Northwest Biotherapeutics, Inc. · OTC:NWBO
Northwest Biotherapeutics — Glioblastoma Drug Development Summit 2023
33 slides from Northwest Biotherapeutics's conference presentation, Mar 15, 2023
Slide 1: Immunization With Autologous Dendritic Cells is Associated With Extended Survival in Glioblastoma Patients
Immunization With Autologous Dendritic Cells is Associated With Extended Survival in Glioblastoma Patients Glioblastoma Drug Development Summit March 15, 2023 Boston, MA Marnix L. Bosch Northwest Biotherapeutics, Inc. 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: Presentation Overview
Overview Presentation overview 1. Introduction to DCVax®-L 2. DCVax®-L Mechanism of Action 3. Clinical Results a) Phase III trial results b) Compassionate use cases 4. Conclusions 3
Slide 4: DCVax-L Introduction
DCVax®-L Introduction • DCVax®-L is autologous dendritic cells (DCs) loaded with autologous tumor cell lysate – Uses dendritic cells, which are the master cells of the immune system • DCs instill both targeting and direction of the response – Uses tumor cell lysate to ensure a broad spectrum immune
Slide 5: DCVax-L: Mechanism of Action
DCVax-: Mechanism of Action 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 and acquire cytotoxic capability 5
Slide 6: Mechanism of Action (1): Antigen Uptake
Mechanism of Action (1) Antigen Uptake Proteomics analyses were conducted on the following materials: ➢ Tumor lysate ➢ Unpulsed DCs ➢ DCs pulsed with tumor lysate ➢ Peptides eluted from pulsed DCs Conclusion: The dendritic cells in DCVax-L take up (tumor) antigens from tumor cell lysate and express
Slide 7: Mechanism of Action (2): T cell stimulation
Mechanism of Action (2) T cell stimulation • Antigen-loaded DCs induce a primary T cell response through a combination of different signals: – Interaction of the T cell receptor (TCR) with peptide antigens associated with MHC molecules – Costimulatory signals such as CD40, CD80, CD86 – Cytokine prod
Slide 8: Mechanism of Action (3): T cell Infiltration in GBM Post Vaccination
Mechanism of Action (3) 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. 8
Slide 9: Phase III Trial Overview
Phase Ill Trial Overview NORTHWEST BIOTHERAPEUTICS
Slide 10: JAMA Oncology Original Investigation
JAMA Oncology | Original Investigation Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma A Phase 3 Prospective Externally Controlled Cohort Trial Linda M. Liau, MD, PhD; Keyoumars Ashkan,
Slide 11: DCVax-L Trial Sites
DCVax-L Trial Sites U.S. & Canada Germany U.K. 92% (303 out of 331) patients were enrolled during 2012-2015 1
Slide 12: Screening and Enrollment; Treatment Schedule
Screening and Enrollment Treatment Schedule 3 treatments 3 booster Treatments 2X per year in Month 1: treatments: for maintenance Days 0, 10, 20 Months 2, 4, 8 12
Slide 13: Trial Design; Statistical Analysis Plan
Trial Design; Statistical Analysis Plan Primary Endpoint: OS in newly diagnosed GBM DCVax-L arm (n=232) vs. External controls (n=1,366) (control arms of external studies) Secondary Endpoint: OS in recurrent GBM Placebo arm crossovers* (n=64) vs. External controls (n=640) *(Placebo arm patients recei
Slide 14: External Controls (ECP)
External Controls (ECP) Criteria used to identify the trials included the following: • Randomized controlled trials • Control arm with SOC or physician’s choice • Patients must be 18 years or older • Contemporaneous with DCVax-L • KM plots for OS (and subgroups) included for digitization ➢ Independe
Slide 15: External Control Populations (ECPs)
External Control Populations (ECPs) Survival outcomes Newly Diagnosed Glioblastoma Study Agent under study n Median OS (months) 95% CI (months) Gilbert et al 2013 dose-dense tmz 411 16.6 14.9 – 18.0 Gilbert et al. 2014 bevacizumab 309 16.1 14.8 – 18.7 Weller et al. 2017 rindopepimut 374 17.4 16.2 –
Slide 16: Validation of the ECP
Validation of the ECP For each comparator study, the treatment arm was compared against the external controls determined for DCVax-L trial. All results were same as originally reported. Indication Study HR vs. ECP Lower bound Upper bound Gilbert 2013 1.01 0.89 1.14 Newly Gilbert 2014 1.13 0.72 1.33
Slide 17: Overall Survival in Newly Diagnosed GBM
Overall Survival in Newly Diagnosed GBM mOS of DCVax arm = 19.3 mos from randomization; 22.4 mos from surgery mOS of controls = 16.5 mos from randomization 17
Slide 18: Overall Survival in Subgroups
Overall Survival in Subgroups 18
Slide 19: Probability of Overall Survival: Significant Residual Disease
