Hi. Good morning, everyone, and it's our pleasure to have Kailera with us today, who is somewhat new to the public markets. We have with us CEO Ron Renaud, an industry veteran, CFO Doug Pagán, and then CMO Scott Wasserman. Kailera has a very full pipeline of obesity products with dual agonist and injectable and oral form single agonist, soon triple agonist. Maybe first you can give us an overview of your pipeline and tell us in a crowded development landscape, what Kailera brings to the table in terms of differentiating features.
Yeah. Good morning, Annabel.
Good morning.
Sure. Thank you. Thanks for having us. As Annabel said, I'm Ron Renaud. I'm the President and CEO here at Kailera. Look, we were put in place, we were built with one goal, and that's to elevate the next era of obesity care. As you've written about, Annabel, and I think everybody on this call knows and understands, obesity is clearly one of the largest opportunities in medicine. My guess and my sense is it will be for the foreseeable future. I don't see that changing anytime soon. We know that current GLP-1 medications have changed patients' lives, but demand for all of these GLP-1 based therapies far, far outstrips supply. Most eligible patients are not treated, and patients and physicians want more choices, and I think that's where Kailera comes in.
They want stronger weight loss, they want better tolerability, they want oral options, and they want combinations. There are very few companies that can actually provide that kind of breadth in terms of an obesity-based pipeline. I think history tells us that big categories, we can go back in time, we can look at statins, we can look at immunology, we can look at immuno-oncology. The third, fourth, fifth entrant can win when it brings meaningfully better data, and Kailera intends to be that company in obesity. As you point out, we've got a robust multimodality pipeline. Scott can take you through the details of each of the programs, and Doug can clearly tell you how we're going to make sure that we leverage our great balance sheet to get all of this done. I'll just give a high level in terms of where we are.
Our lead program is ribupatide. We've got ribupatide injection. It's formerly known as KAI-9531. This is our lead. It's a once-weekly GLP-1/GIP receptor dual agonist. This morning we announced that our KaiNETIC program is fully enrolled. Nearly 5,000 patients across 200 sites in 11 countries. Really, really a global approach to developing this program. Behind that is the exact same molecule in a once-daily pill. That's our ribupatide oral program. Very, very excited about this. Scott can talk about the phase II data that generated some very, very compelling weight loss with some of the, I think, what is the best GI tolerability and AE side effect profile that we've seen in the business. Behind that is safiglipron, formerly known as KAI-7535. That's our oral small molecule GLP-1 receptor agonist.
Then, of course, we've got a once-weekly GLP-1/GIP/g lucagon receptor tri-agonist. Really, that's KAI-4729. Really multiple approaches to treating obesity. Hopefully can meet any patient living with obesity anywhere where they are in their treatment path. Couple other items I think that are really, really important to point out here is how we built this portfolio so quickly. Why is it so robust—
Yeah.
—and how did it get so deep so quickly? That is through our Hengrui relationship. This is a pipeline that was built on the basis of this relationship. It allows us to do a lot of things that other companies in the space can't do. First of all, we get human data before we commit capital. Each program that we enter basically has clinical data that is generated by our colleagues at Hengrui before we have to make a capital investment decision. Then they keep producing data that we don't pay to generate. From a capital allocation, from a cost efficiency perspective, this really, really helps us make well-educated decisions that are risk adjusted and in terms of capital allocation, making sure our money is going in the right place.
Lastly, what I'll say here is we've got a team that's done this before. Doug has done this before, Scott has done this before, and we've got a deep bench. We've got Jamie Coleman, who leads our commercial efforts, and I don't think there's anybody in the business that knows more about the obesity marketplace than she does. Really a great team of people that have been there and done that. With that, we're happy to jump into questions.
Yeah. That's fantastic. Thanks for the overview. Going right into ribupatide, that delivered 21% placebo-adjusted weight loss in the phase II-B, which clearly exceeds tirzepatide. What factors do you think contribute to that molecule being so potent? Is it the ratio? What is it exactly, and how is that balanced against tolerability? You mentioned you have some of the best tolerability, so talk to us about that potency versus tolerability and how you got there.
I'll let Scott take you through that. He knows it inside and out.
Yeah. Thanks, Ron, and thanks, Annabel. Good morning to everybody. Just very, very quickly, when Hengrui designed ribupatide or KAI-9531, they designed it to be better than tirzepatide. What we mean by that is they purposefully engineered the molecule to have 3x potency on the GLP-1 receptor, 0.5x on the GIP versus tirzepatide, and a seven-day half-life, which is two days longer than tirzepatide. In and of itself, how they designed molecule was to be better than tirzepatide. At least preclinically, that played out as they were developing it, and that's how they ended up choosing to move it forward. At least clinically to date, based on the data that they've generated, we have a very compelling profile.
