Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — Technical Presentation (June 2025)
14 slides from Northwest Biotherapeutics's technical presentation, June 2025
Slide 1: Next Generation Dendritic Cell Treatments to Improve Anti-Tumor Responses
Next Generation Dendritic Cell Treatments to Improve Anti-Tumor Responses Marnix L. Bosch, Lekhana Bhandary Northwest Biotherapeutics, Inc. June 2025 1
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 is DCVax-Direct?
What is DCVax®-Direct? • DCVax-Direct is autologous, unloaded, partially activated dendritic cells for intratumoral injection • DCVax-Direct is manufactured in a closed and automated system that is specifically designed to maximize therapeutic effects: – The resulting DCs are uniformly immature – Ac
Slide 4: Local and Systemic Effects
Local and Systemic Effects: Tumor infiltrating T cells (TILs) Local effect: rapid infiltration of CD4+ helper cells and CD8+ killer cells increased from baseline in 15 of 27 (55%) of assessed patients Day 0 Example: clear cell CD3 CD4 CD8 sarcoma Day 7 Systemic effect: TILs sharing sequences with pe
Slide 5: Local and Systemic Effects on Tumor Growth
Local and Systemic Effects on Tumor Growth • Clear cell sarcoma • Patient failed multiple other treatments • Only single lesion injected • 5 measurable tumors Substantial T-cell infiltration (week 8): CD3 cells CD4 cells CD8 cells 5
Slide 6: Phase I Trial Summary
Phase I Trial Summary • The trial treated 40 patients with 13 types of locally advanced or metastatic cancer • All patients were heavily pre-treated, had failed all other treatments, and had progressive disease at study entry • 23 of 37 (62%) of evaluable patients achieved SD at week 8 • SD at wk8 i
Slide 7: Correlations Between Cytokine Production and Survival
Correlations Between Cytokine Production and Survival TNFα Production vs. Tumor Control TNFα Production vs. Survival 100 Probability of Survival High producers Low producers 50 p=0.08 0 0 12 24 36 48 Months IL-12 p40 Production vs. Survival 100 Conclusion: patients whose Probability of Survival High
Slide 8: Supercharging Dendritic Cells
Supercharging Dendritic Cells 1. Judicious combinations of DC booster agents can be combined to supercharge the DCs prior to injection. These agents include: – TLR agonists (A, B, C1) – biological response modifiers (I1) – activators of antiviral pathways (V1) – danger signals (D1) 2. The ensuing in
Slide 9: Increasing Production of Relevant Cytokines: TNFα and IL-12 p70
Increasing Production of Relevant Cytokines: TNFα and IL-12 p70 • In the Phase I trial, both TNFα and IL-12 were found to be associated with tumor control and improved survival • Production of e.g. TNFα and IL-12 p70 can be increased by 1 – 2 orders of magnitude in response to additional booster age
Slide 10: Broadening the Cytokine Response
Broadening the Cytokine Response (examples) Addition of the right combination of booster agents also dramatically increases the production of other cytokines that are relevant for anti- tumor activity T cell polarising cytokines Innate immunity cytokines 100% 100% 80% 80% 60% IAVC 60% IAVC IBV IBV 4
Slide 11: Enhanced Functionality
Enhanced Functionality • Various booster agents in combination enhance the production of molecules associated with cell migration Migratory and chemotactic cytokines 100% 80% 60% IAVC IBV IAV 40% IABDV IADV 20% IBDV IAB IA 0% 11
Slide 12: 'Rescue' Low Cytokine Producers
‘Rescue’ Low Cytokine Producers Subjects who are low cytokine producers to a single TLR agonist + IFNγ can be converted to high producers through the addition of booster agents. IA 100 90 IAVCBD 80 IAD 70 60 50 40 30 IABDV 20 IAV 10 0 IABD IADV IAB IAC 12
Slide 13: Results 5: Additional Findings
Results 5: Additional Findings • RNAseq analysis provides an unbiased approach into gene activation pathways, which may uncover novel and unexpected responses • These results provide further guidance towards choosing the most effective combination of booster agents Selected Gene Ontology Groups of I
Slide 14: Summary and Conclusions
Summary and Conclusions • Various combinations of booster agents significantly enhance the potency of DCs for intratumoral injection • There is significant complexity in the system, in that both additive, complementary, and antagonistic (re)actions are observed • Applying a broad-spectrum view, as o
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