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spk10: Good morning. My name is Rob and I will be your conference operator today. At this time, I'd like to welcome everyone to the call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again press the star one. Thank you. I'd like to introduce Beth DelGiaco, Vice President of Corporate Communications and Investor Relations. You may now begin your conference.
spk07: Thank you, Operator. A press release was issued earlier today with our full year 2022 financial results and the recent business update. This can be found on our website along with the presentation for today's webcast. Before we begin, I'd like to remind you on slide two that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical development, regulatory timeline, the potential success of our product candidates, financial projections, and upcoming milestones. Actual results may differ materially from those indicated by these statements. Argenix is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law. I'm joined on the call today by Tim Van Hauwenmeren, Chief Executive Officer, Carl Gubitz, Chief Financial Officer, and Keith Woods, Chief Operating Officer. I will now turn the call over to Tim.
spk06: Thank you, Beth, and welcome, everyone. Next slide. Reflecting on 2022, it was a year of many achievements for Argenix as we evolved from an R&D organization into a fully integrated R&D and commercial organization. We launched our first-in-class FCRN blocker, RISCARD, in the U.S., Japan, and Germany and exceeded our own expectations, generating $401 billion in global net product revenue. I'm very proud of the team for the strategy they built and executed, solidifying our reputation with our key stakeholders. With this significant momentum, we start 2023 in a position of strength. We also have our marching orders in hand for multidimensional expansion to reach more patients with DivGuard through anticipated regulatory approvals and launches in new regions and by driving usage earlier in the GMG treatment paradigm. Next slide. This year, we also generated a significant amount of data on our first-in-class SCNN blocker through clinical trial readout, translation research, and peer-reviewed publications. We reported phase III data from our sub-Q bridging study in GMG, which demonstrated non-inferiority to the IV, based on IgG lowering, as well as consistency across secondary efficacy endpoints and safety. We have now filed for approval with the FDA, EMA, and PMDA, and have a PDUFA target action date in the US of June 2023. we received a communication from the FDA in January notifying us of a three-month clock extension. Since that time, the FDA's review continues, and we are engaging regularly with the agency, being responsive to inquiries as we advance through some anticipated approval. We reported phase III ITT data from our first registration trial last May, and presented these data during a plenary session at ASH in December, which triggered significant interest from the hematology community. We are preparing to submit an MAA in Japan in the middle of this year for approval based on the first ADVANCE trial and will await the data readout of ADVANCE SubQ in the second half of this year to support filing in the US and Europe. Across all of our FGATIGAMA studies, we also generated significant data in 22 to broaden the scope of our safety database, which now includes more than 3,000 commercial patients globally, more than 1,300 clinical subjects, up to 19 cycles of intermittent cyclic dosing, and more than two years of weekly chronic dosing, all with a cumulative exposure of more than 1,000 patient years. Lastly, before we look ahead to 2023, I want to call out a strong sign that continues to serve as the cornerstone of Argenix, solidifying our leadership in SCRN as both the first in class and likely best in class therapy. Our teams are committed to building a deep repertoire of preclinical and translational data, which can serve as an important basis for indication selection or to underscore the clinical or commercial data we are generating. We had several key publications in 22, including on, one, the long-term remissions we observed in pemphigus and the underlying reduction of autoreactive B cells. Two, the differentiation of our FC fragment and its intercellular fate, keeping FCN in its recycling path without interfering with albumin homeostasis. Three, review of the humoral immune response to vaccines during Avogadro treatment. And four, multiple publications and presentations on the health economic outcomes front, highlighting the value that DivGuard can bring to GMG patients from a quality of life perspective.
spk08: Next slide.
