Could GPCR's Oral Amylin Be Once Weekly? New Half-Life Data at ADA Are Very Supportive

Research evidence excerpt

Could GPCR's Oral Amylin Be Once Weekly? New Half-Life Data at ADA Are Very Supportive

June 7, 2026

sub-nanomolar in vitro functional activity on the amylin and

calcitonin receptors.

●Key new preclinical data disclosed at ADA was that the half-life of '2671

in NHPs (non-human primates) is very long, at >60 hours.

●We do not have any precedent from other oral amylin drugs for NHP-

to-human half-life conversion, since '2671 is first in class.

●Typically, we use a 2-4x conversion factor in humans. Thus, the half-

life of '2671 in humans could be 5–10 days, which should support

weekly dosing for amylin monotherapy, in our view.

○Caveat: Drugs can be metabolized/eliminated differently in

humans than in NHPs, while we are using simple allometric

scaling assumptions.

○For example, in the case of orforglipron, the elimination half-

life in NHPs was 3.4–4.6 hours, while in humans it was 29–49

hours. NHP data for orforglipron under-predicted half-life in

humans.

●Positive takeaway is that GPCR could have a once-weekly oral amylin,

at least in the maintenance phase, once the drug has reached steady

state.

●However, with any small molecule with a very long half-life, we worry

about drug accumulation and, consequently, safety/tolerability. That

said, a few factors work in favor of GPCR’s oral amylin:

○GPCR’s oral amylin is very potent and requires very low doses

- Phase 1 SAD human doses are ≤20 mg. Thus, the chances of

off-target effects due to high doses are quite low.

○GPCR management also noted that the drug looks very clean

preclinically.

○Once amylin drugs have been titrated and reach steady state

in 8–12 weeks, high drug accumulation has no negative

consequence for safety/tolerability. This was also the case

for injectable selective amylin agonist eloralintide (LLY), which