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ONCOLOGY FOCUSED IMMUNOTHERAPY COMPANY
Targeting Cancer Survivorship
2
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 and Quarterly Report on Form 10-Q and in other filings 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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LATE-PHASE, ONCOLOGY FOCUSED IMMUNOTHERAPY COMPANY
Targeted, 1st in Class therapies for prevention of cancer recurrence
Focused in large markets in areas of major unmet medical need• Phase 3, PRESENT, breast cancer
clinical trial ongoing under SPA
Pioneering immunotherapy technology for cancer • Induce, activate and cause
proliferation of Cytotoxic T-Cells
• Proven Mechanism of Action through Expansion of Tumor Specific CTLs
0
5
10
15
20
25
0.5 1.5 2.5 3.5 4.5 5.5 6.5 7.5 8.5 9.5 10.5Year
Haz
ard
of re
curr
ence
by
year
ly in
terv
al
TotalNode 0
Node 1-3Node (4+)
Tumour size (<1cm)Tumour size (1.1-3cm)
Tumour size (>3cm)ER+
ER-Premen
Postmen
Source: Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451 ; Update of Houghton. J Clin Oncol. 2005; 23(16S):24s. Abstract 582 Saphner et al., J Clin Oncol. 14: 2738-2746, 1996
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DEVELOPMENT PIPELINE
Product Therapeutic Area Phase 1 Phase 2 Phase 3 BLA / NDA
Immunotherapy: Breast Cancer
NeuVax™ (nelipepimut-S) Node-positiveHER2 IHC 1+/2+
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)
Immunotherapy: Gastric Cancer
NeuVax™ Gastric, HER2 IHC 1+/2+/3+
Immunotherapy: Gynecological Cancer
GALE-301 Ovarian & Endometrial
GALE-301 + GALE-302 Ovarian & Breast
GALE-301 + GALE-302 Ovarian
Hematology
GALE-401 (Anagrelide CR) MPN-related thrombocytosis
PRESENT
*NeuVax is an investigational product. Efficacy has not been established. Herceptin is a registered trademark of Genentech.
Ongoing Planned
VADIS
2b
1b
2b
5
Adds ~10k patients>$3B
Combo: High risk, HER2 3+
NEUVAX:SIGNIFICANT U.S. COMMERCIAL OPPORTUNITY
adds ~10k patients>$2.5B
Combo Node Pos or NegHER2 1+, 2+
HLA-A2, A3, A24, A26
PRESENT50-60k patients
>$2B
Source: Global Data 2015/Medtrack. Pricing estimates based on a 20% premium to the current average annual price of Herceptin® (U.S. Dollars).
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REDEFINING THE STANDARD OF CARE
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NOVEL DEVELOPMENT STRATEGY: SECONDARY PREVENTION IN CANCER SURVIVORS
RECEIVES PRIMARY TREATMENT
• Surgery
• Chemotherapy
• and/or Radiation
Disease free“survivor”
Breast: HER2, 1+/2+25% recurrence rate in 3 yrs
No FDA Approved targeted therapies
Breast: HER2, 3+ High Risk20% recurrence rate
DECLAREDTO PREVENT RECURRENCE / METASTATIC DISEASE
Breast: Ductal Carcinoma in Situ 8-10% progression to invasive
Ovarian Cancer
~50% recurrence rate in 1 yrNo FDA Approved targeted therapies
• Watch & Wait, or
• Repetitive therapies
TOLD
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PREVENTING RECURRENCE: UNMET MEDICAL NEED
NEUVAX PHASE 3 PRESENT TRIAL DEMOGRAPHIC:
Node positive, Stage 2a - 3a, HER2 1+/2+, HLA A2/A3
Local or Metastatic recurrent disease =
Poor prognosis and/or Death
Patients have a ~25% Recurrence Rate
Prevention of recurrences saves lives!
