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WELCOMEInvestor Day 2012

Forward Looking Statements

Statements contained in this presentation that are not historical facts are forward looking statements which involve certain risks and uncertainties including, but not limited to, risks associated with the uncertainty of managing rapidly changing technologies, limited access to capital, competition, the ability to attract and retain qualified employees, our ability to execute our strategy, the uncertainty of the future performance of our partner companies, acquisitions and dispositions of additional partner companies, the inability to manage growth, government regulation and legal liabilities and the effect of economic conditions in the business sectors in which our partner companies operate, negative media coverage and other uncertainties as described in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K.

Safeguard does not assume any obligation to update any forward looking statements or other information contained in this presentation.

NYSE:SFE

Investor Day 2012

NYSE:SFE

Survey

NYSE:SFE

• Expect to be Contacted Shortly

• Your Participation is Critical

• Findings will Assist Management in: • Understanding any Misperceptions within the Investment Community• Developing Strategies to Maximize Value and Communicate Effectively

Peter J. BoniPresident and CEOInvestor Day 2012

The Safeguard Difference (NYSE:SFE)

NYSE:SFE

SIGNIFICANTLY UNDERVALUED

Why Own Safeguard?

• Full Value Yet to be Realized

• Ownership Stakes in Exciting Partner Companies

• Top Performance of Proven Team

• Financial Strength, Flexibility and Liquidity

• Strong Alignment of Interests

NYSE:SFE

Experienced Team

NYSE:SFE

The Company We Keep

NYSE:SFE

http://www.bioadvance.com/

http://www.constellationpartnersllc.com/

http://www.pfizer.com/home/

http://www.fidelity.com/

http://www.umassmed.edu/

Safeguard Today

NYSE:SFE

Safeguard Positioning

NYSE:SFE

Go To Market Strategy

> Growth Financing

> Typically Deploy Up to $25M

> Generally Primary Shareholder

> Realize Value

GROWTH DRIVERS CRITERIA

•Maturity•Migration•Convergence•Compliance•Cost Containment

•Management•Market•Model•Momentum•Moat

NYSE:SFE

Attractive Sectors

Represents % of Capital Deployed in Current Partner Companies as of June 30, 2012.

NYSE:SFE

Recent Success Stories

NYSE:SFE

Acquired By Proceeds*Cash-on-Cash

Return

$38M 4x

$138M 13x

$41M 3x

$208M** 3x

* Includes amounts held in escrow as of June 30, 2012 which are deemed likely to be realized during 2012, if any, but not unearned milestones / earnouts, where applicable.

** Proceeds include $61M from sale of CLRT shares during Q3’09.*** Based on achievement of difficult earnout provisions.

Return Potential Could Approach 8x***

Market Cap Increased 5x

Revenue Stages

NYSE:SFE

Safeguard Partner Companies

•16 Partner Companies Today

•26 Board Seats Across 16 Companies

•15 Companies Generating Revenue

•Deployed $176.7M in Current Partner Companies as of June 30, 2012

•Realized $643M Since January 2006

* Aggregate revenue guidance for 2012 and prior years, presented above, reflects revenue on a net basis. Revenue figures utilized for certain companies pertain to periods prior to Safeguard’s involvement with said companies and based solely on information provided to Safeguard by such companies. Safeguard reports the revenue of its equity method and cost method partner companies on a one-quarter lag basis.

NYSE:SFE

RANGE:$185M to $190M

Strategy for Growth

• Build Value in Current Holdings

• Realize Some Valuable Exits

• Replenish The Holdings with Winners

• Expand the Platform

NYSE:SFE

Stephen T. ZarrilliSVP and CEOInvestor Day 2012

Key Financial Fundamentals

* At 6/30/12** At/Since 1/1/06

• Strength, Flexibility and Liquidity• Cash and Equivalents and Marketable Securities: ~$241M*• Realized $643M in Proceeds (Excluding Amounts held in Escrow)**• Deployed $327M in Safeguard Capital**• Tax Loss Carryforwards in Excess of $150M*

• Strict Management of Operating Expenses• $0.85 Per Share on Annual Basis

• Continued Expansion of Capital Under Management• Income

NYSE:SFE

Cash Use

6/30/12 YTD(in millions)

New Capital Deployments 12$ Follow-On Funding for Existing Holdings 7 Operating Expenses 10 Penn Mezzanine 2

