Immunotherapy Safety and Efficacy track banner

Cancer immunotherapy has taken the industry by storm the past few years, yet in some cancers and some patients, the success rate of immunotherapy agents is limited. Much of the challenge lies in its safety and efficacy limitations. To improve outcomes, drug developers are looking at enhancing efficacy and reduce toxicity through combination therapies, focusing on CD4+ cells, targeting B cell malignancies, shifting from T cells to NK and gammadelta cells, and many other unique approaches. CHI’s inaugural Immunotherapy Safety & Efficacy conference will bring to light some of these exciting developments that promise to reduce toxicities and improve clinical outcomes.

Thursday, 4 November

07:30 Registration and Morning Coffee

ENHANCING EFFICACY AND REDUCING TOXICITIES

07:55

Chairperson's Opening Remarks

Aude De Gassart, PhD, Director, Preclinical Research, Imcheck Therapeutics
James Keck, Ph.D., Senior Director, Innovation and Product Development, The Jackson Laboratory
08:30 KEYNOTE PRESENTATION:

PD-1 Antibodies as Precision Medicine Informed Mono- and Combination Therapies Are Transforming Cancer Care

Roy Baynes, MD, PhD, Senior Vice President & Head, Global Clinical Development; CMO, Merck, Sharp, and Dohme

PD-1 antibody treatment has shown broad based activity as monotherapy in numerous cancer types and in multiple lines of treatment. Precision medicine tools have enriched for outcomes in a number of tumor types, have provided useful information regarding mechanisms of resistance and thereby informed combination therapy choices. PD-1 antibodies are proving to be foundational in a number of highly effective combination therapies across multiple cancer types.

  • NEW TALK - This Presentation Will be Given for the First Time
09:00

A Pivotal Role for Concurrent Chemotherapy and γδ T Cell Therapy (Drug Resistant Immunotherapy – DRI) in the Post-Induction Primary Disease Setting for Reducing the Immunosuppressive Properties of the Tumor Microenvironment

Lawrence Lamb, Jr., PhD, Executive Vice President & CSO, IN8Bio

Chemotherapy reduces tumor mass, increases vascular permeability, disrupts immunosuppressive networks, and upregulates expression of stress induced NKg2DL, while also depleting immune effector cells. We have genetically modified γδ T cells, which broadly recognize tumor stress signals to function in therapeutic concentrations of specific chemotherapy agents enabling delivery at the time when the tumor is at highest vulnerability. We are currently evaluating this approach in ongoing preclinical models and clinical trials.

  • NEW DATA - This Presentation Contains New Data
Sophie Vermond, Early Discovery Scientist, Immunology, Immuno-oncology and Cell Therapy, Charles River

Within cell therapy development the use of in vivo animal models can present significant hurdles in translatability to humans. As a result, the establishment of complementary high-quality in vitro efficacy and safety studies to foster the development of such therapies has become critical before filing for Investigational New Drug (IND) status.  Charles River has developed an in vitro efficacy package aimed at determining cell therapy activity, specificity and potency.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45

Targeting B Cell Malignancies with Multi-Specific Cytotoxic CD4+ T Cells

Baochun Zhang, PhD, Assistant Professor, Medical Oncology, Dana Farber Cancer Institute

CD8+ CTL-based therapies, including CD19-targeted CAR T cell therapy, have seen substantial limitations in B cell malignancies, producing durable remissions only in less than one-half of treated patients; relapses result primarily from the target epitope loss or poor in vivo persistence of the CD8+ T cells. To overcome these limitations, we develop a novel form of immunotherapy for B cell malignancies using multi-specific CD4+ CTLs with superior ability for in vivo persistence. Here, we present results from preclinical and translational studies.

  • NEW DATA - This Presentation Contains New Data
11:15

The CD25 Antibody RG6292 Selectively Depletes Tregs while Preserving IL-2 Signaling and CTL Activity for Tumor Control

Maria Amann, Senior Scientist, Drug Development, Roche Innovation Center Zurich

Despite advances in immunoncology, many patients fail to respond to CPI. High Treg counts correlate with poor prognosis to CPI. RG6292 is an ADCC/ADCP competent monoclonal antibody (human IgG1) with an afucosylated Fc region binding with low affinity but high avidity to CD25. RG6292 preferentially depletes CD25++ Tregs over CD25+/- activated CTLs. RG6292 preserves IL-2 signaling to allow effective anti-tumor responses. Preclinically, RG6292 promoted eradication of established tumors and synergized with CPI. RG6292 provides a novel therapeutic approach to alleviate one mechanism of immune suppression in the tumor microenvironment. Clinical testing is currently ongoing in patients with advanced solid tumors (NCT04158583).

11:45 Visit Sponsored Presentations in Other Tracks
12:25 Enjoy Lunch on Your Own

PLENARY KEYNOTE SESSION

13:45

Chairperson's Remarks

Ruud M. De Wildt, PhD, Director & Biopharm R&D Head, Lead Discovery, GlaxoSmithKline
13:50

The Role of Monoclonal Antibody Therapeutics in Tackling Global Health Challenges

Pauline Williams, CBE, MBBCh, FFPM, FMedSci, Senior Vice President and Head of Global Health R&D, GlaxoSmithKline

Monoclonal antibody therapies have historically been dismissed as viable global health interventions because of cost, supply chain and healthcare system limitations. The global response to the COVID-19 pandemic has demonstrated how disruptive approaches to R&D can transform therapeutic and preventative approaches in a short timescale. There is an increased awareness of the role mAbs can play in addressing public health challenges, including infectious diseases and anti-microbial resistance.

