argenx SE

We continue to deliver strong results from our global ZipGuard launch, making progress towards our goal of bringing a paradigm-shifting treatment to people living with generalized myasthenia gravis. We set out at the beginning of the year to prove that we could launch a drug that, with our experienced team and core strategies, we could transition into a global, integrated immunology company. Now, three full quarters into the launch, we have generated almost $230 million in net product revenue, demonstrating that our capabilities as an organization extend beyond antibody engineering, immunology research, and clinical development, and into bringing in new therapy and new modality to patients. Slide four. We have identified three key drivers of our launch success, which we hope to replicate as we plan for the anticipated approval and launch of our sub-Q products in the first half of next year. First, the unmet need and severity of the disease was even more significant than we realized, and the demand for a new treatment option has been high. During the third quarter, we crossed the 2,000 mark of patients on drugs globally. We hear every day how debilitating the disease is And in fact, our market research shows that severe Mg is second only to ALS as the worst disease neurologists treat. Many patients give up their jobs due to the severity of symptoms or side effects from current medication. They require walking support or feeding tubes because they have difficulty swallowing. Many GMG caregivers are also out of work to provide full-time care to their loved ones. To quantify this burden, we have invested a lot of time in gathering real-world evidence, which has corroborated the anecdotes we heard on significant loss of productivity and impact on quality of life. Second, the data with healthcare providers is setting a new standard of treatment based on the efficacy and safety profile observed in the data and ADEPT+, and these data are translating in clinical practice. We hear positive feedback from physicians on the speed of onset and depth of response, including patients achieving minimum symptom expression. In fact, we observed 40% of all treated patients achieving MSP in ADEPT after just one treatment cycle. This is quickly becoming an essential outcome measure for patients and physicians. And third, the core strategies we put in place appear to be the right ones, and we have strong engagement with our patients, physicians, and payers. We still provide updates on these strategies, but I'm very proud of our cross-functional team, which has worked closely in collaboration to achieve these results. Slide five, as you know, We believe GMG is just the beginning for this card, and next year will be a busy year with label expansion opportunities. Topline data are expected from our ongoing registration trials in CIDP, ITP, and PV, and each of these indications represents a sizable opportunity given the treatment gaps patients still face. We implemented innovative trial designs across the board that will provide us with important data for physicians in how they treat their patients. This year, we continue to anticipate top-line results in CRDP in the first quarter of 2023. Slide six, we'll enhance our learnings from precedent trials to design a year in an innovative way. Patients need to have confirmed, active CRDP in order to roll into stage A. where they must demonstrate a response to Epgraftigemot before advancing to stage B. In stage B, patients are randomized to stay on Epgraftigemot or switch to placebo, and the study stops once you have 88 events or relapses. Remember, this is an event-driven trial, which means you monitor the rate of dropouts to assess timing to data. We will, of course, continue to update you on this timing as necessary. We're also expecting top line results in the second half of 2023 from our second IPP trial, Advanced SubQ. The two advanced studies will support registration in the effort. Slide seven highlights results from the first advanced IV trial. Shortly after we reported data from the advanced IV study in May, we held an advisory board to gain feedback from the hematology community. The physicians were very excited by the fast onset of action and increased separation between the placid counts of treated patients and placebo throughout the study. They were also encouraged by the safety profile, which was consistent with what we observed in ADAPT. Consensus was that these data support positioning of VIFGAC as a third-line treatment option after a first TPO. They agreed that depending on additional data, there could be potential in early life patients as well. Slide eight. Many of the physicians on our advisory board were part of the ITP International Working Group that was formed to build assessment criteria of clinical trials more aligned to clinical practice. The IWG agreed that the goal of an ITP therapy should be to get patients to a safe place at camp to prevent clinically significant bleeding and to do so with little toxicity. In advance, 51% of treated patients were responded based on the IWG criteria, defined as achieving platelet counts over 30,000, a two-fold increase from baseline, and the absence of any bleeding. This IWG response rate resonated particularly well with our hematologists and further support our expected disregard positioning With the Drascopenticus, we expect data in the second half of 2023 as well. By 9, this is an indication where we launched translational studies to uncover more about the carcinoma based on the durable remissions we observed in phase 2. In these patients, autoantibody levels did not return to baseline in the same way as total IgG levels. Looking deeper, is correlated with a reduction in the autoreactive B cells, which are responsible for producing the autoantibodies. We are now looking more broadly across the indications to see if we observe a similar disease-modifying outcome. This type of translational work