Pharming Group N.V.

Good morning or good afternoon, ladies and gentlemen. I'm here with my three colleagues, Stephen Thor, our Chief Commercial Officer, Anne Radwellen, our Chief Medical Officer, and Jeroen Wakkamon, our Chief Financial Officer. And we are delighted to take you through the third quarter results of this year. Before I do that, however, I would like to point you to the forward-looking statement slide, because we may contain, this presentation may contain or will probably contain forward-looking statements that, as you know, statements of future expectations that are based on our current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. And the rest I leave to you to read. So let's just move on to the next slide, and then, of course, to the next slide, about building a sustainable business in rare diseases. And that's what we are about, and this is, of course, you know, a very interesting moment in time for the results of 2023. And you see that on the left-hand side, how we are going to build, start to build that rare disease, sustainable rare disease business. We have significant positive cash flows for more than 200 million of, you know, moving annual total sales of Rukinest that confront the Joenja launches and pipeline development to start with. And we are very pleased, of course, with the results and the strong revenue growth of Rukines, 18% up on the second quarter and 11% up on last year's third quarter. And also, if you look back nine months, so year to date, 2% up on last year. That means that we are on track to deliver our low single-digit revenue growth for Rukines for 2023. And then, of course, you move to the middle pillar, and you see there, of course, the global approvals and commercialization of Joe and Ja that can be funded from those cash flows from Ruconest. And, of course, we were pleased, very pleased, to get that very fast approval from the FDA back in March, brought the product to the market, and got reimbursable, reimbursed patients almost immediately when we were on the market, such that we could already record revenues in the second quarter of this year, which was the first quarter Joenja was on the market. And now, of course, we're very proud of the continued growth of Joenja, where in this quarter we've booked 6.5 million of revenues, and year-to-date, 10.3 million. In addition to that, of course, regulatory reviews are ongoing for Joenja in Europe, Canada, Australia, Israel, and we have a pediatric clinical trial program ongoing as our label is currently 12 years and upwards. And, of course, on the right-hand side, you see further growth accelerators beyond Joangia in APDS. First and foremost, and that is where we will come back to you before year-end to update you on that, we are in dialogue with the FDA about the second Lelionis indication, and we'll provide you with more details towards the end of the year, and colleague Anurag will talk about a lot more. And last but not least, as we have a very... strong commercialization infrastructure in both the U.S. and Europe. We're hunting, as we speak, for new in-licensing opportunities or acquisitions for additional products in rare diseases that we can actually continue to develop, critical development, and bring to the market and then successfully commercialize. So we're looking for products that have clinical proof of concept. And if you see at the next slide, you see that there is actually space. to have such products in our pipeline. You see here the extensive work we do by enlarging our footprint by means of bringing Laniolisip to markets, a field like, as far a field as Japan, but also Canada, Australia, and Israel, and of course the other indications. So you see there's space in this pipeline to further accelerate the growth of the company going forward. And with that said, I would like to now hand over to my colleague, Steven Tor, who will give you some more insights in the commercialization operations on Ruconest and GeoEngine. Steven, over to you.

