Corporate Overview. Jefferies 2014 Global Healthcare Conference. June 4, 2014

Transcription

1 Corporate Overview Jefferies 2014 Global Healthcare Conference June 4, 2014

2 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 and others 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 most recent Form 10K. 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. 2

3 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. 3

4 DCVax : Personalized Immune Therapy for Cancer Active ingredient: dendritic cells (master cells of the immune system) Key Characteristics: Active immune therapy: mobilizes the whole immune system Full set of tumor targets: hits the full set of tumor antigens (including cancer stem cells). not just one or a few cherry picked biomarkers. makes it harder for the tumor to escape Personalized tumor targets: uses the relevant tumor antigens; solves the patient to patient variability of cancers => response rates over 80% Non-toxic 4

5 Strengths of DCVax-L vs. Other Immune Therapies DCVax-L Uses Full Set of Tumor Antigens (targets) Scores/hundreds of antigens. Selection done by dendritic cells. Personalized antigens => ensures the relevant/correct antigens used. NO screening for patient or tumor characteristics treat all. Other Immune Therapies Use Only Selected, Standardized Antigens (targets) Only 1 or a handful of antigens. Pre-selection overrides nature overrides selection by dendritic cells. Standardized antigens => Russian roulette (may or may not be expressed on patient s tumor). Must screen for patient or tumor characteristics: lose significant % of mkt. No Serious Adverse Effects No serious adverse events caused by DCVax-L over a decade of clinical trials to date. Significant Adverse Effects Various other therapies have significant adverse effects, can be highly toxic (e.g., checkpoint inhibitors, carts, some Abs). 5

6 Dendritic Cells Mobilize the Whole Immune System DENDRITIC CELLS the master immune cells Signals activate & biomarkers educate Dendritic Cells INNATE IMMUNE SYSTEM First-responders (within hours/days) Response is automatic Response is non-specific (not tailored to each particular threat) Natural Killer Cells, Neutrophils, Granulocytes, Macrophages ADAPTIVE IMMUNE SYSTEM Follow-on defense (within week or weeks) Response is triggered by exposure to particular threat (activation + education ) Response is specific & creates memory (tailored to each particular threat) HUMORAL IMMUNITY B Cells Antibodies CELLULAR IMMUNITY Helper T Cells Killer T Cells Tumor Cell Death 6

7 Large Multiplier: Each Educated Dendritic Cell Activates Hundreds of Anti-Cancer T Cells Dendritic Cell activated anti-cancer T cells travel to tumor site tumor target proteins anti-cancer T cell activated resting anti-cancer T cell attaches to DC activated anti-cancer T cells divide rapidly Northwest Biotherapeutics, Inc., All Rights Reserved

8 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 Small ovarian cancer Phase I/II trial completed All Inoperable Solid Tumors DCVax -Direct Dendritic cells injected directly into tumor(s) + biomarkers picked up onsite in tumor All solid tumor cancers 60-patient Phase I/II trial underway Other Hormone independent prostate cancer DCVax - Prostate* 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 8

9 Lead Program: DCVax-L for Newly Diagnosed GBM Phase I/II Trials 20 newly diagnosed GBM; 14 recurrent GBM; 5 lower grade gliomas Standard of care (surgery & 6 weeks radiation & chemo) + DCVax-L Primary endpoint: safety; Secondary endpoint: progression free survival Progression (Tumor Recurrence) Standard of Care* Matched Concurrent Controls** DCVax-L 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 To date: 33% alive >4 yrs 27% alive >6 yrs 2 pts alive >10 yrs * N Engl J Med 352: , 2005 **matched for age, gender, Karnofsky score, extent of surgical resection, and same std of care treatment, at same hospital, in same time period 9

10 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 10

11 Highlights in Europe: Phase III Trial; UK Adoption; German Hospital Exemption & Reimbursement Eligibility Phase III Trial Approval in UK & Germany: one of first ATMPs (Advanced Therapy Medicinal Product) Adoption by UK NHS (NIHR): chosen as a nationwide priority Hospital Exemption in Germany: 5 yrs; all gliomas; new & recurrent First new product not previously on market & grandfathered First immune therapy First product with pharmacologic (drug-like) effects in the body First somatic cell therapy First non-german company Eligibility for Reimbursement in Germany: Extraordinary to be eligible while still in clinical trials Vetted both by hospitals & by Central Reimbursement Authority 11

12 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 12

13 DCVax -Direct for Inoperable Tumors: Overview DCVax-Direct is the DCVax product line for inoperable solid tumors Active ingredient is dendritic cells, similar to DCVax-L for resectable tumors Precursors of DCs are obtained through leukapheresis, same as for DCVax-L DCs are only partially matured, unlike for DCVax-L, and activated with BCG & IFNg Such partially mature, activated DCs are directly injected into 1 tumor(s) anywhere in body (interior locations reached by ultrasound guidance)

