For joining us this year at the Guggenheim SMID Cap Biotech Conference, day two. I'm Vamil Divan, one of the Biopharma analysts here, joined on this stage by Daniel Krizay from our team. And next up in this room, we have the Keros team. And we have Jasbir Seehra, who's the CEO of the company. So obviously, it's been an interesting time. A lot of people are excited for Keros. Maybe if you want to just, for people who maybe haven't followed it that closely, just kind of get people up to date on the Keros story and what's happened over the last, since December, I guess. And then we can dive deeper into some of the questions. Keros is focused on developing therapeutics targeting the TGF-β superfamily. We have three products in the clinic. Our most advanced program, Elritercept, in MDS and MF, was partnered at the beginning of December with Takeda, where I think we found a partner that was really aligned with our vision for the product. Our second product, Cibotercept, is in PAH. We had safety findings of pericardial effusion, whereby in early December, we stopped dosing at the two highest doses. Then in January, the low dose of one and one-half per kg also showed safety signals, and we stopped the trial. We're waiting to unblind the data in the second quarter of this year. Our third product candidate, KER-065, is in a healthy volunteer study. It has the potential to increase skeletal muscle, reduce fat mass, increase bone mineral density. Therefore, there are numerous indications that it can be taken into. We have recently announced that our first indication would be a neuromuscular indication, Duchenne's. We can talk a lot more about that, so three product candidates and behind that, we've got a research pipeline of multiple ligand traps that can go in different indications. Ok, great. So let's start with Cibotercept, because that's gotten the most attention over the last couple of months. And I know you're limited in what you can say because you're still waiting to unblind the data. But maybe just more from a scientific perspective, and you have a long history and you're working in the space, how do you think about the pericardial effusion development? Because I know there's patients with PAH who can be at higher risk for getting pericardial effusions. Is there something about the, as you're thinking about this and you're waiting for the full data set, is there something about the patients that were in the trial? Is there something about the drug? Is there something about the dose of the drug? What are the things that you're thinking about that could provide answers in a few months? Yeah, so I think, first of all, we completed our chronic tox studies with Cibotercept, where we dosed very high at 50 milligrams, that's 50 milligrams per kilogram. And we had exposure levels so high that your safe starting dose in a human would have been 16 mg-17 mg per kilogram. Ok? And as you know, we completed a healthy volunteer study with three months of treatment. So nothing in the tox studies, nothing in the healthy volunteer study. So the drug was well tolerated there. So I think this is unique to PAH, but we're going to have to wait for the data. The top line will be in the second quarter. Is it a background of a certain subset of patients that are more prone to pericardial effusions? And the drug is augmenting that biology. Ok? Or is it certain patients on certain therapies, and you're augmenting that? After all, when you think about it, PAH patients, because of the pathophysiology of the disease, they have vasculature that is no longer normal in the lung. You've got thickening of the blood vessels, walls, so narrowing, and also pruning of the fine vasculature. But they have alterations in vasculature throughout their body, as has been exemplified by Sotatercept, where it was tested in many, many patients in many different indications, and bleeding events weren't there. However, in PAH patients, you're seeing bleeding events rapidly. So what is it about that biology in PAH patients? And recently, we've shown preclinically that in a model of PAH, just an increase in hemoglobin is sufficient to have bleeding events. Therefore, that vasculature in the PAH model, therefore in PAH patients potentially, has been remodeled so that it is prone to damage even with an increase in hemoglobin. You wouldn't have predicted that from all the other studies. So we're, I think, uncovering new biology that none of us understand. There's a background of pericardial effusions in PAH patients. We don't know what the numbers are because there's only small studies that have been conducted. Numbers range from small to large, but they're all very small studies. So I think there is a background. There's biology there. And we are seeing that biology be augmented. You didn't see it with Sotatercept in the trials. More recently, there's reports, Ok, right, as people have become aware of this from the news that we'd released in December. So I don't know today. Right? That's a long-winded way of saying, I don't know today. And I need to wait until we get the top line data. But then we may still have to dig deep, Ok, right, look at biomarkers. Is there something that we can tease out that tells us that this patient, that patient is at higher risk? Because that's what you need in order to go forward. Yep. Ok. So then another question we get commonly, and I'm not sure how much you can say here either, but just in terms of what's transpired over the last few months, initially the first two doses, higher doses being stopped. So obviously, there's all these cases, but what sort of led to these cases being identified? Was it the patients that were becoming symptomatic? I don't believe you had echo sort of routinely being done in the trial, if I have that correct. So what happened there to lead to the initial announcement? And then presumably more cases were identified in the lower dose, and that led to that stopping. But maybe you can just take us through the timeline there in terms of what you saw when it led to these decisions. I'm blinded to all of this, ok, right? But what I do know is that at some point last year, there was symptomatic observation. It had to be because the Drug Safety Monitoring Committee asked us to amend the protocol and have routine echoes. Ok? So I think there was