Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — Technical Presentation (February 2021)
30 slides from Northwest Biotherapeutics's technical presentation, February 2021
Slide 1: DCVax-L Phase 3 Clinical Trial: Where Are We, and How Did We Get Here?
DCVax®-L 020221 Phase 3 Clinical Trial Dendritic Cell Therapy for Brain Cancer Where Are We, and How Did We Get Here? Marnix L. Bosch, MBA, PhD Chief Technical Officer Northwest Biotherapeutics
Slide 2: Key Characteristics of DCVax-L
Key Characteristics of DCVax-L 1. Fully personalized • Addresses complexity and heterogeneity 2. Uses ALL tumor antigens • Minimizes tumor escape 3. Uses the Master Cell of the immune system • Dendritic cells direct the immune response 2
Slide 3: Each Dendritic Cell Activates Hundreds of Anti-Cancer T Cells
Large Multiplier: Each Dendritic Cell Activates Hundreds of Anti-Cancer T Cells activated anti-cancer T cells travel to tumor site Dendritic Dendritic Cell Cell tumor target proteins anti-cancer T cell activated resting anti-cancer activated anti-cancer T cell attaches to DC T cells divide rapidly 3
Slide 4: First Clinical Trial
First Clinical Trial Autologous dendritic cells were pulsed with acid-eluted peptides from cultured autologous GBM cells to stimulate a class I – restricted CTL response Survival data from this trial are highly encouraging Linda Liau et al., Clin. Cancer Res. 11: 5552. 2005 4
Slide 5: Process Optimization
Process Optimization • Initial assessment identified GBM as an interesting target but raised questions about scale-up of acid elution of cultured GBM cells – Culture of autologous GBM cells often requires months of culture time to obtain sufficient numbers of cells – Acid-elution process proved diff
Slide 6: Second Clinical Trial
Second Clinical Trial • This trial used autologous DCs pulsed with autologous tumor cell lysate • Overall survival data from this trial were similar to the first trial • The survival benefit appears greatest in patients with mesenchymal subtype Robert Prins et al., Clin. Cancer Res. 17: 1603. 2011 6
Slide 7: T cell Infiltration in GBM Post Vaccination
T cell Infiltration in GBM Post Vaccination Infiltration of T cells in the tumor is observed in patients treated with DCVax-L Both CD4 and CD8 cells are seen L. Liau et al. 7
Slide 8: Phase III Trial
Phase III Trial • The trial was conducted at >80 sites in 4 countries: – USA, Canada, UK, Germany • Patients with possible GBM are consented prior to surgery – GBM confirmed through independent review • Surgical tissue is used to generate tumor cell lysate • Leukapheresis to collect monocytes is con
Slide 9: Crossover option
Crossover option (Every eligible patient will get the treatment) • Patients with documented progression are allowed to receive DCVax-L – NWBio, the investigators and patients are kept blinded • Patients originally assigned to placebo are eligible to ‘cross over’ to DCVax-L treatment • Patients origi
Slide 10: DCVax-L Phase III Trial in Glioblastoma Multiforme
DCVax-L Phase III Trial in Glioblastoma Multiforme Screening Timeline Screening based on Randomization and symptoms and MRI leukapheresis enrollment 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: Recruitment, Inclusion, and Randomization of Patients
Recruitment, Inclusion, and Randomization of Patients 1) Patients are screened prior to surgery, so glioblastoma (GBM) determination is made from pathological diagnosis after surgery. 2) Insufficient tumor lysate generated to meet threshold. 3) Progressive disease or pseudoprogression (which are ind
Slide 12: DCVax-L Phase 3 GBM Trial: Treatment Timeline
DCVax-L Phase 3 GBM Trial: Treatment Timeline Randomization & Crossover at time of Enrollment recurrence TMZ (approx.) month 0 12 24 36 DCVax-L doses Induction Booster Maintenance Phase Phase Phase (Day 0, 10, 20) (Month 2, 4 8) (Every 6 mos.) 12
Slide 13: First Interim Blinded Data
First Interim Blinded Data DCVax®-L for Newly Diagnosed Glioblastoma Multiforme (GBM) Status report on Phase III Trial Liau et al. 2017
Slide 14: DCVax-L administration
DCVax-L administration • DCVax-L is shipped frozen to the hospital pharmacy – each dose is drop-shipped to arrive 2-3 days prior to appointment • Two vials are thawed at the pharmacy just prior to administration • DCVax-L is drawn up into syringes at the pharmacy • Filled syringes are picked up by t
Slide 15: Safety Overview in ITT Population
Safety Overview in ITT Population no SAE Unrelated SAE Possibly Related SAE 15
Slide 16: Patient Demographics
