Keros Therapeutics, Inc. Common Stock Chardan's 10th Annual Healthcare Conference

Sure. Well, thank you for the opportunity to have this conversation. Keros is a company that's focused on a signaling pathway called the TGF-beta pathway. We have an advanced product that was partnered with Takeda in 2024 in three phase III trials with good economics on that. We had a second asset that had a safety signal in a phase II trial, that we have deprioritized, and are no longer pursuing it. We have a third asset that is now increasing skeletal muscle by increasing muscle regeneration that is going into neuromuscular indications.

Well, I think what happened was that we did the deal in late 2024, and shortly thereafter, we saw the safety signals. That resulted in our stock price declining. In 2025, we had activists move into the stock. We'd returned $375 million last year, and it was a reboot for us. I think, for investors, they're waiting for us to be closer to data on rinvatercept, but elritercept is in the hands of a partner. I think until there's line of sight on data from those phase III, we're really not going to get much credit, which could be in the 2028, 2029 timeframe. Takeda has recently indicated that they will be filing a BLA in the 2028, 2029 timeframe, so data should be coming around that time.

Yeah. Even with the $375 million of capital returned, we have received a milestone from Takeda last quarter. With that milestone, we are guiding runway into the second half of 2028. So we have got a good runway. The rinvatercept phase II trial in DMD has initiated, and we will be able to share data from that in the first half of 2027. It is an open-label study, so we will have multiple readouts from that. In addition, we guided that in the second half of 2026, we will engage with the regulators on design of a phase II trial in ALS, and that is moving along. So that trial will start sometime in 2027. So 2027 becomes a year of data readouts and additional trial initiations. Okay? So I think we are resetting the stage for those data readouts.

I think with all of those, what they're trying to do is to replace the dystrophin that's lacking in the muscle in boys with DMD. I want to really talk a little bit about how our products are very different, because we're not trying to replace the dystrophin. What we're trying to do is to increase the muscle regeneration. I think when you look at the progression of the disease in boys with DMD, they get diagnosed between 18 months and 3 years of age because they're slow to start ambulating. But they all ambulate, every single one of them. Even this muscle that's missing dystrophin, it's functional, and they get stronger, and then eventually go into the decline phase. What's going on? This muscle that's lacking dystrophin has a homologue protein that's there at very low levels.

It is functional, but it's subject to easily being broken down. That breakdown then leads to inflammation, and with time, that inflammation accumulates. That then retards the muscle regeneration. If you could prolong that muscle regeneration, you would continue to have functional benefit from that muscle. That's exactly what glucocorticoids do, right? They tamp down the inflammation, and as a consequence, you have a delay in the loss of ambulation by about 2 years. But glucocorticoids are also catabolic on muscle. While initially they're tamping down the inflammation and the boys get stronger, but they're also wasting away the muscle. Okay, right. A drug that doesn't do that could actually prolong it longer. What does rinvatercept do? It actually inhibits two of the key ligands that are negative regulators of skeletal muscle. By inhibiting those two ligands, you're allowing muscle regeneration to take place.

In addition, one of those ligands, activin A, is actually a powerful inflammatory cytokine in the TGF-beta pathway, and it also then results in inflammation and fibrosis in the skeletal muscle. At the same time, activin A leads to bone loss. Okay, right. When you look at the pathology of the patients that are lacking this dystrophin protein, they're wasting away the muscle. The muscle is getting replaced by fibrotic and fatty tissue, and they're also osteoporotic. Okay, right. The glucocorticoids just make it worse. Rinvatercept sort of really deals with all of the pathologies that arise from the current standard of care and the disease itself without replacing the dystrophin. Now, the good news is that it can be used in combination with all other treatments. Okay, right. It's not exclusive of those treatments because when you increase muscle regeneration, you actually increase the population of cells that can pick up those exon skippers, gene therapy, and fuse it, okay, right, to the myofiber.

As a consequence, you actually see higher levels of expression of those truncated dystrophin. Really you can think of rinvatercept going on top of glucocorticoids regardless of the mutation, and then if there are other therapies that are available, it can still be on top of those.