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spk15: Good morning. My name is Rocco, and I will be your conference operator today. At this time, I would like to welcome everyone to the conference 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 that time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, please press the star key followed by the number two. We do ask that you please limit yourself to one question and a single follow-up. You may re-queue if you have further questions. Please also note today's event is being recorded. Thank you. I would now like to introduce Beth DelGiaco, Vice President of Investor Relations. You may begin your conference.
spk13: Thank you, Rocco. A press release was issued earlier today with our third quarter 2020 financial results and business updates. 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 timelines, 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, Keith Woods, Chief Operating Officer, and Erica Staldy, Chief Financial Officer. I will now turn the call over to Tim.
spk17: Thank you, Beth, and welcome, everyone. We appreciate you joining the call today. This has been an exceptional year for Argenix. We have achieved several significant milestones, most notably the positive readout of our face-to-death trial and also in an unprecedented environment. While we are still managing the impact of COVID-19 on our lives and business, I'm continually impressed by the team we have built and their ability to definitely maneuver around the challenges which we've been presented with. We are in a very strong position as we close out 2020 and look forward to our first commercial launch next year. We know that FCNN antagonists as a new class of medicines have tremendous potential to transform the treatment of serious autoimmune diseases and we are closer than ever to reaching people living with our first indication, generalized myasthenia gravis. We are excited to discuss the continued progress we have made in advancing our first and potentially best-in-class FC fragment. As we focus on maximizing our leadership position with FGATIGIMOD, we remain equally committed to investing in R&D and enriching our deep pipeline of differentiated early and late-stage assets to generate long-term value. You'll find today's agenda on slide number three. I will share details on the progress we've made with Avocatigemot, specifically the new data we presented from ADAPT, updates on our ITP, PV, and CIDP trials, and our fifth indication. I will then move to the rest of our pipeline, including Cusatuzumab and Regenix 117. It will provide more context on our commercial readiness activities, followed by a financial update from Eric, before we take your questions. Let me begin with Abkhatijamot. In May, we reported that a global phase three ADAPT trial met its primary endpoint, which was a responder analysis in acetylcholine receptor antibody positive patients during the first treatment cycle. 67.7%. of abgadigemot-treated patients compared to 29.7% of placebo patients achieved a greater than two-point improvement on the MG-ADL score for at least four consecutive weeks. Similar results were seen on the QMG score. 84.1% of responders had an onset of response in the first two weeks. Slide five shows that 40% of all patients or about two-thirds of responders achieved an MJADL of zero or one, classified as minimal symptom expression. And a substantial proportion of responders saw impressive durability, with almost 60% of patients experiencing a benefit of eight weeks or longer, and one-third of patients experiencing a benefit of 12 weeks or longer. Additional data from ADAPT were presented earlier this month, at the MGFA Scientific Session by our principal investigator, Dr. James Howard. These data confirmed the rapid and clinically meaningful responses to F-gartigimab that we saw from the top line, but also showed additional analyses on the magnitude and repeatability of response. On slide six, to assess the magnitude of response, We looked at the MG, ADL, and QMG score reductions at week four or one week after the last infusion. As you can look at increasing thresholds of improvement, the treatment arm continues to show benefit while the placebo arm goes to zero. We were particularly pleased to see that 50% or more of patients achieved at least a five-point improvement on the MG-ADL and at least a six-point improvement on the QMG. A third of patients achieved a QMG improvement of at least nine points. These responses and the proportion of patients achieving minimum symptom expression are unprecedented and capture the most important component of this trial. These are not just scores. These are patients who are feeling better. and a substantial number are virtually symptom-free. With regards to repeatability, if you look across cycles one and two, almost 80% of abgartigem of patients were considered MgADL responders. This included 36.8% of patients who were not MgADL responders in cycle one, but were in cycle two. We saw that the MgADL score reduction was consistent in both cycles with a mean change from baseline of 4.6 in cycle one and 5.1 in cycle two. We also showed some additional analyses on the acetylcholine receptor antibody-negative patients. You'll recall we saw a high placebo response in these patients based on the MGA-ADL score by including the more objective measure QMG in the analysis. we started to see more separation from treated and placebo patients. Put simply, the data show that if patients responded to Avgarditumab, they did so quickly and with a significant depth and duration of improvement. This is supported by a safety profile comparable to placebo with no reduction in serum albumin. These data further demonstrate how Avgarditumab is uniquely differentiated and has the potential to be the best-in-class FCRM antagonist. On slide nine, you can see on our pipeline that next steps for Afghan teacher model in GMG are on track and we are pleased to confirm that we plan to file the BLA by the end of this year. In addition, our interaction with the FDA regarding the subcutaneous bridging strategy in MG is set to occur before year end, and we will communicate on the path forward once we have regulatory feedback. We have heard from patients, physicians, and payers that having both an IV and a subcutaneous formulation for Afgafigimab will be a significant competitive advantage in NG and other indications. Our exclusive access to the HeloSign technology for the FCRN targets enables our subcutaneous administration to be a single, fast injection, which we also believe is optimal for patient comfort and convenience. As we talk through our other indications and the specifics of those trials, you can see that we are actively prioritizing sub-Q development to accommodate patient preferences and to adjust to this new normal where patients may not always have easy access to all types of care. So this brings me to the evolving strategy of our ITP program on slide number 10. We discussed the strategy on our last update call to address the enrollment delays we've been facing due to COVID-19. We consolidated the original three registration studies into two. One is the ongoing