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HEMATOLOGY & ONCOLOGY FOCUSED COMPANY February 28, 2017
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Page 1: Galena presentation

HEMATOLOGY & ONCOLOGY FOCUSED COMPANY

February 28, 2017

Page 2: Galena presentation

FORWARD LOOKING STATEMENT

This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about future expectations, plans and prospects for the development and commercialization of the Company's product candidates, including patient enrollment in our clinical trials, present or future licensing, collaborative or financing arrangements, expected outcomes with regulatory agencies, and projected market opportunities for product candidates are subject to a number of risks, uncertainties and assumptions, including those identified under “Risk Factors” in the Company’s most recently filed Annual Report on Form 10-K, Quarterly Report on Form 10-Q and in Current Reports on Form 8-K the Company periodically makes with the SEC. Actual results may differ materially from those contemplated by these forward-looking statements. The Company does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this presentation.

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Page 3: Galena presentation

DIVERSIFIED PIPELINE

Diversifiedpipelinewithmultiplemid-tolatestageclinicaltrials

HEMATOLOGY•GALE-401(AnagrelideControlledRelease)

•TargetingMPNs•Phase3 readyinETpatients

IMMUNOTHERAPY•NeuVax™(nelipepimut-S)• TargetingHER2•MultiplePhase2clinicaltrialsongoinginbreastcancer IMMUNOTHERAPY

•GALE-301/GALE-302•TargetingFolateBindingProtein

•Earlystagetrialscompleted

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Page 4: Galena presentation

DEVELOPMENT PIPELINE

PRODUCT THERAPETIC AREA PHASE 1 PHASE 2 PHASE 3 BLA / NDA

Hematology

GALE-401 (Anagrelide CR) Essential Thrombocythemia

Immunotherapy: Breast & Gastric Cancer

NeuVax™ + Herceptin® Node-positive or node negative/triple negative, HER2 IHC 1+/2+

NeuVax™ + Herceptin® High risk, node-positive or negative, HER2 IHC 3+

NeuVax™ Ductal Carcinoma in Situ (DCIS)

NeuVax™ Gastric, HER2 IHC 1+/2+/3+

Immunotherapy: Gynecological Cancer

GALE-301 Ovarian & Endometrial

GALE-301 + GALE-302 Ovarian & Breast

*NeuVax is an investigational product. Efficacy has not been established. Herceptin is a registered trademark of Genentech.

Completed Planned

4

2b

VADIS

Ongoing

2a

Page 5: Galena presentation

GALE-401

Anagrelide Controlled Release (CR)

Page 6: Galena presentation

ANAGRELIDE

u Anagrelide immediate release (IR) approved by the FDA to treat Myleoproliferative Neoplasms (MPNs) • Indicated for the treatment of patients with thrombocythemia,

secondary to myeloproliferative disorders to reduce the elevated platelet count and the risk of thrombo-embolic events

• Only drug approved to treat Essential Thrombocythemia (ET)

u Anagrelide suppresses megakaryocytopoiesis by inhibiting PDE III-dependent and PDE III-independent mechanisms

u No DNA damaging or cytotoxic effect

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Page 7: Galena presentation

GALE-401:ANAGRELIDE CONTROLLED RELEASE (CR)

u A proprietary, controlled release (CR) formulation of anagrelide• 505(b)2 regulatory path allows for abbreviated submission package and

potentially faster approval timelines • Strong IP through 2029

u Six trials conducted to date• Five Phase 1 studies in healthy volunteers• Phase 2 pilot study in patients with myeloproliferative neoplasms (MPNs)

u Potential Clinical Benefits • Consistent efficacy • Potentially faster onset of action and indication of improved tolerability

compared to anagrelide IR• More convenient treatment regimen • Favorable PK profile

u Multiple life cycle management opportunities

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Page 8: Galena presentation

Results ReducesCmax

MaintainsAreaUndertheCurve(AUC)

Lowerspeakplasmaconcentration

MaintainsPlateletLowering

GALE-401 PHASE 1 TRIALS

8Multiple Phase 1 studies in n=98 healthy volunteers; Agrylin is a registered trademark of Shire.