spk06: We are well on our way to achieving the Argenix 2025 vision, which we laid out a couple of years ago. Specifically, we are now reaching patients with VivGuard globally, evaluating Evgard-Tigermoth in 13 severe autoimmune indications, preparing for the first clinical efficacy data from Argenix 117, our next pipeline in a product candidate, and we are investing in our ecosystem of innovation. We have an impressive track record for molecules that have emerged from our immunology innovation program, both within our own pipeline, and dose with our partners. Beyond F. graptigamot and ARGENIX 117, some of these include ARGENIX 119, an agonist to muscle-specific kinase. We dosed the first subject last month. Our third pipeline candidate is now clinical stage. Q-satuzumab targeting CD70. We formed OncoVarity with the University of Colorado last year based on the translational work of Dr. Clayton Smith on the CD27-CD70 pathway, which when combined with our clinical studies is a pretty robust data set. ARGENIX-112 targeting IL-22 receptor in development by Leo Pharma and moving forward in development. And ARGENIX-115 targeting GARP in development by AbbVie, which is also advancing. Next slide. We had a very busy year ahead. that will progress us even further on our path as an integrated immunology company. We continue to expect top-line data from the ADHER trial of Afgafigamab in CIDP in the second quarter of 2023. There remains a significant unmet need for CIDP patients for a safe, effective therapy with a manageable dosing schedule and delivery. With ADHER, we hope to address these needs and demonstrate the potential for Avgazigimab to provide patients with a differentiated therapeutic profile across efficacy, safety, and convenience measures. In addition to the advanced sub-Q readout in the second half of this year, we also expect pivotal data from the ADDRESS trial for PEMFIGUS. With ADDRESS, we hope to see efficacy data, which build on the exciting results from Phase 2, a fast onset of action, driving patients into disease control and ultimately complete remission with the ability to taper to a minimal dose of steroids. We will have our first proof of concept data in post-COVID parts in the fourth quarter of 2023. This was an indication that was brought to us, particularly with the growing incidence in the wake of COVID. Physicians report that IVIG and FLEX work well in these patients. and we know that anti-adrenergic and anti-nuclear antibodies are involved in disease pathophysiology. All of this is a strong rationale for evaluating FGAT-Tigamot in what could be a very sizable indication. Finally, we're also planning for the first clinical efficacy data from ARGENIX117 in patients with multifocal motor neuropathy. IVIG is the only treatment option for NMN, and it comprises a significant proportion of that market. With our interim analysis in the middle of this year, we will have data from the first cohort of nine patients. Our goal with this data snapshot is to determine whether to advance to a second, larger cohort and at which dose. We continue to produce translational data supporting the pathological role of IgM autoantibodies in MNN and the rationale for the C2 inhibitors as a new treatment modality. Before I turn the call to Carl, I want to spend a few minutes on the leadership transition we announced today with Keith's planned retirement. We are very excited to welcome Cara Massey to the team as our Chief Operating Officer as of March 13, 2023. She is a very talented and inspirational leader with significant operational and commercial experience. She's joining us from Genentech Roche, where for the last three years, she led a global clinical operations team of over 2,000 people. She has a broad commercial experience, including specific experience within the neuroinflammation space, having launched first-in-class medicines, which disrupted the treatment paradigm. I was very impressed to hear about her role with the Oculus launch, taking an already successful launch and accelerating it in a crowded market. Beyond these remarkable achievements, the quality that most caught my attention is her focus on building teams, creating a company culture and community, and designing nimble, global, innovative organizations, all of which will benefit Argenix. I would also like to share with you my gratitude to Keith for his partnership and his friendship. He is a visionary leader who has always kept both science and the patients at the center of everything we do. We're so fortunate for the role he's played in our growth over the last five plus years of his distinguished career in biopharma. He joined Argenix after the release of his 2MG data, when he convinced me that Argenix could launch F-Graftigamot. He saw a vision for Argenix commercially, not only in the US, but also Japan, Europe, and Canada. I could never imagine at that time the impact we could have on patients even in the first year of launch. He was committed throughout our search process to find the right person to fill his role. I knew I could count on him to stay until we all agreed we had the right successes and we are both very confident we have that in Karen. We are also fortunate he will be staying with the company not only during the transition period through the SCF Gratikamot launch, but also after he retires. He will transition to serve as a board advisor on our commercial committee, where he will continue to make a significant impact on our commercial strategy and for our patients.
spk08: And with that, I will turn the call to Carl. Thank you, Tim.
spk05: Our full year 2022 results are detailed in our press release from this morning, so I will keep this section of the call short. On the next slide, you will find global net with card revenues for the fourth quarter and the full year 2022. We generated $401 million in global net product revenues in 2022 and $173 million in the fourth quarter, specifically which was comprised of $159.1 million from the U.S., $8.3 million from Japan, and $6 million from Europe and our distributor markets. Next slide. Total revenues for the full year 2022 were $445.3 million, which also includes $10 million in collaboration revenues and $34.5 million in other operating income. Cost of sales for the year were $29.4 million. Our total R&D and SG&A expenses for the full year 2022 were approximately $663 million and $472 million, respectively, and can mainly be attributed to FCAR TikiMote and other pipeline research expenses, as well as marketing and headcount expenses, related to our global launch. The research and development expenses includes the recognition of a priority reveal voucher submitted with a PLA filing for SE F. Cartigamot. We ended the year with $2.2 billion in cash, cash equivalents, and current financial assets. Based on our current operating plans and a projected 2023 cash burn, of approximately $500 million, we expect our existing cash, cash equivalents, and current financial assets together with anticipated future product revenues to fund the company to profitability. You can find additional details behind these numbers in the press release we issued this morning. Before I turn the call over to Keith, I would also like to share my gratitude. Under his leadership, we were ready to launch with Carl, and it has been a very successful first year, both with our performance but also seeing the team of leaders that Keith has built across the commercial organization. I am confident that Karen is the right person to build on this momentum and lead us to the next stage of our growth as a global company. Keith?
