Roche and Carmot's GLP1 pipeline

We take a look at Roche (via Carmot)'s GLP1 pipeline development, and figure out how CT-388, CT-996, and CT-868 are trending.

Roche and Carmot's GLP1 pipeline

Roche is a large multi-national pharmaceutical company that's well known for a huge number of new drug discoveries (one of the most popular being Accutane for acne).

Roche entered the GLP1 Receptor Agonist marketplace with their acquisition of Carmot (a US company based out of Berkeley, California) at the end of 2023:

Roche enters into a definitive merger agreement to acquire Carmot Therapeutics, including three clinical stage assets with best-in-class potential in obesity and diabetes
Carmot Therapeutics’s R&D portfolio of clinical stage incretins has great potential to treat obesity, diabetes and potentially other diseases both as standalone medicines and in combination with…

At the time, Carmot's lead drug was a GLP1 + GIP dual agonist (similar to but not the same as Tirzepatide AKA Mounjaro/Zepbound) called CT-388.

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Roche acquired Carmot specifically for it's "clinical stage incretins [with] great potential to treat obesity, diabetes and potentially other diseases" – a smart move given how huge GLP1s look to be to the future of obesity and healthcare worldwide in general.

That said, CT-388 wasn't alone – there were two other drugs in focus:

  • CT-996 is a once-daily oral pill, and a "simple" GLP1 receptor agonist (single agonist)
  • CT-868 was a subcutaneous injection of a dual agonist (GLP + GIP) that was aimed towards sufferers of type 1 diabetes who are overweight or suffering from obesity.

When Roche purchased Carmot, it had already shown great results in phase 1B trials, which made the rounds, achieving 8% weight loss in 4 weeks:

Carmot Therapeutics Highlights Clinical Data from its Pipeline of Treatments for Obesity and Diabetes at the 83rd American Diabetes Association Scientific Sessions | Carmot Therapeutics | Drug Discovery and Development
– Once-weekly administration of CT-388 delivers clinically meaningful weight loss and metabolic control with a favorable tolerability profile over a 4 week treatment period in overweight and obese otherwise healthy participants – – Mechanism of Action study achieves robust weight-independent effect of CT-868 on glucose homeostasis in overweight and obese adults with type 2 diabetes […]

(Unfortunately Carmot has since updated the page where it announced it's results, so you have to use a resource like The Internet Archive to find the page. the findings were also celebrated in Diabetes research journal)

Things have changed since then, but we're going to take a look at what Roche and Carmot have developed, and how it's progressing so far.

What is CT-388?

As mentioned earlier (for those skimming), CT-388 is a dual agonist of GLP1 and GIP – it interacts with two hormones that naturally occur in the body, and importantly (at least in the case of GLP1) it suppresses appetite (and often what might be addictive behavior) in the brain.

This drug is similar to Tirzepatide, and while that does not guarantee that results will be similarly spectacular (Tirzepatide is the most effective FDA approved GLP1 at this point), they have promised to be similar so far.

What is CT-996?

CT-996, unlike CT-388 is a single agonist that targets the GLP1 receptor, that is meant to be taken orally, once a day.

This is similar to medications like Rybelsus:

GLP1 weight loss without a needle: Rybelsus
There are lots of popular GLP1 Receptor Agonist (GLP1 RA) drugs and most of them are injections under the skin (“subcutaneous injections”). Here’s a short list of the most popular ones that do require injections: * Ozempic * Mounjaro * Wegovy * Saxenda * Trulicity But we’re not here to talk about those – we’re here

And more recently Eli Lilly's Orforglipron:

Eli Lill’s oral GLP1 delivers stellar results
Eli Lilly’s new drug oral GLP1 Orforglipron delivers fantastic results in phase 3 trial -- 7.6% weight loss for just a pill!

As is probably obvious, being able to take a GLP1 orally and achieve significant results is a game-changer:

  • More sustainable distribution (no more injection pens)
  • More convenient user experience
  • Easier manufacturing and logistics

Importantly, the differences between CT-996 and others mean that approvals will likely be separate, it is not simply a reformulation of CT-388.

What is CT-868?

CT-868 is covered much less than the other drugs in the Carmot (now Roche) pipeline, but is valuable nonetheless to people who are struggling with type 1 diabetes and obesity.

