Corporate Overview - Northwest Biotherapeutics

Corporate Overview
Biotech Showcase
January 13, 2014
Disclaimer
Certain statements made in this presentation are “forward-looking statements” of NW Bio as defined
by the Securities and Exchange Commission (“SEC”). All statements, other than statements of
historical fact, included in this presentation that address activities, events or developments that NW
Bio believes or anticipates will or may occur in the future are forward-looking statements. These
statements are based on certain assumptions made based on experience, expected future
developments and other factors NW Bio believes are appropriate in the circumstances. Such
statements are subject to a number of assumptions, risks and uncertainties, many of which are
beyond the control of NW Bio. Investors are cautioned that any such statements are not guarantees
of future performance. These forward-looking statements could cause actual results and developments
to differ materially from those expressed or implied in such statements, including our ability to raise
funds for general corporate purposes and operations, including our clinical trials, the commercial
feasibility and success of our technology, our ability to recruit qualified management and technical
personnel, our ability to scale up the manufacturing of our product candidates for commercialization,
the success of our clinical trials and our ability to obtain and maintain required regulatory approvals for
our products. Furthermore, NW Bio does not intend (and is not obligated) to update publicly any
forward-looking statements. The contents of this presentation should be considered in conjunction
with the risk factors contained in NW Bio’s recent filings with the SEC, including its Form 10K/A filed
April 30, 2013. This communication is neither an offer to sell nor a solicitation of an offer to buy any
securities mentioned herein. This publication is confidential for the information of the addressee only
and may not be reproduced in whole or in part; copies circulated, or disclosed to another party, without
the prior written consent of Northwest Biotherapeutics (NW Bio) are strictly prohibited.
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Corporate Highlights
Unique
Technology:
DCVax®
Late Stage Trials
Simple Delivery;
Non-Toxic
Consistent &
Striking Results In
Diverse Trials
Superior
Manufacturing
•
Applicable to all types of solid tumor cancers, both operable & inoperable.
•
Hits the full set of biomarker targets on tumor, making it harder for tumor to
escape.
•
DCVax-L in 312-patient Phase III trial for GBM in US & Europe.
•
DCVax-Direct in 60-patient Phase I/II trial for all inoperable solid tumors:
direct injection into tumors anywhere in body.
•
Simple intradermal injection under skin in arm, similar to a flu shot.
•
No toxicity in over 1,000 treatment cycles in clinical trials to date.
•
Clinical trials in brain, ovarian & prostate cancers; >80% of patients respond.
•
Median PFS & OS extended by 1-1/2 years or more beyond results with SOC.
•
8-day process yields 3-5 years of doses in cost-effective batch; then frozen
in single doses.
•
Manufacturing facilities in both US and Europe, at major logistics hubs.
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2013 Highlights: DCVax‐L Clinical Program
DCVax®-L Program
•
Long-term survivors from Phase I/II Trials, including 2 patients exceeding 10-years
•
Phase III Trial reached 50+ sites in US
•
Phase III Trial launched, enrollment begun in UK; additional UK sites in process
•
After multi-stage evaluation, Trial “adopted” by NHS/NIHR as national priority in UK
•
Regulatory & institutional approvals completed in Germany & UK for cross-border
manufacture and supply of DCVax-L product
•
Phase III Trial approved by German regulator; 20+ sites in process
•
Establishment of German subsidiary; hiring and training of >20 technical staff
DCVax-Direct Program
•
Final pre-clinical product development work completed. Further development of
TFF automated system for first stage of manufacturing process.
