Futura Medical plc (FUM) Earnings Call Transcript & Summary

Hello, everyone. I am James Barder, the Chief Executive of Futura Medical, and I'm pleased to welcome you to the webcast of Futura's audited results for the year ending 31st of December 2019. And also our investor seminar where Ken James, Executive Director and Head of R&D, will provide a detailed analysis of the very exciting results from our Phase III study, known as FM57. I'm also very pleased to welcome back Professor David Ralph, who has kindly agreed to provide his presentation on current treatments for erectile dysfunction on unmet needs. David's presentation will be found in part 2 of our webcast. First of all, can I please draw your attention to the disclaimer issued on Slide 2 of this presentation? Futura is located at the research park in Guildford in Surrey. We describe ourselves as a virtual organization with 13 staff and a significant outsourced infrastructure with over 30 consultants. I think this is particularly relevant for us in recent circumstances of COVID-19. The move to working from home has been completely seamless, and I'm pleased to say to date COVID-19 has had very limited impact on us. Futura's key asset is our transdermal science technology collectively known as DermaSys. Each time we look at developing a new product, we apply the principles of DermaSys with the aim of delivering a clinically proven innovation. MED3000 is a topical gel for the treatment of erectile dysfunction and is a highly differentiated treatment with the rapid speed of onset. For some patients, it works immediately with 60% of patients within 10 minutes. We also have our pain relief portfolio, which comprises of TPR100, a topical gel containing diclofenac and CBD100 a tropical gel containing cannabidiol. Key highlights during 2019 was, I think, a strategic decision to continue derisking our R&D pipeline. And in particular, MED3000 with the regulatory submissions in both the U.S. and the EU. Also increasing the general awareness of MED3000 within the scientific and pharmaceutical communities. MED3000 results were reported in December '19 with the potential of MED3000 being a highly effective, clinically proven treatment for erectile dysfunction. However, I will let Ken provide full details on this shortly. We continue to lend our support to Thornton & Ross on their TPR100 submission to the MHRA in the U.K. However, the work is taking longer than expected, which is likely to delay submissions by at least 6 months. Finally, optimization of a cannabidiol tropical gel is progressing, and we hope to update the market further by the end of July on this. Our strategic outlook is very simple: one, gain approval for MED3000 in the U.S. and EU and then actually other countries; two, realize shareholder value for MED3000. And now that dossier submissions are underway, we are increasingly turning our attention to this; and three, expand our portfolio of potential products using our DermaSys technology. I will now hand you over to Angela Hildreth, Futura's Finance Director and COO. Angela?

Thanks, James. Good morning, everyone. I think the first thing to note for our full year results is that there is nothing unexpected within these results. We ended the year with a net loss of just under GBP 9 million of which GBP 8.27 million was related to R&D. That is an increase on the year before, but that is not surprising given that we were running and completed our Phase III FM57 study, which I will say, completed on time and within budget. The balance of the losses are made up of our core central and administrative overheads, which were broadly similar to the year before, if not slightly lower, and that is demonstrative of our commitment to keep our central costs as lean as we can. We ended the year with cash resources of just over GBP 2.5 million. We add that to the GBP 3.25 million gross fundraise that we completed in January. And we're expecting a GBP 2.2 million R&D tax credit refund in the middle of this year. Our cash burn in 2020 is expected to be significantly lower than it has been in 2018 and 2019. And that is in the main because we're not running any extensive clinical studies. Our resources are focused on the completion and the submission of our regulatory dossiers, which are to be completed mainly with existing internal resources. So that gives us current cash resources sufficient until at least Q2 2021, and that is our lower R&D cash requirements. I'm going to hand you over to Ken James now, who is going to take you through the FM57 results.

