Allergy Therapeutics (LSE:AGY) — Interim Results 2022

0:02 Good morning, and welcome to the Allergy Therapeutics PLC interim results investor presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and can be submitted anytime by the q and a tab situated on the right hand corner of your screen. Just simply type in your questions and press send. The company may not be in a position to answer every question it receives during the meeting itself. However, the company will review all questions submitted today and publish responses where it is appropriate to do so. Before we begin, I'd like to submit the following poll.

0:29 I'd now like to hand you over to Manuel, CEO. Good morning. Okay. Thank you. Thank you very much, Alessandro, and good morning, everybody. Thank you for joining us. And here, we have the presentation team. Joining me is Nick Wyman, chief financial officer, and Alan Bolimir, head of business innovation. I'm CEO, of the company, Manuel Lobet, of AGY Therapeutics, and we are here to present, the half year results, of the fiscal year, and the six months ending in on 12/31/2021.

1:17 This is a pivotal year because we are, running two very important clinical trials, one phase three trial for grass allergic patients and one, phase one trial for peanut allergic patients. But before getting into details, we are showing here the typical disclaimer slide for compliant purposes. And then we have here a snapshot of bullet points about our company. We are a fully integrated biopharmaceutical company based in The UK. We are a leading provider of subcutaneous, aluminum free vaccines. We provide treatments that have the potential to cure the disease, not just the symptoms.

2:09 In fact, we cure most of the cases allergic rhinitis. We are focused on severe patients. We became a company as a result of a spin off from GlaxoSmithKline in 1999 as a result of a spin off, of JSK in Worthing, West Sussex. And we started as a very small business unit. Since then, we've been growing almost double digit for more than two decades. We listed the company in 2004 in the London Stock Exchange in the AIM market to finance the development of our key products in The US market.

3:01 Today, we have a market cap of 166 roughly £166,000,000 with the ticker AIM. We are headquartered in Worthing with about 600 employees. And and our flagship product is the PQ platform that enable, a unique concept in the market, which is ultra short course treatments. The process of desensitized patients, which is how do we cure allergic rhinitis, it's, most of the time, cumbersome. It takes a long time, and we have developed, thanks to our disruptive technology platforms, these ultra short course concepts that allow us to desensitize patients in a fraction of the time than our competitors do.

3:58 And do we do apply these disruptive technologies in areas like allergic rhinitis with the Mata NPL platform or, recently most more recently in the food allergy market with the BLP platform where we are developing, a state of the art vaccine for peanut allergic patients. These are the headlines of the six months to December. £48,700,000, commercial revenue on a nominal, base. That represents a 10 percent decline, 5% decline on a constant currency basis. We had headwind on currency, and that's the the one of the few declines we've got on our twenty three years of existence, and it's mainly explained by a strategic decision we have made to streamline all the non high value products.

5:06 Therefore, we have stopped selling kind of me too products that were not high margin, highly differentiated products in order to be able to focus on the really high value, highly differentiated products. And that has had a one off impact that we are happy to take. But as you can see here, the underlying portfolio is growing 4%. That's not in line with our average because we have got experienced also some other factors like COVID and some others that we'll explain a bit later. But in spite of that, we have generated a good revenue of operating cash flow, a profit of twin 12,500,000, a net profit of 6,700,000, and a good cash balance of 41,400,000.

6:05 The the two key relevant points on the clinical part is the BLP, peanut trial that, Alan will explain in bit more detail later and the GRASS Mata NPL, the GRASS vaccine phase three trial that also will give you more details, in a couple of slides. These are the three, key pillars of our development. The the first one and probably the base of this business is the, the business in Europe that's expanding our business in Europe. We have, we are running a proper revenue business model with, as I said before, fully integrated. We have two manufacturing facilities. We have our own sales team. We have presence in 32 markets, most of them in Europe, but also in in North America and Canada and Asia and in South Korea.