Anagrelide CR Platelet LoweringGALE-401 Median Cmax

Anagrelide IR Median Cmax

Page 9: Galena presentation

GALE-401: PHASE 2 PILOT STUDY FINAL RESULTS

9Source: Verstovsek et al, Final Results of Anagrelide Controlled-Release (Gale-401) Safety, Efficacy and Pharmacokinetics in Subjects with Myeloproliferative Neoplasms (Mpn)-Related Thrombocytosis, ASH 2015 Poster Presentation.

u Well tolerated with primarily Grade 1 and 2 toxicities in n=14/18

u Efficacy compares favorably to historical anagrelide IR

• Platelet response: § ORR = 83.3% (15/18) § CR = 61.1% (11/18)§ PR = 22.2% (4/18)

• Time to response was 1 to 9 weeks (defined as platelet count ≤ 600 x109/L)

§ Anagrelide IR historical time to response ranged from 4 to 12 weeks

u Safety profile indicates a potential benefit for GALE-401 compared to anagrelide IR

Page 10: Galena presentation

GALE-401 DEMONSTRATES IMPROVED AE PROFILES IN KEY CATEGORIES

RelatedAdverseEvents(AEs)GALE-401*(N=18)n(%)

AGRYLIN^

(n=942)%

Cardiac 6 (33) 42

General# 5(27.8) 83

Gastrointestinal 9 (50) 92

Respiratory,thoracicandmediastinal 2(11) 18

Skinandsubcutaneous tissue 2(11) 14

Musculoskeletalandconnectivetissue 1(6) 6

Nervoussystem 9(50) 65

Vascular 3(16) <5

Hepatobiliary 2(11) <5

BloodandLymphatic 1 (6) <5

NumberofAEs/patient 2.3 3.3

10Not a head-to-head trial. *GALE-401 related AE data from Phase 2 study; ^Anagrelide IR data from the product label. #General AEs referred to fatigue, peripheral edema, and malaise

Page 11: Galena presentation

ADVANTAGES OF CR FORMULATION

11

AnagrelideIR^ GALE-401*Benefitsw/CR Formulation

Therapeuticindex# Limited - doseescalationtooptimaleffect ischallenging

Larger- Possibilityofachievingdesiredeffectwithlowerdose

Pharmacokinetics(PK)• Halflife• Cmax

• 2-3 hours• 4xGALE-401

ImprovedPKprofile• 20hours• 25%ofIR

Onset ofAction Asearlyas4weeks Asearlyas1week

Dosesperday 2 to4timesaday 2timesadayTargeting1x/dayinfuturetrials

Dosing regimen 2to10mgperday Mean 2mgperday

Safety Profile• TreatmentRelatedAEs• #ofAE/Patient

• 42.1%• 3.3

• 30%• 2.3

Not a head-to-head trial. ^Anagrelide IR data from the product label/Agrylin Package Insert. *GALE-401 profile from Phase 1 and 2 studies. #Therapeutic Index distance between therapeutic dose curve and toxic dose.

Page 12: Galena presentation

ESSENTIAL THROMBOCYTHEMIA (ET)

u One of the major MPNsu Characterized by increased

number of platelets• ET is a neoplastic stem cell disorder

causing dysregulated production of large numbers of abnormal megakaryocytes

u Chronic condition• Median Overall Survival: 14.7 years

• Up to 50% of patients may be asymptomatic at presentation

u Associated with vascular complications

12

Arrows indicate Megakaryocytes

ET has Larger Number of Megakayocytes

Sources: Haematologica. 2009 June; 94(6): 865, Am J Hematology. 2008 May;83(5):359)

Page 13: Galena presentation

ET OVERVIEW

Diagnosis

• Chronichematologicmalignancywithnoknowncause

• Clinicalpresentationofsymptoms

• Diagnostictools• Bloodtest• Bonemarrowbiopsy

• Genemutationtest

CommonSymptoms

• Headache• Visiondisturbancesormigraines

• Dizzinessorlightheadedness

• Coldnessorbluenessoffingersortoes

• Burning,redness,andpaininthehandsandfeet

ThromboticComplications

• Stroke• Transientischemicattack(TIA)

• Heartattack• DVTorpulmonaryembolus

• Bloodclotting inunusuallocations

RiskFactors

• Women1.5xmorelikely

• Patients>60yearsold,with20%<40years

• Mutations• JAK2- 50%• CALR~25%

13Source: MPN Research Foundation

Page 14: Galena presentation

ET: CURRENT TREATMENT OPTIONS

Hydroxyurea

OtherTherapies

•Generally initial treatmentoption•Cytotoxicmyelosuppressive drug(alsoreducesotherbloodcells)

