argenx SE (ARGX) 2021 Q2 法說會逐字稿

Good morning, everyone. My name is Jamie, and I will be your conference operator today. At this time, I would like to welcome everyone to the conference. (Operator Instructions)

At this time, I'd like to introduce Beth DelGiacco, Vice President of Corporate Communications and Investor Relations. Ma'am, you may begin.

Thank you, operator. A press release was issued earlier today with our first half 2021 financial results and second quarter business update. This can be found on our website along with the presentation for today's webcast. I also encourage you all to visit our R&D Day microsite, also on the Investor page of our website, to watch a replay of the presentations and engage with the additional resources we've provided as part of the event.

Before we begin, I'd like to remind you on Slide 2 that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory time lines, the potential success of our product candidates, financial projections and upcoming milestones. Actual results may differ materially from those indicated by these statements. Argenx 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 Hauwermeiren, Chief Executive Officer; Karl Gubitz, Chief Financial Officer; and Keith Woods, Chief Operating Officer.

I will now turn the call over to Tim.

Thank you, Beth, and good morning, everyone. We appreciate you joining us today to discuss our half year results and second quarter business update. We're going to keep the prepared remarks brief because we provided a substantial update during our R&D Day last week.

The first half of 2021 has been marked by several achievements across our immunology pipeline. Notably, the progress we had made in advancing our first-in-class FcRn antagonist efgartigimod in 6 indications. We are on track to reach generalized myasthenia gravis patients later this year, and have been busy with hiring activities and key stakeholder engagements in anticipation of our December 17 PDUFA date.

Slide 3. We have registrational trials ongoing in 4 severe autoimmune indications: MG, ITP, CIDP and pemphigus. And we announced 2 new efgartigimod indications last week, myositis and bullous pemphigoid. We are preparing to launch trials this year in both of the new indications, pending FDA interactions. With regard to our ongoing registrational trials, we have said that this year would develop execution and we would provide clarity on enrollment as able. We are delivering on that commitment today.

We expect to complete enrollment this year in the ongoing ADAPT subcu trial in gMG and the ADVANCE IV trial in ITP. This sets us up to have top line data for both trials in the first half of 2022. Recall that with ADAPT-subcu, the primary endpoint is based on PD effects and is taken at day 29. The trial continues out to 12 weeks before patients roll over into an open-label extension study. The ADVANCE IV trial follows patients out to 24 weeks before they can roll over into an open-label extension.

The other registrational trials of efgartigimod, ADVANCE subcu, ADHERE and ADDRESS, are all making progress. We additionally expect our partner, Zai Lab Limited, to start enrolling patients into these global trials by the end of this year. We continue to believe that efgartigimod is well positioned to be not only first-in-class, but also be a leader in the FcRn space with its unique structure as an Fc fragment with optionality with both intravenous and subcutaneous formulations in development with clear clinical proof-of-concept established in 4 out of 4 indications and perhaps most importantly, a growing safety database which supports a favorable benefit-to-risk ratio.

On Slide 4, you can see that specifically, over 600 patients and healthy volunteers have been dosed with efgartigimod. This includes 125 patients who have been on efgartigimod for over 12 months and 100 patients for over 18 months. Across all studies, we have seen no evidence of dose-limiting toxicities and no reduction in human serum albumin, a topic on which we provided new perspectives during the R&D Day. We believe the broad therapeutic window that we have observed allows us to dose efgartigimod to the maximum benefit of patients and enables our indication selection strategy, which will continue to be our guide as we expand the efgartigimod program further.

Slide 5. The list of IgG-mediated diseases, which efgartigimod can potentially address, is vast. And as we expand our development program, we will stick to our strategy, which has been successful to date, starting first with a clear biology rationale. Our fifth indication, myositis; and our sixth indication, bullous pemphigoid, both align to this strategy.