•
60-patient Phase I/II Trial launched and enrollment begun at MD Anderson Houston
& MD Anderson Orlando; additional sites pending
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2013 Highlights: Other Programs
Other Operations Highlights
• Manufacturing expansion in both Europe & US; further expansions
planned
• Key patent issuances: processes for more potent dendritic cells
automated manufacturing
Financial Highlights
• 3 equity financings totaling >$50 million; major strengthening of
balance sheet
• NWBO added to MSCI Global Microcap Index
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DCVax®: The Future of Cancer Medicine… Now
Personalized immunotherapy using dendritic cells (master cells of the immune system)
 Active immune therapy: mobilizes the whole immune system
 Multiple cancer targets: hits the full set of tumor biomarkers (including
cancer stem cells)…. not just one or a few “cherry picked” biomarkers….
makes it harder for the tumor to escape
 Personalized medicine: the relevant tumor biomarkers…. solves the
patient to patient variability of cancers => response rates over 80%
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Dendritic Cells Mobilize the Whole Immune System
DENDRITIC CELLS
Signals activate &
biomarkers educate
Dendritic Cells
the master
immune cells
INNATE IMMUNE SYSTEM
ADAPTIVE IMMUNE SYSTEM
“First-responders” (within hours/days)
Follow-on defense (within week or weeks)
Response is automatic
Response is triggered by exposure to
particular threat (activation + “education”)
Response is non-specific
(not tailored to each particular threat)
Response is specific & creates memory
(tailored to each particular threat)
Natural Killer Cells, Neutrophils,
Granulocytes, Macrophages
HUMORAL IMMUNITY
B Cells
Antibodies
CELLULAR IMMUNITY
Helper T Cells
Killer T Cells
Tumor Cell Death
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DCVax®-Direct: Novel Technology for Inoperable Tumors
Immature DCs
DCVax‐Direct:
Partially Mature DCs
Mature DCs
Antigen Uptake
Antigen
Communication
Results: Some Tumor Response
But Transient
Potent & Sustained Tumor Response
Little Tumor Response
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DCVax® Applicable to All Solid Tumors
(Both Operable & Inoperable)
Market
Product
Composition
Lead Program
All Operable
Solid Tumors
DCVax®-L
Dendritic cells + biomarkers
from tumor tissue sample
surgically removed
Brain cancer
312-patient Phase III trial
underway
All Inoperable DCVax®-Direct Dendritic cells directly injected All solid tumor
into tumor(s) + biomarkers
cancers
Solid Tumors
Other
Hormone
independent
prostate cancer
DCVax®Prostate*
picked up onsite in tumor
60-patient Phase I/II trial
underway
Dendritic cells + recombinant
prostate cancer biomarker
(PSMA)
Prostate cancer
600-patient Phase III trial
previously cleared by
FDA
* The Company will seek to out-license this program
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Robust Pipeline of Clinical Trials
Pre-clinical
Ph I
Ph II
Ph III
DCVax®- L:
Brain cancer – Phase III under way
Metastatic ovarian cancer – Phase I complete
DCVax®- Direct:
All solid tumor cancers – Phase I/II underway
Colon cancer metastases – Phase I/II planned
DCVax®- Prostate:
Prostate cancer – Phase III previously
cleared by FDA; awaiting partnering
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Lead Program: DCVax-L for Newly Diagnosed GBM
Phase I/II Trials
•
20 patients with newly diagnosed GBM; 14 with recurrent GBM; 5 with lower grade gliomas
•
3 dose levels: 1, 5 and 10 million Dendritic Cells (1 and 5 million were best)
•
Patients received standard of care + DCVax-L (surgery & 6 weeks radiation & chemo)
•
3 DCVax-L treatments upfront, weeks apart, then booster treatments several months apart
•
Primary endpoint was safety; secondary endpoint was Progression Free Survival
Standard of Care*
Matched Concurrent
Controls**
DCVax-L
Progression
(Tumor Recurrence)
6.9 mos
8.1 mos
2 years
Overall Survival
14.6 mos
17 mos
3 years
Long Tail of Survival
2 – 3% alive
at 5 years
* N Engl J Med 352:
987-96, 2005
To date: 33% alive >4 yrs
