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

leokitcat

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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 said:
The structure/sequence is fully published here in this paper, so I expect research peptide availability will follow soon
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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...
 
leokitcat said:
The structure/sequence is fully published here in this paper, so I expect research peptide availability will follow soon
Click to expand...
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.
 
I will absolutely 100% switch my, uh, research subject over to Elora from Cagri as soon as it becomes available.

Throw Away Make It Rain GIF
 
I'm curious how expensive this'll be. I know cagri can be pretty expensive, so this one will probably be more.
 
yeddie said:
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...
Click to expand...
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.
 
yeddie said:
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...
Click to expand...
Elora looks like will be stronger and have some fewer side effects. But cagri is strong at appetite control so you should still probably take advantage and use it as a combo with tirz / sema / reta if you need.
 
m100568 said:
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.
Click to expand...
Latest trial is tirz or sema (depending on what your on) and elora stack I imagine they trial Reta/elora when Reta is fully approved might just buy a bunch of Lilly calls
 
Definitely looks like a more complicated peptide than reta or tirz with multiple non standard amino acids and a funny bridge / circle link at one end, as well as the standard fat molecule to make it bind to albumin and last longer. Will be harder to manufacture. Hopefully not beyond the Chinese labs.
Other than that looks good , less side effects and more effective than cagri. Perfect to go with reta for severe obesity.
 
lessthanhalf said:
Definitely looks like a more complicated peptide than reta or tirz with multiple non standard amino acids and a funny bridge / circle link at one end, as well as the standard fat molecule to make it bind to albumin and last longer. Will be harder to manufacture. Hopefully not beyond the Chinese labs.
Other than that looks good , less side effects and more effective than cagri. Perfect to go with reta for severe obesity.
Click to expand...

Supposedly, one of the larger grey suppliers is very close to dropping the first grey version of eloralintide maybe next month or early in the 2nd half of 2026. Not really sure if anything said online can be relied upon to any degree of certainty, but it looks close.

But, yes, the "ring" you mention at one end of the chain represents an issue not only in the manufacturing process, but also in the testing process. As I understand it, identifying that that ring is properly located and formed can't be done with standard mass/purity equipment. Good news is that Jano supposedly has already ordered the equipment and is ready to go. Bad news is that based on the novelty, availability, and increased testing costs, elora will likely be expensive, even in grey markets.
 
Grogu said:
Supposedly, one of the larger grey suppliers is very close to dropping the first grey version of eloralintide maybe next month or early in the 2nd half of 2026. Not really sure if anything said online can be relied upon to any degree of certainty, but it looks close.

But, yes, the "ring" you mention at one end of the chain represents an issue not only in the manufacturing process, but also in the testing process. As I understand it, identifying that that ring is properly located and formed can't be done with standard mass/purity equipment. Good news is that Jano supposedly has already ordered the equipment and is ready to go. Bad news is that based on the novelty, availability, and increased testing costs, elora will likely be expensive, even in grey markets.
Click to expand...
Not as expensive as it will be when it comes to market, so it’ll still be a bargain.
 
wheymaster1 said:
Not as expensive as it will be when it comes to market, so it’ll still be a bargain.
Click to expand...
Yeah id be game to pay a premium for it. I mean im close to going jnto maintenance and an amylin agonist with little side effects seems like a good way to go about it while reducing my GLP1s dosages.

So yeah, id definitely give it a shot!
 
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