Spring Bank Presentation Jan 09

Nucleic Acid Chemistry for a New Generation of Pharmaceuticals

Corporate Presentation

Confidential

Spring Bank Corporate Vision

Utilize our proprietary nucleic acid chemistry platform to design and develop molecules which closely mimic the bodies’ natural disease signaling pathways resulting in therapies with superior specificity, safety and efficacy in antivirals, autoimmune diseases and cancer

Investor Overview

Breakthrough nucleic acid based therapeutic platform– Orally bio-available, natural-like nucleotides are effective and non-toxic– Ability to leverage chemistry profile for rapid clinical advancement and low investment

Multiple therapeutic targets: viruses, autoimmune diseases, cancer

Initial anti-viral application targets $16 billion worldwide hepatitis market– Non toxic– Effective in vitro against known resistant strains– in vitro synergy data indicates promise for combination therapy use

Hepatitis programs have made significant preclinical progress towards IND

NIH validates as “new class” of drugs, has committed $7 million to date

Technology evaluation in process with major pharmaceutical company

Exploring development collaborations in Asia

Seeking Series A financing to build organization and advance programs into humans

Spring Bank Corporate Overview

Founded in 2002

Proprietary nucleotide-based therapeutic platform– Orally bio-available, natural-like nucleotides are effective and non-toxic– Ability to leverage chemistry profile for rapid clinical advancement and low investment

Proprietary manufacturing technology allows:– Rapid synthesis of lead compounds for development– Cost effective commercial scale manufacturing

Multiple therapeutic targets: Viruses, autoimmune diseases, cancer

2 candidates in preclinical development– SB 9000 for Hepatitis B– SB 9200 for Hepatitis C

NIH validates as “new class” of Hepatitis drugs, has committed $7 million to date– Significant preclinical progress funded by NIH

Initial anti-viral lead candidates (SB 9000, 9200) target $16 billion Hepatitis market– Non toxic in vitro and in animal models– Effective in vitro against multiple genotypes– In vitro synergy data indicates promise for combination therapy use

Spring Bank Platform Allows for Multiple Points of Influence

Proteins are key to almost all biological functions

DNA

DNA provides the blueprint for protein assembly

Naturally occurring nucleotides interact with proteins and nucleic acids in the body to perform important cellular functions

Nucleic acid therapeutics are natural-like and have multiple options/binding targets at the nucleic acid or protein level to interfere with specific disease processes

NORMALPROTEIN

RNA Protein

Spring Bank Technology Platform Applicable to a Wide Range of Therapeutic Targets

Proprietary nucleic acid chemistry platform produces families of compounds with consistent biological properties and superior pharmaceutical attributes

Similar safety, ADME and dosing profiles reduces development risks and speeds time to market for follow-on compounds

Nucleic acid compounds can be designed rationally against well-established molecular targets associated with diseases

– Selectivity - to the target tissue– Specificity - to the molecular target– Safety - non-toxic to cells and tissues, ingested and excreted without breaking down

Proprietary solution phase manufacturing process scalable for commercial quantities

Spring Bank Technology Platform – Strong Competitive Advantages

Nucleoside/Nucleotide Analogs

Immune Modulators

RNAi/Antisense SB 9000

Mechanism of Action

Chain terminators –target HBV/HCV polymerase

Activate natural immune response

Complementary RNA strands bind with viral DNA/RNA

Targets viral DNA primer that initiates viral replication

Major DrawbacksViral mutation and resistance/Toxicity

Toxicity/Delivery Delivery/Toxicity N/A

Delivery Oral Injection Injection Oral

Viral mutation/resistance

Yes Not known Yes No

Combination Therapy

Limited Options Required Not known Possible

Toxicity Significant Significant SignificantNon-toxic, not metabolized by liver Cyt P450

Long Term Administration

No/Toxic No/Toxic No/Toxic Probable

Manufacturing Economical/scalable Expensive/difficultNeed to develop specialized facility

Economical/scalable

Urgent Need for New Hepatitis Therapies

HBV– 1/3 world population (2+ billion) infected– ~350 million chronically infected– 1 million deaths per year

HCV– 4 million+ chronic carriers in the US– Limited treatment options – interferon plus ribavirin– 170 million chronically infected worldwide

