Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — ASCO 2019
35 slides from Northwest Biotherapeutics's conference presentation, Jun 2, 2019
Slide 1: Program Update
Program Update ASCO, June 2, 2019
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: Presentation Overview
Presentation Overview 1. DCVax®-Direct – Review of the technology and how it works – Follow up data from Phase I trial – New clinical trials 2. DCVax®-L – Progress on the road to unblinding – Follow up data on Information Arm 3
Slide 4: DCVax-Direct for Inoperable Solid Tumors
DCVax®-Direct for Inoperable Solid Tumors
Slide 5: 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 6: Key Points
Key Points v DCVax-Direct uses a unique and proprietary manufacturing approach that dramatically increases cytokine levels v The amounts of cytokines produced (e.g. IL-8, Il-12, TNFα) correlate with survival in the Phase I trial v DCVax-Direct may have multiple modes of action, and the produced cyto
Slide 7: DCVax-Direct – Automated Manufacturing
DCVax-Direct – Automated Manufacturing GM-CSF BCG+IFN g Product Release Sterility, potency Leukapheresis TFF purification DC culture Treatment
Slide 8: Advantages of the DCVax-Direct System
Advantages of the DCVax-Direct System • The system initially produces fully immature DC – Consequentially, one has full control over the DC activation process – To produce DCVax-Direct, the cells are partially activated, retain antigen uptake capability, and progress irrevocably to fully mature DCs
Slide 9: Growing Recognition of the Importance of Cytokines Roles in Cancer Therapy
Growing Recognition of the Importance of Cytokines Roles in Cancer Therapy 3 key roles for cytokines in immune therapy • Priming of the local tumor microenvironment for immune attack • Stimulation of systemic immune cell function • Direct killing of tumor cells 9
Slide 10: Renewed Attention to Cytokines for Cancer Therapy
Renewed Attention to Cytokines for Cancer Therapy • Cytokine monotherapy for cancer (e.g. interferons, interleukin 2, interleukin 12) has been hampered by low efficacy and high toxicity • Cytokines are [now] being considered to better direct the nature of the T- cell infusion product, T-cell functio
Slide 11: DCVax-Direct and the Role of Cytokines
DCVax-Direct and the Role of Cytokines 1. DCVax-Direct DCs produce very large quantities of cytokines, such as TNF-α and interleukin 12 2. These cytokines have 2 key functions: Ø direct biological effects Ø indicators of potential effectiveness of DCs 3. There are multiple observed major biological
Slide 12: Cytokine Production and Survival
Cytokine Production and Survival IL-8 IL-12 p=0.016 p=0.029 TNFα p=0.081 >median <median • IL-8: mOS of 24 months vs 10 months • IL-12: mOS of 22 months vs. 10 months 12
Slide 13: RMH and MDACC Scores
RMH and MDACC Scores • Patients in the DCVax-Direct Phase I trial had exhausted other treatment options • For such patients, several methods can be used to predict survival Ø Royal Marsden Hospital (RMH) Score Ø MD Anderson Cancer Center (MDACC) Score • The MDACC Score uses 5 risk factors to predict
Slide 14: DCVax-Direct Phase I Trial: Actual vs. Predicted Survival
DCVax-Direct Phase I Trial: Actual vs. Predicted Survival Using the MDACC Score, predicted survival was determined for all DCVax- Direct Phase I patients and compared to actual survival (the MDACC Score was calculated from patients treated with other experimental therapies) Outcome: 76% of evaluable
Slide 15: DCVax-Direct Phase I Trial: Key Observations
DCVax-Direct Phase I Trial: Key Observations • Activated DC can be safely administered to patients with unresectable solid tumors • Early T-cell infiltration demonstrates modulation of the tumor microenvironment to allow influx of pre-existing anti-tumor T-cells • T-cell infiltration, coupled with t
Slide 16: DCVax-Direct Phase I Trial: Key Observations (cont.)
