OxMIF, the disease-related isoform of macrophage migration inhibitory factor (MIF), was discovered by OncoOne’s founders as an attractive target for the development of novel treatments for patients with solid tumors due to its exclusive presence in diseased tissue. OncoOne is combining their extensively engineered lead therapeutic candidate targeting oxMIF with a corresponding radiolabeled anti-oxMIF antibody as companion diagnostic. This combination will guide future combination trials and enable the targeted treatment of patients with oxMIF-positive tumors.

The costimulatory immune receptor CD137 has been recognized for its potential as a drug target alongside checkpoint inhibitors, but this promise has not been realized for patients due to toxicity and limited efficacy of current biologic-based therapies. Bicycles are small, structurally constrained peptides discovered via phage display and optimized using medicinal chemistry. We have developed BT7480, a multifunctional molecule that induces tumor antigen-dependent agonism of CD137 that leads to complete tumor regressions and subsequent resistance to tumor re-challenge in syngeneic mouse models.

Using cutting-edge gene editing and targeted replacement technologies, we have engineered the Singularity Sapiens Mouse that produces heavy chain only antibodies from the entire human VH repertoire, but none of the conventional antibodies (IgM/IgD/IgG/IgE/IgA). A rapid sequence-driven pipeline has been established to profile, select, clone, and express nanobodies for large scale high-throughput screens to identify target-specific binders for developing nanobody based next generation biologics, including multispecific antibodies, intrabodies, and CAR-T therapies.

Mesothelin is shed from cells by the action of proteases that cut close to the membrane. MAb15B6 binds to the protease-sensitive region of mesothelin proximal to the membrane, inhibits mesothelin shedding, and makes a very active CAR T cell that is superior in activity in mouse tumor models to CAR T cells made with mab SS1 that binds to a distal epitope. MAb 15B6 is humanized and ready for clinical development.

Our laboratory has developed, optimized, and translated mesothelin-targeted CAR T cell therapy. We have treated 41 thoracic cancer patients (mesothelioma, metastatic breast, and lung cancers) with remarkable safety and anti-tumor efficacy. We further translated strategies to overcome barriers to successfully translating CAR T cell therapy for solid tumors. One such strategy already in the clinic for patients with pleural mesothelioma is combination immunotherapy with CAR T cells and checkpoint blockade (CPB) agents. Following demonstrated safety and efficacy of this approach, we translated PD1 dominant-negative receptor within the CAR T cell, patients are being treated in an ongoing clinical trial. These preclinical supportive rationales and clinical trial results will be presented.

This presentation will give an introduction to the TRuC T cell platform, and outline the advantages of TRuC T cells over CAR T cells in solid tumors. Details around the ongoing clinical trials with TRuC T cells will also be shared.

Here we describe a target identification and cross-reactivity screening platform (3T-TRACE) and its utility to identify novel, intracellular targets, and their corresponding T cell receptors (TCRs) for the treatment of solid tumors. We focus on patient tumor profiling to identify key TCR populations for our immune-response guided approach for target identification and the development of TCR-based therapeutics against broadly expressed novel targets. The described work highlights the utility of the platform to identify novel therapeutic targets in other disease areas including autoimmunity and the amelioration of disease in animal mouse models.

Protective immune responses and immunotherapies rely on T cell recognition of peptides presented in MHC class I and MHC Class II. Identifying MHC-presented peptides through immunopeptidomics provides opportunities to understand and modulate immune responses. We will highlight this powerful approach and how it can be used in drug discovery research for oncology and beyond.

The Major Histocompatibility Complex (MHC) is critical to the immune response. Immunitrack has world-leading expertise in manufacturing and studying MHC I and II molecules and their interactions with peptide epitopes. In this presentation we will present our capabilities within the MHC area and how they can be applied as the best starting point for generating MHC/epitope targeted therapeutics

eBAT (EGF bispecific angiotoxin) consists of full-length epidermal growth factor (EGF) linked to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) and to a genetically modified Pseudomonas exotoxin (PE). EGF and ATF direct the toxin to EGF receptors (EGFR) on tumor cells and to uPA receptors (uPAR) on tumor cells and cells in the tumor microenvironment (TME). In addition to killing EGFR+/uPAR+ cancer stem cells, eBAT promotes anti-tumor immunity by depleting immunosuppressive macrophages, promoting phagocytosis by myeloid dendritic cells, and altering the organization of the TME to allow infiltration of T cells.

TIGIT-Fc-LIGHT was designed to block all TIGIT-ligand interactions and provide broad immune co-stimulation to CD8+ T and NK cells via HVEM, and myeloid cells by LTBR. TIGIT-Fc-LIGHT does not depend upon DNAM-1 co-stimulation for activity, like TIGIT antibodies, and unlike DNAM-1, HVEM is not down-regulated on TIL in advanced tumors, nor directly inhibited by PD-1. We demonstrate this translates to TIGIT-Fc-LIGHT anti-tumor activity in PD-L1-low and CPI acquired resistant tumors.

At Alchemab, we are harnessing the power of the immune system to counter complex diseases. By mining the antibody repertoires of individuals who demonstrate exceptional resilience to disease we are able to pinpoint antibodies that are linked to improved outcomes or delayed disease onsets. Selected antibodies are characterized by function and target specificity before entering preclinical disease models. We will show examples to illustrate the platform’s applicability across our discovery pipeline, including Infection, Oncology, and Neurodegeneration.

Membrane proteins are important drug targets yet are notoriously difficult to work with. Our proprietary approach, Salipro DirectMX, incorporates membrane proteins directly from cells into lipid Salipro nanoparticles. Salipro DirectMX presents new opportunities for de novo development and characterization of biologics and small molecule drugs. We will present our latest developments and showcase how CXCR4 oligomers can be reconstituted into Salipro-CXCR4 nanoparticles, enabling new possibilities for development of oncology therapeutics.

The advanced biological drugs seeking for more therapeutic benefit in smaller patient populations are behind a paradigm shift toward precision medicine. However, these drugs rarely reach the brain at relevant concentrations and patient-to-patient variability can be high, so patients with brain diseases insufficiently benefit from the current biotechnological progress. The field of molecular imaging and image guided neurointerventions are rapidly unfolding and they provide an outstanding opportunity especially for early phase clinical trials to get report on how much of the drug got to the brain and where it is exactly located and if it overlaps with pathological changes. In this way the drug administration could be continuously improved until therapeutic effects are achieved. I will talk about how image guidance allows to see advantages of various routes of delivery of therapeutic agents to the brain.

Tonic signaling by inhibitory co-receptors, even in the absence of ligand engagement, results in constitutive suppression of T cell activation. This potentially reduces the effectiveness of immunotherapeutics, as tonic signaling at cell contacts can not be affected by blockade due to the antibodies relatively small size. We re-engineered blocking antibodies targeting checkpoint receptors by inserting stable non-immunogenic mucin into the Fc hinge domain. This PLUS antibody format increases its size and upon receptor engagement forces the immune checkpoint receptor out of cell contacts. These antibodies are expected to suppress both tonic and ligand-dependent signaling to further improve immune checkpoint blockade.