7:02 We have subsidiaries in the most important European markets and distributors anywhere else. We have been growing, as I said, almost double digit for more than two decades in a market that is mature and crowded. So we've been growing at expense of others mainly, taking market share from our competitors and leveraging on on our current infrastructure. So we've been, in general, growing more on the top line than on our operational expenditure. That has put us in a position where we are profitable before r and d and therefore gives us stability and and makes us our company unique in the sense that we have a hybrid component.

7:52 We have this revenue model that gives us cash flow generation before r and d, but, also, we have the potential to to be a fast grow

8:05 company by developing our pipeline and and have this kind of biotech upside by developing the pipeline. And this is what we do with equity issues from time to time to develop the pipeline where we have latest stage assets like in grass in its grass pollen version or rugby version or three slides ragweed version. Or recently, as I said before, we made the first inroad in the food allergy market with this state of the art peanut vaccine. So the the pipeline development is probably the most valuable part of the business.

8:52 The the the project that takes more attention from investors typically is the is the peanut vaccine, and we understand this because it's a totally a a breakthrough product. Alan will talk a little bit more about this. And the third pillar of our strategy is the preparation for The US entry. This is a project that we've been working in for the last fifteen years probably, developing three clinical development projects, the PQ franchise, pollinates quattro grass, pollinates quattro rugweed, and pollinates quattro trees. We reached phase three with two of them, grass and rugweed, and phase two with trees. We have completed 16 clinical trials, invested more than $100,000,000 on these programs.

9:50 And with the with the most advanced ones, which is GRASS, we are going to perform the last study before submission that this g three zero six study will be the base for our submission in The US and in Europe. In Europe, we'll submit right after the trial. In The US, we'll have to complete the safety database before, submission of our, biological license application. So I will now hand over to Alan to give us a bit more flavor of our, technology. So hand over to you, Alan. Thank you, Manuel. As Manuel said in in in in his section, you know, the the immunotherapy area that we focus on is is is in those patients with moderate to severe allergic rhinitis.

10:49 We have a number of products that are marketed and registered primarily in Europe. You can see those at the top of this slide for grasses, trees, and venoms, and ragweed, which is registered in Canada. But the key parts of the portfolio are those two products, highlighted in red on this slide. So the the first is the GrassMarter NPL, where we are currently running the the phase three studies. We have, recently completed an exploratory phase three, and we're now moving forward in into the pivotal phase three later this year. I'll touch on that a little bit later. And the second, product in the pipeline that is is most exciting is the peanut, subcutaneous immunotherapy product, the VLP peanut.

11:40 This product has recently completed an ex vivo study in collaboration with Imperial College London and is about to enter first in human trials later this year. So we are we are very excited by that. So I'll kick off with the peanut program. Peanut is is is an incredibly severe allergy. The the the onset of symptoms is is almost immediate and it requires a very delicate approach in order to in order to successfully switch the immune system to become intolerant without running the risk of causing an allergic reaction, by using the product itself.

12:33 We have to remember, allergen immunotherapies is using the very thing the patient is allergic to in order to drive that immune response, and peanut is incredibly severe. So what we have done, for those on the call who may be less familiar with us, is we have taken, the peanut allergens and we have bound them to the surface of a virus like particle. Now this virus like particle is is based on the cucumber mosaic virus, so it's completely harmless. It it can never infect a human. And what it does is it acts a little bit like a Trojan horse. So when the, VLP peanut is injected into the patient, the immune system does not see, an allergen.

13:19 So it doesn't trigger the allergic responses that are associated with peanut exposure. The body instead recognizes a virus and it activates parts of the immune system that are specialized to deal with viral infections. Now what this means is the, the the virus complete with the, you know, the peanut allergens that are bound to the surface are taken up by the immune system. They're spread through the lymph lymph nodes, and the virus is broken down and the peanut allergens are are released, past the initial defenses that would ordinarily cause an allergic reaction. This means we're able to train the immune system to become tolerant without kicking off those, you know, those first line of defenses. We're we're in effect fooling the immune system to to to to to give a change in in the immune response without initiating an allergic reaction.

