Formulation and Intellectual Property Development Specialists

LATITUDE: The Company

San Diego-based formulation development boutique

Founded: 2003

Core strengths/specialties

Formulations for insoluble & unstable drugs

Drug delivery systems

IP creation

> 700 CRO projects completed

> 21 products out-licensed; 1 approved, 2 NDAs

18,600 sq ft., self-contained R&D labs/pilot facility

Team and Experience

Andrew Chen, PhD, RPh, President, 30 yrs

Matthew Singer, PhD, VP, Business Development, 20 yrs

Anna Ridenour, BS, Director, Sales and Marketing 23 yrs

Wei Lin, PhD, Manager, 14 yrs

Damian McCloud, BS, MS, MBA, Manager 11 yrs

Jianmin Xu, PhD, Manager 12 years

Stephen Wu, BA, General Manager, 22 yrs

BS, MS formulation researchers: 15

Business Model

CRO – focused and specialized client services

Fee-for-service

Pre-formulation

De-formulation

Client-owned formulation/IP development

NCEs and reformulations

Out-licensing

Proprietary Latitude-originated drug delivery

technologies and products

NCEs and reformulations [e.g., 505(b)(2)]

Formulation Development Capabilities

All NCEs – small molecules & biologics

All dosage forms

Specialty: Problematic APIs

Highly insoluble, unstable, high and/or bulky dose, poor absorption,

vein irritating, deficient PK profile, etc.

Intellectual property creation

Reformulations

API Experience

Small organic & inorganic molecules

Peptides

(hormones, growth factors, etc.) 1-25K MW

Proteins

(antibodies, blood factors, etc.) 15-150K+ MW

Oligos & Plasmid DNA

Adenovirus

Polymers

Drug combinations

Human & veterinary drugs

We do NOT use:

Allergenic detergents

Strong solvents

Hemolytic surfactants

Proprietary solubilizers

Unapproved ingredients

“Secret recipes”

Dosage Forms

Oral

Solid filled capsules (immediate & sustained

release)

Liquid filled capsules (bioavailability-

enhancing & SR)

Tablets & coated tablets (IR, SR, ER,

delayed release & orally-disintegrating)

Stable amorphous powder matrices (RFAP)

Multi-particulate systems (IR, SR)

Solutions (BA-enhancing)

Suspensions (SR)

Fast-dissolving films

Ophthalmic

Solution and suspensions

Topical

Lotions, ointment, pastes, gel, patches

Others

Vaginal tablets & gels

Nasal sprays

Injectable

Solutions (IV, IM & SC)

Emulsions (IV & SC vaccines)

Liposomes (Organ-targeting)

Suspensions (IV & IM)

Depots (gel & microspheres)

LATITUDE DDS Platforms

Patented or patent pending

Nano-E (Nanoemulsion)

PG Depot (Phospholipid Gel Depot)

ARTSS (Aqueous RT-Stable Solutions)

RFAP (Rapidly-dissolving Amorphous Powders)

ALLDAY 24 hr ER tablets

SR Oral MiniSpheres

Topical GelPatch

Nano-E

A versatile, refined nanoemulsion drug delivery system

Parenteral or ophthalmic formulation platform for

insoluble drugs

e.g., taxols, glucagon, sterols, amiodarone, fat-soluble

vitamins etc.

Reduces irritation

e.g., vinorelbine, vancomycin

Semi-transparent

Controllable PK profile (solution-like vs. depot)

505(b)(2) NDA enabling

Established CMC (2 NDA-stage programs)

Nano-E™ is a Highly Refined Emulsion

Typical emulsion Nano-E™

200-400 nm 500-100 nm

Av: particle size

Nano-E: Controllable PK Profiles

80

100

120

140

160

180

200

220

240

260

-10 0 10 20 30 40 50 60 70 80 90 100

Blo

od

glu

cose

in r

ats

(mg

/dL)

Time post-injection (min)

Solution

Fast-acting Nano-E

Slow-acting Nano-E

Control of In Vivo Release Rate of Glucagon by Nano-E

Phospholipid Gel PG Depot™

1-7 day delivery depot by SC/IM

Single-phase gel, ready-to-use, pen injectable

Biodegradable & approved ingredients

Tailored release (burst control, peak-less, etc.)

Small organics or biologicals. Protein friendly!!!