IV only advanced trial, and the other is the subcutaneous only advanced sub-Q trial, which is on track to begin by the end of this year. This program realignment shows our ability to adapt and be nimble as an organization, and I'm pleased with the direction in which we are headed. Ultimately, we hope this change will expedite the path for FGAT-TGMO in ITP. Moving on to CITP on slide 11. The Phase II adhered trial of subcutaneous FGAT-TGMO is enrolling well, and the go-no-go decision to expand the trial up to 130 patients will occur after the first 30 patients are treated in part A. As stated in today's specialties, we now expect that decision to occur in the first half of 2021 with a specific timing dependent on the impact of COVID-19 delays. Based on initial interactions with the FDA, we believe the expanded trial could be sufficient for registration in CIDB. We will also be evaluating sub-Q F-graftigimab in our Phase III ADDRESS trial in Pemphigus, which is on track to start soon. I'd like to take a moment to describe this trial in more detail. As we did with developing our Phase III trial in MG, we are working closely with patients and physicians to design the ADDRESS trial as well. By paneling with key stakeholders, we can more fully understand the remaining unmet needs for pemphigus patients and identify how FGAT-TGEMOT might best offer a solution to fit into the existing treatment paradigm. Pemphigus is a skin barrier disease, so speed of onset is a crucial aspect of potential therapy. Patients want to see healing of lesions and achievement of disease control and clinical remission as quickly as possible. We also learned that patients prioritized the ability to taper off steroids to manage the side effects. Slide 12, the Phase III Address Trial will be a randomized, double-blinded, placebo-controlled study where the objective is to assess efficacy, safety, and tolerability in up to 150 newly diagnosed or relapsing patients with moderate to severe pathologies. The trial will include both pentacus vulgaris, or PV, and pentacus volatilis, or PF, though the PF population will be kept in a similar manner to the acetylcholine receptor negative population in V and G study. Patients will be randomized to receive either sub-Q F-gatigemot or placebo for 30 weeks. Patients will start on concomitant steroids based on what we determine to be the optimized dosing regimen from the phase two study. The primary endpoint will assess the proportion of patients who achieve complete remission on a minimal steroid dose at 30 weeks. Before I move to the rest of our pipeline, I'd like to briefly mention the fifth indication for abratitumab, which will be discussed in more detail during an investor event in the first half of 2021. So this program is modulate. Everything is on track and we're moving forward. We're just not sharing yet what this indication exactly is at this time. Given the evolving competitive landscape in the FCRM class, we have decided that it would be most prudent to provide full context around this new indication closer to the phase two trial initiation mid next year. Our team is on track that all phase two preparation work and they're working hard to design a possible trial as we've done with all indications to date. While we wait to share details until next year, we can say that we are very excited by the opportunity this indication presents to rare disease patients. It meets the criteria we use for our indication selection strategy. There is a clear biology rationale around the role of autoantibodies and the defined clinical and regulatory path forward. It also fits greatly into our emerging franchise structure with an attractive commercial opportunity across more than one of our potential therapeutic franchises. In this way, it aligns with our broader strategy to leverage our growing commercial capabilities across multiple indications. We continue to have the broadest development program among FCLN antagonists and are committed to roll out new indications at the pace of at least one per year. Going forward, we will take an approach to talk about each indication just before the phase two initiation, so not to share information before it's necessary. Now I want to choose a tissue map, Endergenics 117. On slide 13, We will be sharing top-line data from the Phase II Culminate trial in early 2021 as promised. Based on an early look from Culminate, we have selected 20 mg per kg as the go-forward dose and will be prioritizing a combination approach of Cusapusumab with the emerging standard of care Venetoclax. The Phase I B-Elevate trial, evaluating double and triple combinations of Cusa, Aza, and Ven, continues to enroll following a pause due to COVID-19. Slide 14. We started the Phase I Healthy Volunteer Study of ARGENIX 117, targeting C2. Data from this study are expected mid-2021. The Phase I trial will assess pre-KPD, pre-C2 levels, and bioavailability of both IV and sub-Q formulations. We will also use the phase one study to identify a phase two dose. That's with our approach to agratizumab. We plan to launch multiple phase two proof of concept trials on the use of strong phase one data. We're looking at severe autoimmune diseases and have already selected multifocal motor neuropathy, or MMM, as an initial indication. We also continue to look at potential kidney indications. Finally, as part of our Argenix 2021 vision, we aim to be a global integrated immunology company, prioritizing both our commercial efforts as well as our R&D engine through our immunology innovation program. Argenix 118 is the lead optimization stages as we determine how best to address the groundbreaking biology on the role of Charcoal-Leyden crystals in severe airway inflammation out of the lab of Bartlett and Ray. We are also on track to finalize ARGENIX 119 this year and will likely be communicating more on this pipeline candidate early next year. As we've said many times about our IIP, this is a program about co-creation which is at the heart of everything we do at ARGENIX. We recognize that partnering with leading disease biologists will allow us to unlock in our key commercial franchises and bring forward the most innovative therapies to patients. Continued investment in our antibody engineering capabilities is a key component of our role in IIP relationships. We recently announced two new technology partnerships with Shugai and the Clayton Foundation, underscoring our commitment to the IIP by enhancing our capabilities to build the best antibodies possible and broaden the range of targets that we may address. We also announced that we will be expanding the scope of our collaboration with Herozyme for access to the enhanced drug delivery technology. Under the expansion, we gained three additional exclusive targets upon nomination, which brings the total to six potential targets. We have already exercised access for two targets, FCRM and C2. We believe that having access to the enhanced technology for current and future product candidates will allow us to reach more patients with our therapeutic antibodies. With that, I'd like to turn the call over to Keith to discuss our commercial preparations in more detail. Keith?