Hello, everyone. It's a real pleasure to be able to talk to everyone today, albeit under very difficult circumstances. So what I'm going to cover today are details around our pivotal Phase III study, FM57, and then I'm going to move on to compare the results of that study with published data in the literature on competitive products and placebos, talk about how we think the product is working, a unique evaporative action, as we call it. And then finally, cover the regulatory status both in the EU and with the FDA in the United States. So the headline here is that we have created a unique gel for erectile dysfunction as a medical device, which has very strong overall efficacy across all erectile dysfunction patient severities. It has a rapid speed of onset, begins to work immediately in some patients with 60% of patients seeing onset of their erection within 10 minutes after application, has a really first rate safety profile and potentially could be used in patients who are currently contraindicated from using oral pills, such as patients on cardiovascular drugs who are taking nitrates, alpha blockers, anti-hypertensives and so on. And another opportunity for us is that the product could potentially be used in combination with drugs like Viagra and Cialis, where some key opinion leaders have said, well, maybe there are groups of people who don't respond particularly well to these PD-5 inhibitors, and therefore, having something to boost the effect would be quite useful to us. So FM57. And as you know, because we published the headline data before Christmas and was a large Phase III clinical study. It was run in 1,000 patients over a 12-week period. It's a double-blind study. It was run in 9 countries, 60 centers, and in fact, used 2 CROs as well, clinical research organizations, to run the study for us on our behalf. And the product was used in the study, either applied by the male or the male's partner. There were 4 legs to the study, 4 formulations studied. Firstly, there was the MED3000 gel, which is the proprietary DermaSys formulation and that was the vehicle. So that was the control product used in the study. And then we added 2 MED3000, different doses of glyceryl trinitrate. So before I come on to talk about the results, we often quote numbers at you, which can be quite confusing. So I just wanted to spend a moment explaining what the different measures are with the primary end points. So the primary measure is what we call IIEF EF domain, and that's the International Index for Erectile Functionality, the erectile function domain. This, along with the other endpoints, internationally recognizes standards, fully validated endpoints. In fact, these 3 endpoints were requested by the FDA for us to use when we had our pre-IND meeting with them a couple of years ago. And these 3 endpoints have been used in all Phase III ED drug trials leading to approval in recent years. So what is IIEF EF domain? It's a combination of 6 questions, which are laid out here. Question 3, for example, how often were you able to penetrate? So there are all questions relating to the degree of functionality in the erection. Each of these 6 questions are scored on a 5-point scale. And therefore you can assess the degree of ED severity as a result of that. If you get a score between 26 and 30, then you have no ED; mild ED, 17 to 25; moderate ED, 11 to 16. And with severe erectile dysfunction, if you get a score of 0 to 10 across these 6 questions, than that's classified as severe. And the way we go about applying these measures is that before people actually take the test product, they are subject to a baseline measurement. So during the screening phase, they are assessed, they have to have a minimum of 4 intercourse attempts over 4 weeks. And that is scored on the IIEF scale. And then people take the test product over a 12-week period, and they're rescored at 4 weeks, 8 weeks and 12 weeks. And therefore, you're able to take an average of the 4, 8 and 12 weeks and then compare it with the baseline reading. And I'll be talking about baseline comparisons a lot as we go through this, and that's really what it means. You measure the baseline before people go into treatment, and then after they've been on treatment up to 12 weeks, you remeasure and you're able to take the difference between those 2 values. On SEP2 and SEP3, these are the questions that are asked. And it's a binary answer, you get a yes or no value. And then you look at the percent improvement over baseline of the number of people answering yes and so on. So that's how you measure the primary endpoints. And now I want to go on and look at the results that we got from FM57. Now these include results for MED3000, and they include the 3 doses of glyceryl trinitrate in comparison with MED3000. And they present a number of mean values. And I just want to explain a little bit about this because this is quite important because there are 2 ways of calculating means. There are observed means, which are means of the actual values that are generated during the study. And then there is, what we call, least squared means. And this is a corrected value. It's a statistical correction, which is to compensate