galena presentation 9 feb 17
TRANSCRIPT
HEMATOLOGY &
ONCOLOGY FOCUSED
COMPANY
February 9, 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
GALE-401
Anagrelide Controlled
Release (CR)
ANAGRELIDE
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)
Anagrelide suppresses megakaryocytopoiesis by inhibiting
PDE III-dependent and PDE III-independent mechanisms
No DNA damaging or cytotoxic effect
6
GALE-401:ANAGRELIDE CONTROLLED RELEASE (CR)
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
Six trials conducted to date
• Five Phase 1 studies in healthy volunteers
• Phase 2 pilot study in patients with myeloproliferative neoplasms (MPNs)
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
Multiple life cycle management opportunities
7
Res
ult
s 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
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.
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)
• 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
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 day2 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)
One of the major MPNs
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
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
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
Contains the immunodominant peptide derived from the extracellular region of the HER2 protein
Binds to antigen presenting cells (APCs)
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
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
% N
eu
Va
xsp
ecific
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
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
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
19
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
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
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
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
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
PhaseTreatment
HER2 StatusIndication Trial Status
TargetedEnrollmentCompletion
PlannedData
ReadoutsCollaborations
2bCombination
w/trastuzumabHER2 1+, 2+
BREAST Node Positive or High Risk Node
NegativeHLA A2+, A3+,
A24+, A26+
EnrollingU.S. only
33 centersn=300
Q2 2017
Q4, 2017Interim Analysis
1H, 2019Final Data
2
Combinationw/trastuzumab
high risk HER2 3+
BREASTNode PositiveHLA A2+, A3+
EnrollingU.S. only
28 centersn=100
Q4 20171H, 2019Interim Analysis
2
Single agentVADIS StudyHER2 1+, 2+,
3+
BREASTDuctal Carcinoma in Situ (DCIS)
HLA A2+
EnrollingU.S. only4 centers
N=48
2
Single agentHER2 1+, 2+,
3+GASTRIC
HLA A2+, A3+
PlannedIndia 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 201623
Folate Binding Protein (FBP) is over-expressed (20-80 fold) in >90% of ovarian and endometrial cancers
High unmet medical need in ovarian cancer patients
Relatively shorter development timelines
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
24
LEADERSHIP TEAM
25
Bijan Nejadnik, M.D.
Executive VP, Chief Medical Officer
Jazz Pharmaceuticals, Johnson & Johnson,
Stanford, Johns Hopkins, UC Davis
Stephen Ghiglieri
Executive VP, Chief Financial Officer
MedData Inc., NeurogesX, Hansen Medical,
Inc., Oacis Healthcare Systems, Oclassen
Pharmaceuticals
Tom Knapp, Esq.
Interim General Counsel
Sucampo, Exemplar Law Partners,
NorthWestern Energy, Paul Hastings, The
Boeing Company
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
2017 MILESTONES
26
PROGRAM MILESTONEPROJECTED
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+ CombinationTrial
Q2
Interim safety data presentation for NeuVax/trastuzumab 1+/2+ CombinationTrial
Q2
Complete enrollment in NeuVax/trastuzumab 3+ Combination Trial
Q4
Interim data analysis: NeuVax/trastuzumab1+/2+ Combination Trial
Q4
GALE-301GALE-302
Final GALE-301 data presentation Q1
THANK YOU
NASDAQ: GALE