Hepatocellular Carcinoma (HCC)– Persistent, chronic HBV and HCV infection responsible for 95% of HCC– Most common malignant tumor worldwide – 1.2 million new cases every year – 5-year survival rate less than 5%– 15,000 US deaths/year from HCC

Major NIH initiative under way to develop new Hepatitis therapeutics

Combinations of oral antiviral therapies will likely be the future gold standard for treatment of Hepatitis

>8% High

2–7% Intermediate

<2% Low

Total CHBV: ~375MM

Annual New Inf.: 2–3MM

Annual Deaths: 1.3–1.5MM

2003

Source: World Health Organization

Chronic HBV is a Global Health Problem: 350–400 Million Infected

E. Mediterranean18.5MM

North America

1.5MM

Africa71.9MM

Latin America 8.7MM

Southeast Asia69.8MM

Western Pacific

181.1MM

Europe22.9MM

HBV– 1/3 world population (2+ billion)

infected– ~350 million chronically infected– 1 million deaths per year

HCV– 4 million+ chronic carriers in the US– Limited treatment options– 170 million chronically infected

worldwide– Progression to cirrhosis, liver cancer

Hepatocellular Carcinoma (HCC)– Chronic infection responsible for 95%

of HCC– Most common malignant tumor

worldwide – 1.2 million new cases every year – 5-year survival rate less than 5%

Major NIH initiative under way to develop new Hepatitis therapeutics

SB 9000 Target Indication: Hepatitis B

Hepatitis – – Liver is host to Hepatitis B virus, and is target organ for therapy– Disease progression leads to liver failure, hepatocellular carcinoma – Liver transplants become re-infected

Limited effectiveness of existing therapeutics – Resistance– Chain terminator mechanism of action leads to non-specific host toxicity – Competitive drugs need to be metabolized by the liver to become active,

leading to toxicity and limiting dosage

SB 9000 is an excellent anti-viral candidate– Oral bioavailability– Non-toxic– Not metabolized by the liver (CytP450) – Synergy with other classes of antivirals may allow for combination therapy with SB

9000– In vitro activity against all known resistance mutations for HBV

SB 9000 Demonstrates Anti-HBV Activity in 14 Day Transgenic Mouse Model

Initial high-dose study Dose response study

EC50 of SB 9000 is <1 mg/Kg

More potent than Adefovir

14-day daily administration IP route SB 9000 safe at 100 mg/Kg Adefovir 10 mg/Kg Quantitative PCR and Southern

blot analysis Near-complete absence of liver

HBV DNA by day 14

**P < 0.05, ***P < 0.001

SB 9000 Demonstrates Potent Suppression of Liver HBV DNA in 14 Day Transgenic Mouse Model

Southern blot analysis of liver HBV DNA following 14-day treatment

No treatment-associated toxicity with SB 9000

SB 9000 in CES

Adefovirin CES

CES (control)

SB 9000 in Saline

Saline (control)

Southern Blot Analysis of Liver HBV DNA

Treated Control

Oral SB 9000 Prodrug Shows Potent Antiviral Activity in 14-Day Transgenic Mouse Model

0

10

20

30

40

50

Liv

er

HB

V D

NA

(p

g/u

g c

ell

DN

A)

EC50 < 3mg/Kg

SB 9200 Target Indication: Hepatitis C

Hepatitis – – Liver is host to Hepatitis C viruses, and is target organ for therapy– Disease progression leads to liver failure, hepatocellular carcinoma – Liver transplants become re-infected

Limited effectiveness of existing therapeutics – Resistance– Chain terminator mechanism of action leads to non-specific host toxicity – Competitive drugs need to be metabolized by the liver to become active,

leading to toxicity and limiting dosage

SB 9200 is an excellent anti-viral candidate for HCV– Oral bioavailability– Non-toxic– Not metabolized by the liver (CytP450) – Synergy with other classes of antivirals may allow for combination therapy with

SB 9200

In Vitro and In Vivo Safety Studies of SB 9200

Has CC50 > 1000 uM in a panel of cell lines including bone marrow (HFF), kidney (MDBK), Hep G2.2.15 (liver) and PBMC