31$

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Current Holdings

Acquisition Year

Ownership %

Carrying Value* Cost

Life Sciences Partner Companies:Alverix 2007 50% - 8.4 Good Start Genetics 2010 29% 6.2 10.5 Medivo 2011 30% 5.8 6.3 NovaSom 2011 30% 15.7 20.0 PixelOptics 2011 25% 13.4 27.1 Putney 2011 28% 9.0 10.0 NuPathe (Nasdaq:PATH) 2006 18% 10.9 18.3

TOTAL: 61.0 100.6

Technology Partner Companies:AdvantEdge Healthcare Solutions 2006 40% 8.1 15.3 Beyond.com 2007 38% 10.6 13.5 Bridgevine 2007 23% 6.5 10.0 DriveFactor 2011 24% 1.6 1.7 Hoopla Software 2011 25% 1.2 1.3 Lumesis 2012 32% 2.2 2.2 MediaMath 2009 22% 11.7 16.9 Spongecell 2012 23% 10.0 10.0 ThingWorx 2011 30% 3.1 5.0

TOTAL: 55.0 75.9

Total: Life Sciences + Technology 116.0$ 176.5$

($ in millions)

*As of 6/30/12** Figures above do not include amounts deployed relating to Penn Mezzanine since inception or amounts previously deployed in private equity funds.

****

NYSE:SFE

• Purpose/Objective• Asset Diversification• Expansion of Capital Platform• Revenue/Fee Income Generation

• Economic Attributes• 36% Ownership • Income• 8% Preferred Return• $30M to be Deployed• Rollover of Capital into Future Pools

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Equity Incentive Compensation

• Aligned with Shareholder Interests

• Primarily Performance Based Vesting

• Target Returns on Deployed Capital and Market Cap Thresholds

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Questions & AnswersInvestor Day 2012

James A. DatinEVP and Managing DirectorInvestor Day 2012

Bridgevine, Inc.

NYSE:SFE

Bridgevine is a leading performance based digital marketing company that has consolidated the fragmented digital media ecosystem through a proprietary up-sell and cross-sell optimization platform.

•Migration from offline to online advertising

•Acquires Customers for Internet, Phone, TV, Wireless and Entertainment

•75+ Marquee Advertisers Fully Integrated Into Bridgevine Platform

•Partners include AT&T, Comcast, DirecTV, Amex, Dell, Intel and more!

•Named to INC. 500|5000 Six Years in a Row

•Highly Scalable Business Model

•New CEO – J. Patrick (“JP”) Bewley

$10.0M 23% AUG’07CAPITALDEPLOYED

SFE STAKE INITIAL CAPITALDEPLOYED


Cloud Based Research & Analysis Platform for the Municipal Fixed Income

Market

Safeguard Scientifics Investor Day Presentation

October 9, 2012 Yale Club

Company Age:

• Founded 2010• Youngest company in the Safeguard portfolio

Location: Stamford, CT Team:

• Founders: Gregg Bienstock, Ambac, Tim Stevens, Ambac• Board: Jim Ashton, Ex-CEO Sungard; Robin Wiessmann, MSRB Board &

Ex-Treasurer State of PA; Philip Moyer, Ex CEO EDGAR Online, MD Safeguard

Funding:

• $850,000 Invested by Co-Founders• $250,000 Seed Financing from Friends and Family• $2.2mm Series A from Safeguard + $300k others

Market US Muni Market

$4.0 Trillion Market, 1.5mm CUSIPS, 54,000+ Issuers 30% Institutional: Portfolio & Risk Managers, Credit Analysts: estimate 6,000 as target 70% Retail: 275,000 Financial Advisors; estimate 63,000 as target

Opaque Market Facing Increasing Scrutiny and Regulation State and Local Government Fiscal Reality Unfunded Liabilities: $2 to $3 Trillion of Unfunded Pension and OPEB Liabilities Stale Financials: 190 days from Fiscal Year Close and Financial Reporting Insurance and Ratings: Decreased Reliance Increased Regulatory Framework: Dodd Frank, MSRB and FINRA

Alternatives to Ratings Required to Disclose to Investors Information “Reasonably Available” Report Material Events Timely

Investors Chasing Yield

Limited Analytical Tools

Lumesis DIVER Platform

Parsed 1.5 million Muni Bonds by CUSIP and Geo-Locate to State, County, City and School District Level

Built Massive Cloud-Based Data Store Integrated Nearly 200 Private and Public Data Sets Housing, Employment, Education, Commerce, Disasters, Healthcare, Income,