With myositis on Slide 6, we are building an innovative trial design, exploring 3 subsets of myositis in which the unifying feature is muscle weakness. In the best characterized subsets, immune-mediated necrotizing myopathy, we clearly understand the role of the autoantibody in driving the muscle weakness. In anti-synthetase syndrome and dermatomyositis, patients present with a similar muscle weakness, but the role of the autoantibody is not as well characterized in driving it. The proposed myositis trial will be the first time the company is pursuing a basket trial design based on a unifying biology. In this way, we aim to maximize the potential opportunity to reach a broader population of myositis patients while also minimizing the potential risk of interrogating biology while doing so.

With bullous pemphigoid on Slide 7, the role of the autoantibody is very clear in the disease pathogenesis. And based on the robust efficacy and favorable safety we have observed in the pemphigus Phase II trial, we believe we can advance directly to a registrational trial within bullous pemphigoid.

Having announced our next efgartigimod indications, we can start to look ahead at how we ramp up to more indications as quickly as possible, whether through our own registrational programs, proof-of-concept trials in the hands of a partner such as Zai Lab or through externally sponsored research.

Slide 8, during our R&D Day last week, we introduced our argenx 2025 vision, outlining specific goals as we transition to a global integrated immunology company. First, we aspire to make efgartigimod available for patients globally and to expand the commercial and development footprints of efgartigimod into 15 indications across our expanding therapeutic franchises in neuromuscular diseases, hematology and dermatology.

Second, we seek to advance our second immunology pipeline candidate, ARGX-117, into multiple late-stage trials. The Phase I data we showed last week indicates that ARGX-117 has the potential to be an efficient C2 blocker that can durably knock down free C2 levels by 99%. The safety data, while still blinded, showed primarily grade 1 events and no increased risk of infection. The Phase II trial of ARGX-117 in multifocal motor neuropathy is on track to start this year in which we evaluate the potential for an attractive infrequent dosing based on the observed PK and PD profile.

Third, as we shift to be a commercial organization with a deep development pipeline, we are not taking our foot off the gas when it comes to our investment in discovery and earlier stage programs. Slide 9. This is exemplified by the breadth of assets which have emerged from our immunology innovation program. We talked for the first time last week about ARGX-119, a simple antibody that aims to boost the neuromuscular junction across a range of indications. This is another pipeline and a product focused on orphan indications that fit squarely into our therapeutic franchise.

With efgartigimod, ARGX-117 and now ARGX-119, we have a company within a company emerging from our neuromuscular franchise. This is why we like the franchise model so much. The strategic investments we are making now with our current pipeline will continue to benefit us in the long term as we recognize the economies of scale and synergies across multiple assets and multiple indications.

I would now like to turn the call over to Karl Gubitz, who is joining us for the first time as our newly appointed Chief Financial Officer. Karl brings significant commercial expertise to argenx and has already made important contributions ahead of our expected launch. Karl?

Thanks, Tim. Slide 11 covers our first half 2021 operating results, which are detailed in today's press release and regulatory filings. Total operating income increased to $487.5 million over 6 months ended June 30, 2021, compared to $34.3 million during the same period in 2020. The significant increase was primarily due to the recognition of a transaction price as a consequence of the termination of a collaboration agreement with Janssen, resulting in the recognition of $315.1 million; and the closing of a strategic collaboration with Zai Lab, resulting in the recognition of $151.9 million in collaboration revenue.

R&D expenses increased by $84.7 million for the 6 months ended June 30, 2021, to $273.9 million compared to $189.3 million for the 6 months ended June 30, 2020. The increase in the first 6 months of 2021 resulted primarily from higher external research and development expenses, mainly related to the efgartigimod program in various indications and our clinical and preclinical programs.

SG&A expenses totaled $129.6 million for the 6 months ended June 30, 2021, compared to $67.9 million for the 6 months ended June 30, 2020. The increase resulted primarily from higher personnel expenses. The change in fair value on noncurrent financial assets amounted to $11.2 million for the 6 months ended June 30, 2021, which is the result of a closing of a Series B financing round of AgomAb Therapeutics for which argenx maintains a profit share in exchange for granting the license for the use of HGF-mimetic antibodies from the SIMPLE Antibody platform.

