
Sophia Karagiannis
Reader in Translational Cancer Immunology, Head of Cancer Antibody Discovery and Immunotherapy, King’s College London
When
10th-11th Oct 2019
Registration from 8am
Where
London, United Kingdom
London Heathrow Marriott Hotel
With our expert speakers you will explore the latest advances in antibody-based therapeutics in oncology. Talks will review the recent developments in bispecific antibody technology, as well as exploring the potential of new antibody and antibody-mimicking formats. Plus, a dedicated checkpoint blockades session will also examine new approaches in neutralizing cancer cell immune blockades, including advances in PD1, PD-L1 and CTLA4 targeting therapeutics, and the discovery and targeting of new biomarkers.
“I liked the fact that the conference was really focused … allowing to learn and discuss specific subjects with experts in the field”
“Excellent opportunity to discuss topics in detail and to network”.
“The research sessions were very good and of high quality”
THURSDAY 10TH OCTOBER 2019 – ANTIBODIES FOR ONCOLOGY
Keynote Address: Development of a next generation immune checkpoint modulator towards the clinic; a humanized BTN3A antibody (ICT01) activating gamm9delta2 T cellsRENE HOET, CSO, Imcheck Therapeutics
ImCheck Therapeutics is advancing the first activating butyrophilin BTN3A (CD277) antibody towards the clinic. The humanized antibody to BTN3A, ICT01, specifically activates human gamma9delta2 T-cells in-vitro and in-vivo and is planned to enter phase I studies early 2020. Additionally, therapeutic antibodies against 5 novel butyrophilins are currently validated. This opens a completely new space clearly different from the current B7/CD28 superfamily targets and has the potential to become the next generation immune checkpoint modulators.
Keynote Address: Cancer Bispecific Biologics: Current Status and Learnings From Successes and FailuresRAKESH DIXIT, VP, Research & Development and Global Head Biologics Safety, MedImmune
• Overview of landscape of bispecifics targeting cancers
• Preclinical and clinical landscape of bispecifics in oncology
• Five rights of bispecifics: A case study of unique immune checkpoints targeting bispecific
• Learnings from success and failures of bispecifics.
Morning Refreshments / Poster Presentations
Triple Negative Breast Cancer targeted therapy with anti-Folate Receptor alpha antibodies
SOPHIA KARAGIANNIS, Reader in Translational Cancer Immunology, Head of Cancer Antibody Discovery and Immunotherapy, King’s College London
Employing a multi-omics approach we show that the folate carrier Folate Receptor alpha (FRα) is upregulated in triple negative breast carcinomas and that expression of molecules involved in the folate metabolism are dysregulated. FRα is expressed in post-neoadjuvant chemotherapy residual disease, and participates in cancer cell signaling and cancer cell growth. We demonstrate that FRα and the folate cascade could be targeted with specific inhibitors. Furthermore, FRα may present a target for antibody immunotherapy that primes an Fc-mediated anti-tumor immune response, and an antibody-drug conjugate approach that can deliver a pathway inhibitor to FRα-expressing cells. These findings may point to a new treatment avenue for patients with triple negative breast cancer.
Targeted Thorium Conjugates: Novel first in class targeted alpha therapy
JENNY KARLSSON, Head of TCR Biochemistry, Bayer
• Targeted thorium conjugates (TTCs) represent a new class of therapeutic radiopharmaceuticals for the targeted alpha therapy (TAT) of cancer.
• TAT has become an established modality in the treatment of metastatic castration-resistant prostate cancer
following the approval of radium-223 dichloride.
• TATs are highly cytotoxic due to the high linear energy transfer of the alpha-particle emitting radionuclide which induces complex DNA double-strand breaks in the targeted tumor cell.
• TTCs consist of a targeting moiety, a chelator covalently linked via an amide bond to the antibody and thorium-227 complexed to the chelator with high affinity.
• Important advantages of TTCs are the lack of known resistance mechanisms to alpha-particle emission and their ability to also kill non-dividing cells.
• Preclinical in vitro and in vivo data will be presented.
Lunch
PANEL DISCUSSION:
Next Generation Antibodies: beyond bispecifics
Speakers include: SYD JOHNSON & RAKESH DIXIT
Bi-specific T-cell Engagers (BiTE®) in Hematological Malignancies
FRANCESCO GALIMI, Global Product General Manager, Early Development, Amgen
The bispecific T-cell engager (BiTE®) blinatumomab (Blincyto®) has recently been approved for Philadelphia
chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It consists of two single chain variable fragments (scFvs) specific for CD19 present on the B-cell lineage, and CD3 expressed on almost all T cells. Based on the potent anti-tumor activity of Blincyto® in B-cell malignancies, BiTE® antibody constructs directed against other target antigens are being tested in a number of malignancies, in particular acute myeloid leukemia and multiple myeloma. We will review the ongoing activities in this field.
