Zai Lab - Q4 2022

Transcript

Operator (participant)

Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab full year and Q4 2022 financial results conference call. Through the call, I'd like to remind you that the audience who are joining via the webcast can refer to the presentation slides and follow along with management presentation. The slides will be available for download in the investor relations section of Zai Lab's website after this call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. An instruction will follow at that time. As a reminder, today's call is being recorded. It's now my pleasure to turn the floor over to Billy Cho, Chief Financial Officer of Zai Lab, who will make introductory comments.

Billy Cho (CFO)

Thank you, operator. Good morning, good evening, and welcome everyone. Zai Lab recently issued a press release providing the details of the company's full year 2022 financial results, as well as some recent product highlights and corporate updates. The press release is available in the investor relations section of the company's website at ir.zailaboratory.com. Today's call will be led by Dr. Samantha Du, Zai Lab's Founder, Chief Executive Officer and Chairperson. After Dr. Du provides opening remarks with an overview of 2022 highlights, Josh Smiley, Chief Operating Officer, will further discuss key business updates and 2023 strategic priorities. Dr. Rafael Amado, President and Head of Global Development, Oncology, will discuss advances with our oncology product candidates. Dr. Harald Reinhart, President and Head of Global Development, Neuroscience, Autoimmune and Infectious Diseases, will speak about progress we have made in those three therapeutic areas.

I will discuss the performance of our market products and conclude with comments on our full year and Q4 financial results. Additional executives will be available to answer questions during the Q&A portion of the call. As a reminder, during today's call, Zai Lab will be making certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including with respect to our business plans and objectives, clinical trials, sales and revenue forecasts for our products and product candidates, regulatory applications, and commercial launches. These forward-looking statements are not guarantees of future performance, and therefore you should not put undue reliance upon them. These statements are subject to numerous risks and uncertainties, and actual results could differ materially from what we expect due to a variety of factors, including those discussed in our SEC filings.

At this time, it is my pleasure to turn the call over to Zai Lab's Founder, Chief Executive Officer and Chairperson, Dr. Samantha Du.

Samantha Du (Founder, Chairperson and CEO)

Thank you, Billy. Hello, everyone, thank you all for joining us today. On this call, I'll discuss highlights from 2022 and what we expect to accomplish in 2023 and in the longer term. In 2022, despite challenges from the COVID-19 pandemic in China, our four market products each had substantial sales growth, and we made exciting progress across our broad and advanced platform. Our pipeline assets continue to demonstrate potential best-in-class and, or first-in-class profile globally. The numerous positive late-phase data readouts announced during the year, including adagrasib in non-small cell lung cancer, CAR T in schizophrenia, and efgartigimod in ITP and TMT. We are also pleased to have contributed to several successful registrational studies, including the Tumor Treating Fields LUNAR study and the repotrectinib TRIDENT-1 study. We're pleased to have added QINLOCK NUZYRA to China's National Reimbursement Drug List in 2023.

We further deepened our women's cancer franchise through our strategic collaborations with Seagen for TFAB, and we continue to significantly enhance our talented global team, further building on our solid foundation. Zai Lab is already a leading global biotech with very good scale, a world-class pipeline, and a growing commercial portfolio in China. We expect to achieve commercial profitability this year and are preparing to launch at least 8 additional products and achieve overall corporate profitability by end of 2025. We will continue to invest in R&D as we seek to advance our product pipeline, including our internal discovery activities in the federated medicines for patients in need. We also aim to strengthening our portfolio and strategic positioning with potentially transformative assets and partnerships. We believe that the global regulatory environment will continue to be supportive of innovative biopharmaceutical companies like Zai Lab.

We'll continue to build on our success in pursuit of our overall goal of improving human health in China and globally. I would like to now turn the call over to Josh to discuss other key business updates and 2023 strategic priorities in more detail. Josh?

Josh Smiley (COO)

Thank you, Samantha. As Samantha mentioned, in 2022, we continued to attract top talent with deep domain expertise.

I'd like to highlight a few recent additions to our global leadership team. In December, we were pleased to welcome Dr. Rafael Amado to our team as President, Head of Global Oncology Research and Development. Rafael joined us from Allogene, and he has experience in leading worldwide discovery and clinical development across a broad range of oncology products. In November 2022, Dr. Peter Huang joined us as our Chief Scientific Officer. Dr. Huang will lead and oversee our discovery efforts in translational medicine. We were also pleased to appoint Michel Vounatsos to our board of directors in January 2023. Mr. Vounatsos brings to the board extensive global leadership and management experience in the biopharmaceutical industry, including more than 25 years of service as an executive at leading companies. His expertise includes a significant amount of commercial experience in China and worldwide.

