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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.
2
DIVERSIFIED PIPELINE
Diversified	
pipeline	with	
multiple	mid-
to	late	stage	
clinical	trials	
HEMATOLOGY
•GALE-401	(Anagrelide	
Controlled	Release)
•Targeting	MPNs
•Phase	3 ready	in	ET	
patients
IMMUNOTHERAPY
•NeuVax™	(nelipepimut-S)
•Targeting	HER2
•Multiple	Phase	2	clinical	
trials	ongoing	in	breast	
cancer
IMMUNOTHERAPY
•GALE-301/GALE-302
•Targeting	Folate	
Binding	Protein
•Early	stage	trials	
completed
3
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
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
6
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
• Consistentefficacy
• Potentially faster onset of action and indication of improved tolerability
compared to anagrelide IR
• More convenienttreatment regimen
• Favorable PK profile
u Multiple life cycle managementopportunities
7
Results
Reduces	Cmax
Maintains	Area	Under	the	Curve	(AUC)
Lowers	peak	plasma	concentration
Maintains	Platelet	Lowering
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
9
Source: 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
Related	Adverse	Events	(AEs)
GALE-401*
(N=18)
n	(%)
AGRYLIN^
(n=942)
%
Cardiac 6 (33) 42
General# 5	(27.8) 83
Gastrointestinal 9 (50) 92
Respiratory,	thoracic	and	mediastinal 2	(11) 18
Skin	and	subcutaneous	tissue 2	(11) 14
Musculoskeletal	and	connective	tissue 1	(6) 6
Nervous	system 9	(50) 65
Vascular 3	(16) <5
Hepatobiliary 2	(11) <5
Blood	and	Lymphatic 1 (6) <5
Number	of	AEs/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
11
Anagrelide	IR^ GALE-401*	Benefits	
w/CR Formulation
Therapeutic	index# Limited - dose	escalation	to	
optimal	effect is	challenging
Larger	- Possibility	of	achieving	
desired	effect	with	lower	dose
Pharmacokinetics	(PK)	
• Half	life
• Cmax
• 2-3 hours
• 4x	GALE-401
Improved	PK	profile
• 20	hours
• 25%	of	IR
Onset of	Action As	early	as	4	weeks As	early	as	1	week
Doses	per	day 2 to	4	times	a	day
2	times	a	day	
Targeting	1x/day	in	future	trials
Dosing regimen	 2	to	10	mg	per	day Mean 2	mg	per	day
Safety Profile
• Treatment	Related	AEs
• #	of	AE/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 MPNs
u 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)
ET OVERVIEW
Diagnosis
• Chronic	
hematologic	
malignancy	with	
no	known	cause
• Clinical	
presentation	of	
symptoms
• Diagnostic	tools
• Blood	test
• Bone	marrow	
biopsy
• Gene	
mutation	test
Common	
Symptoms
• Headache
• Vision	
disturbances	or	
migraines
• Dizziness	or	
lightheadedness
• Coldness	or	
blueness	of	
fingers	or	toes
• Burning,	
redness,	and	
pain	in	the	
hands	and	feet
Thrombotic	
Complications
• Stroke
• Transient	
ischemic	attack	
(TIA)
• Heart	attack
• DVT	or	
pulmonary	
embolus
• Blood	clotting	in	
unusual	
locations
Risk	Factors
• Women	1.5x	
more	likely
• Patients	>60	
years	old,	with	
20%	<40	years
• Mutations
• JAK2	- 50%
• CALR	~25%
13Source: MPN Research Foundation
ET: CURRENT TREATMENT OPTIONS
Hydroxyurea
Other	
Therapies
•Generally	initial	 treatment	option
•Cytotoxic	myelosuppressive drug	
(also	reduces	other	blood	cells)
•Increased	risk	of	developing	
acute	leukemia	over	long	term
•Avoided	in	younger	patients
•~25%	of	patients	
intolerant/refractory
• Anagrelide IR
• Interferon
• Busulfan
• Retry hydroxyurea
• Observation
14
PIVOTAL, PHASE 3 TRIAL
15
Failed	or	Intolerant	to	
Hydroxyurea
GALE-401	
(Anagrelide	CR)
BEST	AVAILABLE	THERAPY
Anagrelide	IR	(sizable	population)
Interferon
Busulfan
Retry	hydroxyurea
Observation
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
0.7
0.5
0.0
0.5
1.0
1.5
2.0
2.5
%NeuVaxspecificCD8+Tcells
NeuVax Specific CD-8 CTLs:
Pre-, Post, Mean and Long-Term (6 months)
Pre Max Mean Long-Term
T-Cell
CD28
OX40
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
18
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
19
COMBINATION IMMUNOTHERAPY ENHANCES
ANTIGEN PRESENTATION
Trastuzumab/HER2 complexes are internalized and
processedby proteasomes into short peptides
which are then presentedon MHC class I molecules