Obviously, as Ron just alluded to, we just announced this morning that we completed the enrollment of KaiNETIC, our phase III program, three different studies. We're really looking forward to having that data in the mid-2028 timeframe.
That's great. Maybe you can talk about that phase III KaiNETIC program. It's designed not just for obesity but type two diabetes, and you have an interesting component of greater than 35 BMI. Why the segmentation in that direction for that very obese population? What discussions have you had with FDA on how you're setting yourself apart there, and what is the actual efficacy bar there? Maybe you can address those questions.
Yeah. I'm more than happy to take those questions. First and foremost, KaiNETIC, the program, is three different studies. KaiNETIC-1 and KaiNETIC-2 are kind of brother-sister studies. They are very consistent with global regulatory guidance in terms of how trials in people living with obesity or overweight are conducted. KaiNETIC-1 and KaiNETIC-2. KaiNETIC-1, adults living with obesity or overweight. KaiNETIC-2, that same population with type two diabetes. Again, that is consistent with global regulatory guidance. Then we have maintenance doses there of 4 mg, 6 mg, 8 mg, and 10 mg. The 4 mg and 6 mg are really meant to be kind of a semaglutide and tirzepatide-like. Then the 8 mg and 10 mg are really meant to be potentially category-leading in terms of weight loss. KaiNETIC-3 is the one that you were alluding to with the BMI of 35 +.
The rationale behind doing that study is when we look at the people that are living with obesity globally right now, about half of them have BMIs of 35 +. Based on an analysis of SURMOUNT-1, if you began that study with a BMI of 35 +, after 72 weeks on tirzepatide, about 2/3 of the patients remained obese. In other words, they were still living with BMIs of 30 +. To us, that is an unmet medical need. That is a real opportunity for high-efficacy agents, and we wanted to highlight that in KaiNETIC-3. KaiNETIC-3, there are four different arms. There is an 8-mg and 10 -mg arm of ribupatide, there is a placebo arm, and there is an open-label semaglutide arm. The rationale behind that, very, very simply, semaglutide being open label is because it is in a proprietary pen, so we were unable to blind it.
I think the reason that we chose that as our first head-to-head was that will be the first GLP-1 based medicine to go off patent. We wanted to be proactive and be prepared to inform patients, physicians, and payers about the utility of ribupatide, particularly in patients that need more weight loss and are living with high BMIs. That is the KaiNETIC program.
Okay, great. Thanks for going through the dose selection up to 10 mg, but there is also possibly a 20- mg arm.
Yeah.
I think you're doing a phase II there, or maybe you just talk about that and—
Sure.
—what the possibilities are there?
Thanks, Annabel. We do have an ongoing phase II-B high-dose study that is testing doses up to 20 mg. I think this is what I would call a true phase II-B, right? In that we are really trying to push the dose. The rationale behind that is very simple, right? We wanted to be proactive and not leave efficacy on the table. That study is already enrolled. We'll have data in mid-2027 on that. We're confident in terms of the dose selection. Again, the rationale for trying to push the dose and not leave efficacy on the table is that when we looked at the totality of the Hengrui data, at doses above 3 mg or beyond about three months of dosing, we did not see a significant increase in the amount of nausea, vomiting, or diarrhea.
Obviously that begs the question, can you go higher and not see a concomitant huge increase in nausea, vomiting, diarrhea, and get additional efficacy? Because again, there will be patients that need more efficacy, and we want to be able to provide that with ribupatide.
Okay. Well, you just answered my next question about the titration scheme in light of tolerability. Do you have a simpler titration scheme because of this tolerability, or is it just your standard?
Our titration scheme was based on the kind of start low, go slow philosophy.
Yeah.
Over the first three months, we basically increased by 1 mg a month. It starts off at 1 mg, goes to 2 mg, then 3 mg. After the third month, then we go to 4 mg, 6 mg, 8 mg, and 10 mg. In the high dose study, we then also go to 13 mg, 16 mg, and 20 mg. Obviously, I think when we talk to clinicians that are seeing these patients actively right now, the way that they treat their patients is obviously a lot different than the way that we conduct clinical trials, right?
Yeah.
