24-26 April, 2018

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Day One
Wednesday 25th April, 2018

Day Two
Thursday 26th April, 2018

Breakfast & Networking

Advancing Cell & Vaccine-based Therapies

Reinvigorating Cancer Vaccines with Neoantigen Targeting Individualised mRNA-based Vaccines for the Treatment of Cancer


• Harnessing mutation-derived neoantigens for the manufacture of RNA-based vaccines for the treatment of cancer
• Personalised vaccines against cancer (IVAC®)
• Clinical development of IVAC® MUTANOME

Live-Attenuated Double Deleted Listeria Monocytogenes (pLADD) Immunotherapy Targeting MSS CRC


• Aduro’s Live attenuated Listeria (LADD) engages the innate immune response and remodels the tumor microenvironment in both mouse cancer models and in patients
• Proprietary methods have been established for the rapid construction of pLADD strains by site-specific placement of neoantigen expression cassette on bacterial chromosome expressing at least 25 epitopes together with immunoproteosome processing motifs
• pLADD is being evaluated in advanced liver metastatic MSS colorectal cancer (CRC), a malignancy of large unmedical need in which immune checkpoint inhibitors have poor efficacy as single agents
• MSS CRC has a medium mutational burden of ~10 to 100 mutations/tumour cell, simplifying identification and selection of immunogenic neo-epitopes
• Have developed a streamlined needle-to-needle workflow from biopsy to treatment of 12 weeks
• Presentation of data from a Phase 1 clinical trial initiated at Stanford in collaboration with George Fisher, MD (clinical PI) and Hanlee Ji, MD, PhD (neo-antigen prediction)

Morning Refreshments & Networking

Personalised Onco-Immunotherapy: in vivo and ex vivo Vaccination Trials


• GAPVAC – Glioma Actively Personalized Vaccine Consortium: A personalized peptide vaccination trial
• ACTolog®, a personalized multi-target Adoptive Cellular Therapy (ACT)
• XPRESIDENT®: Quantitative HLA ligandomes in cancer and normal tissues
• Targets for bispecific T-cell recruiters

Fast and Cost-Effective Oral Delivery Technology of Personalized T-Cell Vaccines Based on a Live Attenuated Bacteria Platform


• The platform is based on the live attenuated bacterial vaccine strain Ty21, which has been administered to millions of people as a prophylactic vaccine to temporarily protect them from typhoid fever. This strain has been proven to be very safe and well tolerated. All immunotherapies resulting from this platform are taken orally by the patient
• The oral bacterial technology enables delivery to the most immunocompetent organ of the body, targeting the lymphatic tissue of the gut, and has been shown to generate robust T-cell responses against many different antigens in animals and humans in first clinical studies
• The low therapeutic doses required for specific T-cell activation make this approach suitable for continuous dosing (prime & boost administrations, without raising anti-carrier immunity) and provides another safety margin for carrier-related toxicity
• The platform is suitable for addressing multiple targets, full-length proteins as well as small peptides including neo-epitopes, with one treatment and can be combined with additional immune therapies. Another major advantage of this approach is the high modularity, and the low cost and robustness of the production process
• Different prediction strategies have been established to identify tumor-specific mutations, which lead to neoantigens or neoepitopes. Targeting neoantigens by generating specific cytotoxic T-cells is becoming a major factor in the development of clinical immunotherapies against cancer. Our platform technology allows for a fast generation and delivery of personalized T-cell vaccines for the treatment of cancer
• In preclinical studies the technical proof of concept and the ability to raise robust epitope-specific immune responses after administration of polyepitope constructs have been shown

Panel: Maximizing the Potential of Neoantigen-based Targeting for Cancer Vaccines


• How can we harness combination approaches for successful cancer vaccination?
• Lessons learned from examining neoantigen-based cancer vaccine clinical trials to date
• What level of dosage is required?
• Can the benefit of multiple-neoantigen therapies justify the cost, or is it possible to bring the cost down significantly?
• Should we be selecting naturally occurring T cells or TCR gene engineered cells?
• How can we rapidly identify TCRs against neoantigens that could be used to generate personalised cell therapies?

Lunch & Networking

Guaranteeing Immunogenicity

A New Source of Highly Immunogenic Neoepitopes for Cancer Vaccines

  • Stephen Johnston Director, Centre for Innovations in Medicine, Biodesign Institute, Arizona State University


• MisTranslation through microsatellites and mis-splicing produce 100x more neoantigens than DNA mutations
• Frameshifts (FS) produced by MisTranslation and Splicing are highly immunogenic
• These FS are protective in mouse models
• People and dogs with cancer raise immune responses to these FS
• This FS reactivity can be detected using a peptide array
• In a mouse model this array-based system can be used to rapidly create a personal vaccine that shows protection

Overcoming Manufacturing Challenges for Personalised Therapies

Individualised Cancer Neoantigen Vaccines: How can we Make it a Viable Product?


• What is the rationale to pursue development of individualized cancer vaccines?
• How can we customize and manufacture one vaccine per patient at reasonable cost?
• How does the therapeutic modality affect the immunogenicity of individual neoepitopes?
• How do we design a clinical trial for private cancer neoantigen based vaccines?

Panel: Advancing Manufacturing Practices for Personalized Cancer Vaccines


• How do manufacturing priorities change between key modalities?
• How can you ensure you neoantigen based therapy is affordable?
• Examining cost of materials and sourcing
• Where can the key benefits arise from the implement the automation of manual steps
• Ensuring operational efficiency
• How fast can you define neoantigens, manufacture and provide them in a formulation for patient treatment?
• Best practice takeaways

Chairman’s Closing Remarks

Close of Summit