Sources: 1 http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-survival-by-stage; 2 Sledge GW Jr: Curing Metastatic Breast Cancer. J Oncol Pract 12:6-10, 2016
5 year survival rate of metastatic cancer = 22%1
“Low Tumor volume” equates to improved overall survival 2
Occult tumor cells micrometastasis macrometastisis metastatic disease
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UNIQUELY POSITIONED
14.5 million cancer survivors in US (NCI Cancer Survivorship)
• Projected to 19 million survivors in 2024
Increase in survival due to decades of productive research, improved screening/prevention, and effective treatments
Survival leads to patients living longer• 64% alive after 5 years of diagnosis• 41% alive after 10 years of diagnosis• 15% alive after 20 years or longer
Galena peptide vaccines – NeuVax and GALE-301 are uniquely positioned to maintain survivorship
Source: DeSantis CE et al. CA Cancer J Clin 2014: 64:252-271
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CANCER IMMUNOTHERAPY WITH INNOVATIVE TECHNOLOGY
Overcoming Cancer by Activating and Expanding Cytotoxic T-Cells
FIRST-IN-CLASS, TARGETED IMMUNOTHERAPY PIPELINE
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Harnessing the power of the
immune system in the adjuvant setting
Exploits specificity of natural immune surveillance
Adjuvant patients have healthy immune systems
Systemic protection
Goal is to prevent recurrence
Recurrences are almost always fatal
Minimal toxicity and improved safety profile
Boosters provide long term protective effect
Well-validated targets
HER2 Folate binding
protein (FBP)
Current Programs
NeuVax™ (nelipepimut-S)
• Breast: HER2 1+, 2+ and 3+; DCIS
• Gastric trial planned
GALE-301 & GALE-302
• Ovarian
Adjuvant Setting = Minimal Residual Disease
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T-Cell
Activating Receptors Inhibitory Receptors
CD28
OX40
GITR
CD122
CD27
CD360
HVEM
CD137
CTLA-4
PD-1
TIM-3
BTLA
VISTA
LAG-3
IMMUNO-ONCOLOGY:UNLOCKING THE POWER OF THE T-CELL
Checkpoint inhibitors
Indirect Immune Modulators
Co-stimulators
Immune Inhibitory Enzymes
CAR TTechnology
TCRTechnology
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TUMOR-SPECIFIC CYTOTOXIC T-CELLS ARE CRUCIAL FOR EFFICACY OF IMMUNOMODULATORY ANTIBODIES
Peptide based vaccination such as NeuVax effectively induce, activate and expand Cytotoxic T-Cells (CTLs)
Immunomodulatory antibodies should be administered when tumor-specific CTLs are present. If the number of CTLs is insufficient, they should be induced.
Source: Aerts, Cancer Res; 73(8) April 15, 2013 2385
It is evident that approaches to increase T-Cell expansion, homing, and effector functions while simultaneously targeting immunosuppression are needed
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T-Cell
Activating Receptors Inhibitory Receptors
CD28
OX40
GITR
CD122
CD27
CD360
HVEM
CD137
CTLA-4
PD-1
TIM-3
BTLA
VISTA
LAG-3
LACK OF REACTIVE T-CELLS MAY RENDER SOME TOOLS INEFFECTIVE IN MANY CANCERS
Checkpoint inhibitors
Indirect Immune Modulators
Co-stimulators
Immune Inhibitory Enzymes
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T-Cell
CD28OX40
GITR
CD122
CD27
CD360
HVEM
CD137
CTLA-4
PD-1
TIM-3
BTLA
VISTA
LAG-3
Activating Receptors Inhibitory Receptors
OUR VACCINES STIMULATE T-CELL PROLIFERATION AND EXPANSION
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
GALE-301
NEUVAX™ (nelipepimut-S)
Targeting HER2
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NEUVAX: HER2 IMMUNODOMINANT PEPTIDE
NeuVax contains the immunodominant peptide derived from the extracellular region of the HER2 protein
Peptide (aa 369-377) immunotherapy administered as intradermal injection
MHC Class I: HLA A2/A3
K I F G S L A F L
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ELICITS A STRONG CD8+ T-CELL RESPONSE
