Shield Therapeutics (LSE:STX) — Company update

0:02 Good afternoon, ladies and gentlemen, and welcome to the SHIELD THERAPEUTICS Investor Presentation. Company may not be in a position to answer every question it receives during the meeting itself. However, the company will review all questions submitted today and publish responses where it's appropriate to do so. Before we begin, we would like to submit the following poll. And if you give that your kind attention, I'm sure the company would

0:34 be most grateful. And I'd now like to hand over to Greg Madison, CEO. Good afternoon. Great. Thank you, Mark. And first off, thanks everybody for joining us today. It's a pleasure to be here and speak to you all, at least virtually, and look forward to at some point doing this potentially live in person. I'm joined here today by my colleagues on the senior management team at here at SHIELD. First and foremost, Hans Peter Rudolf, who is our chief financial officer, and then doctor Jose Manoio, who is our chief medical officer, are joining me today for the call. They'll probably disappear during the the presentation mode, but will be available and come back for our q and a process as well. And I think, you know, for us, I think the the objective here is quite simple. Right? Wanna provide, you know, fairly comprehensive update on, you know, a lot of the activities we're working on here at SHIELD with a particular emphasis on The US market. Our goal really is to provide some additional context, understanding, and really calibrate everybody's expectations on exactly where we are with The US launch, the progress that we've made, and certainly what looks forward to, to coming ahead with a very, very promising compound urine aquifer. So, you know, we'll probably present here for the next, you know, call thirty minutes or so and then open up things for q and a, and look forward to getting some of those questions, answered that you have in your mind.

1:52 As always, we'll be making forward looking statements, so please refer to all of our documentation, etcetera, and filings, for additional information regarding, you know, potential risks. So what excites me about SHIELD? You know, what is, you know, some of the reasons I think about why I joined, why Doctor. Manoio came on board, Hans Peter, and the rest of the team you have here as well. And it's kind of encapsulated in many ways on this slide. You know, there is a vastly significant unmet need, for a well tolerated oral iron to treat iron deficiency, which is a highly, highly prevalent disease overall in a big market, especially here in The US. We believe we have a potential best in class product with AcroFert that we'll certainly talk about as we go out the presentation. And you've got a new team here. Really, this is a a new launch, particularly in The US. We're gonna talk a lot about, you what it takes to launch a product, you know, the time, the investment, everything that's needed there to properly launch that product. But you've got a team here that is absolutely dedicated to making this product the potential leader in oral iron replacement therapy.

2:55 We've got a lot of near term value inflection catalysts that we'll speak about during the conversation, and our last reported cash position was $15,000,000 as of December thirty first of this year. However, you know, looking at, you know, our opportunity, the nice thing is we also have very strong patent coverage that runs all the way through 2035. So we have many, many years of opportunity growth sitting here in front of us, as we go forward. We put an r s pardon me. We released an r and s, you know, probably ten, fifteen days ago or so. This, you know, highlights some the operational financial highlights we put out there at that time that, you know, as we look in The US market, our awareness of Acrofor is increasing. We'll talk about, you know, the importance of that and what that looks like. And we have a lot more to go, but we're making good progress there.

3:44 We had very good generation of 2,500 prescriptions for Acrofor with a really significant quarterly growth from the third quarter to the fourth quarter. And our payer coverage, importantly, has increased nicely since we put out an r and s in December even in the month of January that jumped up by about 20,000,000 commercial lives. Again, all three of those points, we're gonna go into a lot more detail here during the presentation. From an ex US perspective, we announced that we had 60% year over year growth, for Faracru sales volume in Europe. And our total revenue for the year, probably for the last six months, was 1,500,000, pounds. And as I've mentioned before, our cash on hand in pounds at the end of the year, was 12,100,000. So before I spend, you know, a lot of time on The US, which is gonna be the the bulk of this presentation, I it's important to take, just a quick moment and comment on, you know, all the work that's going on in the, the Ex US and update you on some of our progress here. So importantly, China.

4:41 Big, big opportunity. Our partner, ASK Pharma, has been working very hard over there to kinda get through the regulatory and clinical process because we believe it's a very significant market opportunity based on the population size and the prevalence of iron deficiency in that China market. They've made excellent progress. We've completed our, required pharmacokinetic study, late last year, early this year that completed overall. If you recall, that's one of two key clinical, milestones from a regulatory perspective that they need to complete. Right? So we need to complete the PK study, and we need to complete a phase three clinical trial that in many ways mimics the trials that we already conducted, you know, to approve the product. So the PK study is now complete. They're actively enrolling patients in that phase three trial.

5:30 And as a reminder for folks, people recognize that, you know, upon approval in China, there's a nice, you know, $10,000,000 US dollar, milestone here that's, sitting out there. So they continue to make excellent progress. They're very enthused, and we're happy with, what we're seeing there so far. On the Europe's perspective, NordGen continues to make progress. We commented earlier I've commented earlier that you saw 60% year over year growth overall, in Europe. So they continue to make progress there in terms of, you know, garnering further adoption and getting more people to prescribe Acrefer. Importantly, we work very closely with the team there. We're happy to see that the reimbursement dossier for Spain was submitted very late last year overall. That could open up potentially another very, very important market for us, in addition to some of the work we're doing primarily in Germany and The UK. And the spam reimbursement process does take time, but yet first step of getting that dossier submitted was critically important. And now we're starting to work with them on other big countries, including Italy and France, as we go through the year. So good progress there.

6:36 You know, clearly, I think, you know, the work that we're doing with Norgeen, particularly on emphasizing who the right call point is and this call point, not dissimilar to The US, it's primarily primary care and OB GYN call point, and is starting to make progress towards, you know, shifting some of their time and attention, into that market where the biggest opportunity lies. You know, Republic Of Korea, very good progress there in terms of, you talked about a a very, very motivated and enthusiastic team. That is to say the least. They are working very hard on a number of different fronts that, you know, I won't comment on specifics just yet. And then our most recent deal we signed with CHI Pharmaceuticals in Canada, you know, again, a very, very strong and motivated team there as well, and we're hoping that we can get the, potential submission for approval done and completed and submitted during this 2022.