spk10: Thank you, Tim. If we could go to slide 16, please. It has indeed been a very exciting year for Orogenics. I'm pleased to report that our commercial readiness activities remain on track as we prepare to file our first BLA by the end of the year and reach patients in 2021. An important part of our ongoing rolling BLA submission is our safety database, which we accrue from our ongoing ADAPT open label extension. The retention rate in the open label extension has been impressive, and we expect to be able to share data from this study at future medical meetings. We also are on track to file the JMAA in Japan in the first half of 2021 and prepare for a launch there in 2022. We continue to progress our launch strategies in Europe and will file with the EMA shortly after filing in Japan. We expect to be able to share with you more details about our European strategy early next year. We have committed to our first three priority regions for the commercial launch of FGAR-Tigamod. But we also recognize the importance of making FGAR-Tigamod available globally, and we are working through our strategy in the rest of the world, likely relying on a partner for some regions. Of course, the use of additional phase four clinical trials in many regions of the world, as well as an expanded access program, is a key factor in our patient-centric values. In terms of commercial preparation, we are building an outstanding team in our three key regions. hiring leaders with significant launch experience in rare disease and even MG specifically. There is no doubt the right team to launch FGAR Tigamod has been given their deep knowledge in the neurology space, their excitement around the potential of FGAR Tigamod, and their commitment to patients. We continue to grow our field team, including medical research liaisons, thought leader liaisons, and key account directors on the payer side, and we expect to start hiring our planned 70-person U.S. sales force by the end of this year. We recently launched our disease awareness campaign, which we know will be a crucial component to our commercial success, particularly around engaging physician customers and building awareness of this new mechanism of action. We want to ensure that our key audiences understand FCRN as a target and the role that the autoantibodies play in MG. We continue to gain important insights from patients, from advocacy groups, and physicians. We have been pleased and even surprised by our ability to have very productive conversations virtually, whether through advisory boards or events such as the MGFA or AANEM. This will be a good practice for the team as we do expect to launch in at least a partially virtual environment next year. Furthermore, While we're still in the early phase of engaging with U.S. payers, feedback from both regional and national payers has been positive. The potential for individualized dosing offered by efcar-tigamod is attractive, and it offers the opportunity for patients to only receive treatment when they really need it. We continue to build out and scale our global supply chain to ensure continuity of drug supply when we launch in the U.S., Japan, and Europe. As you know, we have a long-established alliance with Lonza for our manufacturing with facilities in both the UK and Singapore and the potential to expand even further as we launch into additional geographies or indications. We partnered with Vetter for our fill and finish of our drug product and now with Cardinal for our third-party logistics here in the US. We trust that our partnerships with these three well-established players is the right decision for such a key component of our launch. Now, before I hand the call over to Eric, if we take a look at slide 17, I want to quickly mention an important project that we've been working on to engage with MG patients and build awareness of this devastating disease. Next month, we're excited to premiere A Mystery to Me, a documentary film about myasthenia gravis. We partnered with film producer Swarovski to capture the hidden toll that MG can take on those who live with it every day. We hope that by watching this docuseries, we can give a voice to MG patients and encourage broader empathy for people who not only suffer from MG, but from any rare disease that can leave people feeling isolated and misunderstood. And with that, I'll turn the call over to Eric.
spk16: Thank you, Keith. Slide 18 covers our third quarter 2020 operating results, which are also detailed in today's press release and regulatory findings. Total operating income for the nine months and this September 30, 2020 was 42.6 million euros, a decrease of 18.6 million euros from the same period in 2019. Due to a milestone payment we received last year under the AbbVie collaboration agreement and partially offset by the revenue recognition of the transaction price related to the Janssen collaboration, and also an increase in other income driven by higher payroll tax rebates. R&D expenses for the nine months ended September 30, 2020 were 246.3 million euros compared to 122.8 million euros for the same period in 2019. Selling, general and administrative expenses were 100.4 million euros for the nine months of year, compared to €41.7 million for the same period in 2019. The increases in R&D and SG&A expenditures over the prior year have been driven by the progress made within our late-stage pipeline, including higher clinical trial costs and manufacturing expenses, the recruitment of additional employees to support ongoing activities, and higher consulting and personal expenses. We expect operating expenses to continue to increase this year as we further advance our pipeline and prepare for future commercialization. For the nine months ended September 30, 2020, financial expenses, which mainly relates to interest received and changed in fair value of current financial assets, amounted to 1.7 million euros compared to a financial income of 10.8 million euros for the same period in 2019. Exchange losses totaled 55.9 million euros for the nine months ended September 30, 2020 compared to an exchange gain of 26.9 million euros for the same period in 2019. The total net loss for the nine months ended September 30, 2020 was 205.6 million euros compared to a net loss of 45.1 million euros and an operating loss of 54.5 million euros for the same period in 2019. We ended the first nine months of 2020 with 1.8 billion euros in cash, cash equivalents and current financial assets compared to 1.3 billion euros on December 31, 2019. The increase was principally due to the closing of a global offering last June including a US offering and a European private placement, resulting in the receipt of 730.7 billion euros of net proceeds. I will now hand back the call to Tim.
