Cambridge Healthtech Institute’s 3rd Annual
Neoantigen Targeted Therapies
Personalized Cancer Immunotherapy in the Genomic Era
August 30-31, 2018
Fueled with advances in genomic technologies, personalized oncology promises to innovate cancer therapy and target previously undruggable space. Developments in NGS technology enabled systematic analysis of patient-specific mutanome and opens the door
to developing personalized cancer vaccines and other therapies targeting neoantigens. Cambridge Healthtech Institute’s Third Annual Neoantigen Targeted Therapies meeting brings together thought leaders from pharmaceutical
and biotech companies, leading academic teams and clinical immuno-oncologists to share research and case studies in implementing patient-centric approaches to using the immune system to beat cancer, including utilizing NGS to identify tumor-specific
neoantigens, using in silico tools to predict immunogenic neoepitopes, and targeting them with personalized vaccines, novel antibodies or combination therapies.
Final Agenda
THURSDAY, August 30
7:45 am Registration & Morning Coffee (Harbor Level)
8:25 Chairperson’s Opening Remarks
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
8:30 NEW: FEATURED PRESENTATION: Neoantigen-Based Vaccines for Breast Cancer
Glynn Wilson, PhD, Chairman and Strategic Advisor, TapImmune
Breast cancer causes 500,000 deaths each year. Rather than continue to add to the costs of treatment, we should advance promising approaches for prevention such as vaccination. One approach for a breast cancer vaccine is to target aberrantly expressed
‘self’ antigens. To produce such a vaccine, we’re aiming to achieve key milestones, namely identifying peptide epitopes from cancer antigens and identifying systems that induce durable T cell responses.
9:00 In situ Vaccination and the Power of Ignorance
Robert Pierce, MD, Scientific Director, Immunopathology Core, Fred Hutchinson Cancer Research Center
9:30 Development of a Rapid Personalized Self-Assembling Vaccine for Cancer
Mark C. Poznansky, MD, PhD, Director, Vaccine & Immunotherapy Center, Massachusetts General Hospital;
Associate Professor, Harvard Medical School
We have developed a novel personalized self-assembling vaccine (SAV) for cancer that has the potential to be synthesized and delivered to the patient in 20 days. The vaccine consists of a fusion protein containing the broadly immune activating Mycobacterium
tuberculosis derived heat shock protein 70 and avidin which self assembles with selected biotinylated immunogenic peptides derived from identified neoantigens. We have demonstrated proof of concept that SAV works in the context of generating T cell
specific responses to infectious agents.
10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing) (Commonwealth Hall)
10:45 Vaccibody’s Approach to Cost-Effective Personalized Cancer Neoantigen Vaccines Inducing a Unique CD8-Dominated T Cell Response
Agnete Fredriksen, PhD, President and CSO, Vaccibody AS
Vaccibody’s technology potentiates vaccines by attracting, activating and delivering antigens to antigen presenting cells which generates a unique CD8-dominated T cell response. By administering the DNA vaccine format of the Vaccibody vaccine, a
rapid, cost-effective and robust manufacturing process can be applied which lends itself perfectly to develop commercially viable patient-specific vaccines on demand. A clinical study using targeted Vaccibody neoepitope DNA vaccines in multiple advanced
cancer indications is ongoing.
11:15 Agenus’ Synthetic Neoantigen Vaccine Platforms, Including Novel Phosphopeptide Tumor Targets
Daniel Levey, PhD, Senior Director Vaccine Research, R&D, Agenus, Inc.
Agenus’ vaccine platform of synthetic neoantigens complexed to recombinant heat shock protein 70 (HSC70) and administered along with QS-21 Stimulon® adjuvant elicits an antigen-specific immune response in both mice and humans. Leveraging our
in silico Agenus Immunogenic Mutation (AIM™) workflow, we are able to generate an optimal immunogenic vaccine blueprint for our AutoSynVax™ vaccines, which are uniquely designed and manufactured for each
patient based on NGS profiling of their tumor. Our PhosphoSynVax™ vaccine is an off-the-shelf vaccine targeting a novel class of tumor neoantigens arising from post translational modifications of self-peptides due to dysregulated cell signaling
pathways in cancer. Using mass-spectrometry, we have identified a large library of cancer-specific phosphopeptide tumor targets (PTTs) recognized by TCRs. Given Agenus’ diverse IO portfolio, we have the opportunity to combine our immune education
strategies with immunomodulatory antibodies to increase therapeutic efficacy.