7:27 And the teams are very excited about what that opportunity looks like. So across the board, good progress with our US partnerships overall. You know, continue to kind of focus on, you know, the European and the Norgine piece overall to kinda increase that demand while the other kind of geographies progress to the regulatory and clinical milestones. So I'd like to spend the rest of the presentation talking about The United States. Obviously, you know, in a nutshell here, that is the biggest opportunity. Right? We launched here in The US, in July. It's a $2,200,000,000 market opportunity. On the left hand side, we talked about, you know, very, very prevalent disease. On the lower left hand side, you can see that, you know, the issues with conventional oral iron therapies that are fairly well known physicians really just you know, the tolerability drives this unsatisfactory cycle of switches and discontinuations, and they're seeking, you know, an oral iron that potentially can be tolerated and well effective both effective and well tolerated, I should say.

8:29 We estimate a very strong potential revenue opportunity here in excess of $500,000,000. And the key points that we'll certainly talk about in detail today, you know, payer coverage, you know, in terms of, like, getting that access for patients to to increase their prescriptions. We've seen very positive market feedback. Now, obviously, we have a commercial plan that's focused on the top 65,000 prescribers in The US, which drive about two thirds of the total oral iron volume, and that's mainly driven by primary care physicians as well as, OB GYNs or women's health, to use maybe a broader terminology here. So before we get into some of the the specifics in The US, let's just kinda check back, make sure that the you know, is there a need for the product? What does the market look like overall? Is there a need? And, you know, right now, iron deficiency, either with or without anemia, again, very prevalent.

9:19 There's fifteen million US patients. You'll hear me say again that there's about 13,400,000 prescriptions written in The US on an annual basis. Iron deficiency, as many people know, cuts across a very wide swath of different diseases. You know, iron deficiency in many ways is considered a disease of a disease. Right? So it happens because of something else going on, whether it be chronic kidney disease, inflammatory bowel disease, you know, women's health related issues, you know, all kind of have things underlying diseases, which unfortunately create a high prevalence of iron deficiency and iron deficiency anemia. So the nice thing here in The United States is that, this is not novel where in terms that physicians can absolutely readily recognize, you know, when iron deficiency is in place.

10:05 Right? So a patient comes in and presents with, you know, the symptoms of extreme fatigue or mental confusion or just, you know, overall, you know, lethargy that just you just can't do the daily tasks. Physicians, when they see a patient present, they understand how to diagnose it, and they will actively treat it. Right? So this is not a educating the the need to treat. They see it. You know, what they're looking for is actually a better and new solution overall. When we think about treatment options here, you know, clearly, you have the three treatment options of oral iron replacement therapy or injectable iron replacement therapy. In The US, ninety percent of all the prescriptions in The US are oral iron. And to be very clear as we think about, you know, where we are competing, you know, where who are we competing with here? We are competing on the oral iron side. You know, we'll we'll table that, you know, for a future, opportunity here, but, clearly, as you'll see, the opportunity here is on the oral iron side.

11:04 You know, why is that? So physicians, as I mentioned before, they readily understand how to diagnose and how to treat it, and, typically, that first line treatment option is oral iron. You know, why is that? Because, a, it's convenient. You know, b, it's readily available, and, c, it doesn't require patients to go into a a hospital or a hematology clinic to get injections of iron. So that is typically the first line route. If you talk to any or any patient, the first thing you typically will hear is something around tolerability. That is the single biggest challenge you hear come up. And more specifically, it's around GI related adverse events. You know, constipation, diarrhea, nausea, vomiting, those are typically things where constipation jumps up to the to the start. So the way to think about this is physicians will actively treat it. They'll typically try the oral irons, but let's just say they don't have a good, you know, confidence that it's going to work. But up until aquifer, that's all they really had. On the other end of the spectrum, you have injectable iron or IV iron. So the nice thing about IV iron is it really gets your iron stores up very, very rapidly. Right? So very effective, very rapidly.

12:10 I mentioned before that the biggest challenge is just the logistics of actually going to get the iron. Right? Patients have to take time off of work, go into, here in The US, either a hospital infusion center or hematology clinic, get multiple infusions, and you're there for several hours while this takes place. So not exactly the most convenient, certainly pre COVID. And, you know, with the the COVID crisis, you know, there's many, you know, many examples across, you know, not just The US, but the globe. Let's just say patients, the first place they're not they don't wanna go to is in the hospital or hematology clinic today. Right? So that's really added another hindrance here as well. Now if you're a patient that needs to get your iron stores up rapidly, let's say you have surgery coming in a couple of weeks and you've gotta get your iron stores up overall, IV iron's gonna be the way to go.

12:55 So maybe a way to think about this is, you know, severe patients on the right hand side that need IV iron. If you're dramatic, low on iron stores and need it up quickly, IV iron is the way to go. But the more prevalent and typical mild to moderate that still needs to get treated, that's the oral iron opportunity, and that's exactly where Acrofor fits in extremely, extremely well, as a potential opportunity here for us.

13:20 Commented, previously in in in previous discussions, and, again, you'll hear this over and over again, adverse events with current oral iron treatments limit overall adherence. And, you know, this is you know, various data points have been out there and published in different studies overall, around some of the OTC irons that are available here in The United States and, you know, many other countries as well. But, you know, typically, it's a ferrous based iron. There's a plethora of different OTC options that are out there available. And, you know, almost all of them, whether or not you're talking about overall adverse events, GI related adverse events, or discontinuation rates, physicians have in their mind that about half the patients are gonna fail the first course of iron because of some GI related adverse events overall. So what this creates is a very kinda inefficient system. Right? So people perhaps sometimes have the misunderstanding of the iron marketplace in The US that because there are so many oral ROTZ irons, it's a satisfied market. I'll tell you straight up, it is not a satisfied market, and this new pictorial tries to depict that, if you will, where a patient typically will go into a clinician. They'll get a diagnosis of iron deficiency anemia. They'll try an OTC iron, and, you know, more than half of them get some kind of GI adverse event and discontinue that treatment. Or they'll cycle and try another or different OTC iron in hopes that that won't be might be the the magic bullet. Then we'll try perhaps a third one.

