ARECOR THERAPEUTICS PLC (AREC) March 2026 Conference Transcript

Morning, everyone. Siraj Kavri, a senior medical device analyst at Oppenheimer. Really pleased to have an interesting diabetes company under the radar so far present this morning. And I hope a lot of you guys, you know, when you 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 resurface five minutes towards the end with Q&A.

Perfect. Thanks, Saraj. And good afternoon, everybody. It's a real pleasure to be here and presenting to you today. As Saraj said, I'm Dr. Sarah Howell. I'm the CEO of Aricor Therapeutics. We're based in Cambridge in the UK and we're developing superior therapeutics that can reduce treatment burden and improve outcomes for people living with diabetes, obesity, and other cardiometabolic diseases. This is AT278. This is an ultra-concentrated, ultra-rapid-acting insulin. It's 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. I'm really addressing unmet need in multibillion dollar market opportunities here. We also have an R&D effort developing a technology delivery platform for the oral delivery of peptide. exploding now in development but there's a real issue here with the oral delivery of those and the bioavailability and again I'll talk through that in a little bit more detail here and hopefully what you'll see through the presentation today and I think leading on from Siraj 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 us 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 at 278 and we have conducted two phase one clinical studies for this product in the relevant patient population so in type 1 diabetics and also type 2 diabetics with high bmi and i'll talk you through the clinical data later in the presentation today. We've also partnered with Sequel MedTech, a US-based insulin pump company, to combine AT278 with their innovative AID system. And again, I can talk about that in a little bit more detail. Then 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. But what's important to note here for our proprietary pipeline, we're taking existing therapeutics that have already been approved and this is important because it means the safety and efficacy of these products is proven so that clinical risk is much lower for our alcohol but 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 so it's very much a de-risked pipeline. We also partner on a very selective basis with leading pharma and medtech companies. This is where we use our drug development expertise and delivery platforms to develop versions of their pipeline or on-market products there. This is under a licensing model. And 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 I'm sure you've seen very recently IPO'd. So 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. So this means it's the fastest acting insulin available as well or in development today. And it's really been designed with this profile to meet some very specific unmet needs when used in combination with AID systems. So just as a very brief introduction so an AID system is where a patient will wear a continuous blood glucose monitor which measures their glucose levels in real time these measurements are fed to an algorithm which calculates based on those blood glucose readings how much insulin is required to keep them inside their target blood glucose range so it's all around keeping inside this time in range and improving the amount of time they spend and it's basically delivered by the insulin pump so 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 so 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 be born for a period of time due to the amount of insulin that we can get on board here. So it's these very real challenges that we're looking to address with AT278. And despite this significant growth in the AI market, so this in the US and globally. Last year, the estimated sales, so this is insulin devices, so this is the AID market, today was around $5.7 billion. But despite this, it still remains a fairly underpenetrated market. If we look towards the US, 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. And 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 have a system, they have better blood glucose control, which leads to improve longer term outcomes. So the question is, why are so few still using these AID systems and 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? And there's still specific challenges around moving across to AID. So first and foremost, from a patient perspective, this is around reducing burden whilst improving their outcomes. And 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 seven days plus and 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 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. So you need this ultra concentrated insulin for use in this next generation of AID systems. And then there are people with diabetes who have high total daily dose requirements so these are patients requiring more than 100 units in 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 then 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 outcomes we're really striving here to improve clinical outcomes to improve control and improve quality of life and 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 meal times 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 and achieve that higher time in range so that needs a combination of then highly concentrated insulin but it must be ultra rapid and of course we need this to be cost effective for patients and payers here so 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 and AT2 is insulin with this profile so this highly concentrated ultra rapid acting insulin to drive this adoption of the next generation of aid systems so maybe zoom in and look at this in terms of patient numbers here so if we look at the longer wear and it's going to seven day wear so for people on intensive insulin therapy and so that's the addressable patient population here for the types nearly 50 percent and this is US data currently would not achieve even standard of care of three days but if we move to seven day wear then almost all of that type 2 patient population won't make it to seven day wear before they run out of insulin and this is based on modelling with the largest insulin capacity that's available today so three mil cartridge and using those that are available so 100 unit per mil or u100 insulin now if we look at at 278 so u500 insulin all of the type 2 patient population would make it to three days and almost all of them could make it to um seven days but it's not just a type 2 problem we're also seeing this for um type 1 diabetics as well over 50 percent of type 1s won't make it to seven day wear with the current insulins that are available today but all of them again to seven day wear with u500 and this longer wear time is very much the focus of the major insulin pump companies today medtronic and tandem have seven 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 seven day wear plus here so that's very much focus of at278 if you then obviously miniaturize these pumps further so you make it smaller maybe going to a two mil or a one mil cartridge you will clearly exacerbate this issue and then you most certainly need a much more concentrated insulin such as AT278. If you look at the size of this patient population so in the US there are around four million people that are on intensive insulin therapy that have diabetes around a million of those require more than a hundred units of insulin a day so this is a patient population even three-day wear in those current systems and you have about a million of people with diabetes currently using AID systems in the US and they're looking for longer wear smaller form factors and of course better outcomes better time and range all of which come with a highly concentrated ultra rapid acting insulin and that two million patient population translates to an insulin revenue opportunity of over three billion dollars today and then we can look at opening access and aid access to the rest of the patient population that leaves another two 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. We have entered a partnership with Sequel MedTech. Sequel MedTech are a company with a rich history in innovation. They've brought to market the twist aid system in just over two years since they were founded back in 2023 and they've achieved full um u.s national coverage and now which they announced last week and they