spk22: Thank you, Carl, and thank you both for the kind words. While I'm very much looking forward to this next phase, spending more time with my family and transitioning to an advisory role for Argenix, it was still a difficult decision to make. The last five plus years have been the most rewarding of my career. Being able to build a commercial team and launch a truly transformative first-in-class medicine for patients. I am proud of the success we had in the first year and know that this is just the beginning for Argenix and for patients, especially with Karen at the helm and the team of impressive leaders behind her. We closed out the first year of our VivGuard launch in a very strong position. We were able to reach more than 3,000 patients in 2022 with our transformative therapy, well beyond the expectations we set for ourselves at the beginning of the year. Our commercial and medical teams have done an outstanding job, working hard every day on our path to redefine how autoimmune diseases are treated, and the work has just begun. First on patients. We continue to see a steady demand from new GoodGuard patients, both in new scripts and patients on therapy. We also see positive trends in moving earlier into the treatment paradigm. We still see approximately half the patients coming from IVIG as their most advanced therapy, but the dynamic is shifting in the other half, with more coming from earlier lines than refractory. We still continue to learn about our launch and the trends, but we are going in the direction that we want. We are seeing a similar positive trend with physicians. Increasing numbers of repeat prescribers and the growth in the number of physicians have written greater than five or even greater than 10 prescriptions. Our field teams have reached more than 90% of their key targets and almost 8,000 healthcare professionals overall across targets and non-targets. Our medical affairs teams have had a significant presence at all major neurology conferences broadly reaching the prescribing community. They also worked on more targeted engagement through scientific roadshows to reach the typically difficult-to-access institutions. The field teams were nimble throughout the year, leaning in on tactics that worked well, which led to an overall successful year of physician engagement. Payer interactions also continued to be an area of strength for this launch. We ended the year with approximately 90% of commercial logs covered, and almost 80% of these policies are favorable. the team is still successfully working to switch unfavorable policies to favorable, removing IVIG as a step through, just as an example. The recertification dynamic does appear to exist as we are switching to a new year, but this is something we are watching closely, and for the most part, re-approvals have been smooth and occurring every six to 12 months, which allows the physicians to re-dose as they see fit. We presented data last month on the time distribution between cycles one and two from over 400 VivGuard patients. As we saw in ADAPT and ADAPT Plus, it is a true distribution, with 32% of patients receiving a second cycle less than six weeks after the conclusion of the first. But on the other side, we also had 32% of patients receiving a second cycle greater than nine weeks after their last dose of the first cycle. The rest fall in the middle. Based on the data we see and the feedback we hear, individualized dosing is doing what it's supposed to do. Patients asked for this when we were designing our trial, and we're pleased to see that a substantial number of patients are benefiting from that decision. Next slide. We are now looking ahead to the expected FDA approval of subcutaneous efgartigamide in June. The team is using the extra three months to refine our strategy and expand our opportunity to reach patients both with IV infusion and subcutaneous administration. We're taking a similar early engagement approach with payers as we did with the IV launch, but we still expect several months where we won't have a published policy in place post-approval. Beyond subcutaneous approval, we also expect to drive VidGuard expansion geographically this year. with anticipated regulatory approvals in China, Canada, and additional launches in Europe as we work through price negotiations. Before I turn the call to Tim, I want to end with one VivGuard patient story from my trip to Japan earlier this year. I heard from a young mother who was really struggling when she learned that she had a chronic disease because she was feeling very socially isolated. She was not being able to participate in family activities play with her children, or pick them up and give them a hug. She had lost her job because she could not use the equipment or perform small manual tasks. DivGuard worked quickly for her, and within a week or two, she had restored more movement than she had in several years. Her gratitude was so rewarding. We shared her story more broadly with our teams to remind them of the impact that we can have. This is the motivation we are taking forward as we build on our momentum for 2022 and apply it to our successful strategies for the year ahead.
spk08: Back to you, Tim. Thanks, Keith. Next slide.
spk06: 2022 was a historic year for us. Our first year as a commercial company, and we are very happy with the outcome. We built momentum across our key stakeholders. with physician and patient demands, and a smooth payer process. We know from precedence that the initial six months of the launch often defines its trajectory, and now we have our trajectory. We're looking forward to the rest of 2023, focusing on multidimensional expansion into new geographies, the anticipated launch of SC Epidartigma, and moving into early-aligned GMG patients. We also see the opportunity to transform the treatment paradigm in many other autoimmune indications as we look ahead to our upcoming data readout in TIDP, ITP, and PV, and the first efficacy look at Algenics 117 and MLM. Thank you for your time today. I would now like to open the call to your questions.
spk10: At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad. We ask that you please limit yourself to one question and then rejoin the queue for further questions. And your first question today comes from the line of Tazin Ahmad from Bank of America. Your line is open.
spk20: Hi, guys. Good morning. Thanks for taking my questions. Keith, I want to wish you really well. It's been great to get to know you, and you've been an amazing head of commercial, and all companies deserve to have someone as good as you. Maybe my question will be on MMN for the interim rate in mid-2023. What level of data should we be expecting to see at the top line, and what would you consider to be clinically meaningful? Thank you.
spk06: Thank you, Tasina, and thank you for joining us in today's call. Beth, what do you think will be the level of disclosure detail for the first nine patients?
spk07: Yeah, so what we really want to see from those first nine patients is to understand, you know, early clinical activity, but also what level of dose we want to take forward into that second cohort. We haven't decided what exactly we'll share, but that's really the goal of that first cohort, and the disclosure will be around that.
