Good afternoon, ladies and gentlemen. I'm sitting here with Chief Financial Officer, Jeroen Wakkerman to take you through the half year results 2021.

But before I do that, next slide, please, I would like to draw your attention to the slide that you will see in front of you now, showing -- the slide on forward-looking statements, because we will be making some forward-looking statements that are based upon our current plans or believes, and that may change from time-to-time, as it's impossible to predict any new risks and uncertainties that may emerge from time-to-time.

So having said that, let's go and have a look at the next slide please. And whilst that slide is coming up, I'll start introducing the company. So we are a revenue generating and profitable dual listed biopharmaceutical company and we're really investing at this point in time in building up our company towards the long-term.

That means we are investing in the in development of recombinant human proteins from our own platform.

And of course, our lead product is in this case, recombinant human C1 esterase inhibitor, RUCONEST, which is approved for the treatment of acute angioedema attacks in patients with hereditary angioedema, and where we have additional indications and clinical developments, but we're also investing in extensions of in-licensed development pipeline, we in-licensed late-stage compound leniolisib for the treatment of APDS from Novartis about a good year and a half ago, that is late-stage.

And we recently in-license an early stage, ex-vivo hematopoietic stem cell therapy from Orchard Therapeutics for the potential treatment of hereditary angioedema. And we are -- and we can do this from our own means.

That means we are profitable from revenues from our own commercial infrastructure and selling RUCONEST in the US and in the European Union. And we have some partnerships in other territories of the world. And that means we can fund all these investments from our own from our own cash flows. Next slide, please.

And I would like to take you on this slide through the operational highlights; we had a very busy first half of 2021. And there, we got reimbursement in Spain for RUCONEST. So we will soon be able to bring RUCONEST to the -- into the Spanish market as a result of that.

We also announced a successful completion of patient enrollment in the pivotal trial for leniolisib for APDS. And that means that we still aiming for an anticipated launch of leniolisib at the end of 2022 next year subjects, of course, to regulatory approval.

And because the launch is coming near, we also started working and investing in pre-marketing activities and we launched the navigate APDS program sponsored genetic testing program in collaboration with Invitae Corporation that is designed to assist clinicians in identifying those patients and their family members with APDS.

Then, we were very pleased that we could finally start the Phase IIb double blind randomized control study for leniolisib in the prevention of acute kidney injury after myocardial infarction at the University of Basel in Switzerland and other centers.

And where we got a few new colleagues, we got three confirmed new Board members in our annual meeting of shareholders in May, Staten Bart, Leon Kramer, and you'll be amazed with our Board.

And last not least, we got two new colleagues in the Executive Committee of the company; Anurag Relan as Chief Medical Officer, and Robert Friesen, as Chief Scientific Officer as new members of our Executive Committee.

So post-operational highlights too, we entered into an exclusive new license agreement with NewBridge Pharmaceuticals for distribution of RUCONEST in the Middle East, North Africa.

We announced a strategic collaboration with Orchard Therapeutics to develop manufacturer of commercialized OTL-105, which is a new investigational ex vivo autologous hematopoietic stem cell therapy for the treatment of hereditary angioedema, and OTL is designed to increase the C1 esterase inhibitor concentration in HAE patients serum to prevent HAE attacks similar mode of action as RUCONEST therefore.

So, very busy times, and lots of new developments in the company. And that brings me to the next slide, please. Because the last collaboration that we've just discussed on Orchid Therapeutics is exactly what we are working on with regards to our three pillar strategy for growth.

On the left hand side, you see the growth enabling sales of RUCONEST by bringing the revenues that enable us to invest in all these other opportunities. And of course, the long-term view that we have here by in-licensing the early-stage asset OTL-105 hereditary angioedema as a very good example.

Although we are executing against this three pillar strategy for growth. In the middle, you see the developing continuous clinical development for g rhC1-Inhibitor for additional large unmet medical indications, and the transgenic manufacturing technology where we are developing next-generation protein replacement therapies.

And there we have, of course, the early stage compound alpha-glucosidase for Pompe's disease development. And then we move on to the right hand side, where we continue to execute on the in-licensing, and searching for new candidates for late-stage candidates. And of course, leniolisib, it is very good example of where we got the first product in.

