Zoe Biosciences - PAI-1 Antibody Therapeutics

Background

Zoe Biosciences is an early-stage preclinical biotech developing breakthrough therapeutics for age-related diseases and aging itself focusing on drug targets that are well-validated both for longevity and aging-related diseases, high-leverage (pleiotropic), and low-hanging. They currently have a pipeline with two assets, both with the potential to extend human healthspan. The first program is PAI-1 biologic inhibitors with high target selectivity and affinity, relevant for diseases including elevated FGF23 syndromes and metabolic disorders. The second program is APJ small-molecule agonists for similar age-related indications. The two assets can also be advanced in combination.

Aims, Hypothesis & Results

PAI-1 - Zoe Biosciences' lead antibody was raised against human PAI-1 and is reactive towards human, mouse, and rat PAI-1. It has a high affinity KD (0.2 nM) and converts active PAI-1 to substrate PAI-1, which has been confirmed in vitro and in vivo. The antibody is undergoing early preclinical/POC testing. Additionally, they will use these early tests to finalize indication selection. Zoe has PAI-1 nanobodies they are advancing as well.

APJ - Zoe has a lead small molecule with good PK and efficacy in rodent models with no off-target or toxicological effects in preclinical models (non-GLP).

Timeline

With the seed round funding, Zoe plans to advance its PAI-1 antibody program by selecting a lead candidate, optimizing it for subcutaneous delivery, and filing for fresh IP. The company also intends to formalize an exclusive licensing option with Sanford Burnham Prebys for Dr. Layton Smith's APJ agonists and complete preclinical studies to finalize indication selection for sarcopenia/cachexia.

Advancing PAI-1 and APJ Drug Development
Duration: 24 months

‍VitaDAO Board Evaluation Writeup

PAI-1 is genetically validated in humans, and their CSO has done high quality research on it. APJ is validated in the sense BioAge is working on the same target. Both MOAs are applicable to both age-related disease and longevity, with the potential to treat many disease indications and potentially prevent aging in general. PAI-1 and apelin synergistically antagonize each other, which would potentially offer a combined treatment approach at later stages of development. The company has a strong IP portfolio with exclusive licenses for multiple PAI-1 monoclonal antibodies (mAbs) and APJ agonists. There are competitors and previous failures targeting PAI-1 with small molecules. Zoe has promising efficacy studies in mice with a murine antibody. It remains an uncertainty if a chronic mAb treatment at an affordable price will be a viable approach. Creating a systemic PAI-1 inhibitor could bring unforeseen consequences, considering PAI-1 has diverse functions on different tissues. There are many directions this project can go, with a need to zero in on the best indication.