Arecor Therapeutics plc

Good afternoon, ladies and gentlemen, and welcome to the Aracor Therapeutics PLC Interim Results Investor Presentation. Throughout this recorded presentation, investors will be in listen-only mode. Questions are encouraged. They can be submitted at any time via the Q&A tab that's just situated on the right-hand corner of your screen. Please just simply type in your questions and press send. The company may not be in a position to answer every question it receives during the meeting itself. However, the company can review all questions submitted today and will publish those responses where it's appropriate to do so. Before we begin, I would just like to submit the following poll. And if you could give that your kind attention, I'm sure the company would be most grateful. And I would now like to hand you over to CEO Sarah Howe. Sarah, good afternoon.

Good afternoon and welcome, everybody. Thank you for taking the time to join us today. So I'll be talking through our interim results for the six month ending the 30th of June, 2024, and also a little bit more about the outlook and upcoming milestones for our core therapeutics. So I'll draw your attention to our legal notice. So for those of you that might be joining us for the first time today, I'll just spend a few minutes really giving some background information, a high-level view of ARACORE. So at ARACORE, we're very much focused on transforming patient care by bringing enhanced therapeutic medicines to market that are more effective, easier to use, and safer. And we do this by leveraging our innovative and proprietary formulation technology platform, Aristat. So we're essentially developing novel formulations of existing therapeutic medicines that bring these enhanced properties. We have a very diverse and de-risked portfolio of both in-house proprietary products as well as partner programs. In our in-house proprietary pipeline, we're focused in areas where there is high unmet patient need. but in high value markets. So very much focused within the diabetes and obesity space there. We have two clinical stage insulin products where we have best in class, superior data compared to the best insulins that are available for the patient population today. And I'll talk about AT278, one of our insulin products in more detail as we've just announced some significant clinical data related to that programme. We also have technology collaborations and new areas of research in oral GLP-1 and also key collaborations with some of the largest pharma companies and medtech companies in the world, such as Medtronic here in the diabetes space, which is for a novel insulin for implantable pumps. Then on our partnering programs, this is where we partner with major pharmaceutical and biotech companies. And this is where they come to us looking for an enhanced version of their proprietary products that they've not been able to achieve themselves. These partnerships are revenue generating from day one. So they're paying for access to our technology and our expertise and the IP that sits behind that. We're a very IP rich company. And the real upside here from this model is that when we have developed novel formulations that meet their target product profiles, they have the option to take those forward into further development or commercialization. under a licensing model, and these tend to be milestone and royalty bearing. And then within our commercial organization by Tetris Pharma, we are very much focused on the increasing use and sales and marketing of our lead product, Agluo, which is a ready-to-use glucagon pen for the treatment of severe hypoglycemia. And again, I'll talk about that in a little bit more detail. So we have growing revenue streams through our partnerships and licenses with major pharmaceutical companies and very significant upside potential from our diabetes and obesity proprietary pipeline. So I'm not going to talk in great detail around our portfolio today because I'll touch on many of these products as we walk through the presentation. But just a couple of key points to note here is Because we're taking existing therapeutic medicines, it means that their safety and efficacy is already known and demonstrated. So this means that we can follow abbreviated regulatory and development pathways to market so that they're lower cost, faster to market, and of course, lower risk here. These products are not going to fail on safety and efficacy. It's all around the improvements that we can bring to the table. So just to talk about some of the operational highlights within the first half of the year, this also includes some post period events. So across our proprietary pipeline within the diabetes and obesity space, we announced headline results earlier this year for AT278. So this is our highly concentrated ultra rapid acting insulin. This was a study in type two diabetic patients with high BMI. So these are overweight and obese patients. And this data was presented as a late breaking oral abstract at a major diabetes conference in September, which I think demonstrates how meaningful this data is to that patient population and the prescribers across the endocrinologists as well there. And this means I can also talk today in more detail around that data and show you some of that data. And we also have initiated a program in the oral GLP-1 space. We've partnered with TRX Biosciences here to co-develop here a oral GLP-1 with improved bioavailability. And we have very promising early data from that program. And again, I'll talk about that. AT367, this is a fully funded collaboration with Medtronic that we entered into earlier this year. And this is where we're using the Aristat technology platform to develop a novel thermostable, so heat stable formulation of insulin that could be used in their implantable pump