Finally, cash, cash equivalents and current financial assets totaled $2.7 billion as of June 30, 2021, compared to $2 billion on December 31, 2020. This increase is primarily from the closing of a February 2021 global offering, resulting in approximately $1.1 billion in net proceeds; secondly, the $73.1 million noncreditable, nonrefundable development cost-sharing payment received from Zai Lab; thirdly, the payment of $98 million related to the purchase of a priority review voucher from Bayer HealthCare Pharmaceuticals; and other net cash flows used in operating activities.

I'd now like to turn the call over to Keith Woods to provide an update on our commercial launch preparation. Keith?

Thank you, Karl. The first half of this year has been marked by several achievements, which have brought us closer than ever before to reaching patients with myasthenia gravis.

As Tim mentioned, we expect to complete enrollment by the end of this year in our ADAPT subcutaneous trial in MG. To satisfy the safety database requirements for a subcutaneous trial, we are encouraging patients from our ADAPT-Plus open-label extension study to switch over to the ADAPT subcutaneous trial. While this may mean that we won't have a bolus of patients to switch from the ADAPT-Plus trial to commercial drug launch, we continue to believe that having both IV and subcutaneous formulations will provide optionality to patients and offer a potential competitive advantage when it comes to physician and payer preference.

Similarly, as part of our continued commitment to the MG community, we launched our pre-approval access program in the U.S., Canada and several countries in Europe. This program ensures that we can offer efgartigimod to MG patients who don't have available options. In addition, we know that continued engagement with the broader MG community will be critical.

Slide 12, please. Ongoing initiatives like our patient marketing programs and our real-world evidence study, MyRealWorld MG, help us to learn about the significant toll this debilitating disease takes on both patients and their caretakers. We have and we will continue to listen to and learn from the MG community. With our approaching December 17 PDUFA date, we continue to build out our team such that we can be fully staffed and trained well in advance.

Slide 13, please. Specifically, the hiring of the U.S. sales force will be completed during the third quarter, including our Head of Sales, 8 regional business directors and 70 territory business managers. This team, along with our broader field team of thought leader liaisons, medical research liaisons, nurse case managers and field reimbursement experts, will be well equipped to drive engagement and education efforts with patients, physicians and payers. While we do expect the initial launch trajectory to be gradual yet consistent, these efforts to educate the provider community on FcRn and the role of the antibody in MG will position us for long-term success.

Before I turn the call back to Tim for concluding remarks, I want to talk about our global commercial plans, prioritizing Japan and Europe after the U.S. Slide 14, please. We have filed our marketing authorization application for efgartigimod in MG in Japan and expect an approval in the first half of 2022, after which we will negotiate price ahead of a commercial launch. We plan to have a fully staffed team in Japan by the end of this year. The filing in Europe is expected in the second half of 2021, setting us up for an approval in the second half of 2022. We have hired key functional leaders in Europe as well as country managers in our priority markets.

I want you to know that we are committed to other geographies outside of the U.S., Japan, Europe and China, but we are still evaluating what the commercial plans for the rest of the world will look like. I look forward to sharing more specifics on this in the future. As it stands today, we are in a strong position to execute on a series of MG launches over the next 2 years across multiple geographies and our 2 formulations.

I will now turn the call back over to Tim. Tim?

Thank you, Keith. I would like to conclude with the following on Slide 15. Earlier this year, we laid out our strategic priorities for 2021. Notably, we stated that MG is just the beginning. Today with our fifth and sixth indications for efgartigimod in hand, our growing commercial organization to support not only efgartigimod in MG, but also our earlier-stage pipeline assets across our therapeutic franchises, this is more true than ever. We are united in our commitment to improve the lives of patients, and we believe we're well on track to reaching those living with MG and other serious autoimmune diseases.

I will now hand the call to the operator to start the Q&A. Operator?

(Operator Instructions) Our first question today comes from Joon Lee from SunTrust.

Just curious if you can comment on the breadth and magnitude of the pre-approval access program in the U.S. and Canada and the EU as well. And related to that, I appreciate that you are sacrificing the initial bolus of your IV patients by switching them over into the subcu. By doing that, how much are you -- by how much are you speeding up the potential submission of the subcu formulation?