11:45 Development of Synthetic Self-Replicating RNA Platforms for Oncology Vaccines and Therapeutics
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
RNA as a vaccine and therapeutic modality has become a focus of significant interest. SGI has developed a self-amplifying RNA replicon that overcomes existing limitations and has shown improved protein expression, immunogenicity, and resistance to immune
shutdown. This improved RNA replicon is also compatible with formulation technologies, which lower the effective dose required for immunization and improve cellular immunological memory. These engineered advantages enable novel applications of this
platform for oncology vaccines and therapeutics.
12:15 pm Luncheon Presentation: Overcoming the Obstacles of Neoantigen Detection for Cancer Vaccine Development
Kedar Hastak, PhD, Field Applications Scientist, Personalis, Inc.
Conventional exome assays often have gaps in sequencing coverage, leading to missed neoantigens. Personalis developed the ACE ImmunoID platform to overcome this and other challenges for more comprehensive neoantigen identification. ACE ImmunoID combines
augmented exome/transcriptome assays with state-of-the-art bioinformatics, optimized sample preparation, and automated processes to accelerate personalized cancer vaccine development.
12:45 Session Break
1:40 Chairperson’s Remarks
Philip Arlen, MD, President & CEO, Precision Biologics
1:45 FEATURED PRESENTATION: T Cells against Tumor Neoantigens: How Many Are Likely Needed for Clinical Efficacy and Can Contemporary Vaccines Get Us There?
Andrew Allen, PhD, CEO & President, Gritstone Oncology
Two key challenges in neoantigen-directed therapeutics are: 1) accurate neoantigen identification from “sea” of tumor mutations (achieved with deep learning approach, trained on human tumors); 2) induction of large numbers of polyfunctional
neoantigen-specific T cells. Novel vaccine approaches to problem (2), in combination with checkpoint modulators, can drive extremely high and sustained T cell responses in non-human primates. We can compare these to T cell numbers observed in successful
adoptive cell therapy.
2:15 The Discovery and Development of Novel Monoclonal Antibodies Targeting Neoantigens
Philip Arlen, MD, President & CEO, Precision Biologics
Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer. The membrane was separated into various fractions by molecular weight and screened for immunogenicity. An immunogenic fraction was identified and
used as a vaccine in a clinical trial for patients with chemotherapy refractory disease. There was a correlation observed in patients who developed antibody responses to therapy with both antitumor responses as well as prolongation in overall survival.
This vaccine was used as platform to screen monoclonal antibodies as potential therapeutic candidates.
2:45 An Integrated Machine-Learning Approach for Improved Prediction of Clinically Relevant Neoantigens
Trevor Clancy, PhD, CSO, OncoImmunity AS
Current neoantigen discovery algorithms are not optimal to predict antigen presentation to the tumor cell surface. Here, we outline a high-performing machine learning approach, that predicts naturally processed and presented antigens. The predictor is
integrated with several immune parameters in a deep learning layer to predict bone fide neoantigens. We illustrate its application to significantly improve the identification of neoantigen targets for personalized cancer immunotherapy.
3:15 Refreshment Break (Commonwealth Hall)
3:45 Improving Checkpoint Blockade by Improving Tumor Antigen Cross-Presentation
Joshua Brody, MD, Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount
Sinai; Director, Lymphoma Immunotherapy Program
Checkpoint blockade therapy of cancer has had tremendous impact, yet only a subset of patients responds. Although increased tumor mutational burden and tumor-associated antigen (TAA) load correlate somewhat with response to checkpoint blockade, we have
shown that Hodgkin’s lymphoma, despite a high anti-PD1 response rate, has significantly fewer mutations than highly mutated tumors such as lung cancer. This demonstrates that response to checkpoint blockade is determined by factors beyond mutation
burden. Our hypothesis is that checkpoint blockade is limited by suboptimal cross-presentation of TAA by suitably activated dendritic cells.
4:15 Th1 Epitopes for Versatile Tumor- and Patient-Tailored Vaccine Combination Therapies (VCT)
William C. Watt, PhD, President & CEO, EpiThany
Th1 epitopes from overexpressed tumor antigens constitute a rich source of active ingredients for cancer vaccine combination therapies (VCTs). Mining the “Th1 epitoire” for flexibility in vaccine antigen selection enables targeting of diverse tumors, patients and settings. EpiThany is incorporating its a priori validated tumor-specific Th1 epitopes into VCTs using multiple delivery platforms and combination agents to treat breast and ovarian cancers at multiple stages of disease.
4:45 Induction of Potent Neoantigen Targeted CD8+ T Cell Responses via Optimized DNA-Based Immunotherapy
Niranjan Y. Sardesai, PhD, CEO & President, Geneos Therapeutics
Tumor neoantigen targeting for the development of patient specific immunotherapies has emerged as a viable approach for cancer immunotherapy. Considerable efforts are being directed towards the accurate identification and prediction of targetable neoantigens
for each patient. However equally critical is the platform deployed for the administration of the selected neoantigens to generate patient T cell responses in vivo. We will discuss the use of optimized plasmid DNA
based approach.