And, as I said before, we're aiming for a launch – late next year for leniolisib into the market. And we're very active at the in-licensing acquisition of additional late-stage assets in rare or ultra- rare diseases.

Our business development group has continued discussions with several candidates in various stages of development of – of such discussions. Next slide, please.

And that brings us down to the current pipeline of the company, as you can see here RUCONEST of course, is the process in the market, followed by leniolisib that we expect to be able to launch by the end of next year.

And then of course, followed by the further development of rhC1-Inhibitor, alpha-glucosidase, of course at the bottom, the HAE gene therapy that we in-licensed recently from Orchard. Now let's take a look at the hereditary angioedema market that is driving all the revenues for the company at this point in time. Next slide, please.

And here, of course, if you see this picture, we're looking at a disease that is caused by a deficiency of C1 inhibitor, and that results in attacks of severe swelling, unpredictable effects angioedema in various parts of the bodies.

So we're providing the only recombinant version of the C1 esterase inhibitor protein that is serving as protein replacement therapy. And RUCONEST is use for the treatment of acute attacks but there's also compounds in the market that prevent the attacks. Now to prevent this –therapies have - all have breakthrough attacks to a different degrees.

So it means that all the patients that are suffering from hereditary angioedema will have access to multiple medications, if they are on prophylactic therapies, they will have to have rescue therapy at hand for their unpredictable breakthrough attacks that come through in varying frequencies.

So therefore, RUCONEST plays a role, not only on the right hand side of the segment, where we serve severe patients that have frequent attacks, with high dose -- with RUCONEST as a high dose protein replacement therapy.

But also we serve the left-hand side of the market, the breakthrough attacks segment because despite the fact that there is a lot of innovation has taken place and breakthrough attack frequency has significantly reduced to patients, which is very good news, there's still a significant need and an increasing need for the user RUCONEST in the segment of breakthrough attacks.

And that is exactly what we see happening. Our traditional segment was serving the right-hand side of the market for all, sorts of, historical reasons. And the left-hand side, sthe breakthrough attacks is a segment where we see increasingly patients coming into our patient group that are using RUCONEST.

Of course, they use RUCONEST lot less frequently, because they have already had uses for breakthrough attacks, but there is definitely a good position for RUCONEST to be achieved in this breakthrough attack segments going forward.

So we're very confident that the positive trend that we have seen starting with RUCONEST that is actually the result of increasing numbers of patients and increasing demand to be continued in the coming in the coming year.

Of course, subject to further breakouts of corona where basically the medical practices book grow again because that is really been the hindering of the sales in the beginning of the year. So next slide please. And then I move on to Leniolisib briefly for the treatment of APDS.

APDS is a rare -- ultra rare primary immune deficiency that is caused by a dominant variation in one of the two genes for -- that actually results in hyper activation of phosphoinositide-3-kinase, this is enzyme. And that results in not good -- not functioning immune system in these patients.

It means that these patients have a non-functioning B-cell compartment and cannot defend themselves against infections. Therefore, the only way to treat this is symptomatic for this so far, and therefore, this is a disease that actually needs a treatment that takes root cause. That's exactly what leniolisib does.

Leniolisib brings back the PID-kinase delta to normal expression, and therefore, actually can make a real impact on this disease. And the good news is, this diagnosis can be made by commercially available genetic tests.

And all these patients are already treated by immunologist because they form this part of the population -- patient population that's called primary immunodeficiency that is treated symptomatically by these immunologists, and are actually waiting for that disease to be formally discovered and confirmed.

And then there could be a treatment of Leniolisib in the future for them. Let's look at the disease a little bit more in detail, please next slide. And you see that the burden of APDS is very significant. And there's about 1,350 patients estimated to be available in the world. We haven't discovered them all yet, at all.

And there is -- and as you can see on this slide they spend years sometimes to be undiagnosed or misdiagnosed.

And they spend a life of seeing specialists in their childhood and develop from, you know, from the left-hand side from severe infection to permanent lung damage, and GI disease, swollen organs, autoimmunity, and a very high frequency of fatal lymphomas.

So it's a very nasty disease, where there is only symptomatic treatments available or treatments with very severe side effects that still treat -- only treat the symptoms. So the possibility for the Leniolisib to bring actually a way to treat this disease at the root cause is a very unique one, I would say. Next slide, please.