14:20 Now we've got some great data that we have, received from the ex vivo study in collaboration with Imperial College. We did this with blood samples from peanut allergic patients. Obviously, we need to demonstrate that the product is safe before we go in into humans. And what we saw is a 24 fold reduction in basophil activation and therefore subsequent histamine release after we had exposed these blood samples to VLP peanut compared to if you had exposed the blood samples to natural peanut extract. This is a a a huge reduction. It demonstrates that the vaccine itself is hypoallergenic, and yet, analysis of biomarkers further down the, further down the line indicate that the drug itself, whilst not causing an allergic reaction, does trigger the immune cells that we would associate with, inducing tolerance in in a patient. So this is this is great news. This is exactly what we want. We're activating the parts of the immune system we want to activate,

15:23 and we are not activating the parts of the immune system that we don't want to activate. Then moving forward into, into this year, the the phase one study, the first in human study, have called the PROTECT study. And we had the great news earlier this year in January, that the FDA in The US had cleared our IND. We are now able to to progress, we will we will be doing that later this year. The study design itself is is based upon, a number of different cohorts. So we will start with the injection in, healthy volunteers before we move into skin prick testing in peanut allergic patients, and then we will go into subcutaneous injections into peanut allergic patients. So as you can appreciate, because of the, again, the severity of a peanut condition, you you you you increase your intervention, in a stepwise fashion as you go through evaluating, the the safety of the product. We will have some biomarker data, some idea of efficacy, but, obviously, it's a phase one study. It is not a powered study, to look at efficacy.

16:36 But we will be, in a position to, to announce some of the data in a in a stepwise fashion as we receive it. And we're expect expecting top line around half one twenty three, looking at our our current timelines. The batch itself, the the the the the manufacturing process for for making making the product has been successfully made. It has been QC tested and released. So we have managed to go from from from bench in the labs up to large scale manufacturing. I think we're up I think it's around a 400 liter batch size. So it's quite a it's quite a huge increase, and and everything is ready to everything is ready for the trial. So we are incredibly excited by the opportunity to to enter, you know, the the food allergy market, which the total market is is estimated to be around 8,000,000,000 a year.

17:35 The second key product and the, you know, the next thing that that makes this year and next year a pivotal year for our company is is the grass product. The PQ grass, we ran the exploratory field study, the g three zero nine study last year, and we met the primary endpoint. And just to note, the primary endpoint is a combined symptom and medication score. So that is a measure of how the patient feels. So nasal, ocular, etcetera, different different symptoms, and how much medication they had taken. Did they need to take any, antihistamines? Were there any corticosteroids, for example? And the combination of, symptoms and medication act as the primary endpoint, and what we demonstrated was a statistically significant difference between active and placebo.

18:29 In the extended as you can see on the table, we had a nearly forty percent reduction in combined symptom medication score. That is a huge result. I am not aware of any field trial in the allergy immunotherapy world that has approached a 40% reduction, in in in symptoms. So we're incredibly excited to kick off the the the the clinical study, the g three zero six, which will start later this year. We also have some additional data from the g three zero six trial, that's probably worth mentioning. The first is, that we ran quality of life questionnaires and we saw, improvements in patient quality of life, in the active compared to placebo.

19:22 The graph that you can see in the middle of this slide indicates that the benefits that were seen were comparable regardless of geographies. So whether the patients were based in The US or whether they were based in Germany, because remember, this was a trial that was run over over over different sites, different countries, The effects were the same. So there's no geographical there's no geographical factors that will that are appear to be influencing the drug performance. We've got a huge work, a huge body of work looking at biomarkers and analyzing those, and I've picked out a couple here. So specific IgE and specific IgG were consistent with what you would expect to see if a patient had been treated with allergen immunotherapy. So therefore, you know, a reduction in IgE IgE is the antibody that causes the symptoms of allergy, and IgG is we saw an increase, and that's the antibody associated with a a protective efficacy.

