HEMATOLOGY & ONCOLOGY FOCUSED COMPANY November 28, 2016
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.
2
DIVERSIFIED PIPELINE
Diversified pipeline with multiple mid-to late stage clinical trials
HEMATOLOGY
•GALE-401 (Anagrelide Controlled Release)
•Targeting MPNs
•Phase 3 Initiation Q2, 2017
IMMUNOTHERAPY
• NeuVax™ (nelipepimut-S)
• Targeting HER2
• Multiple mid-stage trials ongoing & planned
IMMUNOTHERAPY
•GALE-301/GALE-302
•Targeting Folate Binding Protein
•Early stage trials ongoing
3
DEVELOPMENT PIPELINE
PRODUCT THERAPETIC AREA PHASE 1 PHASE 2 PHASE 3 BLA / NDA
Hematology
GALE-401 (Anagrelide CR) Essential Thrombocythemia
Immunotherapy: Breast 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)
Immunotherapy: Gastric Cancer
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.
Ongoing Planned
VADIS
4
2b
ANAGRELIDE
Anagrelide suppresses megakaryocytopoiesis by inhibiting PDE III-
dependent and PDE III-independent mechanisms
No DNA damaging or cytotoxic effect
Immediate release version indicated for the treatment of patients with
thrombocythemia, secondary to myeloproliferative disorders to reduce
the elevated platelet count and the risk of thrombosis, and to ameliorate
associated symptoms including thrombo-hemorrhagic events
Approved to treat Myleoproliferative Neoplasms (MPNs)
• Only drug approved to treat Essential Thrombocythemia (ET)
6
GALE-401 (Anagrelide Controlled Release)
GALE-401 is a proprietary, controlled release (CR) formulation of anagrelide
• FDA approved product with known mechanism of action
• Advantageous 505(b)2 regulatory path to be confirmed with the FDA
• Strong IP through 2029
Six trials conducted to date
• Five Phase 1 studies in healthy volunteers
• Phase 2 pilot study in patients with MPNs
Potential Clinical Benefits
• Potentially faster onset of action
• Consistent efficacy
• Indication of improved tolerability vs anagrelide IR
Multiple life cycle management opportunities
7
GALE-401: PHASE 1 TRIAL RESULTS
8 Multiple Phase 1 studies in n=98 healthy volunteers; Agrylin is a registered trademark of Shire.
Anagrelide CR
Plasma Levels
pg
/mL
Anagrelide CR Platelet Lowering
Res
ult
s Reduces Cmax
Maintains Area Under the Curve (AUC)
Lowers peak plasma concentration
Maintains Platelet Lowering
GALE-401: PHASE 2 PILOT STUDY RESULTS
9
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
Vaccine Control
% o
f S
ub
jec
ts
Recurrence
24.0% 13.3%
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
Figure 2. Platelet Response
1 8 15 22 29 36 43 50 57 64 71 78 85 99 113 127 141 155 169 197 225
18 18 18 18 18 18 15 14 14 14 13 13 13 13 13 13 12 12 11 11 11
1.0 1.4 1.8 1.9 2.0 2.2 2.4 2.5 2.4 2.2 2.0 2.1 2.1 1.9 1.8 1.9 2.0 1.9 1.8 1.9 1.8
Study Days
N=
Avg. daily dose
0
200
400
600
800
1000
1200
1400
Mean Platelet Count (± SD)
Pla
tele
t C
ou
nt
(x10
9/L
)
Figure 2. Platelet Response
1 8 15 22 29 36 43 50 57 64 71 78 85 99 113 127 141 155 169 197 225
18 18 18 18 18 18 15 14 14 14 13 13 13 13 13 13 12 12 11 11 11
1.0 1.4 1.8 1.9 2.0 2.2 2.4 2.5 2.4 2.2 2.0 2.1 2.1 1.9 1.8 1.9 2.0 1.9 1.8 1.9 1.8
Study Days
N=
Avg. daily dose
0
200
400
600
800
1000
1200
1400
Mean Platelet Count (± SD)
Pla
tele
t C
ou
nt
(x10
9/L
)
Figure 2. Platelet Response
1 8 15 22 29 36 43 50 57 64 71 78 85 99 113 127 141 155 169 197 225
18 18 18 18 18 18 15 14 14 14 13 13 13 13 13 13 12 12 11 11 11
1.0 1.4 1.8 1.9 2.0 2.2 2.4 2.5 2.4 2.2 2.0 2.1 2.1 1.9 1.8 1.9 2.0 1.9 1.8 1.9 1.8
Study Days
N=
Avg. daily dose
0
200
400
600
800
1000
1200
1400
Mean Platelet Count (± SD)
Pla
tele
t C
ou
nt
(x10
9/L
)
Figure 2. Platelet Response
1 8 15 22 29 36 43 50 57 64 71 78 85 99 113 127 141 155 169 197 225
18 18 18 18 18 18 15 14 14 14 13 13 13 13 13 13 12 12 11 11 11
1.0 1.4 1.8 1.9 2.0 2.2 2.4 2.5 2.4 2.2 2.0 2.1 2.1 1.9 1.8 1.9 2.0 1.9 1.8 1.9 1.8
Study Days
N=
