Cambridge Healthtech Institute's 3rd Annual

Emerging Tech for IO Targeting and Discovery

Unlocking Precision IO: Innovative Tools, Targets, & Solutions

August 8 - 9, 2024 ALL TIMES EDT

Immuno-oncology has completely transformed cancer treatment by leveraging the body’s own immune system to combat the disease. However, significant problems persist in this field. Some of the key issues we address include predicting immune response, overcoming resistance, addressing tumor heterogeneity, optimizing delivery, and understanding tumor escape. Explore innovations in CRISPR for next-gen targets, computational tools, STING-driven approaches, sustained release of therapeutics, groundbreaking clinical trials, and much more. Improve patient outcomes through high-throughput manufacturing and deep-learning predictions for personalized treatment solutions. Join us for the 3rd Annual Emerging Tech for IO Targeting and Discovery conference where we address some of the most challenging issues in this space.

Thursday, August 8

Registration Open10:30 am

PLENARY KEYNOTE SESSION

11:20 am

Organizer's Remarks

Nikki Cerniuk, Conference Producer, Cambridge Innovation Institute

11:30 am

Accelerating Cell and Gene Therapy: Current Challenges and Future Directions

Daniel J. Powell Jr., PhD, Professor, Pathology & Laboratory Medicine, University of Pennsylvania

New designs for genetically modified T cells include switches and potency enhancements that will be required for targeting solid tumors. Determining the critical quality attributes, dose, potency, and anticipating pharmacokinetics of a living, dividing drug presents unique challenges. Improving patient access depends not only on scientific progress in targeting, gene modification and cellular manipulation, but also on meeting automation, engineering, clinical site onboarding, and health policy challenges.

12:00 pmTransition to Lunch
12:15 pm LUNCHEON PRESENTATION: LUNCHEON PRESENTATION: HCAb Harbour Mice Advances Multispecific, CAR T, and ADC Therapy to a New Level

Joe Zhao, PhD, Vice President, Head of External Innovation, Nona Biosciences

HCAb Harbour Mice of Nona Biosciences is the first fully human heavy chain only antibody (HCAb) transgenic mice platform in history.  It is optimized, clinically validated with global patent protection. Fully human heavy chain only antibodies have high affinity and have excellent biophysical characteristics. They are the ideal antibody format to generate a multitude of next-generation therapeutic modalities, including bispecific/multispecific antibodies, ADCs, CAR-based, and mRNA therapeutics.

12:45 pm

The Outlook for Innovation in IO: A VC Perspective

Jakob Dupont, MD, Executive Partner, Sofinnova Investments

Immuno-oncology treatments from checkpoint inhibitors to cytokine therapies to bispecific antibodies and cell therapies have made a profound impact on patients' lives. There have been significant IO products successes but also notable failures in the development of these drug candidates. This talk will present a perspective on how IO agents are assessed by VCs and what VCs are looking for to create value for patients and investors in IO.

Transition to Sessions1:15 pm

DISCOVERY AND DESIGN FOR PRECISION IO

1:25 pm

Chairperson's Opening Remarks

Sean P. Arlauckas, PhD, Director, B Cell Platform, Be Biopharma

1:30 pm

Breaking Innate Immune System Tolerance: A Novel Approach to Cancer Immunotherapy

Ethan Shevach, MD, Senior Investigator, Cellular Immunology, Laboratory of Immune System Biology, NIAID, NIH

Checkpoint blockade reverses the inhibitory pathways manifest by anti-tumor effector cells. Leukocyte-Ig-like receptors (LILRs) are immunomodulatory receptors which are expressed on cells of the innate immune system and bind to a determinant on HLA. Pan-HLA-mAbs block the binding of LILRs, do not block TCR recognition, activate dysfunctional NK cells from human cancers, and enhance tumor immunity in humanized mice. HLA/LILR interactions represent a target for the treatment of cancers in humans.

2:00 pm

Uncovering Heterogeneity in Specific Immune Cell Populations in the Tumor Microenvironment

Shahin Aslam, Associate Principal Scientist, Merck

This study explores the diversity within specific cell populations residing in the tumor microenvironment. Using advanced techniques, we identify distinct subgroups within these cells, shedding light on their varying functions and potential implications for cancer immunotherapy. Our findings underscore the complexity of immune responses within tumors and highlight the importance of understanding heterogeneity for developing targeted therapeutic strategies.