And because the Leniolisib launch is coming near, we started investing significantly in uncovering APDS, so we're looking at target and targeted patient identification strategy that is actually kicked off in the US and will be rolled out across Europe as well.

And you can see here, we build an APDS network, KOL network and referral pathway of prescribers, that are been actively supported by field medical and diagnostic liaisons from our company that were -- that we started to work recently on this.

We use analytics and artificial intelligence to look at the databases and the patient group that is immunology pass and there we have an outreach and education.

And we offer free of charge genetic testing to confirm the disease and then in the future offer -- be able to offer these patients treatment for Leniolisib, that is an important step for a company to start the pre-marketing activities for Leniolisib because Leniolisib is a good year – is only a year and a half away potentially from the mark.

That brings me to the next slide. And there of course as I stated before, we were quite busy as well because we were able to finally start the acute kidney injury study for Ruconest C1 assay inhibitor, we're going to study up to 220 patients.

The lead is in university hospital Basel, Switzerland, except several other centers evolve there and it is actually quite a severe complication of patients undergoing these contrasts. This contrast, procedures following their myocardial infarction where they get stents implanted.

Unfortunately, the clinical trial for preeclampsia is still halted due to COVID-19, there are complications, but we hope that this study may in the future start again. And then of course, last but not least, we're still working, of course on the clinical trials for patients hospitalized with COVID-19.

Two studies, there's a multinational study, that investigator left in Switzerland, Brazil and Mexico. And there's our own study that we started in the US in New Jersey. And in both of these we -- in one study, we look up to 150 and other up to 120 patients those are adaptive designs.

So we are free to do interim analysis and these things and we expect that towards the end of this quarter we actually can come with some updates on results or signals that we see from these studies and with some further thoughts or ideas how we could actually follow on these studies. And that brings me down to the last slide of my presentation.

Next slide, please. That is, of course, very excited, and technically speaking, this was one day after the period we're talking about today.

The deal was closed on the 1st of July, because we're very pleased that we got a collaboration with Orchard Therapeutics to develop this ex vivo autologous hematopoietic stem cell therapy for hereditary angioedema. And, you know, OTL has already shown gene expression via the lentiviral mediated transduction ex vivo in multiple cell lines.

And of course, also already achieved to production of functional C1-inhibitor as measured by a clinically validated asset. So this is a real program, work is in progress, preclinical -- further pre-clinical work is ongoing with orchard at Pharming.

But we think that this is collaboration with their expertise and their validated gene cell therapy, gene therapy platform, which is already, uses as an approved product, and our expertise in hereditary angioedema are a very good combination to bring a potential cure to the market for the hereditary angioedema patients.

So without further ado, I would like to now, hand over to Jeroen, our CFO to take you through the financial highlights, for the first half of this year. Next slide, please..

the first one is a reduction in operating profit, as I said, mainly because of an increase in operating expenses; Second part is less cash inflow or more cash outflow from working capital than we had last year; and there is a plus of €3 million in other operating cash flow elements.

Going down on the cash flow statement, we see again the vouch payment €25 million under the payment on contingent consideration. So overall, we increased the cash by €60 million. Obviously, the last year we increase the cash by €95 million, but that was because of the issue of the convertible bonds, less than from operational cash flow.

With that, I would like to hand over again to Sijmen..

Thank you very much, Jeroen. And please next slide. So, if I look at the investment summary here. We're well funded business. We’re supported by commercial sales and a growing pipeline for the treatment of rare diseases and other medical needs.

We’re funded really, as you heard from Jeroen, by the sales of RUCONEST and we brought an another $93 million a Dodge of sales in the first half this year. We have a potential near term inflection point with the 2022 launch of Leniolisib for APDS for treating retargeting new large indications for RUCONEST, recombinant human esterase Phase 2 studies.

We also strengthened our early stage pipeline, with the in-licence, potentially curative gene therapy treatment HSC and we have our own transgenic platform candidate for pompous disease in the pipeline.

And we're able to leverage commercial infrastructure for in licence for an expanding manufacturing capacity to support the continued RUCONEST demand and C1 inhibitor inhibitor pipeline.