observation of symptomatic pericardial effusion. And then echoes were implemented. And it takes time, ok, to do protocol amendments and get that going. And in early January, there was echo data, both from the 1 and 1/2 and the placebos, as well as earlier small subset from the, would have been from the 3 mg and 4 mg and 1/2 mg per kg. And looking at that, the Drug Safety Monitoring Committee, along with the Keros team, said we're going to stop treating even at the 1 mg and 1/2 mg per kg. Okay. And then so now, obviously, you're waiting for the full data in the second quarter. In terms of communication with the agencies or what we should expect in terms of sort of next steps going forward, I guess it's just a matter of waiting to see what the data shows. You'll release that publicly and then talk to the agencies after this. That's right. Right. And I think it really comes down to, can we glean from the data who are the patients that are at high risk? And therefore, design a Phase II trial that allows us to go forward, not putting patients at risk, Ok, right? And you don't want the same things being repeated again and again. So we need to understand that. And that will be a discussion that we will have with the regulators. Ok. And then maybe there's one more thing. We've talked about this a little bit over the last couple of months, but just, again, not knowing the data and kind of needing time to understand this better. If you had to think, I know there's other history with other drugs that are in the same general class. Maybe that's had issues with pericardial effusions or not. So if you had to think about sort of where, what ligand or what's kind of driving this, what's your sort of working theory at this point? Yeah, I don't know if there is a ligand. I honestly do believe it's a background in the PAH patients, not necessarily a ligand driven. Because you're right, there were other molecules in this pathway, the Sotatercept, as well as Pfizer's neutralizing antibody to the receptor ALK1. And therefore, with both of those, you would inhibit BMP-9 and BMP-10. Ok? And in the clinical studies with both molecules, there was edema, pleural effusion, pericardial effusion. I will tell you that what you saw clinically was a replication of what was seen preclinically. And I'm also telling you that we didn't see any of that with 012. So I don't believe it's BMP-9, BMP-10 inhibition. But nevertheless, in PAH patients with treatment, you're augmenting it, right? Yeah. Ok. And then maybe last question, then we'll switch gears. So just, again, what should we expect in terms of data disclosure plans, like around when you get the top line data? I assume you'll be having some sort of investor call or debrief kind of to give people. Yeah, that is what we're thinking. Because normally, you're presented at a medical meeting. There's no medical meeting that we can present in the second quarter because the deadlines for all that were long gone. So we will do a top line press release and have an investor call. Ok, let me turn to Daniel, then maybe jump ahead. Yeah, great. Thanks, Vamil. So yeah, so shifting over to 065, you announced that you deprioritized obesity for this product and shifted the focus purely on neuromuscular diseases like DMD. So can you maybe expand on what drove this decision? Yeah, the decision was really primarily driven by the fact that when we had Elritercept in Phase III trials, unpartnered asset, Cibotercept in Phase II, potentially heading into Phase III, we as an organization did not have the human resources nor the capital resources to be bringing along the asset that we fully owned all the way to commercialization. And therefore, it made sense for us to think of 065 in obesity where it would become partnered. Do a Phase I, Phase II, partner it. Once we had partnered Elritercept, with that transition, we would have the capacity to bring forward another asset that we fully owned all the way through to commercialization, especially in small indication. We always planned that 065 would be one molecule that increased skeletal muscle, but there would be others. The original plan would have been the next molecule would then go into neuromuscular indication. So there's a gap, Ok, right? Well, with Elritercept gone to a partner who's now going to invest in that and develop it, we needed to bring forward an asset and not wait another two, three years, Ok, to go through Phase I in a set of indications that we can commercialize. So it's deprioritizing just switching, Ok, right, where 065 is now in neuromuscular. And we'll bring along a preclinical asset that we could partner in obesity, Ok, right, or any other indication, Ok, right? We need to control our own destiny, right? And I think that's the way to do it. I think the other thing, Ok, is it is always about partnership in obesity for us. It always was. And I don't see the type of partnerships that bring significant value, Ok, right? I just don't see that at this point in time. And I think we've seen the hunger for a muscle anabolic in obesity peaked beginning of last year. And since then, it's somewhat declined. Ok. Yeah, that all makes sense. So then maybe focusing on DMD, can you maybe discuss a little bit what preclinical data you've seen to date that gives you confidence for this drug in this disorder? Yeah, so preclinically, the team has demonstrated that you can increase muscle regeneration. Therefore, you can build the muscle, but also maintain that muscle, and that through that increased regeneration, you're actually seeing upregulation of the homolog of dystrophin, utrophin. And in combination with dystrophin salvaging drugs like the PMOs, you can actually have more increased expression of the truncated dystrophin than with the PMO alone. And I think this is all because you're increasing the regenerative capacity. If you look on our website, you'll see data that supports that. You see, as a consequence, functional benefits in these animals, so you can increase lean mass. You can decrease fat mass. You can improve bone mineral density. Boys with DMD go on glucocorticoids. Glucocorticoids are catabolic on both muscle and bone. These boys have increased adiposity as a consequence of being on glucocorticoid. KER-065 can ameliorate all of the side effects of glucocorticoid treatments, right? So