Patient Demographics Patient demographics are comparable to other GBM trials, especially with regard to known prognostic factors. • 75% are over 50 • more unmethylated than methylated MGMT The trial excluded early progressors and pseudoprogressors, similar to other large, published, recent GBM trial
Slide 17: Background Survival Data
Background Survival Data Historical Data (Temodar + Radiation) • Stupp et al. 2005: median* overall survival (mOS) = 14.6 months • Hegi et al. 2005: mOS in MGMT-methylated** patients = 17.0 months Recent Clinical Trials (Temodar + Radiation groups) These trials have similar inclusion criteria to the
Slide 18: Survival of Whole ITT Population From Surgery
Survival of Whole ITT Population From Surgery (interim data: 2017 vs. 2018) Median OS Survival at Survival at Survival at Population n since surgery 1 year 2 years 3 years 2017 data 331 23.1 months 89.3% 46.2% 25.4% 2018 data 331 23.1 months 89.3% 46.4% 28.2% 18
Slide 19: Prognostic Factors in ITT Population Comparable to Other Key Trials
Prognostic Factors in ITT Population of DCVax®-L Trial Comparable to Other Key Trials Celldex Celldex Optune Optune Stupp DCVax-L1 Months Controls2 Treated2 Controls2 Treated2 20091 (Weller 2017) (Weller 2017) (Stupp 2017) (Stupp 2017) (updated 2018) Age 33% <50 58 59 57 56 56 (median) mMGMT 44% 35%
Slide 20: Survival From Surgery by MGMT Methylation Status
Survival From Surgery by MGMT Methylation Status (interim data: 2017 vs. 2018) Median OS Survival at Survival at Survival at Data set n since surgery 1 year 2 years 3 years 2017 methylated 131 34.7 months 94.5% 66.7% 46.4% 2018 methylated 131 35.1 months 94.6% 66.6% 49.1% 2017 unmethylated 162 19.8
Slide 21: Survival from Surgery: Impact of Prognostic Factors
Survival from Surgery: Impact of Prognostic Factors in Blinded Interim Data (2017) Age Performance Status Surgery Lymphocyte Count 21
Slide 22: MGMT Status and DCVax-L
MGMT Status and DCVax-L The difference in mOS between MGMT unmethylated and methylated patients is typically around 7 months (e.g. Stupp et al. 2017: 14.7 vs. 21.7 months in the control population) Ø In this trial, the difference is approximately 15 months Ø This increase in the delta cannot be attr
Slide 23: Survival From Surgery of Top 100 Patients
Survival From Surgery of Top 100 Patients (interim data: 2017 vs. 2018) Extended survival not fully explained by known prognostic factors n KM- derived mOS 95% CI Top 30% (2017) 100 40.4 mos 35.5-46.5 Top 30% (2018) 100 58.4 mos 45.9-94.5 23
Slide 24: Top 100 Patients: Demographics
Top 100% Patients: Demographics Prognostic Factor Top 100 ITT Age <50 + methylated MGMT + 8% 6% Complete resection Median age and range 56 (21, 70) 55 (19, 73) Age >65 years 16% 17% Age <50 years 28% 25% KPS median (range) 90 (50, 100) 90 (40, 100) KPS ≥80 95% 82% Methylated MGMT 66% 39% Complete re
Slide 25: Long-Term Survivors
Long-Term Survivors The top 100 patients (those with the longest survival times) were assessed for known prognostic factors Ø An average eligible patient has a 30% chance to fall into this group Ø Median KM-derived overall survival for this group is 58.4 months What is the makeup of this group in te
Slide 26: Survival Findings: Key Points
Survival Findings: Key Points • Overall survival in the ITT population is longer than observed in historical and contemporary controls • This extended survival is observed both in patients with favorable prognostic factors and in patients with unfavorable prognostic factors – Age ≥50 years and Age <
Slide 27: Take Home Messages/Conclusions
Take Home Messages/Conclusions • DCVax-L is very well tolerated in patients with newly diagnosed GBM • Blinded, interim data from the study population, in which ~90% of patients received the vaccine, either early or upon disease progression, suggest a possible survival benefit • This potential survi
Slide 28: (Near) Future Plans in Brain Cancer
(Near) Future Plans in Brain Cancer • Unblinding and analyzing the Phase III data • Combination trials of DCVax®-L with checkpoint inhibitor molecules • Intratumoral injection of DCVax®-Direct (a related product) in brain metastases • Intratumoral injection of DCVax®-Direct in diffuse intrinsic pont
Slide 29: Acknowledgements (1)
Acknowledgements (1) • Patients and 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; Lucy Brazil MD; Jason Heth, MD; Sarah Taylor, MD; Stacy D’Andre, MD; Fabio M. Iwamoto, MD; Yaron Moshel, M
Slide 30: Acknowledgments (2)
Acknowledgments (2) UCLA Northwest Biotherapeutics Linda Liau Meghan Swardstrom Robert Prins Linda Powers Alton Boynton Biostats Solutions, Inc. Anthony Maida Ena Bromley Laura Gillis Cognate Bioservices Lin Li Mike Stella Lori Noffsinger Synteract Kyle Hendricks Cheryl Johnson Ted Preston NWBio Sci
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