14:41 Right? And you end up in this really unsatisfactory cycle of just hunting around trying to find that iron that can provide not only effectiveness but good tolerability here as well. The important part here is usually these types of patients, they aren't severe enough where they require injectable iron. Now, eventually, over time, they'll get sick enough where they have to go get IV iron, but patients typically run through this overall cycle, and this is kinda what happens in The United States right now. So you can think about where the place placement of aquifer in this kinda continuum here could be a big, big benefit, again, from an iron that is both effective and well tolerated. We have to think about the from a a scientific perspective. You know, what is it about the OTC irons, these ferrous based irons that causes a lot of problems?

15:27 Right? So, typically, these OTC irons are are are ferrous salt combination. And so quite simply, on a scientific perspective, in order for the iron, the ferrous to be absorbed in the small intestine, it actually has to separate from the the salt structure. And so that typically happens as soon as the patient takes the medication and it hits the stomach, that dissociates. Right? So now you've got kind of ferrous iron or free iron circulating in the stomach, and, again, it needs to travel all the way down to the small intestine before it can get absorbed. The issue with this free iron now in the gut, it was it was a couple different things. So one, it obviously irritates the the lining of the gastric mucosa, but it also reacts and creates reactive oxygen species, which now start this whole cascade of GI related events in the gut. Right? So, obviously, as physicians talk about that, you know, those earlier numbers that, you know, fifty percent experience GI related adverse events, high discontinuation rates, this is why. You know, it has to, you know, really dissociate in the gut. You've got that free iron circulating.

16:26 So if you ask physicians today in The United States, and this is market research that we conducted both in the June time frame of this past year as well as the December time frame of last year, you'll consistently hear that that physicians have low satisfaction rates with the variable oral line treatments, and that's depicted on the left hand side. Doesn't matter if it's a primary care physician, an OBGYN, or a nurse practitioner that operates in a primary care OBGYN office, very consistent results overall, just low satisfaction rates. What they want to see when you ask them what's important when they select an iron replacement therapy is you see on the right hand side. We want it to be safe, well tolerated, affectable, affordable, and convenient. So very straightforward. And think about those as we go forward here around, you know, how does Aquifer kinda fit into that and how does that check those boxes.

17:16 So why is Aquifer a good fit here overall? Right? And what makes us different scientifically than what we see out there with the ferrous based irons? It really comes back to the structure and the the, I guess, what I call it, the the elegant design. You've designed an iron that is designed to both deliver effectiveness and tolerability and kinda offset some of the, issues that you had here with some of the other OTC irons. The cartoon structure in the lower right hand side, you know, kinda depicts this, but our product is ferric iron surrounded by a maltol structure. This maltol structure basically shields the iron and allows it to travel all the way down into the small intestine where it's delivered to be absorbed. So this does two things for us. Number one, we use a very low dose of iron. Our our iron is thirty milligrams twice a day, so a total dose

18:02 of sixty milligrams of iron is used versus the OTC irons. You typically see numbers more in the three hundred milligram range. So lower dose of iron, which also allows, you know, potentially lower, side effect profile. But the single most important piece is what it doesn't do. It doesn't dissociate in the stomach. It doesn't cause free iron to be circulating in the gut. You know? So when we look at our clinical trials, because we can deliver the iron to where it's absorbed, our adverse event profile and our discontinuation rates were both less than five percent. So this is really what starts to be eye opening when you compare it to what physicians are used to seeing out there overall. And this is, you know, our big, big advantage that we can be able to be both effective but also tolerable. Right. So let's spend just a a few minutes here kind of on the The US launch and dive into a little bit more specific detail, on what that looks like, overall going forward.

18:53 And, you know, we spent a lot of time here kind of thinking about The US launch and, you know, our progression as well. And I wanna make sure that we're calibrating everybody's expectations on not only where we were and where we are, but also where we go forward here, as well. So this pictorial, I think, is important for peep people to, to think about and understand. So this is you know, depicts a kinda typical standard prelaunch activity, for a US, launch. Right? So in other words, this is the the myriad of activities that, you know, most companies would undertake as they think about a US launch. There's a variety of different things that happen. But importantly, what you see is, you know, two things. One, it starts about twenty four months ahead of launch. Right?

19:34 So this is kind of the the typical playbook that playbook that twenty four months ahead of launch, you start a lot of these different activities, and companies spend and invest the time and millions of dollars in order to kinda get these things done. Now why is this done? You know, why is this the typical playbook? So number one, first and foremost, is trying to create awareness. Right? You wanna create a buzz and awareness about not only your product, but also your company, and that's one reason you do it. The second thing is to make sure that you've got your commercial infrastructure fully set up and ready to go. That includes, you know, people, data systems, etcetera. That's the other key piece here. And the third and final piece of why people do this, you know, this far in advance is to engage with payers in advance as well. Right? So, typically, you can kinda start talking to payers about a year out, start preparing them for the product so they understand it with a goal to try to shorten that time frame on the back end, as well.

20:26 But circle back on the awareness. I think that's probably the single biggest thing that you, you know, would wanna take away from this of why the companies invest time and money into this overall. It's really to drive that awareness again, not just on your product, but your company. You know, maybe just a a side note on a a story. So my my wife's friend, she's a dialysis nurse, operates down at dialysis center down in Atlanta. And, you know, she she was telling me the story that, you know, years ago, it was a product called Renagel, which was coming out in the dialysis centers. Think this is back in probably late nineties, early two thousand overall. But she was telling me the story that, you know, as she operated in there, she was like, look. Eighteen months, you know, before this thing was coming out, there was buzz starting to create it. Right? There were KOLs talking about it. We go to the medical meetings. We'd be hearing about this product overall.

21:13 There was data presentations. There were CME events where you kinda look at it, and there was a just a buzz even in the chat rooms and physicians. Everybody was talking about this new novel, you know, phosphate binder that was coming down the line here. And by the time it actually launched, people couldn't wait to get their hands on it. Right? So you really this those pent up demand, if you will. And that's really what the awareness driving does is, in

21:37 many ways, what you wanna do is make sure you hit the ground running and give yourself the best opportunity to have a quick and a fast running start overall, and that awareness is something that we just really wanna have that pent up demand. Now look. For a variety of different reasons, this is when this all started for Acquifer in The US. Right? So, you know, I joined the organization literally one month prior to launch. You know, commitments have been made to the launch. Salesforce had already been hired. And as I said, for a variety of different reasons, this is when things started for us overall. So what does that mean? So number one, we as we launch, we are trying to do all of this prework stuff at the same time as we're launching. Right? And, you know, please don't take this. This is not an excuse by any stretch of imagination.