And after release, we have an experienced leadership team and board and a very strong balance sheet, both in terms of cash generative potential, and of course, the cash that we have on hand to support our ambitious growth strategy, including potential M&A.

And of course, we have this secondary listing on the NASDAQ to be able to finance such transactions in the future, and we are very keen on this and we're very focused on getting transaction -- getting another transaction with the late stage asset in. So next slide, please. Last slide, I will share with you the outlook for the remainder of 2021.

So for the remainder, we expect a continued increase in revenues from the sales of RUCONEST, because the pharmaceutical market looks to be normalized -- continue to normalize further and return hopefully to its pre-COVID-19 state. Although, we will continue to monitor the situation and continue to expect some periodic market disruptions.

We, however, are maintaining positive earnings during the year.

And as Jeroen was explaining, we will continue to invest in the expansion of production facilities for RUCONEST and Leniolisib and the launch -- critical medical affairs and pre-marketing activities for Leniolisib and the registration-enabling study for APDS, as well as the ongoing clinical trials and other development activities including OTL-105.

And last but not least, we will look to invest in acquisitions and in licensing of new development opportunities that are near term to the market. So we can launch additional products very rapidly beyond Leniolisib. And we provide no further specific guidance for 2021. So this completes our presentation.

I would like now to hand over back to the operator for any questions that you may have that we can answer. Thank you..

Thank you. [Operator Instructions] We have a question from Joe Pantginis from Wainwright. Please go ahead, Joe. Your line is now open..

Hey, guys. Thanks for taking the question..

Hi..

Nice to see the first half results. So a couple of my questions are based on essentially blocking and tackling of the underlying business.

So first, can you give us any sort of visibility as to potential next EU territories that might be coming online? Obviously, since you've mentioned for quite some time now that the different regulatory structures there are the rate limiting factor?.

Yes. Yes, Joe. Spain, now, we -- after a long period, we got reimbursement. We’re working on Italy as well to get reimbursement. And we're looking at some of the smaller markets as well. I think North Macedonia and Ireland are territories that come to mind. But we're also looking to get reimbursement.

And it's not necessarily the regulatory activities, because that, they’re of course -- is of course, approved by EMA as it is by FDA. But in Europe, there’s market access hurdles that, in some cases, are tremendous. And take a long, long time. And that's what you're looking at here.

And that's what you're looking at in markets like Spain and Italy and the markets I just mentioned as well..

No, that makes sense. Yes. Sorry..

No. No worries..

Okay. So -- and then just curious, because as the business continues to expand and we'll just ignore COVID right now, that would be great.

How are your manufacturing initiatives going? What do you consider to be any rate limiting steps? And then, I guess, I will bring COVID back for my last question about, do you have any potential projected timelines with regard to the COVID data?.

Yes, yes. So the first one, we're -- we're executing on the manufacturing expansion strategy, the third facility to produce milk is now nearing its completion. So will soon be populated with those rabbits.

And from there on, of course, we will have to generate products from that facility, and process the products all to the finished product and show that to the regulators that we make exactly the same product, which we have done before, of course, so that should not be an issue, but it takes time. But it is in progress.

And Pants, we're working on the DSP facility to the purification plant, according to plan, which, of course in a couple of years will come online as well. So we're really insourcing the manufacturing process into the company, and we're executing against it according to plan.

With regards to, to the COVID results, we do expect that we could look for some interim analysis results, by the end of Q3 also because our recruitment has significantly slowed down in the studies by now. And that's a good sign, of course, because we want we all want to go back to normalcy.

And I think that's what you should be looking at towards the end of the quarter, I would say, we will be coming with some, some updates on that, and some potential next steps.

So following these, these two -- these two studies and of course, you were already mentioning it COVID is by far, the normally I mean 50% of the doctors, practices in the US are still not interacting life with pharmaceutical companies.

So we're still suffering from this inability to now face to face contact this which of course, is very important when you're dealing with rare diseases, with patients transferring from one to another product in rare diseases situation where you have to go to incredible big, administrative hurdles.

And of course, I can fully understand that even when these doctor's offices are open, that may not be their first priority.

So that's really an ongoing challenge with PCI turning slowly back to normality and US and therefore, we're optimistic for the rest of the year that, the increase in revenues that we see, should continue for the remainder of the year. Okay..