No evidence of toxicity in mice in dose-ranging studies up to 300 mg/kg/day by oral administration for 14 days

No evidence of toxicity in dose-ranging studies in rats by oral administration at 1g/kg/day for 7 days

Non mutagenic in the Ames assay at high doses

*Replicon cell line containing H/FL-Neo (genotype 1a (H77), full length construct) (Blight, et al., 2003, J. Virol. 77:3181)**Replicon cell line AVA5 (sub-genomic (CON1), genotype 1b; (Blight, et al., 2000, Science 290:1972)

EC50 and EC90 are drug concentrations which results in a 2-fold, or a 10-fold depression of intracellular HCV RNA relative to

that of the untreated controls [ Dot blot hybridization assay normalized to b-actin RNA].

SB 9200 Shows Potent Anti-HCV Activity In Vitro

Viral Genotype

Compound

1A* 1B**

EC50 EC90 EC50 EC90

micromolar micromolar

SB 9200 2.2 8 1 6

SB 9400 NA NA 0.16 NA

SB 9300 2.9 8.5 3.2 NA

Interferon (alFNB2) U/mL

1.8 8.0 2 8.5

2CMeCyt (NM 283) 1.6 6.2 NA NA

Inhibition of HCV Replication Using the Replicon Assay

SB 9200 Has Demonstrated Synergy with Several Drug Combinations in Vitro1

Drug EC50

(uM)

Ratio EC50Comb

(uM)

Comments

SB 92001.5 - 2.3

+Interferon α 2.1 3:1

1:1

1:3

0.662

0.643

0.658

Synergistic

Synergistic

Synergistic

+Ribavirin >30 1:30 2.3 Synergistic

+Ribavirin + interferon α 3:1

1:1

1:3

0.777

0.629

0.686

Synergistic

Synergistic

Synergistic

+ 2CMeCyt (NM 283) 1.4 3:1

1:1

1:3

0.522

0.494

0.462

Synergistic

Synergistic

Additive

+Vertex (telaprevir) 0.250

(CC50<80)

100:1

30:1

10:1

0.108

0.126

0.118

Synergistic

Synergistic

Synergistic

1In collaboration with Brent Korba, Georgetown University

Strategic Plan for Value Creation

Build world class management and scientific teams, establish relationships with key international opinion leaders

Advance key development programs through Phase IIa proof of concept– Phase IIa endpoint (demonstration of reduction in viral load) maximizes partnership value

Establish partnerships to generate non-dilutive capital and reduce risk– Development and commercialization partnerships– Research collaborations in autoimmune diseases and cancer– Product, discovery platform and manufacturing technology licensing

Leverage technology platform to build pipeline of new drugs for high value disease targets

Management

Douglas Jensen Co-founder & CEO

Co-founder and CEO, Origenix Technologies

VP Administration & Corporate Development, Hybridon

Sr. VP Oppenheimer & Company

R.P. (Kris) Iyer, Ph.D. Co-founder & CSO

Co-founder & VP Discovery, Origenix

Senior Scientist & Associate Director of the DiscoveryProgram and Technology Development, Hybridon

Don Mitchell, MBAVP Corporate Development, CCO

Exec Director, Corp Development, Idenix Pharmaceuticals

Director of Marketing/Strategic Planning, Amgen

Principal Consultant, PricewaterhouseCoopers

Director, Marketing/Business Development, Novartis

Academic Collaborators

Professor Brent Korba, Ph.D. Georgetown University (HBV, HCV)

Professor John Morrey, Ph.D. Utah State University (HBV)

Professor Nigel Bourne, Ph.D. University of Texas (HCV)

Professor Norman Kneteman, Ph.D. University of Alberta, KMT Hepatech

Investment Highlights

Patented nucleic acid platform technology with wide range of potential disease targets

Clinical candidates SB 9000, 9200 demonstrate excellent safety and efficacy profiles in preclinical studies

– Orally bioavailable– Non-toxic– Potential for use in combination therapy– Effective against multiple genotypes

$7 million NIH support to date validates “first-in-class” therapeutic platform and need for new approach to hepatitis

Technology evaluation in process with major pharmaceutical company

Exploring development collaborations in Asia

Seeking Series A financing to build organization and advance programs into humans