Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — Investor Presentation (August 2017)
31 slides from Northwest Biotherapeutics's investor presentation, Aug 31, 2017
Slide 1: DCVax Update on Clinical Programs
DCVax Update on Clinical Programs Cancer Vaccines and Neoantigens August 31, 2017 Marnix L. Bosch, MBA, PhD Chief Technical Officer Northwest Biotherapeutics
Slide 2: Disclaimer
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 tha
Slide 3: DCVax® Personalized Immune Therapy
DCVax® Personalized Immune Therapy Personalized Product: personalized dendritic cells (master cells of the immune system) Allows repeat doses, ongoing treatment Personalized Targets: tumor antigens from patient’s own tumor Ensures proper targeting of the immune response Broad Scope of Targets: f
Slide 4: DCVax Potentially Applicable to All Types of Solid Tumors
DCVax Potentially Applicable to All Types of Solid Tumors Market Product / Composition Lead Program Administration All Operable DCVax®-L Dendritic cells and full Brain cancer Solid Tumors array of tumor antigens 331-patient Phase III trial Intra-dermal from tumor tissue sample underway injection in
Slide 5: DCVax®-L for Newly Diagnosed GBM Phase III Trial Update
DCVax®-L for Newly Diagnosed Glioblastoma Multiforme (GBM) Phase III Trial Update
Slide 6: DCVax-L Phase III Trial Design
DCVax-L® Phase III Trial Design Newly diagnosed Glioblastoma multiforme (GBM). Double-blind, randomized, placebo-controlled, multi-center, International trial. 331 patients enrolled, randomized 2:1 (DCVax-L: placebo). Key eligibility and efficacy determinations through central review by independent
Slide 7: DCVax-L Phase III Trial Design -- Treatment Schedule
DCVax-L Phase III Trial Design -- Treatment Schedule Randomization and enrollment TMZ (approx.) Month 0 12 24 30 DCVax-L doses Induction Booster Maintenance phase Phase phase (Month 1) (Months 2, 4, 8) (Twice a year) 7
Slide 8: DCVax-L Phase II Trial Design -- Crossover
DCVax-L Phase II Trial Design -- Crossover • DCVax-L made for all patients during their 6 weeks of chemo/RT • Patients initially randomized to SOC + DCVax-L may continue DCVax-L after progression • Patients initially randomized to SOC + placebo may also receive DCVax-L after progression (“cross over
Slide 9: DCVax-L Phase III Trial Design -- Endpoints
DCVax-L Phase III Trial Design -- Endpoints 1 primary endpoint: progression free survival (PFS) 1 secondary endpoint: overall survival (OS) Trial is powered both for PFS and for OS, independently Multiple tertiary endpoints: • Immune responses • Decline in Karnofsky Performance Status (KPS) • Landma
Slide 10: DCVax-L Phase III Trial -- Enrollment Process
DCVax-L Phase III Trial -- Enrollment Process Initial screening & Baseline screening, initial consent Leukapheresis enrollment & Surgery randomization Radiation + temozolomide week 0 4 8 12 Tumor lysate DCVax-L manufacturing DCVax-L preparation and release first dose Main Reasons for Screen Failure:
Slide 11: DCVax-L Phase III Trial -- Enrollment Timeline
Percent enrolled 100 0 25 50 75 Jun-08 Oct-08 Feb-09 Jun-09 Oct-09 Feb-10 Jun-10 Oct-10 Feb-11 Recruiting paused for economic reasons Jun-11 Oct-11 Feb-12 Jun-12 Oct-12 Feb-13 Jun-13 Oct-13 Feb-14 Jun-14 Oct-14 Feb-15 May 2014 Jun-15 50% Enrolled Oct-15 DCVax-L Phase III Trial -- Enrollment Timeline
Slide 12: DCVax Phase III Trial – Update
DCVax Phase III Trial – Update mOS with SOC is 15 - 17 months Last enrollment in DCVax-L Phase III trial was 19 months ago Last screening/recruitment was 22 months ago Median point of the overall trial enrollment was 37 months ago Approx. 90% of all 331 patients in Phase III trial treated with DCV
Slide 13: Third Party Observations
Third Party Observations (not specifically endorsed by the company) • ”The new blinded data released at ASCO further strengthens the hypothesis that we are seeing longer patient survival in the trial due to DCVax—L.” (Larry Smith, independent analyst) • “We know that the lower end of the range is 22
Slide 14: DCVax-L -- Excellent Safety Profile
DCVax-L -- Excellent Safety Profile DCVax-L administered more than 2,000 times to the 331 patients in the Phase III trial Only 7 patients had an SAE “related” or “possibly related” to the DCVax-L treatments or placebo • 5 nervous system disorders (e.g., seizure, edema); 1 gastrointestinal (nausea);
Slide 15: Acknowledgments
Acknowledgments Patients and their families Investigators: Linda M. Liau, MD, PhD; Robert M. Prins, PhD; Jian Li Campain, MD, PhD; John Trusheim, MD; Charles Cobbs, MD; Keyoumars Ashkan, MD; Jason Heth, MD; Sarah Taylor, MD; Stacy D’Andre, MD; Fabio M. Iwamoto, MD; Yaron Moshel, MD, PhD; Kevin A. Wa
Slide 16: DCVax®-Direct for Inoperable Solid Tumors Program Update
DCVax®-Direct for Inoperable Solid Tumors Program Update
Slide 17: DCVax-Direct
