The presentation will discuss structure and mode of action of BiTE antibody constructs, provide an update on the development of the BiTE antibody platform, and showcase clinical data for a novel BiTE antibody construct targeting AML.

Triclonics Engagers are multivalent molecules with three Fab arms that bind up to three different targets and are designed to have long half-life, stability and low immunogenicity. The presentation will highlight the novel features and therapeutic opportunities of the platform, and functional screening of thousands of Triclonics Engagers in T cell assays.

This presentation will describe key preclinical data from Regeneron’s clinical stage T cell-redirecting bispecific programs (REGN1979, REGN4018, REGN5458), as well as status updates from the ongoing clinical trials. In addition, data from new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy, focusing on costimulatory bispecifics, will be discussed.

Tumor-targeted immune agonist antibodies increase the therapeutic index of cancer therapies. Using NGS-based discovery with humanized rats, we created a large collection of fully human antibodies targeting a variety of tumor antigens and activating receptors on immune cells. Our lead program, TNB-383B (BCMAxCD3) is currently in clinical studies for the treatment of multiple myeloma. In addition to CD3 bispecific antibodies, immune-stimulatory platforms recently developed at Teneobio will also be discussed.

This presentation will describe preclinical data on the potent anti-tumor activity of FS120, a first-in-class dual-agonist, tetravalent bispecific antibody targeting CD137 and OX40. FS120 delays tumor growth by improving the activation and proliferation of T cells. FS120 can activate both CD4⁺ and CD8⁺ T cells in an FcγR-independent mechanism, therefore promoting focused immune stimulation. F-star’s proprietary mAb²™ technology platform will also be discussed. 

We developed MGD019, a bispecific DART protein designed to maintain full blockade of both PD-1 and CTLA-4, while limiting Fc-mediated effector function. MGD019 demonstrated increased CTLA-4 blockade on dual-expressing cells that recapitulate tumor-infiltrating T lymphocytes, and T cell co-activation in vitro at least as potent as combination of ipilimumab and nivolumab, although with a somewhat different pattern. MGD019 was well tolerated in cynomolgus monkeys, while providing evidence of CTLA-4 blockade. Preclinical pharmacology and additional information relevant to a Phase 1 clinical trial will be discussed.

Targeting of the PD-1/PD-L1 axis with monoclonal antibodies is the basis for cancer immunotherapy and has transformed the therapy of various cancers. However, many patients still do not respond to cancer immunotherapy and relapse after treatment. We have generated bispecific PD-1/TIM-3 and PD-1/LAG-3 checkpoint inhibitory antibodies with superior properties over PD-1 monotherapy as well as a novel PD-1 targeted PD1-IL2v immunocytokine to specifically target PD-1+ T cells. The design and preclinical properties of these PD1-X molecules will be discussed in depth during this presentation.

PRS-343 is a first-in-class bispecific antibody-Anticalin fusion protein targeting HER2 and the costimulatory immune receptor 4-1BB on T cells. This presentation will describe the rational for tumor localized 4-1BB agonism with PRS-343 together with supporting preclinical and clinical data. PRS-343 is currently in early clinical testing where it has demonstrated a good safety profile and single agent efficacy.

ATOR-4224 is a novel tumor-targeted dendritic cell (DC) activator, acting as an endogenous neoantigen delivery vehicle to prime tumor-specific T cells. Simultaneous targeting of patient-specific tumor debris to DCs and DC activation leads to T cell priming, activation and induction of an anti-tumor response, with potential to turn cold tumors hot. ATOR-4224 is built in the RUBY format, a novel plug-and-play tetravalent bispecific format with favorable developability properties.

Safe and selective blockade of the ubiquitously expressed immune checkpoint CD47 can be achieved using bispecific antibodies (bsAb) incorporating two arms with different affinities. This dual targeting concept has been validated in different preclinical models of human cancer and applied to different tumor associated antigens. This approach is now been explored in patients with a bsAb generated using our kappa-Lambda body platform.

Initial successes in cancer immunotherapy largely relied on therapeutics that inhibit a specific receptor wherever it exists. This can lead to anti-cancer immunity and autoimmunity, and consequent limitations in the clinical benefit. Novel approaches that leverage an increasing appreciation for immune biology, biophysics and advances in therapeutic engineering are likely to be important. These principles and a case study of an Anti-PD-L1 x IL-15 IgM therapeutic antibody will be presented. 

Emicizumab is a factor (F)VIII-function mimetic therapeutic antibody for treating persons with haemophilia A (PwHA). Currently, it plays a central role in treating PwHA, although there is some room for improvement in dosing frequency/volume and/or haemostatic activity to achieve non-haemophilic status. In this presentation, a novel antibody engineering technology to further improve the property of emicizumab will be presented.

A next-generation FVIII-mimetic bispecific antibody for treatment of Haemophilia A was developed based on the robust and versatile arm-exchange DuoBody® technology. The preclinical route from idea to antibody screening, engineering, and final selection of the development candidate, Mim8, and manufacturability aspects of using the arm-exchange technology will be presented. In vivo studies highlighting potency and efficacy of Mim8 in a rodent bleeding model will conclude the presentation.