20:23 And as you can imagine, for a product that's been on the market in Europe for a number of years, the both dosing regimens were were shown to be safe and well tolerated. Looking forward to later this year and then the results the year after, we're now moving into the pivotal phase three study. This is the g three zero six study. We've taken the learnings that we've received from the exploratory study, we've put them into the g three zero six, and that is planned to commence later this year. For field studies of aeroallergens, we have to run the studies according to the pollen season. So, typically, we would dose the patients, say, October, November, December, January, ready for the pollen season in March, April, May, for example, something like that.

21:12 So so we're always we're always bound by by a calendar for for when we can start. So we expect this study to start in q three. We've increased the sample size to give us further confidence in in the data that that that we've got. And once the study is completed and should the data be what we what we expect it to be, we will then just need to complete the safety database for the US FDA before we can launch the product there. And then in Europe, this should satisfy the needs of the TOB process, and we could launch the product through Europe. The US market itself is around $2,000,000,000, and about a quarter of that is GRASS. So peak sales could potentially be circa 3 to $400,000,000.

22:00 And I think another thing that's worth pointing out, especially looking at that 40% improvement in efficacy, improvement in in combined symptom medication score, is that it it it it really meets the unmet needs, you know, specifically in The US currently where patients, you know, are faced with, know, up to a 100 injections, you know, no no one's going to no one's gonna want to to take that much time off school or or work. You know, sixteen percent of patients finish the treatment as it currently stands in in The US. Fifty percent of patients don't even start the the the the therapy once they hear how much they have to do. So by by by being able to, you know, have this level of efficacy in just six injections is is outstanding, and and it really, really could be could be a a game changer.

22:54 So with that, I will hand over to Nick, and thank you very much. Thank you, Alan. Moving on to the second pillar. Alan's talked about the the pipeline, which is one of the as as Manuel discussed, one of those drivers for potential biotech change to the to the to the business. The second pillar that has the potential to do that is The US market. Alan's already talked about the size of the market for grass, the 2,000,000,000 as overall allergic rhinitis size of market with the potential for 300 to $400,000,000 peak sales for grass.

23:41 I should point out that grass is just the first of of three products within our portfolio, which could be brought forward into that market. The second one would be ragweed, where we've already done phase one, two, and three trials, and we sell a product in in Canada

24:00 using the platform. And the third one is a virtual tree product, which potentially would have about half the peak sales of the grass, but would also add to a nice portfolio of products together. As Alan has said, the The US market has a huge potential. Currently, most patients who go to a to to an allergist, they they receive up to a 100 injections. And the reason for that is that the allergists start with a a concentrate and dilute it down and start treating the patients at almost a homeopathic level and gradually move up to a maintenance dose, which takes a long time. It's not a a GMP manufactured product.

24:49 And, also, it has the problem that if you actually move states or move doctors, you have to start all over again. So it's very, very cumbersome process. And as Alan's pointed out, it's it's demands a lot of time off both from school or from

25:07 work, and and that's the reason for the only sixteen percent of people who actually complete it and the fifty percent of the patients who actually turn up at the surgery never even starting the treatment. So there's there is a huge potential for this this product and the whole portfolio within The US market. I should also mention that The US market tends to have pricing levels, which are a fact about two to European price as well, which makes it a very advantageous market to be in. Moving on to the I'm sorry. Bigger pond. And as already mentioned, the other products in the portfolio, the ragweed, birch trees, which we would have, and as well as that, potentially, in the in the midterm future, we also have the VLP peanut, which we would see going through the same channel. In other words, being treated by the allergists in their clinic.

26:14 Moving on to the third pillar of the strategy, which is the European trading business. As Manuel mentioned, that business is a is a is a successful business, which has grown quite significantly over the last twenty three years. This year, we've done some streamlining of of the the portfolio to remove some of the me too and not so technically advanced products from the from the portfolio in order to focus in on the the skip products. That's the subcutaneous products that that we think bring the most benefit to patients.