for some minor differences in disease severities noted across different countries. So -- and it presents a slightly more conservative view of the data, if you take the least squared means. Now as I go through the presentation, sometimes I'll be using least squared means and sometimes I'll be using observed means. And the reason for that is -- depends on the chart that I'm showing and the comparison that I'm trying to make. And at all times, I'm trying to do a like-for-like comparison. I'll explain more about that as I go through. And you can see the relevance of why I'm getting a little bit into the weeds here on the statistical treatment of data. So this chart contains a number of data points. You'll see down the left-hand side that we have the 3 co-primary endpoints, IIEF EF domain, as I've described it, the average of the 6 questions, SEP2 and SEP3. And as you go across the chart, you can see the values between MED and the 3 doses of GTN. And you'll see very quickly that there isn't really a lot of difference between MED3000 and the 3 doses of GTN. And that was what -- really what we set out to try to show during the course of the study that there would be a difference and the glyceryl trinitrate would add to the effects of the DermaSys control vehicle. What we actually showed was that if you look at the MED3000 results on the left-hand side of the chart, the results were really quite impressive in their own right, if you compare with the baseline that I talked about earlier. So we've looked at the change from baseline using the least squared means, the corrected mean values, as I've described them. And you can see that in all cases, the -- against the 3 co-primary endpoints that we get a highly statistically different improvement with the MED3000 over the baseline reading. And by the way, there was a high degree of consistency in the data across the 9 countries and even across the 2 CROs. So given that this was a large study involving 60 centers, this result was not a fluke. It really is a genuine result. This breaks the results out into a little bit more detail. On this chart, I have the observed means and the least squared means, so you can see the difference between the 2 data sets. And it looks at the overall effect, and it looks at the effect in mild, moderate and severe sufferers. And on the right-hand side of the chart, you can see the p-values, the statistical differences between the least square means, which has taken a more conservative view of the data and the baseline. And a p-value of less than 0.05 is regarded as significant. And in all cases and across all disease severities, mild, moderate and severe, you can see that we achieved statistical significance with MED3000 without the glyceryl trinitrate. And also, you will see that if you look at the values that were achieved between mild, moderate and severe, actually, the more severe the condition, the bigger the differences that we were getting, the bigger the improvement we were getting, and that was actually quite a surprise to us when we looked at the study results. Moving on to the next slide. This is a very, very important slide because it looks at clinically important differences. Now a real hot button with regulators and leading scientists, when they look at clinical trial data these days is not just the statistical significance that I've just told you about, but it's whether patients can really notice a difference. Because you compare a study up with thousands and thousands of patients and show that very small differences are recurring that are statistically different, but the patient really doesn't notice. So this is a way, and it's an internationally accepted standard using criteria developed by 2 guys called Rosen and Araujo for assessing results for individuals in a clinical study and assessing whether they're clinically important. And if I look at the overall responder column there, you'll see 63%, 75% and 68% of people noticed a real meaningful clinical difference. And if you look at the right-hand side of the chart, you can see that broken out for mild, moderate and severe. And for the severes, for example, 80%, 77%, 71% of severe ED suffers were noticing a real difference when they applied MED3000. And these numbers would be regarded as very impressive actually for any therapy, let alone MED3000. The next chart reminds us that we didn't just mention -- didn't just calculate the primary endpoints. There were a number of secondary endpoints. We've put some of them down here. And in all cases, we got very high grow consistency that we got, where it was calculated, statistical improvements over baseline for MED3000. So that was good. The secondaries are very much in line with the primary conclusions that we draw as well. How fast did the product was? It's a question we often get asked, and actually, it's a main differentiator for us with MED3000. So here, you can see cumulative percentages of people who noticed the first onset of an erection at certain time points. So med was applied on the left-hand side there, around 8%, almost immediately noticed something happening; 32% in under 5 minutes; and 60% cumulatively under 10 minutes. And then 75% under 