Future Therapies for Exudative AMD

1

David Boyer, MDClinical Professor Ophthalmology

USC/Keck Medical School Retina Vitreous Associates

Los Angeles, Ca

David Boyer, MDClinical Professor Ophthalmology

USC/Keck Medical School Retina Vitreous Associates

Los Angeles, Ca

Future Therapies for Exudative AMD

Future Therapies for Exudative AMD

Financial DisclosureFinancial Disclosure

• Consultant/Advisor: Alcon, Allergan, Bausch&Lomb, Regeneron, Genentech, Neurotech, GSK, Santeen, Pfizer, Allegro

• Consultant/Advisor: Alcon, Allergan, Bausch&Lomb, Regeneron, Genentech, Neurotech, GSK, Santeen, Pfizer, Allegro

Angiogenesis in AMD is a Complex Cascade of events

Griffioen and Molema. Pharmacol Rev. 2000;52:237; Das et al. Prog Retin Eye Res. 2003;22:721;Davis and Senger. Circ Res. 2005;97:1093.

Basementmembranedegradation


Tubeformation +remodeling


VEGF

Vascular Endothelial Growth Factor

Endothelial cell activation


Endothelial cell proliferation,

migration


migration

Current Paradigm – Block VEGF






VEGF





migration


migration

2

UpstreamUpstream

DownstreamDownstream

ExtracellularSpace

ExtracellularSpace

UpstreamUpstream


ExtracellularSpace

ExtracellularSpace

PegaptanibBevacizumabRanibizumabVEGF Trap

0102030405060708090

100

PDT(n=143)

Ranibizumab 0.5 mg(n=139)

90%‡

% o

f su

bjec

ts 66%

% o

f su

bjec

ts

0102030405060708090

100 90%†

53%

Sham(n=238)

Ranibizumab 0.5 mg(n=240)

*Month 12 was the primary endpoint in both trials; month 24 was a secondary endpoint.†P<0.01 vs sham; ‡P<0.01 vs PDT.

ANCHOR at month 24MARINA at month 24

Fibrovascular Proliferation

RPE Atrophy

Retinal Damage

Anti‐VEGF Non‐Responders

3

New Therapeutic Trials

Fusion protein of key extracellular domains from human VEGF receptors 1 and 2 combined with human IgG Fc

All human amino acid sequence

Binds VEGF tighter than native receptors, bevacizumab, or ranibizumab

Blocks all VEGF-A isoforms and placental growth factor (PlGF)

Increased dimerization efficiency

Lower isoelectric point (PI) than VEGF Trap-Eye which prolongs clearance time

Fusion protein of key extracellular domains from human VEGF receptors 1 and 2 combined with human IgG Fc

All human amino acid sequence

Binds VEGF tighter than native receptors, bevacizumab, or ranibizumab

Blocks all VEGF-A isoforms and placental growth factor (PlGF)

Increased dimerization efficiency

Lower isoelectric point (PI) than VEGF Trap-Eye which prolongs clearance time

1

2

3

4

5

6

7

1

2

3

4

5

6

7

Kinase Kinase

Kd 10-30 pM Kd 100-300 pM

VEGFR-1 VEGFR-2 KH902

Fc

Kd ~10 pM

KH902KH902

2

3

2

3

44

+19.61

0

5

10

15

20

25

0 1 3 5 7 14 28 42

Time (Days)

Cha

nge

in V

isua

l Acu

ity (

Lett

ers)

N=28

Mean Change in Visual Acuity Mean Change in Visual Acuity KH902KH902

Phase III clinical trial completed in naïve patient population in China Phase III clinical trial completed in naïve

patient population in China

12

4

Anti-VEGF Gene Therapy for AMD

AAV2-sFLT01 gene therapy

vector

Cells within the patient’s eye direct production of the

therapeutic protein

VEGF receptor-Ig chimeraPromoter

sFLT01

PlGF

IgG1 Fc

sFLT01

VEGF

IgG1 Fc

The sFlt01 protein binds VEGF and PlGF

The duration of the AAV2 sFlt01 effect is at least 12 months

OS: untreatedOD: rAAV2-control

OD: rAAV2-sFlt01 OS: untreated

Phase I Gene Therapy

• Dose escalation

• Single intravitreal injection

• Duration up to 1 year

• Multi‐center

16

5

Encapsulated Cell Technology Neurotech

• Device contains human RPE cells (ARPE‐19) genetically modified to secrete a drug