are well funded they raised over 500 they were founded and they have fda approval for this twist system now the reason that we've partnered with sequel medtech and vice versa here is that we have very much a shared vision of bringing that next generation of aid systems to people with diabetes to improve their outcomes and lower the burden and also within the twist system they have what they call eyeshore technology and this is technology that very precisely measures each in a very safe system for the delivery of a very highly concentrated, a five times concentrated insulin. So we've entered into initial partnership to get ready for phase two clinical development, which we're doing at the moment. So both companies are co-funding those studies and manufacturing, et cetera, to get into filing the IND with the FDA. And we'll be ready to enter is a pivotal day to clinical study in the second half of this year and that's subject to the final terms of the broader strategic co-development agreements that we're putting in place with SQL MedTech at the moment and also of course subject to funding. I'm going to talk you through some of our clinical data. I'm going to show you the data just for the type 2 study at this stage in the interest of time but happy to talk through the type 1 data as well with anybody that's interested offline so this is a double blind randomized two-way crossover study in 41 type 2 diabetics here comparing the pharmacokinetic and pharmacodynamic profile of AT278 to Novolog so this is Novo Nordis U100 insulin compared to AT278. And then an additional open comparison to Humulin RU500. So this is concentrated insulin. It's the only highly concentrated insulin available to patients, the same concentration as AT278. So now if we look at the data here, so what you're looking at here is the pharmacokinetic profile. So this is showing insulin exposure. Insulin is injected at time zero here, and then we measure the insulin and the blood serum over time. And what you can very clearly see here is the shift to the left. So AT278 is in orange here, and we see the shift to the left. So we have the onset of appearance of AT278 much faster, and we're getting more AT27 in the blood much faster than Novarapid or Novalog, as you would call it in the US here. And what you can also see, if you look at Humulin RU500 in the purple, it has this very long and slow profile. So it slows up to get that maximum exposure into the blood, and then there's very slow clearance over time. And this very much translates to the So dynamic profile, which is probably shown in the next slide. So, again, what we're looking at here is the PK profile on the left here. So this is the appearance of insulin in the circulation. We saw this five minutes faster compared to NovaLog, which is a substantial reduction in terms of that appearance time. And then 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 RU500, it normally depresses its time action profile, so you'd expect it to be slower acting. we've overcome this technology to be able to develop this very ultra rapid but ultra concentrated insulin here and then looking over to the right on the pharmacodynamic profile this translated directly across the pharmacodynamic profile so we see that onset of glucose lowering and profile five minutes faster and this much faster and greater and blood glucose lowering profile which is exactly the profile of insulin you need for those systems you can be more aggressive with those algorithms and keep the individuals in that very tight timing range without them having to interact with the system without them having to announce they're having a meal or count their carbs here and then 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 a used glycemic clamp study so you can see here first it's the pharmacokinetic profile is 48 percent in favor of AT278 and then if we look across the pharmacodynamic profile we've got 66 percent more insulin on board in that first hour and 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 touch now i haven't shown you the type results today but they're very similar in our type 1 and diabetic study we compared at278 again to novolog we didn't have the open label humulin ru 500 arm in that but essentially we saw the same results here we saw this shift to the left and showed superiority compared to Novolog and in both studies they met all of the primary and all of the secondary endpoints here. So the combination of these studies shows that 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. So, this demonstrates to us we have the only highly concentrated ultra-reflective 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 steps, we've been to the FDA and had a very positive type C meeting. So we've locked down our phase two clinical study design. It's a pretty innovative clinical study design here. We're using time and range as our primary endpoint. So this will be really data rich for us and demonstrating where we're looking for that superiority. It will also be in type one and type two diabetics. So 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 MedTech's twist pump here as we perform this study in combination with Sequel MedTech. We anticipate then requiring a phase three clinical study to be able to file for approval in the US and in other major territories here. But 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. So we'd anticipate this to be a less than 500 subject study. So very focused here, very focused on the outcomes of that study. So I'm just very briefly going to talk about our oral delivery of peptides and platform development here. So 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. But despite this, the fact that there's over 800,000, there are only two peptides on the market today that are oily delivered. And these have very low bioavailability, less than 1%. And this is because the oral delivery of peptides is extremely challenging. it's due to their molecular characteristics lead to this very low bioavailability so the challenges here are really twofold and through oral delivery the peptides themselves are subject to harsh ph and digestive enzymes which lead to portions of the peptide due to the degradation by these digestive processes and we also see what we have seen that's worked and has worked in the two products that are available today albeit with less than one percent by availability is permeation enhances to get across that absorption barrier but unfortunately these suffer from poor solubility in this harsh environment which means there's a low uptake by the cells of the digestive system so our core is using it's 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 glp1 however if we're successful in developing a glp1 with improved by availability 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 so in terms of our status um there we've had initial very positive results using the aracore proprietary matrix here in both stabilizing semaglutide so this is a glp1 that we're working on it's the glp1 and behind rebelsus and also maintaining that solubility of the permeation enhancers here. And then 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. So this has obviously commercial um applicability in its own right for glp1 rebelsis semi-glutide the all of the posted sales of 3.4 billion dollars last year and that's remember is with and by availability of less than one percent so if we can improve that and that would bring benefits in its own right and then we can translate to a broader set of peptides i think you 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 and Matsera, and I'm sure you would have all have seen. So, sort of outlook and 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 US is a 3 billion plus opportunity with upside to grow within the US and of course ex-US as well. We've demonstrated PKPD superiority going to head to head decisions that are available today. We have a partnership with SQL MedTech to be able to develop this through phase two and beyond all the way through to commercialization and this real opportunity to catalyze this next generation of smaller wear smaller longer wear aid systems and the next value inflection point here of course is entering into that phase two clinical study in the second half of next year this year which would then read out in the second half next year just mentioned developing a oral delivery technology platform for delivery 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.