20 minutes. And with 10%, as in any clinical trial, there are some people who just didn't respond to the product, 10% really didn't notice an effect at all. But 60% under 10 minutes. Interestingly, the result was not instantaneous. Although, we got 8% almost immediately, if the effect of the product was just acting through massage, you would have expected a much higher number. There was a bit of a lag time between when the product is applied and when you first noticed the erection occurring, which give us confidence that we've got something above and beyond a regular placebo happening here, which has a unique action. So when you compare the result of 60% of subjects having the beginnings of an erection at 10 minutes, it is significantly faster than the PD-5 inhibitors. These are oral pills that have to be absorbed, that have to travel around the body to the site of action and that all takes time. So for example, Viagra Connect, which is the OTC product in the U.K. They say, it starts to work in 30 to 60 minutes. So clearly, we have big differentiation here with the gel, which is applied or massaged for 15 seconds and then works pretty much for most people within 10 minutes. What kind of adverse events were we getting? Well, this is for both patients and partners. These are the ones that were most noticeable. We got 2.8% headache rate in men. And remember that we have approximately 3,000 intercourse attempts here. So people get headaches. And I don't think that there's any kind of physiological reason related to the product while they're getting a headache here. I think it's just biology that people occasionally get headaches. There was a very low level of penile burning. I think as the evaporation occurs, it may, in a very low percentage of people, 1.2%, be described as burning. For most others, I think it's a very kind of pleasant cooling and then subsequent warming effect. And we got virtually nothing happening in females. We got 0.4% vulvovaginal burning, but that's almost at the level of being kind of background noise, so to speak. How does MED3000 compare with products in the literature, other products in the marketplace, and indeed with placebos? And there was a paper published in 2009 by Araujo again. And he looked at the effect of placebos in erectile dysfunction. And you see a reference there on the left-hand side of the chart. But on the right-hand side of the chart, these are the number of responders who responded to the Araujo placebos. These were regular oral placebos that are used, and they got 36.8% response, which is there is some effect there, but it's a fairly modest effect. And then when we overlay the MED3000 data on that, the middle bar is when we just take our data on face value and apply the same criteria, it's 63.8%. But when you get to the right-hand chart, this adjusts for disease severity. And what I mean by that is that Araujo used quite a large number of severe sufferers in his study, and we used quite a large number of mild sufferers. And as I've already explained, the effect is bigger with MED in severe sufferers. So we've made some adjustments here, so it's very much an apples-to-apples comparison and the number jumps up a little bit to 77.9%. But whether you take the 63.8% or the 77.9%, it's still substantially more responders responding to MED3000 than would occur in the Araujo paper with regular placebos. If I move on to the next chart, these are scientific publications. There are dozens of them literally and were just chosen 3 here by way of illustration. Typically, a placebo in a clinical trial for a PD-5 inhibitor would have an IIEF value of between 0 and 2. And you can see that in the Montorsi study and the Hellstrom study 1.0 and 1.2. There was a somewhat bigger result achieved in the Carson study result of 3.9. But then if you draw your eye towards the baseline reading there, had a baseline of 6. What that means is that pretty much all the subjects in that study were severe ED sufferers. And then if you look at our results down the bottom there, for our severe population, we got a difference of 12.1. So you can see, looking at all this placebo data and looking at the results that we get, that we are substantially greater effect with MED3000 than placebos. How does it compare with PD-5 inhibitors? And in fact, another product that's sold in Europe called Vitaros that some of you may have heard of. We've chosen Cialis for the comparison here. We didn't choose Viagra because it's a very old data set. And in fact, the measures aren't exactly equivalent because it was in the early stages of the development of these compounds. Cialis in their pivotal studies used exactly the same endpoints as us, IIEF EF, SEP2 and SEP3. So it's relevant to do the comparison here. And we believe that Cialis in this data set used observed means, not least squared means. So we've used the -- that data set for comparison rather than the least squared mean data set. And you can see that, just at a glance, actually, that DermaSys on IIEF EF is broadly comparable to 5 milligram Cialis, maybe slightly less than 10 mg, a little bit behind 20 mg Cialis. Vitaros is topical alprostadil. It's sold in Europe, as many of