April 11, 2014

Needham & Company 13th Annual Healthcare Conference

April 9, 2014

April 11, 2014

Safe Harbor Statement

This presentation and other matters discussed today or answers that may be given to questions asked contain “forward-looking” statements that are within the meaning of federal securities laws and are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include information concerning our possible or assumed future results of operations, business strategies, financing plans, competitive position, industry environment, potential growth opportunities, potential market opportunities and the effects of competition. Forward-looking statements include all statements that are not historical facts and can be identified by terms such as “anticipates,” “believes,” “could,” “seeks,” “estimates,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would” or similar expressions and the negatives of those terms. Forward-looking statements represent our management’s beliefs and assumptions only as of the date of this presentation. Our operations involve risks and uncertainties, many of which are outside our control, and any one of which, or combination of which, could materially affect our results of operations and whether the forward-looking statements ultimately prove to be correct. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. We have filed a prospectus pursuant to Rule 424(b) under the Securities Act of 1933, as amended, with the Securities and Exchange Commission (the “SEC”) on February 5, 2014. This presentation contains a summary of selected information contained in our prospectus. Because this is only a summary, it does not contain all of the information you should consider about us. This presentation does not constitute (or serve as the basis for) an offer to sell or a solicitation of an offer to purchase any securities in any jurisdiction. Before you invest, you should read the prospectus and other documents we have filed with the SEC for more complete information about. You may get copies of these documents for free by visiting EDGAR on the SEC website at http://www.sec.gov.

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April 11, 2014

April 2014

Harnessing T cells to create life-changing vaccines and immunotherapies

Focused on a Clear Vision

April 11, 2014

• Innovative T cell target discovery engine • Unique positioning via strong IP

ATLAS Platform

• Positive Phase 1/2a clinical results • Significant commercial opportunity

HSV-2 Immunotherapy

• Novel universal vaccine concept • Significant advance in $5 billion market

Pneumococcus Vaccine

• Experienced management team • Advisors include leaders in vaccinology

Strong Leadership

• HSV-2: 12-month results in Q2 • Pneumococcus: Phase 1 results in Q2

Near-Term Value Creation

Compelling Investment Thesis

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April 11, 2014

T Cell Targets: Enabling Next-Generation Products

• New vaccines

• Cancer immunotherapy

• Autoimmune disorders

T cells matter T cell discovery challenges

New capabilities required

• More potential targets

• Comprehensive, high throughput screening

• Evaluate multiple T cell types & cytokine readouts

A large need . . . but significant discovery hurdles

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• Evaluate diverse human samples

• Diversity of human T cell responses

• Disease-specific characteristics

April 11, 2014

Cohorts of humans exposed to a pathogen

Novel pathogen proteome library

“Responder”

“Non- Responders”

T cell-enabled product

candidates

Novel assays, bioinformatics

T cells APCs

A novel, protected platform

ATLAS

ATLAS: Discovering T Cell Targets by Mining Human Immune Responses

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April 11, 2014

GEN-003 (HSV-2 Immunotherapy)

GEN-004 (Pneumococcus Px)

HSV-2 Px

Chlamydia

Malaria

Discovery

Pipeline of T Cell-Enabled Product Candidates

Pre-clinical Phase 1 Phase 2 Phase 3

Oncology

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April 11, 2014

Herpes Simplex Virus-2 (HSV-2) Immunotherapy

GEN-003

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April 11, 2014

Significant Need for an Immunotherapy

• Lifelong sexually transmitted disease – Painful, recurrent genital ulcers – Significant emotional distress

• Public health epidemic

– 500 million people infected worldwide (16% of U.S. adults) – Contributes to transmission of HIV-1 – Serious complications from maternal-to-infant transmission

• Oral anti-viral drugs have limitations

– Incomplete control of recurring ulcers – Continued risk of transmission – Daily therapy needed for optimal benefit

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April 11, 2014

Rational Product Design; Robust Trial Design

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• Patients: 143 with HSV-2 infections – Moderate-to-severe disease (3-9 outbreaks/year)