Siraj? I hope you'll share my enthusiasm for what's going on in the story. Sir, a few questions, if I could. You'll admittedly have partnered with SQL, And yes, SQL has a very intriguing platform from an accuracy perspective, but let's say you want to expand into, let's say, Tandem's CIGI or IMED's foot pump. Does it mean new trials like drug device combos, or how do you envision post-SQL, you know, or is 8278 going to be on a standalone basis? I know there are many questions in the run. Hopefully you get the point.

Yeah, no, it's a good question. So the data that we're generating here, the phase two and the phase three clinical data, really there we're demonstrating when delivered via continuous infusion via an AID system, we'll be demonstrating both time and range and then the industry, so average blood glucose. And that data there is highly translatable then to the other AID systems. So 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. And then 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. So AT278 would very much follow that pathway. So there wouldn't be a need, for example, to repeat a large phase three clinical study. That clinical data would underlie and support the use in any AID system with that would be required on market.

Fair enough.

And Sarah, in the minute we have left quickly, what are the lessons learned from once weekly icodec or ephistora you know that you're avoiding right now or at least incorporating in your development process yeah i mean it's a good question so those weekly insulins i think for 8278 where it deficit we you know we're very much going and it's very applicable for the type 1 and type 2 i think that was some of the challenges there within the weekly basils being you know are they are they a product for type 1 diabetics so i think you know that was some of the challenges there so this is very much an insulin design 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 so we have this you know fast on off profile. So, you know, I don't think we'll... And 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. Fair enough. Sarah, thank you so much for presenting a very unique story. We do appreciate your time today. Thank you so much.

Thanks, Siraj.