you know. And it's not really a true topical. It is actually injected into the urethra, and it's quite an uncomfortable product to use, as you might imagine. And actually, if you look at the IIEF data, you get quite small differences in comparison with MED3000. Likewise, with SEP2 and SEP3, particularly, on SEP3, we get quite comparable differences to Cialis and on SEP2, broadly the same as Cialis 10 milligram. So I think what we would determine from this is that we would think that we would be superior to Vitaros and broadly equivalent to the lower dose of Cialis in this data set here, the 5 mg. This presents the data numerically rather than graphically. And you can see the data I've ringed here, which is a comparison with Cialis. We get a difference with observed means of 5.1, the 5 milligram is 4.6. Statistically, there's no difference between those 2 values. The placebo and the Cialis studies was an 0.6. So to make the point again, we're greatly in excess of regular placebos here, 5.1 versus an 0.6 is statistically in favor of MED3000 at the highly significant level. But no difference between the 5.1 and the 4.6, which is the 5 mg Cialis. And we fall a little bit short of the higher doses of the Cialis. Importantly, though, you can compare the side effect profile of MED3000 versus Cialis 5 milligram. And you can see that with Cialis headache, dyspepsia, back pain, myalgia and so on and virtually clean in respect of equivalent adverse events with MED3000. So really what's going on? It's clearly not acting as a regular placebo. And what we postulate, and we're generating data in support of this is that MED3000 contains volatile solvent components and they evaporate. The glans penis, the head of the penis, is very highly innovated and that means that they've got a lot of nerve endings, which respond very well to different sensory effects. So they react to a range of physical sensations, touch pressure and temperature. The cooling from the solvent evaporation with subsequent recovery warming following the topical application of the MED3000 gel, we think stimulates more than one such sensor so that they react synergistically and then you get the erection occurring without the inclusion of the drug substance. If I move on, lastly, to talk about the regulatory side of things. We've had discussions now with the U.S. FDA, and the notified body who are authorized to clear products on behalf of the European regulators. On the latter side of the chart, you can see a simple chart of where we are with the U.S. FDA. We requested a meeting in December. We had the presubmission meeting a few weeks ago. We're still waiting for the final minutes of that meeting to come out. But obviously, attending the meeting, we know the feelings that FDA have in respect of that. And the bottom line is they're looking upon the application quite favorably. They do agree that it can be classified as a de novo medical device. We have some ongoing discussion with them on whether our clinical data package as is using some of the comparisons with data and the literature that I've described to you already will be sufficient. They were very receptive to the arguments that we're making, and they've asked us to provide them with more detail on that. We're putting that data page together. And then usually within 2 to 3 months, FDA will grant a meeting. They've actually asked us for another meeting to discuss the clinical sufficiency. And provided that goes well, there's always an element of doubt when you're dealing with the regulatory authority, but provided that goes well, we anticipate filing in the U.S. around September this year. As far as Europe is concerned, we had a very good preliminary discussion with the notified body, and they've agreed that we can work them on the filing. The next stages for us are to update our quality management system to reflect the new product, and there are new medical device regulations coming in, in Europe, in any case. That will be complete in July. We have to put our technical file together as well. And therefore, we're looking to file with the notified body in July this year. So making bigger progress there on both sides of the Atlantic with the notified bodies. So moving then on to my last slide and summarizing where we are. We think MED3000 is a breakthrough clinically proven treatment for erectile dysfunction. It's a first in the world, easy-to-apply gel. There is really nothing like it that works like this. It's highly effective in mild, moderate and severe ED. Works in 5 to 10 minutes for spontaneous sex as opposed to the preplanning that's often required with the oral tablets and can be used as part of foreplay. And we found that a number of people were using it as part of foreplay in the clinical study. A very low and favorable side effect profile. No drug interactions because we're not putting a drug in it. As patent protected, we think there's potential for the product to be available over-the-counter or Rx, depending on how we choose to go forward with that. And it's a faster regulatory pathway through the medical device pathway. And therefore, represents, in our view, a major near-term opportunity. Thank you very much.