technology. And this is important because Medtronic are the largest insulin device company in the world today. And this is an important product for a very fragile patient population, but also shows our close relationship with Medtronic. and the potential there for us to further collaborate with them across our diabetes and obesity portfolio. And then for Agluo, we're very much focused on accelerating growth in two key territories, and I'll talk about why. We've picked those territories, both the UK and Germany. Now, across our partner programs, I've drawn attention to AT220. So this is the first product on the market that incorporates the Aristat technology. So it demonstrates the the value that technology can bring to the table here, but also the approvability by the major regulators here. And this is now returning growing royalty revenue streams to Aracor under a worldwide royalty agreement. And we do have a very strong pipeline of what we call technology partnerships. So this is where we're working on our major pharma or medtech companies' products here under that revenue generating model with that upside potential as they convert to royalties. And we're working with companies such as Eli Lilly, the largest pharmaceutical company in the world, and Medtronic, as I've just spoken about. AT292 is also a product under license that incorporates the Aristat technology. Now, this product is in Hibbrids 101. was actually acquired by Sanofi earlier this year and is now in a potentially registrational enabling clinical study. So this could be the last clinical study prior to Sanofi filing for approval for this product. So that's getting much closer to market. And now under the leadership of Sanofi and their rare disease division, that increases the probability of this product coming to market and it's successful. once it is on market also. And that again is under a license agreement that brings both milestones and commercial payments post launch. We also have expanded our technology partnerships here. So we have multiple opportunities for value creation and license conversions there and a strong pipeline of additional opportunities that are under active negotiation currently. Now, earlier this year, at the end of July, we closed a successful pacing and subscription retail offer and raised 6.4 million before expenses. And that was really for us to focus on doubling down in areas of R&D investment where we can return transformational values, such as the oral delivery of peptides and GLP-1. And we also appointed at the beginning of the year, Dr. Helen Paris as Senior VP of Commercial and and also general manager of Tetris Pharma. So we can really drive the awareness and the sales of our key product, Agluo. So I'm now going to talk in a little bit more detail about AT278. So just to give some background to this product, AT278 is a highly concentrated, it's a five times concentrated standard concentration of insulin, but ultra mild. rapid acting insulin. We've used the Aristat technology here to modulate and accelerate the absorption of insulin post injection. And the reason that we're developing this product is there's very much a need and we're seeing a growing need for people that are requiring high daily doses of insulin. And we're also seeing a move and transition over to using insulin pump therapy. We know that patients do better on pumps. They have better outcomes, better blood glucose control. But despite this in the US, where we see the highest use of insulin pumps, still at less than 40% of type 1 diabetics and less than 10% of type 2 diabetics use insulin pumps today. And one of the main issues and the main barriers to use of these insulin pumps is their size. and their duration of wear. So currently they're used for and worn for up to three days before you either throw the pumps away for the patch pumps, which are disposable or need to refill the insulin cartridges here. And you can see the size of the insulin pumps here on the screen. And it's very much a drive and a pull from the patient population, but also a drive from the insulin device manufacturers here to move to much longer wear. So we're talking about seven-day wear and to much smaller miniaturized pumps. Now, if you want to move to longer wear and also reduce the form factor of these pumps, then you need to be able to have on board a highly concentrated but rapid-acting insulin. This is a particular acute need in the type 2 patient population, whereas we look in the U.S., On average now, they offer an average type 2 diabetic that's using insulin is requiring around 100 units of insulin a day. And if we look at the patch pump that you can see on the screen here, that can hold 200 units of insulin. So these patients can't get to two day wear with the current insulin formats and size. So if we want to move those across to seven day wear as well, we clearly need some innovation on the insulin side. So we very much see the future here around body worn, very small, longer wear devices and being able to move more of these type two patient populations over to insulin pumps, which will improve their outcomes and quality of life. Now, in terms of market size, it's a significant market. The insulin device market is worth around five and a half billion dollars. today and is estimated to grow to greater than 500 billion by 2030. And there's a real upside opportunity in that type 2 diabetic patient market where the penetration currently is less than 10%. And the key here is that Aracor has the only highly concentrated rapid acting insulin. It's a particularly difficult profile to achieve. As you concentrate insulin up, it slows down its time action profile, and that reduces those outcomes in terms of blood glucose control. So I'm just going to move on to talking through the headline data from the recent phase one clinical