Pension, Population, Taxes and More Users Securely Import Portfolios of Any Size

Sophisticated Analytical and Visualization Tools that Scale

Deep IP: Patents Pending

Two Products

DIVER AnalyticsTarget Users: Credit Analysts Portfolio and Risk Managers

Target Market: Global Banks Regional & Bankers’ Banks Mutual Funds Investment Advisory Asset Managers Insurance Companies (P&C, Life) Bond Insurers Hedge Funds

DIVER AdvisorTarget Users: Financial Advisors Legal/Compliance Credit Analysts

Target Market: Global Banks Regional Banks & Broker/Dealers Investment Advisory Insurance (w/ Advisory Networks)

Released: Sept 2010 Scalable Analytical and Visualization Tools for Risk/Portfolio Management Analyze an Entire Portfolio or a Single CUSIP

Highlight and Manage Risks/Opportunities Enhance Credit Research Capabilities Compare to Benchmarks Easily Upload Portfolios

Save Time and Money Eliminates Time-Consuming Data-Mining and Preparation Track Drivers of Municipal Revenues and Expenditures Alerts and Monitoring Pinpoint Issuers/Positions of Concern and Shape Portfolios Integration with Leading Portfolio Management Tool

Business Model: Over $15,000/User/Annum

DIVER Analytics

DIVER Analytics

DIVER Advisor Released: October 2012 Compliance and Information Delivery Solution

Addresses Regulatory Requirements: • FINRA, MSRB, SEC and Internal Reporting Adherence• Dodd Frank/OCC Guideline Support

Generates Client Ready Report Identifying Risks and Characteristics of Every CUSIP• From 30 Minutes to 3 Seconds

Offers Communication Efficiencies Dissemination of Research from Credit Analyst to FA

Serving: Financial Advisor and PWM Networks Simple to Generate and Easy to Deliver to Client Protects from Reputational Risk Improves Client Service with Real-Time Information

Business Model: Between $1,000-$2,500/User/Annum

DIVER Advisor

Product Pipeline

DIVER MBR: “Easy” Button – CUSIP/Sector Based Bond Report

DIVER API: Programmatically deliver DIVER Data to 3rd Parties

DIVER Issuer: Assist Issuers in Analysis and Reporting

Growth Strategies (Use of Funds)

Building Sales & Marketing Team Hired MD of Sales Hired Part Time CMO Adding Dedicated Customer Service Undertaking Significant Branding Effort & New Web Presence

Expanding Development Team

Expanding Data Team

Expanding Strategic Alliances with Established Muni Market Tools Vendors

Financials/Metrics

Revenue Growth at >75% Over 2011

Client CAGR 75%+

Renewal Rate: 88%

Financial Data Company M&A Multiples - 3-5X Revenues

Goal: $15mm++ for 2014

Summary

Municipal Fixed Income Market Underserved Changed Dynamics Increased Regulation

Lumesis Early Stage Company Providing Patent Pending, Cloud-Based Platform Analytics and Visualization Serving the Portfolio & Risk Managers, Analysts, Financial

Advisors and Issuers

Cloud Based Research & Analytical Platform for the Municipal Fixed Income Market


AdvantEdge Healthcare Solutions October 2012

AHS CONFIDENTIAL INFORMATION – Do Not Distribute

Enabling Healthcare Providers to Thrive

AHS is a technology enabled provider of Revenue Cycle Management Services,

Informatics, and Expertise that enables healthcare providers to maximize

financial performance and eliminate compliance risks.

AHS is a technology enabled provider of Revenue Cycle Management Services,

Informatics, and Expertise that enables healthcare providers to maximize

financial performance and eliminate compliance risks.


About AdvantEdge

AdvantEdge Healthcare Solutions Top 10 medical billing, coding and practice management company Over 675 employees in 8 regional offices in the US and 1 office in Bangalore, India Collecting over $1.25B for its physician clients

Recognized industry leader - uniquely positioned

Clients are typically large medical group practices with a high propensity to outsource due to practice characteristics

Since 1966, AdvantEdge (and/or its acquired entities) has served some of the nation’s most respected healthcare institutions

Hospital for Special Surgery North Shore-LIJ Health System

Advocate Healthcare System Wellspan

St. Barnabas Health System SUNY Downstate Med Center

Erlanger Health Centers Partners Healthcare

The Company continues to enjoy outstanding growth opportunities “Thoughtful” acquirer yielding 5 year CAGR of 41% in a consolidating market Organic growth rate (annualized revenue of new sales closed) average of 19.8% annually over past 5 years

