Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — I-O Summit 2018
21 slides from Northwest Biotherapeutics's conference presentation, Aug 29, 2018
Slide 1: DCVax: Clinical Development of Dendritic Cell-Based Immunotherapy for Cancer
DCVax® Clinical Development of Dendritic Cell-Based Immunotherapy for Cancer Boston, August 29, 2018 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: What are Dendritic Cells (DCs)
What are Dendritic Cells (DCs) Dendritic cells (DCs) are antigen-presenting cells, that are required for the induction of an antigen-specific (adaptive) immune response, through cell- to-cell contact (CD80, CD86) and through soluble factors (cytokines). 3
Slide 4: How to obtain DCs?
How to obtain DCs? 1. Directly from the blood: 1- 5% of blood white cells are DCs – The presence of specific markers allow one to isolate these cells – The condition of these cells is dependent on patient pre-treatment 2. From the bone marrow – CD34+ stem cells in the bone marrow can be converted to
Slide 5: DCVax Potentially Applicable to All Types of Solid Tumors
DCVax Potentially Applicable to All Types of Solid Tumors Indication Product / Composition Lead Program Administration All Operable DCVax®-L Monocyte-derived DCs + Brain cancer Solid Tumors full set of tumor antigens 331-patient Phase III trial underway1 Intra-dermal from tumor tissue sample shot in
Slide 6: DCVax-Direct for Inoperable Solid Tumors Program Update
DCVax®-Direct for Inoperable Solid Tumors Program Update
Slide 7: Key Points
Key Points DCVax-Direct uses a unique and proprietary manufacturing approach that dramatically increases cytokine levels The amounts of cytokines produced (e.g. IL-8, Il-12, TNFα) unexpectedly correlate with survival in a Phase I trial IL-8: broad acting cytokine IL-12: essential in mediatin
Slide 8: 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 9: DCVax-Direct – Automated Manufacturing
DCVax-Direct – Automated Manufacturing GM-CSF BCG+IFN γ Product Release Sterility, potency Leukapheresis TFF purification DC culture Treatment
Slide 10: 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 • The potency of the produced DC, e.g. measured through cytokine production, is enhanced Donor 1 Donor 2 Donor 3 Donor 4 Donor 5 • Will this
Slide 11: DCVax-Direct Mechanism of Action
DCVax-Direct Mechanism of Action DCVax-Direct DCs may attack the tumor in three ways: - Direct killing of tumor cells - Induction of a systemic anti-tumor immune response - Rendering the tumor microenvironment more conducive to immune attack DC-produced cytokines may play a role in all three postu
Slide 12: DCVax-Direct -- Mechanism of Action
DCVax-Direct -- Mechanism of Action Change 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-L1 12
Slide 13: Long Tail of Durable Outcomes: DCVax-Direct Phase I Trial
Long Tail of Durable Outcomes: DCVax-Direct Phase I Trial; 13 Cancers Pancreas NET Pancr Melanoma Melanoma NET Lung Ovarian mCRC Sarcoma Lung NET Sarcoma Bladder Bile duct Pancreas Breast mCRC Sarcoma Sarcoma Sarcoma Sarcoma Sarcoma mCRC Melanoma Melanoma Sarcoma Alive Pancreas Sarc Desmo Poorly dif
Slide 14: Cytokine Production and Survival
Cytokine Production and Survival Patients whose DCs produced higher levels of cytokines during the manufacturing process had better survival outcomes • IL-8: mOS of 24 months vs 10 months • IL-12: mOS of 22 months vs. 10 months IL-8 IL-12 p40 p=0.016 p=0.029 TNFα p=0.081 >median <median
Slide 15: Stable Disease and Survival
Stable Disease and Survival Patients with stable disease (SD) at week 8 Patients with higher TNFα levels (left panel, dashed line) live longer than had a greater likelihood of having SD patients with progressive disease (solid (solid bars) at week 8 line): mOS of 22 months vs. 8.8 months. (ng/ml)
Slide 16: 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 17: Survival: Actual minus Predicted
Survival: Actual minus Predicted Pancreas NET Pancr For each patient, Melanoma NET Lung the predicted survival Ovarian time was subtracted mCRC Melanoma from the observed Sarcoma NET survival time Lung and the results are Bladder Bile Duct plotted. mCRC Pancreas Sarcoma Breast Sarcoma Sarcoma Sarcom
Slide 18: 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 19: 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 20: Phase I Trial: Key Observations (cont.)
DCVax-Direct Phase I Trial: Key Observations (cont.) • 28% 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 21: 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