May 8, 2013

www.healthadvances.com

Health Advances, LLC BOSTON SAN FRANCISCO ZURICH

Skip Irving Partner and Managing Director

Advancing Research to Treatments: Unmet Needs In Glioblastoma

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 2

Unmet Need

Senator Ted Kennedy - 2008 Democratic National Convention in Denver, Colorado August 25, 2008. –

REUTERS

Senator Kennedy’s tragic death brought greater visibility to the tremendous need for improved brain tumor treatment options.

§ 76 years old at diagnosis

§ May 17, 2008: Seizure at his home in Hyannis, MA

§ Medflight from Cape Cod Hospital to Mass General Hospital in Boston

§ Diagnosed with Glioblastoma Multiforme

§ August 25, 2009: Died15 months after diagnosis

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 3

By annual incidence, glioblastomas are the most common type of malignant brain tumor.

Gliomas

Other Malignant

Non- Malignant

0%

25%

50%

75%

100%

Brain Tumors Gliomas

Perc

enta

ge

Other Gliomas

Oligoastrocytic Tumors

Pilocytic Astrocytomas

Anaplastic Astrocytomas

Oligodendrogliomas

Ependymal Tumors

Diffuse Astrocytomas

Glioblastomas

US Distribution of Brain and CNS Tumor Incidence By Histology

2005-2009

Unmet Need

Source: CBTRUS, American Brain Tumor Association website.

Glioblastomas Most malignant, most

aggressive and shortest survival

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 4

Note: Relative survival rates for primary malignant gliomas are from SEER, 1973-2004. Source: DataMonitor, CBTRUS, SG Cowen, Medscape.

Relative Survival Rates for Primary Malignant Gliomas

Unmet Need

Glioblastomas progress rapidly without therapy.

0%

20%

40%

60%

80%

100%

120%

0 12 24 36 60 96 120

Rel

ativ

e Su

rviv

al R

ates

Months After Diagnosis

Mixed Glioma

Oligodendroglioma

Anaplastic Astrocytoma

Glioblastoma

Ependymoma

Astrocytoma, NOS

Clinical history is less than three months in majority of patients; Prognosis worse for

elderly patients

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 5

The best current standard of care extends overall survival to about 14 to 16 months.

Therapeutic Options

* Data for bevacizumab represents newly-diagnosed glioblastoma and is from a phase II clinical trial with no placebo control. Source: UpToDate; Gil-Salu, J., Neurocirugia, 2004; Walker, M., J. Neurosurgery, 1978; Westphal, M., Neuro-Oncology, 2003; Stupp, R., NEJM, 2005; Athanassiou, H., JCO, 2005;

Stewart, L., Lancet, 2002; Lai, A., JCO, 2011.

Median Overall Survival Time of Glioblastoma Patients by Therapy

0

6

12

18

24

Surgery Only

+ Radiotherapy (RT)

+ RT + Carmustine

+ RT + Carmustine

Implant

+ RT + Temozolomide

+ RT + Temozolomide + Bevacizumab*

Mon

ths

Treatment Regimen

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 6

Surgical Resection

Treatment Paradigms Temozolomide with radiation is the first line treatment of choice.

MRI and/or CT Suggestive of Glioblastoma

Biopsy

Confirmation of Glioblastoma

Clinical Trials

Second-Line Therapies

Nitrosoureas

First-Line Therapies

Radiotherapy GLIADEL WAFER (polifeprosan 20 with carmustine implant

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 7

Current Therapies The basic patent on Temodar will expire in 2014.

Source: Compant 10ks, websites, Datamonitor, UpToDate, Analyst Reports.

67% ~$920 25%

~$350

8% ~$110

§ Oral and IV §  Approved 2005 § Generic launch in

August 2013

§  IV §  Approved for 2nd line

glioblastoma in 2009 §  Evaluation as addition

to 1rst line

§  Implant §  Approved

1996

GLIADEL WAFER (polifeprosan 20 with carmustine implant

Total Market: ~ $1.4B

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 8

Drug Development Challenges Anticipating the path to market involves a series of connected questions.

Proof-of-Concept Evidence

Clinical Trial

Endpoints

Differentiated Clinical Utility

Label Claims

Revenue Potential

Basic Research

Pathway and

Targets

Translational Medicine

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 9

Dramatic unmet needs will drive interest in any new therapy.

Opportunities

Development Challenges

Challenges

Blood-Brain Barrier §  Formulation and delivery?

Tumor Heterogeneity §  Breadth of use?

Lack of Screening Tools §  Risk factors? §  DX prior to malignancy?

Low Incidence/Rapid Progression §  Market potential? §  Trial recruitment?

High Unmet Need §  Incremental improvement §  Risk tolerant §  Rapid market uptake

Small Population, Orphan Drug Potential

Survival Drives Prevalence §  Increased population §  Extended duration of therapy

Pricing Flexibility §  Extreme mortality §  Low generic impact

Combination Therapy §  Multiple mechanisms

Centers of Excellence §  Focused call points §  Specialty market strategy

Paucity of Biomarkers §  Assessing prognosis? §  Patient segmentation? §  Differential treatment?

And

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 10

Development Challenges Better understanding of specific patients sub-segments can be valuable for clinical development and precision in selecting treatment options.

Frequency 25% 75% 45% 55% 50% 50%

Overall Survival 23 months1 15 months 22 months2 13 months2 15 months2 9 months2

Negative for

EGFRvIII

Positive for

EGFRvIII

EGFRvIII

Unmethyl-ated

MGMT

Methylated MGMT

MGMT Gene

Over 65 Under 65

Age

1 Data based on general patient populations treated with rindopepimut immunotherapy and temozolomide and lacking a placebo control. 2 Data based on patient populations receiving radiotherapy and temozolomide.

Source: Babu, R., Core Evidence, 2012; Hegi, M., NEJM, 2005; Oszvald, A., Journal of Neurosurgery, 2012.

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 11

Pipeline Activity An active early stage pipeline with a multiple different approaches.

Number of Glioblastoma Therapies in Development

By Category

0

20

40

60

80

Preclinical Phase I Phase II Phase III

Num

ber o

f The

rapi

es

Clinical Trial Phase*

Other Therapies

Immunotherapies

Biologics

Small Molecules

* Clinical Trial Phase refers to the highest regulatory phase reached worldwide and excludes therapies already launched in another indication. Source: Pipeline databases, company websites, clinicaltrial.gov.

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 12

Today’s Presentations § Small molecule glycolysis inhibitor § Drug-resistant cellular therapy

§ Therapeutic vaccine § Bi-specific antibody

Pipeline Activity Presentations today reflect the diversity of therapeutic approaches being investigated.

Small Molecule

Chemotherapy

Monoclonal Antibodies

Other Approaches

§ Gene therapy §  Lytic viruses § Nucleic acid

therapies § Nanoparticles §  Stem cell therapy

Immunotherapies §  Active immunization §  Adoptive therapies

New Options for Glioblastoma

Patients

Unmet Needs in Glioblastoma CONFIDENTIAL — May 8, 2013 13

Skip Irving Partner

sirving@healthadvances.com

Health Advances LLC 9 Riverside Road

Weston, MA 02493

781-647-3435 www.healthadvances.com