Thank you, Simon. Good morning, everybody. As Simon said, I'll give you a brief overview of Ruconest performance and also some insights around the GeoEngine launch and update you on that progress to date. Next slide, please. So as communicated at the end of Q1, and as you're all aware, the HA market underwent a significant event which affected all products. The event was short-lived, and as we said we would, we bounced back strongly in Q2 and Q3. As you can see in the first bullet, we posted strong growth in Q3, and even with the soft nipper Q1, as Simon showed, we have grown versus prior year. So we're really pleased with that performance. And this has been driven by strong performances across all of our leading metrics, but I especially want to flag new patient enrollments, which have exceeded 70 over each of the past three quarters, which is stronger than we've seen in the past. And so hence, as Simon said, we continue to guide the low single-digit growth for Rukaness this year. Next slide, please. So as many of you know, Rucanest was launched in 2015. We've actually, though, been active in the HA community since around 2000. And over those 23 years, we collaborated with all key stakeholders, including the clinical ones and patient advocacy groups such as the HAEA. And that has been the major driver for the consistent success of Rucanest over the nine years post-launch. And it's why the prescriber base continues to grow with 700 in the U.S. to date. and also why we've treated over 2,000 patients. And that metric continues to grow as well. So I think what that clearly underlines is the importance and the ongoing need for a recombinant IV C1 esterase inhibitor. And that's despite the fact over 70% of patients are now on prophylactic treatment today. So next slide, please. So moving to Joe Enger, as Simon showed earlier in the presentation, we're off to a very strong start in the US with our launch. And as indicated in previous calls, and I think as everybody on this call knows in relation to the environment more broadly, access, once a patient is diagnosed, is one of our key pillars for success and the ongoing success of this launch. And we partnered with an organization called Panther of RX that specializes in ultra-rare or rare diseases to build a program that we thought would enable us to quickly provide patients with access to Joengia once they're covered for chronic use. And I'm pleased to report that in only six months post-launch, Farmers Access and Medical Teams, in partnership with key opinion leaders across the country, have secured APDS coverage policies in over 90% of our target plans across commercial and government payers. And the result is a 93% approval rate with zero denials. And so I just want to repeat those two. 93% approval rate with zero denials, despite the rarity of this condition and the heavy lift on education. So that's really a very strong performance. Also, as you know, from enrollment to shipping to patients, the gold standard in rare disease is 30 days. And I'm pleased to report to you that we're averaging 26 days typically, and sometimes we're getting from enrollment to putting product in patient's hand in less than 20 days. And really, this is based on exceptional customer focus and execution, which further instills, I believe, in our confidence in our stakeholders, but most importantly, you know, the patients and treating physicians. So next slide, please. So I've mentioned, you know, farming strong customer and patient focus, and I think combined with the exceptional execution I've already mentioned, our U.S. team have delivered strong results in that first six months since launch. We have, as the slide shows, 76 eligible patients, 63 shipping, and that represents well over half of the eligible patients we have on therapy. This has led to the revenues of $10.3 million that Simon also showed. And as already mentioned, payer discussions have and continue to go very well, which creates, importantly, an excellent environment for us to pull those patients through once they're diagnosed and enrolled. So finally, I just want to flag now that we're through the immediate launch phase, and with many of the previously identified patients on therapy, we'll be placing additional time and resources now on family testing. Most of the patients we have are patient zero, so to speak, so we believe there's a lot of opportunity there to help those families by better educating them and testing all of them to see whether there are others in need of therapy. And with that, I'd like to hand over now to our CMO, Dr. Anurag Raman.

Thanks, Steve. I'll begin on the next slide with a little background information about APDS. So APDS was first described in 2013, and based on our estimates and literature review, we believe that there are more than 1,500 patients worldwide diagnosed with APDS, or 1,500 patients with APDS. We have already found more than 640 of those patients. These patients who have APDS have really had limited treatment options until recently to only treat the symptoms of the disease. The disease manifests itself in childhood and worsens over time, but without anything specifically indicated for treatment, physicians and patients were quite limited in their treatment options. And as with most rare diseases, the signs and symptoms vary across patients. This makes the challenge of diagnosis even more difficult beyond just a rare disease. Fortunately, there is a genetic test that can provide a definitive diagnosis for APDS, and I'll be spending more time in the coming slides talking about our plans and efforts to help find more patients with APDS. On the next slide, we can see what Joenja now brings to patients in the U.S. as a potential treatment option for them for their condition. It is approved by FDA for the treatment of APDS in adults and pediatric patients from ages 12 years of old and older. We have randomized clinical trial data showing that Joangia met both primary endpoints, as well as meeting several significant other clinically relevant endpoints. In addition, we've seen a well-tolerated and generally safe adverse event profile. There were no drug-related serious adverse events in the study or withdrawals due to the drug in the study. And more importantly, we have long-term data, and I'll be sharing some of that with you that we've been publishing and presenting at conferences recently, about the long-term benefits of using Joenja over several years in many cases. And this includes for patients in some cases to discontinue