Joon, it's Keith. Thank you for the question. Let's address that in 2 different parts. First, let's talk about the subcu program which you asked. So if you think about the subcu program, we've offered that as an opportunity for not only the subcu bridging study, which you may have noticed. We increased the total number enrolled for that, and that's because we've had such rapid participation in the trial. We wanted to take an opportunity to continue to fill that trial for our safety database. We have also offered our ADAPT open-label extension patients from the IV trial the opportunity to switch over to subcu. We have some very satisfied patients on IV and so not all of them have elected to switch over to the subcu.

And finally, you asked about the pre-approval access program that's available here in the U.S., also in Canada and in parts of Europe. There has been a nice demand for that. I want to call out to you that we do this in the interest of the commitment to the patients of which we serve, and that's our #1 priority. We also prioritize by offering them to participate in the subcu trial prior to the PAA. So with that, I would give you -- I wouldn't have great expectations that the PAA is going to put a bolus of patients for commercial transition at launch in the U.S.

Our next question comes from Tazeen Ahmad from Bank of America.

Just wanted to follow-up on cusatuzumab and what the update there might be. How are you thinking about future developments and what level of priority is it to partner it up?

Thanks for the question, Tazeen. So what concerns of cusatuzumab, we're going through the data. So we have now full access to the interim data readouts. The scientists and the clinicians are working hard on that as a team. We did inform our audience in the past that this is becoming a business development priority and activity. So we think we have a commitment to fulfill towards AML patients based on the data we have seen so far, clear dose response, clear signal in that study, interesting signal in certain subsets of patients and importantly has a clean safety profile in line with the historical safety profile of the molecule.

So we believe there is value in the data. It's a business development priority, but we're not going to distract the internal clinical development machine to take cusa back on in-house. So we stay fully focused and committed to expanding efgartigimod as fast as we can, ramping up ARGX-117 and bringing ARGX-119 on line.

Our next question comes from Matthew Harrison from Morgan Stanley.

This is Max Skor on for Matthew Harrison. So as you continue to engage with stakeholders, can you speak to the potential payer dynamic? Will patients need to fail standard of care before starting efgartigimod?

Max, it's Keith. Thanks for the question. And yes, we are engaging with the regional and national payers throughout the U.S. You can see where you've had some restrictions that have been placed by payers on eculizumab, and that is due to the inclusion trial of the -- inclusion/exclusion criteria of the REGAIN trial. I call out to you that we have a different inclusion criteria for our trial and so that we are treating patients across the entire treatment paradigm. I think where the rubber hits the road on what will take place will be when we're actually talking with them with our price in place. But we aim to be able to serve out of the 65,000 MG patients, our target audience is about 20,000. So we'll be able to give you more information as those discussions take place and as we get closer to launch.

Our next question comes from Yaron Werber from Cowen.

This is Brendan on for Yaron. Congrats on the progress. Just a quick question from us. So I know you mentioned the ADAPT subcu and ADVANCE IV studies will be enrolled by the end of this year. I just wanted to check in on the subcu in ITP and kind of just see how you're now thinking about that fitting into the dosing scheme when you finally launch there. Like maybe what are the 2 different -- or what from the 2 different trials maybe you're kind of looking at this point to really inform how we should think about the 2 would be used?

Brendan, it's Keith. So yes, we did share that the IV enrollment is going on at a good pace, and we expect to have that fully enrolled by the end of the year. We are also concurrently enrolling a subcu clinical trial for ITP. It did start a little bit later. But overall what the FDA had asked us for was 2 Phase III clinical trials. So what we're doing is running 2 very similar Phase III clinical trials, just 1 with IV and 1 with subcu. This should position us for the optionality that we talk about for all of our patients, our payers and our health care professionals when it comes to treating ITP patients. So the subcu trial is not going to be concluding by the end of the year like the IV one is because it started a little later, and they will both be included in our file.

Our next question comes from Andrew Galler from Wolfe Research.

