DCVax-Prostate

Company Overview
OneMed Forum
January 10, 2012
Disclaimer
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 (NWBT)
are strictly prohibited.
Information and opinions presented in this report have been obtained or derived from sources believed to be reliable,
but NWBT makes no representation as to their accuracy or completeness. NWBT accepts no liability for loss arising
from the use of the material presented in this report, except that this exclusion of liability does not apply to the extent
that such liability arises under specific statutes or regulations applicable to NWBT. This report is not to be relied upon in
substitution for the exercise of independent judgment. NWBT may have issued, and may in the future issue, other
reports that are inconsistent with, and reach different conclusions from, the information presented in this report. Those
reports reflect the different assumptions, views and analytical methods applicable when made, and NWBT is under no
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Investors must make their own determination as to the appropriateness of an investment in any securities referred to
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Past performance should not be taken as an indication or guarantee of future performance, and no representation or
warranty, express or implied is made regarding future performance. Information, opinions and estimates contained in
this report reflect a judgment at its original date of publication by NWBT, and are subject to change without notice. The
price, value of and income from any of the securities mentioned in this report can fall as well as rise. Securities offered
or sold by NWBT: (1) are not insured by the Federal Deposit Insurance Company; (2) are not deposits or other
obligations of any insured depository institution; and (3) are subject to investment risks, including the possible loss of
principal invested. Additional information about NWBT can be found on the company’s website: www.nwbio.com.
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NWBT Overview
• Immune therapies for cancer: right time, right place.
• Multiple chances to win.
 Multiple cancers
 Programs in both US & Europe
• Late stage: lead program in Phase 2 trial, powered as Phase 3
• Striking clinical results to date: adding years, without toxicity
• Attractive product economics, due to cost effective batch mfg.
• Solid intellectual property: >130 issued & pending patents
•
Experienced management team; consistent performance
• Investment opportunity: low market cap, poised for inflection.
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Recent Events
• Capital
 $3 million -- Whitebox
 $4.55 million -- Shulze Family Foundation
 $5.4 million -- Existing Shareholder & Institutional Investor
• Clinical
 Phase II brain trial expansion
 Phase III prostate partnering plans
• Commercial
 Fraunhofer Institute
 Broader European treatment initiatives
• Management
 Senior team expanded with additional experienced talent
Multiple Value Elements, Near Term Timeframes
Potential major value inflection within 18-24 months:
primary endpoint of Phase II GBM brain cancer trial.
Opportunity to achieve first-mover advantages:
• 2nd active immune therapy to obtain FDA approval, and first one that
can apply to most cancers
• 1st active immune therapy to obtain approval in Europe
• 1st fully personalized cancer therapy to reach approval
• 1st immune therapy/personalized therapy with affordable pricing
• 1st immune therapy/personalized therapy deliverable everywhere
• extendable to pediatric and metastatic brain cancer
Multiple interim value milestones during the 18-24 month period.
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NWBT’s DCVax® Mobilizes
Potent Immune System Attack on Cancer
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Dendritic Cells Direct the Whole Immune System
DENDRITIC CELLS
the “General” of
the immune army
DCVax® gives 2 signals
(“marching orders”):
“shift into attack mode”
and
“attack what”
ADAPTIVE IMMUNE SYSTEM
Follow-on defense (within week or weeks)
INNATE IMMUNE SYSTEM
Response is triggered by exposure to
particular threat (activation + “education”)
“First-responders” (within hours/days)
Response is specific & creates memory
Response is automatic
(tailored to each particular threat)
Response is non-specific
(not tailored to each particular threat)
Natural Killer Cells, Neutrophils,
Granulocytes, Macrophages
HUMORAL IMMUNITY
B Cells
Antibodies
CELLULAR IMMUNITY
Helper T Cells
Killer T Cells
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NWBT’s DCVax® Technology Applies to Most Cancers
Multiple complementary product lines:
Basic DCVax® (DCVax-L, -LB, -LBG)
 Brain cancer
 Ovarian cancer
DCVax® with recombinant antigens (biomarkers)
 Prostate cancer
DCVax® -Direct
 Liver, colon, head/neck cancer, etc.