is part of who we are as a company. Through our commitment to both patients and the science, we want to advance our leadership in FCRN biology with new data and publications on the differentiation of our FC fragments. You'll also see our commitment to immunology innovation with our earlier stage pipeline and our partner programs, both of which emerged from our immunology innovation program. Our partner programs can take two forms, whether a licensing relationship or a spin-off company based around an Argenix asset. ARGENIX117 is our first-in-class sweeping antibody targeting C2 in a complement cascade. Last year, we shared Phase I data indicating that with repeat dosing, we can reduce C2 levels by over 95% for a sustained period of time. This would indicate the potential for an effective dosing profile. We are currently evaluating ARGENIX117 in a Phase II trial for the treatment of multifocal motor neuropathy, another very serious neuromuscular autoimmune disease, and the second largest IVIG indication within neuro. We believe there's a lot of opportunity with our C2 inhibitors across several of our therapeutic franchises, and we will aim to show the first set of clinical data next year. Rounding out the efforts in our neuromuscular franchise on slide 11, We are on track to file a CTA by the end of the year for our musk agonist, Argenix 119. We will start a phase 1 trial in the first quarter of 2023, in which we will assess patient cohorts at the higher doses, including congenital myasthenic syndrome and musk MG. Like 12, we are also seeing exciting recent progress with two of our partner molecules. with ASRI advancing ARGENIX 115 to the next stage of development and LEO exercising its option on ARGENIX 112. If you look back at our ARGENIX pipeline of antibody candidates, we have demonstrated human proof of concept in eight candidates out of our immunology innovation program, whether in our own hands or with a partner. This is exactly the reason we continue to invest in our innovation engine because it is efficient and productive with a strong track record to date. Before I turn the call over to Carol for a financial update, I want to spend a few minutes talking about my co-founder Hans de Haag, who will retire at the end of this year. Hans leaves us with an incredible legacy of scientific innovation. We founded the company based on his breakthrough in antibody engineering, which has been the backbone to most of our pipeline candidates. But it was his humility and drive to always learn about the scientific breakthroughs of others that led us to assets like Afgat-Tijemot and Argenis-117. We are very grateful that he will continue as an advisor to our Immunology Innovation Program, pushing us to find novel disease targets and promising new pathways, and as a strategic advisor to the R&D committee of our board. He will still gain from Hans' sound scientific guidance while he moves to the next stage of his career. We're also fortunate that we have such strong successes to step into the important role of chief scientific officer. Peter Ulrich has been with the company since 2010 was foundational to the creation of F-cathetumab and has been committed to the development of F-cathetumab since its creation. He watched the first subject ever to be dosed with the drug and has been leading F-cathetumab clinical science since that time. He served as the scientific leader of our neuromuscular franchise, strategizing on F-cathetumab, Argenix 117 and Argenix 119, and most recently took over as head of all theoretical science. This will be a very natural transition for the company, and Hums and Peter will be working side by side for the next couple of months, as they have been now for more than a decade. And with that, I will turn the call to Carl.

Thank you, Tim. Our third quarter 2022 results are detailed in your press release from this morning. so I will only highlight the key points here. On slide 13, you will find global net product revenues from the VivCard launch for the first three quarters of the year. In the third quarter, we generated $131.3 million in global net product revenues, which was comprised of $124.1 million from the U.S., $6 million from Japan, and 1.2 million from Europe and our distributor markets. Together with the 21 million from the first quarter and the 75 million from the second quarter, this puts our year-to-date global product revenues at 227.3 million. As with previous quarters, inventory in the channel at quarter end was well-managed, and reflects less than two weeks' worth of vials. Slide 14. Total revenues for the quarter were 146.5 million, which also includes 6.7 million in collaboration revenue driven by a 5 million euro milestone from Lille Pharma following the option exercise for Organics 112 and $8.5 million in other operating income. Cost of sales for the quarter were $10.3 million. Our total R&D and SG&A expenses for the third quarter were approximately $236.7 million and $108.2 million, respectively, and can mainly be attributed to FCAR Digimod and other pipeline research expenses as well as marketing and headcount expenses related to our global launch. The increase in research and development expense was mainly driven by the recognition of a priority review voucher submitted with a DLA filing for sub-Q at Cartigamot. On the cash balance, we ended the third quarter with almost $2.4 billion in cash, cash equivalents, and current financial assets. We continue to expect to utilize up to $1 billion of available cash in 2022, which will support our ambitious growth plans, specifically the rollout of our global launch, clinical development of Epcot Igimot in 10 indications and Organics 117 in 2 indications, investment in the global supply chain, and the pipeline expansion through our immunology innovation programs. You can find additional details behind these numbers in the press release we issued this morning. I'll now hand the call to Keith for a commercial update.

