This presentation provides an overview of an oncology-focused immunotherapy company. It discusses the company's lead product, NeuVax, which is an immunotherapy targeting HER2-positive breast cancer in both the adjuvant and metastatic settings. Key information includes:
- NeuVax is currently in a Phase 3 clinical trial (PRESENT) in the adjuvant setting for HER2 1+/2+ breast cancer patients. Enrollment is complete for the trial.
- An interim analysis of the PRESENT trial is expected in late Q2 2016 which will evaluate safety and futility based on 70 recurrence events.
- Additional clinical trials are exploring NeuVax in combination with Herceptin and in other HER2-positive cancers like
One in 8 U.S. women will develop invasive breast cancer over her lifetime, with approximately 266,000 new breast cancer patients and 3.1 million breast cancer survivors in 2018. Following breast cancer surgery in the adjuvant setting, a HER2/neu 3+ patient typically receives Herceptin® in the first year, with the hope that their breast cancer will not recur, and with the odds of recurrence slowly decreasing over the first 5 years after surgery. Herceptin® has been shown to reduce recurrence rates from 25% to 12% in the adjuvant setting. In the neoadjuvant setting, a patient receives treatment before surgery and based on the results of a biopsy at surgery, will receive the same or more potent treatment after surgery. Kadcyla® has been shown to reduce recurrence rates from 22% to 11% in the neoadjuvant setting. Accordingly, we believe that GP2 may be used to address the 50% of recurring patients who do not respond to either Herceptin® or Kadcyla®.
Breast Cancer - Molecular Basis of HER2+ DiseaseFaryn
This presentation was part of a graduate level advanced molecular cell biology course. It reviews Breast Cancer epidemiology, signs 7 symptoms, diagnosis, genetic testing, hormonal testing and treatment options (briefly), then discusses the specifics of HER2+ cases at the cellular level. It shows how Herceptin and Tykerb work in the cell to block signal cascades, etc.
One in 8 U.S. women will develop invasive breast cancer over her lifetime, with approximately 266,000 new breast cancer patients and 3.1 million breast cancer survivors in 2018. Following breast cancer surgery in the adjuvant setting, a HER2/neu 3+ patient typically receives Herceptin® in the first year, with the hope that their breast cancer will not recur, and with the odds of recurrence slowly decreasing over the first 5 years after surgery. Herceptin® has been shown to reduce recurrence rates from 25% to 12% in the adjuvant setting. In the neoadjuvant setting, a patient receives treatment before surgery and based on the results of a biopsy at surgery, will receive the same or more potent treatment after surgery. Kadcyla® has been shown to reduce recurrence rates from 22% to 11% in the neoadjuvant setting. Accordingly, we believe that GP2 may be used to address the 50% of recurring patients who do not respond to either Herceptin® or Kadcyla®.
Breast Cancer - Molecular Basis of HER2+ DiseaseFaryn
This presentation was part of a graduate level advanced molecular cell biology course. It reviews Breast Cancer epidemiology, signs 7 symptoms, diagnosis, genetic testing, hormonal testing and treatment options (briefly), then discusses the specifics of HER2+ cases at the cellular level. It shows how Herceptin and Tykerb work in the cell to block signal cascades, etc.
Targovax is developing two complementary and highly targeted approaches to cancer immunotherapy: a peptide-based targeted immunotherapy platform for patients with RAS-mutated cancers and a virus-based oncolytic immunotherapy platform based on engineered oncolytic viruses armed with potent immune-stimulating transgenes for patients with solid tumors.
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.
2
3. 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
3
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 10.5
Year
Hazardofrecurrencebyyearlyinterval
Total
Node 0
Node 1-3
Node (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
4. DEVELOPMENT PIPELINE
Product Therapeutic Area Phase 1 Phase 2 Phase 3 BLA / NDA
Immunotherapy: Breast Cancer
NeuVax™ (nelipepimut-S)
Node-positive
HER2 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
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
4
2b
5. Adds ~10k patients
>$3B
Combo:
High risk, HER2 3+
NEUVAX:
SIGNIFICANT U.S. COMMERCIAL OPPORTUNITY
5
adds ~10k patients
>$2.5B
Combo Node Pos or Neg
HER2 1+, 2+
HLA-A2, A3, A24, A26
PRESENT
50-60k 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).