22:22 We knew what the job was coming in, but the reality is we need to accomplish all of these different things exactly at the same time we're launching. Right? There was no running start. There is no pent up awareness. There are no KOLs that are engaged. We're working on all of that as we go forward here. So I think as you think about the progress that we're making and what we need to do,

22:42 unfortunately, many of this takes time. Right? There are some things here that you can kinda truncate, and that's our job as a management team is figure out how do we accelerate this launch as quickly as possible. And there are certain things you can move fast, but other things you have to go to that process and awareness building, KOL engagement, and other things like that are part of that. It just takes time to get out there in front of doctors, raise their awareness about the company, the product, and we're all working as hard as we can to kinda get that accomplished right now. So it kinda adds a

23:11 little color to why our priorities are such. Right? When we launched back in July of this year, what were these short term priorities that we need to accomplish? So number one, you've heard me say that now multiple times, increased brand awareness. You know? So we did our initial market research in June just before we dropped our 30 reps out there in the field. Our brand awareness was zero. So out of a 105 doctors actually we interviewed, nobody had heard about Acmeber. So, again, we gotta start that process going forward here and kinda build and increase that awareness. Let's talk about what some of the things we're doing. So I just referenced our 30 reps. There's a lot of data on this slide that maybe focus on the right hand side here, which represents an oral iron market in totality. Right now at the very top of that pyramid, we have about 4,000, health care professionals, and you'll see that, you know, shortened here to HCPs perhaps during this

24:04 presentation. So 4,000 health care professionals that we are calling on with our 30 reps in the field. You know, those 30 reps came on board literally a month before we launched. They don't have pharmaceutical experience, but they're out there working hard to kinda get in front of the doctors and start to raise that awareness. And for the launch, this was our awareness building, you know, tactic, if you will. Right? So we'll talk about some of the media and some of the other things that came on board in the fourth quarter. But for the initial part of the launch, it was 30 reps in the field trying to work and get in front of doctors and start that initial awareness that, hey, doc. Let me tell you about this new product called Acrefer, and, you know, kinda go forward from there. So on the positive side, right, what are we doing with that? We've made really nice progress. This is what they call, aided awareness. Right? So physicians, when we do the market research, there's a list of products that they see in front of them, and they check off the box of which products they heard about.

24:55 Right? So the first time we did the research with physicians was in June 2021. You know, you had about 31% of physicians said, yeah. I kinda heard of this product, Aquifer. You know, with the zero that I

25:06 mentioned before, that is what they call unaided awareness, which is you don't give them a list. You just ask them what they know about, and that was the 0% that are heard of AcroFer. So I will tell you, at a launch, 31% as far as aided awareness, it's really low. That is really low. Again, if you wanna do all that work ahead of time, you typically wanna see that more what we see reflected in the December side. Right? So we've made really good progress. We did the second wave of research here in December 2021. We're up to sixty five percent of physicians that have kinda now heard about Acrefer and have that awareness, so good progress. Ideally, you would have liked to have that number more like 75% at launch, but, again, very good progress in a really short period of time, primarily driven by reps, but also by driving some of our multichannel engagement strategies, which kicked in during the fourth quarter. Again, these are, websites, you know, media placements overall, again, to help drive that awareness. So in addition to the reps, trying to get in front of a doctor and educate them about AcroFer, you need to have that, you know, surround sound, if you will, where physicians are hearing and seeing about AcroFer in a multitude of different ways, not just kind of a rep driven focus overall.

26:14 Our second key objective was to generate clinical experience. And we knew as we think about this list, you look to the the right hand side that, you know, again, we had engaged with payers. We knew it's gonna take time to get that payer coverage overall. Typically, in The US launch, it takes about twelve months to kinda get to a level of payer coverage that you're satisfied with. So in the meantime, as physicians become aware of Acrefer and understand about it and say, you know what? I'd like to prescribe it even though

26:38 you don't have payer coverage yet. How do I do that? The way that that's done is through our patient assistance program. Right? In in The US, we have our it's our brand name is it's a company called Co Assist that we work with here. So it's kind of a reimbursement hub where mechanically physicians see the product. They wanna write it. They write a prescription. It goes into our reimbursement hub called Co Assist. That hub understands, does a patient have coverage from an insurance perspective? If they do, that's kind of a a paid prescription. Right? That was virtually zero during the first six months of launch until we have payer coverage. So the other way to kind of then do it is to ensure that you get that clinical experience for the physician and for the patient and get paid pardon me, physicians in the habit of writing your drug. You do it through a patient assistance program where if they don't have coverage, we turn around and sell it directly to the patient for a very nominal cost. Now those aren't revenue generating prescriptions, but they're really, really important, again, to get

27:33 physicians in the habit of writing the drug and start to generate that clinical feedback, which is critical for future adoption and use. So we're very pleased with the numbers that we see here in terms of, you know, where we started in the q three time frame and then moving up into the q four time frame as well. Now are these numbers will we satisfied with these numbers?

27:52 Absolutely not. Yep. We can and will do a lot, lot better overall. But, again, I provide that context to you that, you know, there was zero awareness in the field. Our reps went out there starting July 1. And for those of you who may understand pharmaceutical selling, you know, this is one of those where our representatives, they have a target list of their doctors. They go to see them on about a three or four week basis. So call it, you know, once a month, maybe twice every two months, you're seeing a physician to try to get in front of them and start that education process. Right? And physicians' first step is become aware of AcreFer. And like anything else, it takes about six, seven, eight calls in order for that message and that resonance to kinda stick in with physician where they've had this habit of writing OTC irons for years. We're trying to break that habit, and it takes time. It takes getting in front of the doctor on multiple different occasions here to kinda break that habit overall. So we've done a really nice job thus far in the initial stages of launch to generate that clinical experience. You can see on the right hand side who's writing the products.