• The device is surgically implanted in the vitreous through a tiny scleral incision and is anchored by a single suture through a titanium loop at one end of the device

• The semi‐permeable membrane allows the outward diffusion of drug and other cellular metabolites

• Allows inward diffusion of nutrients necessary to support the cell survival in the vitreous cavity while protecting the contents from host cellular immunologic attacK

• “Immunologically privileged”

• Biologic activity demonstrated in CNTF trial

Encapsulated Cell Technology Neurotech

• Neurotech device (NT‐503) encapsulating VEGF receptor Fc‐fusion protein (VEGFR‐Fc)‐releasing cells.

• This VEGFR‐Fc is 20‐fold more efficient in neutralizing VEGF compared with ranibizumab NT‐503 is confirmed to release VEGFR‐Fc constantly up to 1 year in the rabbit vitreous.

• A phase 1 clinical trial of NT‐503 for neovascular AMD is ongoing outside of the United States.

Patient A2301 –76 Y/O WomanGen 2 Double Implant

19

2 Months50 Letters295 um

40 Letters639 um

46 Letters355 um

Baseline 1 Month 3 Months53 Letters

301 um

4 Months54 Letters

324 um

5 Months52 Letters

314 um

6 Months60 Letters

288 um

8 Months65 Letters

283 um

+25 letter vision gain and ~350µ decrease in central foveal thickness

UpstreamUpstream


ExtracellularSpace

ExtracellularSpace

6

PI3K

S6

TSC1 TSC2

PIP3

Akt

PT‐308

PS‐473

Rheb GTP

HIF VEGF PathwayAngiogenesisVascular Permeability

Cell ProliferationAngiogenesis

TORC2

TORC1

PDK1

GSK Cyclin D1

P

P

Cell ProliferationAngiogenesisBCL‐2/BAX

Cell SurvivalAnti‐Apoptotic

MMP‐9

Migration

Growth Factor Receptors(GPCR, RTK, Integrin, Cytokine)

Upstream Pathways

MMP‐2

SirolimusEverolimus

SirolimusEverolimus

PI3K

S6

TSC1 TSC2

PIP3

Akt

PT‐308

PS‐473

Rheb GTP



TORC2

TORC1

PDK1

GSK Cyclin D1

P

P



MMP‐9

Migration


Upstream Pathways

MMP‐2

SirolimusEverolimus

SirolimusEverolimus

PF-655PF-655

PI3K

S6

TSC1 TSC2

PIP3

Akt

PT‐308

PS‐473

Rheb GTP



TORC2

TORC1

PDK1

GSK Cyclin D1

P

P



MMP‐9

Migration

P529X

X

XX


X

X

P529

P529 Signaling Pathway Inhibition

MMP‐2

Dissociationof complex

Dissociationof complex

Palomid 529Control 0.5 mg Palomid 529

0.5 g Anti-VEGF 0.25 mg Palomid 529

0.5 g anti-VEGF

• Oxygen‐induced retinopathy (diabetic retinopathy) model–Like anti-VEGF antibody, P529 inhibits aberrant vascularization (lower right, upper left )–Unlike anti-VEGF, P529 allows normal angiogenesis (central area remains vascularized)–Synergizes with anti-VEGF–May provide greater safety than anti-VEGF as does not abrogate “normal” VEGF activity

7

P529 Phase I Study

• A Phase I Open‐Label Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of Single Intravitreal and Subconjunctival Doses of Palomid 529 in Patients with Advanced Neovascular Age‐Related Macular Degeneration

25

UpstreamUpstream

ExtracellularSpace

ExtracellularSpace

Flt-1 Flk-1 (KDR) Flt-4

Lymphangiogenesis Developmental angiogenesis

Angiogenesis: • Migration

• Proliferation •Vascular permeability


Integrin Antagonists

Receptor Blockers

IntegrinsIntegrins

• Family of transmembraneheterodimeric proteins

• Mediate adhesion to the extracellular matrix and between cells

• Direct roles in signaling and modulation of downstream kinase signaling pathways

• Involved in EC migration and prevents EC apoptosis

• Family of transmembraneheterodimeric proteins

• Mediate adhesion to the extracellular matrix and between cells

• Direct roles in signaling and modulation of downstream kinase signaling pathways