• Design:

– Double-blind, placebo-controlled – ~30 subjects in each of 5 groups:

• Placebo • Proteins only • GEN-003 (10 µg per protein + 50 µg adjuvant) • GEN-003 (30/50) • GEN-003 (100/50)

– 3 immunizations at 21 day intervals – 4 x 28 day monitoring periods

• Pre-immunization, post dose 3, at 6 months, at 1 year

• Objectives: – Safety, tolerability, immune response – Impact on viral shedding – Impact on clinical disease (exploratory)

GEN-003

Matrix- M2

adjuvant

T Cell Antigen ICP4.2

B Cell Antigen gD2/TMR

Novel T cell antigen prioritized via ATLAS

Phase 1/2a Trial Overview

April 11, 2014

Highly Significant, Durable Impact on HSV-2

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Baseline After dose 3 After 6 months

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10 µg

100 µg

30 µg

Placebo

Proteins only

*** *** ***

Genital Lesion Rate (a)

*** = p<0.001 (a) Normalized so that rate at baseline = 1

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Baseline After dose 3 After 6 months

*** ***

***

Viral Shedding Rate (a)

10 µg

100 µg

30 µg

Placebo

Proteins only

April 11, 2014

A Potential Cornerstone Treatment for HSV-2

*From Genocea-sponsored survey of 411 patients in US, UK, France and Germany with HSV-2 infections Q: Based on the profile, how likely would you be to use Product X? (instead of current treatment/with current treatment/would not use)

Current Anti-Viral

Usage %

Respondents % Intent to Use

GEN-003* (alone/combo)

Treatment Goals

Chronic (daily use) 26% 93

(37/56) • Additive efficacy • Fewer pills

Episodic (with outbreaks) 38% 90

(60/30) • Additive efficacy • Protection off pills

None 36% 80 (65/15)

• Benefits with low burden to treat

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April 11, 2014

Value-Creating Phase 2 Trial Imminent

• Objective: Optimize GEN-003 dose

• Trial design: – ~300 subjects with moderate-to-severe HSV-2 infections – Factorial design:

• Randomization to 30 or 60 µg per protein; and 25, 50 or 75 µg of adjuvant

• Endpoints:

– Reduction in viral shedding – Reduction in symptoms (exploratory)

• Timing:

– Enrollment to start Q2 2014; initial readout in mid-2015

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April 11, 2014

GEN-003 Program Summary

• Rationally designed using ATLAS

• Positive Phase 1/2a results

• Clear path to additional Phase 2 results

• Large commercial opportunity with best-in-class vaccine

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April 11, 2014

Pneumococcus Vaccine GEN-004

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April 11, 2014

Significant Need for a New Vaccine

• Pathogenic bacterium causing pneumonia, sepsis, meningitis, otitis media – A leading cause of infectious disease mortality

• Global vaccine market value of $5 billion in 2013

– Led by Prevnar/Prevenar (Pfizer): $4 billion

• Commercially available vaccines sub-optimal – Limited serotype coverage – “Non-vaccine serotypes” increasing in incidence – Manufacturing complexity

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April 11, 2014

Natural clearance (TH17 CD4+ T cell-mediated)

Prevnar et al (antibody-mediated)

Intervening against Pneumococcus

http://www.ohiohealth.com/ http://www.childrenscentralcal.org/HealthE/P02948/Pages/P02950.aspx

GEN-004

Alum adjuvant

Novel T cell antigens prioritized via ATLAS

T Cell Antigen SP1912

T Cell Antigen SP2108

T Cell Antigen SP0148

• Cover all pneumococcus serotypes

• Reduce colonization via TH17

• Complement antibody MoA

GEN-004 Proposition

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GEN-004: T Cell-Enabled Path Forward

April 11, 2014

0

50

100

150

200

250

Alum GEN-004 WCV

Am

oun

t of C

olon

izat

ion

(C

FU

s)