28:53 It's primary care physicians, it's OBGYNs,

28:56 and it's nurse practitioners. So 80% of the oral iron ball in The US comes out of these kind of three specialties, if you will, and that's where it kinda zoomed in our field force overall. Importantly, we think about the clinical side. Right? So we're driving awareness, and, you know, I mentioned it's important to generate this clinical experience. You know, we get qualitative feedback thus far in the field that the product exactly as we hope to see, but we did market research in December and said, alright. Of physicians who have written the product, what comes back to you? What are you hearing? What are you perceiving overall? I would zoom you into the advantages. Right? What I wanna hear and what you know, you think about our message, what physicians are telling us they think about the advantages of Acrofor are, it's well tolerated, it's effective, we have less GI constipation side effects, and it's oral.

29:42 That is music to my ears. That is exactly think about our message. It's well tolerated, and it's effective. If physicians are turning around and telling us it's well tolerated and effective, that is perfect. Our message is exactly on point. Now we need to continue to drive this home. There's a terminology that they call making sure that your brand message is sticky. Right? Does it resonate? You know, does it stay there where physicians think about instantly, accrefer, tolerability, efficacy. That's what you kinda want in that instant. So a good good start. You know,

30:12 the ends here are relatively low, but we need to continue to do that. Now look at the disadvantages, not to ignore those by any stretch. Anyone, you want. They do gonna hear early on our cost and insurance coverage, right, which, you know, are very natural. So those are things that we can control in some degree, but the clinical benefits of the product, extremely, extremely important. Additionally, in this research, you when you think about physicians that haven't used Acrefer, right, this ties back to that awareness. Right? Hey. I don't know about Acrefer. Tell me about it. When you put something in front of them that says, here's Acrefer, this is kind of a a static profile is the way you do this, it's lifted off the package insert. It's not a promotional piece. It's just like, alright. Here's the clinical data. You you look at this. You hadn't heard about it before. Are you likely to prescribe? You see here very, very strong numbers, you know, whether it be primary care, OB GYNs, nurse practitioners, that they see it, become aware of it, they indicate they wanna learn more. Right? They wanna learn more, and they're likely to prescribe.

31:09 Now that doesn't happen automatically. That's not the way it works, right, like anything else. You see it once, you become

31:14 aware of it, then you need to follow-up. And that's where it's critical that either your field force and all of your kinda, you know, digital marketing strategies and other ways to kinda continue to drive not just awareness, but move awareness to engagement and then engagement to prescriptions. Right? But a very good start here because when physicians hear about it, they wanna learn more, and that door is kinda opened, if you will. Our third critical piece was on the payer coverage side, and we have made excellent progress here. I just mentioned before how important it is, you know, that, you've gotta get your payer coverage set up. In December, as we previously announced, we announced four agreements with four large pharmacy benefit managers. You'll hear them referred to as PBMs oftentimes. That is a very important first step as, you know, there's about three pharmacy benefit managers, three or four that drive probably 70% of all the commercial lives in The United States.

32:05 And so, you know, we started the year in January at 22% coverage and 40,000,000 lives. In January, we kind of added some additional plans here. We're now up to 60,000,000 lives. We have 33% coverage of the commercial market, and we fully expect that that's gonna continue to progress as we move through the year. So as I step back and just reflect on, you know, the first six months, you know, what what have we observed? What have we seen, you know, based on where we are right now? You know, I sound like you're broken record, but awareness is absolutely critical. Right? And we are working very hard to kinda think about how do we drive that awareness, not just with our reps, but, you know, investing in all of our digital marketing strategies. And we just wanna make sure that we need to be resourced appropriately here in order to really drive that awareness. So as I just said, awareness leads to interest. Interest leads to a opening there to kinda create engagement and ultimately a prescription. And, you know, while we've made very nice progress considering we started from a pretty much a dead stop and a zero level of awareness, we made really good progress on the next the first six months, but we have a lot more room to grow. I mentioned before, our messages around tolerability and effectiveness is absolutely on point. This is not you know, we don't need to change our message. We don't need to, you know, tweak the the the adjustments or the strategy there. It's on point. We just gotta continue to get that to reinforce, again, not with just with reps, but in a multitude of different ways to get out there in front of, physicians.

33:28 Payer coverage continues to grow. Excellent. You know, that's a very big gating item for me, obviously. You know, was very happy to see the agreements come forward here at the end of December. We expect that's gonna continue to evolve and grow. And the last piece for us is discontinued evolution in the organization. Right? Just all of those, you know, things that we're trying to accomplish while we launch. Right? A lot of commercial infrastructure, a lot of the data systems, even our approach to how we get that awareness out to physicians. You know, I wanna make us, you know, a bit more of a progressive organization and more rapidly moving towards that frontier as well. So all that leads to what are the key priorities for us as we look ahead in 2022. You know, number one, no surprise. Increased brand awareness. Gotta happen. Gotta continue to improve that. Number two is how do we expand and accelerate, you know, the health care professional or HCP adoption? Right? And I I use terminology like breadth and depth of prescribing. So breadth, what we mean by that is how do we get new writers to start to write a prescription of Acrofor? Somebody who hasn't written Acrofor before, do how we get in front of them? How do we initiate that first or two first one or two prescriptions, get some experience, and then start to move them through the adoption scale? So breadth is new writers, and then depth is writers that are writing the product, how do we get them to write more? How do we expand the utilization from, you know, I'm trying it in a couple of patients to really move through that adoption scale? So that's a critical piece for us, as we go through 2022.

34:49 Number three, continuing to minimize any patient barriers to access. So what does that mean? That means when a physician wants to write the product, how do we make it as easy as possible and as affordable as possible for that patient to actually get on the drug? Right? So payer coverage is a continued big piece of that as our patient assistance programs going forward. And then fourth is, you know, really how do we think about raising awareness and activate the patient. Right? This type of product could work very, very well in a more kind of direct to consumer type of approach here, particularly in certain subsets. We are very interested in the women's health area, for example, and it's really utilizing our digital and social media to kind of efficiently, you know, make awareness. So we talked about the importance of driving awareness from the from the health care professional side. Do How we start to think about driving awareness from the consumer side or the patient side here about Acreverse? That's something that we haven't really done just yet. But to do all of these four things, we have to make sure that we are resourced appropriately. Right? So if nothing else that you see through this kind of conversation we've gone through, yeah, we are making tremendous progress on a lot of different fronts, but we can do so much more.