• Involved in EC migration and prevents EC apoptosis

8

α5β1 Integrin Key Featuresα5β1 Integrin Key Features

Adhesion molecule

Blockade can lead to vessel regression

“Turned on” in disease

Up-regulated on several cell types involved in pathological neovascularization

Adhesion molecule

Blockade can lead to vessel regression

“Turned on” in disease

Up-regulated on several cell types involved in pathological neovascularization

FibronectinEndothelial cell

8

VolociximabVolociximab

• Volociximab is a chimeric (82% human/18%murine) IgG4 monoclonal antibody (Mab) against α5β1 integrin

• Volociximab is a chimeric (82% human/18%murine) IgG4 monoclonal antibody (Mab) against α5β1 integrin

IIA1 M200

Parent 82% human

Control D13 Control D20 Control D27

M200 D13 M200 D20 M200 D27

Inhibition of CNV: FA LeakageInhibition of CNV: FA Leakage

Rmakrishnan V. et al J Exp Ther Oncol. 2006;5(4):273-86


Tyrosine kinases

VEGF Activation


Tyrosine kinases

VEGF Activation

•Tyrosine kinases are enzymes that provide a central switch mechanism in signal transduction pathways

•Phosphorylation of proteins

•Involved in cell proliferation, metabolism, survival and apoptosis

•Tyrosine kinases are enzymes that provide a central switch mechanism in signal transduction pathways

•Phosphorylation of proteins

•Involved in cell proliferation, metabolism, survival and apoptosis

9


Tyrosine kinases

Tyrosine Kinase Inhibitors:

Pazopanib (gtts)Vatalanib (po)

AG013958 (pst)AL39324 (pst)

X-82X-82 is a potential new treatment for wet AMD

It is unique because: It is given orally

It blocks both VEGF and PDGFThis study is designed to evaluate its safety and

preliminary efficacy in patients with wet AMDCompleting a Phase 1/2 trial

Orally administered

X-82 for wet AMDX-82 is able to inhibit pVEGFR, pPDGFR, HUVEC cell growth, and blood

vessel tube formation at very low concentrations (~50nM), much lower than what is required for cancer.

X-82 at 50mg is able to reach and exceed the concentration required for anti-angiogenesis

Average AUC of cancer pts 4,6,9 (5732 ng.hr/ml) is 4.5x that of pts taking 50mg QD (1282 ng.hr/ml)

QOD will evaluate if constant inhibition is necessary for efficacy

The effect of CM082 on HUVEC tube formation induced by VEGF

0

20

40

60

80

100

control VEGF VEGF+Sutent VEGF+CM082

Nu

mber

of

tubes

50nM

100nM

Effect of X-82 on HUVEC tube formation induced by VEGF Concentration (ng/ml) – time (hr) curve of X-82

Oncology Patient with AMD

Started X-82 100 mg tablet on 10-25-12AMD Diagnosed 11-06-12 Symptoms noted at baseline

Official diagnosis: Peripapillary atrophy with peripapillary choroidal neovacular membrane and

subretinal bloodBCVA improved from 20/60 to 20/25

Leakage from peripapillary subretinal neovascular membrane has improved

Subretinal fluid is much less

10

Oncology Patient with AMD

11-12-12 12-12-12 01-23-13

PazopanibPazopanib

• Topical tyrosine kinase inhibitor

• Inhibits multiple targets• VEGFR

• PDGFR

• c-kit

• Phase II study - 70 patients – Topical administration

• Mean 4.3 letter increase in Va

• Patients with the CFH TT genotype (the naturally occurring wild type gene) exhibited the best visual and anatomic response



• PDGFR

• c-kit




PazopanibPazopanib



• PDGFR

• c-kit






• PDGFR

• c-kit




Beyond the VEGF Cascade






VEGF





migration


migration

11

PDGF inhibitionPDGF inhibition

• Platelet derived growth factor (PDGF) regulates cell growth and division

• Block PDGF-B to prevent pericyte recruitment to neovascular vessels -destabilize and shrink CNV.

• E-10030• Pegylated aptamer containing 32 monomeric

units (32-mer) against PDGF-B

• Platelet derived growth factor (PDGF) regulates cell growth and division

• Block PDGF-B to prevent pericyte recruitment to neovascular vessels -destabilize and shrink CNV.

