CritiCally Caring about CritiCal Care

A s a fully integrated biotherapeutics

company, we have a deep

understanding of critical care.

This understanding drives us to focus on

the needs of critically ill patients both inside

and outside the ICU.

In life’s most fragile moments, we know

what it takes to make a difference. We have

a keen insight into the complete clinical

picture, and a strong understanding of the

biology of the conditions affecting critically

ill patients. This combination fuels our

scientific and research endeavors. And

it’s this work that we hope will have an

impact on critically ill patients and the

healthcare professionals who care for them.

Above all, we recognize the urgent needs

of this environment. Which is why helping

clinicians succeed and giving patients a

fighting chance is what fuels us to move ahead.

Over the last several decades there have

been very few breakthroughs in critical

care therapies. We are committed to

changing that. When the next significant

breakthrough occurs in critical care,

we plan to be on the front lines leading

the way.

Superb clinical and biologic insight drives our exploration into critical conditions

Disclaimer:This document includes or may include certain statements, estimates, and forward-looking projections with respect to our anticipated performance. Such statements, estimates, and forward-looking projections reflect various assumptions of our management that may or may not prove to be correct and involve various risks and uncertainties.

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More than 56,000 patients are in the iCu on any given day.1

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Ikaria was formed in 2007 when research

and discovery company Ikaria, Inc. joined

forces with INO Therapeutics, a company

with expertise in developing and commercializing

novel treatments for critically ill patients.

Today, Ikaria boasts a robust and growing

product pipeline that spans commercial,

preclinical, and clinical development. Rapid

global expansion and strategic licensing and

acquisitions are helping propel Ikaria forward.

The basis of our growth is a unique business

model and a range of product and proprietary

drug-delivery systems supported by an

all-inclusive offering seen nowhere else

in the industry.

At Ikaria, we are rapidly establishing a

leadership role in providing innovative solutions

to advance critical care for the future.

Fueled by passion, a mission that leads to results

our ideas drive us forward

• Our innovative therapies that directly influence patient outcomes and provide hope to families

• Our dedication to healthcare professionals who provide care when it is most critical

• Our value of the diverse talents, energy, and pride of all our employees

• The integration of our scientific,clinical, and caregiver expertise

• Our foundation, which is built on integrity and unwavering quality standards

Our mission is to address

the significant unmet needs

of critically ill patients every

single day through:

A t Ikaria, our competencies run deep, enabling

us to advance innovative solutions and provide

critical support. Our approach of critically caring

underpins everything that we do.

Fully integrated and focused on the needs of patients and customers

a strong team for a complex world

Throughout Ikaria, we work hard, smart, and with urgency,

because that’s the environment of critical care. We are a

customer-centric organization, and never forget that patients,

families, and clinicians are counting on us.

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More than five million patients are admitted annually to iCus in the united States.2

research & Development Along with investigating additional potential benefits

of our flagship product INOMAX® (nitric oxide)

for inhalation, we currently are investigating the

therapeutic potential of other promising critical care

compounds, and are aggressively pursuing the

development of new therapies across the spectrum

of drug and drug-delivery systems.

Clinical research With significant capabilities in pharmacology,

preclinical development, and clinical development

across all phases, we focus on applications in

ischemia/reperfusion injury, cardiovascular and

pulmonary medicine and surgery, transplantation,

and neonatology.

Sales & Marketing Our relationships with clinicians and hospital

staff are based not only on technical and clinical

expertise but also on our commitment to go the

extra mile at a moment’s notice. Our elite sales team

is supported by a growing integrated marketing and

customer service staff. The combined efforts of this

group embody the highest level of customer care.

Manufacturing We are the only company to develop and

commercialize an endogenous signalling

molecule in gas form for human use. In fact,

Ikaria’s drug manufacturing facility is the only

FDA-regulated nitric oxide manufacturing site

in the US. Separately, we manufacture the

complementary device that delivers the therapy

safely and reliably through an integrated

drug-delivery system.

Delivery System Development Beyond providing novel biotherapeutics, we have

special competencies in developing drug-delivery

systems for proper administration of our therapy.

Our marketed product INOMAX (nitric oxide)

for inhalation and some of our development-stage

compounds require drug-delivery systems for

proper administration.

DistributionWe meet the needs of our North American customers

with seven regional service centers that are on call

24/7/365. Overseas, we work with local partners to

assure the same high level of competence, access,

and service.

global relationships To share our critical care expertise and impact upon

patients worldwide, we have established our presence

in Canada, Japan, and Australia, and have teamed

with like-minded organizations in Europe, Mexico,

and South America.

business Development & licensing With a goal of bringing additional much-needed

solutions to the critical care market, we actively pursue

development and commercial opportunities that will

benefit from our unique expertise in this arena.

IkarIa CapabIlITIeS

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Our flagship commercialized

product, INOMAX® (nitric oxide)

for inhalation, demonstrates

our ability to develop unique therapies

that meet the significant unmet needs

of the most fragile patients. But that’s

just the start.

