We present a platform of brain-targeting shuttles comprising differentiated VHH panels binding TfR, CD98hc, or both, with optimized dual shuttles providing an additive increase in brain uptake over either individual shuttle. We first optimized these shuttles for brain delivery of antibodies, followed by optimization of our anti-TfR shuttles for oligonucleotide payloads, including siRNAs and antisense oligonucleotides (ASOs). Our lead shuttles are highly efficient in brain transport and meet developability criteria.

Interleukin-7 (IL-7) is essential for immune cell development, survival, and homeostasis, making this cytokine an attractive therapeutic target. The anti-IL-7 antibody M25 antagonizes cytokine activity in vitro but paradoxically potentiates cytokine activity in vivo. We assessed the biophysical and immunomodulatory effects of M25 and showed how this antibody can be leveraged to enhance T cell therapies. Our insights reveal the underlying basis of antibody-induced cytokine potentiation, informing next-generation immunotherapeutic design.

The rapid evolution of AI is reshaping antibody drug discovery, opening opportunities to move beyond the traditional paradigm of screening and optimization toward the computational generation of antibodies with desired properties. De novo antibody design has emerged as a particularly promising frontier, where generative models can explore sequence and structural space and propose novel molecules tailored to specific therapeutic targets. In this presentation, I will discuss recent advances in AI-driven de novo antibody generation and their integration into the drug discovery process.