• E-10030• Pegylated aptamer containing 32 monomeric

units (32-mer) against PDGF-B

pericyte

Combination TherapyCombination Therapy

Does not strip

pericytes from mature

limbal vessels

Control VEGF PDGF VEGF+PDGF

Phase I: Combination Rx Mean VA Change from BaselineVisual Acuity (ETDRS Letters)

Phase I: Combination Rx Mean VA Change from BaselineVisual Acuity (ETDRS Letters)

Phase 1: Combination TreatmentMean Change from Baseline

Central Foveal Thickness

Phase 1: Combination TreatmentMean Change from Baseline

Central Foveal Thickness

12

Phase I: Combination RxPhase I: Combination Rx

+21 Letters+21 Letters +27 Letters+27 Letters

BaselineBaselinePost-combination therapyPost-combination therapy

1 month1 monthPost-combination therapyPost-combination therapy

2 month2 month

20/80 20/32 20/2520/80 20/32 20/25

706 microns706 microns 264 microns264 microns 238 microns(-468 microns)238 microns

(-468 microns)

Role of Microtubules: ShapeRole of Microtubules: Shape

• Microtubules are essential to maintain cell’s elongated shape (cytoskeleton)

• As the cell matures, the shape is maintained by actin

• Microtubules are essential to maintain cell’s elongated shape (cytoskeleton)

• As the cell matures, the shape is maintained by actin

Combretastatin A4 phosphateCombretastatin A4 phosphate

• Tubulin-binding agent destroys the internal skeleton of immature endothelial cells changing the shape from flat to round, plugging the vessels

• Reduces blood flow in neovascular vessels

• Tubulin-binding agent destroys the internal skeleton of immature endothelial cells changing the shape from flat to round, plugging the vessels

• Reduces blood flow in neovascular vessels

Combretastatin A-4-Phosphate Study with Neovascular AMD

Combretastatin A-4-Phosphate Study with Neovascular AMD

13

Combretastatin A4 phosphateCombretastatin A4 phosphate

• Phase II study completed

• Targeting patients with Polypoidal Choroidal Vasculopathy

• Phase II study completed

• Targeting patients with Polypoidal Choroidal Vasculopathy

OC-10XOC-10X

• Lipid soluble quinazolinone

• Inhibits tubulin in neovascular vessels

• Administered topically with good target concentrations in the back of the eye

• Significant antiangiogenic and angiolyticactivity in laser induced mouse CNV model

• Lipid soluble quinazolinone

• Inhibits tubulin in neovascular vessels

• Administered topically with good target concentrations in the back of the eye

• Significant antiangiogenic and angiolyticactivity in laser induced mouse CNV model

SqualamineSqualamine

• Small molecule aminosterol

• Novel intracellular, anti-angiogenic mechanism of action

• Potent at low nano-molar tissue concentrations

• Inhibitor of VEGF, PDGF, and bFGF signaling through chaperoning of the modulatory protein Calmodulin

• Small molecule aminosterol

• Novel intracellular, anti-angiogenic mechanism of action

• Potent at low nano-molar tissue concentrations

• Inhibitor of VEGF, PDGF, and bFGF signaling through chaperoning of the modulatory protein Calmodulin

Control Squalamine treated

*FITC (green fluorescence) labeled anti-calmodulin antibody

SqualaminePrevious Intravenous Clinical Program


• Studied in over 450 patients using an intravenous formulation

250+ patients with Wet-AMD

200+ oncology patients (solid tumors, ovarian, lung, and prostate)

Safely tested in wet-AMD at doses of up to 160mg per infusion

• Clinical Data in wet-AMD trials

Demonstrated biologic effect

Some gains in visual acuity

Strong maintenance of vision

? Effect in advanced, low vision wet-AMD

• Studied in over 450 patients using an intravenous formulation

250+ patients with Wet-AMD

200+ oncology patients (solid tumors, ovarian, lung, and prostate)

Safely tested in wet-AMD at doses of up to 160mg per infusion

• Clinical Data in wet-AMD trials

Demonstrated biologic effect

Some gains in visual acuity

Strong maintenance of vision

? Effect in advanced, low vision wet-AMD

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• Entered phase III trials for wet-AMD under fast track status and a Special Protocol Assessment (US FDA)

Discontinued due to

Enrollment difficulty of an IV approach

Changing competitive landscape of ranibizumab and bevacizumab Lack of commercial potential for chronic IV infusions