26:59 And you'll see on the right hand side, what what I've done there is to take the the net sales and take a like for like on the current portfolio as it looks. And you'll see we have seen good growth over over the last few years for for that portfolio. Revenues were affected in the in the year partly by phasing. We had an impact of COVID within the the manufacturing facility, and also COVID affected our markets both in Italy and Germany.

27:39 Italy's been been affected throughout the whole COVID period as most doctors actually sit within clinics sorry, sit within hospitals, and therefore, they they'd be pulled off to either look after COVID patients or to or to create vaccines. In Germany, the the clinic sits separate to the hospital, so there's been less disruption. But in this last year, particularly in December, a lot of the in fact, all of the allergists were pulled off of allergy in treatment to go and give booster vaccines in Germany, and that's obviously affected the sales. Overall, though, there is there are areas of the business that that are still growing very strongly.

28:27 We have strong growth in Spain, Netherlands, UK, and parts of the rest of the world. And also in the product portfolio with Pollenex, Venomil, which is the treatment for bee and wasp sting, and a Caravac, which is a house dust mite product we sell in Spain.

28:51 Moving on to the financials. Looking at the revenue, as Manuel has already mentioned, we had revenue of 48,700,000. That was down 10% in actual terms and 5% in constant terms. I should remember, listeners, that actually we sell about 95% of our product within the EU. So we are quite exposed on the on the revenue side to to the euro.

29:21 The gross margin dropped from 78 to 74%. That was driven by the by the lower sales, the impact of COVID on the manufacturing facility where the volume production slowed down in December. So we're producing less less batches and, obviously, creating less stock. So therefore, more of the cost flowed through the p and l and FX. There's been good control on the the overheads, and that left us with an operating profit pre R and D of 12,500,000. That's our measure of how well the trading business is going. As Manuel pointed out, we consider the research and development as part of the investment in the future. That's what's driving the pipeline, whereas this trading business is is something separate.

30:14 So overall, a a good good half year considering the situation, solid solid performance and a profit after tax of €6,700,000

30:29 Moving on to the balance sheet. I think the main areas to talk about here are within the working capital. The inventories were up slightly despite that slowdown in the in the factory, and that was really really caused by the fact that with Brexit, we have a longer supply chain as we ship product through Spain for its second testing and release, then on into Germany and Austria and so on. We finished the half year with a cash balance of 41,400,000. We've publicly stated that's enough to pay for the GRASS phase three trial, which Alan was talking about, the g three zero six, and the phase one peanut trial with a certain amount of debt.

31:18 And speaking of debt, we finished the period with debt of 2,900,000. That's actually the the debt that we have sitting within the Spanish subsidiary as we acquired a business some years ago that that included a certain amount of long term debt. Just after the year end, we also announced that we've we've replaced the 7,000,000 overdraft with a £10,000,000 revolving credit facility to give us more security over our funding. And finally, I'd move on to the summary and outlook. So as Manuel said at the beginning and Alan talked about, this year is a really pivotal year for us with two very exciting trials starting this year and reading out in the next calendar year.

32:14 First is that Phase one PROTECT VLP peanut trial, first in human trial for this highly innovative new peanut product. And the second one is that Phase three pivotal GRASP trial, which is taking place in The U. S. And Europe, which is our key last trial subject to the completing the safety database before we can file that product in The U. S.

32:43 We expect a continued solid commercial performance in Europe and to continue focusing on our SCIT, an innovative approach to patient treatment. And finally, just a quick summary of what the time lines look like. And as we've already talked about with those PEANUT and GRAASS trials starting in 2022, We're expecting the PEANUT Phase one trial to read out in the midyear of twenty twenty three and the GRASS Phase three trial to read out in the autumn of next year. So some very interesting inflection points. Although I should point out that the phase one peanut, as Alan has talked about, will be done in cohorts, and we will be reporting as we move from one cohort to the next. So we should get some news during the period before we get to the final results.