spk17: Thanks, Eric. Please turn to slide 19. Before we take your questions, I want to take this opportunity to offer my gratitude to our exceptional team, whose hard work and unwavering devotion to patients continue to fuel us towards our first commercial launch. We see the broad potential for FCLM antagonists to be a transformative option for patients suffering from serious autoimmune diseases. With our positive phase three ADAPT data in hand, our growing team and commercial infrastructure, a deep pipeline of differentiated early and late stage programs, and our strong balance sheet to drive our company forward, I believe we are well positioned to realize our Argenix 2021 vision and to generate long-term value for our shareholders. Operator, you may now open the call for questions. Thank you.
spk15: Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your touch-tone phone. If you're using a speaker phone, we ask that you please pick up your handset before pressing the keys. To withdraw your question, please press stars and two. We do ask that you please limit yourself to one question and a single follow-up. Today's first question comes from Yatin Suneja with Guggenheim. Please go ahead.
spk03: Hey, guys. Thank you for taking my question and congrats on all the progress. Can you maybe just talk conceptually about the pricing? I mean, it seems like there are certain indication where you might need a little bit more chronic treatment or dosing and certain indication where you can get away with intermittent chronic dosing. So if you can conceptually talk about that, so that's the first question. The second question is, could you maybe remind us what the infusion time is for the halazine sub-Q and what volume are you targeting? Thank you.
spk17: Thank you, Yatin. So your second question is very simple. It's a sub-Q injection of an infusion, which is a very important difference. This is a 30-second sub-Q injection with a volume of just above 5 ml. Keith, maybe you would like to take the first question, the conceptual question on pricing across different indications?
spk10: Yeah, happy to, Tim. So, Yatin, last call we actually discussed the pricing and how we were thinking around MG. And we actually set some kind of some goalposts and said, you know, looking at chronic IVIG as the floor given our strong efficacy, safety, and convenience. And remember, we said chronic IVIG on average is about $146,000 per year to treat an MG patient, and that's just the average. So your more frequently treated patients, it goes up. We've also talked about the other bookend being Solaris, but we've also said that we plan on pricing, grounding our pricing and value, and do not expect to be up there towards Solaris. So, you know, we have the opportunity to price based on the data that Tim shared with you in the call today, which right now is the most impressive data that's been released in a Phase III study. So we do have this opportunity to bring value to patients. As far as the individualized dosing schedule, compared with some additional indications that might be more chronic, I just want to remind you that in ITP, for example, although we are using a more chronic dosing schedule, you also know that physicians that treat ITP, after they get their patient managed, the main thing that they want to do is slowly trim them off of medication. We also know that pemphigus, for example, we're able to treat patients and get them into complete remission, and once we do, you'll see where that will not be treated chronically, but yet the next flare. So we've done a lot of homework on this, and we've had the opportunity to study a great deal of our data from the ADAPT study, and we now feel very comfortable in moving forward with our pricing strategy that will tie into MG, but also think about, you know, second, third, fourth, fifth, and even more indications.
spk15: Thank you. Our next question today comes from Jeroen Warber with Cowen. Please go ahead.
spk18: Yeah, hi. Thanks for taking my question. So I have just a couple about the trial design, maybe, Tim. Number one, for MG, and I'm not sure what you can comment, the subcutaneous bridging study, you know, historically within Haines, FDA has wanted to see efficacy data. If you look at Rituxan, you look at Darzit, Herceptin, and Darzilex, but Those indications don't have a biomarker like IgG. So how does that factor in and can you use IgG as sort of a primary surrogate and then maybe like an eight-week, you know, clinical endpoint? And then secondly, for PV, I see that, you know, the trial design makes a lot of sense. Another trial design that some KOs were talking about is maybe doing something concomitantly with Rituxan. It's sort of an acute and then chronic. Any thoughts? Is that something you might want to do down the line? Thank you.