Thank you, Sijmen..

Okay. .

We have another question from Alex Cogut from Kempen. Please go ahead, Alex..

Hi, thanks for taking my questions. I have a couple of questions in pipeline so on RUCONEST, so thanks for kind of describing the dynamics in patients and where you see RUCONEST playing in. But I would like to understand a little bit better.

What's actually happening with volume assuming, patients are – you’re getting new patients are using RUCONEST mostly to take HAE attacks.

But losing patients that were using a kind of prophylactically off label, aren't you overall experiencing them lower volume of drugs?.

Yeah, sometimes we do. Sometimes we don't. It's very difficult, Alex. You're right, there's a mechanism like that. There's also a mechanism that we see that there's a certain saturation point now reached of patient switching over to these new prophylactic therapies that at least will be taught to KOLs, what they tell us.

And that means that indeed, you have to replace if you have a severely affected patient, and they go on prophylaxis, they often mostly continue to use RUCONEST but on a lower frequency. That's correct. And if you replace them with patients that are using root canals for breakthrough attacks, you need to replace them with more patients. That is correct.

But the good news is, it is happening and the good news is that you can see that we're recovering the sales from where we were hit really hit by COVID, but to more normal levels and we remain optimistic going forward.

The challenge here, in addition to that, of course, is face-to-face contact with these doctors, because it is as I already was saying, it's an extensive administrative hurdle to do this.

And our experts, internal experts are helping those doctors practices jumping through all these hoops, and sometimes these hoops are very significant before patients actually get their commercial -- their first the delivery of products.

However, when patients subscribe to RUCONEST solutions, they get a bridging medication until such time that they are that are reimbursed. So, that's -- that is basically the mechanics that are ongoing in the market.

And you see we remain optimistic about the future prospects of RUCONEST in this respect that certainly has its place, and will continue to have its place in this market with this very unpredictable disease..

Got it.

And just to clarify the visibility into the volumes per patient, that there are over the last first half?.

Yes, we do have insights and that is, of course, all anonymized data. But it is because it's your we working with the specialty pharmacies, we know the patient journeys, and we support patients as well, of course, because these patients are often very much in need of support in all sorts of ways. And we do support them in all sorts of ways.

So, yes, we're very close to our patients..

Okay. Got it.

On just a question on your qualitative guidance, when you say increased continuous growth in sales, do mean year-over-year or quarter-over-quarter, how should we think about that?.

That's always a very nice question, of course. I would say that we started with -- that we increased quarter-on-quarter. I can't speculate on that is really -- that the sales will be higher as last year, because that is certainly very much dependent on how quickly situations turn to normal.

And as you know with all pharmaceutical companies are suffering from this issue, that a lot of the CARE is not being delivered, and they suffer from lower revenues, because CARE focused on COVID, takes away resources from CARE that is given otherwise, and I think we're in the same boat here.

So, it really depends on the situation returning to normality. And you know what, last year, we lost sales that we didn't get back because our growth was lower than we expected.

On the other hand, we got a lot more sales in the end of the year, especially the fourth quarter that we weren't expecting and which turned out to be a certain amount of hoarding by patients, because of that tremendous COVID wave that hit the United States at the end of last year. And that was not foreseen, and you saw the drawback of that.

So, it's very difficult to predict that in these kinds of circumstances. But I think it's generally -- you see a general trend of that happening in the pharmaceutical markets. So, we're no exception that..

Okay. Understood.

On the pipeline, so when do you expect to report the Leniolisib in the results then?.

That's a study that's done by Novartis. So, it's either the end of the year or the beginning of 2022 -- of next year that this comes out -- that the final report is coming out. And we're aiming to bring in the results very quickly to the FDA and EMA and we're aiming for PDUFA date in Q4 of 2022.

So you can see that it should be somewhere in the beginning of the year or maybe even towards the end of the year. That's very difficult to predict. As I said, it's in the hands of Novartis. The details. Yeah..

Got it.

And on OTL-105, when do you expect to enter the clinic?.

Yeah, that's an interesting question. We're doing a lot of preclinical work now. Now with gene therapy as you know your clinical pathway is slightly different because you don't do healthy volunteers. So you go straight into patients here. So we expect somewhat longer preclinical trajectory.