NeuVax binds to antigen presenting cells (APCs)
NeuVax stimulates APCs to activate CD8+ cytotoxic T lymphocytes (CTLs)
CTLs rapidly replicate to seek out and destroy HER2 expressing tumor cells and micro-metastases
Booster series maintains long term immunologic response
Demonstrated inter- and intra-antigenic epitope spreading
Sources: 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
0.00.20.40.60.81.01.21.41.61.82.0
0.4
1.8
0.70.5
NeuVax Specific CD-8 CTLs: Pre-, Post, Mean and Long-Term (6 months)
% N
euV
ax s
peci
fic C
D8+
T c
ells
Pre Max Mean Long-Term
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POSITIVE SAFETY PROFILE
NeuVax is well-tolerated in multiple clinical trials
Phase 1/2 showed predominantly Grade 1/2 Adverse Events caused by GM-CSF (n=53) • Injection site reactions in nearly all patients
demonstrating the activated dendritic cells• Systemic toxicities caused by GM-CSF
Fatigue (64%) Headache (42%) Myalgia/Other Pain (30%)
August 2015 • Independent Data Monitoring Committee
(IDMC) recommended to the Company that it can reduce the cardiac toxicity monitoring in its Phase 3 PRESENT clinical trial
Sources: Choy, et al, poster presentation 33rd Annual Chemotherapy Foundation Symposium: Nov 2015; Mittendorf- Annals of Oncology 25: 1735–1742, 2014
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NEUVAX: SN-33 PHASE 2 HER2 IHC 1+/2+
Source: 2012 San Antonio Breast Cancer Poster, Mazanet, et al.
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PHASE 3, PRESENT TRIAL
Prevention of Recurrence in Early-Stage, Node Positive Breast Cancer with Low to Intermediate Her2 Expression with NeuVax Treatment Trial being run under FDA-approved SPA
Enrollment completed in April 2015 (n=758)• Adjuvant breast cancer patients, Node Positive, HER2 1+/2+, HLA A2/A3+
Patient friendly regimen via intradermal injection• Primary Vaccine Series – injection once a month for 6 months
• Booster Series – injection once every 6 months
Upcoming Key Milestones• Interim safety/futility analysis: 2Q16
• Final Endpoint: 2018
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PHASE 3 PRESENT TRIAL PER SPA
1 2 3 4
Interim analysis by DSMB at n=70 events
Endpoint DFS at n=141 events /36 months
Dosing by Month + 1 booster dose every 6 months thereafter
5 6
Adjuvant breast cancer patients, randomized 1:1
Double blind
Node positive
HLA A2/A3+
HER2 IHC 1+/2+
Stratified by stage, type of surgery, hormone receptor, and menopausal status
Enrollment complete: n=758 Patients
Study Population + GM-CSF
Placebo + GM-CSF
Prevention of Recurrence in Early-Stage, Node Positive Breast Cancer with Low to Intermediate Her2 Expression with NeuVax Treatment
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NEUVAX: BREAST CANCER FRANCHISE
Phase Treatment HER2
Status Indication Trial StatusProtocol Defined
# of PatientsCollaborations
3Single agent
PRESENT Study
1+, 2+ Node PositiveHLA A2+, A3+
Enrolled13 countries~140 centers
700(enrolled 758)
2bCombination
with trastuzumab
1+, 2+Node Positive or High
Risk Node NegativeHLA A2+, A3+,
A24+, A26+
EnrollingU.S. only
34 centers300
2Combination
with trastuzumab
3+ high risk
Node PositiveHLA A2, A3+
EnrollingU.S. only
30 centers100
2 Single agentVADIS Study
1+, 2+,3+
Ductal Carcinoma in Situ (DCIS)HLA A2+
Planned4 U.S. sites 48
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PRIMARY PREVENTIONExpansion potential for safe vaccine in DCIS
METASTATIC DISEASEExpansion potential in combination with checkpoint inhibitors /immune modulators
NEUVAX: ACROSS THE BREAST CANCER TREATMENT SPECTRUM
PROOF OF CONCEPT: Established in population with no standard of care treatment options
SECONDARY PREVENTION
IDEAL SETTING: Adjuvant treatment in patient population with no evidence of disease