7. NOVEL DEVELOPMENT STRATEGY:
SECONDARY PREVENTION IN CANCER SURVIVORS
7
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
Risk
20% recurrence rate
DECLARED
TO PREVENT
RECURRENCE /
METASTATIC DISEASE
Breast: Ductal Carcinoma in
Situ
8-10% progression to invasive
Ovarian Cancer
~50% recurrence rate in 1 yr
No FDA Approved
targeted therapies
• Watch &
Wait, or
• Repetitive
therapies
TOLD
8. 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 =
8
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
9. 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
9Source: DeSantis CE et al. CA Cancer J Clin 2014: 64:252-271
11. FIRST-IN-CLASS, TARGETED
IMMUNOTHERAPY PIPELINE
11
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
12. 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
12
Checkpoint
inhibitors
Indirect Immune
Modulators
Co-stimulators
Immune Inhibitory
Enzymes
CAR T
Technology
TCR
Technology
13. 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
13
Checkpoint
inhibitors
Indirect Immune
Modulators
Co-stimulators
Immune Inhibitory
Enzymes
16. 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
16
K I F G S L A F L
17. 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
17
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
%NeuVaxspecificCD8+Tcells
NeuVax Specific CD-8 CTLs: Pre-, Post, Mean and
Long-Term (6 months)
Pre Max Mean Long-Term
18. 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
18
Sources: Choy, et al, poster presentation 33rd Annual Chemotherapy Foundation
Symposium: Nov 2015; Mittendorf- Annals of Oncology 25: 1735–1742, 2014
19. NEUVAX: SN-33 PHASE 2 HER2 IHC 1+/2+
19Source: 2012 San Antonio Breast Cancer Poster, Mazanet, et al.
20. 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
• Primary Endpoint: 2018
20
21. 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
21
Prevention of Recurrence in Early-Stage, Node Positive Breast Cancer with
Low to Intermediate Her2 Expression with NeuVax Treatment
22. PRESENT INTERIM ANALYSIS
70 Events
Confirmed
by the EAC
• Endpoint Adjudication Committee confirms
70 events
• Independent team of 2 Oncologists and 1
Radiologist
Galena
Compiles
Data
• Prepares a detailed review on 70 patients with events
and overall safety data set (n=758)
• Submits to IDMC
IDMC
Evaluates
• Evaluates 70 patients with events and overall
safety data set (n=758)
• Makes recommendation on futility and
continuation of trial
Interim
Analysis
Results
•Estimated
timing:
End of Q2
22
23. PRIMARY PREVENTION
Expansion potential for
safe vaccine in DCIS
METASTATIC DISEASE
Expansion potential in
combination with
checkpoint inhibitors
/immune modulators
NEUVAX: ACROSS THE BREAST CANCER
TREATMENT SPECTRUM
23
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
24. NEUVAX: DEVELOPMENT COLLABORATIONS
Phase Treatment
HER2
Status
Indication Trial Status
Protocol
Defined
# of Patients
Collaborations
3
Single agent
PRESENT
Study
1+, 2+
BREAST
Node Positive
HLA A2+, A3+
Enrolled
13 countries
~140 centers
700
(enrolled 758)
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
24
26. GALE-301 & GALE-302
26Source: 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
27. GALE-301: OPTIMAL DOSE GROUP SHOWS
PRELIMINARY EFFICACY
Source: Peoples, et. al, Poster Presentation, European Cancer Congress 2015 27
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
28. GALE-301 & GALE 302: PHASE 1
DELAYED-TYPE HYPERSENSITIVITY
28
LEGEND
EE = 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 PVS
RC6 = 6 months after completion of the PVS and pre-booster
Source: Mittendorf et. al., Poster Presentation, Society of the Immunotherapy of Cancer 2015
30. 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 Results
•Well tolerated with primarily Grade 1 and 2 toxicities
•Efficacy compares favorably to historical anagrelide IR
30
32. 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
Head & Neck
Folate Binding
Protein
Ovarian
Endometrial
Breast
32
33. LEADERSHIP TEAM
33
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 Communications
IR Sense, Hana Biosciences, Knight Equity
Markets, Bear Stearns, Goldman Sachs
Gavin Choy, Pharm.D., SVP, Clinical Sciences &
Operations
Otsuka, 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 &
Compliance
Nektar Therapeutics, Bayhill Therapeutics,
Berlex Laboratories, Serono, Parexel, Biogen
34. 2016 MILESTONES
34
PROGRAM MILESTONE
PROJECTED
DATE
NeuVax™
(nelipepimut-S)
PRESENT: Achieve 70 Qualifying DFS Events ✓
Fast Track Designation ✓
Initiate DCIS trial Q2
PRESENT: Interim analysis Q2
Combo H&N 1+/2+ Interim safety data Q4
Combo H&N 1+/2+ A24/A26 data Q4
GALE-301
GALE-302
Present 301/302 booster data ✓
Present GALE-301 Phase 2a two year data Q4
GALE-401
(anagrelide CR)
Present combined safety data Q2
Confirmation of 505(b)2 pathway 2H
Publish final Phase 2 report Q4
35. FINANCIAL OVERVIEW
Cash Position (as of March 31, 2016) $34.7 million
Debt Financing (May 10, 2016) + $23.4 million
Payoff Remaining Oxford Debt (May 10, 2016) - $3.1 million
Q2 Projected Operating Burn $13 - $15 million
Includes legal settlement & fees ~$4-$5 million
Future Projected Quarterly Burn $9 - $11 million
Shares Outstanding 182 million
Market Cap (as of June 2, 2016) ~$375 million
35
36. WHY WE’RE HERE
36
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
