Interestingly, Opus 4.8, and not Mythos Preview, succeeds on TNFα, a target multiple expert groups have struggled with. TNFα is a signaling protein released by the immune system to trigger inflammation, and blocking it is the therapeutic basis for some of the most impactful drugs ever made, including Humira. It’s a challenging target to design against because of its multimeric structure, which requires targeting a binding site in the groove formed by two proteins. Although Mythos Preview was unsuccessful, Opus 4.8 designed multiple binders, including some that worked across species, binding human, cynomolgus monkey, and mouse TNFα, which is important for conducting animal studies. We’re not sure why Opus 4.8 was successful on this target and Mythos Preview was not. When we assess our models capabilities, we do so holistically. Given the inherent complexity of protein design, it’s unsurprising that there would be specific areas where an overall less capable model could still outperform one that was generally more capable.