Clinical trials are based on the regulatory guidance. But really, at the end of the day, what patients and physicians do quite eloquently is that careful dance of how much weight loss they desire as well as the tolerability that they're having in terms of the GI side effects. We suspect, again, I think Ron did a nice job in the opening of alluding to it. Obesity is a chronic disease. We intend to be around for a long time as a company. It's our aspiration to be able to meet any patient where they are in their journey and get them to where they want to be. In order to do that, right, ribupatide, making sure that we have the appropriate doses available to patients so that as they age and as the disease progresses, that we have options for them.
Okay, great. You made a good point that the reason why you got your program so quickly and so cost efficiently is because of Hengrui conducting the trials in China. Just wanted to understand the translatability between China-based trials, and these global trials that you are going into. Can you talk about the differences in the population, maybe differences in the doses, and maybe the quality of the data translating from China into global phase III studies?
Yeah. The top line here is that in general, in the obesity space, it translates pretty well. I think there are a few things that people just need to be aware of when they think about data in the obese or overweight population in China versus outside of China. First and foremost, the definition of obesity and overweight in China is different, right? It is based on BMIs of 28 and 24 with a comorbidity, versus 30 and 27 globally. What that translates to in general is a slightly lower baseline BMI, a slightly lower baseline weight, and theoretically based on peptides and exposures, right, you can use a slightly lower dose in China.
Additionally, at least historically, what we have seen is that in that population, in China in particular, there tends to be a more even distribution between males and females versus outside of China, where typically we are seeing about 2/3 female population. In general, I would say that it is pretty translatable. The few things that we have noticed, is that at least looking at our data, but then also looking at, I should not say our data, I should say Hengrui's data- but then also looking at Lilly's data with tirzepatide in SURMOUNT-1 versus SURMOUNT-CN, and Novo's data. Diarrhea tends to be a little bit more prominent of a symptom in China than outside of China. The last thing I would say is, I think it is just a reflection on where we are in the clinical trial landscape and where we are in development, right?
When tirzepatide and semaglutide started this journey, I think it was a very different environment to where we are today. I think consumer-driven healthcare was not as top of mind. Patients didn't have options. It's a much more complicated but a really great opportunity for us, in terms of being able to really generate meaningful data that can help patients.
Got it. I wanted to switch over to your oral, because that's also part of your story. I think the oral saw about 10% placebo-adjusted at 26 weeks. Where do you see this fitting into the oral landscape, or is this something that you're trying to develop as a similar molecule that you can switch from an injectable into an oral as a type of maintenance treatment maybe, or just maybe to reach a different population with the orals? Can you talk about how you think about that?
Yeah. I'll let Scott kind of get into the details of the data, but clearly, having the oral version of the injectable peptide really puts us, I think, into somewhat of an exclusive category. There's not that many folks that actually have the injectable and the oral version of the exact same drug. That gives us a lot of flexibility. The dosing of the oral peptide where we saw positive data at 25 mg, I think also gives us a lot of cost flexibility as well. As we know, on the oral side, these are pretty expensive drugs to make. I think you talked about kind of going from an induction to a maintenance phase or vice versa. We have maximum flexibility to do that. You're going to have patients that, for example, Scott talked about our focus on the patients with a BMI above 35.
That's an important category. That's going to be 50% of patients in 2030 that right now don't really have a good option for managing weight loss. For that, ribupatide is where we're going to target that at that patient population. You're also going to have patients where they're not going to have a BMI above 35, and they're going to be looking for less significant weight loss. That's where the oral options are going to be important. That's also in that oral category, where you basically see a band of efficacy that's probably somewhere between 10% or 11% and 16% on a placebo-adjusted basis. Oral ribupatide fits right in that. But where oral ribupatide is standard deviations away from the rest of the category is on the GI tolerability that we've seen so far.
From a nausea and vomiting perspective, it is very possible that oral ribupatide could be the drug of first choice for patients that are looking for that 10%-15% weight loss and a very, very tolerable side effect profile. I think the flexibility there, Annabel, is pretty wide-ranging.
Got it. Do you have an idea yet of the phase III design for this oral, like the titration? What are the limiting steps to initiation at this point?
Scott?
Yeah, no, we have not disclosed that yet, Annabel. What we are guiding to is starting our phase IIIs in the first half of 2027. We are cautiously optimistic on executing towards that. As Ron alluded to, we look at ribupatide as a franchise, and really being able to span the breadth of everybody, and every body that is living with obesity out there. From people that do not need as much weight loss, but really value an oral and want tolerability, to patients that need high efficacy and are not getting their needs met with the current agents out there. In many ways, I used to say ribupatide is kind of a franchise in a peptide or a program in a peptide.