5:15 End of Day
FRIDAY, August 31
7:45 am Registration (Plaza Level)
8:00 Breakout Discussion Groups with Continental Breakfast (Beacon Hill)
This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking.
Details on the topics and moderators are available on the conference website.
9:00 Chairperson’s Remarks
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
9:05 An HLA-Agnostic Functional Neoantigen Discovery Platform for Personalized Cancer Vaccines
Stephen Schoenberger, PhD, Co-Director, San Diego Center for Precision Immunotherapy; Professor, La Jolla Institute for Allergy and Immunology
Accurate identification of patient-specific neoantigens (NeoAg) is essential to develop effective personalized cancer vaccines. We have developed WES/RNAseq-guided platform which combines a filtering algorithm based on sequencing metadata, rather than
predicted HLA-binding, with in vitro functional T cell analysis. We report that >35% of selected expressed mutations can be verified as neoantigens in low mutational burden tumors by CD4+ and CD8+ T cells recognizing
common activating mutations in driver oncogenes and numerous patient-specific “passenger” mutations.
9:35 Functional and Unbiased Neoantigen Calling as a Basis for Personalized Vaccines
Ezra Cohen, MD, Professor, Medicine, University of California, San Diego
Cancer presents a unique opportunity for the clinical application of precision immunotherapy due to the frequent expression of somatic mutations that can be recognized as tumor-specific neoantigens (NeoAgs) by a patient’s T cells. Meaningful translation
of this concept, however, has been hampered by the lack of reliable methods for identifying NeoAgs in cancers of low mutational burden and by the absence of suitable preclinical animal models for evaluating and optimizing the ability of NeoAg-specific
T cells to recognize and eradicate autologous tumors. Through a collaborative effort within the San Diego Center for Precision Immunotherapy we have developed a set of novel bioinformatic and cellular tools which allows for the functional validation
of NeoAg recognized by both CD4+ and CD8+ T cells at a higher rate than previously reported. This platform has allowed effective identification of NeoAg in solid tumors with low-to-moderate mutational burden through precision immunotherapy which is
now being applied as a vaccine using synthetic long peptides.
10:05 Rapid High-Throughput Functional Selection of Neoantigens and Assessment of Their Safety
Slavoljub Milosevic, PhD, Director, Technology Innovation, Medigene AG
Neoantigens are an important class of highly specific target molecules for specific vaccine and TCR-based immunotherapies. Identification of neoantigens by next-generation sequencing and prediction of binding to the HLA allotypes of a patient, still leaves
open the issue of actual immunogenicity and safety of neoantigen targets for therapeutic use. Medigene combines high throughput functional screening with sophisticated in silico tools to overcome several current limitations
in selecting relevant neoantigens.
10:35 Coffee Break (Plaza Level)
11:00 Harnessing the Innate Immunogenicity of Foreign Viral Antigens to Fight Solid Tumors
David Anderson, PhD, CSO, Research & Development, VBI Vaccines, Inc.
CMV is expressed on over 95% of glioblastoma, medulloblastoma and breast cancers. Like neoantigens, it provides an opportunity to target a non-self antigen that has inherently higher immunogenicity than traditional tumor associated antigens. Recently
CMV-specific autologous approaches have demonstrated over a 2X increase in overall survival in glioblastoma. VBI’s approach utilizes its eVLP platform to restimulate CMV immunity by preferential uptake and presentation to dendritic cells. It
offers an off-the-shelf approach to target CMV+ tumors.
11:30 Validation of Real Neoantigens with Mass Spectrometry
Harpreet Singh, PhD, President & CEO, Immatics US, Inc.
While neoantigens are a promising target class for immunotherapies in some patient populations, many researchers overlook that only a small fraction (presumably less than 1%) of all non-synonymous mutations are actually presented as pMHC targets and can
thus act as neoantigens. Most strategies utilizing in silico prediction deliver more than 90% false-positive results. Such irrelevant antigens are currently often used in clinical trials and likely will not result
in clinical benefit. Here, we show how Immatics’ proprietary XPRESIDENT platform, an ultrahigh-sensitivity, high-throughput, high-fidelity mass spectrometry setup allows to validate real neoantigens. Furthermore, data from clinical applications
of highly personalized applications is shown underlining the promise of tailored immunotherapies using both neoantigens and shared antigens.
12:00 Close of Neoantigen Targeted Therapies