Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept

[leokitcat]

https://www.sciencedirect.com/science/article/pii/S2212877825001784

Objectives​

Eloralintide (LY3841136), a novel amylin analog, was evaluated in translational studies to characterize its therapeutic potential for treating obesity.

Methods​

In vitro assays were performed in cell lines selectively expressing rat or human amylin 1 receptor (AMY1R), amylin 3 receptor (AMY3R), or calcitonin receptor (CTR). In vivo studies were conducted in rats and monkeys. A phase 1, randomized, placebo-controlled, participant/investigator-blinded trial evaluated the safety and tolerability of single-ascending eloralintide doses (0.04–12 mg) in healthy participants (NCT05295940).

Results​

In vitro, eloralintide preferentially activated human AMY1R (12-fold > CTR, 11-fold > AMY3R), while in rats, both AMY1R and AMY3R were activated more potently than CTR. Eloralintide induced significantly less conditioned taste avoidance in lean rats than cagrilintide, a non-selective amylin receptor agonist (p < 0.05). Eloralintide dose dependently reduced food intake and lowered body weight, primarily through fat mass loss, in diet-induced obese rats. Eloralintide demonstrated favorable pharmacokinetics in both rats and monkeys. In the phase 1 trial, 48 healthy participants had a mean body mass index of 27.5 kg/m2. Nine participants in the eloralintide cohorts reported 16 adverse events, with most being mild (n = 15/16). Two participants reported 4 gastrointestinal events, including one moderate vomiting event. The pharmacokinetic profile of eloralintide supports once-weekly dosing. In eloralintide cohorts receiving single doses of 4 or 12 mg, week-4 mean percent change from baseline in body weight was −2.5% (p < 0.01) and −4.4% (p < 0.001), respectively, vs placebo (+0.6%).

Conclusions​

Once-weekly dosing with eloralintide, an AMY1R-selective agonist, may offer a promising new therapeutic with favorable gastrointestinal tolerability for the treatment of obesity.

 

[leokitcat]

The structure/sequence is fully published here in this paper, so I expect research peptide availability will follow soon

 

[leokitcat]

 

[yeddie]

The structure/sequence is fully published here in this paper, so I expect research peptide availability will follow soon

Ha yeah, how many people on this forum see the early results from Eloralintide and wonder how long it will be before it shows up on the grey market?

I have some cagrilintide I bought early in my glp1 journey, thinking I might need it if my weight loss plateaus before reaching goal weight. Now it sounds like it has been obsoleted before I even needed it...

 

[m100568]

The structure/sequence is fully published here in this paper, so I expect research peptide availability will follow soon

Thanks for posting this. I am really excited about Eloralintide. I am using Tirz and Reta in maintenance. I tried Cagri and it gave me a 24 hour a day headachache that went away when I stopped using it. I think Eloralintide and Reta would make the ultimate stack, and I'm guessing that maintenance would require a fairly low dose of both. I can't wait to start experimenting.

 

[penewbie]

Cagri really helps me out, so Elora is probably going to be amazing. Can't come soon enough.

 

[teabitten]

I will absolutely 100% switch my, uh, research subject over to Elora from Cagri as soon as it becomes available.

 

[IshimaruKenta]

I'm curious how expensive this'll be. I know cagri can be pretty expensive, so this one will probably be more.

 

[nonyabizznez]

Ha yeah, how many people on this forum see the early results from Eloralintide and wonder how long it will be before it shows up on the grey market?

I have some cagrilintide I bought early in my glp1 journey, thinking I might need it if my weight loss plateaus before reaching goal weight. Now it sounds like it has been obsoleted before I even needed it...

Cagrilintide won't be obsolete. It's still a long-acting amylin that increases satiety and aids in weight loss. Aleve doesn't make make Tylenol obsolete. Jiffy doesn't make Skippy obsolete.

If there's no fibril/oligomer issue that might be another story. Elora sounds like a nice name for a queen oligomer in a Pixar movie though.

 

[gulangaloid]

I'm curious how expensive this'll be. I know cagri can be pretty expensive, so this one will probably be more.

cagri isn't very expensive considering how low the effective doses are