Harnessing powerful science to produce promising therapies

We discovered that certain naturally

occurring or endogenous signalling

molecules, when properly delivered in low

doses, may demonstrate several essential

critical care benefits. Our investigation of

these powerful therapeutic molecules is

an ongoing journey.

Our drug development program is broad

and far reaching, with roots in nitric oxide,

carbon monoxide and hydrogen sulfide

molecules. Through groundbreaking

research, these molecules have been

established as powerful influencers

of many cellular functions. They are just

the beginning of our further exploration

into developing promising products for

critical care.

Leveraging our deep clinical insight and

understanding of pathophysiology, we also

are exploring other promising compounds

that will help address significant unmet

needs of critically ill patients.

Proven execution of complex clinical studies in iCu settings

Ikaria brings substantial clinical development

expertise to all aspects of critical care trial

design and management, executing clinical

trials in more than 4,000 critically ill patients

across multiple ICU settings in the US,

Canada, the EU, and Australia.

Vast clinical and preclinical critical care experience

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the five primary iCu admitting diagnoses are, in order, respiratory insufficiency/failure, postoperative management, ischemic heart

disorder, sepsis, and heart failure.2

Critically ill patients can’t wait for a traditional approach to r&D

Research & development is vital

for clinicians and their patients

in the critical care community.

Meeting their unmet needs is a powerful

driver for Ikaria.

Where breakthroughs are born

Our preclinical discovery and exploratory

research facility is equipped to conduct

state-of-the-art synthetic chemistry, analytical

and bioanalytical chemistry, formulation,

pharmacology, and toxicology studies.

reducing risk and shortening development time

Translational medicine and adaptive trial

design have emerged as two powerful

alternatives to traditional research and

drug development. At Ikaria, we also utilize

biomarkers to help guide and de-risk clinical

development. These strategic approaches have

the potential to reduce costs by facilitating

more efficient clinical trials. Additionally, they

can determine at a significantly earlier date

which formulations are likely to fail in later

trials, potentially saving money and time.

What this means for patients

By identifying earlier which compounds may

have a therapeutic benefit and which patients

may benefit most, translational medicine has

the potential to offer breakthroughs sooner for

patients who need them.3,4 This can make all

the difference for patients who can’t wait.

transforming the future

At Ikaria we continue to define our

leadership role. Fully integrated and

critically positioned, we intend to

advance critical care well into the future

and plan to be on the forefront of the

next major breakthrough.

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nearly 80% of all americans will experience a critical care illness or injury, as a patient, a family member, or as a friend of a patient.5

inoMaX® DS Delivering and maintaining precise levels of a pharmacological gas is complex. but our state-of-the-art transportable INOMaX DS is engineered to simplify the complex administration of INOMaX® (nitric oxide) for inhalation and is fully compatible with more than 45 makes of ventilation devices and anesthesia machines.1,6-8

Our proprietary INOMaX DS delivery system features multiple back-up systems to ensure safe, consistent, and reliable delivery and monitoring at any ventilation setting for all patients.

Warning: The INOMaX DS delivery system must only be used in accordance with the indications, usage, contraindications, warnings, and precautions described in the nitric oxide drug package inserts and labeling.

inoMaX®—a therapy of great possibilities

From the moment it was discovered, nitric oxide has inspired

countless researchers and clinicians to realize the benefits of

this potent pulmonary vasodilator. A compound that is naturally

produced in the human body, nitric oxide is the active substance in

INOMAX, the first and only FDA-approved endogenous signalling

molecule in gas form for use in humans.

At Ikaria, we have been equally inspired by this Nobel Prize-winning

discovery and are dedicated to realizing its full potential. Nitric oxide is

able to penetrate cell walls to deliver a signal to nearby muscles to relax.9

As these muscles relax, blood flow increases, helping the heart and lungs

process more oxygen and deliver more oxygenated blood to the body.

therapy that calls for state-of-the-art medication management

Delivering the full benefit of INOMAX requires advanced medication

management technology for accurate dosing, patient monitoring,

and individualized record keeping. To facilitate optimal delivery,

Ikaria designs, develops, manufactures, and globally distributes

these drug-delivery systems through its FDA-regulated facility.

Please visit www.inoMaX.com.

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offering sophisticated multifaceted support

Whether we’re scheduling an emergency

delivery of medication, flying in equipment

from one of our regional centers, or providing

middle-of-the-night technical assistance,

we do what it takes to ensure that clinicians

and their patients are able to benefit from

this vital therapy.

Clinical & technical Support

• Emergency technical, medical,

and respiratory therapist support;

medical affairs assistance; in-service

training; technical support; and

reimbursement services

Distribution Services & Support

• Emergency deliveries in 4 hours in most

cases; seven wholly owned and operated

regional service/distribution centers;

service and maintenance of all devices;

technical training

ongoing training

Clinical professionals provide on-site training,

education, and scientific and technical

expertise to both new and existing customers.

On average, we interact with and train

approximately 1,800 customers each month.

inotherapy®—an exclusive offering

The value of INOMAX includes a comprehensive, all-inclusive offering of service and

technologies called INOtherapy. This includes the drug, device, distribution, emergency

supply, technical assistance, clinical assistance, and quality maintenance. INOtherapy

is delivered by an exclusive interdisciplinary team of clinical and logistical professionals who are

available to customers 24/7/365.