PBMC from HER2/neu peptide, E75,
vaccinatedpatients efficiently recognize and
lyse trastuzumab-treatedHER2/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	%	Cytotoxicity	51	Cr
0	ug 10	ug 50	ug
* 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 weeksfor 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
Primary
Endpoint
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
21
NEUVAX: MULTIPLE SETTINGS AND
COMBINATION STRATEGY
Phase
Treatment	
HER2 Status
Indication Trial	Status
Targeted
Enrollment
Completion
Planned
Data	
Readouts
Collaborations
2b
Combination
w/trastuzumab
HER2	1+,	2+
BREAST	
Node Positive	or	
High	Risk	Node	
Negative
HLA A2+,	A3+,				
A24+,	A26+
Enrolling
U.S.	only
33	centers
n=300
Q2	2017
Q4,	2017
Interim	
Analysis
1H, 2019
Final	Data
2
Combination
w/trastuzumab
high	risk				
HER2	3+
BREAST
Node Positive
HLA A2+, A3+
Enrolling
U.S.	only
28	centers
n=100
Q4	2017
1H,	2019
Interim	
Analysis
2
Single	agent
VADIS Study
HER2	1+,	2+,	
3+
BREAST
Ductal	Carcinoma	
in Situ (DCIS)
HLA	A2+
Enrolling
U.S.	only
4	centers
N=48
2
Single	agent
HER2	1+,	2+,	
3+
GASTRIC
HLA	A2+,	A3+
Planned
India Only
N=50
22
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 DiseaseFree
Survival by Dosing Cohort
CORPORATE
OVERVIEW
24
LEADERSHIP TEAM
25
u Stephen Ghiglieri
Interim Chief Executive Officer
MedData Inc., NeurogesX, Hansen Medical,
Inc., Oacis Healthcare Systems, Oclassen
Pharmaceuticals
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
26
PROGRAM MILESTONE
PROJECTED
DATE
GALE-401			
(anagrelide	CR)
Finalize	Phase 3	Clinical	Trial	Protocol Q1
Determine	Phase	3	initiation 2H
NeuVax™
(nelipepimut-S)
Complete	enrollment	in	
NeuVax/trastuzumab 1+/2+	Combination
Trial
Q2
Interim safety	data	presentation	for	
NeuVax/trastuzumab 1+/2+	Combination
Trial
Q2
Complete	enrollment	in	
NeuVax/trastuzumab 3+	Combination Trial
Q4
Interim	data	analysis: NeuVax/trastuzumab
1+/2+	Combination	 Trial
Q4
GALE-301
GALE-302
Final	GALE-301	data	presentation Q1
THANK YOU
NASDAQ: GALE

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Galena presentation

  • 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, 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. 2
  • 4. 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
  • 6. 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 6
  • 7. 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 • Consistentefficacy • Potentially faster onset of action and indication of improved tolerability compared to anagrelide IR • More convenienttreatment regimen • Favorable PK profile u Multiple life cycle managementopportunities 7
  • 8. Results Reduces Cmax Maintains Area Under the Curve (AUC) Lowers peak plasma concentration Maintains Platelet Lowering 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
  • 9. GALE-401: PHASE 2 PILOT STUDY FINAL RESULTS 9 Source: 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
  • 10. GALE-401 DEMONSTRATES IMPROVED AE PROFILES IN KEY CATEGORIES Related Adverse Events (AEs) GALE-401* (N=18) n (%) AGRYLIN^ (n=942) % Cardiac 6 (33) 42 General# 5 (27.8) 83 Gastrointestinal 9 (50) 92 Respiratory, thoracic and mediastinal 2 (11) 18 Skin and subcutaneous tissue 2 (11) 14 Musculoskeletal and connective tissue 1 (6) 6 Nervous system 9 (50) 65 Vascular 3 (16) <5 Hepatobiliary 2 (11) <5 Blood and Lymphatic 1 (6) <5 Number of AEs/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
  • 11. ADVANTAGES OF CR FORMULATION 11 Anagrelide IR^ GALE-401* Benefits w/CR Formulation Therapeutic index# Limited - dose escalation to optimal effect is challenging Larger - Possibility of achieving desired effect with lower dose Pharmacokinetics (PK) • Half life • Cmax • 2-3 hours • 4x GALE-401 Improved PK profile • 20 hours • 25% of IR Onset of Action As early as 4 weeks As early as 1 week Doses per day 2 to 4 times a day 2 times a day Targeting 1x/day in future trials Dosing regimen 2 to 10 mg per day Mean 2 mg per day Safety Profile • Treatment Related AEs • # of AE/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.