Avg. daily dose
0
200
400
600
800
1000
1200
1400
Mean Platelet Count (± SD)
Pla
tele
t C
ou
nt
(x10
9/L
)
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
10 Not 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 ANAGRELIDE CONTROLLED RELEASE (CR): GALE-401
11
Anagrelide IR^ GALE-401*
Benefits
Therapeutic index# Narrow - dose escalation to optimal effect is challenging
Wider - 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 for
faster onset of action
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)
MPN characterized by
increased number of platelets
• ET is a neoplastic stem cell
disorder causing dysregulated
production of large numbers of
abnormal megakaryocytes
Chronic condition
• Median Overall Survival: 14.7
years
• Up to 50% of patients may be
asymptomatic at presentation
Associated with vascular
complications
12
Arrows indicate
Megakaryocytes
ET has Larger Number
of Megakayocytes
Source: Haematologica. 2009 June; 94(6): 865, Am J Hematology. 2008 May;83(5):359)
Essential Thrombocythemia (ET)
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%
13 Source: MPN Research Foundation
Current ET Treatment Options
Hydroxyurea
• Generally initial treatment option
• Cytotoxic Myelosuppressive drug (reduces other blood cells as well)
• Increased risk of developing acute leukemia after long term
• Avoided in younger patients
• ~25% of patients intolerant/refractory
Anagrelide IR
• Only approved therapy for ET
• Poor tolerability and compliance thought to be related to blood concentrations
• Non cytotoxic drug
• Not associated with increased risk of leukemia
• Significant side effects
Aspirin
• Given to reduce the risk of blood clotting
• Does not lower platelet counts
• May help relieve the burning sensation in patient’s hands and feet (erythromelagia)
Other Therapies
• Interferon
•Busulfan
•Retry hydroxyurea
•Observation
14 Sources: Leukemia and Lymphoma Society: Essential Thrombocythemia Facts Cervantes, F. Hematology 2011; 215-221
PIVOTAL, PHASE 3 TRIAL STRATEGY
Targeting the reduction of platelets in ET patients
• US Prevalence: 135,000 - 175,000
~75% of diagnosed patients receive treatment
• Limited competition with very few agents in development
Planned next steps
• End of Phase 2 meeting with the FDA (Q4, 2016)
• Finalize the Phase 3 clinical trial design
• Initiate pivotal trial (Q2, 2017)
15 Sources: Harrison et al N Engl J Med 2005;353:33-45; Mehta et al, (2014) Epidemiology of myeloproliferative
neoplasms in the United States, Leukemia & Lymphoma, 55:3, 595-600, DOI: 10.3109/10428194.2013.813500
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
17
K I F G S L A F L
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
18 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
0.4
1.8
0.7
0.5
0.0
0.5
1.0
1.5
2.0
2.5
% N
eu
Va
x s
pe
cific
CD
8+
T c
ells
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
19
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
NEUVAX: MULTIPLE SETTINGS AND COMBINATION STRATEGY
Phase Treatment HER2 Status
Indication Trial Status Protocol Defined
# of Patients Collaborations
2b Combination
with trastuzumab
1+, 2+
BREAST Node Positive or High Risk Node Negative
HLA A2+, A3+, A24+, A26+
Enrolling U.S. only
33 centers 300
2 Combination
with trastuzumab
3+ high risk
BREAST Node Positive HLA A2+, A3+
Enrolling U.S. only
28 centers 100
2 Single agent VADIS Study
1+, 2+,3+
BREAST Ductal Carcinoma in
Situ (DCIS) HLA A2+
Planned U.S. only 4 centers
48
2 Single agent 1+,
2+,3+ GASTRIC
HLA A2+, A3+ Planned
India Only 50
20
CORRELATION BETWEEN HER2 & MHC-1
There is an inverse
correlation between
HER2 and MHC class I
HER2 overexpression is
associated with
decreased expression of
components of the
antigen processing/
presentation pathway
21
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
22
