1) The company has a diversified pipeline including hematology and immunotherapy programs with multiple clinical trials in mid to late stages.
2) Their lead hematology candidate, GALE-401, is a controlled release formulation of anagrelide for the treatment of essential thrombocythemia that has demonstrated an improved safety profile over immediate release formulations in clinical trials to date.
3) Their immunotherapy programs include NeuVax for HER2-positive breast cancer, which has shown strong CD8+ T-cell responses in clinical trials both as a single agent and in combination with trastuzumab.
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
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
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
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