you can improve the bone. And boys with DMD that have been on glucocorticoid are osteoporotic. They have high fracture rates. Ok? They are metabolically challenged. They lose the regenerative capacity of that muscle and, as a consequence, lose ambulation. So you can correct all of those things, right? And when you go back and you look at all of the myostatin antibodies that have gone into DMD, while they didn't meet their primary endpoint, look closely and you see signals of activity. And then when you look at the Acceleron ACE-031, the wild-type activin receptor 2B sequence that's fused to an Fc ligand trap, it showed increase in lean mass, decrease in fat mass, improvements in bone from three months of treatment. And when you look closely at the older boys, those nine and above, very small number of patients in that study fell into that category of nine and above. Placebo, four placebo boys lost 39 m of ambulation over five months. Whereas the treatment arms lost much less, Ok, right? And that's the one mg per kg given every two weeks. There was no loss of ambulation. So I think there's proof of mechanism from that molecule. But that molecule was terminated in its clinical development because of nosebleeds and gum bleeds. So I think the evidence is there that intervening in this pathway can lead to benefit in boys with DMD. And when you really start thinking about all of the indications in neuromuscular diseases, where it is some structural protein that is missing. And as a consequence, the pathophysiology that arises from that is the same. So whether it's DMD, whether it's myotonic dystrophies, whether it's congenital muscular dystrophies, there's similarity in all of the pathophysiology. So DMD is a good starting point because it's rapidly declining, but it's not so rapid that you have to treat six-month-old babies, right? So you can actually get to a data set relatively quickly that you can then have conversations with the regulators about what is your approval endpoint. So we can, I think, really have a study where you have biomarkers, imaging, biopsy to look at all of these things along with functional measures, right? That's a pretty powerful set of parameters that you can look at. And therefore, that can lead to very compelling data that you can then take to the regulators. What do we need to do to get a registration? Quickly. Ok, great. Yeah, no, that all makes sense. So maybe can you expand upon maybe the competitive landscape in DMD or other neuromuscular disorders for these muscle-preserving or muscle-building type? Yeah, so look, I think in DMD, let's just stick to that for today. You've got the gene therapies. You've got the exon-skipping therapies, right? You've got molecules now that are somehow stabilizing the muscle, Ok? I think 065 is not going to be competitive. It's in combination with this, it can provide greater benefit. So with the exon-skipping, you're looking for that subset of patients. With With 51, it's about 12% of the patient population. We don't need to think about it that way. Any boy with DMD is eligible to go on 065. So let's talk about for a second just for gene therapy. Well, with gene therapy, you're looking at microdystrophin. It has two business ends. But it's truncated in the middle so that you only have about three of those repeats. Whereas dystrophin has 20+ repeats. Utrophin has 17 repeats. During embryogenesis, all of us express utrophin, not dystrophin. Dystrophin is expressed postnatal. We all have utrophin still, but it's localized to the neuromuscular junction. In boys with DMD, it's still there at low levels, right? So why is that nature thought it appropriate to switch expression from utrophin to dystrophin? It probably withstands the rigors of carrying larger weight around better than utrophin. So if you've got microdystrophin, is that really going to be as good as utrophin? So I do believe that while those therapies are beneficial to patients, there's a limited life, Ok, on those. And at the end of the day, it's all about that muscle regeneration. If you can keep that muscle regenerating, you can prolong the time, Ok, that can remain functional. Ok, we just have a couple of minutes left, Jas. Maybe we just wrap up quickly on Elritercept. That transaction's closed now. Yes. Hopefully, share boosted the balance sheet. I'm just kind of thinking what we should look for from that program going forward, and then more from your company perspective, just your cash runway and kind of upcoming events. Yeah, so you know it's now partnered. That means, Ok, we will be having conversations with our partner on what data to present at future meetings. But I think both teams are enthusiastic about presenting additional data at appropriate meetings, which have been in the past, the European Hematology Association meeting and the American Society of Hematology. So what will be presented, I don't know, Ok, right? But with that program, the Phase III RENEW is moving along, Ok, right? And as Takeda solidifies their own development plan in MDS and myelofibrosis for broadening it beyond just the second-line RENEW, we'll share that, Ok? So it's in good hands. My baby, Ok, right? And I really feel that it's in good hands. And they're enthusiastic about it. They're being aggressive about it. So from that perspective, I'm delighted, Ok, right? With respect to cash, at the end of the third quarter, we reported we had $530 million. We will be updating that soon. We also did raise additional capital in the fourth quarter using the ATM that we have not disclosed, along with the $200 million that is there as the upfront payment for Takeda. So cash-wise, we're really well-financed. That allows us to move 065, understand 012, Cibotercept. I'm still very excited about our molecules. Yes, we took a gut punch with Cibotercept, but you know just the way this drug development is, you learn something in the clinical setting. Then you look at it and see, Ok, what is the opportunity as a consequence? But it does take you time to do that. Okay. Well, we really appreciate you coming. Obviously, it's been a challenging few months. So appreciate you coming here, supporting the conference, and hearing your updated thoughts. So look forward to seeing the progress going forward. Well, thank you for giving us the opportunity. Thanks.