2:30 pm PHC Solutions in Cell and Gene Therapy

Tia Harmon, Technical Product Sales Specialist, PHC Corporation of North America

Metabolism is the key activity by which individual cells process nutrients and is closely associated with cell proliferation and differentiation. In the fields of stem cell research, immunotherapy, and cell processing, the understanding of metabolic mechanisms is crucial. To meet this need, PHC Corporation will launch a continuous metabolic analyzer, LiCellMo, which achieves real-time monitoring of the metabolic condition of living cells, and driving new insights into metabolic research.

Refreshment Break in the Exhibit Hall with Poster Viewing3:00 pm

SPEED-NETWORKING

3:20 pm How Many New Contacts Can You Make? IN-PERSON ONLY

Nikki Cerniuk, Conference Producer, Cambridge Innovation Institute

Virginia Maxwell, Senior Associate Producer, Cambridge Healthtech Institute

Join us for a dynamic speed networking session at the IO Summit. Make quick and impactful connections! Be yourself, share your background, business cards (or LinkedIns), and connect with potential collaborators in a fun and focused environment. Briefly summarize your research in one minute and get ready to meet fellow attendees who share your interests. We'll provide the space, timers, and exciting group of researchers to make introductions a breeze.

3:40 pm

Epigenetically Suppressed Tumor Cell Intrinsic STING Promotes Tumor Immune Escape

Jian Cao, PhD, Assistant Professor, Pathology, Rutgers Cancer Institute

STING activation for induced anti-tumor immunity is an attractive approach but shows limited efficacy in the clinic. The epigenetic silencing of STING in many tumors suggests that STING silencing contributes to immune escape and may limit STING agonists applications. Here we use a MC38 and CT26 mouse model to show STING loss accelerates tumor growth. KDM5 inhibitors activate STING expression in mouse cancers and suppress growth in a STING-dependent manner.

4:10 pm

STING-Driven Activation of T Cells for the Adoptive Cell Therapy of Cancer

Lionel J. Apetoh, PhD, Professor, Microbiology & Immunology, Indiana University

Adoptive cell therapy (ACT) shows promise against some cancers, but limitations exist. We explore how stimulating a cellular pathway called STING can enhance ACT. This approach may improve T cell function within the tumor environment, leading to better infiltration, persistence, and ultimately, tumor cell-killing.

4:40 pm

High-Throughput Screen to Identify and Optimize NOT Gate Receptors for Cell Therapy

Tanveer Gill, Research Associate II, Discovery Research, A2 Biotherapeutics

Logic-gated cell therapy systems are considerably more complicated than conventional therapeutics and, therefore, more challenging to optimize. Here we describe the design and testing of a flow-cytometry-based screening system to rapidly select functional inhibitory receptors from a pooled library of candidate constructs. In proof-of-concept experiments, this approach identifies inhibitory receptors that can operate as NOT gates when paired with activating receptors.

Close of Day4:55 pm

Friday, August 9

Registration Open7:30 am

BREAKFAST BREAKOUT DISCUSSIONS

8:00 amBreakfast Breakout Discussions

Breakout Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Breakout Discussions page on the conference website for a complete listing of topics and descriptions.

IN-PERSON BREAKOUT TABLE 4:

Leveraging Biomarker Technologies for Understanding PD-1 Innate and Adaptive Resistance to Inform New Targets and New Combinations.

Theresa M. LaVallee, PhD, Chief Development Officer, Coherus Biosciences

  • Approaches to characterize PD-1 resistance
  • Applications of PD-1 resistance characterization for target discovery
  • Uncovering novel and next-gen combination treatment approaches through PD-1 findings
IN-PERSON BREAKOUT TABLE 5:

Next-Gen Tech for Improved IO Outcomes Through TAMs

Nir Chetrit, PhD, PI, Weill Cornell Medicine

  • Modulating the tumor-supporting functions of TAMs: current approaches & challenges
  • Novel strategies and technologies to overcome limitations of TAM reprogramming
  • Scalable TME models and platforms for high-throughput discovery
9:00 am

Chairperson's Remarks

Yuguo Leo Lei, PhD, Associate Professor, Biomedical Engineering, Pennsylvania State University

