Morning, everyone. Suraj Kalia, Senior Medical Devices Analyst at Oppenheimer. Really pleased to have an interesting diabetes company under the radar so far present this morning. I hope a lot of you guys, you know, when you'll look at this presentation, connect the dots as to why I find this really intriguing. We're pleased to have CEO Sarah Howell with us this morning. Sarah, it's a pleasure. I'll let you take the floor, and I'll reserve us five minutes towards the end with Q&A.
Perfect. Thanks, Suraj, and good afternoon, everybody. It's a real pleasure to be here and presenting to you today. As Suraj said, I'm Dr. Sarah Howell. I'm the CEO of Arecor Therapeutics. [audio distortion] We are based in Cambridge in the U.K., and we're developing superior therapeutics that can reduce treatment burden and improve outcomes for people living with diabetes, obesity, and other cardiometabolic diseases. I would say what is AT278, this is an ultra-concentrated, ultra-rapid acting insulin. The unique thing, the only insulin of its kind to have this profile. I'll talk you through the unmet patient need here. It's very much designed for use in automated insulin delivery systems, which I'll talk about as AID systems from now on, and really addressing unmet need in multi-billion-dollar market opportunities here.
We also have an R&D effort developing a technology delivery platform for the oral delivery of peptide. I think you all know GLP-1s exploding now in development, but there's a real issue here with the oral delivery of those and the bioavailability. Again, I'll talk through that in a little bit more detail here. Hopefully, what you'll see through the presentation today, and I think leading on from Suraj's introduction here, we have multiple near-term value inflection points, furthering our ambitions here to bring significant benefits to people living with these chronic conditions and building significant value for our shares. Taking a look at our pipeline here. In terms of our internal proprietary products, as I've mentioned, we're very much focused on our lead clinical product, AT278.
We have conducted two phase I clinical studies for this product in the relevant patient population, so in Type 1 diabetics and also Type 2 diabetics with high BMI. I'll talk you through the clinical data later in the presentation today. We've also partnered with Sequel Med Tech, a U.S.-based insulin pump company, to combine AT278 with their innovative AID system. Again, I can talk about that in a little bit more detail. For the oral delivery, it's very much at R&D stage here, and I'll be able to update you on our progress there. What's important to note here for our proprietary pipeline, we're taking existing therapeutics that have already been approved. This is important because it means the safety and efficacy of these products is proven, so that clinical risk is much lower for Arecor. We're bringing enhancements here.
We're refining and improving their profiles and their superiority to meet unmet patient need in areas of high-value markets as well. It's very much a de-risked pipeline. We also partner on a very selective basis with leading pharma and med tech companies. This is where we use our drug development expertise and delivery platforms to develop versions of their pipeline or our market products there. This is under a licensing model. As you can see here, we've partnered with some of the largest companies in the world in the healthcare space, Eli Lilly, Ligand, and MiniMed, who you, I'm sure you've seen very recently IPO'd. Just now zooming into AT278. As I mentioned, AT278 is the first and only ultra-concentrated, ultra-rapid acting insulin. It's five times the concentration of standard best-in-class insulins that are available to patients today.
We have demonstrated superiority in its pharmacokinetic and pharmacodynamic profile. This means it's the fastest-acting insulin available as well or in development today. It's really been designed with this profile to meet some very specific unmet needs when used in combination with AID systems. Just as a very brief introduction. An AID system is where a patient will wear a continuous glucose monitor, which measures their glucose levels in real time. These measurements are fed to an algorithm which calculates based on those glucose readings, how much insulin is required to keep them inside their target glucose range. It's all around keeping inside this Time-in-Range and improving the amount of time they spend in range, and it's constantly delivered via the insulin pump. These systems are available today.
All of this technology is available, but there's still some very real challenge. The burden of use is still relatively high, with patients needing to carb count to announce that they're going to have a meal, and this is due to the speed of insulin. We need much faster insulins that are much more physiological and can react in real time to those fluctuations in blood glucose, and they can only afford a period of time due to the amount of insulin that we can get on board here. It's these very real challenges that we're looking to address with AT278. Despite this, we've seen significant growth in the AID market. This, in the U.S. and globally. Last year, the estimated sales, so this is insulin, devices, so this is the AID market, today was around $5.7 billion.
Despite this, it still remains a fairly under-penetrated market. If we look towards the U.S., where the uptake of AID systems by the patient population is largest, still only around 40% of people with Type 1 diabetes and only around 5% with Type 2 diabetes use an AID system today. This is despite the fact there's a whole wealth of clinical and real-world data out there today showing us that people do better if they use an AID system. They have better blood glucose control, which leads to improved longer-term outcomes. The question is, why are so few still using these AID systems? How can we, as a combination of AT278 with the AIDs, drive that adoption and drive those patient populations to move over from multiple daily injections to AID? Obviously, still specific challenges around moving across to AID.
