Sizemic Shift

Jan 4, 2024

In Star Wars, Master Yoda says, “Size matters not. Look at me. Judge me by my size, do you?”

Not to compare the oncolytic adenovirus, AdAPT-001, to Yoda or vice versa, but despite a diameter of 90 nm or 90 billionths of a meter, AdAPT-001 is forceful enough to do battle with drug-resistant tumors that are tens of millions of times larger than it.

AdAPT-001 not only directly eliminates cancer cells, but it also expresses a TGF-β trap that targets the immunosuppressive tumor microenvironment.

The main takeaways from an ongoing Phase 2 clinical trial are that AdAPT-001, at least so far, is well tolerated both alone and in combination and that it appears to sensitize immunotherapy-resistant tumors to checkpoint inhibitors.

Which, if true, would represent a seismic or rather a “sizemic” shift in the treatment paradigm. This is because checkpoint inhibitors for all their life-saving benefits are only active in a minority of patients with certain tumor types like melanoma, non-small cell lung cancer (NSCLC), and renal and urothelial cancers. Combinations with other large molecule checkpoint inhibitor antibodies, for example, are well known to increase efficacy but only at the expense of significantly more toxicity.

A massive “casting call” is out to find other agents that increase the anti-cancer activity of checkpoint inhibitors but not their toxicity.

To date, the audition of AdAPT-001 with a checkpoint inhibitor has greatly impressed, reinforcing Yoda’s tenet that size matters not.