27% alive >6 yrs
2 pts alive >10 yrs
**matched for age, gender, Karnofsky score, extent of surgical resection,
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and same std of care treatment, at same hospital, in same time period
DCVax®-L in Newly Diagnosed GBM:
Progression Free Survival (PFS) in Phase I/II Trials
Proportion not progressed
1.0
0.9
Std of care + DCVax-L Treatment
0.8
Std of Care Treatment
0.7
P value of this comparison
p < 0.00001
0.6
0.5
26.4 mo
0.4
0.3
8.1 mo
0.2
0.1
8.1
0.0
0
26.4
20
40
60
80
M onths
DCVax®-L showed an 18.3 month PFS benefit over
standard of care in newly diagnosed GBM patients
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DCVax®-L in Newly Diagnosed GBM:
Overall Survival (OS) in Phase I/II Trials
Proportion surviving
1 .0
0 .9
Std of care + DCVax®-L Treatment
0 .8
Std of Care Treatment
0 .7
P value of this comparison
p = 0.0003
0 .6
0 .5
36.4 mo
0 .4
0 .3
17.0 mo
0 .2
0 .1
3 6 .4
17
0 .0
0
20
40
60
80
100
120
M o n th s
DCVax®-L showed an 19.4 month OS benefit over
standard of care in newly diagnosed GBM patients
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International Phase III Trial With DCVax-L for GBM
• Newly diagnosed GBM; trial under way in both US & Europe
• 312 patient, randomized (2:1), double blind, placebo controlled
Phase III trial: the “gold standard” in clinical trial design
o
Primary endpoint: PFS (progression free survival)
o
Secondary endpoints include OS (overall survival)
o
2 interim analyses for efficacy & 1 interim analysis for sample size
o
3 DCVax-L treatments upfront (Day 0, 10, 20), then 3 boosters (months 2, 4, 8)
then 4 treatments twice/year for maintenance phase (months 12, 18, 24, 30)
• Multiple protections built into trial design
 6-month extension of PFS required to meet primary endpoint –
only 1/3 as long as extension of PFS seen in Phase I/II trials
 Trial is also powered for secondary endpoint of Overall Survival
 Interim analysis for sample size allows adjustment as needed for power
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DCVax®-L: Phase I/II Pilot Trial In Ovarian Cancer
•
Target cancer:
– Advanced metastatic ovarian cancer
– Patients who had failed standard therapy, including Avastin
•
Two-stage trial: 6 patients
– Stage 1: DCVax-L treatments
– Stage 2: autologous T cell infusions
•
Efficacy endpoints: tumor response (shrinkage), PFS and OS
•
Site: U Penn Center of Excellence in Ovarian Cancer
•
Results after DCVax treatment:
– Partial tumor clearance in 2 patients with strong immune response
– Disease stabilization (stopped the existing active disease progression) in 2 patients
with moderate immune response, with one remaining disease free for 14 months
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DCVax®-Direct: Striking Pre-Clinical Results
250
Tumor Size (mm2)
250
200
Tumor Size (mm2)
chemo
only
150
100
150
100
50
0
0
7
14
21
Day
28
35
7
14
21
28
35
42
Day
42
250
Tumor Size (mm2)
250
Tumor Size (mm2)
50
0
0
+
immature
DCs
+
partially
activated
DCs
200
200
150
100
+
optimally
partially
activated
DCs
200
150
100
50
50
0
0
0
0
7
14
21
28
35
42
7
14
21
28
35
42
Day
Day
Tumor clearance throughout body
after direct injection into a few tumors in animal studies
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DCVax-Direct Phase I/II Trial Design
• 60-patient Proof of Concept “All Comers” Phase I/II Trial
for all inoperable solid tumor cancers
 Phase I stage: 36 patients – safety, feasibility, dose-finding
(Colon, breast cancer with brain metastases, liver, pancreas, melanoma & other/misc.)
 Phase II stage: 24 additional patients in one selected cancer – e.g., colon
Primary efficacy endpoint: tumor regression (shrinkage)
Additional efficacy endpoints: progression free survival & overall survival
• Intra-tumoral injection into one tumor. Can reach ~any location in body
with ultrasound guidance. 6 treatments: Day 0 and weeks 1, 2, 8, 16 & 32.
• Primary efficacy measure: regression (shrinkage/elimination) of tumors.
• Trial under way at MD Anderson-Houston & MD Anderson-Orlando.
Additional sites pending.