spk17: Thank you, Jeroen, and thank you for being with us on the call today. So concerning the bridging strategy, I think you're spot on. Strategy means that you're playing your strengths, and we believe that Ascarpigamot is a unique drug when it comes to the literally linear correlation between its PD effects i.e., the reduction in IgGs and clinical benefits. I think the ADAPT study has again clearly demonstrated that, and it's with these data in hand that actually we have prepared the meeting request with the FDA. So there is a science-based case to be made, but let's wait until we have the meeting behind us. I don't want to preempt that meeting, and we will certainly communicate about the outcome of the meeting as soon as we have the written minutes. On your pentagus study design, you're right. I think there are several entry points into the space of pentagus. Actually, we decided to, after careful work with patients and physicians, to really leverage the fast onset of action and the ability to reduce steroids as fast as possible in our first study. So I think this placebo-controlled trial in the background of suboptimal prednisone or corticosteroid dosing is actually going to replicate, hopefully, the success of the Phase II study. And that's a very compelling proposition to get into that space. Ultimately, how F-captigamot is going to coexist with rituximab is, of course, topic of further studies if and when we prove success with the first study.
spk15: And our next question today comes from Tezeen Ahmad with Bank of America. Please go ahead.
spk01: Hi, good morning. Thanks for taking my question. Hopefully you can hear me clearly. Hi, Tim. I just wanted to ask you, as we await the culminate top line data in early 2021, can you give us an idea of what type of information we should expect at this first look at the study? and what data we should consider to be encouraging for the program. Thanks.
spk17: Thank you, Tazine. So obviously in newly diagnosed EML patients unfit for chemotherapy, what you would look to see in these data would of course be the number of responses and the quality of the responses on the one hand, and of course then the duration of these responses. We think also the safety information is going to be very important because we see the future for newly diagnosed M50ML patients to be combination therapy. So the combinability of your drug with venetoflax with or without Vydeza is going to be very important also from a tox point of view. And then also expect data which will clearly explain why the dose is what we chose it to be. So, the 20 milligram versus the 10 milligram, 50 gram data.
spk15: Thank you. Our next question today comes from Derek Archula with Steeple. Please go ahead.
spk05: Great. Hey, good morning, and thanks for taking my questions. So, Tim, just two on CIDP. Maybe first, just wondering if you could provide any color on some of the challenges you are or were facing with the CIDP study enrollment and what gets you confident that you'll be able to put out the results in the first half of 2021. And then second, I'd love to get your insights on the type of responses that would make this a go decision for And if there are any good reference points in terms of maybe IVIG responses that could kind of inform us, you know, here on the investor side. Thanks.
spk17: Thank you, Derek, for this excellent question. So, CNDP, you know, it was a very thoughtful trial design in close partnership with physicians and patients. So we see a study which is being very well received by the community and a very high level of motivation of both physicians and patients to participate. I think the slowing down factor here is, of course, the COVID-19 pandemic. More specifically, the work on sites to initiate sites, open sites, and get patients to sites. So I think the study has really picked up momentum after the first wave of the pandemic cooled off. And now I think the art will be to navigate through what clearly is the second wave going through Europe and soon probably the US. So it's COVID-related, and to our delight, I think the study has lots of traction with the community, and we see plenty of patient excitement around innovation entering their space, a space which is actually staffed for innovation. After 30 days IVIG, people really want to see something else and something better. On your second question, response. We have not been public on the definition of the go-no-go decision points, but clearly I can call out, for example, the response rate which was seen in the only blinded randomized placebo-controlled IVIG study, that's the ICE trial, where we saw a 53% response for IVIG versus a 21% response for placebo. So I think that's an interesting point of reference.
spk15: And our next question today comes from David Nierengarten with Wedbush Securities. Please go ahead.
spk09: Hey, thanks for taking the question. Maybe looking a little bit farther in the future, you know, we're likely to see opomerase from electron get use in myasthenia gravis at a bit lower price point than saliris and, of course, a much less frequent infusion. How are you thinking about the competitive dynamics between your both IV product and your subcutaneous product relative to a less frequent C5 inhibitor? And, you know, in particular, you have both the competitive dynamics and the potential for, you know, out-of-pocket costs affecting the decision between a subcutaneous format and the IV format from a competitor. Thank you.
spk17: Thank you, David. Maybe Keith, you would like to take this question?
spk10: Yeah, happy to. David, thank you for the questions and both very good questions. Ultimately, we are bringing forth both formulations, IV and sub-Q, into hopefully all indications, but certainly into MG up front. Remember, we went forward with IV because of a speed-to-market strategy. And that strategy is paying off. As we said, we'll be able to launch in 2021. But as we bring the bridge forward, we know that weekly dosing, when you can have a response rate that, as Tim shared in the prepared remarks, that was up to almost 80% of patients that responded between cycle one and cycle two, and you have a safety profile of which we've had, when we talk to patients and we ask them to rank what is important to them, The number one thing is efficacy and relieving of symptoms, and number two is safety. Actually, they recommend ranked their route of administration towards the bottom of the five measures that we took a look at with them. So when we're producing this type of efficacy and safety for a patient, you're going to have patients that are going to want to be on therapy. I think our sub-Q, as Tim mentioned, with a simple, single, easy injection that they will be able to administer to themselves at home, you combine that with an individualized dosing schedule, can provide quite some convenience for our patients as well. So I guess the answer to you is individualized dosing schedule with IV and a combination of the self-injection at home. is how we think about, with the overall efficacy rate, is how we think about how we compete. I guess the last thing that I'll say in regard to the C5, David, is that, you know, we believe that an FCRN plays upstream of a C5. And by utilizing an FCRN and removing the autoantibody from the neuromuscular junction, you therefore have fewer autoantibodies to recruit complement. So we can... affect the neuromuscular junction in three different ways with our mechanism of action versus just one being complement. Lastly, you mentioned out-of-pocket expense, and that's where we have great optionality because of the out-of-pocket expense that could be experienced with a sub-Q. We have the IV formulation that will be available. Additionally, the work that we are doing right now in our pre-commercialization is to be able to address to make F-cortigamot accessible to patients that require it, whether that would be with some type of patient assistance programs or even in some situations, compassionate use. So we're looking into all of these things so that we can bring forth the product competitively.
