Main Conference Day 2 - BST (British Summer Time, GMT+1)
The talk will focus on Specifica’s design of tools and strategies to improve the pH sensitivity of existing antibodies and select antibody leads with differential pH binding.
Camelid derived VHH domains are versatile building blocks for the construction of multifunctional antibody architectures. In this talk, I will present examples on how VHHs can be exploited for the activation of immune cell subsets by engineering efficient effector cell engagers as well as by constructing cytokine mimetics. I will also give insights on a novel library approach for the isolation of fully humanized VHH domains following camelid immunization.
Multispecific antibodies offer unique opportunities through the combination of binding arms to different epitopes or antigens. These engineered antibody formats can result in specificities or functions that are unattainable to a classical monovalent antibodies. To generate successful drugs, multispecific antibodies need to be safe and active but also developable and manufacturable. This presentation explains how we screen through large panels of multispecifics that meet all these requirements.
Latest update with validation data of Explorer; a novel Diverse Modular Antibody Platform that combines phage and mammalian display to deliver a large diversity of functional developable (multispecific)antibodies to your target. The modular system of the library allows HT IgG functional screening and our unique propriety mammalian display technology enables quick optimization of functional properties and developability of your molecules (including multi-specifics) in the final desired therapeutic format. Explorer provides a shortcut to develop high quality functional developable bispecific molecules faster to the clinic.
ISB 1442 is a bispecific biparatopic antibody targeting CD38 and CD47 for the treatment of relapsed/refractory multiple myeloma in clinical trials. The co-crystal structures of the two anti-CD38 Fabs with CD38, reveal atomic level details of their unique epitopes. Combined with negative staining electron microscopy, this explains the unique mechanism of action of ISB 1442 and superior killing potency, compared with Daratumumab, against both CD38low and CD38high cancer cell lines.
Targeted fluorescence-guided surgery (FGS) is set to play a pivotal role in the intraoperative management of solid paediatric tumours. Short-wave infrared (SWIR) imaging has shown advantages over conventional near-infrared I (NIR-I) imaging with higher tumour-to-background ratios and improved image quality. This presentation highlights the potential of GD2-targeted SWIR FGS to enhance neuroblastoma surgery by combining the specificity of anti-GD2 antibodies and the advantages of SWIR fluorescence guidance.
Tumour response in metastatic melanoma might be heterogeneous in which additional local treatment for nonresponsive metastases may be needed, especially in the case of brain metastases. Non-invasive imaging, for example with 18F-BMS986192 might be a technique to allow characterization of (brain) metastases to predict response.
With limitations of conventional imaging and biopsy, accurate and noninvasive techniques to risk stratify patients with renal masses remain an unmet need. Girentuximab is a moncolonal antibody that has a high affinity for carbonic anhydrase IX, which is highly expressed in clear cell renal carcinoma (ccRCC). We report results from the ZIRCON trial that evaluated 89Zirconium-girentuximab PET/CT imaging for detection and characterization of ccRCC, showing that it is a highly accurate, non-invasive, well-tolerated imaging modality for this purpose with promising clinical utility and practice-changing implications.
This presentation will describe pre-clinical data from Regeneron’s new clinical approaches to enhancing anti-tumor efficacy of T cells, focusing on the combination of costimulatory bispecific antibodies with checkpoint blockade and T cell redirecting bispecifics. In addition, data from new classes of T cell targeted enhancement strategies in pre-clinical development will be discussed.
CD137 agonists have shown promise in the clinic, with emerging data indicating their potential to drive anti-tumour activity as conditional agonists. This presentation provides an overview of our preclinical data from our clinical stage CD137 bispecific antibody programs: FS120, a OX40/CD137 T cell dual agonist and FS222, a CD137/PD-L1 T cell re-director.
T-cell engaging bispecific antibodies have had tremendous success in treating hematologic tumors but have shown limited efficacy in solid tumors. Alternative strategies for engaging the immune system employing safe and tunable bispecific antibodies are needed to overcome the challenges of solid tumors. In this presentation, we describe the bispecific platforms developed at Rondo Therapeutics and how we plan to use these to treat solid tumors in the clinic.
T cell costimulation via CD28 signaling (Signal 2) enhances anti-tumor activity. However, solid tumors lack CD28 ligands. We hypothesized that tumor-associated-antigen x CD28 bispecifics could focus a strong Signal 2 in the tumor microenvironment. Such bispecifics enhanced T cell degranulation, cytokine secretion, and tumor-cell cytotoxicity only when coupled with TCR engagement (Signal 1). To promote a favorable therapeutic index, we also tuned bispecific formats and affinities to preferentially target cancer cells with high antigen expression relative to normal tissue.
Success of bispecific antibodies (bsAbs) in solid tumors is still limited due to the lack of (i) accessibility of the tumor site for immune effector cells, (ii) sufficiently tumor-specific target antigens and (iii) missing costimulatory “signal 2” to enable long-lasting T cell activation. Our approach overcomes these limitations by a combination of functionally interrelated bsAbs that target two different antigens on the tumor and the tumor vasculature, and stimulate CD3 and CD28 on T cells.