35:57 There's a very, very big market that is out there right now. There are millions of patients waiting for the drug, but physicians can't write the drug if they don't know about it. Right? So we gotta make sure, again, we get them aware of the product and then start moving them towards that awareness, engagement, and adoption. There's a multitude of things that we can and should be doing right now, but it's important that we gotta make sure that we're resourced appropriately to really go after and take advantage of this full opportunity. And the last thing I would say is you've got a team here dedicated to doing just that. Right? The team here, the US commercial team that's in place, here now as well are very dedicated because we the opportunity. We are very encouraged by the early feedback we've seen. You know, I've done nothing else but be more bullish based on what I kinda hear and understand within the marketplace, and we're gonna make sure that we're resourced the right way to go after this.

36:47 So think that's the the end of the the scheduled presentation, but happy to open up here for Mark. That's absolutely brilliant, Greg. Thank you very much. And apologies, Greg. I think we're just gonna keep the cameras off to keep your connectivity. I know you are very keen to have the cameras on, but I just think your quality of audio should remain. If that's fair enough. You. Yes, that's fair enough. And thank you for your very kind presentation. Ladies and gentlemen, please do continue to submit your questions using the Q and A tab Greg, as you know, investors had the ability to pre submit questions. So perhaps if I may, I could start off with a few of those. The first one reads as follows.

37:34 What in your mind has been the single biggest challenge during the launch of Acuffer? Let's see. If I can narrow it down to one single biggest challenge, I again, I would say it's it's it's awareness. Right? I just I can't emphasize enough. You know, we've got a great product overall. And I think, as I said before, you know, when we launch, you know, for a variety of different reasons. Look. You it would have been great to have, like, this awareness built up, build up that pent up demand. You've got, you know, KOLs that bear with the product. You've got, you know, physicians kinda anxious to get their hands on it. You for know, variety of different reasons, we would have that. Right? So we gotta start that process now, and that's exactly, you know, what we're doing. But, again, it's almost like you got this great product. You get patients in need, but if physicians don't know about it, nothing's gonna happen. Right? So it's not like they were waiting for us to come. You know, we gotta kinda drive that awareness, you know, for lack of better expression and kinda get in front of people and force it on them and do it that right way.

38:34 So I think that is probably the the single biggest, you know, call it, you know, challenge slash opportunity, however you wanna phrase it overall. And, again, it really gets back to making sure that there's a variety of ways we can do that. Right? And what we don't wanna do, know, the reps are really important as part of this because they are front and center to help this, but we've gotta do a better job of surrounding them with, you know, just other ways that we can kinda drive awareness on different media tactics, social media, digital strategies, a real what they call omnichannel approach, which is delivering the right message to the right doctor at the right medium. Right? And there's a variety of ways that we have plans that you know, to accelerate that as well. And I think the when I say awareness, what we wanna think about is it's almost like if if a if you got a headache, you immediately think of Advil or Tylenol.

39:19 Right? Generally speaking, like, headache, Advil, Tylenol. What we wanna drive to is, hey. Iron deficiency anemia, you know, tolerability. I wanna think about. That's exactly what we're trying to drive here. So I think that, in my mind, would probably be the the the single biggest challenge slash opportunity that we're working on. That's great. Thank you very much indeed. If I may turn to the next question, could you please explain the trade off between payer coverage, patient assistance, and the resulting net revenue per prescription? What are your plans to expand market access in 2022? No. That's a that's a a really great and important question. Hans, Peter, Rudolf, would you mind taking the first stab at that to walk people through that? I think that's an important element here. Sure. Thank you, Greg. Yeah. I think, first of all, we need to recognize that the the payer landscape is completely different in United States than anywhere else in Europe.

40:11 It's also rather complex. A significant portion of the pricing in The U. S. Pharmaceutical market is controlled by three to four large pharmaceutical benefit managers or PBMs, as Greg explained in his presentation. Those are companies that manage prescription drug benefits on behalf of health insurers and other payers. Pharmaceutical companies must negotiate a reimbursable price for their product with each of these PBMs. The negotiated price will be a percentage of the so called wholesale acquisition cost, which is essentially a theoretical sales price, but which will never be achieved because of the negotiated discounts. In some cases, the price negotiated with the PBM will be accepted by the individual health insurer and payers underneath the PBM.

41:00 In other cases, a successful negotiation with the PBM only opens the door to then start negotiating a price with the underlying insurers. So a rather cumbersome and time consuming process to really get full or near full payer coverage. By December 2021, SHIELD had successfully negotiated prices to cover a total of about 40,000,000 patients. Since then, that number increased to 60,000,000 patients, which now represents about a third of all patients covered with the large PBMs, so pretty good progress. Until the first payer contracts became effective in December, SHIELD had to fully subsidize virtually all prescription sales to a nominal net selling price. This was important to create awareness about the ensuring right and ensuring writers and patients who start developed a demand for Acrefer.

41:54 Only once the initial payer contracts became effective, some, but still not all of the prescription sales started to generate revenues. And as additional contracts become effective during the first quarter of this year, we expect the mix of prescription sales to insured versus non insured patients to increase, which would then also increase the average net selling price. But because the process to achieve a reasonable level of payer coverage may take up to twelve months or even longer, a portion of the product sales will likely continue to be subsidized for some time. Thank you very much indeed, Hans Peter. If I may turn to, the next question, and it reads as follows. What has been the feedback from physicians and patients as it relates to ACUFA efficacy and tolerability?

42:42 Jose, you wanna jump in? Yes. Thank you, Greg, and thank you for the question, Mark. So, you know, we have spent a lot of our time in from all the physicians, the KOL, and the prescribers, the MPs, and PAs through, you know, one on one interactions, KOL events, and advisory boards. And the feedback that we are receiving, is the same across the board. They are very impressed with the efficacy and the safety of the product from the clinical data. They're looking for a tool that allows them to basically treat the condition of iron deficiency, iron deficiency anemia that is prevalent in this country.

43:28 And they're looking for a product like you mentioned, Greg, that have the efficacy is well tolerated and the efficacy that they're looking for. And, you know, AccruFresh checks all those boxes. So in every single instance, in terms of all those interaction, the feedback is the same, and they're seeing kind of the clinical trial experience translating into the clinical experience in front of the patients. Or like you mentioned, awareness and then knowing about it is very, very important. You know, like I mentioned, we had conducted advisory boards, and I just tell you a story about, you know, one provider that mentioned to me at the last of life advisory board that we conducted a couple of weeks ago is like, why did I not know about this before?

