Xencor has used its bispecific antibody platform to create a second type of T cell engager, TAA x CD28 bispecific antibodies, which safely promote the activation of signal 2 in T cells via tumor-selective agonism of CD28. This new modality synergizes with classic TCEs and checkpoint blockade to promote greater T cell activation and expansion. In parallel, potency-reduced cytokines (signal 3) bring additional opportunities to activate T cells to maximize therapeutic benefit.

Lonza has applied it’s 35 years of CMC experience in Biologics to develop an end-to-end comprehensive DS/DP DNA to IND strategy in 13 months. This presentation will highlight key approaches and technologies that enable this timeline. Case study examples will be shared for application in vector, process, analytic and formulation development of bispecific molecules during pre-clinical development.

This presentation will describe key preclinical data from Regeneron’s new clinical approaches to enhancing anti-tumor efficacy, 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 bispecifics in pre-clinical development will be discussed.

The therapeutic window of T cell engagers for solid tumors is limited by expression of tumor-associated antigens (TAA) on solid tumors as well as on healthy tissue. Triclonics, Merus trispecific antibody platform, provides the technology for solid tumor-specific T cell engagers. The solution is a trispecific TAA1×TAA2×CD3 T cell engager co-targeting two tumor targets that are only co-expressed on solid tumors and not on healthy tissue. This paper discusses Triclonics: common light chain trispecific antibody platform, the therapeutic opportunities of trispecific T cell engagers, and dual-targeting: Avidity driven tumor selectivity.

Developing bispecific antibodies and fusion proteins for combination therapy of solid and hematological tumors. Co-stimulatory fusion proteins including FAP-4-1BBL, CEA-4-1BBL, and CD19-4-1BBL for combination with T cell bispecific antibodies. Novel approaches for co-stimulatory pathways.

We focus on engineering antibodies that replicate the function of Wnt pathway proteins to repair tissue damages. We have developed technologies to modulate the Wnt pathway, Wnt mimetics, and R-spondin mimetics, that provide robust and flexible platforms. Our strategy is to harness the full breadth of potential by identifying disease states responsive to Wnt pathway modulation, design specific antibodies, and advance candidates into development in indications with unmet needs.

The use of recombinant IL-2 as a therapeutic has been limited by significant toxicities despite its ability to induce durable tumor-regression in patients. We have developed a novel bispecific heavy-chain only antibody which binds to and activates signaling through the IL-2ßγ receptor complex, expanding T and NK effector cells while avoiding IL-2Ra and the toxicities associated with the trimeric IL-2 receptor.

New therapies that promote antitumor immunity have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways. However, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new molecules that could be exploited in the next generation of immunotherapy. Natural Killer (NK) cells can recognize and destroy cancer cells. NK cells also produce cytokines and chemokines that shape a multicellular immune response, which can lead to a long lasting control of tumors. We have previously reported on Innate Pharma's proprietary platform for developing next-generation, multi-specific NK cell engagers to treat certain types of cancer called ANKET (Antibody-based NK cell Engager Therapeutics). We are now reporting on tetra-specific ANKET molecule, which is the first NK cell engager technology to engage two NK cell activating receptors, NKp46 and CD16, a tumor antigen and the interleukin-2 receptor via a single molecule. ANKET molecules were more potent than therapeutic antibodies targeting the same tumor antigen in pre-clinical models. They had similar pharmacokinetics to IgG1s and no off-target effects. We will present an update on our ANKET platform as a new generation of therapeutic molecules against cancer.

This presentation will introduce Berkeley Lights’ Opto™ Plasma B Discovery 4.0 workflow that enables recovery of 1000s of hits by screening up to 100,000 plasma cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally-characterized antibodies all in 1 week. By maximizing the diversity of antibodies through direct functional profiling of plasma cells, the OPBD 4.0 workflow allows users to tackle even the most challenging targets.

The OmniAb platform couples cutting edge screening and data mining technologies with highly validated antibody generation systems. This session will provide an overview of OmniAb and offer a few examples of how the platform can be implemented for a variety of antibody discovery campaigns.

Cytokines are secreted immunomodulatory proteins that activate key signaling pathways by receptor dimerization.  While many cytokines have been approved as therapeutics, native structure restricts their therapeutic potential to pathways activated by their cognate cytokine receptors.  At Synthekine we have implemented a platform to dimerize native and non-native pairs of cytokine receptors using single domain (VHH) antibodies, allowing us to design synthetic cytokine mimics that generate targeted and modulated signals on key cell types to improve on first-generation cytokine therapeutics.

Successfully developing novel highly-targeted protein therapies for injection and inhalation requires comprehensive platform understanding. Our Anticalin platform has translated to clinical successes and we will present the key features of our advanced platform including accelerated discovery, a comprehensive developability framework, and sophisticated data science capabilities.

The best way to generate advanced biologics with requisite activity and drug-like properties is to generate large panels of leads with diversity along several axes: sequence, epitope, affinity and geometry. A case study details generation of diverse panels of lead antibodies against two targets and characterization for binding, function, kinetics and developability. A matrix of 200 bispecifics was generated, resulting in multiple lead candidates with favorable expression, potency and stability.

Biparatopic antibodies are designed to simultaneously bind two non-overlapping epitopes on the same target and are promising next-generation antibody formats. We review our approach to biparatopic antibody development and characterization, including design tools and high-throughput screening techniques. As a case study, we review the mechanisms of action of zanidatamab, an anti-HER2 biparatopic antibody, with improved activity and unique functionality not observed with the parental or combination of parental antibodies.

This presentation discusses the rationale and initial results of studies that are evaluating bispecific and biparatopic antibodies in esophagogastric cancer, including several novel anti-Her2 therapies.

Bispecific antibodies represent a major class of molecular modality in current global biopharmaceutical development. Based on FIT-Ig, EpimAb's bispecific antibody technology, a number of therapeutic molecules have been developed and several are in clinical development, including cancer cell targeting cMET/EGFR (EMB-01) and dual check-point PD-1/LAG-3 (EMB-02). Current data reveals more aspects concerning the clinical validation of the FIT-Ig technology, as well as the synergistic mechanism of these dual-targeting bispecific antibodies.