Okay, so I guess that begs the question for the oral small molecule, which is a GLP-1. So you have a dual agonist that seems to be pretty versatile right now as a peptide, so why go for a single agonist, GLP-1 small molecule? Is it more for combinations? Is it for other purposes? What is the intention for this product or program?
Yeah, I think, look, it is a great question because what it does is it highlights the breadth and depth of our portfolio, right? Outside of big pharma, I do not think there is another portfolio of obesity medications that is as consequential as what we have at Kailera. We can let the data drive that decision, Annabel. So far we love what we have seen so far with our oral peptide. But we also have a significant phase II program with safiglipron, with our oral small molecule. We will get the data from that program, and we can make a decision. As you know, small molecules are a lot easier to work with, very combinable. From a scale-up perspective, there is a bit more simplicity to small molecules than there are to oral peptides.
So we will let the data develop itself, and we will make a decision when we have that data. Quite frankly, that is a great position to be in my opinion.
Okay, great. I want to be able to talk also about your triple -G, and how are you setting that apart from other triple -Gs? What do you hope to achieve with this asset? Are you expanding beyond obesity at this point?
Yeah, look, again, that's a bit of an earlier program for us, but we've got some great data that our colleagues at Hengrui are sharing at EASD this week. That was a drug that we hear a lot about the triple- Gs. The glucagon activity potentially having an impact on liver fat and going beyond obesity, other places to go there. That's something we are excited about, gives us optionality. As Scott mentioned at the beginning, ribupatide was designed to be better than tirzepatide. KAI-4729 was designed to be better than retatrutide. We're going to let, again, in that same instance, we're going to let the data play out. Ribupatide so far as a dual agonist is very,very competitive with everything that we've seen out there. Other triple agonists, even some of the data that's coming forward this week at EASD—
Yeah.
—ribupatide, the data keeps coming to us, and I think ribupatide is holding its own quite well.
Yeah. I guess one more question about the landscape is, some programs are starting to push to monthly dosing. Do your pharmacokinetics give you the possibility for that at any point, in any way?
Yeah. Look, I don't want to get into the details of some of the things that we're looking at, but if you look at what goes on in the compounding industry, I think that's a very good proxy for what's going on. We spend a lot of time as companies talking about data per protocol analyses and the way the studies were run. But if you look at what goes on in the real world, even with the branded medications and the compounded, they get used once a week, once every other week. In some instances, we've heard about patients taking, whether it's 15 mg of tirzepatide or 7.2 mg of Wegovy, they're not doing it every week. The vast majority of patients are doing it less frequently, and they're still getting very desirable outcomes.
I think we'll wait and see, but together with our colleagues at Hengrui, we're looking at a lot of different potential pathways there.
Great. In the last few minutes, maybe you can review the catalysts that you're going to be seeing in the next 6- 12 months just to get us all excited.
Sure. Doug, do you want to walk through that?
Yeah, absolutely. We are very excited as we turn the corner on the year to 2027 and some meaningful data readouts for ourselves. Scott and Ron both spoke about the high-dose phase II-B ribupatide study that will read out mid-next year, as well as the phase II KAI-7535. We also are embarking on a phase I for KAI-4729 later this year, which will read out in 2027 as well. So that will be a data-rich year for us. As we turn the corner subsequently into 2028, the KaiNETIC program will read out. That, of course, will be very meaningful for the lead. We haven't guided yet to when we will see data on the oral, but as Scott mentioned oral ribupatide phase III should start in the first half of 2027.
Okay, great. Any IP and partnership issues you have with your partnership with Hengrui, does that limit you in any kind of way as far as finding a partnership or even licensing the asset for commercial use?
Yeah.
Is there any limitation there?
No, the Hengrui team has done a great job building a very formidable IP portfolio. They've been very aggressive from the very early days. We're the beneficiary of that. We're also continuing to generate our own intellectual property, as they've passed the baton to us with all of these programs. I think this is a very strong IP portfolio. Then, look, we're focused on building the best obesity company that we can. We've got a great portfolio. We've got a great management team. We're building this to go the distance. That doesn't mean we don't keep all strategic options open. But we're focused on really leveraging what we think is the best obesity portfolio outside of pharma.
Great. Fantastic.
Ann, I'll just append on that.
Yeah.
We have global rights outside of the China region for all of the assets we've in-licensed from Hengrui.
Awesome. All right. I think we're just about out of time. Thank you very much for your time today, and look forward to 2027.
Thanks for having us, Annabel.
Thanks so much. We appreciate it.
Take care. Bye bye.
Bye.