33:46 And with that, I hand over to Alan, who will talk about sorry, who will do the Q and A. Manuel, Nick, Alan, just could I just come in and say thank you very much for your presentation. Ladies and gentlemen, please do continue to submit your questions using the Q and A tab situated in the top right hand corner of your screen. But just while the company take a few moments to review those questions submitted today, I would like to remind you that recording of this presentation along with a copy of the slides and the published q and a can be accessed via your investor dashboard. As you can see, we've received a number of questions throughout today's presentation, And thank you to all the investors for submit for submitting those. Alan, could I please ask you to read out the questions and delegate the responses appropriately, and I'll pick up from you at the end.

34:32 Perfect. Thanks, Alexandra. So the first question is, I noted that the 39.5% reduction in the GRASS MARTA NPL three zero nine trial, whilst it was statistically significant, it does not seem particularly high. Was the effect as strong as we had hoped for? It it is an incredibly high figure. I I know 40% might not sound like a huge improvement. And if if if if if if you're thinking you know, if you're comparing it to to a 100%. But as I mentioned, you know, there there's there's no trial that I'm aware of that's even come close to forty percent. This is, by far and away, it exceeds what we had what we had hoped for.

35:22 And it links a little bit to this another question that's that's that's come in that says, assuming you get a similar level of effect in the in the pivotal phase three, how likely is it that the regulatory body will approve it for use? To give some kind of gauge onto what that 40% means, products have been approved on 20% currently. And, you know, so to see a 40% increase is is a huge improvement on on current treatment paradigms. So I hope I hope that that answers answers that question. The next question, for the VLPs, how do you plan to execute trials, market entry, and funding?

36:16 Nick, do you want to cover that one? Well, I've already talked about the the VLP peanut, phase one trial. Naturally, Naturally, if if we if that's successful, we will look to get further funding to carry forward those trials to the phase two and the phase three trials. Thinking about the rest of the portfolio, we haven't really talked today about the very early part of the pipeline. We do also have some other VLP candidates, which are actually outside of the allergy area but use the immunotherapy technology. And and, again, we would look to get further equity funding to to bring those those products through.

37:05 At the moment, they're simply being assessed to ensure we have a have a good route good route forward for them. But, obviously, having brought the the VLP peanut all the way through, as Alan explained, we've done all the scale up and so on. We've learned a lot about this technology, which we can apply to other products. Perfect. Thank you, Nick. The next question, I think, is for me. Could you please update us on the current situation regarding competitors' peanut allergy products. So there's obviously Palforzia, which is registered, which which which is launched, the peanut powder.

37:53 They are they are they are in the market. They're first to market. There are some other companies that are attempting to enter the space. So there's DBV with their patch offering. So this is a this is a a a dermal patch, much like a like a nicotine patch, that that delivers a a controlled dose of, again, native peanut allergen through the skin. I I am aware that they had some issues with the FDA. They had some concerns regarding CMC so so sorry, chemistry manufacturing control components.

38:38 They had some issues with, I think, patch adherence, and I think they're reworking that. I don't know exactly where they are with with that product, but I know that they are continuing. But broadly speaking, it's a very similar strategy to to the DVB, to the to the AMEEN product in in terms of, you know, a set dose of of peanut delivered to the patient. And then there are some other products that are looking at using, you know, monoclonal antibodies. These function very well, but they're incredibly expensive. And they are transient in their nature. So if you stop delivering the monoclonal antibody, the effect wears off. So the the benefits, you know, the upside to the VLP peanut product product that that that we're developing is that you should be able to have a limited number of injections.