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NWBT Has A Robust Product Development Pipeline
Preclinical
Ph I
Ph II
Ph III
Approval
DCVax®-L (Brain Cancer)
DCVax®-Prostate
DCVax® Direct:
DCVax®-Liver
DCVax®-Head & neck
DCVax®-Pancreas
DCVax®-Ovarian
DCVax®-Lung
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NWBT’s DCVax® Is Achieving
Impressive Clinical Results
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Prior Clinical Studies With DCVax®-Brain:
Impressive Clinical Benefits
Newly diagnosed GBM brain cancer patients
1
Standard of care1
DCVax®-Brain
Time to
recurrence
6.9 months
2 years
Overall survival
14.6 months
3 years
Stupp data from 573 patients -- the “gold standard” benchmark
for GBM brain cancer treatments. N Engl J Med 352: 987-96, 2005
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Newly Diagnosed GBM: Progression Free Survival
1.0
P = 0.00001
Proportion not progressed
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
8.1
0.0
0
26.4
20
40
60
80
Months
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Newly Diagnosed GBM: Overall Survival
1.0
0.9
p = 0.0003
Proportion surviving
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
36.4
17
0.0
0
20
40
60
80
100
120
Months
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Phase II Brain Cancer Trial Currently Under Way
• Newly diagnosed GBM
• 240-patient, randomized (2:1), double blind, placebo controlled:
the “gold standard” in clinical trial design
• Primary endpoint: PFS (progression free survival)
• Secondary endpoints include OS (overall survival)
• Crossover arm for patients who progress
• 25 clinical sites now; substantial additional sites in process
• 18-24 mos. to reach primary endpoint, enrolling at maximum sites
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Fraunhofer Institute
• Leader in Cell/Immune Therapies
• $2.3 billion annual revenue
• 18,000 Scientists, Engineers and Business People
• DCVax® Treatment Costs Captured
• European Manufacturing Base
• Access to Grants – Up to $4 million
• Clinical Trials Expansion
• A Cornerstone of Broader European Programs,
In Parallel With US Program
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DCVax®-L for Brain Cancer Offers Large Market Potential
Metastatic
Brain
Cancers:
500,000
1/3 US, 1/3 Europe, 1/3 RoW
Market Potential of just GBM… US & Europe… 50% market share:
12,000 patients/year x $110K/patient = $1.32 billion
Comparison: Temodar -- adds 10 weeks survival -- market saturation
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Prostate Cancer Course of Disease
Diagnosis
30-40% fail in 5 yrs
Hormone
Dependent
All fail in 1-10 yrs
No metastasis
No metastasis
First line therapy:
Second line therapy:
• Surgery
• Radiation
• Brachytherapy
• Anti-androgen
hormone therapy
Hormone Independent
Period w/o
Metastasis
(85-90% of patients)
Metastasis
(occurs immediately
in 10-15% of patients)
36 mos.
18 mos.
