TheraRadar

Briefs tagged "antibody engineering"

2 briefs

8 min read

Can an IBD Biologic Last Six Months?

Several companies want to stretch IBD antibodies from a shot every few weeks to one every three months, or even six. Keeping the drug in the blood that long is the easy part. Whether the disease stays controlled right up to the next dose is the hard part, and the bet the newest programs are making.

“Long-acting” hides three claims: the drug stays in the blood (PK), keeps blocking its target (PD), and keeps the disease controlled (durability). Only the last proves a long interval works. Across 1,147 IBD trials, TL1A is the most crowded emerging target, with 7 antibodies, 6 sponsors and 36 trials, and 3 already in Phase 3. The leading long-acting candidates report 56–85 day half-lives, a 3–5× leap. But the trough, how much drug is left at the next dose, tells the real story: at the proposed quarterly and six-month intervals it sits at roughly 19–47% of peak, inside the range today’s biologics already tolerate. The PK was never the wall; durability is, and only XmAb942 is yet testing a long interval in patients.

14 min read

Fifteen Drugs by Blocking. None by Switching On.

The TNF receptor superfamily has produced fifteen approved medicines, and every one of them works by shutting something down. Six receptors have been pushed the other way for twenty years, and not one agonist antibody has been approved.

Adalimumab, etanercept, denosumab and belimumab target different ligands, but they all modulate signalling through the TNF receptor superfamily, and every one works by turning a pathway off. For about twenty years the field has also tried the opposite, activating CD40, OX40, 4-1BB, GITR, TRAIL-R and CD27 with agonist antibodies. That has produced nothing approved, in the United States or Europe. These receptors only signal when several copies are clustered into a particular arrangement, and the clustering has to be supplied by the patient's own FcγRIIB, so potency depends on the tissue as much as on the molecule. Romiplostim shows agonism is not impossible — its receptor just asks for something a two-armed drug can deliver.

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