spk08: Okay. How many patients will that be again? Sorry, Beth. Nine patients.
spk20: Nine patients. Thanks.
spk06: The way to think about it, Suzanne, is all MMN patients today are on IVIG. So the way that the proof of concept is designed is that we first establish the dependency of these patients. So we basically document that IVIG cycle, and then we switch either to placebo or Argenix 117 and see whether we can keep the patient stabilized compared to placebo. So we think this first dose cohort should give us a very clear idea of, you know, whether the drug works, and more importantly, what level of C2 inhibition we need going forward.
spk20: Okay. Thank you, Tim.
spk06: Thanks for the question.
spk10: Your next question comes from a line of Rajan Sharma from Goldman Sachs. Your line is open.
spk23: Hi. Thanks for the question. So I was just wondering if you could get your thoughts on kind of VivGuard's trajectory this year and whether kind of the slight delay to the PDUFA for the subcutaneous formulation has changed your expectations. Thanks.
spk06: Thank you for this question, Lateef. Do you want to run with this one?
spk22: We're happy to do so, Tim. So first of all, the delay by three months in the PDUFA date for sub-Q, I mean, it does change the fact that we were going to have two different opportunities to serve patients with two different formulations for nine months of the year. That only turns into six months of the year. As you know, we haven't given guidance at this time. And so all I can say is that we believe that the trend that we're currently on will continue to allow for growth. And we believe that SubQ will expand the total potential market for patients that would receive VivGuard.
spk08: Your next question comes from the line of Thomas Smith from SVP Securities.
spk10: Your line is open.
spk15: Hey, guys. Good morning. Thanks for taking the questions. And let me add my well wishes to Keith on his transition and retirement. Just, I guess, one quick one on the sub-Q PDUFA. It sounds like the dialogue here is pretty dynamic regarding the application. Can you comment on whether there's been, I guess, any area of particular focus for the FDA in the review, or whether there's been any unanticipated asks for further data?
spk06: I would say that the review continues, you know, at a good cadence. The way we would describe the ongoing Q&A is, you know, rather routine, rather standard. we get your typical questions in review of the files. So no specific area to call out. So we believe in the strength of the data of our file, and we see continued good progress in the review of the files. So we're all hopeful for the June 20 PDUFA date.
spk08: Okay, great. Thanks.
spk15: And if I could just squeeze in one follow-up just on the commercial trajectory. If you could just comment on expectations, I guess, for Q1. relative to Q4 and how to think about combination of seasonality and kind of payer reset there would be very helpful. Thanks.
spk06: Keith, would you like to take this question, please?
spk05: So it's Carl here. So I think for Q1, I mean, we launched adding new patients, consistent growth. Two things to call out in Q1. We do see the impact of seasonality. If we lose the selling day because of an holiday or a winter storm, that cells do not move to the next day. We basically lose those cells. And also, we do see re-verification of benefits, which typically happens in Q1.
spk08: Understood. Thank you, guys. Thank you.
spk10: Your next question comes from the line of Yaron Werber from Callan. Your line is open.
spk16: Hi, guys. This is Brendan on for your own. Thanks for taking the question. First, quickly on CIDP, can you maybe just tell us how many patients you have randomized into stage B as of today? That's something you're able to share with us. And then just looking back at the ice and past studies, it looks like there may be some slight difference in the rate of relapse in treatment naive versus IVIG experienced patients. So are you able to give us a little bit of a sense of what the breakdown of patients enrolled and in here thus far is looking like, just in terms of background therapy? Thanks.
spk06: Yeah, Brenton, thanks for the question. So we're not public on the number of patients randomized in stage B. I think what we said earlier is that we have exceeded the number you would normally need to successfully come to the 88 events. So that all continues to progress well. In terms of representation of patients with the different backgrounds being newly diagnosed or naive, being on steroids or being on IVIG, I believe the last disclosure we did is a disclosure to go for. I think it was about 40 patients in the process. We think there may be a relative increase in IVIG patients. It was the second half of the trial because we had more U.S. sites getting online and involved, but it's my speculation. From a biology point of view, looking at the mode of action of Graftigimab, I cannot think of a reason why an IVIG patient or a steroid patient would react differently to VivGuard's mode of action. So let's wait for the data and see if we can create or see any correlations between, for example, baseline characteristics of prior therapy and your ability to respond on VivGuard.
spk08: Thanks for the question. Very fair. Thanks, guys.
spk10: Your next question comes from the line of Yatin Soya from Guggenheim Partners. Your line is open.
spk02: Good morning, everyone. Keith, it's been great working with you. Good luck with the future. So just following up on a question on the CIDP, could you provide some detail on the baseline NCATS score that you should or you might be expecting in Stage B? And the reason I ask is because For the first 40 patients in a year, the baseline was around five, which seems to be a little bit higher than previous study. And there seemed to be this inverse correlation between a higher NCAT score and the probability of relapsing. So just trying to get a sense of, you know, how the placebo might perform. Is there a particular NCAT score that you are looking for? And then the second part is, like, what about the maximum number of patients that can be enrolled in stage B? Thanks.