med. survival med. survival
•No approved •Taxotere
treatments
NWBT
vaccine
Death
Early Stage
Provenge
vaccine
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DCVax®-Prostate -- Unparalleled Clinical Benefits
Hormone independent (late stage) prostate cancer:
§ Group A: Patients with no metastases (85% of market)
§ Currently no approved treatments/standard of care for these patients
Natural course of
disease1
DCVax®-Prostate
Median time to
disease
progression
28-34 weeks
59 weeks
Median survival
36 months2
>54 months &
continuing
1 No
2
Standard of care
Schulman et al, J Urol,: 172:141, 2004
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DCVax®-Prostate: Unparalleled Clinical Benefits
Hormone independent (late stage) prostate cancer:
§ Group B: Patients with metastases (15% of market)
§ Currently only 2 approved drugs
Std. of care
(Taxotere)
Median survival
18.9 months
Overall survival
at 3 years
11%
Dendreon3
DCVax®Prostate4
25.9 months 38.7 months
33%
64%
Petrylate et al., N Eng J Med., 351:15
Small et al., J Clin Oncol 24: 3089-94, 2006
3 Phase III trials
4 Phase I/II trial
1
2
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NWBT’s DCVax® Prostate vs. Dendreon’s Provenge®
DCVax® Prostate
Provenge®
__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Target
PSMA-Attractive
PAP-Problematic
__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Active Drug
High Concentration
>80% Pure
Low Concentration
≤ 15%
__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Delivery
Intra-dermal
Similar to flu shot
IV Infusion
Invasive, cumbersome
__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Economics
1 Mfg Run = 3 Years Trtmt
Approx. $37K/yr
1 Mfg Run = 1 Month Trtmt
$93K for 1 month
__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Addressable Mkt
80-85 %
15-20 %
Unique Batch Manufacturing,
Enables Affordable Pricing
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Cost-Effective, Rapid Batch Manufacturing
• DAY 1:
Tumor tissue & blood at manufacturing facility.
• DAY 2:
Precursors of dendritic cells isolated.
• DAY 2-7: Precursors differentiated into dendritic cells.
• DAY 7:
Dendritic cells “educated” by exposure to
biomarkers from tumor tissue.
• DAY 8:
“Educated” dendritic cells harvested & frozen.
Manufacturing finished. (Release tests follow.)
Single run yields 3-year supply of drug.
Complex Technologies Behind the Scenes
Enable Simplicity and Delivery Anywhere
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Simplicity Through Advanced Technologies
Front end
simplicity
Advanced technologies
behind the scenes
Back end
simplicity
Batch manufacturing
Automation (TFF and other)
Collection of
tumor tissue (in kit)
instead of throwing away
Cryopreservation, banking
Shipping/distribution
Information technologies
Blood draw (leukapheresis)
to obtain immune cells
Simple intra-dermal
injection, similar to
flu shot or insulin shot.
Immune monitoring, timing
No processing steps
at clinic.
Proteomics (future product)
No special equipment –
ordinary syringe.
3D cell culture (future product)
No toxicity.
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Strong Intellectual Property
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Solid Intellectual Property Coverage:
DCVax Product and Platform
Over 130 patents issued and pending, worldwide
DCVax-Brain:
§ orphan status granted in US (allows 7 years market exclusivity)
§ orphan status granted in EU (allows 10 years market exclusivity)
DCVax-Prostate:
§ composition and methods coverage issued
Other platform coverage:
§ isolation, maturation and “education” of dendritic cells
§ TFF system -- automation of manufacturing
§ methods of delivery to patients
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Freedom to Operate
Inaccurate claims by various parties about IMUC patent.
IMUC patent covers only narrow situation:
1. Administration of a dendritic cell vaccine
AND
2. “AFTER glioma recurrence” administration of chemotherapy alone
IMUC patent does not cover what NWBT is doing – no infringement
IMUC patent does not cover what IMUC is now doing – no protection
If doctors choose to follow the specific regimen in IMUC’s
narrow patent, the potential infringers would be the doctors.