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DCVax®- Prostate
Completed multi-center Phase I / II trial with 36 patients
 Showed positive efficacy signal and good safety (no toxicity)
Hormone Independent
Non-Metastatic Prostate Cancer
Time to progression Median survival
Course of disease
DCVax®‐
Prostate
28‐34 weeks
59 weeks
36 months
>54 months (>half were
still alive ) Hormone Independent
Metastatic Prostate Cancer
Dendreon’s
Std. of care (Taxotere)
Provenge**
DCVax®‐
Prostate4
Median survival
18.9 months
25.9 months
38.7 months
Overall survival at 3 years
11%
33%
64%
FDA has approved 612-patient Phase III prostate cancer trial design
Company is seeking to out-license this program
** Zytiga & Xtandi
add 4‐5 mos OS beyond
Taxotere/chemo,
comparable to amount
of OS added by Provenge
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Rapid and Cost-Effective Batch Manufacturing
One Manufacturing Batch Produces 3-5 Years of Personalized Doses
To Be Stored Frozen Until Needed; Only 2 Grams of Tumor Tissue Needed.
Robust
Manufacturing,
> 10 years in
Development
2. Blood draw (leukapheresis)
to obtain patient’sdenritic cells.
1. Tumor surgically
removed; tissue sent
in kit to manufacturing
facility.
Quick:
8 days
Low Cost:
Batch
Production
High Yield:
3-5 Years of Doses
In One Batch
3. Precursors of fully mature
dendritic cells
isolated from blood draw.
(1 day)
Total time from initial
blood draw to
completion of
DCVax-L production:
~8 days.
7. “Educated”
dendritic cells
injected
back into patient.
6. “Educated”
dendritic cells are
re-isolated from biomarker
mixture, and frozen
in single doses
for later treatments.
4. Precursor cells
matured into fresh
dendritic cells in the lab
(in vitro). (6 days)
5. Dendritic cells
exposed to full set of
cancer biomarkers from
patient’s own tumor
cells, thereby being
“educated” about
tumor to attack.
(< 1 day)
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Manufacturing Established At Logistics Hubs In US & Europe
•
Memphis, TN: worldwide hub
for both FedEx & UPS
•
50,000 sq ft facility; capacity for
5,000 DCVax patients/year
•
Leipzig, Germany: Europe-wide hub
for DHL, Lufthansa Cargo, others
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Large Intellectual Property Portfolio
• DCVax®-L for brain cancer:
– Orphan status granted in US and EU
• DCVax®-Prostate and DCVax®-Direct:
– Composition and methods
• Other platform coverage:
–
–
–
–
Manufacturing for more potent dendritic cells
Isolation, maturation and “education” of dendritic cells
TFF system - automation of manufacturing
Methods of delivery to patients
Over 180 patents issued and pending, worldwide
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Experienced Management Team
Linda F. Powers – Chairman & Chief Executive Officer
–
–
–
12+ years’ experience building biotechs, developing cell therapy products
15+ years’ experience in corporate finance, M&A, joint ventures, and IP
Largest shareholder of NW: >$20 million invested
Dr. Marnix Bosch – Chief Technical Officer
–
–
–
Former Head of Molecular Biology at Dutch National Institutes of Health
Former Associate Professor at Univ. Washington
Author of >50 research publications in immunology, virology & cancer
Dr. Alton Boynton – Chief Scientific Officer & Co-founder
–
–
–
Formerly Director of the Department of Molecular Medicine of Northwest Hospital,
Director of Foundation from which Fred Hutchinson Cancer Center was spun off
Associate Director of Cancer Research Center of Hawaii.
Dr. Anthony Maida – Chief Operating Officer
–
–
Over 20 years’ experience building oncology companies; expertise in the business, financial,
clinical, regulatory and science.
Former controller of multi-billion dollar division of public companies
Les Goldman – SVP, Business Development
–
Former Partner at Skadden, Arps; over 30 years’ corporate finance, legal and media experience
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Financial Overview
Shares Outstanding
45 million
Share Price 1-10-14
$4.44
Market Capitalization
$200 million
Funding 11-25-13
$ 25+ million
Additional Funds
Available
$5.5 million of grant money from the
German Government
Prior investors exercising warrants
Monthly burn rate
Approx. $2.7 million
•
•
•
312-patient Phase III DCVax-L trial
60-patient Phase I/II DCVax-Direct trial
Development program
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