44:16 Why are telling me now? I think certainly my patients will benefit from AcroFresh. So I think awareness is gonna be important. The feedback has been very positive, and I think it's our job, like you just mentioned, Greg, to continue to increase that awareness and make sure that physicians know about the product because once they know about the product, they prescribe it. Yeah. I think to add to that too, you know, qualitatively, we kinda, you know, monitor, obviously, field feedback and things like that. And, you know, generally speaking, you know, for good or for bad, if something bad is occurring, I e, like, know, there's a lot of, you know, GI issues, the tolerability, you know, typically, you hear the negative feedback first from the field, right, and from their doctors. Right? That's just the way things work. So far, so good. Right? I mean, we're not really you know, there's not a lot of requests coming in on the medical information side.

45:02 You have rep feedback, clinician feedback. Qualitatively, it's really good. So, you know, at this stage, the product appears to be working as it's supposed to, right, delivering good results, but also from a well tolerated perspective. And, so, you know, again, encouraged. Right? That's really what you want. Right? You want the product to behave just like it did in clinical trials, and we've heard that consistently even from some of the clinicians over in Europe and Germany, where they've been maybe a couple of years ahead of us. It's pretty consistent across the board. So again, a reason to be very bullish on that side. Yes. And Greg, I will add that the insights that we're getting from the physicians in terms of the patient experience is also very positive. And, you know, one of the comments that, you know, we have received many times is that the patients also like the idea that this is a low dose of elemental iron that basically does the trick from the perspective of treating their condition. So they take thirty milligrams twice a day, and that's enough to basically increase the hemoglobin, increase the iron stores.

46:03 And, you know, as we have seen in our clinical trials, they can maintain that for, you know, a longer period of time. So, you know, the the the feedback from the patients as well has been very positive. That's great. Thank you. What I might do is join at the I mean, we've had questions from Mohammed S, John F, James W, and we received a number of questions before today's event around cash and capital raising. So what's the need, I guess, in terms of your what's your position with the cash burn and the need of potentially raising additional funds? I mean, could you give a little bit of clarity around that whole concept of that position? Yes, I'll take that. Yes, please go ahead, Hans Peter. Thank you. As you may have seen, we previously reported cash balances of GBP 22,600,000 at the 06/30/2021, and then six months later at 12/31/2021, GBP 12,100,000.

47:00 This would indicate an average monthly cash burn in the last six months of about one point seven five million. Additionally, like all prudent management teams of companies, we are not yet cash flow positive. The company is continuously monitoring its cash balance, levels of expenditure and assessing opportunities to strengthen its liquidity position. As you heard from Greg's presentation, SHIELD has made tremendous has a tremendous opportunity here with aquifer in The United States, and a lot of progress has already been made. At the same time, there's a lot more which could be done to properly invest in this business opportunity and to ensure it is adequately resourced. Thank you. Thanks ever so much indeed. Have you made any changes or adjustments to the strategy related to your launch?

47:50 Yeah. I mean, yes, we have, as you would expect. Right? I mean, first, he's coming in. Right? My job our job or my job coming in is, like, the the launch is almost, like, ready to go. Reps are hired, then it's like, alright. Let's you know, understanding, you know, what we didn't do early on, let's make sure we do this as quickly and efficiently as possible and try to get this, you know, launch up and running. So, like, any team, you definitely start diving into details, understand what's going on, you know, underneath the hood for lack of better expression. So one of the, you know, the good news is, like I said, strategically from a messaging standpoint, we've got that right. Right? That and that's really critical. Right? So we got that right. You know? So kudos to, you know, our marketing team. They got the message right here. What we have changed, however, is on the the, you know, kind of more of the targeting and the Salesforce effect. So those are kind of two key areas that I've kind of zoomed in on. So early on in the launch, you know, I guess the best way to say it is, you know, our data systems and our targeting for our reps were nowhere near as tight as I would like to see them. Right? So we had kinda a little bit of drift out there from a representative perspective calling on, you know, variety of different specialties, primary care physicians, OB GYN, some GIs, some nephrology, etcetera. You know, we have gone back, you know, worked with our, you know, data team and really tightened up that target list, right, where, as I said before, 80% of the business is primary care, women's health, and nurse practitioners and PAs.

49:14 That's who the reps are now calling on. Right? So we kinda refresh the target list, ensure that that is who want you to stay, that is the folks we want you to have. You know, don't drift off anywhere and make sure that that is done. So that, you know, falls under kind of the targeting piece. I also mentioned Salesforce effectiveness. You know, we've got a brand new Salesforce. Right? The people that were hired had no pharmaceutical experience, so we gotta make sure that we're giving them the right training, you know, expectations, and importantly, coaching, kinda get them up to speed as quickly as possible. Any rep, no matter which, you know, position or or, especially dealing with, it takes some three, four months to kinda get things figured out, right, to figure out who they're calling on, getting the flow, how things work overall. One of the actively as well is I've kinda we were using a contract model, for both our field Salesforce and our field sales management team. I've taken the field sales management team, and we have hired new individuals that are now part of SHIELD. Right? So my head of sales, our three regional sales directors are now SHIELD employees, not contract employees, and I wanted to have that, you know, better kind of alliance line of sight. You know, I just mentioned the importance of getting these reps up to speed from a coaching and a strategy and targeting perspective, and I'm really, you know, happy with the early results here. We made those changes in the, the January time frame to bring those folks on board. So you're investing in the business, getting the right people in the organization, ensure that we've got the right targets we're focused focused on, ensuring as well that, we are doing the right things from a, a training and a messaging perspective.

50:45 Thanks very much indeed. Let's turn to the next question. After leading the company now for six months, how's your view on the opportunity with a Accafa changed? Not one bit. Not one bit. And it I came here because I believe in the product. Right? And, you know, as I mentioned before early on, you know, this is not an excuse by any stretch of imagination. It's a reality of, like, when we launch, what we did, and what we didn't do, and what we need to do. Right? And, you know, based on what I see from the product profile, like, nothing has changed my mind. Right? The opportunity is there. And in fact, we've now done rounds of research. We got feedback from clinicians on the product overall. We're generating prescriptions. We're building up that payer coverage.