First and foremost, from a patient perspective, this is around reducing burden whilst improving their outcomes. What patients are asking for here is they want to be able to wear these AID systems and their insulin pumps for longer. Current standard of care is three-day wear. They want to be able to wear them for 7 days plus, in almost a fit-and-forget model here. They would like them to be much smaller and more discreet. It's a very visible indicator of the fact that you are living with a chronic disease. Now, if you want to be able to wear these insulin pumps for longer, and you want them to be much smaller, it means you need to be able to get much more insulin on board in a much smaller space. You need this ultra-concentrated insulin for use in this next generation of AID systems.
There are people with diabetes who have high total daily dose requirements. These are patients requiring more than 100 units of insulin a day, and they can't even achieve current standard of care three-day wear. They'll run out of insulin before they get to that three-day wear time, which means they would need to change out their insulin cartridges, change their infusion sets. If they're using a disposable patch pump, throw that away and apply another patch pump. This is all high burden and obviously high cost as well. It's making AID use simply not practical for this segment of the patient population. We're really striving here to improve clinical outcomes, to improve control, and improve quality of life.
To do this, you need much faster-acting insulins that are more physiologic and react more in real time to those fluctuations in blood glucose, particularly around mealtimes where we see blood glucose rising really rapidly. You need a very rapid-acting insulin to be able to bring that blood glucose back inside the healthy target range and achieve that higher Time- in- Range. That needs a combination of then highly concentrated insulin, but it must be ultrarapid. Of course, we need this to be cost-effective for patients and payers here. If we can improve outcomes and long-term care, we can reduce the cost burden across the whole health ecosystem and of course significantly improve quality of life for patients and their carers.
AT278 is the insulin with this profile, so this highly concentrated, ultrarapid-acting insulin to drive this adoption of the next generation of AID systems. Maybe we can zoom in and look at this in terms of patient numbers here. If we look at the longer wear, it's going to 7-day wear. For people on intensive insulin therapy, that's the addressable patient population here. For the Type 2 nearly 50%, and this is U.S. data, currently would not achieve even standard of care of three days. But if we move to 7-day wear, then almost all of that Type 2 patient population won't make it to 7-day wear before they run out of insulin.
This is based on modeling with the largest insulin capacity that's available today, so 3 ml cartridge, and using those that are available, so 100 units per ml or U-100 insulin. Now, if we look at AT278, so U-500 insulin, all of the Type 2 patient population would make it to three days, and almost all of them could make it to 7 days. It's not just a Type 2 problem. We're also seeing this for Type 1 diabetics as well. Over 50% of Type 1s won't make it to 7-day wear with the current insulins that are available today, but all of them, again, make it to 7-day wear with U-500. This longer wear time is very much the focus of the major insulin pump companies today. Medtronic and Tandem have 7-day wear approved.
We have others following this. We have this real challenge here of being able to then practically get the patient population to this 7-day wear, plus here. That's very much the focus of AT278. If you then obviously miniaturize these pumps further, so you make smaller, maybe going to a 2 ml or a 1 ml cartridge, you will clearly exacerbate this issue. Then you most certainly need a much more concentrated insulin, such as AT278. If you look at the size of this patient population. In the U.S., there are around 4 million people that are on intensive insulin therapy that have diabetes. Around 1 million of those require more than 100 units of insulin a day.
This is a patient population [audio distortion] three day wear in those current systems. You have about 1 million of people with diabetes currently using AID systems in the U.S. and they are looking for longer wear, smaller form factors and of course better outcomes, better Time-in-Range, all of which come with highly concentrated ultra-rapid-acting insulin. That's 2 million population translates to an insulin revenue opportunity of over $3 billion to today. Then we can look at opening access and AID access to the rest of the patient population.
That leaves another 2 million people with diabetes that are on intensive insulin therapy in the U.S. that could move across to a next generation AID system, giving a total addressable market opportunity of $5 billion, of which we would expect AT278 in combination and partnership with the AID companies here to be able to take a significant market share. Now if we look at the data here. What you're looking at here is the pharmacodynamic, pharmacokinetic, sorry, profile. This is showing insulin exposure. Insulin is injected at time zero here, and then we measure the insulin in the blood serum over time. What you can very clearly see here is a shift to the left. AT278 is in orange here, and we see the shift to the left.