spk15: Thank you. Our next question today comes from Akash Tulare with Wolf Research. Please go ahead.
spk07: Thanks so much. For CIDP, how many naive patients are you targeting to be included within your first 30 go or no-go decision? I think we've seen from the eye trial that 66% of those patients were IVIG naive. What internally gives you confidence that NFCRN will have efficacy in that patient population? And will your go or no-go decision look at refractory and naive patients separately? And then I have a follow-up.
spk17: Thank you, Akash. We are certifying within the CIDP population for subsets of CIDP, and as you correctly point out, we are allowing in both naive and refractory patients. Basically, what we see in the study so far is a good split between the two. I mean, there hasn't been a predefined number. So I think we will be in a position at the go-to-go decision point for the first 30 patients to look and try to correlate signal VC, not just with subtype of CRDP, but also with disease status. So I would say stay tuned. We have a good representation of both classes in the study.
spk07: Okay, great. And just Alexia, at the recent Investor Day, talked about for the GMG market, looking at the 80,000 patients who were potentially even not poorly controlled on steroids, you've talked about NFCRN being upstream of a C5, how much do you think you could penetrate that market, and is there a possibility that you can expand into that larger patient pool?
spk10: Thank you. Thanks for the question. I'm going to tell you what our KOLs are telling us right now, which is I've heard a Dr. Howard just recently talked about where he would use F-Gar-Tigamod. And first place he started is he would replace IVIG. He would replace plasma exchange with this product. The second thing that he talked about was being able to use it in a bridging manner because of its rapid onset of action, using it in patients where it would take a little while for another therapy to kick in, like a broad immunosuppressive therapy. So he mentioned using that up front and maybe either replacing ISTs or certainly bridging patients to ISTs. The next area that he shared was patients hate steroids. And what the ADAPT trial showed was safety. And he repeated that over and over. And so patients hating steroids, he could be replacing the steroid use with that. So you get this broad utilization of F-partigamide. The last two areas is, remember in this trial, it's a broad enrollment criteria. So we play all the way from second line down to the defined relapsed refractory patients. and we also go into the broadest set of patients because we included the seronegative patients in our trial. So to answer your question with one answer, yes, I think we will land into the MG space, and then I think we will expand as physicians get comfortable. But remember here, this is a brand-new mechanism of action of which most physicians in the U.S. have never utilized, and so it is going to be about education and getting them comfortable with it as we expand into that broader set of patients.
spk15: And our next question today comes from June Lee with Tourist Securities. Please go ahead.
spk08: Hi, thanks for taking my question and congrats on the progress. Just looking at the safety section of your presentation at a recent medical conference, the infection rates are largely similar between the drug and the placebo, but the drug arm does have a bit of a numerically higher value by about 10 percentage points. And for both placebo and the drug, they're between 30% and 40% ranges. which appears to be a little bit high, but I'm just not sure. Is that typical infection rate for GMG patient population? And along that line, assuming there's a COVID-19, a mass COVID-19 vaccination program on a global scale, possibly in 2021, would that impact your commercialization strategy in any way? Just wondering if the FDA would be curious to know. what the impact of F-cortisomide will be on the immune system, possibly eliminating some of the therapeutic antibodies that the body generates. Thank you.
spk17: Hi, Gil. Thanks for joining us today. I will pass on the second question to Keith in a minute. But in terms of safety profile, when you look at it, basically speaking, we see a safety profile which is comparable to placebo. So there is no signal. Maybe you see a numerical difference, but it is small numbers. Basically, on one of the parameters we studied, you see actually a signal for increased risk of infection. Remember that these patients were on broad immunosuppressants already, some of which actually do suppress the immune system to the extent you may see some increased risk of infection anyhow. Mind you, before I hand over to Keith, that the mode of action about GAPTI-GEMOT is to interfere with the recycling of IgGs, but not with their production. We do not target B cells. We do not target the ability of B and plasma cells to produce IgGs. We only interfere with their persistence. And there's plenty of scientific literature out there showing that with an S-cell and antagonist, you're basically not impacting the ability of the immune response to see and react effectively to an infectious agent. How we think about commercialization in the COVID-19 environment may be key. You're best placed to give a few comments on that.
spk10: Yeah. So, June, we are actually fully expecting that we would be launching this product in a COVID environment. And so I'm hopeful that we could even be in a cross-functional type of launch where it could be some live and some virtual. But we have been studying the launches. You know, Horizon has had a very successful launch here during COVID environment with an IV product. And so we have been studying the launches and particularly how they're engaging with the healthcare professionals so that we can replicate that type of launch. So all I can tell you is what I've said before. I'm glad that we did not wind up launching in 2020. because there's been a great deal of learning and a great deal of adapting that the team has had to go through.