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Since its commercialization in 2000, we believe that approximately 360,000 patients have been treated with inoMaX® worldwide.1

Committed to advancing critical care worldwide

We have established wholly owned operations in Canada,

Japan, and Australia and have created relationships with

organizations in those regions, as well as in Europe, Mexico,

and South America. This global reach is part of our commitment to

provide advanced critical care therapies around the world.

Our US regional service centers are located

in or around New York, Chicago, Dallas, atlanta,

los angeles, San Francisco, and baton rouge.

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european union Austria Belgium Czech Republic Denmark Finland France Germany Hungary Iceland Ireland Italy Netherlands Norway Poland Portugal Spain Sweden Switzerland United Kingdom

Southeast asia/ South Pacific Australia Japan (as INOflo) Malaysia Singapore

north america Canada United States

latin america Argentina Chile Colombia (as INOflo®) Mexico Uruguay

inoMaX® (nitric oxide) for inhalation is available in the following countries:

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building alliances for the future

Partners

Born of collaboration, Ikaria pursues

paths that lead to the development

and commercialization of acute care

therapies for the significant unmet needs of

critically ill patients. At Ikaria, we are looking

to create future relationships that build upon

our three unique areas of expertise:

• Our insight into the clinical needs

of critically ill patients

• Our deep understanding of the

biology of critical conditions

• Our intimate understanding of the

needs of healthcare providers who

practice critical care medicine

Expertise in preclinical and clinical development

through product commercialization makes us

an ideal partner for any company with assets

focused on critical care conditions. We seek

to acquire additional products and technologies,

including drugs, devices, and drug-delivery

systems at any stage of their development.

therapies on the horizon

In addition to our organic work on NO, CO,

and H2S, strategic licensing and acquisition

enhances the Ikaria pipeline. Our acquisition of

the North American rights to terlipressin puts us

on the forefront of delivering the first treatment

for hepatorenal syndrome Type 1, a rare

and often fatal condition of advanced kidney

failure in patients with cirrhosis.

The acquisition of several exclusive worldwide

licenses further expands our offering of

novel therapies: 

• IK-5001* is a potential breakthrough

treatment for preventing pathological

cardiac remodeling following acute

myocardial infarction†10 

• Investigational fibrin-derived compounds,

known as IK-6001, IK-6002, and IK-6003,‡

preserve endothelial barrier function,

prevent tissue injury,† and hold great

promise for exploration in a multitude

of critical care conditions11,12

For a full list of our areas of focus, visit www.ikaria.com. 

*IK-5001 – Licensed from BiolineRx (BL-1040).† In animal disease models.‡ IK-6001, IK-6002, IK-6003 – Licensed from Fibrex Medical (FX06, FX201, FX107).

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there are approximately 6,000 iCus in the united States.2

References

1. Data on file. Clinton, NJ: Ikaria Holdings Inc.; 2009.

2. Society of Critical Care Medicine. Critical care statistics in the United States. http://www.sccm.org/AboutSCCM/Public%20Relations/Pages/ Statistics.aspx. Accessed July 24, 2009.

3. Littman BH, Di Mario L, Plebani M, Marincola FM. What’s next in translational medicine? Clin Sci. 2007;112(4):217-227.

4. Chow SC, Chang M. Adaptive design methods in clinical trials: a review. Orphanet J Rare Dis. 2008;3:11.

5. Society of Critical Care Medicine. Critical care questions. http://www.myicucare.org/Critical_Care_Questions/Pages/default.aspx. Accessed July 24, 2009.

6. Datex-Ohmeda, Inc. INOvent Delivery System Operational and Maintenance Manual.  Madison, WI: Datex-Ohmeda, Inc; 2000. Publication 1605-0014-000. 

7. INO Therapeutics. INOmax DS Operation Manual. Clinton, NJ: INO Therapeutics LLC; 2002.

8. INO Therapeutics. INOblender Operation and Maintenance Manual. Clinton, NJ: INO Therapeutics LLC; 2001. 

9. Bryan NS, Bian K, Murad F. Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci. 2009;14:1-18.

10. Landa N, Miller L, Feinberg MS, et al. Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation. 2008;117:1388-1396. http://circ.ahajournals.org/cgi/content/abstract/117/11/1388. Accessed August 28, 2009.

11. Gröger M, Pasteiner W, Ignatyev G, et al. Peptide Bß15-42 preserves endothelial barrier function in shock. PLoS One. 2009;4(4):e5391. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005391. Accessed August 28, 2009.

12. Roesner JP, Petzelbauer P, Koch A, et al. Bß15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion. Crit Care Med. 2009;37(2):598-605.

www.ikaria.com

In the United States:6 Route 173 Clinton, NJ 08809Voice +1-908-238-6600Fax +1-908-238-6633

Customer Service 24/7/365: +1-877-KNOW-INO (+1-877-566-9466)

© 2009 Ikaria, Inc. October 2009.The product information here is presented for use in the United States. IMK111-01164R 10/09