This concludes the end of Part 1 of the webcast. Please, if you're interested in listening to Professor David Ralph's presentation, will you now click on the second link, Part 2?

Good morning. My name is David Ralph, Professor of Urology at University College London. And today, for the next 15, 20 minutes, I'm going to talk about the management of erectile dysfunction in our patients in clinical practice. Erectile dysfunction is often known as a lifestyle issue. But certainly, over the last 20 years, we realized that it's a marker of organic disease. And if you only have to look at these 3 studies to show that actually, if you have a healthy sexual life then you're likely to live longer. You'll certainly have less cardiac events, and you'll see later in the talk how this issue is one of the main markers for cardiac disease. It does alter the quality of the life, not only of the partner -- the patient but also the partner. The patient often has low self-esteem and confidence, not just sexual confidence, but confidence in everyday life. The partner has concerns that perhaps she's less attractive and/or the patient is having an affair with someone else. And so they'll then have relationship breakdowns. The easiest way, of course, to avoid this issue is to not have sexual intercourse, and therefore, bury your head in the sand. This unfortunately will give loss of intimacy and further relationship problems. So it's not only the family that it affects but also at workplace. And eventually, most of these patients will be pretty depressed, if not clinically depressed, up to half of the patients. It's a fairly big issue. You can see from the numbers of patients globally that this is increasing all of the time as we all live longer. This -- you can see even in the Europe alone there's almost predicted to be 12 million patients that will seek treatment for erectile dysfunction in the next few years. This is the Massachusetts Male Aging Study. It's a study -- an observational study that we use quite regularly, which shows that just over half of the patients at any one time will have erector dysfunction. Sometimes it's pretty severe, other times, minimal, so-called performance anxiety. But by and large, 52% at some stage are going to have erectile difficulties. You can see this was in men between 40 and 70. That's backed up by other studies, which show that with the increase in age, so the prevalence of erectile dysfunction increases. But it's also quite common in men under 40 years of age. And of course, these patients are unlikely to have any organic disease. And so are likely to have a condition known as performance anxiety. Performance anxiety, of course, is the patients they have normal erector functions. But in certain circumstances, unable to perform because of the anxiety, which has an effect of reducing blood flow and constricting the smooth muscle and therefore, either losing the erection or not being able to get the erection in the first place. Often these patients, therefore, need help. And as you can see from this study, almost 20% of patients before -- below the age of 30 were using PD-5 inhibitors recreationally, really as a sort of a safety aspect for them. So they have it in their back pocket, but of course, sometimes they don't use it. Looking at across the ages, and this is a meta-analysis over a 10-year period. And you can see that this is related to the ages. And if we just take the men over on this side of the chart, you can see anxious about their performance and troubles with their erections, and these are the different age groups. And even the younger age groups, you can see here in the blue, have quite a significant amount of performance anxiety. I mean, all age groups do, but particularly so in the younger group. And this is some data from the U.K. And again, in the men, you can see anxiety -- performance anxiety and difficulty with the erections are quite common. And this is relatively easy to treat because these patients have mild erectile dysfunction. They don't have any significant organic disease. And therefore, the treatment is more likely to be successful. There are organic conditions and diabetes being the most obvious in the western world, really. It's well known that it causes both diseases of the blood vessels, arthrosclerosis as well as neuropathy. And you can see in the diabetics between 30% and 70% of them will develop erectile dysfunction. Also, of course, once the patients have been diagnosed, they will know that erectile dysfunction is a consequence of this condition, and that may cause anxiety particularly in the younger patients, so they'll then have the performance anxiety as well. It is our duty to make a diagnosis. Remember that 20% of patients, the diabetes is diagnosed at the time of their erectile dysfunction first appointment. And all the guidelines will suggest that you really should exclude diabetes when you see a patient for the first time. Also, of course, we try when we see our patients, we