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
Ave
rage
% C
yto
toxi
city
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
DFS at
12 months
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
Primary
Endpoint
DFS at
24 months
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
23
GALE-301 & GALE-302
25
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
Vaccine Control
% o
f S
ub
jec
ts
Recurrence
24.0% 13.3%
Source: U.S. Ovarian Cancer http://seer.cancer.gov/statfacts/html/ovary.html
Targeted cancer immunotherapies: GALE-301 (E39) & GALE-302 (E39’)
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
GALE-301: OPTIMAL DOSE GROUP SHOWS PRELIMINARY EFFICACY
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
Vaccine Control
% o
f S
ub
jec
ts
Recurrence
24.0% 13.3%
Source: Peoples, et. al, Poster Presentation, American Society of Clinical Oncology 2016 26
Phase 1/2a trial ongoing
Phase 1: Determined optimal dose and demonstrated safety and potent immune response
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 is 73.5% vaccine vs. 38.1% control (p=.03)
• GALE-301 plus GM-CSF is well tolerated and elicits a strong in vivo immune response with primarily Grade 1 and Grade 2 toxicities
Estimated 24 months Disease Free Survival by
Dosing Cohort
CURRENT CLINICAL DEVELOPMENT
Phase Treatment Cancer Type Current Status
# of Enrolled Patients
1/2a GALE-301 Ovarian, Endometrial
HLA A2+ Ongoing 51
1b GALE-301 &
GALE-302 Ovarian, Breast
HLA A2+ Ongoing 39
Multiple data presentations inform the design & target patient populations for future trials
Low expressors appear to show improved disease free survival (DFS) due to
immunotolerance from significantly higher endogenous exposure to the FBP antigen
Different doses/schedules appear to correspond to various types of cancer:
• Breast patients = lower FBP exposure and may require lower 500mcg dose
• Ovarian patients = higher FBP expression and may require higher 1000mcg dose
• E39’ (GALE-302) may prevent T-Cell exhaustion
Sources: Peoples, et. al, 2016 poster presentations at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy
Conference, American College of Surgeons Clinical Congress, and Society for Immunotherapy of Cancer Conference 27
LEADERSHIP TEAM
29
Mark W. Schwartz, Ph.D.
President & CEO
Apthera, Bayhill Therapeutics, Calyx
Therapeutics, Trega Biosciences, Incyte
Genomics, DuPont Diagnostics
Bijan Nejadnik, M.D.
Executive VP, Chief Medical Officer
Jazz Pharmaceuticals, Johnson & Johnson,
Stanford, Johns Hopkins, UC Davis
Stephen Ghiglieri
EVP, Chief Financial Officer
MedData Inc., NeurogesX, Hansen Medical,
Inc., Oacis Healthcare Systems, Oclassen
Pharmaceuticals
Remy Bernarda,
SVP, Investor Relations & Corporate
Communications
IR Sense, Hana Biosciences, Knight
Equity Markets, Bear Stearns, Goldman
Sachs
John Burns, CPA
VP, Finance & Corporate Controller
Pixelworks, Moss Adams
Tom Knapp, Esq.
Interim General Counsel
Sucampo, Exemplar Law Partners,
NorthWestern Energy, Paul Hastings, The
Boeing Company
FINANCIAL OVERVIEW
Cash Position (as of 30 Sept 16) $24.5 million
Restricted Cash (as of 30 Sept 16 - $18.5 relating to Debenture)
$18.9 million
Projected Q4 Cash Burn from Operations $7 - $9 million
Shares Outstanding (as of 31 Oct 16) 10.85 million*
Market Cap (as of November 28, 2016) ~$36 million
30 *Shares adjusted to account for reverse stock split effective November 14, 2016
2H, 2016 MILESTONES
31
PROGRAM MILESTONE PROJECTED
DATE
GALE-401 (anagrelide CR)
Present combined safety data ✓
Confirmation of 505(b)2 pathway 2H
NeuVax™ (nelipepimut-S)
Fast Track Designation ✓
Combo H&N 1+/2+ Interim safety data ✓
Initiate DCIS trial Q4
GALE-301 GALE-302
Present 301/302 booster data ✓
Present GALE-301 Phase 2a primary analysis ✓
Orphan Drug Designation ✓
Present GALE-301 Biomarker & Dosing Data ✓