And I would like to reserve the answer on that until we have some more insights in that. And we will come out with some more timelines, but it will of course be a few years from now before we go into clinic, but then with the shorter and typical clinical development program, because it's gene therapy. Okay..

Okay. Understood. Thank you very much. That's it..

Thank you, Alex..

We have one more question from Christian Glennie from Stifel. Please go ahead, Christian..

Hi. Thanks for taking the questions. Follow-up then on Leniolisib.

Firstly, on -- in terms of who's responsible for the regulatory filing? Is that down to the Novartis or you guys? And then just on the -- think about the tests and that collaboration? Have you thought that yet, is there any information has come out of that, that might inform sort of diagnosis rates? You say, obviously, there's a patient population out there, but it's hard to find them and get the diagnosis, right.

So is there anything to come out of that particular initiative as yet?.

Yeah. Okay. So first of all, we do the regulatory filing for the product. And then with regards to that APDS testing program with Invitae and navigateAPDS, that's just started, as announced earlier.

And we have patients in the market now testing those immunologists there -- immunology practices, and going through those patients and defining the most likely symptom combinations for APDS and educating those immunologists on that and then they offer the genetic testing.

And that is actually ongoing, so we have had a number of these tests already being commissioned. We also have a patient registry in Europe and we're building a patient registry in the US. And we have of course, patients identified there.

So we start in all owners to build that registry and to build relationships in the community and with the patient organization. There's no specific APDS based organization. There is of course for these primary immune deficiencies. There are several patient organizations where we are collaborating together with.

And there is a very high motivation of these patients to actually collaborate with us because of course, if you have an primary immune deficiency and if you happen to have APDS, in this case, you're lucky because you could get some therapy into the future as they are very motivated to work with us.

So we look forward to that continuing and of course, in due time, we will inform about where this is going..

Do you have a rough sort of number at this point or any insight into what the diagnosis rate is at the moment for this condition?.

Oh, yeah, there are several hundreds of patients already diagnosed for the disease. There's definitely -- we're not starting from scratch at all. We estimate according to the -- estimated prevalence that there could be about 13 out of 50 patients in the market -- in the main markets.

And there's a couple of 100 already identified on both sides of the ocean, so we're not starting from scratch at all. Okay, okay..

Okay.

And then, just turn to the AKI trial that's underway looking through 200 odd patients, anything to say in terms of recruitment so far in that trial and potential timings of data?.

I would say that, I think we're earlier we said that, towards the end of next year, second half of next year, we expect to be able to complete that trial. For now, I would like to stick to that. We're trying to accelerate this study. And again, we will of course, if we're in the market when we are finished the recruitment as per usual.

And I think, we should wait for that..

Thank you.

And then Suhas [ph] who was asking, the key part, one of the key strategies on business development, something coming on terms of adding new products then to the platform, can you characterize anything versus what you might have said last time in terms of habit, what level of discussions are happening and expectations?.

Yeah, we have a very active business development Group. And we are interacting with several potential targets or partners at the same time. And these discussions sometimes go very far and sometimes, we, we stopped very early. So there's a continuous activity going on. But as you know, business development is a real numbers game.

And we, of course, are quite precise about the opportunity we're looking for. We're looking for compounds that are in a rare or ultra rare space, because the development is always seeable. We're looking for compounds that are sort of within the window of three years from now to be able to launch.

So, if we have a rapid succession of launches following the LENIOLISIB and sia, it has to be of course, we have to be convinced about the data. And then of course, last but not least, the other party will have to dance as well. And that is of course, takes too.

So all in all, we're working very hard on this, and we're quite keen that we have continued discussions. But as you know, business development is all nothing until you have a deal, you don't have anything. And that's, we're no exception here, I'm afraid..

So, okay, thank you..

Thank you, Christian..

We do not have any further questions at this stage. I’ll pass it back to Sijmen..

Thank you. Thank you, very much. And thank you very much, ladies and gentlemen. I would like to remind you that we are optimistic about the rest of the year. We are well for the business. We have our own commercial sales. We have a near term inflection points. We're looking at large indications for our lead compounds.

We have recently added a very interesting gene therapy to our long term pipeline. And we are looking forward to meet you again with our next results conference. Thank you, very much for your attendance. Goodbye..