AdvantEdge has been recognized as one of the fastest growing companies by regional and national publications, such as INC magazine (4 years running) and NJBusiness (top 10 growth company in 2010)


Business Characteristics

Highly predictable recurring revenues and strong cash flow

Superior client retention

Significant Operating Leverage: Scalable platform based on proprietary technology and workflow

Effective buy-and-build strategy: Integrate, Migrate, Operate

Sales & marketing focus with aggressive organic growth strategy

Management Team has extensive industry, acquisition and integration experience


Market Leading Strategy

Creating Value for Clients, Employees, and Stakeholders through:

GROWTH EFFICIENCYZERO CLIENT ATTRITION

TECHNOLOGY

Organic &

Acquisition

Margin &

Profit E

xpansion

High leverage of synergies

Processing C

ost per Procedure

Client 1 st P

hilosophy

Perform

ance Enhancem

ent

Market D

ifferentiation

INTEGRATION

One C

ompany

One B

rand

One Vision

One P

latform


AHS has a broad footprint across the US and Bangalore, India

AHS Office

AHS Client

AHS Clients (Multiple/many clients)

Geographic Presence


AdvantEdge Value PropositionThe Problem

Constant threat of reduced reimbursement rates

Increasing complexity & regulatory requirements

Technology and staff

investments are expensive

Attract & retain high-quality

staff

The AHS Solution More Money, Faster Compliance, Built-in Business Intelligence and Reporting – Anytime/Anywhere Client First™ Service


The market for the Company’s services is estimated at $4B - $8B

Billing and Practice Management Service Market (Falcon Capital): $8.0BTotal RCM Market (Wallingford Capital/HBMA, 2007): $4.7 B; top 10 billing cos.: $1.0B

In-House:Practice Management Hospital Based MD

RCM

Office-basedRCM

AHS Target Market

Target markets

Large and growing market: Physician expenditures

increasing by 8% + / yr. Increasing shift to

outsourcing (RCM); currently less than 20% of total

Largest competitor has under 5% of total market

Large and growing market: Physician expenditures

increasing by 8% + / yr. Increasing shift to

outsourcing (RCM); currently less than 20% of total

Largest competitor has under 5% of total market

Market Opportunity


Financial Performance

2009 Revenue and EBITDA growth of 116% and 125% respectively 2010 Revenue and EBITDA growth of 85% and 280% respectively 2011 Revenue and EBITDA growth of 41% and 67% respectively

**EBITDA reflected throughout this report is adjusted to add back capital and acquisition related costs and Investor Group management fees


October 2012Company Overview

MediaMath provides the technology to plan, execute, optimize and analyze marketing programs across all digital channels.

Technology Results TeamStrategy,

Support and Vision

“Empowering the new marketing professional”

MediaMath: The New Marketing OS

Com

pany

Fas

t Fac

ts Industry Leadership Operating system for digital marketers

Over 1,000 clients and growing quickly

176 employees in 7 offices worldwide

Over 120% CAGR – Inc. 500 Fastest Growing

World-class support, services and training

Technology Leadership Delivers the complete ad tech stack

Largest access to supply

Highest quality infrastructure

© 2012 MediaMath, Inc. All rights reserved. Confidential.

The ProblemThe ad tech

landscape is getting more complex

My vendors are slow to innovate

Digital media usage is eclipsing

offline and TV

CMO’s under pressure to “figure out” digital

Average CMO tenure is just

36 months

Innovation at scale is difficult


2011 Advertising Spend in US

Source: emarketer 2011, Forrester 2011


2011 Estimated Stats for Exchange Buying & RTB

RTB MARKET:Grew from $0 in 2008

Source: emarketer, Forrester, AMG Industry Interviews


New York

ChicagoSan Francisco Boston

Los Angeles

International Footprint & Expansion

= Current Office or Datacenter

Washington

= Region with Active Clients

Hong Kong

Berlin (JV)LondonParis


Forrester Ranks DSP’s: MediaMath is #1

“MediaMath is a great all-around choice for buyers in market for a DSP.”

“Its large employee base and diverse, well-tenured management team also provide the necessary foundation for it to execute effectively on its strategic vision: to empower marketing professionals with a flexible, easy-to-use, multichannel platform.”