• Increasedriskofdevelopingacuteleukemiaoverlongterm

•Avoidedinyoungerpatients•~25%ofpatientsintolerant/refractory

• Anagrelide IR• Interferon• Busulfan• Retry hydroxyurea• Observation

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Page 15: Galena presentation

PIVOTAL, PHASE 3 TRIAL

15

FailedorIntoleranttoHydroxyurea

GALE-401(AnagrelideCR)

BESTAVAILABLETHERAPYAnagrelideIR(sizablepopulation)

InterferonBusulfan

RetryhydroxyureaObservation

Sources: Mehta et al, (2014) Epidemiology of myeloproliferative neoplasms in the United States, Leukemia & Lymphoma; Sever et al (2014) Therapeutic options for patients with polycythemia vera and essential thrombocythemia refractory/resistant to hydroxyurea, Leukemia & Lymphoma

u Targeting the reduction of platelets in ET patients • Limited competition with very few agents in development• US Prevalence: 135,000 - 175,000

§ Estimate up to 25% of those patients who fail or are intolerant to initial treatment with hydroxyurea may be trial candidates

Page 16: Galena presentation

IMMUNOTHERAPY

NeuVax™ (nelipepimut-S)GALE-301/GALE-302

Page 17: Galena presentation

NEUVAX™ (nelipepimut-S):ELICITS A STRONG CD8+ T-CELL RESPONSE

u Contains the immunodominant peptide derived from the extracellular region of the HER2 protein

u Binds to antigen presenting cells (APCs)

u Stimulates APCs to activate CD8+ cytotoxic T lymphocytes (CTLs)

u CTLs rapidly replicate to seek out and destroy HER2 expressing tumor cells and micro-metastases

u Booster series maintains long term immunologic response

u Demonstrated inter- and intra-antigenic epitope spreading

17Sources: Peoples GE, et al (2005) JCO, 23(300, 7536-7545; Mittendorf EA, et al (2006) Surgery, 139(3): 407-418. Peoples, et al, ASCO 2012 Poster Presentation

0.4

1.8

0.70.5

0.0

0.5

1.0

1.5

2.0

2.5

% N

euVa

xsp

ecifi

c CD

8+ T

cel

ls

NeuVax Specific CD-8 CTLs: Pre-, Post, Mean and Long-Term (6 months)

Pre Max Mean Long-Term

Page 18: Galena presentation

T-Cell

CD28OX40

GITR

CD122

CD27

CD360

HVEM

CD137

CTLA-4

PD-1

TIM-3

BTLA

VISTA

LAG-3

Activating Receptors Inhibitory Receptors

NEUVAX STIMULATES T-CELL PROLIFERATION AND EXPANSION

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T cells

Checkpoint inhibitors

Indirect Immune Modulators

Co-stimulators

Immune Inhibitory Enzymes

T cells

T cells

T cells

T cells

T cells

T cells

T cells

T cells

T cells

Page 19: Galena presentation

CORRELATION BETWEEN HER2 & MHC-1

uThere is an inverse correlation between HER2 and MHC class I

uHER2 overexpression is associated with decreased expression of components of the antigen processing/ presentation pathway

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Page 20: Galena presentation

COMBINATION IMMUNOTHERAPY ENHANCES ANTIGEN PRESENTATION

Trastuzumab/HER2 complexes are internalized and processed by proteasomes into short peptides

which are then presented on MHC class I molecules

PBMC from HER2/neu peptide, E75, vaccinated patients efficiently recognize and

lyse trastuzumab-treated HER2/neu-expressing tumor cell lines

20

Trastuzumab

HER2/neu

Breast tumor cell

HER2/neu –derived peptide presented on MHC-I

HER2/neu-derived peptide

20.0

25.0

30.0

35.0

40.0

45.0

50.0

55.0

60.0

Average%Cytotoxicity51C

r

0ug 10ug 50ug

* p=0.015

Trastuzumab

Hypothesis: Trastuzumab treatment will enhance response to vaccination by making tumor cells more

visible to T-cells/immune system

Page 21: Galena presentation

Interim Analysis

at 6 months DFS

Standard of Care: Standard Herceptin dosing every 3 weeks for 1 year

6 doses of NeuVax given every 3 weeks starting with third dose of Herceptin

+ 1 booster dose every 6 months thereafter

+ Dosing to disease progression;

36 mo follow up

PrimaryEndpoint DFS at 24 mos.