We have the onset of appearance of AT278 much faster, and we're getting more AT278 in the blood much faster than NovoRapid or NovoLog, as you would call it in the U.S. here. What you can also see, if you look at Humulin R U-500 in the purple, it has this very long and slow profile. It's slow to get that maximum exposure into the blood, and then there's very slow clearance over time. This very much translates [audio distortion] to the pharmacodynamic profile here, which is probably best shown in the next slide. Again, what we're looking at here is the PK profile on the left here. This is the appearance of insulin in the circulation. We saw this five minutes faster compared to NovoLog, which is a substantial reduction in terms of that appearance time.
When we look at the half maximal concentration, which is a really robust measure of how fast insulin is absorbed, it's 24 minutes faster compared to NovoLog, which is really significant here. Physiologically, as you concentrate insulin up, as we've seen with Humulin R U-500, it normally depresses its time action profile, so you'd expect it to be slower acting. We've overcome this with our technology to be able to develop this very ultra-rapid but ultra-concentrated insulin here. Looking over to the right on the pharmacodynamic profile, this translated directly across the pharmacodynamic profile.
We see that onset of glucose lowering profile 5 minutes faster and this much faster and greater blood glucose lowering profile, which is exactly the profile of insulin you need for those. We can be more aggressive with those algorithms and keep the individuals in that very tight Time-in-Range without them having to interact with the system, without them having to announce they're having a meal or count their carbs here. If we look at the tables at the bottom here, essentially on the left-hand side, this is showing how much insulin is available in the first and second hour, and then through the whole duration of the clamp. This was an euglycemic clamp study. You can see here first, it's the pharmacokinetic profile is 48% in favor of AT278.
If we look across the pharmacodynamic profile, we've got 66% more insulin on board in that first hour. This is really key. This is that time if you've eaten some food, your blood glucose has risen really rapidly. You need to get that insulin on board and lowering the blood glucose as quickly as possible to keep inside that healthy time. Now, I haven't shown you the Type 1 results. I say that they're very similar. In our Type 1 diabetic study, we compared AT278 again to NovoLog. We didn't have the open label Humulin R U-500 arm in that. Essentially, we saw the same results here. We saw this shift to the left and showed superiority compared to NovoLog. In both studies, they met all of the primary and all of the secondary endpoints here.
The combination of these studies [audio distortion] AT278 can maintain this very fast and superior onset of action and glucose-lowering profile irrespective of the type of diabetes that the individual has, and very importantly, irrespective of their BMI, as well as the Type 2 study was in overweight and obese Type 2s, and no safety signals were detected here. This demonstrates to us we have the only highly concentrated ultra-rapid profile that can meet all of these key requirements and address the unmet needs for the patient population when used in combination with AID systems. In terms of next, we've been to the FDA and had a very positive Type C meeting, so we've locked down our phase 2 clinical study design. It's a pretty innovative clinical study design here.
We're using Time-in-Range as our primary endpoint, so this will be really data-rich for us in demonstrating where we're looking for that superiority. It will also be in Type 1 and Type 2 diabetics. This will be a six-week crossover study where we will be comparing AT278 to NovoLog again, but via continuous infusion in an AID system, and we'll be using Sequel Med Tech's twiist pump here as we perform this study in combination with Sequel Med Tech. We anticipate then requiring a phase III clinical study for to be able to file for approval in the U.S. and in other major territories here. It should be noted here, these are because the clinical efficacy and safety of insulin is already demonstrated here, that these are very targeted studies.
We're looking to demonstrate the superiority of our highly concentrated ultra-rapid-acting insulin. We'd anticipate this to be a less than 500-subject study, very focused on the outcomes of that study. I'm just very briefly going to talk about our oral delivery of peptides and platform development here. Firstly, look at the challenge here. We know therapeutically, peptides are becoming really important agents, particularly in the treatment of diabetes and obesity and other cardiometabolic diseases. Despite this, the fact that there are over 800, there are only two peptides on the market today that are orally delivered, and these have very low bioavailability, less than 1%. This is because the oral delivery of peptides is extremely challenging. It's due to their molecular characteristics lead to this very low bioavailability. The challenges here are really twofold.
Through oral delivery, the peptides themselves are subject to harsh pH and digestive enzymes which lead to poor bioavailability of the peptide due to the degradation by these drug digestive processes. We also see what we have seen that's worked, and it's worked in the two products that are available today, albeit with less than 1% bioavailability as permeation enhancers to get across that absorption barrier. Unfortunately, these suffer from poor solubility in this harsh environment, which means there's a low uptake by the cells of the digestive system. Arecor is using its proven delivery challenge here that we have across a very broad range of injectable peptides and proteins and translating this across to oral delivery. We've started in the area of GLP-1.