DCVax-Direct Phase I Trial: Key Observations (cont.) • DC quality, defined by the production of soluble cytokines, is predictive for survival • The correlations between cytokine production and survival supports the mechanisms of action of DCVax-Direct: Ø Direct killing of tumor cells Ø Making tumor
Slide 17: DCVax-Direct – New Trials
DCVax-Direct – New Trials • Restart of DCVax-Direct manufacturing recently announced • Multiple new clinical trials have been in preparation • The first 2 of these new trials are anticipated to start in the coming months Ø Brain metastases of lung- and breast cancers Ø Pediatric diffuse intrinsic po
Slide 18: Brain Metastases – Severe Unmet Medical Need
Brain Metastases – Severe Unmet Medical Need • Brain metastases incidence in breast cancer patients, depending on subtype, ranges up to nearly 40% • Patients with triple negative breast cancer (TNBC) or HER-2 positive subtypes have a significantly higher incidence of brain metastases; median surviva
Slide 19: Brain Metastases Clinical Trial
Brain Metastases Clinical Trial • DCVax-Direct will be administered through a reservoir that is placed under the skin and which drains into the tumor 19
Slide 20: Brain Metastases Trial Design
Brain Metastases Trial Design • The trial has been designed with and will be conducted at the Mayo Clinic • Approximately 10 patients, expandable to 24 patients, 18-75 years of age • Dose escalation design to identify the maximum tolerated dose • 7 injections of DCVax-Direct administered over 10 wee
Slide 21: DIPG – Pediatric Severe Unmet Medical Need
DIPG – Pediatric Severe Unmet Medical Need • 90% of patients with DIPG die within 2 years • The disease strikes early, typically at 6-9 years of age • Radiation therapy provides some symptomatic improvement • Numerous clinical trials with chemo or biologic therapy added to radiation have failed to i
Slide 22: DIPG and Pediatric SHGG Trial
DIPG and Pediatric SHGG Trial DCVax-Direct will be administered directly into the tumor through stereotactic injections following biopsy of the tumor 22
Slide 23: Pediatric DIPG/SHGG Trial Design
Pediatric DIPG/SHGG Trial Design • The trial is being designed together with several leading Cancer Centers • Approximately 18 patients, 3 - 21 years of age • Dose escalation design to identify the maximum tolerated dose • 3 injections of DCVax-Direct, at Day 1, Day 7, and Day 22 • Injections are ad
Slide 24: DCVax-Direct: Conclusions
DCVax-Direct: Conclusions v DCVax-Direct has activity in multiple different cancers v High cytokine production is directly related to the magnitude of clinical benefit v DCVax-Direct may extend life beyond what can be achieved with other experimental therapies v Novel clinical trial designs using DC
Slide 25: DCVax-L for Newly Diagnosed Glioblastoma Multiforme (GBM)
DCVax®-L for Newly Diagnosed Glioblastoma Multiforme (GBM) Status report on Phase III Trial
Slide 26: Key Elements Differentiating DCVax-L
Key Elements Differentiating DCVax®-L 1. Uses the Master Cell of Immune System Ø Mobilizes the whole immune system (Many active agents rather than just 1 active agent) 2. Fully personalized Ø Addresses complexity and heterogeneity; fits the patient’s version of the cancer 3. Uses ALL tumor antigens,
Slide 27: Summary of Phase III Trial
Summary of Phase III Trial • Patients with newly diagnosed GBM were considered for the trial • 331 patients were randomized to either DCVax-L or placebo, in a 2:1 ratio • Randomization occurred after the 6 weeks of chemo-radiation that is part of standard treatment • DCVax-L/placebo treatments are g
Slide 28: The Road to Unblinding
The Road to Unblinding • Generation of the draft Statistical Analysis Plan (SAP) • Presentation of the draft SAP to regulators – Obtain feedback – Finalize the SAP taking the feedback into consideration In parallel … • Checking and validation of the data by the CRO – Review case report forms: hundre
Slide 29: Statistical Analysis Plan (SAP)
Statistical Analysis Plan (SAP) • The SAP contains all of the planned analyses for the data that will emerge from the Phase III trial • An effective SAP considers the original trial design, protocol, and subsequent scientific advances • The SAP analyses, taken together, should provide the best insig
Slide 30: SAP Update
SAP Update • We have worked for the past 5 months with 3 world class, independent statisticians to develop a draft SAP using state of the art statistical methods – This stage required the most extensive work by the Company and its advisors • The draft SAP is nearly complete at this point • Next stag
Slide 31: Data Collection Update
Data Collection Update • Several thousands of queries were generated during the data collection process (as is typical for a large clinical trial) • The independent CRO has been working intensively (while the Company has been working on the SAP) to source-verify the data and resolve queries • At thi
Slide 32: Information Arm Summary
Information Arm Summary • The Information Arm was an open label treatment setting for patients with radiographic evidence of disease progression post chemoradiation • Patients were classified as ‘confirmed rapid progressors’ or ‘indeterminate cases’ based on follow-up scans • The indeterminate group
Slide 33: Indeterminate Cases (PD/PsPD)
Indeterminate Cases (PD/PsPD) • 3 of 25 patients still alive at 7 years • 5 of 25 patients lived > 5 years • 10 of 25 patients lived ≥ ~3 years • Median survival 21.5 months mOS on SoC: 15 – 17 months 0.0 12.0 24.0 36.0 48.0 60.0 72.0 84.0 96.0 Survival Time (months) 33
Slide 34: DCVax-L: Conclusions
DCVax-L: Conclusions • DCVax-L is capable of inducing immune responses against glioblastoma tumors • Early, blinded results from a Phase III trial suggest a survival advantage compared to current standard of care • Final analysis of the Phase III data is upcoming 34
Slide 35: Acknowledgments
Acknowledgments Patients and Families Northwest Biotherapeutics Phase III Trial Investigators Meghan Swardstrom Linda Powers UCLA Dr. Alton Boynton Dr. Linda Liau Dr. Anthony Maida Dr. Robert Prins MD Anderson Cancer Center Cognate Bioservices Dr. Vivek Subbiah, colleagues and staff NWBio Scientific