14 DCVax -Direct for Inoperable Tumors: Overview DCs secrete cytokines locally in tumor(s) where injected DCs also potentially mobilize overall immune system (take up antigen in situ in tumor(s) where injected, travel to lymph nodes, mobilize T and B cells) Systemic immune activation potentially targets tumors not injected with DCVax-Direct (in addition to tumors injected), and shrinks or eliminates them Systemic immune activation may potentially develop immune memory which prevents or delays recurrence of tumors

15 DCVax -Direct: Underlying Biology Immature DCs will effectively take up antigens (biomarkers) in situ in tumors, but will not activate T cells. Also, immature DCs are highly susceptible to suppression by the tumor. Mature DCs will not effectively take up antigens in situ in tumors, but will present antigens to T cells and activate them. ****************************** Partially mature, activated DCs. at a certain stage. will effectively take up antigens (biomarkers) in situ in tumors, and will effectively present to T cells and activate them.

16 DCVax -Direct: Novel Technology Partially Mature DCs Both Take Up & Communicate Antigens 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 16

17 DCVax Direct: Potential Clinical Effects Possible Clinical Effects Causes Seen in Pre-Clinical Studies? Local effects in tumors injected with DCVax-Direct Tumor necrosis Secretion of cytokines (e.g., TNFα, IL-6, IL-8) by activated DCs Systemic effects in tumors not injected Tumor shrinkage or elimination Immune system activation Immune memory Lack of recurrence even when re-challenged with same cancer Immune system activation 17

18 DCVax -Direct: Striking Pre-Clinical Results Treatment With Chemotherapy Treatment With Partially Activated Dendritic Cells Tumor Size (mm2) Day Tumor Size (mm2) Day Tumor clearance throughout body after direct injection into only a few tumors. No recurrence when animals later injected with same tumor cells as originally. 18

19 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, lung, pancreas, melanoma & other/misc.) Phase II stage: 24 additional patients in one selected cancer e.g., colon Primary efficacy endpoint: tumor response (necrosis or 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, 7 & 14, weeks 8, 16 & 32. Primary efficacy measure: regression (shrinkage/elimination) of tumors. Trial under way at MD Anderson-Houston & MD Anderson-Orlando. Additional sites pending. 19

20 Results to Date In DCVax-Direct Phase I/II Trial 23 out of 36 patients enrolled and undergoing treatments; remaining 13 patients starting treatments now through approx. end of June 19 patients have completed at least half of the 6 total treatments; 58% of these patients (11 of 19) have shown early positive responses In 8 of these 11 patients, biopsies show extensive tumor cell death and substantial accumulations of immune cells in the tumors In 6 of these 8 patients, imaging scans also showed either tumor shrinkage or stabilized disease with no progression In 2 of these 8 patients, imaging scans seemed to indicate some tumor enlargement but biopsies showed the tumors filled with necrosis (dead tumor cells) and immune cells In 3 of these 11 patients, the disease has stabilized (stopped progression) but has not yet shown definitive necrosis or infiltration of immune cells 20

21 DCVax-Direct Case Study: Sarcoma Patient had very large primary tumor (19 x 15 x 17+ cm) and multiple metastases in lungs Patient received 4 injections of DCVax-Direct, only into the primary tumor, on Day 0, 7 and 14 and week 8 Imaging scans at week 12 and tumor biopsies showed: high necrosis (tumor cell death) and tumor collapse in the primary tumor that was injected shrinkage of 1 non-injected lung metastasis 21

22 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 Course of disease DCVax - Prostate weeks 59 weeks Hormone Independent Metastatic Prostate Cancer Std. of care (Taxotere) Dendreon s Provenge** DCVax - Prostate4 Median survival 18.9 months 25.9 months 38.7 months Median survival 36 months >54 months (>half were still alive ) 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 22

23 DCVax -L: Cost-Effective, Rapid Batch Manufacturing DAY 1: DAY 2: Tumor tissue & blood at manufacturing facility. Precursors of dendritic cells isolated. DAY 2-7: Precursors differentiated into dendritic cells. DAY 7: DAY 8: Dendritic cells educated by exposure to biomarkers from tumor tissue. Educated dendritic cells harvested & frozen. Manufacturing finished. (Release tests follow) Single manufacturing run yields 3-5 years of doses of DCVax-L product. Only 2 grams of tumor tissue needed for full batch. With <2 grams of tumor tissue, a partial batch can be produced. 23

24 Automated Manufacturing With TFF System Enhances Efficiency, Enables Scale-Up TFF system automates key stages of DCVax manufacturing Sharply reduces time and personnel required Partially eliminates need for clean rooms Enables scale-up in numbers of patients GM-CSF BCG+IFN g Product Release Sterility, potency Etc. 2 weeks Leukapheresis 4 hours Cell purification 90 minutes DC culture 5 days Patient injection 24

25 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 25

26 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 26

27 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 27

28 Financial Overview Shares Outstanding ~57 million Share Price, $5.90 Market Capitalization $336 million Financing $52 million in 2013 $15 million in April 2014 Warrant exercises in Q1 and Q Additional Funds Cash burn rate, 2013 First drawdown of $2.5 million in process from $5.5 million German Govt grant $39 million 28