Main Conference Day 2Tuesday, 15 December 2026 - PT (Pacific Time, GMT-08:00)

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration and pathological TDP-43 mislocalization, aggregation, and loss of nuclear function. We developed an AAV-delivered ScFv that selectively targets cytoplasmic TDP-43 while preserving native protein. By binding the C-terminal domain, it restores nuclear function, reduces aggregates, and improves protein homeostasis. Preclinical studies and biodistribution data demonstrate therapeutic potential, supporting further clinical development as a disease-modifying treatment for ALS and other TDP-43 proteinopathies.

The inability of antibodies to penetrate the blood–brain barrier is a major limitation to their use in CNS therapeutics. We developed dual-targeting bispecific antibodies that engage the transferrin receptor and a neuronal cell-surface protein, enabling increased CNS accumulation and enhanced neuronal localization. Conjugation of antisense oligonucleotides to these bispecific antibody shuttles enabled efficient gene silencing across multiple CNS regions and neuron-specific gene modulation.

Neutralization of genetically diverse viruses can be enhanced by molecules that combine multiple copies of antibodies with various specificities. Here, we discuss the neutralization resilience of such molecules against HIV, as well as pharmacokinetics considerations in higher-order model species to translate IgG-like exposure into broad viral neutralization at low concentrations.

Progressive fibrosis is a key driver of chronic disease progression, with limited therapeutic options. Although TGF-β1 blockade shows potential, safety and pharmacokinetic challenges have hindered clinical development. We developed a pH-dependent anti-latent TGF-β1 recycling antibody to overcome target-mediated clearance. The anti-latent TGF-β1 recycling antibody demonstrated prolonged exposure in cynomolgus monkey and suppressed fibrosis in multiple mouse models, supporting latent TGF-β1 targeting with recycling antibody technology as a promising therapeutic strategy for fibrosis-related indications.

Protein misfolding diseases demand antibodies that selectively target scarce, pathological protein conformations while sparing abundant native forms. Paradox Immunotherapeutics employs a validated, structure-based approach to predict misfolding-specific epitopes, enabling precise clearance of disease-causing proteins. Modality-agnostic in discovery, we're eager to explore partnerships advancing high-value targets in systemic amyloidosis and beyond.