spk06: Thank you, Yatin. So on question one, I need to wait for the answer also until we unblind the study and we look at the data. I have no further information above and beyond what was historically disclosed. It's also very difficult to compare apples with apples between the IV trials and the adhered trial. There is probably a difference in placebo response. But it's premature for us to comment on that. So let's wait until we unblind the data. Is there a limit to how many patients we can enroll in stage B? No, there is no real limit above and beyond the numbers which we highlighted for enrollment on clinicaltrials.gov. And then you can see that we basically stopped screening for the study. We feel that we have ample of patients which now made it into the funnel. So let's see. Let's wait. This is a Q2 event. as far as we can see today, and let's look at the unblinded data together soon. Thank you.
spk08: Very good. Thank you.
spk10: Your next question comes from the line of Myles Minter from William Blair. Your line is open.
spk18: Hi, thanks for taking the question. Just on, you mentioned you stopped screening the study for ADHER. Is your screen-out rate when you do the independent investigator sort of confirmation of the NCATS scores, has that remained consistent with what you presented at AANEM? I think it was about a 50% screen-out rate. Has that remained consistent with the patients that you've been enrolling beyond the 120 to 130 range? Thanks.
spk06: No, Mark. Thanks for the question. My information is that that screening failure rate continues to be consistent. So it is around the 50%. It is also perfectly in line with earlier published studies looking at the accuracy of the CIDP diagnosis. So we feel it's in sync with real world, and we think that there's a constant throughout the study. Thank you for the question. Thanks.
spk10: Your next question comes from the line of Manos Mastarakis from Deutsche Bank. Your line is open.
spk03: Yes, thanks for taking my question. So I wanted to ask, first of all, in terms of the priority review voucher, in the unwanted scenario of an FDA rejection, what happens to the priority voucher? Do you get it back? And maybe a quick follow-up on whether you have any data on duration of the second cycle that is patients going from second to third dose. Thank you.
spk06: Keith, would you mind starting with the second to third dose, the relative distribution we see in the real world, and then I will take on the question on the PRV. Thank you.
spk22: Yeah, so the data that I quoted in the prepared remarks are the first to second dose, and it really shows a nice distribution of about a third, a third, a third. I want to call out that You know, that interval is after the last dose of the first cycle. So when we have about a third of patients that are going nine weeks and some substantially longer than that, just like we saw in the ADAPT trial. We haven't been public with any data on real world on between second and third. But as you might recall from the past, we've referenced that from the ADAPT OLE study, you can typically see that when a patient gets in their individualized cadence, so if they become a nine-week interval between the last dose of one cycle and the first dose of the next one, that cadence typically holds standard. And once they get it dialed in, it just becomes their regularly scheduled dosing. So although we haven't been public with something between second and third, right now I'm not expecting a major change, except for maybe some of those patients that went with shorter interval to see if there isn't an opportunity to stretch a little further.
spk06: Thank you, Keith. And then on the PRV, we continue to understand our options, but technically speaking, guys, we're still in a priority review, and we decided to take a forward-looking approach with the FDA. and try to collaborate as swiftly and expedited as possibly towards the PDUFA date.
spk08: Thank you for the question.
spk10: Your next question comes from a line of Danielle Brill from Raymond James. Your line is open.
spk14: Hey, guys. This is Alex for Danielle. Just another one on CIDP. We had a few questions come our way. Just when did you decide to increase the enrollment And what information, if any, did you have in hand that aided your decision to upsize, or was this just an organic strategic decision? Thanks.
spk06: Well, thank you for this question, Alex. There was not a distinct point in time where we decided to increase enrollment. We decided to just not stop enrollment and continue to enroll. And the reason is that it would be a pity for those patients who all have an opportunity to come on drug not to do that, because not all of them, of course, are going to make it to the end of stage B, but all of these patients would then have the opportunity to roll over to the open-label extension and also contribute to the safety database. Remember, in the background, not only do we need to build efficacy data, but also strong files, strong evidence of safety. So it was a decision not to stop rather than to enlarge the study, if you see what I mean. Thank you.
spk15: Great, thanks.
spk10: Your next question comes from the line of Alison Bretzel from Piper Sandler. Your line is open.
spk21: Hi. Good morning. Thanks for taking my question. Just another one on adhere. It seems like a lot of focus has been placed on the relapse rate in stage B. I guess it's our understanding the endpoint is actually time to relapse rather than the percent of patients relapsing at a given time point. My question is, what is the actual metric we should expect to see from stage B? Is that going to be communicated as a hazard ratio, median time to relapse, something else? And just in that case, would you look to the hazard ratio from PATH as the best comp? And then just related, will you have actual relapse rate data in time for the top line readout, just given that a bunch of patients may not have made it to the end of stage B by the time the 80th event has occurred? Thanks.
spk06: Thank you, Alison. Maybe, Beth, you take on, you know, what we expect in terms of, you know, top-level data disclosures. And then I can take the question on the comparison with the PATH trial. Thank you.