9:05 am

Development of ex vivo Precision Gene-Engineered B Cell-Medicines That Produce Highly Active and Sustained Levels of Transgenic Anti-Tumor Biologics

Sean P. Arlauckas, PhD, Director, B Cell Platform, Be Biopharma

Bispecific T Cell Engagers (BiTEs), consisting of an anti-CD3 scFv fused to an anti-tumor antigen scFv, are highly effective in the treatment of relapsed/refractory Acute Lymphoblastic Leukemia (ALL). However, the short half-life of BiTEs necessitates continuous intravenous administration at high doses for four-week increments. To overcome these pharmacokinetic shortcomings, we developed a method to engineer plasma cell precursors to continuously secrete transgenic biologics. Plasma cells were chosen for their high antibody production capacity (thousands of Ig molecules/cell/sec) and long-term survival (persisting for decades), making them a highly attractive cell-based platform for continuous BiTE delivery.

COMPUTATIONAL TOOLS AND ML-DRIVEN APPROACHES

9:35 am

Utilizing CRISPR Screening for Novel Target Discovery

Nir Chetrit, PhD, PI, Weill Cornell Medicine

Immunotherapies are remarkably effective in a subset of human cancers. These strategies critically rely on robust immune responses in the tumor microenvironment (TME), which are immunosuppressed by robust accumulation of tumor-associated macrophages (TAMs). While TAM transcriptional profiles are well-annotated, modulating their tumor-supporting functions has proved exceptionally difficult, primarily due to the lack of scalable TME models that enable high throughput discoveries. We developed a scalable TME platform and performed a CRISPR screen to convert TAMs into immunostimulatory macrophages. TAM reprogramming leads to rapid regressions of mammary tumors, providing a roadmap for harnessing macrophage plasticity for innate I-O in cancer patients.

10:05 am Predicting Therapy Outcomes with Autoantibody Biomarkers in Melanoma

Iman Osman, MD, Assoc Dean & Professor; Dir NYU Melanoma SPORE, Medicine (Oncology) and Urology, NYU Grossman School of Medicine

Predicting outcomes in cancer treatment is crucial for optimizing therapeutic strategies. This presentation explores profiling autoantibodies using Sengenics custom protein microarrays to identify biomarker signatures predictive of treatment response and toxicity in melanoma patients. This approach has shown promising results, holding great potential to personalize cancer therapy for more effective and safer treatments for melanoma and other types of cancers.

Coffee Break in the Exhibit Hall with Last Chance for Poster Viewing, Poster Winner Announced10:35 am

11:20 am

Re-Imaging Precision Oncology through Deep Learning-Enabled Analysis of Histopathology

Albert Kim, Assistant Professor, Harvard Medical School; Assistant Physician, Massachusetts General Hospital Cancer Center

Tumor and immune phenotypes mediate therapeutic efficacy for most solid tumors. However, there is not a widely available method to measure immune phenotypes for each patient’s tumor. Here, we use deep learning to quantify expression of ten transcriptional signatures from the H&E slide of primary breast tumors. Our efforts illustrate the potential of computational H&E biomarkers that reflect facets of the TME, which hold promise for augmenting precision oncology.

ENHANCING TARGETING AND DELIVERY

11:50 am

Ramifications of Tethering T Cell-Activating Cytokines to the Surface of Tumor Cells

Jacob McCright, PhD, Scientist 2, Deka Biosciences

The combination of IL-2, IL-10 and EGFR (DK210 (EGFR)) binds to T cells via IL-2 and IL-10 receptors, and to the tumor cell via EGFR. Evaluation of the DK210 (EGFR) structure suggests the cytokines are oriented on the opposite sides of the molecule from the anti-EGFR CDRs. DK210 (EGFR) therefore enhances T cell avidity for tumor cells and is clustered in the T cell synapse, enhancing T cell cytolytic function.

12:20 pm

KEYNOTE PRESENTATION: Lipid-Mediated Intracellular Delivery of Recombinant bioPROTACs for the Rapid Degradation of Undruggable Proteins

Andrew Tsourkas, PhD, Co-Director, Center for Targeted Therapeutics and Translational Nanomedicine; Professor, Bioengineering, University of Pennsylvania

A modular approach was developed that enables the efficient delivery of antibodies and proteins into the cytosol of cells. This approach was used to inhibit numerous cancer-associated proteins, including multidrug resistance Protein 1 and NFκB as well as the previously considered “undruggable” targets, Ras and Myc. More recently, BioPROTACs were delivered intracellularly, enabling the specific degradation of target proteins.