“MediaMath boasts excellent algorithmic optimization capabilities (including a multifaceted view of the decisioning engine’s output), and its multichannel media and data access is both broad and deep.”


How It Works: Simple Intuitive Interface

1st & 3rd Party Data

Ad Verification

Privacy Compliance

Ad Serving

Supply-side Platforms

Premium Media Sources

Search Retargeting Creative Optimization

Brand Measurement

Exchanges

Social

Mobile

Video

Contextual Targeting

Web Analytics & Attribution

DMP and Data Aggregators

Private Marketplace

Nielsen PRIZM

How It Works: Deep Ecosystem Integrations


How It Works: Real-Time Decisioning at ScaleThe Brain Algorithm 4.0 Processes 80 Billion Bid Opportunities per Day Worldwide

RMX > Monday > 11pm - 12am > mail.yahoo.com > Philadelphia$0.70 RMX > Day = All Other > 12pm-5:59pm >

tech.cnn.com > ISP = Cable > New York $1.98



BREAKInvestor Day 2012

PixelOpticsElectronic Interactive Eyewear

Large and Profitable Market

$82.5B Global Eyewear Market

$30.0B $30.0B

$9.7B$12.0B

$0.8B

Frames Lenses

ContactsSunglasses

OTC Readers

Global Market Opportunity

$450M

revenue realized with every 1% of progressive

market

PixelOptics Objective: ≥5% market share

Disruption in a Sea of Incremental Change

Digital Is Disruptive

Presbyopia

• Loss of accommodation

• Tear quality changes

• Begins in your 40’s

Problem – Aging Eyes

Presbyopic Options

Spectacle Lensesbifocal 1784

progressive 1959

D

N

I

Peripheral Distortion

Ground Blur

Ground Blur

New Category

SmartphoneNot So Smart PhoneStatic Lens

D

N

I

Dynamic Lens

That Comes with a Switch

emPower!• Widest distance and intermediate

viewing

• Near zone activated without distortion

• Electronics hidden & integrated into frame

DI

N

Peripheral Distortion Resolved

Ground Blur Resolved

Expansive Electronic Platform

A Revolutionary Optical Device

Right Temple

Controls Optical Zone

Left Temple

Other Electronics

Incredible Patent Portfolio & Recognized in the Industry

300+ patents and patent pending applications worldwide

The Gold Edison Award for Quality of Life in the competition’s Lifestyle and Social Impact category awarded to PixelOptics

The Technology Category Award given to PixelOptics for emPower - the world’s first electronically focusing eyewear

Recognition

$100M+ Invested and More To Come

Capital History

• $100M+ funding through D Round

• Major Investors• Safeguard Scientifics• Delphi• Longitude • Brian Stark (purchased incremental interest

from Carlyle, June 2012)

• Strategic Investor• Panasonic Healthcare

Learning's Have Driven: New Generation

Favorable • Global industry anticipation

• Value chain margin improvement

• “Optimized” vision on demand

Experience

Jun 2011 – Jun 2012Unfavorable• Frames, electronics unreliable

• Frames not fashionable

• Optics range limited

• Non-optimized coating technologies

• Complex business model

Improvements① New Electronics

& Frames② Optics & Range

Improved

③ OptimizedCoatings

④De-Risked Business Model

1 2 3 40

5

10

15

Moving from an Analog Industry

Lens Companies Frame Companies

To a Digital Industry

PixelOptics Brings It All Together

D

N

D

N

Summary• Pioneered the world’s first electronic interactive

eyewear

• Superior vision introduced into a large ophthalmic market

Summary

• 300+ global issued/pending patents

• $1 Billion+ opportunity


James A. DatinEVP and Managing DirectorInvestor Day 2012

Putney, Inc.

NYSE:SFE

Putney partners with veterinary practices to provide high quality medicines that meet pet medical needs and offer cost-effective alternatives for pet owners.

$10.0M 28% SEP’11CAPITALDEPLOYED

SFE STAKE INITIAL CAPITALDEPLOYED

•Specialty Pharmaceutical Company

•Developing High-Quality, Cost-Effective Generic Medicines for Pets

•Total Global Market for Companion Animal Pharmaceuticals Approx. $5.7B

•Total U.S. Market for Companion Animal Pharmaceuticals Approx. $3B

•+165M Dogs and Cats in +73M Households in the U.S.

•Only 6% of Drugs Approved by FDA for Dogs/Cats Have Generic Equivalent

•Approx. 20 Drugs in Various Stages of Development and Submission to FDA


© 2012 Good Start Genetics, Inc. All rights reserved. Confidential.