We expect 2023 to be a very exciting year for Zai as we anticipate achieving many significant milestones. First, on the regulatory front for efgartigimod, we expect BLA approval and commercial launch for the IV formulation of efgartigimod in generalized myasthenia gravis, or gMG, in 2023, and a BLA submission for the subcutaneous efgartigimod in gMG in mid-2023. We also plan to submit a new drug application to the NMPA for repotrectinib in ROS1-positive advanced non-small cell lung cancer this year. We're also pleased to obtain the NMPA's acceptance of the NDA for sulbactam-durlobactam for the treatment of infections caused by Acinetobacter baumannii. Regarding our commercial products, we delivered good growth even though we faced COVID challenges last year. Now, with the COVID challenges mostly behind us, we expect strong growth in revenue in 2023.

We expect ZEJULA to become the leader in PARP sales for ovarian cancer in China this year. In the Q4 of 2022, we continued to gain share of hospital sales across all indications, reaching 39% of total PARP hospital sales. Since last September, there's been some concern around ZEJULA's China label for ovarian cancer in the recurrent setting on the back of the FDA decision. As we've previously communicated, we do not expect the US label restriction to impact the approval from the NMPA for ZEJULA in China. For QINLOCK and NUZYRA, we anticipate a significant increase in the sales of both products following their inclusion this year on the NRDL.

Moving to key research and clinical development milestones for both Zai and partners, we are looking forward to the top-line data readouts for subcutaneous efgartigimod for chronic inflammatory demyelinating polyradiculoneuropathy, or CIDP in the Q2 of 2023 and pemphigus vulgaris or PV and chronic immune thrombocytopenia or ITP in the second half of 2023. We also expect the full data readout of the Tumor Treating Fields LUNAR study in non-small cell lung cancer in the first half of 2023. We also look forward to the clinical data update for adagrasib in combination with pembrolizumab in the first-line KRAS G12C-mutated non-small cell lung cancer in the second half of 2023. In terms of clinical developments, we will complete the enrollment in the global phaseIII innovaTV 301

We also plan to join the global phase III FORTITUDE-101 study of bemarituzumab in first-line gastric cancer in China in mid-2023. We anticipate initiating a bridging study of KarXT for schizophrenia in China in mid-2023. I'd like to emphasize the advancement of these potential treatments for lung and gastric cancers continues to add design strength in these areas of large unmet patient need. We will continue to invest in R&D and advance our internal global pipeline. In terms of key research milestones, we plan to move ZL-1102 for potential in chronic plaque psoriasis into full global development with the initiation of a phase II study in 2023. We also plan to initiate a phase I study for ZL-1218 for CCR8 in the first half of 2023.

Of course, we also continue to evaluate business development opportunities, including the addition of potentially transformative opportunities and partnerships for our regional and global pipeline. Zai Lab is a trusted brand and strategic partner of choice, we look forward to entering into more deals that we believe will create significant value and synergies to our existing business. Before I conclude, I'd like to welcome Dr. Rafael Amado to his first earnings call with Zai Lab. Rafael will make introductory remarks before discussing advances with respect to our oncology product candidates. Now I'll turn the call over to Dr. Amado. Rafael?

Rafael Amado (President, Head of Global Oncology Research and Development)

Thank you, Josh. I'm thrilled to be joining Zai Lab at such a pivotal time in the company's history. As a physician-scientist, I've had the privilege to work on the development and approval of cancer therapies across various modalities and to form and lead R&D teams. Zai has a broad portfolio of innovative products, state-of-the-art capabilities for development in Greater China, and the ambition to continue to globalize research and development in oncology. The combination of products with transformational potential, excellence in execution, together with the ambition for global expansion, makes Zai Lab an easy choice as the next step in my career. I look forward to working with outstanding colleagues to continue to build capabilities and to help catalyze the expansion of our oncology pipeline.

In the Q4 of 2022, Zai Lab's oncology franchise continued to make progress on all fronts. We expect to have a productive year in 2023. For Tumor Treating Fields, in January 2023, Zai Lab and Novocure announced that the LUNAR study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival over standard therapies alone. The LUNAR study also showed a statistically significant and clinically meaningful improvement in overall survival when patients were treated with TTFields and immune checkpoint inhibitors as compared to those treated with immune checkpoint inhibitors alone. A positive trend in overall survival when patients were treated with TTFields and docetaxel versus docetaxel alone. TTFields therapies was well-tolerated with patients enrolled in the experimental arms of the study. We are excited about the potential of TTFields to help lung cancer patients.