Thank you, Carl. Slide 15. I'd like to start by saying that I'm really proud of our global team for their execution and accomplishments over the last year. We are now 10 months into our U.S. launch, five months into our Japan launch, and almost two months into our Germany launch. Every day, I see dedication to deliver on our mission to serve GMG patients who are suffering from this devastating disease. We have now filed in Israel, Canada, and China, so 2023 will bring additional approvals that will expand our patient reach even further. As Tim mentioned, our core strategies are working to engage our key stakeholders, patients, physicians, and payers. Slide 16. On the patient side, we saw more than 50% growth of GMG patients globally on therapy, which indicates we had another quarter of significant demand for VivGuard. We believe we are setting a new standard in how GMG patients can manage their disease based on the efficacy and safety data we have shown in ADAPT. Most importantly, the data we saw in ADAPT are translating into the real-world setting. Approximately 50% of our patients are still coming from IVIG, meaning that IVIG is the most advanced therapy that they have experienced. We will be watching closely over the next several quarters to see if we continue to see the shift into earlier treatment segments. We want to expand to reach those patients who have only experienced mestinone, steroids, or broad immunosuppressants. This will be an indicator of our long-term trajectory on our path to reach 17,000 addressable patients. Our sales team has done a great job engaging a broad group of neurologists focused primarily on their top target physicians in the first quarters of launch. We still face the effects of the pandemic, So the decision to hire an experienced sales force has been crucial to our early launch success. By the end of the third quarter, we see continued breadth of prescribers, though most have still only written one or two scripts. The opportunity ahead of us is to drive more experience with current prescribers and reach new potential customers that our field team have not yet engaged with. Moving on to payers. Engaging with the payers prior to approval was a key driver on early uptake of VivGuard, and as a result, patients have been able to successfully gain access. At the start of the third quarter, we received a dedicated J-code, which helped to shorten the time between script and infusion and improve the rate of patients going on therapy. We will be taking a similar approach of the early engagement with payers ahead of the expected subcutaneous decision. Following our European approval in August, we are also spending significant time with payers in this region. We launched in Germany and are able to sell through the Amnog process while we negotiate price. The value dossiers have also been submitted in key countries like France, Italy, and the UK. We would like to point out that the reimbursement process can take several years, so the growth trajectory in Europe is expected to be consistent but much more gradual than what we've seen in the U.S. and Japan. Slide 17, patients and physicians have embraced the individualized treatment approach with VivGuard, feeling that it aligns with the GMG experience. It's still too early to understand the distribution of treatment cycles on an annualized basis, but it seems to be aligning with what we saw in the ADAPT and ADAPT Plus data based so far. We believe the value of individualized treatment approach goes beyond dosing schedule and extends to delivery as well. We are looking forward to the FDA decision on our subcutaneous BLA filing in the first half of next year because it gives the opportunity to bring the patient more ways in which they can individualize their treatment. It also gives us a second opportunity to show our commitment to the patient community by seeking approval in adult GMG patients regardless of antibody status. Slide 18. Before I turn the call back to Tim, I want to once again commend our global team. They have exemplified teamwork and dedication, always putting the patients first as we advance on our mission. We believe we have a truly transformative therapy with VidGuard, and we're motivated every day by the stories we hear from patients. We know that the connections we are building now within our neuromuscular franchise will serve us well as we look ahead to our future launches. There are still many unknowns on the long-term variables of our launch, but we are delivering where we can to generate demand and convert that demand into patients on therapy. Tim?