The New Gold Standard in Carrier Screening


Investment Thesis: Genetic Testing Currently a Large Market opportunity and Expanding Rapidly due to advances in Technology

• Good Start Genetics Tests Target a $1B+ and Fast Growing Segment

• Good Start Genetics Has Developed a Cutting Edge Clinical Next Generation DNA Sequencing Platform

Yields Superior Clinical Results Compared to Older, Less Accurate Technology

Advanced NGS platform from the research setting to routine clinical practice

• Market Strategy

Initial focus: U.S. fertility clinics

Maternal Fetal Medicine & large Ob-Gyn’s selectively & with partner

Selected international markets through partnerships

Technical Risk Eliminated- Market Risk Minimized

Tests are in practice guidelines and generally reimbursed by insurance

Direct sales force with laser like focus will yield a competitive advantage

High touch service will increase “stickiness” of large accounts


Genetic Carrier Testing

Competitors:

• Genotyping (fixed)

• Clinical sensitivity limited by cost / benefit tradeoff

• Test must be re-built to increase sensitivity

Good Start Genetics’ Approach

Good Start Genetics:

• Sequencing – (adaptable)

• Clinical sensitivity limited only by clinical knowledge

• Priced in-line with today’s tests


• Ability to analyze vastly more DNA base pairs than traditional technologies (and without cost limitations)

• Testing for the most comprehensive set of known and novel disease-causing mutations

• Yields higher detection rates, regardless of the Patient’s Ethnic Background

The Power of Next-Generation Sequencing

Detecting More Mutations

Groundbreaking Technology

High degree of confidence in carrier screening results

No need to compromise accuracy for price


A balanced approach uniquely focusing on testing for society guideline mandated disorders, coupled with the most comprehensive set of only disease causing genetic mutations per disorder.

OnlyRecommended

Disorders

Only Disease Causing

Mutations

GoodStart Select Balance of Design

Balance drives clinical value and sets a new standard for

excellence

Responsible


Focus on Society-Recommended Disorders Routinely Ordered in IVF

GoodStart Select™ Test Menu

Responsible

AJ – Tests recommended by professional organizations supporting the Ashkenazi Jewish population.


Disease Causing Mutations in CFTR Gene

GSG Tests for 544 Mutations

Groundbreaking

ACOG (23)

Other Labs (98)

Known (544)

Novel (unknown)

GSG (544+)


GoodStart Select™ Cystic Fibrosis ~ 1000 Patient Experience

• Uncovered 32 pathogenic mutations, which is in line with the generally accepted CF carrier frequency rate (testing performed on a diverse ethnic group)

• 3 of the 32 pathogenic mutations detected would not have been found by the frequently used carrier screening tests

• 1 of the 32 pathogenic mutations detected would not have been detected by any other carrier screening test

GSG’s NGS platform is the new gold standard that captures five times more pathogenic mutations than traditional genotyping


Significant Progress Achieved Across Key Areas

Established Organization:

• Senior Leadership Team experienced in Large Lab Operations, Clinical & Molecular Diagnostics, Reimbursement and Administration

• 60+ FTE’s• Technology development• Clinical operations• Sales & marketing• Bioinformatics• Reimbursement

• Recruited world-class Clinical Advisory Board - 12 IVF Physicians

• Recruited Outstanding Genetic Counselor Advisory Board – 8 GC’s

• State-of-the-art CLIA approved clinical lab facility - Cambridge, MA


Clinical & Commercialization Roadmap

Rapid Clinical Progress Achieved

• Proprietary next-generation sequencing technology developed

• Rigorous technical validation of sequencing platform completed

• Clinical validation on affected DNA & blood samples completed

• Augment test menu on next-gen sequencing platform – 23 tests

Path to Commercialization Progress• Q4/2011, Granted MA State Licensure to begin clinical operations

• Q4/2011, GSG Launch in Select U.S. Fertility Clinics

• Q1/2012, National Launch in U.S. - Fertility Clinics

• Today– 23 Tests--Market penetration 50 Clinics & 120 MD’s


Growth Strategy

• Increase sample throughput of next-gen sequencing platform

• Secure New York State Licensure

• In-license additional products

• Develop commercial partnerships for other markets

• Develop partnerships with therapeutic and diagnostic companies

• Drive Revenue Growth - 2013 $20m+

• Achieve Profitability in 2013


The New Gold Standard in Carrier Screening


Corporate PresentationOctober 9, 2012

© 2012 NuPathe Inc. All rights reserved.

