Thread by @cremieuxrecueil

What comes after GLP-1RAs make everyone skinny?

What comes after myostatin inhibitors make everyone buff?

One new candidate is:

Safe, cheap, and easily-administered injections that locally remove fat. A new drug that just passed through phase 2 seems to do just that🧵

The new drug is called CBL-514.

It has a counterpart on the market in the form of deoxycholic acid injections—brand name Kybella.

Kybella is FDA-approved, and it works: it helps people to get rid of their double chins. But there's a catch.

Kybella, unfortunately, is not all that safe, and though many patients swear by it, there are notable side effects.

This is predictable, since the way Kybella works is through cytolysis: causing cells to die by rupturing them, releasing their contents, causing inflammation.

The main thing that makes CBL-514 so much better than Kybella is that instead of the chaotic, damaging cytolysis process that frequently leads to necrosis, ulceration, neuropraxia, and infections...

CBL-514 causes programmed cell death, or apoptosis: it's clean and controlled!

The action of CBL-514 seems to be entirely local: no systemic side effects, and no adverse effects beyond what you'd expect from giving people large injections

To be sure, almost everyone in the sample had an injection site side effect like pain or warmth. But they resolved fast

Participants were injected with CBL-514 up to four times, in four-week intervals.

They were then followed while being told they had to maintain their weight within a narrow range.

Even with weight maintenance, participants still had considerable fat spot reduction.

Hust saying this probably doesn't give you a good idea of what this means.

So, let's look at one of the participants.

This is from Participant B, a 46-year-old woman. At baseline (left), she had severe fat accumulation warranting intervention. Much-improved by visit 7 (right)!

With just a handful of injections, someone went from fat to still fat, but far less concerningly fat.

If we look at how that fat loss occurred, you can see that virtually all of it was exactly where the injections happened.

This is not what you expect from typical fat loss.

You might be gathering something right about now:

With typical, massive fat loss, you see saggy skin that might even need surgery.

With this, "participants exhibited little or no skin laxity following fat loss".

That's right: targeted weight loss, no skin removal required.

Keep an eye on that, though, because maybe with really large fat loss, we'll still see skin sagging. But at least in typical use, it seems hopeful.

What's more, this might even be usable to help manage saggy skin in a noninvasive way.

CBL-514 helps with cellulite!

CBL-514 also has non-cosmetic uses that are being explored.

In fact, the FDA has fast-tracked CBL-514 for clinical use combatting Dercum's disease, a condition where people develop painful fatty bulbs under their skin.

And guess what: for that outcome, it also seems to work.

The company behind this product has shown remarkable results in Phase II trials for non-surgical spot fat removal, Dercum's disease, and cellulite, and they're now looking into combining their drug with GLP-1RA therapy.

In that case, it seems to prevent weight rebound!

In addition to preventing weight rebound by eliminating rather than depleting fat cells, the company also thinks that its product can be used to contour GLP-1RA weight loss, so as people's weights fall, they lose where they want to:

That means losing more belly and less butt.

And the most amazing part of all of this is that this product is a small molecule drug.

It's going to be cheap to manufacture in bulk, so consumers will be able to get all the benefits of liposuction, without scarring, on the cheap.

Expect low, low prices and no shortages.

Frankly, I expected all products like this to be trash that had tons of adverse effects in phase 1 trials.

The fact that it's succeeded in so many phase 2s suggests this is a drug that's likely to come out soon, and it could end up being a revolutionary cosmetic enhancer.

So now we have:

1. Ways to lose weight, quickly, safely, and easily (you are here)

2. Ways to maintain and gain muscle, quickly, safely, and easily (coming soon)

3. A way to sculpt the body's fat distribution, quickly, safely, and easily (coming soon)

America will get hotter.

The world's first targeted fat destroyer is upon us.

Reading material and sources:

academic.oup.com/asj/article/45…

academic.oup.com/asj/article/42…

caliwaybiopharma.com/en/news-detail…

biospace.com/press-releases…

caliwaybiopharma.com/en/research/15/

pharmacytimes.com/view/fda-grant…

prnewswire.com/news-releases/…