Pharma BD landscape within the molecular glue space

With last week's Lilly / Magnet Biomedicine $1.3B deal, we're now up to 24 deals led by big pharma since 2020, totaling ~$27B in total disclosed deal values

What's causing all of these companies to jump in? Some thoughts:

Molecular glues, alongside PROTACs, are the two most clinically validated approaches within the targeted protein degradation (TPD) space.

At a high level TPD selectively degrades disease-causing proteins by linking them to E3 ubiquitin ligases, causing the cell's own protein disposal system to eliminate them

Benefits of this approach vs. traditional small molecules:

• Enhanced potency at lower doses, minimizing off-target effects and toxicity concerns
• Retain the favorable manufacturing economics (cost & scalability) of small molecules
• Can target "undruggable" proteins that lack active binding sites thus unlocking proteins considered inaccessible to traditional pharmacology

This last point is a huge opportunity. ~85% of the human proteome is considered "undruggable" to traditional biologics or small molecules. Only ~2-5% are both historically "druggable" and relevant to disease - meaning that the modern biopharma industry has largely been built on a fraction of potential targets. Expanding the druggable proteome has massive implications for treating diseases with huge unmet needs today, while opening hundreds of additional opportunities for the coveted 'first-in-class' tag.

Given the magnitude of the prize, Pharma has taken a multi-faceted approach - spinning up internal development efforts + partnering to fill gaps. In addition to the points above, the pace of partnerships can likely be explained by two factors:

• The TPD space is still very early (first clinical trial for rationally designed molecular glues was in 2020 - excluding MGs where glue-like properties were discovered ex post facto), and so a lot of technical expertise and know-how resides in biotechs that helped push the field forward out of academia (i.e. Monte Rosa flagged their know-how around geometric deep learning at JPM 2025)
• The modular nature of drug design in this space (similar to ADCs) rewards companies capable of rapid experimental iteration to identify synergistic properties - a strength of most biotechs versus Pharma