study. So here we were looking at comparing AT278, so that's 500 unit per mil insulin, with Novonordis 100 unit insulin, this is called Novirapid, and also then having an additional arm comparing with the only concentrated insulin that's available to these patients, which is a product from Eli Lilly and it's called Humulin R-U500. So if we look at the data here, what we're looking at is the PKPD data for these patient populations. So on the left-hand side here, we have the pharmacokinetic even, So this is basically showing you absorption of insulin in the blood post-injection. So you inject at time zero and then you measure the amount of insulin in the blood over time. And what's important to note here when we look at AT278 in the yellow versus Novo Nordisk, Novo Rapid, which is in the grey here, We can see here that we have a faster appearance of insulin in circulation. So insulin in the blood, it appears five minutes faster compared to Nova rapid. And then if we look at this minus 24 minutes, this is actually the half maximal concentration of insulin. So this is a very robust measure of how fast insulin is absorbed into the blood And here we saw it's 24 minutes faster to get to that half maximum concentration of insulin, which is very significant here. I mean, what physiology would tell us here is as you concentrate up insulin, you'd expect its absorption to be much slower. So we've managed to counteract that effect with the Aristat technology and also develop a much faster insulin in terms of its absorption. And then we saw this translate directly over to the pharmacodynamic profile. So this is essentially the glucose lowering profile. Again, we saw that initiation of glucose lowering was five minutes faster for AT278 compared to Novirapid. And again, we got to that half maximum glucose lowering profile and 25 minutes earlier compared to Novirapid. And then if we look at the tables here, so this is the area under the curve, what we can see here in the first hour, so if we first look at the PK data, so AUC in nought to one hours, It shows us how much insulin is available on board in the blood. And we saw 48% more insulin available in that first hour with AT278. And that translated to a 66% greater glucose lowering profile in that first hour. And these results are very significant because this is the period of time where a person with diabetes has eaten food, their blood glucose has risen very rapidly. You need to get that insulin on board very quickly. and start bringing down that blood glucose into a healthy target range as quickly as possible. So these are very significant data. And this as well just stresses in type two diabetic patients with high BMI. So these are overweight and obese patients who tend to be poorly controlled and there isn't a good treatment option available for them today. There are no other highly concentrated rapid actin insulins to help them control their blood glucose. And just to talk a little bit around the data then compared with Humulin RU500. So this is the only other 500 unit per mil insulin. So the same concentration as AT278. So this is the pharmacodynamic data, kinetic data here. And what you can see is Humulin RU500 has this very long, slow profile. So it's quite slow to be absorbed. And then we see this very slow uptake of insulin in the blood. And then looking at the pharmacodynamic data here, you can see that again translates. We see this, we've seen this very slow uptake of Humulin RU500, and then it's very slow, long profile then to bring down that blood glucose. So this isn't a good mealtime insulin. It's not reacting quickly to that rapid rise of in blood glucose compared here, as you can see, to AT278, which is on board very quickly and brings down blood glucose very quickly as well. So this provides us data here and confidence that AT278 could be that unique insulin that can catalyze the development of that next generation of insulin pumps, which are long-aware and miniaturized. And also, I'm not showing the data today, but we've previously presented clinical data for AT278 also in type 1 diabetic patients. And again, here we showed superiority compared to 100 unit per mil insulin, so Novo Nordisk, Novo Rapid. So what this is telling us that AT278 regardless of whether you have type 1 diabetes or type 2 diabetes and high BMI. It's very effective insulin. In fact, it's a superior insulin in terms of its onset of action and glucose lowering profile. So in terms of next steps for AT278, We have now two clinical studies after a single injection of AT278 showing that superiority compared to the best insulins available today. The next step for this program would be to conduct an insulin pump study. So this would be looking at AT278 again compared to those best insulins, but when it's delivered via continuous infusion in a pump, we would use an existing pump For this profile, it's important so it can demonstrate compatibility with those pumps and also that we have that pharmacokinetic, pharmacodynamic profile that we would expect to see when it's delivered via this format. Now, for AT278, really the future here is around that profile. combination with a specific device here. So we have a number of strategic and collaboration discussions ongoing and co-development partnering discussions ongoing with device companies. And they are now moving at significant pace since we've been able to announce and present the clinical data here showing the unique profile of AT278 and how it can really fit with the device company's strategy moving forward as well. So I'm going to move track slightly and talk about the oral delivery of peptides and in particular our first programme in terms of the oral delivery of GLP-1. So this was a collaboration that we entered into earlier this year with TRX Biosciences. So TRX Biosciences have the lipid matrix, so the