Broad utility - local or systemic delivery

Low cost of goods, manufacturing

Superior safety profiles

PG Depot Basal Human Insulin

24 hr Response (20U/kg sc in type-1 diabetic rats)

PG#1 – 24 hr PG Depot; PG#2 – long acting PG Depot;

LANTUS® - commercial LANTUS® product

-

100

200

300

400

500

600

700

-2 0 2 4 6 8 10 12 14 16 18 20 22 24

Pla

sm

a g

luco

se

(m

g/d

L)

Time after sc injection (hr)

LANTUS®

PG#1

PG#2

Release Control (Peakless Profile) for

Systemic Anesthetic Buprenorphine

Buprenorphine PG Depot

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 12 24 36 48 60 72 84 96 108 120 132

Time (in hours)

[Pla

sm

a] (n

g/m

l)

ARTSS: Aqueous Room Temperature-Stable Solutions

Stabilizing drugs in aqueous solutions

Transforms lyophilized powders or 2-8 °C

solutions into RT-stable aqueous solutions

Applicable to small molecules, peptides & proteins

Formulation for FDA-approved OraVerse™

Successfully applied to:

Phentolamine

Glucagon

Latanoprost

Human insulin

Formoterol

And others

RFAP Oral Matrix for Insoluble Drugs

Rapidly-dissolving, Free-flowing, Amorphous Particle Matrix

Greatly improves oral BA (up to 16X)

Applicable for drugs that are insoluble in oil and/or water

Rapid dissolution

High (10-20% w/w) drug loading

Thermodynamically stable amorphous drug form

No reversion to crystal form (at least ~1.5 yrs)

Approved and compendial ingredients

Simple manufacturing process, low cost of goods

Automated tableting-capable

Patent pending

ALLDAY 24H ER Tablets

Extended release for up to 24 hr

Near zero-order, low burst kinetics

Compatible with many APIs, including highly water-

soluble drugs

Up to 60-70% (w/w) drug loading

Straightforward manufacture, low COGS

Commercial products on market

NDA-ready, 505(b)(2)

CMC review completed by FDA

2 yr stability study completed

Pre-approval inspections of manufacturing facility completed

NADA approval anticipated 3Q 2010

Low COGS: ~$0.15 per 300 mg dose tablet in 100 ct bottles

24H Tramadol ER Tablet

Equivalent In Vitro Dissolution Results for 24H™ tramadol vs Ryzolt® (left, F2=52.8) and

vs Ultram ER® (right, F2=53.3)

24H™ tramadol vs Ryzolt® Dissolution in SGF

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (hours)

% R

ele

ase

Ryzolt

24H™

24H™ tramadol vs Ultram ER® Dissolution in SGF

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (hours)

% R

ele

ase Ultram

24H™

In vitro dissolution: 300 mg 24H™ tramadol vs. 300 mg Ryzolt® and 300 mg

Ultram ER®

MiniSpheres: SR Oral DDS

SR (12 hr) or ER (24 hr)

Ideal for high dose (>1-2 grams) drugs

Taste-masking

Enteric coatable

Mix/match to customize drug release profile

Convenient dosage format

GelPatch Topical DDS

Topical & transdermal spray or gel rub-on

Dries in <2 min to form a dry, clean, sheer “patch”

Non-irritating, non-greasy, non-staining &

inconspicuous – nearly invisible

24+ hr drug delivery

Removable as needed

Drugs (NSAIDs), OTC (capsaicin, menthol) or

cosmetics (sunscreen)

Local or systemic delivery

Transdermal Delivery:

Franz Cell Study

0

5

10

15

20

25

30

35

-1 4 9 14 19 24Am

ou

nt P

assed

Th

rou

gh

Po

rcin

e

Skin

(%

of a

pp

lied

)

Time (hr)

GelPatch containing 20% Nicotine

GelPatch containing 1% Testosterone

GelPatch containing 1.5% Meloxicam

LATITUDE Pharmaceuticals, Inc. 9675 Businesspark Avenue

San Diego, CA 92131www.latitudepharma.com

MATTHEW SINGER, PhD VP, Head of Business Development

858-546-0924 x 103 matthewsinger@latitudepharma.com

ANNA M RIDENOURDirector, Sales & Marketing

858-546-0924 x 118 | annaherrera@latitudepharma.com