Forward-Looking Statements

This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All remarks and information that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, remarks and information relating to: the Company’s ability to satisfy the closing conditions and complete its recently announced financing; the sufficiency of the proceeds to be received upon closing of the financing, together with recently announced cost-containment measures, to fund operations into the fourth quarter of 2013; the Company’s interpretation of the FDA’s complete response letter (CRL); the timing and prospects for FDA approval of Zecuity (also referred to as NP101 and migraine patch); the therapeutic benefits, pricing, reimbursement and market opportunity for Zecuity; partnering and commercialization plans for the Company’s product candidates; duration and scope of IP protection; and other and all other remarks and information relating to the Company’s projections, expectations, beliefs, future performance or plans or objectives for future operations (including assumptions underlying or relating to any of the foregoing).

Forward-looking statements are based on the Company’s current expectations, plans and beliefs and are subject to a number of risks, uncertainties, assumptions and other factors that could cause actual results to differ materially and adversely from those indicated by such statements including, among others: the Company’s ability to satisfy the closing conditions and complete the financing; the Company’s ability to continue operations until the closing of the financing; the adequacy of activities undertaken to address the issues contained in the CRL; the extent to which the FDA may request or require additional information, studies or redesign of NP101; physician and patient acceptance of the Company’s product candidates; safety or other risks that could require the Company to abandon or delay development of, or preclude or limit approval of, the Company’s product candidates; varying interpretation of study and market data; risks and uncertainties relating to intellectual property; and the other factors discussed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2011 under the caption “Risk Factors” and elsewhere in such report, which is available at on the Company’s website at www.nupathe.com in the “Investor Relations – SEC Filings” section. As a result, you are cautioned not to place undue reliance on any forward-looking statements. While the Company may update certain forward-looking statements from time to time, it specifically disclaims any obligation to do so, whether as a result of new information, future developments or otherwise.

http://www.nupathe.com/

• ZecuityTM: substantial near-term commercial opportunity

The first migraine patch

• Delivers sumatriptan, the #1 Rx migraine treatment

Uniquely designed to overcome migraine-related

nausea & vomiting

• Impacts half of all migraine sufferers

• PDUFA date Jan 17, 2013

• Focused on gaining FDA approval, securing

commercial partners, and select pre-launch activities

• Financing & cost containment measures expected to

provide cash runway into 4Q13

NuPathe – Innovative Neuroscience Solutions

• Applied during migraine

• Rapidly delivers sumatriptan

• Bypasses GI tract

• Simple to use, single use

• Multiple application sites

• Strong intellectual property protection until April 2027

First and Only Migraine Patch

Key CRL Issue Action Taken

Skin events of concern Implemented device enhancement • Prevents patch from activating when misapplied

Packaging• Usability

• Uniformity• Containment

Modified secondary packaging• Usability study demonstrated all patients correctly

applied patch during a migraine• Additional data supports consistent uniformity

and containment

Repeat BE study Successfully completed

Required new in vitro method for product release

Developed and validated new in vitro method

Justification of waiver for CA study

Demonstrated that sumatriptan not passively delivered even in presence of penetration enhancers in two laboratory dermal studies

Zecuity NDA ResubmittedPDUFA Jan 17, 2013

• 31 million migraine sufferers

• Triptan market

94% of migraine prescriptions

97% of migraine sales

• Preferred class of migraine treatment

3 – 4 triptan trials before moving to different classes (e.g. opioids, DHE)

• Key challenge for triptans: circumventing pervasive migraine-related GI issues

Injection is poorly tolerated and orals/nasals are unreliable

Triptans Dominate the Migraine Market

Triptans 94%

AnalgesicCombos

5%Ergots1%

Triptan SensationsMimic a cardiovascular event

• >42% of injection patients• > 8% of oral tab patients

Millions Remain Underserved

* Linked to a variety of factors, including gastroparesis.

GastroparesisUnreliable absorption

Inconsistent Efficacy*• >40% of treated patients

Migraine-Related Nausea(MRN)

• 8 million patients in >50% of attacks

• 4.7 million patients in 100% of attacks

Migraine-Related Vomiting(MRV)

• 3.4 million patients in >50% of attacks

• 1.5 million patients in 100% of attacks

Note: Overlap amongst patient types.