oral delivery matrix, which they've proven on small molecules. But the challenge here was with peptides in particular and with GLP-1, that they weren't stable within this matrix. So this is a perfect combination of technologies here, the oral delivery technology and ARACOR's ARISTAT technology for stabilizing these peptides. In terms of the product concept here, As we know, I think everybody is aware of the GLP-1s and really the explosions of GLP-1s. There's very high disease prevalence here. They've been shown and demonstrated to be highly effective, both in diabetes indications, but primarily in obesity and weight loss there. But despite this, there's relatively low treatment rates here. And that's because they bring some challenges. So if we look at the oral GLP-1 space, There is only one oral GLP-1 available on the market today. It's a product from Novo Nordisk called Rebelsis. And the challenges with Rebelsis are that it has very low bioavailability. It has a less than 1% bioavailability, which means 99% of the activity. is not effective, it's lost through that delivery. And also it's dosed directly to the stomach, which means that for this product, it's very strict dosing criteria that it has to be dosed on an empty stomach, which the patient population do not like here. And it causes constraints around that use and adherence and the effectiveness of that product. So our target here is to develop an improved oral JLP1 that has enhanced bioavailability and also to target that delivery to avoid the stomach, to remove that strict dosing criteria here. And despite those challenges with that existing product, Rebelsis, we saw in 2023, it has sales of 2.8 billion and already in the first half of this year, just over $1.6 billion. So it gives you a sense of the market opportunity here. And then if we can demonstrate effectiveness for oral GLP-1, this really then validates this as a potential to be a platform technology approach that we can enhance oral delivery of peptides more generally. And there are a huge number of peptides in development today or on the market that would benefit from a switch from an injectable product to through to oral delivery. And there's certainly very much a high patient preference for oral delivery. So taking a single pill rather than having to self-inject, for example. Now, in terms of status, the initial challenge with this program was, could we stabilize the GLP-1? We're using semaglutide here, so the same GLP-1 as in Rebelsis. Within the oral delivery matrix, and the answer to that is yes, we've developed here data and novel formulations that stabilize that peptide inside the matrix. And we'd be expecting to enter into non-clinical, so these are animal proof of concept. pharmacokinetics studies. So this is to look at the bioavailability of the GLP-1 during the first half of 25. And I think, you know, perhaps more importantly for this program is its potential really to expand out as a technology platform, which we know would be highly attractive to partners. Each time we talk to a major pharmaceutical company, we're talking to them all the time. We're asked, do we have anything in the oral delivery space? It's a particular difficult challenge to address, but it is a formulation challenge. And we know that we've been able to develop enhanced formulations with enhanced properties that our large pharma counterparts have not been able to achieve. So we have a fantastic opportunity here to develop this platform and to transform this into significant value creation for the company. So now I'm going to talk a little bit around Tetras Pharma and Agluo. So Agluo is a ready to use glucagon pen for treatment of severe hypoglycemia. So this is dangerously low blood sugar in patients. It needs to be administered by a third party. So the individual themselves, when they enter into severe hypoglycemia are not able to treat themselves. And our focus here is on two main markets, the UK and Germany, as I've mentioned. So the UK ready-to-use glucagon market has a market value of around 18 million pounds. On the market today is a gluer. Our first full year of launch was in 2023 and a product called Glucogen. So this is a product from Nova Nordis. It's a rescue kit. It essentially has a a vial of lyophilized powder that requires a relatively complex mixing procedure prior to its use. You have to remember this is a highly stressful emergency situation. So there's benefits here in having a ready to use pen. It's like an EpiPen essentially for dangerously low blood sugar. And last year we achieved 9% of the market by unit share. And really our focus now through the remainder of 24 and into 2025 is to drive awareness of agluo in the UK market and drive that demand there. And then Germany is our second target market here. So Germany is a very traditional market. Prescribing is done by maybe endocrinologists in that market. It has a value of around nine and a half million pounds. Now, the market dynamics are slightly different to the UK. There is one ready-to-use product on the market. It's called Baximi. It's a nasal glucagon product that was launched back in 2019 and now has around 59% of the market share here. And that was a product that was owned by Eli Lilly, but they sold that product to a US company called And we're anticipating within those agreements and that publicly available information that all of the responsibility for vaccine needs to be transferred to Amphistar by the end of 2024. And they have very limited European footprints and that potentially offers us an upside potential in that market also there. So there's a significant growth market opportunity for Agluo. So just to talk very briefly about some of our tactics around Agluo here is really growth in our home UK market. And this is around gaining formulary approval. So we have a reimbursed price and