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HEMATOLOGY & ONCOLOGY FOCUSED COMPANY
February 28, 2017
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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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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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
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2b
VADIS
Ongoing
2a
GALE-401
Anagrelide Controlled Release (CR)
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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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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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
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
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
ADVANTAGES OF CR FORMULATION
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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.
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
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Arrows indicate Megakaryocytes
ET has Larger Number of Megakayocytes
Sources: Haematologica. 2009 June; 94(6): 865, Am J Hematology. 2008 May;83(5):359)
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
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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PIVOTAL, PHASE 3 TRIAL
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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
IMMUNOTHERAPY
NeuVax™ (nelipepimut-S)GALE-301/GALE-302
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
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
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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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
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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
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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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
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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
CORPORATE OVERVIEW
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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
2017 MILESTONES
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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
THANK YOU
NASDAQ: GALE