spk15: Thank you. Our next question today comes from Lenny Van Steenhuis with KBC Securities. Please go ahead.
spk14: Hi, good afternoon, and thanks for taking the question. I was also looking to circle back a bit on the sub-Q formulation of Edgar Tigemont and the FDA meeting you already touched a bit on that. on the discussion and let's say the impact of the biomarker-related data or not. Perhaps could you provide some additional info on the content of the meeting, what we can expect and what the potential outcomes and impact on the development trajectory for the sub-Q formulation would be? And perhaps relating to that follow-up question, sub-Q formulation is of course tied to the partnership with Halozyme. What should we expect in terms of royalty out payments to Halozyme? The company themselves mentioned mid-single-digit on average for their deals. This is also the case for Afkar Tigimot. Are there any specificities on this deal? Can you comment on that, please? Thank you.
spk17: Thank you, Lenny. So on royalties, it is indeed one-size-fits-all in their deal-making. So we're in the same ballpark in terms of royalties, actually identical, and that means mid-single-digit. The strategy for bridging IV to sub-Q for the FDA meeting, we're not going to go into the details. I think we just elaborated on the fact that this is going to be based on science. It's going to be based on a very substantial data set from our ADAPT phase 3 trial. And of course, a growing safety database. I think we have the biggest a safety database in this space, at CRM space, for impact Digimod. So expect a science-based conversation, expect a company which is ready to argue a benefit-risk based on data, and as we said before, we do anticipate some level of exposure needed in EMG patients in order to effectively bridge from IV to sub-Q. But rest assured, we will communicate as soon as we have the minutes from the meeting. Thank you.
spk15: Thank you. Our next question today comes from Danielle Brew with Raymond James. Please go ahead.
spk12: Hi, guys. Good morning, and thanks for the question. I know we have to wait to hear what your fifth indication will be until next year, but curious, given what we've seen with the success of Horizon's drug in thyroid eye disease, what your thoughts are on that opportunity and the potential role for anti-FDRNs in the indication?
spk17: Yeah, look, the list is long. There are many, many indications where there is compelling evidence that pathogenic IgGs actually drive the disease. I think PED is one of them. Actually, there's a whole series of recent publications further documenting the pathogenic role of IgGs in this devastating disease. So it's one of the many indications where I think from a biology point of view it makes sense. I think it's also demonstrated now that, you know, there's a clear clinical and regulatory path to approval in this indication, and therefore we do have this indication on our radar screen. How actually we look at prioritization of this indication is too early to discuss.
spk16: But you're right.
spk17: From a biology point of view, this could be an effective mode indication.
spk15: Thank you. Our next question today comes from Jason Butler. It's AMP Securities. Please go ahead.
spk02: Hi, thanks for taking the questions. Just the first one on ICP, obviously with the program you have ongoing, you'd expect to get both sub-Q and IV formulations approved. But just wondering, when you speak to physicians in the context of the IV and the potential to switch patients at some point to sub-Q, are there additional data or information that physicians would want to inform who the appropriate patients would be and how to do that? And then just second question, on PV, just if you can remind us of the rationale and the epidemiology of including the pemphigus fallacious population as well in that program. Thanks.
spk10: Yes. So, Jason, I'll start with the question on sub-QIV in ITP. I just want to call out that these are two separate studies. One is going to be exclusively IV. And the other one is going to be exclusively sub-Q. So it will allow us to have a standalone advantage for patients with sub-Q. So they'll have both induction and maintenance with sub-Q. So there's not going to be a switching. When it comes to switching patients from IV to sub-Q, what I can tell you is in the discussions that we've had with our KOLs, this has been more around MG, mind you, than it has been ITP. They've shared with us that when given the preference, still 30% to 40% of patients have elected to stay on IV therapy as opposed to sub-Q. They just simply do not want to inject themselves. And finally, lastly, the point of switching from IV to sub-Q, we will have data on that in the future because although we're waiting on the news from the FDA meetings, What we are not doing is standing still. So we are already working on some of our patients that come out of our open label extension from ADAPT and look at potentially switching them to sub-Q so that we would have that type of information.
spk15: Thank you. And our next question today comes from Matthew Harrison at Morgan Stanley. Please go ahead.
spk11: Great. Good afternoon. Thanks for taking the question. I guess Two for me. One, Tim, can you just comment, when you think about CIDP and you obviously felt confident enough to give guidance around timing now, what do you view as still the risk that that timeline could slip? Or can you just contextualize for us what potential issues you could run into that would push that out further? And then secondly, can you comment on the regulatory process in Japan? I'm just wondering how much clarity we have there once you file versus say, a regulatory process in the U.S. Thanks.