ask them to make sure their diabetic control is improved. Because with better control, not only will you delay the severity of the erectile dysfunction down the line, but also it may improve their erectile dysfunction at that particular time. Because the severity of erectile dysfunction is related to how long and how well the diabetes has been present. Now I did talk about earlier cardiac disease. And certainly, we now say that any patient with erectile dysfunction has a significant risk of cardiac disease as well. And this is fairly common sense in that if you have arterial disease of the penile vessels, then you're also likely to have arterial disease of the coronary vessels. And so what -- so there's been other studies to say -- suggest that patients that present with organic erectile dysfunction over a 3-year period, 2/3 of them could have a myocardial infarction. And you can see it's not only myocardial infarctions, angina, strokes and TIAs are also risk factors and can be a cause associated with the erectile dysfunction. Let's move on a little bit now to the treatment of this condition and the first-line therapy, and this is prescribed by general practitioners and secondary care is a tablet, the PD-5 inhibitors. These are a family of drugs, 4 of them on market at the moment, as you can see in this table. And they all are pretty effective and have revolutionized the management of this condition. The only real difference is the onset of action and the duration of action. Some of them are classified as short-acting and others, for example, tadalafil, long-acting. By and large, in the general population, you can see the 3 earlier drugs, about 70% of patients that are prescribed one of these medications have a successful outcome with good erections for sexual intercourse. And that's across the board. So that's including the severe erectile dysfunctions and also those patients with mild. If you look at the diabetic population, you can see it's not 70%. It's more like 50% to 60%. And these are known as the difficult-to-treat. So it is our duty as a clinician to identify these patients because we know which patients are likely to respond to medications, which patients should be treated with alternative medications. Now second line therapy, these are some of the options. You can see here this is Caverject, which is an injection. So each time the patient wants to have sexual intercourse, they will inject this medication into the side of the penis, and they will get an erection 10 to 15 minutes later. It's pretty effective, much stronger than the tablets. But clearly, when you ask a patient, would you rather inject yourself or take a tablet, they'll go with the pills 100% of the time. Other alternatives over here. This is a little pellet of prostaglandin the same drug as in the injections, but it's actually injected or, should I say, placed within the urethra as you can see here. Ideal in that you don't have to do an injection. But unfortunately, the efficacy of this is relatively poor. So it has a fairly minor market share. Other second-line treatments. This is Vitaros, again, prostaglandin. This is a little cream, which is placed in the urethra. You try and get as much as you can down the urethra as you can see here. And then rest -- rub the rest onto the glans penis. Again, this is very good in mild erectile dysfunction, but probably not so good in the severe cases. Vacuum devices have been around for 50, 60 years now, and they are effective in most patients. The idea is that you put the peanuts into the vacuum chamber, you create the vacuum by the pump mechanism on the handle. And then when the penis is erect, you place these little compression rings around the base, and you take those off once you're finished having sex. It works in every patient, but you can see it's a bit cumbersome and hardly spontaneous, and the quality of the erection is slightly different than normal. But again, it's another option which patients can have. Final option, third-line therapy would be penile prostheses, which is, as I said, usually given when everything else has failed. You can see that there different varieties. This is inflatable. So you have the cylinders, which are placed inside the penis, a reservoir of fluid placed in the pelvis and a pump, which is placed in the scrotum which allows penis -- which allows fluid to go from the reservoir into the cylinders for an erection and then the other way to erect the penis to go down. Shock-wave therapy is all the rage at the moment. There's different machines out on the market and patients come in and have their penis shocked for 3 to 12 sessions. It's thought to improve the blood flow within the penis. It's very, very safe, but we still await larger trials to actually confirm the initial success. So here, you can see over time, what's actually happened. And I'd say, in the very early 1960s, we just had primitive surgical techniques and vacuum pumps. The implants got a little bit better in the '80s, and