spk07: Yes, of course. So the primary endpoint, as you said, in Stage B is time to relapse. And I think during our communication, we're committed to showing the primary endpoint of Part A, the response rate, the primary endpoint of Part B. Of course, a review of safety, but beyond that, we're not ready to provide too much information on what that top line will look like. I think what you can expect is exactly what you've seen with ADAPT and ADVANCE is that we are transparent in our communication, and we will make sure that we give, you know, a complete picture of what we're seeing with those data to make sure that you understand them well.
spk06: Thank you, Beth, and you're absolutely correct, Alison. The primary endpoint for stage B is time to relapse. It's a typical endpoint in cancer trials. So indeed, hazard ratio would be a proper way, for example, to look at these data. We're still thinking about how we're going to present the top-line data, but you should be able to draw a fair comparison with the PAT trial in the way we present the data, for example, if you then were to take a specific time point. So we're still mulling it over. But in terms of separation between active and placebo, PATH continues to be, I think, the proper benchmark to match or to beat.
spk08: Thank you.
spk10: Your next question comes from a line of Matthew Harrison from Morgan Stanley. Your line is open.
spk12: Great. Thanks for taking the question. I've asked the flavor of this question before, but I wanted to ask it again in a different way, which is, you know, we're expecting to get some phase two studies from J&J this year, especially some of the larger indications. How should we just think about that impacting your view on what you may or may not be willing to invest in the pipeline and sort of how ready you are to potentially pivot quickly to think about investing in maybe a large phase three study for some of these broad indications? Thanks very much.
spk06: Thanks, Matthew. Thanks for joining us today. I think overall it's exciting to see some other players in the FCRN class venture into other indications than the algenics indications because so far we saw mainly imitation and not too much creativity. So good to see new indications coming on deck where we feel there's a different proposition from a biology rationale point of view And we're actually very happy to see other people deal with these indications. So we have our own list of preferred indications, Matthew. You know how we select them based on biology rationale, technical feasibility, and then medical lead and commercial opportunity. We're not going to deviate from our own list, which starts from the science and the biology. And we're, of course, keenly looking at other indications, you know, which are turning data cards. Overall, I believe they will just show that the F7 opportunity is a real big opportunity, warranting multiple players active in the space. Thank you for your question.
spk10: Your next question comes from a line of Alex Thompson from Stifel. Your line is open.
spk09: Hey, great. Thanks for taking my question. So I guess, Keith, maybe on your commentary as it relates to real-world observations of cycles on DIPGARD, how should we think about net price per patient in 2023? Do you expect that to stay pretty constant as to what you've been guiding in 2022, or how is that going to look moving forward, at least for the IV version? Thanks.
spk05: It's Carl here, so maybe I'll take that question. So we guided at the beginning of last year a typical net price of $225,000, And if we look at all the data points, the average weight per patient, the number of cycles, the gross to net, the value-based agreements, taking all of those things into account, we think that the $225,000 per patient still stands for 2023. Great. Thanks.
spk08: Thank you for your question.
spk10: Your next question comes from the line of Will Olds from Evercore. Your line is open.
spk19: Hey guys, congrats on the great quarter. I'm really curious about the test indication. What is the doctor's positioning and what do you think about the actually registrational trial design?
spk06: I could not understand the question. Did anyone else understand it?
spk07: Yeah, it's about thyroid eye disease and the positioning and the potential trial design.
spk06: Okay. So the only thing we have disclosed at the JPMorgan conference is the choice for this indication. This is for once an indication where we're not leading. I mean, we will not be first to market in that indication. So I think we have been speaking mainly about the biology rationale, but we reserve the right to answer your question until we will disclose the trial design, and then we can expand on competitive positioning. But it's a bit premature for us to comment on it right now. So bear with us. That will come later in the year. Thank you.
spk10: Your next question comes from a line of Joel Beattie from Baird. Your line is open.
spk08: Great. Thanks for taking the question.
spk22: For the current FDA review of sub-Q F-cortisomide, is there potential to add seronegative patients to both the sub-Q and IV labels?
spk06: Now, thank you for this question. In the bridging study, remember, this was a head-to-head comparison, a non-inferiority trial between the IV version of VivGuard and the SubQ product presentation of VivGuard. We basically included, again, both seropositive patients and seronegative patients. And again, VivGuard has shown that it works equally well across the board in a non-inferior manner between SubQ and IV. Together with some other data, which we collected from the real world and the rollover from the ADAPT trial in the OLE, we have been bringing all this data together and we resubmitted them to the FDA, making a case for the synonegatives. But again, this is a review issue. This is not in our hands only. We submitted the data and we look forward to the interaction with the FDA on this topic. Thanks for the question.
spk10: Your next question comes from the line of Douglas Sale from H.C. Wainwright. Your line is open.
spk13: Hi, good morning. Thanks for taking the questions. And first, send my regards to Keith and congratulations. It's been great getting to know him. Maybe a first question to Keith. You mentioned sort of insurance resets and just curious, you know, how that might be, you know, how that's playing out in the real world just given the timing of cycles and redosing and just assuring sort of continuity of treatment?