the use of immune globulin replacement therapy, reduction in infection rates, and persistence of the benefits that we see from the randomized clinical trial. And we can see that both in key measures of what's called lymph proliferation, so their lymph nodes continue to stay not enlarged, and we see benefits also in their immune cell function. And as Steve mentioned, this has led to a strong start for Joenja. I think this speaks both to the unmet need that exists in this APDS population, but also speaks to the seriousness of the condition. On the next slide, you can see some of our things that we're doing beyond the work that we've done in the U.S. As we discussed in August, we received the day 180 list of outstanding issues from the European Medicines Agency, and we can confirm now that in October we have submitted our responses. We remain on track to expect an opinion in this quarter, and with potential approval two months later. If we receive a positive opinion from the CHMP in this quarter, we can then go ahead and file with the UK MHRA agency with potential approval also two months later. And as we previously announced, we've started a program in Japan to enable registration there eventually, and we've also now filed in Australia, Canada, and Israel, and those applications are proceeding along their review We've also started a named patient program to eventually be able to help patients obtain access in territories across the world. And our pediatric study is enrolling quite well with the majority of enrollment already complete in the four to 11 study. And the one to six year old study has now started recruiting. So we expect that first patient also to be treated very soon. And as Simon mentioned, We have been engaged with FDA about the second indication, and we expect to be able to provide further details on the second indication later this quarter. On the next slide, I want to review with you some of the patient-finding efforts that we've initiated and are ongoing at this time. The first, of course, is APDS is a rare disease, and it's critical to raise awareness about APDS. And now we have a plethora of data also on laniolis that we can share. These data highlight the seriousness of APDS, and I think it also highlights, I think, the experience that we have with Leniolis have been treating many of these patients. On top of that, we have our ongoing Navigate APDS program that offers no-cost testing available to patients in the U.S. and Canada. And these patients, once they have this testing available, often have questions. So we have genetic counselors available to help them consider the testing and then also review the results with them. And then a big effort that we're really pushing on right now is that when we look at the diagnosed patients that we have in the US, especially, we find that most of those patients actually don't have family members that have even been tested. And we know that APDS is an inherited disease, but there's this gap in terms of testing. So we've initiated several efforts here, both with physicians and with family members themselves, be able to reduce the barriers to allow further testing amongst family members, which we think will be important to help uncover and find more patients. On the next slide, I want to review with you a little bit of information on something called variants of uncertain significance. And what these are are genetic test results that are basically unclear or, I would better say, unclassified at this point. And with the growth in genetic testing, We get more of these inconclusive results. These are basically variants that have not been previously seen. And this is really frustrating for patients and doctors because they have patients who have clinical symptoms of APDS often, but the genetic test result is inconclusive. And so we have several efforts ongoing. And I'm not going to review all of them with you in detail here, but these efforts involve trying to review the existing data and try to collate all of that information and publish that. We've just started a partnership, for example, with Genominon to develop these genomic landscapes, which will be available to all clinicians to be able to easily access variant information. We have a number of efforts ongoing to increase the availability of functional testing. And then lastly, I think I'm really excited about this possibility of this new effort that we started looking at a way to, in a single experiment, test all possible variants and quickly determine whether a result is pathogenic or disease-causing or not. And I think the nice thing here, in a sense, is that this is a problem, it's a new problem for APDS, but we're really using a playbook that exists already for many other genetic diseases. And we're following that playbook to be able to help these APDS patients who may still have this unclear diagnosis. On the next slide, you can see some of the conferences we've been presenting at and some of these abstracts we presented. These abstracts vary both in terms of what we're talking about in terms of the seriousness of the condition, so the mortality, for example, associated with APDS, but also the healthcare costs associated with APDS and especially untreated APDS. And these data, I think, highlight very nicely the serious burden that these APDS patients face. On top of that, we continue to get more data out of our clinical trial program. So we have a second interim analysis that will be published at the IPIC conference next month. And we also have a number of case series as well as abstracts on single patients. These are from many times from our expanded access program or compassionate use program where, for example, the second bullet under the IPIC heading is a patient who was previously transplanted, unsuccessfully, unfortunately, but then was treated with laniolisib under this compassionate use program, and the data at the abstract will show the benefits that this patient was able to experience. On top of that, on the next slide, you can see some of the publications. So the first publication is the first interim analysis, and that's available now in a full paper. And then the next publication is also a key publication describing the mechanism of action of laniolisib in APDS. And I think it describes clearly how APDS leads to this primary immune deficiency with this immune dysregulatory phenotype and how laniolisib benefits in these patients. And with that, I'll turn it over to my colleague, Jeroen Walkerman, our Chief Financial Officer.