Suboptimal dosing due to relatively short half life when given systemically

• Entered phase III trials for wet-AMD under fast track status and a Special Protocol Assessment (US FDA)

Discontinued due to

Enrollment difficulty of an IV approach

Changing competitive landscape of ranibizumab and bevacizumab Lack of commercial potential for chronic IV infusions

Suboptimal dosing due to relatively short half life when given systemically

SqualamineNew Topical Clinical Program

SqualamineNew Topical Clinical Program

• Preclinical testing

• Safe to ocular tissues

• Anti-angiogenic concentrations achieved in posterior sclera and choroid

• No quantifiable uptake in aqueous humor

• Negligible systemic uptake

• Clinical Trials

Phase II multi-center, randomized, placebo controlled trial

Treatment of wet-AMD

Initiation expected in mid 2012

• Preclinical testing

• Safe to ocular tissues

• Anti-angiogenic concentrations achieved in posterior sclera and choroid

• No quantifiable uptake in aqueous humor

• Negligible systemic uptake

• Clinical Trials

Phase II multi-center, randomized, placebo controlled trial

Treatment of wet-AMD

Initiation expected in mid 2012

• hI-con1 is a recombinant protein designed to target Tissue Factor (TF)

• hI-con1 binds very tightly to TF

• TF present on inner surface of CNV but not normal blood vessels

• Binding of hI-con1 to CNV triggers cell-mediated cytotoxicity via Natural Killer cells

• Anticipated result: REGRESSION of CNV

55

hl-con1

• CNV Regression

• Significant number of laser‐generated lesions (76

spots/eye)

• Single IVT dose of hI‐con1 10 days after laser burn

•Measurement of CNV 4 days later

Pig wet AMD Model: hI-con1 Triggers CNV Regression in a Dose-Dependent Manner

• Longer resorption = longer treatment window = higher

opportunity to assess whether or not pre‐formed CNV can be reversed by I‐con1 treatment

RATIONALE

DESIGN

GOAL

hI‐con1 destroys established laser‐induced CNV in a dose‐dependent fashion

Total Delivered Dose (micrograms)

Control 25 50 100 200

% C

NV

10

20

30

40

50

60

70

80

90

60.3

49.3

38.3

13.53.2 10.2

[ 75%]

[ 50%]

[ 25%]

n = 56

n = 100

n = 85

n = 75n = 111

CONCLUSION

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Phase 1 Trial: hI-con1 for Exudative AMD

• Phase I: Open‐label, dose escalation study

• Objective: Evaluate the safety and tolerability of hI‐con1™

• Study parameters:

• 18 subjects (6 per dose level)

• Dose scheme: 3 dose levels of hI‐con1™ (60 mg, 150 mg and 300 mg )

• 24 weeks follow up

• During Phase 1, the 4th, 5th, and 6th subjects enrolled in each cohort must have total lesion area < 6 DA (total area of detachment) (15.24 mm2), of which at least 50% must be actively leaking, and 30% should be classic on the angiography, and no more than 3 prior injections of any therapy for the treatment of CNV

Phase 1 Trial: Preliminary Results

• Safe at all doses tested

• No safety concerns in patients who received anti‐VEGF after two weeks of hI‐con1

• Signal of biologic activity seen

• Regression of CNV and reduction in OCT leakage in some cases

• Dose response noted

• Effects seen in some anti‐VEGF® partial responders

• Full data presentation at ARVO

Bioactive LipidsBioactive Lipids

• Bioactive lipids may play a role ocular angiogenesis, in particular Sphingosine-1-phosphate (S1P)

• S1P has an effect on angiogenesis, fibrosis, pericyte ensheathment and macrophage recruitment

• Anti-S1P therapy potential target for the treatment of exudative AMD - Sphingomab

• Phase I trial: reduction in CNV activity

• Bioactive lipids may play a role ocular angiogenesis, in particular Sphingosine-1-phosphate (S1P)

• S1P has an effect on angiogenesis, fibrosis, pericyte ensheathment and macrophage recruitment

• Anti-S1P therapy potential target for the treatment of exudative AMD - Sphingomab

• Phase I trial: reduction in CNV activity

PED and Exudative AMDNeither subject was re-treated with anything for 12+ months

PED and Exudative AMDNeither subject was re-treated with anything for 12+ months

Subject #2: 0.2 mg

2 prior injections of bevacizumab + laser

Subject #15: 1.8 mg

16 prior injections of ranibizumab/bevacizumab + laser + dex.