So just on gMG, The Lancet Neurology article on ADAPT noted positive signals on a post-hoc basis in the AChR AB negative patients. Do you think this is sufficient for approval in this population given the unmet need?

Yes. So I want you to know that we honored our commitment to the MG patient community by including the seronegative patients in our trial. We've seen in the data that there was a treatment benefit, but you also see in the data that there's nearly an equivalent placebo effect. Although it was never agreed with the FDA that these results had to be statistically significant and in fact what we see is that they are not statistically significant, we will be speaking with the FDA, and it will completely be a decision of the regulatory body. And we'll get back to you after we have more information on that at the time of approval.

Our next question comes from Danielle Brill from Raymond James.

This is [Alex] on for Danielle. I know it might be a bit early, but do you have any targeting estimates for subcu efgartigimod sNDA submission? And a follow-up, would you consider using your priority review voucher for such a submission?

Thanks for the question, Alex. So the press release this morning was talking about fully enrolling the subcu study before the end of the year. Then, of course, we will be reporting out top line data first half next year. And then I think the trial will take its regular course of action life, I mean, in terms of locking the data, reporting the data and then filing them. We have been saying publicly that it is a possibility that we will use the PRV voucher for this one. You know that efgartigimod has plenty of opportunity to use such a voucher, think of the CIDP study as well. But indeed, the subcu MG trial could be a possibility for using the voucher.

And our next question comes from Laura Sutcliffe from UBS.

This is [Andrew] on for Laura. Just one on BP from me, please. At the R&D Day last week, I think you flagged about 41,000 BP patients in the U.S. Sanofi has previously highlighted a biological eligible population of about 30,000 in the U.S. So just wondering, do you agree with sort of Sanofi's assertion that a significant proportion of the BP population could be biological ineligible?

Yes. Thank you for the question, Andrew. So we're quoting prevalence data from literature sources, which we could identify through our own research. Whatever is the right number, I think we're both pointing at the same possibility or opportunity, right? This is a sizable opportunity, a significant medical needs of patients, which today have very limited treatment options. And as we hopefully explained in the R&D Day, we do believe this disease is really driven by pathogenic IgGs. And therefore, I think that with the mode of action of efgartigimod, we are very well positioned to address a significant portion of these patients. But thanks for the question.

Our next question comes from Yanan Zhu from Wells Fargo.

Could you comment on the dosing frequency in the open-label extension of the Phase III ADAPT study? Now that you're evaluating the kind of real-world dosing, how does the dosing frequency compare with the first randomized 26-week portion? And also, you mentioned that some patients elected to be switched to the subcu study -- Phase III subcu study, which obviously is a weekly dosing schedule but a little more convenient with subcu. Could you talk about the kind of level of interest you saw in the switching? And what does that tell you with regard to whether IV and subcu is more preferred and the relative preference by patients?

Two great questions. Thank you for this. I will take the first question and then I will hand over to my colleague Keith here to comment on the switching over situation. You're absolutely right, in the ADAPT study, initially, patients rolled over in a first open-label extension study where they followed the same cadence of dosing as they were doing in the registrational portion of the trial. And then you're right, after concluding the first open-label extension, but already there was a possibility to [trade the background] medication.

Now we'll have second open-label extension, which enjoyed a very high roll over rate, it was hands-off. So patients were truly treated in a real-world setting from a dosing regimen point of view. We're not public on the data yet. So what we said is that we will, with a certain frequency, report on our open-label extension study data. But we're very fortunate, of course, to be in a position to now see the real-world dosing cadence and therefore, really be able to triangulate a proper price and value for the products we will offer to these patients.

So I would say stay tuned, we will be communicating about it later. And of course, we continue to collect further safety data as we now have a very sizable safety database of more than 100 patients being on 18 months drug or longer. And maybe, Keith, you want to comment on the switching over situation, right?