spk22: Yeah, no, first of all, thanks for the comments, Douglas, and also the question. But the bottom line is, as we go through the insurance re-verification, almost all of our policies, we said 90% covered lives, with 80% of those being favorable. Most of those policies, almost all, are approved for anywhere from six to 12 months. So we just go through the re-verification process. I can tell you that as Carl said about our net that we projected even prior to launch still stands true and goes into 2023. I think it puts us in a very credible position with payers because what we talked about before launch is actually coming to fruition. And so as we go through the recertification, We're not seeing challenges. We're just seeing a little bit more time-consuming.
spk13: Okay, great. That's helpful. And then just as a follow-up, just curious, we're going to start to get data from 1.1.7 this year. I'm just curious, should we think about that development program once we get this sort of initial proof-of-mechanism data sort of expanding as quickly as what we saw happen with F-Fertigimod or will that development program sort of take place at a sort of more measured pace and organically? Thank you.
spk06: Thanks for the 117 question. Look, 117 has its own program and its own plan behind it. We do believe it's a pipeline and a product if you look at the biology, which is so universal across multiple indications. We are already public on NMN, also on delayed graft function. and also on dermatomyositis, and there are more indications to come. You know, whether 117 ever will become as big as abgartigamot is a different question, but we believe, as you know, there is a significant pipeline of indications where the biology of 117 is really in play. And what is similar to abgartigamot is that we invest a lot in the translational biology, showing the right to succeed with a C2 blocker in these indications. For example, the work we presented on multiple occasions for MMN, but now also at the JPMorgan conference, that passive transfer model, think of that type of quality translational biology work, which is taking place in all indications we're addressing. So that is definitely a similarity between 117 and Avogadigamot. Thank you for the question.
spk08: Hey, just as a quick... Yeah, please.
spk13: When should we get more indications beyond this first theory? Do you have a sense of that?
spk06: But leave that to the future. So there are definitely more indications. Guys, if we continue at this pace, soon we will already be in 20 indications. It also needs to be, you know, executionable. So let's continue to roll out, you know, indications in a thoughtful fashion and in a fashion that we can execute, okay?
spk13: Okay, great. Thank you so much.
spk06: Thank you.
spk10: Your next question comes from the line of James Gordon from J.P. Morgan. Your line is open.
spk04: Hello, James Gordon from J.P. Morgan. Thanks for taking my question. A question about CRDP. I guess the question was, is good data, I believe, just showing what the ice trust shows in stage A and past shows in stage B? And if you do that, is that enough, do you think, to be a blockbuster indication that we've got in CRDP? And the other part, just also in CRDP, in terms of what a CRDP launch could look like, If you do show similar data to what IG has shown in CIDP, do you think the Vivgar IV MG launch is a good proxy for what CIDP is going to launch like in 2024? How are you thinking? What are the considerations, please?
spk06: Thank you, James. And it's a bit premature to talk about how a launch would look like in absence of data, but I believe it will feed in a minute to share some conceptual thinking on how a launch could be different between CIDP and MG. I just repeat what I said before. also during our analyst breakfast at the JPMorgan conference, we believe that we are well equipped to compete if we come out with a, roughly speaking, similar response in stage A ASIs and similar effect size to Pat in stage B. We feel we will be equipped to effectively compete in such a position. The launch, of course, in such a well-invented market could look quite different. Right, Keith?
spk22: Yeah, I mean, certainly, James, I think the first thing we need to do is to see the data, to see how we stack up and, you know, not only efficacy, but, you know, as we believe from the profile of the product, we do think we'll probably have an edge on safety and convenience. With all that being said, comparing it to MG is probably not a likely scenario, and that is because the IVIG companies, they can't promote IVIG in MG. It's off-label. However, CIDP is their single largest indication. And this is a satisfied market. I think that there is room for improvement and the possibility to disrupt if the data allows. But we're going into a market where physicians and patients are satisfied with IVIG. So I would not use MG as a proxy to the CIDP launch.
spk08: But let's wait and see those data.
spk10: Your next question comes from a line of June Lee from Truist. Your line is open.
spk11: Hey, thanks for taking our questions. Keith has done a phenomenal job of DivGuard launch and conventionalism is that if it ain't broke, you don't fix it. But I totally understand Keith has personal reasons. Could you elaborate a bit more on what Ms. Karen Matthew brings to the table? And what aspects of our expertise do you think is particularly well-suited to further drive VidGuard uptake? I'm sure you had many qualified candidates to choose from.
spk06: Thank you. Thank you. Thank you for joining us on the call. As you correctly call out, this was a planned transition, right? So Keith is retiring. His aspiration is to spend more time with family and serving on boards, including continuing to be an advisor to our boards. as a participant in our commercial committee. I think with Karen, we have the right person at the right time for Agenix. She brings global operational experience. She has successfully led launches in the neuroinformation space. Specifically, I refer to the Ocrevus launch, where she accelerated an already successful launch. And then I think she has a proven practical of building innovative, global, nimble teams exactly the type of teams which we need if we want to continue to be successful on the commercial side. We also believe that Cadence is going to be a great cultural fit. I think the culture of the company is strong. And not only did we hire a great leader from a technical nasty point of view, we also think we have an excellent cultural fit. So you're right. I mean, there was choice. And I'm extremely excited about Cadence joining us on Marsupil teams.
