Izokibep is a novel Affibody molecule engineered to develop a potentially best-in-class IL-17A blocking ligand trap with femtomolar binding affinity and small molecular size that translates to high therapeutic efficacy in patients with psoriasis, psoriatic arthritis, and hidradenitis suppurativa. Excellent three-year safety and efficacy data support both the IL-17 program as well as the Affibody drug class in general. Izokibep is now in late-stage clinical development.

IL-35 is a strong multi-pathway anti-inflammatory cytokine, but it is difficult to produce. Our computational structural analyses identified the intracellular binding site of IL-35, succeeding large-scale production by mammalian cells. For autoimmune diseases, current therapies are treating the symptoms. We engineered lymph-node targeted IL-35, which achieves therapeutic effects in rheumatoid arthritis and directly suppresses activated immune cells. IL-35 would offer long-term treatment-free periods for patients with many inflammatory diseases.

• IL-35 induces Tregs, Bregs, tolerogenic DCs, M2 macrophages
• IL-35 is reportedly effective in many inflammatory diseases (RA, T1D, MS, scleroderma, AD, ILD, IBD, infections, stroke)
• New cytokine-based therapies for autoimmune diseases

Biomarker-driven therapeutic intervention increases the probability that a novel medicine will benefit the right patient population at the right time. PriveBio is advancing a pipeline of first-in-class therapeutics built in tandem with a precision medicine framework for testing in patients to achieve efficient proof-of-biology and early proof-of-concept in fibro-inflammatory diseases to ultimately achieve disease modification.

TNFR2 is highly expressed on immunosuppressive regulatory T cells (Tregs) that modulate immune homeostasis. We developed a TNFR2-selective agonist, TRB-061, that demonstrates potent in vivo Treg augmentation, providing protection in preclinical inflammatory models. Our deep biology platform reveals the molecular details of TNFR2 agonism on Treg activation and expansion. Interrogation of TRB-061 signaling suggests differentiated clinical opportunities that position TRB-061 as a promising Treg modulator for inflammatory and autoimmune indications.

TAR DNA binding protein-43 (TDP-43) is a hallmark of devastating neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recently, we reported that a monoclonal antibody (mAb) targeting TDP-43, ACI-5891, conferred neuroprotection in ALS/FTD models. To improve brain penetration of mAbs which necessitates high dosing regimens, we created and evaluated the potency of a single-dose vectorized full-length antibody delivered by adeno-associated virus in mouse model.

The genetic code expansion technique enables precise incorporation of noncanonical ncAAs carrying diverse chemical functionalities into proteins expressed within living cells. This technology offers new opportunities to precisely engineer next-generation biotherapeutics with new capabilities. This presentation explores recent strides made in enhancing the scalability of this approach, and its application in generating homogeneous site-specific antibody conjugates, and precisely modified adeno-associated virus capsids for GT applications with heightened precision and efficacy.

From infectious disease to snake venom, mutational diversity of target proteins frequently limits the utility of vaccines and therapeutics. Here we present two examples of in vivo elicitation of broadly neutralizing antibodies. In the case of vaccines, we review how this enables pan-influenza and pan-coronavirus vaccines. In the case of snake envenoming, we review how a cocktail of two bnAbs and an inhibitor enables protection against hundreds of snake species.

Numerous immunotherapy modalities leverage T cells’ unmatched ability to recognize and kill tumor cells; however, clinical responses in cold tumors have been limited. Recently, T cell engagers targeting peptide-HLA molecules (pHLA) have demonstrated transformative responses in these indications. We’ve developed 3T-TRACE to rapidly identify pHLA antigens recognized orphan T cells from patient tumors, and 3T-PRIME, a TCR mimetic platform to expand the development of this promising modality.

Atrial fibrillation and the risk of its lethal complications are worsened by atrial fibrosis. Our recent study implicates osteopontin, which is encoded by Spp1, and secreted by atrial macrophages in this fibrosis. We now find that silencing Spp1 in this subset of cardiac macrophages using an engineered antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib, thus offering an immunotherapy for this common arrhythmia.

GLP-1 and GIP are incretin hormones, whose primary physiologic property are to stimulate postprandial insulin secretion. GLP-1, and more recently GIP, analogues have been used as appetite suppressants to effectively treat obesity. Ironically, genetic disruption of GLP-1 and GIP—which like insulin is overexpressed in obesity—prevents obesity, and antibodies to GIP or its receptor (GIPR) have been shown to effectively treat obesity independent of appetite by decreasing intestinal nutrient absorption and adipocyte lipid storage. Because GIP overexpression is regarded as one of the etiologic factors of obesity, abrogation of GIP signaling may represent a more logical approach for obesity therapy.

Mast cells (MCs) are immune cells that drive or contribute to the pathophysiology of allergic, inflammatory, autoimmune, and fibrotic disorders. Activation of the KIT receptor by its sole ligand, SCF, is required for MC survival. Reduction of MCs through the KIT-directed inhibitory antibody barzolvolimab has shown promising clinical activity in chronic urticarias and prurigo nodularis. SCF neutralization is expected to similarly decrease MC numbers. TSLP neutralization has demonstrated clinical activity in asthma. CDX-622 is a bispecific antibody that simultaneously neutralizes SCF and TSLP and may offer enhanced therapeutic benefit by targeting complementary pathways that drive chronic inflammation.

How we treat heart disease has evolved significantly in recent years. Monoclonal antibodies and RNA-based therapies have dominated new drug development, and CRISPR-based gene editing has entered clinical trials. Large-scale genomics has identified numerous novel proteins for these platforms to target, and nowhere has this been more evident than in hyperlipidemia, where over a dozen new therapies have been developed for four genetically validated therapeutic targets: PCSK9, Lp(a), ANGPTL3, Apo-CIII.

RSV causes respiratory infections in both children and adults globally. This study investigated using anti-idiotypic antibodies as a booster vaccine for RSV by targeting a broad RSV-neutralizing antibody RB1. Cryo-EM analysis confirmed the Anti-ID mimics the binding of RSV prefusion F protein to RB1. Mice primed with RSV-F and boosted with Anti-ID showed specific B-cell responses. This suggests Anti-IDs have potential as booster vaccines for RSV and other infectious diseases.