Afternoon Refreshments / Poster Presentations
POLR2A as a putative predictive biomarker for treatment with Amanitin-based ADCs
CHRISTIAN BREUNIG, Group Leader Biomarker & Cell Biology, Heidelberg Pharma
Heidelberg Pharma develops Antibody Targeted Amanitin Conjugates (ATACs), a new class of Antibody-Drug Conjugates with the cyclic peptide amanitin as the toxic payload. Amanitin blocks the cellular transcription process by specifically binding to the eukaryotic RNA polymerase II. POLR2A, the largest subunit in the human RNA polymerase II complex, is located on chromosome 17p13.1 and in close proximity to TP53. A chromosome 17p deletion is present in any cancer patients correlating with poor survival. Furthermore, we observed that a deletion of POLR2A significantly enhanced treatment efficacy of ATACs in different in vivo models. Based on these observations, Heidelberg Pharma proposes POLR2A as a putative biomarker to identify patients that would benefit the most from treatment with ATACs
Antibody libraries based on an autonomous human variable domain
JOHAN NILVEBRANT, Researcher, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH
Antibodies are tremendously useful for biotechnological applications, diagnostics and therapy. However, their complex architecture has spurred interest in smaller derivatives that can retain the targeting specificity and be more easily produced. We have constructed highly diverse (>1010) libraries based on an autonomous human variable heavy (VH) domain and used these libraries to select specific binders to the human Eph receptor family. Our aim is to use these binders to develop novel tools for specific investigation of blocking or activation of specific Eph receptor homo or heterodimers. Moreover, structural evaluations of first and second-generation binders to EphA1, which have been identified after stress selections on phage, illustrate how VH domains can be stabilized via tailored CDR mutagenesis.
Networking Drinks Reception
FRIDAY 11TH OCTOBER 2019 – IMMUNO-ONCOLOGY FORMATS
Keynote Address: Developing novel checkpoint inhibitors
JUSTIN SCHEER (Reserved), Director, Antibody Engineering, Boehringer-Ingelheim
BiCKI: a novel Bispecific checkpoint inhibitor platform
NICOLAS POIRIER, CSO, OSE Immunotherapeutics
• A proprietary transformative technology restating the current anti-PD-(L)1 standard of care.
• An engineered anti-PD-1 bispecific platform to extend the spectrum of patients responding to immunotherapies.
• BiCKI is the 2nd generation of PD-x inhibitors to increase the efficacy in hard to treat tumor types by addressing
untapped immune evasion mechanisms.
• OSE’s armed anti-PD-1 bispecifics are paving the way to reinstate sustained adaptive and innate immune responses.
Morning Refreshments / Poster Presentations
Engaging multiple cell populations within immune system with a single mAb: designing Swiss Army knives to fight cancer
ROMAN IVANOV, Vice-President, R&D, BIOCAD
• PDL1/CD47 mAb: restoring Teff response and phagocytosis
• PD1/GITR mAb: shifting the Teff/Treg cell balance
• IL15/PD1 mAb: potentiating Teff and NK responses
• Overcoming stability and manufacturability issues
• Cell-based assays for IO bispecifics
• Selection of in vivo models for IO bispecifics
Advancing t cell engaging antibodies for immuno-oncology
JOHN DESJARLAIS (Reserved), Senior Vice President, Research and Chief Scientific Officer, Xencor
Lunch
Novel antibodies beyond PD-1 therapy for cancer immunotherapy
SONIA QUARATINO, Chief Medical Officer, Kymab
An engineered IgG1-IgM tp fusion for enhanced CDC activity
SHIRLEY PETERS, Principal Scientist, UCB
• IgG1-IgM tp fusion promote IgG1 hexamerisation
• Engineering tp fusion leads to on-target hexamerisation.
• On-target hexamerisation results in enhanced C1q recruitment which translates to enhanced CDC activity
Novel multi-drug immuno-oncology and targeted thearpy combinations lead to synergy in preclinical models of B-cell malignancies
EMMANUEL NORMANT, VP Preclinical Sciences, TG Therapeutics New York
• Drug combinations are critical for efficacy in oncology. TG Therapeutics is building a “combinable” pipeline in order to increase the depth of response, decrease the instances of resistance, and tackle financial toxicity.
• The presentation focuses on datasets from in vitro and in vivo preclinical models that demonstrates synergy. The drugs used are the anti-CD20 antibody ublituximab, the PI3K inhibitor umbralisib, and the novel CD47-CD19 bispecific antibody TG-1801.
• We show here that targeting the innate CD47 checkpoint increases the efficacy of antibody-dependent cellular toxicity (ADCC) and phagocytosis (ADCP) driven by the anti-CD20 antibody ublituximab.
• The anti-tumor activity of the ublituximab and umbralisib “U2” combination is also enhanced with the anti-CD47 bispecific antibody, TG-1801, warranting clinical trial evaluating this triple-therapy.
Engineering a novel check point blockade
STEFAN GLÜCK (Reserved), VP GMA, Celgene
Chair’s Closing Remarks / Conference Close