDZaidi Course outline

abicipar pegol phase 3 recruitment Final (2)Safety and Efficacy of DARP in Patients with Neovascular AMDSafety and Efficacy of DARP in Patients with Neovascular AMD