then we went on to the injections. And then the real breakthrough was in 1998 with the launch of Viagra, and that really has revolutionized the management of this condition. It's so easy now to treat with effective medications, and the stigma of the condition has now gone. You all heard of the Viagra jokes and its common place in society. But what we're looking, of course, is that -- I mean, this is now 20-odd years later, and we haven't really had anything else. You've had those 4 tablets, but what we really want is something new. In clinical practice, when you see the patient then obviously, you want to make the right choice for the right patient. And you can see there's 3 elements to this. There's over here the actual medication, the drug itself. And of course, it has to be effective, safe and with minimal side effects and last long enough for them to have sexual intercourse. And then on this side, you have the doctor who's actually doing the prescribing and giving the advice. And of course, his or her experience is important that he or she knows all of the data and therefore, what's best for each particular condition. And then, of course, the patient ultimately makes the choice and each patient has different preferences. There is marital and cultural issues, which may you put into the equation. And of course, ultimately, the cost comes into it quite significantly as well. You can see that the market share, I mean, everyone tends to have a PD-5 inhibitor. And you can see that just over 50%, so half of the patients at 1 year have stopped using their medications for a variety of reasons. Either they haven't responded or perhaps they're contraindicated or they're taking medications. They can't take it or their conditions have deteriorated or just a simple dropout, in other words, it's not what they expected. Perhaps there wasn't the spontaneity and they'd rather just give up. So that means there are 50% of these patients that do -- would like to try something else. So this is really the final slide in that what is the ideal treatment for the erectile dysfunction patient? And as we've said, I mean, it has to be effective. We say rapid onset. And clearly, the faster it works, then perhaps the more spontaneous, the erectile -- the sexual event is. As with any medication, has to be safe and free of side effects and of a good price that patients can actually afford to use it. We talk about no effect on desire. I mean these aren't aphrodisiac medications, but of course, it has an indirect effect on this in that if you give medication that actually works then the patients will want to have more sex because they're actually then enjoying life. And hence, their sexual desire increases. Yes, we wanted to have a discrete. So for example, the vacuum device is hardly discrete, if that is important. If you're in a relationship, then perhaps not. But most patients find that pretty indiscrete spontaneity, spontaneity and spontaneity is what everyone talks about. Everyone wants to be when the moment arises, and so that is most important. And this is where to some extent, local therapy, topical therapy. Patients like topical therapy, I've got a problem with my penis and I just want some medication for my penis. Yes, some of the injections, but sticking needles and pellets down the urethra. So local therapy is what the patients want. So we just have to actually get local therapy to fit in to all of these ideal treatment options. It's also important, of course, that it's not affected by food or alcohol because by and large, sexual relationships revolve around that anyway. And all of this, of course, has to be acceptable to the partner. Otherwise, it's just a nonstarter. Yes, there may be cures in the future with stem cells, but we have been waiting this -- for this for quite some time. And really for the next 10, 15, 20 years, I don't think we're going to see it in erectile dysfunction. But who knows, I may be wrong. So just remember that there's 2 in this equation, it's not just the patient but also the partner. And I'd just like to thank everyone for listening to this talk. Thank you.

David, thank you very much for your interesting presentation. And for me, in particular, the new slides around millennials, I did find fascinating. So in summary, the ideal ED treatment is an effective, rapid, safe, tolerance-free product, which I think MED3000 delivers on. I appreciate people want cheap products. I think we have the flexibility here because we do have a very low-cost of goods. No effect on desire. Again, the easy application, which can form part of foreplay. And we actually did see during the FM57 that over 30% of the time the women applied the gel to the partner's penis. Discrete. Well I appreciate this isn't clearly not as discrete as an oral product. It's spontaneous, it is a local therapy, and it is unaffected by food or drinks. And as already said, an exceptional to partner. This brings to an end to our webcast. Thank you very much for listening.