CT-868 was also in clinical trials way back in 2023, so it's quite far along in the process and a viable candidate going forward.

2024: Industry-leading results for the injectable CT-388 dual agonist

Roche made headlines in 2024 announcing positive results from Phase 1B trials for CT-388:

[Ad hoc announcement pursuant to Art. 53 LR] Roche reports positive Phase Ib results for its dual GLP-1/GIP receptor agonist CT-388 in people with obesity
Over 24 weeks, a once-weekly subcutaneous injection of CT-388 achieved a clinically meaningful and statistically significant mean placebo-adjusted weight loss of 18.8% (p < 0.001) At week 24, 100%…
Over 24 weeks, a once-weekly subcutaneous injection of CT-388 achieved a clinically meaningful and statistically significant mean placebo-adjusted weight loss of 18.8% (p < 0.001)

18.8% in 24 weeks is an insane amount of weight loss (likely high enough to trigger other issues like gallstones which might be a worry).

What's even better is that these results were achieved with similar negative side effects as other GLP1s – there does not seem to be any added danger from the drug itself compared to it's widely-taken peers.

2024: Great stage results for oral single agonist CT-996

Reports surfaced of early results for CT-996:

Pharmaforum post on early data for CT-996

The data revealed a loss of 6% more body weight than placebo when using the oral form (CT-996):

The new results are from a phase 1 trial of a once-daily pill called CT-966, which revealed an average weight loss of 7.3% at four weeks in the study population of obese patients without diabetes, compared to a 1.2% reduction with placebo.

This is quite impressive in both terms of time frame and the efficacy of a GLP1 receptor agonist in pill form.

For contrast, Rybelsus which in the past took over 26 weeks to show changes to body weight in early studies, and reported 3-4kg losses after a year in later studies.

2025: Roche is also working with Zealand Pharma on Petrelintide, an Amylin based weight loss drug

Roche is also working on another approach with the help of Zealand Pharma:

Roche enters into an exclusive collaboration & licensing agreement with Zealand Pharma to co-develop and co-commercialise petrelintide as a potential foundational therapy for people with overweight and obesity
Agreement allows for a range of potentially best-in-class therapy options as monotherapy and fixed dose combination with Roche`s lead incretin asset CT 388Collaboration will complement Roche’s…

This shows that Roche is clearly committed to GLP1s for weight loss, and importantly is taking a multiple paths to get there.

More importantly, Roche is exploring combining petrelintide with CT-388 in order to boost it's effectiveness and tolerability.

The combination of petrelintide with Roche’s dual GLP-1/GIP receptor agonist CT-388 will further strengthen and expand Roche’s pipeline in the field of cardiovascular, renal, and metabolic (CVRM) diseases. This combination offers the opportunity for best-in-disease efficacy while potentially offering enhanced tolerability.

On the less rosy side, this may signal that there was a problem with the side effects that CT-388 caused.

Roche commits 50 Billion to US manufacturing

With the recent moves of the Trump Administration in creating Tariffs and trying to spur US investment, Roche has taken the extraordinary move of investing 50 billion USD over the next 5 years:

Roche to invest USD 50 billion in pharmaceuticals and diagnostics in the United States over the next five years
USD 50 billion commitment includes new state-of-the art research and development (R&D) sites, new and expanded manufacturing facilities in Indiana, Pennsylvania, Massachusetts and California and…

While it's not clear these investments will stay the course/be evenly applied after the Trump administration leaves office, clearly Roche is serious about the US market.

To be clear, Roche already had significant US investment with many R&D centers and manufacturing sites in the US.

So when will any of Roche's drug enter the marketplace?

Unfortunately, Roche's most advanced drug, CT-388, is slated to be filed for in 2028:

CT-388 Pipeline information

This is a long time to wait for a new GLP1 to hit the market, and while results have been spectacular, it shows that there will be a large amount of time until this new GLP1 enters the market.

So how about CT-996?

As you might have imagined, it's even further behind, with no projected filing date.

Last but not least, CT-868:

CT-868 is on a similar trajectory with CT-388, and at least has a projected filing date, though it is further in the future than CT-388.

These new GLP1 receptor agonists are incredibly impressive, but it's important to realize how long it will take until humanity can benefit from their innovations, even in a perfect scenario (assuming no new negative side effects are discovered).

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