Clinic

VisitSDOCT Images FA Images SDOCT Images

Scr = Day -7

Day 15

Day 30

Day 45 (#2)

Day 54 (#15)

16

In vitro VEGF Inhibition Assay

DARPinTarget

DARPin’s

•Novel class of binding proteins

•High affinity and specificity for many targets

MP0112

•VEGF antagonizing DARPin

•IC50 of <10 pM

•Half-life in the eye >6 days

•Stable at RT for >several months

•Produced at 7-8 g/L in bacteria(E Coli)

•Formulation as a liquid

•Well tolerated in phase 1 testing

Designed Ankyrin Repeat Protein

* Molecular Partners and Allergan

DARPin MP0112*

Association for Research and Vision Meeting, May 1-5, 2011 Ft. Lauderdale

Drug activity in the vitreous over time

Days

B

A

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140

10

1

0.1

0.01

0.001

1x10-4

1x10-5

1x10-6

Co

nce

ntr

atio

n (

mM

) MP0112MP0112 high e

MP0112: Possible less frequent dosing

A. PK and stability

Half life: MP0112 >6 days

Half-life: Ranibizumab = 3 days

Stability: MP0112 >>> Ranibizumab

B. Efficacy

IC50 : MP0112 <10 pM

IC50 : Ranibizumab >250 pM

RedosingRanibizumab

RedosingMP0112

Ranibizumabdos

DARPin MP0112

IRay

• X-Ray Beams

• Robotic control with eye stabilization

• Non-invasive

• Outpatient

X-Ray Therapy*

*Oraya Therapeutics

Complement inhibitionComplement inhibition

• Complement protein polymorphisms are associated with drusen formation and all stages of AMD

• Complement inhibition could provide therapeutic benefits at various stages of disease progression

• Choroidal neovascularization

• Transition from dry to wet AMD

• Geographic atrophy

• Drusen formation

• Complement protein polymorphisms are associated with drusen formation and all stages of AMD

• Complement inhibition could provide therapeutic benefits at various stages of disease progression

• Choroidal neovascularization

• Transition from dry to wet AMD

• Geographic atrophy

• Drusen formation

17

Other ApproachesOther Approaches

• Steroids

• Dexamethasone

• Vitreolytics

• AL-78898

• Radiation

• Internal – Surgical Delivery

• External – Office Based Delivery

• Steroids

• Dexamethasone

• Vitreolytics

• AL-78898

• Radiation

• Internal – Surgical Delivery

• External – Office Based Delivery

Sustained Drug DeliverySustained Drug Delivery

• Sustained Release Implant

• Surgically implanted – Retisert, Flucinolone Implant

• External – Replenish device

• Encapsulated Cell Technology

• Miniature drug “factory” - producing drug in implanted device

• Adenoviral Vector

• Viral gene delivery to cells resulting in production of desired drug/agent

• Sustained Release Implant

• Surgically implanted – Retisert, Flucinolone Implant

• External – Replenish device

• Encapsulated Cell Technology

• Miniature drug “factory” - producing drug in implanted device

• Adenoviral Vector

• Viral gene delivery to cells resulting in production of desired drug/agent

Sustained Drug DeliverySustained Drug Delivery

• Iontophoresis

• External anterior delivery of drug using electrical charge

• Microparticles/Nanoparticles

• Small slow release particles containing active drug

• Phase Transition Gel

• Liquid formulation on injection change to sustained release gel in vitreous

• Iontophoresis

• External anterior delivery of drug using electrical charge

• Microparticles/Nanoparticles

• Small slow release particles containing active drug

• Phase Transition Gel

• Liquid formulation on injection change to sustained release gel in vitreous

Summary: Current and Future Therapeutics










migration


migration

PegaptanibRanibizumabBevacizumabVEGF-Trap

KH902MP0112

AAV2 sFlt01

SirolimusEverolimus

P529 RTP801

Integrin - VolociximabRTki - Pazopanib

PDGF

CobretastatinOC-10X

Sphingomab

Complement InhibitorsSteroids

VitreolyticsRadiation

hI-con1Squalamine

18

Thank YouThank You

Documents

Future Therapies for Exudative AMD