Yes, happy to do so, Tim. So as you know, from the open-label extension where patients are on IV, if you total up the response rate on clinical efficacy of patients that had a clinically meaningful response when exposed to efgartigimod, it's at almost 80% of patients respond between their first and second round. You also know that out of those responders, those that went to minimal symptom expression, an ADL of 0 or 1, is almost 2/3 of the responders. I share that with you because we have patients across the treatment paradigm and some that have failed many other therapies. When they are finally getting that relief that they need after failing several other therapies, they don't want to be switched from something that's working. So although we may think, hey, IV will be much more convenient, they're happy because of the clinical response that they're receiving.

Secondly, not all patients want to have a subcu. When we have talked with the physicians, they have said somewhere on a breakdown of up to 30% of patients would prefer to have an IV over a subcu. They don't want to inject themselves, and they don't want their partner to be injecting them.

So look, as far as a projection of will we be 70% subcu and 30% IV, I think we'll let the market test its way out. I also think there will be another component, and that will be the payer situation and reimbursement on whether a patient wants to go in through potentially Part B, Part D, specialty pharmacy, home infusion or actually visiting an infusion center. The good news is we're providing that optionality.

Our next question comes from Thomas Vranken from KBC Securities.

I was wondering about the progress in ITP trial. We saw that enrollment seems to be a bit more difficult than we had anticipated, perhaps related to an impact of COVID. I was wondering how this affects the time lines for the Fc trial.

It is true and we have been talking about it frequently in the previous quarterly calls that COVID has been impacting all our ongoing clinical trials. I think with the ADAPT study, we were lucky to or fortunate to actually conclude that study before the COVID pandemic really hit society, but all the trials have been impacted to some extent. So also the ITP -- IV and the ITP subcu study. Good news is that these studies are global studies that basically are able to adapt and adjust to the global pandemic, the different waves of the COVID pandemic. And the studies are enrolling quite well. So IV is going to be enrolled first, but I think the subcu ITP study, the CIDP study, the pemphigoid study, that's also enrolling quite well. So COVID is a situation we are getting increasingly under control.

And our next question comes from Graig Suvannavejh from Goldman Sachs.

Just a very quick one and apologies if this may have been asked before, but just on time lines with PV and CIDP, I appreciate that enrollment seems to be getting better and you're still in COVID or coming out of the COVID type of landscape. If you're not able to provide at least today exact or approximate time lines, when would you anticipate being in that position? Do you think it could happen at the next quarterly update?

So what we said is that in these quarterly calls, we will give you from time to time, updates on the clinical pipeline, just like we're doing today, right. So we're honoring our commitments. We can now speak with certainty about concluding enrollment in the ITP IV study and the MG subcu study. And I think in the coming quarters going forward, expect us to be getting similar information if and when the situation allows. So when we are there or when we are very close to a completion of enrollment, we're committed to inform you in our quarterly calls. So I would say stay tuned. We should not be naive. I think now with the delta variant, we need to watch out and not shout victory too fast. But our global studies are actually recruiting quite well.

Our next question comes from Yatin Suneja from Guggenheim.

This is Eddie on for Yatin. Just as a follow-up to that last one. I was wondering if you could just sort of give us a sense of the cadence of data from some of these ongoing trials. And if any of the early data releases will derisk any of the later ones. I'm thinking specifically about the pemphigus program. So just give us a sense of sort of what we're going to learn and when over the next sort of 12 to 18 months.

Yes. I think as we said before -- thank you for the question, Ed. What we said before, it's too difficult for us to really predict with certainty given the COVID pandemic situation when studies will have been completely enrolled and therefore, when data readouts will come. We will keep you informed when we feel sufficiently confident about enrollment of trials.

To your second portion of the question, yes, we do believe that a successful readout in pemphigus will have a read-through to bullous pemphigoid because that's the whole rationale why we actually initiated from the get-go a Phase III registrational study in bullous pemphigoid, building from the Phase II proof-of-concept in pemphigus. So there is some connection between this indication or indications. That being said, let's be careful, right? All these diseases remain distinctly different diseases with their own biology. So it will further derisk, but probably not completely. Thanks for the question.

And ladies and gentlemen, with that we'll conclude today's question-and-answer session as well as today's conference call. We do thank everyone for attending. Please have a great day. You may now disconnect your lines.