spk17: Thank you, Matthew, and then Becky. So CIDP, I think the enrollment is going swiftly, as we said. I think now the real COVID-19 exposure is that for those patients who are on study, that actually their ability to perform the visits would be impacted. We have tried to mitigate against that as much as we could through home administration of products, and telemedicine, but still there is some ability required of patients to go to sites from time to time. So it's really during their stay on the study that we, of course, we have to be careful about the impact of COVID-19 on patient logistics. With regards to the registration process in Japan, it's a pretty well understood process. I think we can really leverage the BLA filing. I think especially in the Q&A following the filing, there will be much more intensive Q&A, real-time Q&A, where I think it's more technical complications which have to do with, for example, translation from Japanese to English and everything needs to be checked, of course, double. And there's also a particular attention of the PMDA to all the aspects of the filing as compared to, for example, a European or a U.S. But I think it's a process which is very well understood by us and by the team, and we feel very comfortable going into the process.
spk10: Yeah, Tim, Matthew, the only thing that I would add to this is, you know, going through the process, which is well understood, the only difference that you'll see from that here with the FDA is once we have approval by the FDA, we have a price set and then the product is available on the market. In Japan, the difference is you have approval from PMDA and your product is approved and you're allowed to discuss it, but there's a three-month period after that approval of which you set price with Japan. So there's about a three-month stretch between the actual approval and when you can actually make product available to patients. And that's because of pricing and that's standard in the practice there in Japan.
spk15: And our next question today comes from Douglas Sal with HC Wainwright. Please go ahead.
spk04: Hi, good morning. Thanks for taking the questions. Just curious in terms of feedback you're getting from KOLs in terms of the individualized dosing and how they intend to implement it, do you get a sense that they're going to base this on symptoms, or are they going to be checking IgG levels? And I'm also just curious, obviously you have four-week cycles. Have you heard from KOLs that might be thinking about going with a four-week induction of, you know, sort of weekly treatment, but then sort of maybe, you know, going with shorter cycles in subsequent periods with sort of different sort of intervals? Thank you.
spk10: Yeah, so, Douglas, first of all, the treatment with the individualized treatment, they're not going to be measuring IgGs to make their determination of when they redose a patient. What they have told us is your individualized treatment cycle is, you know, how I start a patient that I'm going to treat with chronic IVIG. I start them on a regularly scheduled dose, right, which would be our cycle with an interval, and then they bring them back in and they evaluate them. As the patient is maintaining their response and doing well, they will continue to stretch that cycle out longer as time goes on. As far as your second question about will they begin to customize the dose from the cycle, I think that they do this with every product available on the market. They create dosing schedules and don't stay completely rigid I'm talking about MG treatment, they don't stay completely rigid to what the package insert says in their intervals on dosing. So we do get questions like that from KOLs. And, in fact, if you take a look at the data that Tim shared, you know, the individualized dosing, what it really is going to allow is for some patients to have, you know, very few cycles per year. And other patients, you may see physicians decide to take them with more of a a chronic dose that could be administered. So they ask the questions because there's no two patients that are the same in MG.
spk15: Thank you. And our next question today comes from Greg Suvannabhas with Goldman Sachs. Please proceed. Pardon me, Greg, your line is open.
spk06: Thank you so much. Thanks for squeezing me in. A bigger picture question maybe for Tim and Keith, maybe you can comment too, but over the quarter we've seen competitive landscape developments, Phase II data for Indian Advance MG program, also the ITP Phase II data from UCB. Just wondering, bigger picture, how you think about how the competitive landscape is shaping and obviously given J&J's acquisition of Momenta, just broad strokes and how you think the FCRN competitive landscape is shaping up. Thanks.
spk17: Thank you, Greg. Maybe I will start and I will hand over to Pete to fill in on probably some of the more commercial aspects. But I think there's one thing becoming very clear, Greg, that is that not all FCRNs are made equal. So I think we see clear baskets of clinical profiles I think IgG4 antibodies clearly have a different efficacy and safety profile from the aglycosylated IgG1 antibodies, which typically commit less side effects, and then I think we're uniquely positioned with the fragments. I think it's fair to say that, of course, we have the largest and most advanced data set of all, but we've put the bar very high. Typically, we like to think about differentiation along the factors of efficacy, safety, and I think on the efficacy side, we've put forward data from large studies now, which basically put down an unprecedented efficacy. We haven't seen anything which is coming close to that from the smaller Phase II data points we saw from competition. I think on the safety side, again, a unique position. I think it's very early, of course, to talk for some of the other molecules. But I think the ADAPT study, and especially the open-label extension, where we now have patients on drugs for up to two years, and I think an impressive pancreas study suggests a pretty clean safety and tolerability profile going forward, with again a key differentiator being the fact that we do not induce any drops in serum albumin. And then I think on the convenience side, as Keith already called out, We think it's important to have both an IV and a sub-Q product available in the US market. There is a need for both. And I think the HaloSound technology is again putting us in a very nice starting position for a single fast sub-Q injection, not to be confused with these more lengthy and more cumbersome, for example, sub-Q infusions. Keith, maybe feel free to step in if you feel I overlooked an important point.
spk10: No, I think, Tim, you know, you covered it from those three points. The only thing that I would add, Greg, is that, you know, we believe that the total space for FCRN is so much bigger than just the four indications that we currently have made public to you. And because of that, actually, other competitors will help grow the FCRN space, we believe, more rapidly than just what we could do by ourselves. So we love the position that we're in. We love the product that we're going into this space with. But ultimately, competition can benefit all of us.
spk15: Thank you. And, ladies and gentlemen, this concludes today's question and answer session and today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.
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