• Frequent nausea patients are less satisfied with their migraine medications

• Frequent nausea patients drive direct medical costs for migraine

5.4 times as many emergency/urgent care visits

8.2 times higher overnight hospital stay costs

• Presence of nausea predicts poor response to oral medications in treating headache pain

Headache pain relief with patch not compromised by presence of nausea*

MRN Drives Tremendous Disease Burden

* Ad hoc data analysis of Phase 3 pivotal study ( P <0.0001 ).

• Insurance is >90% commercial private pay

• Payors see value in Zecuity for migraine

Acknowledge barrier of GI issues

Recognize cost of poorly controlled migraine patients

Accept Zecuity as a unique solution

• Payors indicate broad formulary access for Zecuity

Majority Tier 3; opportunities to contract for Tier 2

• Non-orals priced up to $90 per unit (WAC)

Annual gross revenue per patient using 2 patches/month

• $80/patch = $1,900

• $100/patch = $2,400

Broad Formulary Coverage Expected

• Physicians rate Zecuity superior to oral, nasal, and injectable triptans for MRN patients on key attributes including:

Ability to use early in a migraine attack despite GI issues Frequency of triptan sensations and overall tolerability Elimination of nausea at 1 and at 2 hours

• 77% of MRN patients will ask their physician about Zecuity

Quantitative Research Confirms the Market Opportunity for Zecuity

Physicians (n=409) Priority segments

• Heightened concern about MRN

• High interest in prescribing a migraine patch

Patients (n=400) Priority segments

• Actively seeking new treatments

• Highest % of migraines with nausea

• 1.5 million patients vomit with every migraine

• Branded injection pricing of $90/migraine

• 24 migraines per year

Illustrative Market Opportunity(Only Patients Who Vomit with Every Migraine)

0% 2.5% 5% 7.5% 10%$0

$100

$200

$300

$400

$0 $81

$162

$243

$324

Annual Revenue Potential –Patients that Vomit with Every Migraine

Share of Segment – Vomit with 100% of Migraines

Reve

nue

($m

illio

ns)

1.5 MM vomit during every attack

• Secure commercial partnerships

Zecuity is a versatile asset within a portfolio

• Migraine co-morbidity rates include: sleep disorders (52%), depression (44%), arthritis (26%), GERD (25%)

• Specialists (~10K) drive 1/3rd of triptan prescriptions

Headache specialists and neurologists

• Primary care drives the balance of the market

~30K PCPs account for 1/3rd of the market

• Significant commercial opportunity in ROW

Commercialization Strategy

121

• NP202: 90-day risperidone biodegradable implant to treat schizophrenia and bipolar disorder

Designed to address significant patient non-compliance

Continuous delivery reduces psychotic breaks and improves patient functionality1

Seeking global development & commercial partner

• NP201: 60-day ropinirole biodegradable implant to treat the signs and symptoms of Parkinson’s disease

Designed to address the challenges of “on and off” time due to intermittent dosing and reducing drug-related adverse events

Evidence suggests continuous dopaminergic stimulation delays disease progression and improves treatment2

Seeking partner for continued development

Pipeline

• Financing & cost containment measures expected to provide cash runway into 4Q13

$28 million financing expected to close in Oct/Nov Restructured $7.5 million of outstanding debt Headcount reduction and reduced spend on pipeline and

commercialization activities

• Focused on achievement of key milestones Zecuity approval Securing commercial partnerships Select pre-launch activities

Financial

• ZecuityTM: substantial near-term commercial opportunity

The first migraine patch

• Delivers sumatriptan, the #1 Rx migraine treatment

Uniquely designed to overcome migraine-related

nausea & vomiting

• Impacts half of all migraine sufferers

• PDUFA date Jan 17, 2013

• Focused on gaining FDA approval, securing

commercial partners, and select pre-launch activities

• Financing & cost containment measures expected to

provide cash runway into 4Q13

NuPathe – Innovative Neuroscience Solutions


ConclusionInvestor Day 2012

Why Own Safeguard?

• Full Value Yet to be Realized

• Ownership Stakes in Exciting Partner Companies

• Top Performance of Proven Team

• Financial Strength, Flexibility and Liquidity

• Strong Alignment of Interests

NYSE:SFE

John E. Shave IIIVICE PRESIDENT,BUSINESS DEVELOPMENT &CORPORATE COMMUNICATIONS

[email protected]

P 610.975.4952E [email protected]

NYSE:SFE