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)

PERSONALIZED CANCER VACCINES
Skyline

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 Talk Title to be Announced

Yisrael Katz, MD, Internal Medicine, ABIM, Arizona Biodesign Institute


9:30 Development of a Rapid Personalized Self-Assembling Vaccine for Cancer

Poznansky_MarkMark 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

Fredriksen_AgneteAgnete 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

Levey_DanielDaniel 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

Wang_NathanielNathaniel 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.

Personalis12:15 pm Luncheon Presentation: Overcoming the Obstacles of Neoantigen Detection for Cancer Vaccine Development

Hastak_KedarKedar 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

NEOANTIGEN TARGETED THERAPIES
Cityview 1

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?

Allen_AndrewAndrew 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

Arlen_PhilipPhilip 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.

OncoImmunity2:45 An Integrated Machine-Learning Approach for Improved Prediction of Clinically Relevant Neoantigens

Clancy_TrevorTrevor 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

Brody_JoshuaJoshua 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)

Watt_WilliamWilliam 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

Sardesai_NiranjanNiranjan 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.

NEOANTIGEN IDENTIFICATION AND SELECTION FOR PERSONALIZED IMMUNOTHERAPY
Skyline

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

Cohen_EzraEzra 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

Anderson_DavidDavid 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 Close of Neoantigen Targeted Therapies

#IOSummit