then it's around ensuring that a glue over is on the formulas for the main groups of hospitals so the integrated care systems there so it's easy for them to prescribe and also to drive awareness there through conferences etc where the majority of the healthcare professionals and prescribers attend so that they're aware that this product is now available in the UK and they can prescribe that and then in Germany as I said it's very traditional market so this is around ensuring that the endocrinologists themselves and diabetologists are aware of the availability of the GLUO. There's around 400 HCPs in Germany that relate to around 80% of the prescribing of the GLUO. So there'll be our targets there to ensure that they're aware of the products and also to ensure that we have sufficient stock in country so that we can meet that demand. for Germany and the UK. So just to talk at a very high level around the financials here, we saw an increase in revenues compared to the first half of 2023, a 20% increase there. We also had a slight reduction in our investment in R&D, and this is in relation to the timing a number of clinical studies here. So our investments in R&D and the most significant investments were around the AT278 clinical study, which has now ended. Now, moving forward, as I mentioned, our future R&D expenditure is really to focus in areas where the ARISNAP technology can deliver transformational value creation opportunities, so very much in the diabetes and oral delivery of peptide space and we're anticipating a strong second half of the year of increasing revenues there across our diverse and de-risked portfolio. So we have a number of opportunities for revenue generation, not reliant on one partner or one product for that. So just to talk in a little bit more detail here, you can see we have royalties now and recurring royalties from 80 to 20. That was actually launched at the back end of 2023. It's now available in major territories such as the EU and very recently in the US there. So again, we'd expect to see continued growth and a strong second half for that program. And for the pharmaceutical products, so this is sales within Tetris Pharma, the sales of the glue are very much tempered in the first half of the year as we were managing stock there. We had limited stock available to us. We now have more stock on board post the recent fund raise, which allows us to focus on that awareness campaign and driving that demand because we know we have the stock available to meet demand moving forward. Now, we had cash at the end of June of 2.5 million, but that was before the 6.4 million fundraise, which that was before expenses. So we have a strengthened balance sheet. So just looking at what's coming up and some of the significant milestones, On the back of the AT278 clinical data where we demonstrated that superiority, we've seen an acceleration of pace of strategic co-development and discussions with device companies there. So we're exploring options both with device companies and also across grants for non-diluted funding to progress that three-day insulin pump study. And that's very much a study, as we see, as a major value accretion point for AT278. We've seen that growing revenue stream from 80 to 20. Of course, these 100% margin as well. So go straight to our bottom line. And we'd expect to see continued commercial growth of Aglua, especially now we are able to invest in that stock and to have that stock in country and those awareness campaigns across the UK and Germany. We do have a pipeline of opportunities, both in new licensing and also technology partnerships. So this is where we're working with pharma companies on their proprietary products. So we're confident through the remainder of 2024 and certainly into 2025 that we'll be announcing new collaborations and license deals across that portfolio. As I talked about with Oral GLP-1, We're pretty excited by that program. It's a significant opportunity. And as I've said, we've cleared that first technical hurdle of could we simply stabilize the peptide in that matrix, which has been a challenge that's not been achieved broadly there. And then the opportunity to expand that as a platform technology. So we'd expect to continue to see that year on year growth. As I mentioned, we'd expect a strong second half of the year for all of those dynamics that we've spoken about but we of course continue to closely manage our cash and that includes in certain areas a planned head to count reduction which will bring some annualised savings to the business as well so again we have those growing revenue streams through partnerships and these are partnerships with major pharmaceutical and biotech companies and that's significant upside potential as we progress our diabetes and obesity pipeline So that concludes the formal presentation for today, but I'd be very happy to answer any questions.

Perfect. Sarah, if I may just jump back in there. Thank you very much indeed for your presentation this afternoon. Ladies and gentlemen, please do continue to submit your questions just by using the Q&A tab that's situated on the top right corner of your screen. But just while the company takes a few moments to review those questions that were submitted already, I'd just like to remind you that a recording of this presentation, along with a copy of the slides and the published Q&A can all be accessed via your investor dashboard. Sarah, as you can see there, we have received a number of questions throughout your presentation this afternoon. And thank you to all of those on the call for taking the time to submit their questions. But Sarah, at this point, if I may just hand back to you just to read out those questions and give your responses where it's appropriate to do so. And if I pick up from you at the end, that would be great. Thank you.