300 adjuvant breast cancer patients, randomized 1:1

§ Single blind (subject)

§ Node positive or high risk node negative

§ HLA A2/A3+

§ HLA A24/A26+

§ HER2 IHC 1+/2+

§ Stratified by nodal status and HER2 status

Study Population

NEUVAX+TRASTUZUMAB: HER2 1+/2+ PHASE 2 STUDY

GM-CSF

+ GM-CSF

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Page 22: Galena presentation

NEUVAX: MULTIPLE SETTINGS AND COMBINATION STRATEGY

Phase TreatmentHER2 Status Indication TrialStatus

TargetedEnrollmentCompletion

PlannedData

ReadoutsCollaborations

2bCombination

w/trastuzumabHER21+,2+

BREASTNode PositiveorHighRiskNode

NegativeHLA A2+,A3+,A24+,A26+

EnrollingU.S.only33centersn=300

Q22017

Q4,2017InterimAnalysis

1H, 2019FinalData

2

Combinationw/trastuzumab

highriskHER23+

BREASTNode PositiveHLA A2+, A3+

EnrollingU.S.only28centersn=100

Q420171H,2019InterimAnalysis

2

SingleagentVADIS StudyHER21+,2+,

3+

BREASTDuctalCarcinomain Situ (DCIS)HLAA2+

EnrollingU.S.only4centersN=48

2

SingleagentHER21+,2+,

3+GASTRIC

HLAA2+,A3+

PlannedIndia OnlyN=50

22

Page 23: Galena presentation

GALE-301 (E39) & GALE-302 (E39’): TARGETING FOLATE BINDING PROTEIN

Sources: U.S. Ovarian Cancer http://seer.cancer.gov/statfacts/html/ovary.html; Peoples, et. al, Poster Presentation, American Society of Clinical Oncology 2016 23

u Folate Binding Protein (FBP) is over-expressed (20-80 fold) in >90% of ovarian and endometrial cancers

u High unmet medical need in ovarian cancer patients

u Relatively shorter development timelines

u Phase 2a Preliminary data:

• At 16 months median follow-up:

§ Overall recurrence rate was 44.8% in the VG versus 54.5% in the CG (p=0.58)

§ Recurrence rate of 23.5% in patients who received booster inoculations

• Two year DFS estimate in 1000 mcg dose group: 73.5% vaccine vs 38.1% control (p=.03)

• GALE-301 + GM-CSF is well tolerated and elicits a strong in vivo immune response with primarily Grade 1 & 2 toxicities

Estimated 24 months Disease Free Survival by Dosing Cohort

Page 24: Galena presentation

CORPORATE OVERVIEW

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Page 25: Galena presentation

LEADERSHIP TEAM

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u Stephen Ghiglieri Interim Chief Executive Officer MedData Inc., NeurogesX, Hansen Medical, Inc., Oacis Healthcare Systems, OclassenPharmaceuticals

u Bijan Nejadnik, M.D. Executive VP, Chief Medical Officer Jazz Pharmaceuticals, Johnson & Johnson, Stanford, Johns Hopkins, UC Davis

u Tom Knapp, Esq. Interim General Counsel Sucampo, Exemplar Law Partners, NorthWestern Energy, Paul Hastings, The Boeing Company

u Remy Bernarda, SVP, Investor Relations & Corporate Communications IR Consultant, Hana Biosciences, Knight Equity Markets, Bear Stearns, Goldman Sachs

u John Burns, CPA VP, Finance & Corporate Controller Pixelworks, Moss Adams

Page 26: Galena presentation

2017 MILESTONES

26

PROGRAM MILESTONEPROJECTED

DATE

GALE-401(anagrelideCR)

FinalizePhase 3ClinicalTrialProtocol Q1

DeterminePhase3initiation 2H

NeuVax™(nelipepimut-S)

Completeenrollment inNeuVax/trastuzumab 1+/2+CombinationTrial

Q2

Interim safetydatapresentationforNeuVax/trastuzumab 1+/2+CombinationTrial

Q2

Completeenrollment inNeuVax/trastuzumab 3+Combination Trial Q4

Interimdataanalysis: NeuVax/trastuzumab1+/2+Combination Trial Q4

GALE-301GALE-302 FinalGALE-301datapresentation Q1

Page 27: Galena presentation

THANK YOU

NASDAQ: GALE


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