Interface Biologics, Inc.Spinning out Drug Delivery Technology

Sold Aug 2019 Spin out Q4 2019

SURFACE MODIFICATION LOCAL DRUG DELIVERY

Epidel Technology: patented non-polymeric prodrugs for precise local drug delivery

2

Linker

Prodrug dissolution Prodrug degradation into linker and free drug

Biologically inactive molecule

Active API GRAS list moietyDevice coating or

implant

Zero-Order Release Kinetics from Multiple Form Factors

MICROSPHERES

0

10

20

30

40

50

0 5 10 15 20

Cu

mu

lati

ve T

riam

cin

olo

ne

rele

ase

(%)

Time in incubation medium (Days)

CYLINDERS

0

10

20

30

40

50

0 10 20 30 40 50

Cu

mu

lati

ve D

exa

me

thas

on

e

rele

ase

(%)

Time in incubation medium (Days)

COATINGS

0

10

20

30

40

50

0 20 40 60 80

Cu

mu

lati

ve D

exa

me

thas

on

e re

leas

e (%

)

Time in incubation medium (Weeks)Confidential

Effects of EnvironmentEffects of Formulation

0

10

20

30

40

50

60

70

80

0 10 20 30 40

Cu

mu

lati

ve D

exa

me

thas

on

e

Re

leas

e f

rom

Pe

llets

(%

)

Time in 100% Serum (Bovine) at 37⁰C (Days)

⚫ Release from IBE-814

⚫ Release from IBE-1017

0

10

20

30

40

50

60

70

80

0 10 20 30 40 50 60

Cu

mu

lati

ve D

exam

eth

aso

ne

Rel

ease

fro

m

IBE-

81

4 P

elle

ts (

%)

Time in Release Medium at 37⁰C (Days)

Release in 100% FBS

Release in 1% FBS in PBS

Release in PBS

Engineerable (controllable) drug release kinetics and duration

Effects of Form Factor

0

20

40

60

80

100

0 10 20 30

Dex

amet

has

on

e R

elea

se R

ate

(ug/

day

)

Form Surface Area (mm2)

Ripple Therapeutics Strategic Focus on Ophthalmology

with conditions that are treated with

and a need for

Validated MOAs

EngineerableDuration

Easy Route of Administration

with suboptimal response to current

therapies

Large Patient Populations

DME = Diabetic Macular Edema; RVO = Retinal Vein Occlusion; NIU = Non-Infectious Uveitis, AMD = Age Related Macular Degeneration

IBE-814 Intravitreal (IVT) Implant is a dexamethasone prodrug cylinder delivered from a 30G needle

Competitive advantage over IVT steroid market leader

Potential for ↓ in steroid-related cataracts and IOP AEsNo polymer Carrier

Zero-order drug releaseFor 6 to 9 months

30G needle; direct delivery

Well Characterizeddegradation products

1/10th drug load of a commercial

Dexamethasone product

✓ Rat POC PD Q2 2018

✓ Rabbit PK Q2 2018

✓ Rabbit PD Q3 2018

✓ FDA pre-IND Q4 2018

✓ CMC initiated Q1 2019

✓ Initiate Tox Studies Q3 2019

• Initiate Phase II Clinical Trial Q3 2020

• Interim readout Q4 2020

IBE-814 IVT Development Program Key Milestones

FDA confirmed abbreviated regulatory path visa 505(b)(2)

IBE-814 IVT exhibits zero-order drug release and sustained inhibition of VEGF-induced vascular leakage

1.US 20130302324 A1

N o t T e s t e d

1 W E E K

Ne

ga

tiv

e

Co

ntr

ol

Co

mm

erc

ial

Imp

lan

tIB

E-8

14

Im

pla

nt

1 0 W E E K S 6 M O N T H S

70

µg

Dex

70

0 µ

g D

exSh

am In

ject

ion

David Boyer, MD• President, Retina Vitreous

Associates Medical Group• Professor of Ophthalmology, USC

Keck School of Medicine

Jeffrey Heier, MD• Director, Ophthalmic

Consultants of Boston• Co-Director, Vitreoretinal

Fellowship,Tufts Medical School

Judy Gordon, DVM• President, ClinReg Consulting

Services• FDA & EMA approval for 1st

intraocular sustained-release drug delivery product

• Over 100 IDEs, INDs, 510(k)s, HUDs and HDEs approved

Ike Ahmed, MD• Director, Glaucoma and

Advanced Anterior Segment Surgery, University of Toronto.

• Clinical Professor Ophthalmology & Vision Science at the University of Utah.

Elias Riechel, MD• Professor of Ophthalmology,

Tufts University School of Medicine

• Director, Vitreoretinal Diseases and Surgery Service

Barry Kupperman, MD, PhD• Professor; Chair, Department of

Ophthalmology. UC, Irvine• Director, Gavin Herbert Eye

Institute

Experienced Team of Ophthalmology Experts guiding our Product Development

Xyzagen Inc.

Adrianna Manzi, PhD• Co-Founder Athlen Inc• CMC expert with 30 years of

experience in R&D of small/ large molecules and combination products

Christopher Crean, MSc• Founder & CEO, Xyzagen Inc • Prior experience includes

Founder 1st Order Pharmaceuticals & NA Head of Clinical Pharm/Nonclin Dev, Valeant

Jeff Edelman, PhD• Ocular Research Solutions• Former Allergan Nonclinical

Research Team Leader, Global Team Leader

Low dose (n=18)

High dose (n=18)

Interim Analysis at 3 months supports:

• 1 mo CST

• 2 mo IOP -

• 3 mo BCVA

Low dose (n=7)

1A

High dose (n=7)

S TA G E BS TA G E A n=14 n=36

1B

2B

IBE-814 Phase II Clinical Trial: DME and RVO (50 patients total)

DME + RVO

Patients

AUSTRALIAN

Sites

Primary endpoint (BCVA) at 6 months; all patients followed to 18 months

2A

4 sites 12 sites

TECHNICAL POC Pre -CLINICAL CLINIC

Ripple Therapeutics Pipeline

DISCOVERY

Op

hth

alm

olo

gy

IBE-814Intravitreal Implant

Posterior Inf lammation(DME, RVO, NIU)

IBE-1119Intravitreal Implant

Wet AMD

Post-CataractInf lammation

IBE-119Intracameral Implant

Glaucoma IBE-1020

Intracameral Implant

Dry AMDIBE-1212

Intravitreal Implant

Raising $25M Series A round to

complete Phase II trial for IBE-814

IVT and continue development

of technology platform