DCVax-Direct • DCVax-Direct is comprised of partially activated, autologous dendritic cells for intra-tumoral injection – Partially activated DC retain the capability to take up antigen, and are irrevocably committed to full maturation • In preclinical work, optimally activated DC were meaningfully
Slide 18: DCVax-Direct Mechanism of Action
DCVax-Direct Mechanism of Action Modulation of the tumor microenvironment (TNF-alpha, IL-6, IL-8, etc) FROM: Killer dendritic cells: mechanisms of action and therapeutic implications for cancer A K Wesa and W J Storkus
Slide 19: DCVax-Direct -- Mechanism of Action
DCVax-Direct -- Mechanism of Action Modulation of the Tumor Microenvironment Induction of Necrosis (“cold” to “hot” conversion) Day 0 CD4 CD8 Day 7 Induction of cytotoxic T cells Induction of PD-1 19
Slide 20: DCVax-Direct Phase I Trial
DCVax-Direct Phase I Trial Trial was very information-rich, helping guide further development • 13 different cancers treated, including very aggressive cancers • 3 dose levels tested: 2M, 6M and 16M cells • 2 different product formulations tested • Feasibility of image-guided injections tested (mult
Slide 21: Phase I Trial: Cytokines and Tumor Control
DCVax-Direct Phase I Trial: Cytokines and Tumor Control Cytokine production, especially TNFα, was correlated with tumor control 21
Slide 22: Phase I Trial: Tumor Control, Stable Disease
DCVax-Direct Phase I Trial: Tumor Control, Stable Disease • Stable Disease (SD) at week 8 was used as a measure of tumor control • 23 of 37 (62%) of evaluable patients achieved SD at week 8 • SD at week 8 is predictive of longer survival DCVax-Direct: All Phase I patients 22
Slide 23: Induction of Checkpoint Expression (PD-L1)
Induction of Checkpoint Expression (PD-L1) • 20 of 25 evaluable patients (80%) in DCVax-Direct Phase I trial showed either de novo or significantly increased expression of PD-L1 following DCVax-Direct treatment • Patient-to-patient variation in timing of when PD-L1 expression appears De novo PD-L1 s
Slide 24: Phase I Trial: Survival Update
DCVax-Direct Phase I Trial: Survival Update Pancreas NET Pancr Melanoma Lung NET Lung Ovarian Sarcoma NET Sarcoma mCRC Bladder Bile duct Melanoma Pancreas Breast mCRC Sarcoma 7 patients (18%) have exceeded 30 mos. Sarcoma Sarcoma Sarcoma Sarcoma mCRC 9 patients (23%) have exceeded 24 mos. Melanoma M
Slide 25: Phase I Trial: Actual vs. Predicted Survival
DCVax-Direct Phase I Trial: Actual vs. Predicted Survival • Patients in the DCVax-Direct Phase I trial had exhausted other treatment options • For such patients, several methods can be used to predict survival (e.g., RMH Score, MDACC Score, neutrophil – lymphocyte ratio) • Using the MDACC Score (Whe
Slide 26: Phase I Trial: Excellent Safety Profile
DCVax-Direct Phase I Trial: Excellent Safety Profile • >140 treatments administered to 40 patients in Phase I trial • 4 SAEs “related” or “possibly related” to DCVax-L treatment – Fevers (n=2), fever and chills (n=1), systemic inflammatory response syndrome (n=1) • Most patients developed mild to mo
Slide 27: Phase I Trial: Key Observations
DCVax-Direct Phase I Trial: Key Observations • Activated DC can be safely administered intra-tumorally in patients with unresectable solid tumors • Early T cell infiltration demonstrates modulation of the tumor microenvironment by the injected DC to allow influx of pre-existing anti- tumor T cells •
Slide 28: Phase I Trial: Key Observations (cont.)
DCVax-Direct Phase I Trial: Key Observations (cont.) • 23% of patients show long term survival (>24 months) • DC quality, defined either phenotypically or by the production of soluble factors, is predictive for survival • The noted correlations between cytokine/chemokine production and survival supp
Slide 29: Phase II Trials: Plans
DCVax-Direct Phase II Trials: Plans Enhanced trial design: • More frequent immunizations, spaced closer together • Multiple injections, into multiple tumors, at each visit • Pre-conditioning of patient’s immune system with low dose cyclophosphamide • More biopsies and other analytics Multiple indica
Slide 30: First DCVax-Direct Phase II Trial: Sarcoma
First DCVax-Direct Phase II Trial: Sarcoma Approvals and agreements completed with a leading sarcoma center: Sarcoma Oncology Center (Dr. Sant Chawla) Preparations are ongoing and trial expected to be initiated in the fall of 2017 Both soft tissue sarcoma and osteosarcoma Targeting adult patients
Slide 31: Acknowledgments
Acknowledgments MD Anderson Cancer Center Northwest Biotherapeutics Dr. Vivek Subbiah Meghan Swardstrom Dr. Ravi Murthy Linda Powers Dr. Robert Brown Dr. Mary McGuire Cognate Bioservices Mike Stella Orlando Health Lori Noffsinger Dr. Omar Kayaleh Kyle Hendricks Deepthi Kolli UCLA Robert Morris Dr. R
Northwest Biotherapeutics — Investor Presentation (August 2017) on 6ix