14:20 PLENARY:

Live Q&A

Panel Moderator:
Ruud M. De Wildt, PhD, Director & Biopharm R&D Head, Lead Discovery, GlaxoSmithKline
Panelist:
Pauline Williams, CBE, MBBCh, FFPM, FMedSci, Senior Vice President and Head of Global Health R&D, GlaxoSmithKline
14:30 Exhibit Hall & Last Chance Poster Viewing

ADVANCING NK AND GAMMADELTA CELLS

15:15

Chairperson's Remarks

Maria Amann, Senior Scientist, Drug Development, Roche Innovation Center Zurich
15:20

Mobilizing Gamma-Delta T Cells for Next-Generation Anti-Cancer Immunotherapy–ICT01, an Anti-BTN3A Monoclonal Antibody, Plus IL-2 Triggers Selective g9d2 T Cell Expansion and Activation, While Blunting the IL-2-mediated Increase in Tregs in Non-Human Primates

Aude De Gassart, PhD, Director, Preclinical Research, Imcheck Therapeutics

g9d2 T cells display potent anti-tumor activity and infiltrate into solid and hematologic tumors and are associated with a positive clinical prognosis. ICT01, a novel cancer immunotherapeutic mAb targeting BTN3A and activating g9d2 T cells is in clinical stage development. As an approach to potentiate g9d2 T cell-mediated cancer immunotherapy, we characterized the safety and pharmacodynamic activity (i.e., number of g9d2 T-cells) of ICT01 combined with IL-2 (Proleukin) in non-human primates.

15:50

Shifting from T to NK Immunotherapy

Aviad Pato, PhD, Head Research, Natural Killer Cells, Gamida Cell Ltd.

The evolving field of NK cellular immunotherapy is modifying what has been learned from T cell gene editing to apply knowledge to NK cell manipulation. Gamida-Cell utilizes transient intracellular delivery of mRNA by electroporation, enabling efficient delivery of immunological adjuvants, cytokines, and CAR constructs into Nicotinamide (NAM)-expanded, allogeneic NK cell. This technique can be easily applied to generate improved off-the-shelf NK cancer therapeutics. mRNA Engineering of NK cells allows for manipulations that have the potential in clinical applications, which would benefit from a higher level of expression for a transient period to all for maximum safety.

  • NEW DATA - This Presentation Contains New Data 
  • NEW TALK - This Presentation Will be Given for the First Time
16:20

Maximizing the Therapeutic Potential of Allogeneic Natural Killer Cells

Joanne B.L. Tan, PhD, Director, Translational Biology, Nkarta Inc.

Natural Killer (NK) cells are innate immune cells that can eliminate target cells in an antigen-independent fashion. NK cells can be engineered to express chimeric antigen receptors (CARs), expanded under different conditions, and gene edited to further enhance cytotoxicity, selectivity, and persistence. Nkarta is developing off-the-shelf CAR NK cells to maximize the therapeutic potential of allogeneic NK cells alone or in combination with other agents. 

  • NEW DATA - This Presentation Contains New Data
  • NEW TALK - This Presentation Will be Given for the First Time
16:50 Session Break

TARGETING SOLID TUMORS

17:00

A Novel Bispecific Antibody Platform that Elicits Efficient Tumor Lysis with Minimal Cytokine Release in Liquid and Solid Tumors

Harbani Malik, PhD, Senior Scientist, Group Lead Protein Sciences, Teneobio/AMGEN

Multi-specific antibodies have the unique ability to elicit an immune response at the site of a tumor. By minimizing the toxicities associated with a systemic immune response, tumor-targeted, immune agonist antibodies can increase the therapeutic index for new immune-activating cancer therapies. In summary, we have created multiple platforms for tunable immune activation at the site of the tumor that work with a variety of tumor antigens.

17:30

CYT101, a High-Affinity IL-15Rbg Agonist, Induces Safe and Potent Anti-Tumor Immune Activities in Patients with Solid Tumors and Supports Further Clinical Investigations

Irena Adkins, PhD, Science Lead, Pharmacology, SOTIO a s

High-affinity IL-2/IL-15Rbg agonist SOT101 (CYT101, RLI-15) as a monotherapy or in combination with pembrolizumab increases immune cell infiltration in tumors in clinically responsive patients in Phase clinical I study (NCT04234113) which is accompanied by NK and CD8+ T cell cytotoxicity, proinflammatory chemokine and IFN-g signaling gene signatures. All patients showed dose-dependent pharmacodynamic responses in blood; however, SOT101 activity in the tumor microenvironment might be pivotal for the therapeutic success.

  • NEW TALK - This Presentation Will be Given for the First Time
18:00

Expression of a Pathogenic Virulence Factor Enhances the Efficacy of CAR-T Cell Therapy Against Solid Tumors

Magnus Essand, PhD, Co-Founder, Elicera Therapeutics; Prof, Immunology, Genetics and Pathology, Uppsala University

Heterogenous target antigen expression and immunosuppression in solid tumors impede clinical implementation of CAR Ts. We armed CAR Ts to secrete a pluripotent proinflammatory neutrophil-activating protein (NAP) from Helicobacter pylori upon target antigen recognition. CAR(NAP) Ts were more successful in reducing tumor growth and enhancing survival of mice than conventional CAR Ts. NAP secretion created an immunologically hot tumor microenvironment supporting DC maturation and bystander immunity with infiltration of CD8+ T cells targeting tumor-associated antigens other than the CAR target antigen. The effect was independent of tumor model and target antigen, indicating broad applicability in various solid tumors and warranting translation into the clinic.

  • NEW DATA - This Presentation Contains New Data
18:30 Close of Summit