51:32 Again, it takes time to drive that awareness. It just takes time. I wish I could shortcut it in some way, and that's part of what we're trying to figure out is, like, alright. How can we drive better? What are the different tools we can do? And, you know, how do we ensure that we're resourced in a way that we can rapidly increase that awareness? I think Hans Peter said, we are we are virtually scratching the surface of what we should be doing to really maximize the value of this product. Right? And to do that, we've gotta make sure that we are resourced adequately, in a number of different ways. But as far as what the opportunity looks like, the need out there from patients, the receptivity of physicians overall, as they become aware that they wanna learn more. I mean, everything sits right there where, you know, that long term opportunity. We get IP all the way to 2035.

52:17 We've got a great runway in front of us. In many ways, look. This is this is a marathon out of sprint. We're in the early phases of that marathon right now. So, again, I'm very, very encouraged by the early progress that we've seen, and we've got a ton more that we can and wanna do. Licensing, the question here we we received, what other geographical areas are at the top of your list for further out licensing of Acuffer? Hans, Peter, maybe you wanna grab that one if you don't mind? Sure. Yes. Obviously, we continue actively to look for potential out license opportunities. Right now, as everybody knows, were commercialized the product ourselves in The United States. We have licenses granted in all of Europe, including Germany and United Kingdom, in China, South Korea, Canada.

53:08 And so there obviously, if you go look beyond that, what are the most populous and economically interesting areas that are remaining. And I think it's it's it's quite obvious at that point that we keep our focus in Latin America, The Middle East and North Africa and see if if appropriate opportunities, you know, are available for us to out license the product anywhere in those areas. Thanks very much. Yeah. Look, Mark, I I know we're over our our time here, but I I really appreciate all the investor questions that are coming in here for sure. Why don't we plan to take maybe a couple more questions? I know we're over everybody's time, so I appreciate everybody's patience. But, you know, we're trying to get through as many of your questions. So thank you for your interest, but maybe we'll take a couple more, and we'll go from there. Okay. Perfect. Do you have any updates on the progress of your pediatric clinical trial?

54:00 Yes. I will take that question again, Greg. So we initiated our pediatric clinical trial for patients 17 last fall in q three of twenty twenty one. We have sites activated in UK and US. And the moment, we are currently enrolling patients. So the trial is on track, and we know that there's a high prevalence of iron deficiency and iron deficiency anemia in the pediatric population. It also, you know, differs depending on the age bracket. So we're certainly looking forward to the conduction of that particular story. And since we're talking about clinical trials, I just probably will take a minute to answer a couple of questions that I came off from the perspective of the clinical trials in China as well that I saw in the chat room. So that China is also in the enrolling patients in their phase three.

55:13 So we were excited to continue partnering with SKA to kind of get that trial to completion as well. So thank you, Mark. That's great. Well, thank you very much indeed. You know, obviously, Greg, you've got quite considerable amount of investors on today's call. And thank you to everybody, as Greg has said, for submitting your questions. We will make all these questions available to the company. And hopefully, we've covered some of the areas that have been quite thematic. But perhaps one of the questions here from Tony g is looking at the current share price and the bullish position. Why haven't why aren't directors buying material amounts of shares and putting some skin in the game? In fact, I think we've just lost Greg. I think Greg's just being disconnected. So if we just bear with us while we just be I'll I can try to answer this question here and try to real quick. Yeah.

56:05 Yeah. No problem. Well well, obviously, you know, we can't force directors to to to to purchase. I mean, we have no control over what everybody's personal interests are. You know, I I think each of the directors already has a significant stake in the company. Those stakes are different based on the duration, the term that they that they have been with the company so far, and also different based on their personal appetite in terms of investing in the stock. We certainly can't control that, but I can assure you that everyone of our directors is as committed as we are about the product, and they believe in the opportunity in The United States and, quite frankly, everywhere in the world. That's great. Thank you very much indeed. As I said, we're probably coming up to the hour. Greg is just literally coming through. I'm gonna see if I can just grab Greg just for a few closing comments before I redirect investors to provide you with their thoughts and and expectations.

56:56 So just bear with me one second. And and Greg, can you hear us okay? Oops. No. I just lost Greg. Greg, are you there, sir? Can you hear me? Yeah. I can hear you, sir. Well, look, Peter very kindly answered the the question for Tony G. And as I said earlier, we'll make all these questions submitted from investors that they've kindly submitted today, and we'll make those available to you for your review, and we'll publish the responses on platform and notify everybody when those questions are ready. Greg, I know investor feedback is important to you, and I'll shortly redirect investors to provide you with thoughts and expectations. But perhaps before doing so, if I may, just ask you for a few closing comments just to conclude with. Yeah. And and just a check, Mark. Can you hear me okay? I can hear you clearly, sir. Yep. Great. Great. Sorry about whatever Don't worry. The challenge of trying to do all this virtually in many ways. So apologize for any, inconvenience there as well. No. First off, thank you very much for, a, your interest and, b, your questions that, came through today.

57:54 The goal again today was to provide a little bit additional color, context on the progress we made for the launch. And, look, I think we are making very good progress, you know, across the board in a number of different areas. You know, our goal as a management team is to try to speed things up as much as we can. As I mentioned several times, you know, the the foundational pieces, you know, in many ways, these first six months are you know, we've kinda gone through a lot of these similar prelaunch activities that most companies go forward with, and we're making really good, strides on a number of different areas. I'm bullish. I'm very excited about what can be. Big goal for us is to ensure that we get the right resources to go after this, you know, opportunity. But, again, we've got a very dedicated team here in The US. I wish you could kinda see the office on a daily basis and the buzz that comes around here because it's fairly intoxicating.

58:43 But we're excited about the opportunity. Again, thank you for all of your interest and time today. Greg, Jose, Hans Peter, thank you very much indeed for updating investors this afternoon. Could I please ask investors not to close this session as we'll now automatically redirect you for the opportunity to provide feedback in order that management team can better understand your views and expectations. This will only take a few moments to complete, but I'm sure will be greatly valued by the company. On behalf of the management team of SHIELD THERAPEUTICS PLC, we'd like to thank you for attending today's presentation. That now concludes today's session. Good afternoon to you all. Thank you once again for your time.