  • 12. ESSENTIAL THROMBOCYTHEMIA (ET) u One of the major MPNs u 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)
  • 13. ET OVERVIEW Diagnosis • Chronic hematologic malignancy with no known cause • Clinical presentation of symptoms • Diagnostic tools • Blood test • Bone marrow biopsy • Gene mutation test Common Symptoms • Headache • Vision disturbances or migraines • Dizziness or lightheadedness • Coldness or blueness of fingers or toes • Burning, redness, and pain in the hands and feet Thrombotic Complications • Stroke • Transient ischemic attack (TIA) • Heart attack • DVT or pulmonary embolus • Blood clotting in unusual locations Risk Factors • Women 1.5x more likely • Patients >60 years old, with 20% <40 years • Mutations • JAK2 - 50% • CALR ~25% 13Source: MPN Research Foundation
  • 14. ET: CURRENT TREATMENT OPTIONS Hydroxyurea Other Therapies •Generally initial treatment option •Cytotoxic myelosuppressive drug (also reduces other blood cells) •Increased risk of developing acute leukemia over long term •Avoided in younger patients •~25% of patients intolerant/refractory • Anagrelide IR • Interferon • Busulfan • Retry hydroxyurea • Observation 14
  • 15. PIVOTAL, PHASE 3 TRIAL 15 Failed or Intolerant to Hydroxyurea GALE-401 (Anagrelide CR) BEST AVAILABLE THERAPY Anagrelide IR (sizable population) Interferon Busulfan Retry hydroxyurea Observation 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
  • 17. 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 0.7 0.5 0.0 0.5 1.0 1.5 2.0 2.5 %NeuVaxspecificCD8+Tcells NeuVax Specific CD-8 CTLs: Pre-, Post, Mean and Long-Term (6 months) Pre Max Mean Long-Term
  • 18. T-Cell CD28 OX40 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 18 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
  • 19. 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 19
  • 20. COMBINATION IMMUNOTHERAPY ENHANCES ANTIGEN PRESENTATION Trastuzumab/HER2 complexes are internalized and processedby proteasomes into short peptides which are then presentedon MHC class I molecules PBMC from HER2/neu peptide, E75, vaccinatedpatients efficiently recognize and lyse trastuzumab-treatedHER2/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 % Cytotoxicity 51 Cr 0 ug 10 ug 50 ug * p=0.015 Trastuzumab Hypothesis: Trastuzumab treatment will enhance response to vaccination by making tumor cells more visible to T-cells/immune system
  • 21. Interim Analysis at 6 months DFS Standard of Care: Standard Herceptin dosing every 3 weeksfor 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 Primary Endpoint 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 21
  • 22. NEUVAX: MULTIPLE SETTINGS AND COMBINATION STRATEGY Phase Treatment HER2 Status Indication Trial Status Targeted Enrollment Completion Planned Data Readouts Collaborations 2b Combination w/trastuzumab HER2 1+, 2+ BREAST Node Positive or High Risk Node Negative HLA A2+, A3+, A24+, A26+ Enrolling U.S. only 33 centers n=300 Q2 2017 Q4, 2017 Interim Analysis 1H, 2019 Final Data 2 Combination w/trastuzumab high risk HER2 3+ BREAST Node Positive HLA A2+, A3+ Enrolling U.S. only 28 centers n=100 Q4 2017 1H, 2019 Interim Analysis 2 Single agent VADIS Study HER2 1+, 2+, 3+ BREAST Ductal Carcinoma in Situ (DCIS) HLA A2+ Enrolling U.S. only 4 centers N=48 2 Single agent HER2 1+, 2+, 3+ GASTRIC HLA A2+, A3+ Planned India Only N=50 22
  • 23. 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 DiseaseFree Survival by Dosing Cohort
  • 25. LEADERSHIP TEAM 25 u Stephen Ghiglieri Interim Chief Executive Officer MedData Inc., NeurogesX, Hansen Medical, Inc., Oacis Healthcare Systems, Oclassen Pharmaceuticals 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
  • 26. 2017 MILESTONES 26 PROGRAM MILESTONE PROJECTED DATE GALE-401 (anagrelide CR) Finalize Phase 3 Clinical Trial Protocol Q1 Determine Phase 3 initiation 2H NeuVax™ (nelipepimut-S) Complete enrollment in NeuVax/trastuzumab 1+/2+ Combination Trial Q2 Interim safety data presentation for NeuVax/trastuzumab 1+/2+ Combination Trial Q2 Complete enrollment in NeuVax/trastuzumab 3+ Combination Trial Q4 Interim data analysis: NeuVax/trastuzumab 1+/2+ Combination Trial Q4 GALE-301 GALE-302 Final GALE-301 data presentation Q1