Solid tumors often lack expression of CD28 ligands, so we hypothesized that activation of CD28 signaling in the tumor micro-environment could be beneficial. We designed B7H3 x CD28 and PDL1 x CD28 bispecific antibodies that conditionally costimulate CD28 only in the presence of their respective targets and TCR engagement, and show that they enhance activity of either anti-PD1 antibodies or TAA x CD3 T cell engagers.

Multiple inflammatory disorders involves dimeric IL-17. To exclusively block the homodimeric version only, we used a small protein domain to engineer an Affibody based ligand trap that sequester IL-17 A/A with femtomolar affinity. The novel construct has demonstrated safety and efficacy more than two years in patients with plaque psoriasis.

Novel TCBs and next generation TCB approaches and an update on 4-1BB co-stimulation to boost TCB activity will be discussed.

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.

The design of multispecifiy antibodies is essential to combine superior efficacy and safety. NM21-1480 is a multispecific antibody fragment-based cancer therapeutic in phase 1 clinical testing, that potently stimulates anti-cancer immune responses through concomitant induction of 4-1BB-signaling and PD-L1 blockade in the tumor microenvironment. Careful selection of format, epitopes and affinities resulted in optimized activity and a favorable safety profile in non-human primates. Additional therapeutic approaches based on Numab’s MATCH^TM platform are presented.

Early R&D poses many questions and challenges when determining if a biotherapeutic enters the portfolio. In this presentation we will demonstrate how our new and interactive software tool, systematically investigates the therapeutic characteristics (e.g., format, half-life, affinity, mechanism of action) given target characteristics (e.g., target expression and turnover) necessary to achieve success criteria given the predetermined target profile (e.g., dose, administration, frequency) to help accelerate and de-risk your project.   

Harnessing the immune system has revolutionized cancer treatment, but toxicities limit their potential. Revitope develops T cell engagers (GATEs) designed to elicit an immune response focused entirely on the tumor. The split anti-CD3 paratope requires two antigens on the same cancer cell for activity and may enable greater tumor-specificity. Protein engineering, in vitro and in vivo activity measurements and emerging mechanistic understanding of the GATE technology is covered.

XPATs are masked TCEs that are preferentially unmasked to an active form in the tumor microenvironment by tumor-associated proteases. In mouse efficacy studies, masked XPATs targeting HER2 or other tumor antigens demonstrate efficacy similar to the unmasked, activated forms, while in cyno toxicity studies, the tolerated exposures (Cmax) achieved with masked XPATs are up to 500X higher than those achieved with the unmasked, activated forms.

Designed protein switches perform computations on the surface of cells, enabling specific targeting of tumor cells that express precise combinations of surface antigens. Proximity-dependent activation causes a conformational change only when all conditions are met on each individual target cell, allowing targeting in mixed populations even when off-target cells share common target antigens. The talk will cover design principles and in vitro data.

Tumor-targeted immune agonist antibodies increase the therapeutic index of cancer therapies. Using NGS-based discovery, we have created a large collection of human antibodies targeting a variety of tumor antigens and activating receptors on immune cells. Our lead program, TNB-383B (BCMAxCD3) is currently in clinical development for the treatment of multiple myeloma. In addition to CD3 T cell engaging bispecific antibodies, additional immune-stimulatory multi-specific antibodies developed at Teneobio will be discussed.

In the new era of complex modalities and COVID-19 pandemic, speed, capacity, Traditional hybridoma and phage display methods have failed to yield therapeutic antibodies against difficult targets like most GPCRs and ion channels. This presentation will introduce Berkeley Lights’ new Opto™ Plasma B Discovery 4.0 workflow that enables recovery of 1000s of hits by screening up to 100,000 plasma B cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally-characterized antibodies … all in just 1 week. By maximizing the diversity of antibodies through direct functional profiling of plasma B cells, the Opto Plasma B Discovery 4.0 workflow will allow users to tackle even the most challenging targets.

Oncolytic viruses selectively infect and replicate in malignant cells, ultimately leading to tumor cell lysis and tumor vaccination effects. Due to their oncotropism, oncolytic viral vaccines can serve as vectors for tumor-targeted delivery of immunomodulators. In this talk we will discuss the prospects of using OVs to improve tumor delivery of BiTEs, avoid off-tumor toxicities and possibly achieve synergistic anti-tumor effects.

Several recombinant cytokines have gained marketing authorization for pharmaceutical applications. Most cytokine products tend to be potently active at very low dose and the onset of side-effects may limit dose escalation to therapeutically active regimens. The antibody-based delivery of cytokine payloads to the site of disease represents an efficient strategy to increase the therapeutic index of these biopharmaceuticals. As a consequence, targeted cytokine are increasingly being considered for the therapy of cancer, of chronic inflammatory conditions and of other diseases. In this talk, we show the preclinical development and the clinical performance of targeted cytokines for cancer therapy.

Over the past 5 years Rapid Novor has perfected monoclonal antibody sequencing, and is now sequencing mAbs from polyclonal mixtures using REpAb®.  After successfully launching their proteogenomics based sequencing technology to deconvolute the immune response, the team has further evolved the technology and has derived the most abundant mAb sequences directly from rabbit blood using only proteomics. The talk will surround the development, progress and use cases for REpAb®.