8:00 am
Coffee & Registration
8:30 am Living With Glioblastoma: A Licence to Be Ambitious
Synopsis
– Glioblastoma will become a treatable, rather than terminal, disease in time.
– How a patient-centered approach can accelerate progress to realizing the future where glioblastoma is a treatable disease
-A personal journey and how this illustrates the current challenges and opportunities from a patient perspective
-How recognizing and unleashing patient power can help the medical and scientific communities make progress in GBM and all cancers
Addressing the Major GBM Specific Nuances Limiting Effective GBM Treatment
8:50 am High Level Global Overview of Research & Clinical Development to Date for GBM
Synopsis
- Review the challenges in developing novel therapies for glioblastoma
- Address challenges of tumor heterogeneity, redundant pathway signaling, bloodbrain barrier and immunosuppressive tumor environment
- Discuss the design and development of novel targeted molecular therapies and immunotherapies
- Overview of novel clinical trial designs
9:20 am An Interdisciplinary Approach to Deciphering the Biology of GBM to Develop Innovative Therapies
Synopsis
- Functional biology: Ongoing investigations to show that the interplay between oncogenic signaling and metabolism/cell death pathways can reveal novel therapeutic vulnerabilities
- Establishing a drug development program focused on synthesizing and testing new, potent and brain-penetrant drugs specifically for targeting malignant glioma cells
- Creating a novel patient-derived, orthotopic glioma xenograft that captures the vast molecular diversity of GBM
- Employing non-invasive molecular imaging to examine how imaging can predict tumor response to therapeutics targeting specific molecular alterations in glioma patients and models
9:50 am Developing Next-Generation Oncolytic Viruses for the Immunotherapy of GBM
Synopsis
- Reviewing how oncolytic viruses are an exciting approach to wakening the immune system and turning previously ‘cold tumors’ hot while directly killing cancer cells and promoting antigen presentation
- Analyzing how the Oncorus platform is unique by its large transgene capacity, enabling the tailoring of immune stimulatory payloads to address the immune suppressive drive in GBM
- Exploring unique conditional genetic models of GBM that reproduce human disease to drive transgene selection
10:20 am
Morning Refreshments & Speed Networking
11:20 am Trailblazing a Paradigm Change – Developing a General Protocol of Treatment for GBM Patients: Metabolic Therapy
Synopsis
- Evaluating advances in Press-pulse: a novel therapeutic strategy for the metabolic management of cancer
- Identification of glutamine fermentation as the “missing link” in the metabolic theory of cancer
- Understanding the therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma
- How the restricted ketogenic diet facilitated delivery of DON through the bloodbrain barrier and can be considered a novel drug delivery system for the brain
- Discussing the plan to further explore the combination and to determine if the diet-drug therapeutic synergy found for glioblastoma could also be seen for other malignant cancers
11:50 am TTFields – a Perfect Match with Other Modalities in GBM
Synopsis
- Innovative approaches to treatment of glioblastoma combining TTFields with other modalities: chemotherapeutic agents, radiation therapy and immunotherapy demonstrate enhanced treatment efficacy in preclinical models.
- Ongoing and future clinical studies in TTFields.
12:20 pm Examining the Determinants of Anticancer Drug Permeability in the Blood-Brain Barrier
Synopsis
- Realizing the importance of the BBB in limiting drug delivery and efficacy
- Investigating expression and regulation of transport systems in key tissues that influence drug disposition
- How variability in expression may contribute to variability in drug response in the patient
- Assessing how all GBM patients have tumor regions with an intact BBB, and a cure for GBM will only be possible if these region of tumor are adequately treated
12:50 pm
Networking Lunch
1:50 pm TSC Treats GBM by Reducing Hypoxia: A Novel Approach
Synopsis
• Novel mechanism of action of TSC results in safe, effective oxygenation of any
type of hypoxic tissue. Developed originally for treatment of battlefield casualties
• TSC added to chemo-radiation in Phase 2 open-label clinical study shows
considerable tumor shrinkage. Survival for biopsy-only patients increases by a
factor of 4, equalling the survival for those patients initially having complete
resections
• No serious adverse events attributed to TSC, suggesting a very safe drug.
Functional status of patients excellent over 2 years of clinical trial
• Lead-in to a Phase 3 randomized clinical trial for biopsy-only patients suggests
that also adding TSC to adjunct chemotherapy portion of GBM frontline
treatment is safe and extends survival time
2:20 pm Pre-clinical Justification & Validation for Targeting EGFR Expressing Glioblastoma with Potent Tumor-Selective Antibody Drug Conjugates
Synopsis
- Targeting overexpressed EGFR with a tumor-selective antibody drug conjugate (ADC) is an attractive therapeutic strategy for glioblastoma (GBM)
- Based on preclinical efficacy experiments with GBM tumor models and the demonstration of a suitable safety profile, several EGFR ADCs have advanced to the clinic where objective responses in patients with GBM have been observed
- Tackling the challenges of this therapeutic approach, including sufficient penetration through the blood brain barrier
2:50 pm Targeting DNA Damage Response Pathways for GBM
Synopsis
- Update on clinical trials testing DDR inhibitors (DDRi’s) for the treatment of GBM
- Evaluating emerging, “clinic-ready” biomarkers that may predict for enhanced response to DDRi’s in GBM
- Exploring new targets and DDRi’s on the horizon for the treatment of GBM: where are we headed?
3:20 pm Pre-clinical, Translational & Clinical Development of AZD1390 – the Brain-Penetrant ATM inhibitor in a Phase 1 GBM Clinical Trial
Synopsis
- Summary of the preclinical and translational work that supports AstraZeneca’s clinical investment
- Update on the current Ph1 clinical trial in action across US and UK sites
- Discussing the potential use of AZD1390 as a radiosensitiser beyond GBM
3:50 pm Panel Discussion: Realizing the Economic Reality of Working on GBM
Synopsis
How can we motivate companies to be more interested in glioblastoma and be willing to open up their pipelines as readily as they do with other cancer types?
4:30 pm
Networking Break & Poster Session
5:00 pm Pre-Clinical Evaluation of Novel Therapeutics
Synopsis
- Employing a deliberate strategy to select the best-in-class drugs for evaluation in clinical trials
- Including in vitro and in vivo analysis of drug efflux liability at the BBB coupled with an efficacy evaluation in intracranial patient-derived xenograft models of GBM
- Integration of efficacy, pharmacokinetics and pharmacodynamics in PDX models can be instrumental in developing models to interpret Phase 0 surgical sampling studies and possibly the ultimate clinical success of a therapeutic strategy
5:30 pm A Multi-Mechanistic Approach in Overcoming Tumor Resistance; Combining Existing Approved Drugs for Novel Formulation Techniques
Synopsis
- Identifying the combination of factors that have limited successful glioblastoma drug development and how IP1867B is effective at avoiding these limiting factors
- Revealing IP1867B, a combination of three common ingredients -aspirin, triacetin and saccharin
- Analyzing how IP1867B turns ‘cold tumors hot,’ reverses acquired resistance, boosts combination efficacy and leads to a possible lowering of side effect burden
- Launching IP1867B into ‘first in human’ trial
6:00 pm A Retrospective Look at the Journey of Avastin in GBM: “Back to the Future”
Synopsis
- Overview of the development path of Avastin in GBM
- Review of the hurdles and challenges along the way
- Lessons learned and key takeaways
6:30 pm Panel Discussion
Synopsis
- Week on week, there is an increasing body of drugs that have failed to move the needle in glioblastoma. The failure rates at phase 2 for GBM are tragic.
- Moving forward, what can we learn from the plethora of failed phase 2 trials?