MOST ADVANCED: PRESENT is the largest and only Phase 3 breast cancer vaccine trial
Targeting Folate Binding Protein
GALE-301 & GALE-302
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GALE-301 & GALE-302
Source: U.S. Ovarian Cancer http://seer.cancer.gov/statfacts/html/ovary.html
Targeted cancer immunotherapy Folate Binding Protein (FBP) is
over-expressed (20-80 fold) in >90% of ovarian and endometrial cancers
FBP has very limited tissue distribution and expression in non-malignant tissue making it an ideal immunotherapy target
Current treatments are generic• Carboplatin and paclitaxel• High recurrence rate
Most patients relapse with poor prognosis
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GALE-301/302 FILLS AN UNMET MEDICAL NEED FOR A SIGNIFICANT NUMBER OF OVARIAN CANCER PATIENTS
Limited competition in early stage setting represents a large commercial opportunity
2021 2022 2023 2024 2025 2026 2027 2028 20290
2000
4000
6000
8000
10000
12000
14000
16000
18000Estimated HLA-A2+ Qualified Patient Population
ASSUMPTIONS• Avg 80% of NED
patients post-surgery• 70% Penetration• 80-90% PVS/Booster
compliance• High Recurrence rates• No adjuvant
treatment options outside chemo
Source: DR/Decision Resources, LLC
CURRENT CLINICAL DEVELOPMENT
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Phase Treatment Cancer Type Target Indication
Current Status
# of Enrolled Patients
1/2a GALE-301Ovarian,
EndometrialHLA A2+
Ovarian Enrolled 51
1b GALE-301 & GALE-302
Ovarian, Breast HLA A2+ Ovarian Enrolled 39
GALE-301: OPTIMAL DOSE GROUP SHOWS PRELIMINARY EFFICACY
Source: Peoples, et. al, Poster Presentation, European Cancer Congress 2015 29
Phase 1/2a trial ongoing Phase 1: Determined optimal dose and
demonstrated safety and potent immune response
Phase 2a Preliminary data in 1000 mcg dose group:
• At 12 months median follow-up:
Vaccine group: 2 clinical recurrences (13.3%) n=15
Control group: 12 recurrences (55%) n=22
• Two year DFS estimate in 1000 mcg dose group is 85.7% vaccine vs. 33.6% control (p<.02)
• GALE-301 plus GM-CSF is well tolerated and elicits a strong in vivo immune response with primarily Grade 1 and Grade 2 toxicities
2 Year DFS Estimate by Dose Cohort
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GALE-301 & GALE 302:DELAYED-TYPE HYPERSENSITIVITY
LEGENDEE = E39 (GALE-301) x 6 inoculations (n=12)EE’ = E39 (GALE-301) x 3 inoculations followed by E39’ (GALE-302) x 3 inoculations (n=14)E’E = E39’ (GALE-302) x 3 inoculations followed by E39 (GALE-301) x 3 inoculations (n=13)
R0 = baseline (pre-vaccination)RC1 = 1 month after completion of the PVSRC6 = 6 months after completion of the PVS and pre-booster
Source: Mittendorf et. al., Poster Presentation, Society of the Immunotherapy of Cancer 2015
GALE-401
Anagrelide Controlled Release (CR)
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GALE-401 ANAGRELIDE CONTROLLED RELEASE (CR)
Anagrelide
• Active ingredient• Reduces the elevated platelet count and the risk of thrombosis in patients with
myeloproliferative neoplasms (MPNs)• MPNs are hematological malignancies in which the bone marrow cells develop and function
abnormally
Immediate Release
• Approved for the treatment of patients with thrombocythemia, secondary to MPNs• IR formulation can cause unacceptable side effects believed to be Cmax-related and has largely
limited the use due to early treatment withdrawal
GALE-401
• Controlled Release (CR) formulation may decrease the frequency or severity of side effects • Phase 2, Proof-of-Concept Trial Ongoing• Galena to seek confirmation of the 505(b)(2) regulatory pathway
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GALE-401: PHASE 2 PILOT STUDY FINAL RESULTS
Source: ASH 2015 Poster Presentation, Verstovsek et al.