spk08: Thanks for the question.
spk10: Your next question comes from the line of Simon Baker from Redbird. Your line is open.
spk17: Hi, this is Kesa Dean asking questions on behalf of Simon Baker. Thanks for taking my questions. Two questions, if I may. So the question one is, can you discuss the IP position for Vanguard beyond the March 2036 composition patent expiry, particularly on the subcutaneous formulations? And the question two is, can you give us an update on the European rollout of Vanguard? In which countries do you expect to begin selling in 2023? Thank you.
spk06: Could you repeat question one on patent life, please? I couldn't hear it. I got the second one.
spk17: Yeah. So the question one is, can you discuss the IP position for Vanguard beyond March 2036, compensation patent expiry? particularly on the subcutaneous formulation.
spk06: Oh, okay. I got it. Keith, I will hand over the question to you on what we expect in the context of European rollout for VidGuard this year. From a patent protection point of view, what I would like to leave you with conceptually is that, of course, there are multiple layers of IP protection protecting VidGuard. Of course, we have the specific mutations which we used and in-licensed actually from UT Southwestern. Then indeed we have the composition of matter claims which run roughly speaking to 2035. But then we have additional composition of matter and formulation patterns which we continue to file on the back of clinical data. So we have not been public or explicit on the final IP horizon for the molecule. but there is significant IP life in the making above and beyond decomposition of leather claims you just referred to. Keith, do you want to comment on the European rollout, please?
spk22: Yeah, happy to do so, Tim. So as you know, we are currently in the Amnog process in Germany, and VivGuard is available in Germany, and we're off to a successful launch there. But we will continue to go through that reimbursement process to have final and official approval in quarter three, late quarter three of this year. Also in France, we're in an AP2 program, which makes VivGuard available to patients. It's not quite as broad as the label at this point, but it does give access to patients that need it while we continue to go through the reimbursement process in France. We've submitted dossiers in numerous countries across Europe. including that of Italy. We've been working with the UK and Spain. I want to call out that we have a broad pre-approval access program so that we can begin to serve patients. But basically, this is all going to be based on the timeline of gaining approved reimbursement on a country-by-country basis.
spk10: And your next question comes from a line of Charles Pittman from Barclays. Your line is open.
spk01: Hi, thank you very much for taking my question. Apologies if these are any repeats. But just first on OPEX, could you give us an idea of how this is going to progress over 2023? R&D obviously came in a bit light at 4Q. I'm just thinking in terms of you've got a number of pivotal trials set to read out ahead of the earlier stage trials starting in 4Q23 and kind of how you're controlling costs. And then secondly, we have top line data around the corner for pemphigus vulgaris and bullous pemphigoid. I was wondering if you could just update us on how these trials are proceeding and maybe particularly what you're hoping to demonstrate from the trial readouts. Thanks.
spk06: If you would take the OPEX question, then I will take the pemphigus question, I think. Thank you.
spk05: Thank you. And thank you, Charles, for the questions. I think if we don't give guidance, of course, but just at the high level, conceptually, we can talk about the OPEX numbers for 2023. If you look at Q4, you will see that your R&D spend is roughly $150 million. It is lighter than Q3, but Q3, of course, included $100 million for the PRV. Going forward, I would expect that the Q4 number to increase or to be flat or to increase by inflation for the rest of the year by a quarter. For SG&A, if you look at the Q4 number of around 140 million, a little bit below that, if you think about what's going to happen in 23, we're going to have a second launch in the U.S. for sub-Q. There will not be material headcount increases with that, but there will be marketing spent for the second campaign. And, of course, Steve mentioned about the European launches. And both investments in both countries are stage-scale. We don't put commercial colleagues in the market until such time that we do have pricing and reimbursement in place. So the point is that the SG&A number will increase quarter by quarter throughout 2023.
spk06: Thank you. Thank you, Carl. And I'm very happy with the 10 figures question. 10 figures is a significant unmet medical need. There is hardly any treatment option out there for these patients. And the trial actually has been going very well. This is a global phase three registration trial on the back of very strong phase two data. And I would say that the who's who in autoimmune blistering disease is participating in this trial. The trial enrolled extremely well. And from an endpoint point of view, the primary endpoint is complete remission on minimum dose of corticosteroids. So these patients really need stopping formation of new lesions, the closing of the existing lesions, and then the tapering of steroids as fast as possible. So CR on minimum corticosteroid dose is the primary endpoint. In the secondaries, we will be looking at CR off therapy. We will be looking at quality of life and safety and the cumulative use of corticosteroids. These are the key secondary endpoints. So this is a data point to be expected for the second half of this year.
spk08: Thank you for the question.
spk10: There are no further questions at this time. This does conclude today's conference call. Thank you for your participation. You may now disconnect.
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