We have developed a bispecific antibody approach to selectively block the innate checkpoint CD47 on tumor cells. The most advanced program, CD19/CD47, is in Phase I for hematological malignancies. NI-1801 is a MSLN/CD47 bispecific harnessing the same mode of action and is about to enter clinical trials for the treatment of solid tumors. Multiple aspects of the preclinical development of NI-1801 will be discussed, including toxicology, manufacturing, and assay development.

•    NEW DATA - This Presentation Contains New Data

An elegant highly active transposase equipped with epigenetic readers carries expression units to most active spots in the host genome providing desired expression levels and stability. With this foundation the focus for screening producer clones is entirely on correct pairing and PTMs. We will discuss how this system is adapted to various formats removing a critical bottleneck for bispecifics during clinical development.

Therapeutic approaches based on Numab’s MATCHTM platform are presented, which aim at multi-specific therapeutics with improved efficacy and safety profiles. An update on NM21-1480, our scMATCH3 PD-L1/4-1BB, currently in phase I clinical testing, will be presented. The presentation will focus on the importance of affinity, valency, and epitope selection to optimally address target biology. In addition, the design and preclinical proof-of-concept data on T cell redirecting multi-specifics against MSLN, in combination with NM21-1480, will be discussed.

Innate Cell Engagers (ICE molecules) redirect and activate NK cells and macrophages to kill tumor cells via ADCC and ADCP respectively. The ICE molecules are built on the Redirected Optimized Cell Killing (ROCK) platform and target CD16A, one of the most potent activating receptors on the innate immune cells. They have demonstrated high affinity binding which has been shown to be superior to conventional and Fc-enhanced monoclonal antibody therapeutics. The unprecedented binding affinities allow generation of pre-complexed NK cells without engineering. The modularity of the ROCK platform allows the continuous development of new ICE molecules with customized properties.

VHH are fast becoming accepted as alternatives to standard antibody-based biotherapeutics due to their improved stability, ability to address difficult-to-reach epitopes, and modularity - facilitating the combination of different specificities in a single product. This presentation will expand on the recent advances in the field of VHH-based therapeutics and highlight particular therapy applications where a naturally monovalent antibody domain structure can be combined to generate the next generation of biologics.

TriTAC molecules are T cell engagers (TCE) designed to have a small size for enhanced tissue penetration, in vitro and in vivo molecular stability, and a novel mechanism for half-life extension to limit dose-limiting side effects, thereby improving the therapeutic window. Four TriTACs (HPN424, HPN536, HPN217, and HPN328) are currently in phase 1 dose-escalation trials in both solid and liquid tumors. Key IND-enabling preclinical and nonclinical studies in support of these first-in-human phase 1 trials will be reviewed. Translation of preclinical and nonclinical observations and proof-of-biology of the TriTAC platform in human patients will also be highlighted.

FS120 is a novel tetravalent bispecific antibody incorporating OX40 binding into the Fc-region (termed an Fcab) and CD137 Fabs in a natural human IgG1 antibody. In this presentation key preclinical data and a status update from the ongoing clinical trial will be discussed.

Despite treatment advances, multiple myeloma remains incurable and there is a substantial need for breakthrough therapies. Ichnos is investigating different immune cell engagers and modulators targeting CD38 to bring new therapeutic concepts in multiple myeloma. First-in-class bispecific antibodies CD38 x CD3 and CD38 x CD47 will be discussed.

We present a technology platform that automates R&D of immunotherapeutic modalities such as bispecifics, CAR-Ts, and recombinant viruses. The platform facilitates cell line development, viral production, and design of complex proteins including assessment of potency, efficacy, and developability of bispecific candidates. Use cases show how the platform enables rAAV production, CAR-T cell line development, and systematic discovery, optimization, engineering, and production of complex proteins.

RO7297089 is a bispecific antibody (IgG-scFv) targeting B cell maturation antigen (BCMA) and CD16a (FcRIIIA) that is being developed for the treatment of multiple myeloma (MM). BCMA is exclusively expressed on plasmablasts and differentiated plasma cells (PCs), and is over expressed on malignant PCs in MM patients. CD16a is expressed on natural killer (NK) cells, monocytes, and macrophages. Here, we characterized the mode of action and safety profile of RO7297089 in vitro and in cynomolgus monkeys.

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

Bispecific T cell-engaging receptors (TCER) are fusion proteins consisting of an affinity-maturated TCR and a humanized T cell-recruiting antibody coupled to an effector function-silenced IgG Fc part. The design of TCER molecules allows redirection of T cells towards tumor tissues with expression of designated peptide-HLA targets as validated by our target discovery engine, XPRESIDENT. We present preclinical data supporting proof-of-concept of this novel class of bispecific T cell engagers.

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

• NEW DATA - This Presentation Contains New Data

We have developed a novel T cell bispecific platform that has superior anti-tumor efficacy to conventional CD3 T cell redirect antibody with improved T cell activation status and tumor microenvironment. Detail of the protein engineering and preclinical result will be presented.

• NEW DATA - This Presentation Contains New Data​