Well tolerated with primarily Grade 1 and 2 toxicities in n=14/18
Efficacy compares favorably to historical anagrelide IR
• Platelet response: ORR = 83.3% (15/18) CR = 61.1% (11/18) PR = 22.2% (4/18)
• Median 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
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CORPORATE OVERVIEW
35
1st IN CLASS PROGRAMS WITH EXPANSION OPPORTUNITIES
Mid-stage clinical trials have proven T-cell generation• NeuVax™ (nelipepimut-S) Phase 2 trial demonstrated 2% of the patient’s
T-Cells become CD8+, HER2 directed
• GALE-301 Phase 1/2: Two year DFS estimate in optimal dose group is 85.7% vaccine vs. 33.6% control (p<.02)
Targeting “high value” settings: Prevention of recurrence in breast and ovarian cancer are areas of clear unmet medical needs • No approved drugs for these women with limited late stage competition
Multiple trials ongoing as stand-alone therapies and in-combination with other agents
Breast & Ovarian are just a start – HER2 and Folate Binding Protein expressed in numerous cancer types
HER2
Breast
Gastric
Prostate
Non-Small Cell Lung
Bladder
Colorectal
Ovarian
Folate Binding Protein
Ovarian
Endometrial
Breast
36
LEADERSHIP TEAM
Mark W. Schwartz, Ph.D., President & CEO Apthera, Bayhill Therapeutics, Calyx Therapeutics, Trega Biosciences, Incyte Genomics, DuPont Diagnostics
Bijan Nejadnik, M.D., Executive Vice President, Chief Medical Officer Jazz Pharmaceuticals, Johnson & Johnson, Stanford, Johns Hopkins, UC Davis
Remy Bernarda, SVP, Investor Relations & Corporate CommunicationsIR Sense, Hana Biosciences, Knight Equity Markets, Bear Stearns, Goldman Sachs
Gavin Choy, Pharm.D., SVP, Clinical Sciences & OperationsOtsuka, Astex, SuperGen, Hana Biosciences, Gilead, Stanford University Medical Center, Department of Veteran Affairs
Tom Knapp, Esq., Interim General Counsel Sucampo, Exemplar Law Partners, NorthWestern Energy, Paul Hastings, The Boeing Company
Joe Lasaga, VP, Business Development & Alliance Management
Nektar Therapeutics, Rigel
Pat Murphy, VP, Regulatory Affairs & ComplianceNektar Therapeutics, Bayhill Therapeutics, Berlex Laboratories, Serono, Parexel, Biogen
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2016 MILESTONES
PROGRAM MILESTONE PROJECTED DATE
NeuVax™ (nelipepimut-S)
Initiate DCIS trial Q1
PRESENT: Reach 70 events Q1
PRESENT: Interim analysis Q2
H&N 1+/2+ Interim safety data Q4
H&N 1+/2+ A24/A26 data Q4
GALE-301GALE-302
Present 301/302 booster data Q2
Initiate Phase 2b clinical trial Q3
Present GALE-301 Phase 2a two year data Q4
GALE-401 (anagrelide CR)
Confirmation of 505(b)2 pathway 2H
Publish final Phase 2 report Q4
FINANCIAL OVERVIEW
Cash Position (as of 9/30/15) $34.8 million
Divestiture Impact (non-recurring Q4 to 1H)
$11.75 million income from sale $5-$6 million expenses to close operations
Legal settlement and associated expenses (non-recurring Q4 to 1H) $3-$5 million
Net proceeds from January offering (Q1) $20.1 million
Debt (as of 9/30/15) $5.7 million
2016 Projected Quarterly Burn $11-$13 million
Shares Outstanding 182 million
Market Cap (5 February 16) ~$120 million
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WHY WE’RE HERE
Source: E75 vaccine's final tests start in S.A. By Don Finley, January 22, 2012; Photo credit: Kin Man Hui/San Antonio Express-News/ZUMAPress
“I've had several friends who've had (breast cancer) and then…it came back and they had to go through treatment again. So this would be wonderful, not to have to come back.”
– First NeuVax Phase 3 patient
THANK YOU
NASDAQ: GALE