Transition to Lunch12:50 pm

1:00 pm LUNCHEON PRESENTATION: LUNCHEON PRESENTATION: Advancing Immune-Targeted Cancer Therapies: Leveraging Human Primary Cell in vitro Assays

Robert Benson, PhD, R&D, Antibody Analytics Ltd.

Human primary cell in vitro assays play a crucial role in evaluating immune-targeted cancer therapies. Our team has designed a diverse suite of platforms that utilize primary immune cells—T cells, macrophages, NK cells, B cells, neutrophils, and dendritic cells—to assess candidate therapies within the dynamic context of the TME. By integrating these platforms with our novel dual-inducible expression system, we can comprehensively elucidate a therapeutic’s mechanism-of-action and safety profile.

Session Break1:30 pm

2:15 pm CANCELLED:

Precision-Guided Bicycle IO Therapeutics for the Treatment of Cancer

Philip E. Brandish, PhD, Senior Vice President, Immuno-Oncology, Bicycle Therapeutics

Small constrained bicyclic peptides have PK and PD properties that are optimal for targeted delivery of toxins, radionuclides, or immune agonists for the treatment of cancer. This presentation will highlight the application of the Bicycle technology to anti-cancer immunity, in particular via the activating receptors CD137 and NKp46.

BRIDGING THE GAP: FROM BENCH TO BEDSIDE

2:45 pm

Chairperson's Remarks

Sruthi Ravindranathan, PhD, Senior Scientist, Cellular Immunology, Coherus Biosciences

2:50 pm

Scalable Microbioreactors for Cell and Virus Production

Yuguo Leo Lei, PhD, Associate Professor, Biomedical Engineering, Pennsylvania State University

Culturing cells at large scales remains challenging. We here present a microbioreactor to address this challenge. Cells are cultured in microscale alginate hydrogel tubes (AlgTubes). AlgTubes offer large improvements in cell viability, growth, yield, culture consistency, and scalability over current bioreactors. Cells have high viability, growth rate (3000-fold/passage), and yield (~5x10^8 cells/mL). AlgTubes significantly reduce the culture volume and time-and-production cost, making large-scale cell production feasible.

3:20 pm

Casdozokitug, a Potent and Selective Anti-IL-27 Antibody That Has Demonstrated Clinical Activity in Overcoming PD-1 Resistance and Tumor Immune Suppression in Cancer Patients

Sruthi Ravindranathan, PhD, Senior Scientist, Cellular Immunology, Coherus Biosciences

IL-27, a heterodimeric cytokine expressed by macrophages and myeloid cells, regulates the intensity and duration of immune responses in several pathological conditions, including cancer. Upregulation of IL-27 promotes tumor growth and progression in preclinical models, and is implicated in resistance to PD-1 inhibitors. Casdozokitug is a potent and selective anti-IL-27 antibody that has demonstrated immune activation and single-agent tumor response in Phase 1 clinical trials.

3:50 pm CANCELLED PANEL DISCUSSION:

Putting Patients First: Building Sustainable Models for IO Development

PANEL MODERATOR:

Philip E. Brandish, PhD, Senior Vice President, Immuno-Oncology, Bicycle Therapeutics

  • What are the most significant manufacturing hurdles in bringing IO therapies to the clinic, particularly for complex modalities like CAR-T and cell therapies?
  • Balancing cost, quality, and throughput
  • Patient-centricity: Ensuring that patient needs are prioritized throughout the development and manufacturing process.
  • How can we improve collaboration between manufacturing teams and the clinic?​

PANELISTS:

Julia A Coronella, PhD, Vice President, Immuno Oncology, Poseida Therapeutics Inc

Yuguo Leo Lei, PhD, Associate Professor, Biomedical Engineering, Pennsylvania State University

Predicting Immune Checkpoint Inhibitor Outcomes—A Role for Autoantibody Biomarkers

Iman Osman, MD, Rudolf L. Baer Professor of Dermatology, Professor, Medicine & Urology, New York University Langone Medical Center

Sruthi Ravindranathan, PhD, Senior Scientist, Cellular Immunology, Coherus Biosciences

Conference Wrap-Up3:50 pm

Close of Summit4:05 pm






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