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Experienced Management and
Implementation Team
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NWBT Management and Implementation Team
• CEO: Ms. Linda Powers
• COO: Dr. Anthony Maida
• CSO: Dr. Alton Boynton
• CTO: Dr. Marnix Bosch
• SVP, Business Development: Mr. Les Goldman
• Medical Director: Dr. Vijay Hingorani
• Director, Clinical Operations: Ms. Meghan Swardstrom
• Manufacturing: Cognate BioServices
• Clinical trial management: Synteract
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Centralized US cGMP Facility at Memphis Air Hub
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Cell and Immune Therapies Taking Off:
Right Time, Right Place
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Cell and Immune Therapies Are Taking Off
KCI/LifeCell:
$1.7B
Osiris/Genzyme:
$1.38B+
Pfizer/Avant:
$390M+
Takeda/Cell Genesys
$270M+
Pfizer RM:
$100M
Osiris/Nuvasive:
$85M+
Stem Cell Therapy
Intl/Altadyme: undisclosed
Novocell:
M&A of Cythera/Bresagen
Pall/Euroflow
Undisclosed
Novozyme/Gropep:
$77.9M
Shire/Renovo:
$825M+
AFIRM RM Award:
$85M
Perkin Elmer/Viacell:
$305M
Invitrogen/CellzDirect:
$57M
CryoSave: IPO on AIM
£100M
GSK/Harvard:
$25M
Cellerix/Axcan:
$40M+
Pfizer/
$3M
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NWBT Compares Well With Biovex
(Recently Acquired By Amgen for $1 Billion)
NWBT
Lethal cancers: Grade IV GBM (Glioblastoma)
Hormone indep. prostate cancer
Prior trials:
§ Patient numbers:
GBM+ (Phase I, I/II): 30 patients
Prostate cancer (Phase I/II): 33 patients
§ % of patients who responded:
GBM: >80%
Prostate: >80%
§ Duration of responses/survival:
GBM: 10.3 to >72 mos. (longest so far: 10 yrs)
Prostate: 15 to >18 mos. (with patients still alive)
Current, ongoing trial:
Newly diagnosed GBM: target 240 patients
(160 treatment, 80 controls)
Pending trials:
Prostate: 612 patients (408 treatment, 204 controls)
DCVax Direct (multiple cancers): 36 patients
Biovex
Lethal cancers: Stage III-IV melanoma
Stage IV head & neck
Prior trials:
§ Patient numbers:
Melanoma (Phase II): 50 treated patients
Head & neck (Phase I/II): 17 enrolled patients
§ % of patients who responded:
Melanoma: 28% (CR in 10 patients; PR in 4 patients)
Head & Neck: 93%
§ Duration of responses/survival:
Melanoma: 7-48 mos.
Head & neck: 30 mos.
Current, ongoing trials:
Melanoma: target 360 evaluable patients
(240 treatment, 120 controls)
Head & neck: target 500 patients
(250 treatment, 250 controls)
NWBT’s DCVax® Compares Well With Biovex
Biovex
NWBT-DCVax®
GBM:
Survival
Melanoma: Stage IV
With Std of Care
With DCVax
Survival
With Std of Care
With Biovex
1 yr
72%
90%
1 yr
41%
58%
2 yr
30%
70%
2 yr
17%
52%
4 yr
<3%
33% to date
5 yr
15%
N/A
6 yr
<3%
27% to date
10yr
15%
N/A
Head & neck:
30 mo
57%
82%
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Summary: Investment Considerations
• Batch manufacturing removes major road block to commercialization of
personalized cancer treatments
• Efficacy:
Overall Survival
Recurrence
DCVax® Brain
3 years vs. 14.6 mos control
2 years vs. 6.9 mos control
DCVax® Prostate
38.7 mos vs. 25.9 mos Provenge®
• Safety: Excellent – no “serious adverse events”
• Broadly Applicable: multiple cancers in pipeline
• Moderate Cost: Should facilitate adoption – potential to become std of care
• Phase III Prostate Program: Poised for partnering
• Phase II Brain Trial: Enrollment progressing; 2 largest mkts (US & Europe)
• Fraunhofer: Large, credible partner; supports both compassionate use & trials
NWBT Summary
• Immune therapies for cancer: right time, right place.
• Multiple chances to win.
 Multiple cancers
 Programs in both US & Europe
• Late stage: lead program in Phase 2 trial, powered as Phase 3
• Striking clinical results to date: adding years, without toxicity
• Attractive product economics, due to cost effective batch mfg.
• Solid intellectual property: >130 issued & pending patents
•
Experienced management team; consistent performance
• Investment opportunity: low market cap, poised for inflection.
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