39:33 You don't need to take it every day like you like like the tablet, like the powders or the or the patches. And you you you should you should permanently change the immune response. It it shouldn't be it shouldn't be a transient effect. The next question is for the grass allergy product, what do you anticipate the primary endpoint will be for the pivotal phase three? The primary endpoint will be the the the same. It will be combined symptom medication score. That is the endpoint that is recognized by the regulators, by the allergy societies, and it is the most clinically meaningful relevant measure for improvement in well-being and medication use for allergy trials.

40:30 Given that many of the products you currently sell in Europe are sold under a named patient process, how long will you be able to continue to market these products without submitting new regulatory dossiers? Manuel, do you want to take that one? Yeah. This is depending on the country. Country by country, they have different regulations. The first country that started this process was Germany. That this was called TAV regulation. That means that therapy allergy ordinance started around 2010, and now we are facing the last part of this of this program. We have under this framework, our products that are the upgraded version of the POLINEX products that we have registered in Germany.

41:37 And the POLINEX Quadro are the the the same product but with the NPL adjuvant. And so is is going to be submitted in Germany probably in 2024 after the g three zero six and we'll follow-up on the next quarter three. And so we we are running our our products under the TAV timelines and framework. We we don't know what the other competitors are doing, but but we are within the timelines, and and we have our plan properly structured to be within the timelines.

42:25 It it is an endeavor that we support by regulatory authorities where, most of the named patient products will have to be regulated. There will be few products that will not be under this framework because are considered rare allergens and are allergens that only suffer a limited number of patients, and therefore would not be justified big investments in big clinical trials to get them registered, and therefore, a small percentage of products will remain as NPPs. But most of them in a matter of a few years, let's say, five in five years, will will probably be all the German market regulated and and and other European countries have started the the the process too.

43:21 So probably by 2030, all the EU markets will will have completed the regulatory process. Thank you, Manuel. Our next question is if the peanut vaccine trials are hugely successful and the product launch goes according to plan, do you anticipate to upgrade the current portfolio? I would say that the the the the products that are related to aeroallergens in terms of pollens will stay on the PQ platform. It's a tried, tested, and and and trusted platform.

44:07 And and as you saw from the the g three zero nine with with the 40%, it's it's a platform that that works. However, food allergies, allergies where there is an incredibly strong allergic reaction and maybe some of the more unusual allergens such you know, things like cat dust mite, certainly certainly a a potential to use the VLP technology there. We have the rights. We own the license to use VLP technology in all areas of allergy. And as Nick mentioned, we also are looking at some this is a very, very early phase. We're looking at proof of concept, but looking at using the VLP technologies in areas outside of ALLERGY.

44:53 So we're certainly looking to maximize and leverage the the benefit from the the VLP portfolio. The next question is the placebo effect in allergy trials can be a real problem. So well done on your 40% effect on the GRAAS trial. Can I take this one, Alan? Yeah. Sure. What are your top recommendations for trial designs for minimizing the placebo effect? So thank you, Tim. In in fact, we are really proud because that's the big, big problem on these trials. And there was a previous question where 40% didn't seem that that relevant, and it's extremely relevant. I just want to remind here the audience that there was a very high profile failure of a of an allergy trial a few years ago where there was reached a 60% placebo effect.

45:53 If you add 60% to this 40% that we've got, you get one hundred percent efficacy on severe patients that do not get control, do not cannot control symptoms with antihistamines or corticosteroids. So these are patients that cannot go anywhere else. And we offer them levels of protection of you know, if you had this placebo effect, maybe sixty was extraordinary, but we could add forty, fifty percent. So with this forty percent, we are talking about levels of protection of eighty, ninety percent on patients that cannot control symptoms with symptomatic products. So that's extraordinary, the this result.

46:43 And I think that's the really in injectable vaccines, that's that's the real problem in doing these trials to go through this placebo effect because we have to go through very sub subjective questionnaires to get through the total symptom and medication scores where the placebo effect is is is really big. We have invested a lot in this g three zero nine trial to in biomarkers because what we would love is to get biomarkers where we could take blood samples and only measure some different antibodies, and then you just get, you know, an objective measure. But that's not have been that has not been established yet by authorities, and we still have to rely on, CMCS as as Alan said as the gold standard for these clinical trials.