Significant Residual Disease 1.0 0.9 Hazard Ratio 0.56 (-, 0.71) 0.8 Probability of Overall Survival p-value < 0.001 0.7 1-sided log-rank 0.6 0.5 0.4 DCVax-L External Controls 0.3 0.2 0.1 14.2 17.5 0.0 0 12 24 36 48 60 Months from Randomization
Slide 20: Probability of Overall Survival: Age
Overall Survival - Age ≥ 65 1.0 0.9 HR 0.63 0.8 p-value 0.021 Probability of Overall Survival 0.7 0.6 0.5 0.4 DCVax-L External Controls 0.3 0.2 0.1 13.7 15.6 0.0 0 12 24 36 48 60 Months from Randomization
Slide 21: Sensitivity Analyses
Sensitivity Analyses Known bias: not all trials excluded patients with evidence of progression post chemoradiation. Removing those trials yields the following result: Studies removed n ECP HR 98% CI p none 1366 0.80 0.00, 0.94 0.002 Gilbert 2013, 2014 646 0.77 0.00 – 0.92 0.001 Unknown biases: speci
Slide 22: External Controls: Individual Matching
External Controls: Individual Matching Adjustments for individual patient characteristics: MAIC (Matching Adjusted Indirect Comparison) The MAIC methodology applies a weight to each individual patient in the DCVax-L population in such a way that the sum of the weights for patients in each category f
Slide 23: Overall Survival in Recurrent GBM
Overall Survival in Recurrent GBM mOS = 13.2 months from recurrence with DCVax-L vs. 7.8 months in controls 23
Slide 24: Landmark Survival Data
Landmark Survival Data nGBM Landmark survival rate ECP DCVax-L Relative Rate 36 mo 15.5% 20.2% 130% 48 mo 9.9% 15.7% 159% 60 mo 5.7% 13.0% 228% rGBM Landmark survival rate post progression ECP DCVax-L Relative Rate 6 mo 64.0% 90.6% 142% 12 mo 30.8% 54.1% 175% 18 mo 15.9% 31.8% 200% 24 mo 9.6% 20.7%
Slide 25: Overall Survival (OS) Results – Key Points
Overall Survival (OS) Results – Key Points NEWLY DIAGNOSED GBM: ➢ mOS: 19.3 mos from randomization (22.4 mos from surgery) vs. 16.5 mos from randomization in controls ➢ mMGMT mOS: 30.2 mos from randomization (33 mos from surgery) vs 21.3 mos from randomization in controls ➢ Survival Tail: 13% vs 5.7
Slide 26: Safety Profile
Safety Profile >2,100 doses were administered during the DCVax-L trial Only 5 SAEs at least “possibly related” to DCVax-L treatment ➢ 3 cases of intracranial edema (grades 2 and 3) ➢ 1 case of nausea (grade 3) ➢ 1 case of lymph node infection (grade 3) Overall safety profile in DCVax-L patients is s
Slide 27: Future Opportunities for Combination Therapies
Future Opportunities for Combination Therapies Datsi A, Sorg RV. Frontiers in Immunology, 2021 27
Slide 28: Broader Perspective
Broader Perspective • DCVax-L suitable for combinations with wide range of other treatments (checkpoint inhibitors, oncolytic viruses, cytokines, chemo, etc.) • When a DCVax-L patient has recurrence(s), new batch(es) of DCVax-L can be made (treatment targets not lost, as they are with targeted thera
Slide 29: Compassionate Case #1
Compassionate Case #1: 70 yr old male with GBM confusion Patient is alive and seizure First course of DCVax-L Second course of DCVax-L and doing well 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 First resection: Recurrence: Recurrence: GBM diagnosis 2nd resection 4th resection Chemoradiation +
Slide 30: Compassionate Case #2
Compassionate Case #2 46 yr. old female with GBM unusual Patient is alive headache First course of DCVax-L 2nd course of DCVax-L and doing well 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Adjuvant temozolomide Resection: GBM diagnosis Chemoradiation Notes: - Patient was diagnose
Slide 31: Observations From Compassionate Use Cases
Observations From Compassionate Use Cases Anecdotal observations: • DCVax-L is well tolerated and can be effective in older patients, at least through late 80s ages • When patients experience recurrence, and have an additional resection, a new batch of DCVax-L can be made and patients can respond, w
Slide 32: Conclusions
Conclusions • Survival of GBM patients participating in clinical trials as control subjects is remarkably consistent, creating a landscape in which ECPs can be used as synthetic control arms • Against this background, treatment with DCVax-L is associated with statistically significant and clinically
Slide 33: Acknowledgements
Acknowledgements • Patients and families • Clinical trial investigators • UCLA: Dr. Linda Liau and Dr. Robert Prins • King’s College: Dr. Keyoumars Ashkan • Advent Bioservices: Mike Scott, Alessandra Riva and team • Flaskworks: Lekhana Bhandari and Andrew Kozbial • Cognate Bioservices • Northwest Bi
Northwest Biotherapeutics — Glioblastoma Drug Development Summit 2023 on 6ix