Parenteral administration WCV = unencapsulated killed whole bacteria

+ Alum

p<0.001 p<0.001

Nasopharyngeal colonization after 3 immunizations

GEN-004: Effect in Mouse Colonization Model

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April 11, 2014

GEN-004: Phase 1 Trial

• Patients: 90 healthy adult volunteers ages 18-50

• Trial design: – Randomized, double-blind, dose-escalation – 5 dosing groups of ~18:

• Placebo • Proteins only • GEN-004 (10 µg of each protein + 350 µg alum) • GEN-004 (30/350) • GEN-004 (100/350)

– 3 doses at 1 month intervals

• Objectives: – Safety and tolerability – Immune responses: especially T cell (IL-17)

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Potentially the first protein subunit pneumococcus vaccine to demonstrate TH17 response

April 11, 2014

Value-Creating Phase 2 Trial Imminent

• Objective: Demonstrate GEN-004 impact on colonization

• Trial design: – Double-blind, placebo-controlled – ~90 healthy adult subjects

• Randomized 1:1 to GEN-004 or placebo – Challenged intranasally with pneumococcus

• Efficacy endpoint:

Reduction in colonization

• Timing: – Enrollment to start Q3 2014; initial readout in mid-2015

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April 11, 2014

GEN-004: Program Summary

• Second vaccine designed using ATLAS

• Only TH17-enabled pneumococcus subunit vaccine in development

• Differentiated results in animal model of colonization

• Potential to deliver clinical milestones in near-term

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April 11, 2014

Cancer immunotherapy Other Opportunities

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April 11, 2014

Characterizing T Cell Responses to Cancer Antigens

• Ipilimumab (anti-CTLA-4) therapy takes the brakes off of tumor-specific killer T cells – Some subjects do not respond – Some associated toxicities

• Applying ATLAS™ to profile T cell responses from responders/non-responders – Identify biomarkers that are predictive of response

• May enable novel immunotherapies

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Darren Higgins, PhD Stephen Hodi, MD Glenn Dranoff, MD

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Clear Opportunities to Drive Value-Creation

• GEN-003 clinical milestones: – June 2014: 12-month Phase 1/2a results – Mid-2015: Phase 2 dose optimization efficacy results

• GEN-004 clinical milestones:

– June 2014: Phase 1 TH17, safety results – Mid-2015: Phase 2a efficacy results

• Partnering ATLAS:

– Pipeline programs – ATLAS access for new disease areas

April 11, 2014

Genocea Leadership

Board of Directors Katrine Bosley (Chairman) Former CEO, Avila

George Siber, MD (Exec Director, SAB Chair) Former CSO, Wyeth Vaccines

Kevin Bitterman, PhD Polaris Partners

Chip Clark Genocea

Simeon George, MD S.R. One

Stephen Hoffman, MD, PhD PDL Biopharma

Management Chip Clark – President and CEO Vanda, Care Capital, GSK

Bob Farrell, CPA – VP of Finance & Admin Magen, Oscient

Jessica Flechtner, PhD – SVP of Research Agenus, Mojave, Dana-Farber

Paul Giannasca, PhD – VP of Biopharma Development & Processing Sanofi Pasteur, Acambis

Seth Hetherington, MD – CMO Inhibitex, Icagen, GSK

Jonathan Poole – CFO Shire, Avanti Capital, ING Barings

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April 11, 2014

• Innovative antigen discovery platform enables new vaccine class

ATLAS Platform

• First-in-class program with positive Phase 1/2a data addressing a significant unmet need

HSV-2 Immunotherapy

• Phase 1 program with unique, universal vaccine proposition Pneumococcus

• Experienced team backed by top advisors Strong Leadership

• Multiple clinical milestones in the next 18 months

Near-Term Value Creation

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Compelling Investment Thesis

April 11, 2014

Genocea Biosciences, Inc. NASDAQ: GNCA Cambridge Discovery Park 100 Acorn Park Drive 5th floor Cambridge, MA 02140 USA Phone: +1 617.876.8191 www.genocea.com

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