47:45 It looks like in this g three zero nine study, after many, many trials, after tens of millions of investment, we have found the secret sauce of how to deal with it. And, of course, we are not going to explain how to do it. So we believe that we could be probably the only skid company able to go through this hurdle successfully. So maybe once we we have all our portfolio registered, we will publish how to go through this placebo effect hurdle. Thanks, Manuel. And then our last question is, could you explain in a little more detail what 40% improvement actually means?

48:34 You know, is it a 40% reduction in the use of drugs? Which part of the CSMS contributed most? The combined symptom medication score is a number of different questions that the patient answers every day, how they felt various it's it's it's on a on a on a on a zero to three or one to four scale, And and it's a a set of questions asking about how how they how they feel in their nose, in their eyes, general well-being, any medications that were taken. If you take, for example, one one antihistamine tablet, you give us a score of one. If you take an antihistamine tablet and a, you know, a corticosteroid, it it doubles, etcetera. So it's a compound compounded measure that that that combines all of the different facets of the things that affect a a patient.

49:40 The 40% improvement and linking as well to what Manuel said in in that the placebo effect itself in these trials is is is huge. You know, it's it's well known as well in in asthma trials or in in any trial where you have a patient reported outcome. That's the the the placebo effect is huge. If if if you've had an argument with your other half that morning, it doesn't matter how clear your nose is, you're you're still gonna report that you feel pretty miserable. And this is this is the downside. This is why and as Manuel was talking about why it's important to look for biomarkers, which is a a big tenet of what we're doing. So having a 40% improvement, remember that is on top of the placebo effect that's already built in. So the patients, it's very hard to quantify.

50:30 So in in terms of your question, you know, what what does a 40% reduction actually mean? It's very hard to quantify that in term because everyone feels slightly different. But because the CSMS is the accepted, primary outcome, a 40% improvement is a significant improvement on how that patient feels. It it it makes them feel, like they can live life more fully. You know, perhaps they can go out and and play with their friends, in the height of summer, and they can go take their kids out to the park, you know, where ordinarily that they would have been unable to. And the last part of the question is is which part of the CSMS contributed most. We haven't published that data yet. So that's going to be coming in the peer reviewed publication when the full dataset comes out. So as soon as that is as soon as that's published, notifications will go up on our website, we'll we'll let everyone know that that data is available.

51:26 So that was the last of the questions. So I will I will hand back to Alessandro. Alan, thank you very much for that. I think you actually managed to address all those questions from investors. And, course, if any more come through, we'll give those questions to the company, and we'll publish those responses on the investor meet company platform. Just before redirecting investors provide you with their feedback, which I know is particularly important, Manuel, could I please ask you for a few closing comments? Yes. I would like to thank the audience and thank for these interesting and clever questions. And just to to to remind the audience, this is a company with a a very interesting nature, which is this hybrid component.

52:12 We we are, in a way, a traditional company with a revenue well established revenue base generating good cash flows pre r and d, but which gives us stability and and and safety, but also with a a very exciting upside potential as we develop our pipeline that could be the kind of biotech growth value upside type of company. Next twelve months will be very exciting. We have two catalyst points, the readout of the GRAS vaccine at the end of twenty twenty three and the the end of the phase one trial for the period vaccine at mid twenty twenty three, where we will then start as soon as possible the phase two.

53:13 So thank you very much for for your time, and we are available for for our investors anytime you need. Thank you. Manuel, Nick, Alan, thank you very much for updating investors today. Could I please ask investors not to close the session as you'll now be automatically redirected to provide your feedback in order that the management team can better understand your views and expectations? This will only take a few moments to complete, and I'm sure will be greatly valued by the company. On behalf of the management team of ALLERGY THERAPEUTICS PLC, we'd like to thank you for attending today's presentation, and good morning to you all.