However, if we're successful in developing a GLP-1 with improved bioavailability, it's highly translatable to other peptides, which obviously offers a huge opportunity for us, both in partnering high-value pharmaceutical companies, but also the ability for us to take clinically validated assets ourselves and converting them to oral agents. In terms of our status there, we've had initial very positive results using the Arecor proprietary matrix here in both stabilizing semaglutide. This is a GLP-1 that we're working on. It's the GLP-1 behind Rybelsus, and also maintaining that solubility of the permeation enhancers here. Throughout the rest of 2026, we'll be performing iterative non-clinical PK pharmacokinetic studies here, which are really measuring and informing us on the bioavailability here for us to be able to inform that optimum development approach moving forward there.
This has obviously commercial applicability in its own right for GLP-1, Rybelsus, semaglutide, the oral posted sales of $3.4 billion last year. That's, remember, is with bioavailability of less than 1%. If we can improve that would bring benefits in its own right, and then we can translate to a broader set of peptides. I think we know there's been a huge amount of deal-making. This is just a snapshot really in this space. Huge amount of interest through to the most recent acquisitions of Pfizer, of Metsera and I'm sure you would all have seen. Outlook in those value inflection points. Clearly for AT278, this addresses significant unmet need in a high multi-billion dollar market.
We see that initial first adopters TAM in the U.S. is a $3 billion-plus opportunity with upside to grow, within the U.S. and of course ex-U.S. as well. We've demonstrated PK/PD superiority going head-to-head that are available today. We have a partnership with Sequel Med Tech to be able to develop this through phase II and beyond, all the way through to commercialization. This real opportunity to catalyze this next generation of smaller, longer wear AID systems. The next value inflection point here, of course, is entering into that phase II clinical study in the second half of next year, this year, which would then read out in the second half of next year. As I just mentioned, developing a oral delivery technology platform for delivery of peptides. This would be really game-changing here.
We can improve that bioavailability above 1% across a broad range of peptides, and we'll be generating key PK data throughout the rest of 2026. Suraj.
I hope you'll share my, you know, enthusiasm for what's going on in the story. Sarah, a few questions, if I could.
Sure.
You'll admittedly have partnered with Sequel.
Yes.
Yes, Sequel has a very intriguing platform from an accuracy perspective. Let's say you want to expand into, let's say, Tandem's Sigi or Medtronic's tubed pump. Does it mean new trials, like drug device combos, or how do you envision post-Sequel? You know, when is AT278 gonna be on a standalone basis? I know there are many questions in the room. Hopefully, you get the point.
Yeah. No, it's a good question. The data that we're generating here, the phase II and the phase III clinical data, really there we're demonstrating when delivered via continuous infusion via an AID system, it will be demonstrating both Time-in-Range , and then average blood glucose. That data, there is highly translatable then to the other AID systems. If we look at how traditionally insulins have been developed and approved, they are developed pretty much agnostic to the delivery device essentially, which AID system. Once on market and approved, there are small clinical studies that are usually conducted by themselves to demonstrate the accuracy of delivery, et cetera, and to generate a data package to gain approval on the AID system label for that insulin. The AT278 would very much follow that pathway.
There wouldn't be a need, for example, to repeat a large phase III clinical study. That clinical data would underlie and support the use in any AID system with additional studies that would be required on market.
Fair enough. Sarah, in the minute we have left, quickly, what are the lessons learned from once-weekly icodec or efsitora, you know, that y'all are avoiding right now or at least incorporating in your development process?
Yeah, I mean, it's a good question. Those weekly insulins, I think for AT278, where it differs here, we, you know, we're very much going, and it's very applicable for the Type 1 and Type 2 [audio distortion] and I think that was some of the challenges there within the weekly basals being, you know, are they, are they a product for Type 1 diabetics? I think, you know, that was some of the challenges there. This is very much an insulin designed for both Type 1s and Type 2s, and there's no concerns here. We don't have any concerns around late hypos, for example, here. We have this, you know, fast on/off profile. You know, I don't think we'll. Clearly, you know, the FDA, we've got a good relationship with the FDA. We've had a great Type C meeting with them.
I think we're leveraging, and we will go and seek advice and have conversations with the FDA as often as we can so that we don't get any surprises later in development.
Yep. Fair enough. Sarah, thank you so much for presenting. Very unique story. We do appreciate your time today. Thank you so much.
Thanks, Suraj. Pleasure.