In China alone, lung cancer is the most common cancer type, with approximately 700,000 new cancers diagnosed each year. We are pleased to contribute and to be a part of the LUNAR study. LUNAR met its primary endpoint of overall survival, we're optimistic about its growth potential across a range of hard to treat and prevalent cancers. The late-stage studies underway in certain other cancer types include pancreatic, where Zai is actively enrolling. Moving now to Grazoprevir or Adagrasib. It was granted accelerated approval by the FDA in December 2022 for adult patients with KRAS G12C-mutated, locally advanced or metastatic non-small cell lung cancer who have received at least one prior systemic therapy.

In China, we will continue to accelerate the regulatory pathway for second-line non-small cell lung cancer monotherapy by leveraging the global data package for the FDA approval, the ongoing PK study in China, and the global confirmatory KRYSTAL-12 study which Zai Lab joined in July 2022. In December 2022, the FDA granted breakthrough therapy designation to adagrasib in combination with cetuximab in patients with KRAS G12C-mutated advanced colorectal cancer, whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy, with the results published in the New England Journal of Medicine. Adagrasib demonstrated anti-tumor activity in heavily pre-treated patients with KRAS G12C metastatic CRC, both as monotherapy and in combination with cetuximab. Mirati plans to submit the new supplemental drug application in third line plus KRAS G12C-mutated advanced CRC by year end 2023, and move forward with accelerated approval pathway.

Zai initiated enrollment to the randomized KRYSTAL-10 study in second-line metastatic CRC in June 2022, and the enrollment completion is expected by the end of 2023. We remain confident that adagrasib is potentially a best-in-class KRAS G12C inhibitor in colorectal cancer. For first-line non-small cell lung cancer, recall that in December 2022, Mirati reported results from the KRYSTAL-7 phase II trial and KRYSTAL-1 phase Ib cohort evaluating adagrasib in combination with pembrolizumab in patients for the treatment of first-line non-small cell lung cancer harboring KRAS G12C mutations across all PD-L1 subgroups. We are excited that these results are the first to demonstrate the tolerability and feasibility of a concurrent combination regimen of a KRAS G12C inhibitor and a PD-1, PD-L1 checkpoint inhibitor, and we will continue to work with Mirati on a first-line registration plan for adagrasib.

Moving now to Zejula, we were pleased that NMPA granted full approval to the first-line ovarian cancer maintenance indication on February 3rd, 2023, regardless of biomarker status. In December 2022, we presented new interim overall survival data in Chinese patients with platinum-sensitive recurrent ovarian cancer from the phase III NORA study conducted exclusively by Zai Lab at the ESMO Virtual Plenary Session. Median overall survival was numerically longer for patients receiving Zejula regardless of biomarker status at 46.3 months, compared to 43.4 months in the placebo group. No new safety issues were identified. We expect to present the final OS analysis of the phase III NORA study sometime this year.

Moving now to our internal global research and development programs, the translational and clinical biomarker data for ZL-1211, an anti-claudin 18.2 antibody, will be presented in a poster at an upcoming AACR conference. We plan to initiate a global phase I study in the first half of 2023 for ZL-1218. It's an anti-CCR8 antibody. With an abundance of potentially best-in-class and first-in-class products, we're very excited about our oncology pipeline at Zai Lab. Now I will turn the floor over to Dr. Harald Reinhart to discuss the progress in our autoimmune infectious disease and neuroscience therapeutic areas. Harald?

Harald Reinhart (President, Head of Global Development (Neuroscience, Autoimmune and Infectious Diseases))

Thank you, Rafael. I'm excited for the opportunity to share with you today the progress across our autoimmune infectious disease and neuroscience therapeutic areas. Let's start with VYVGART for efgartigimod. On the regulatory front, we and our partner, argenx, continue to make excellent progress. argenx recently announced that the FDA has accepted for priority review a BLA for efgartigimod subQ for the treatment of adult patients with generalized myasthenia gravis. The PDUFA date is June 20, 2023. As a reminder, we submitted the BLA for efgartigimod IV for the treatment of patients with gMG in China in the Q2 of 2022, and expect approval and commercial launch this year. We also expect to submit a BLA for efgartigimod subQ for gMG in mid 2023. We continue to support argenx on indication expansion China and worldwide.

Indeed, enrollment in two proof of concept trials for autoimmune renal diseases has begun this February. Moving on to KarXT, the combination of xanomeline and trospium, which we are developing with our partner Karuna in acute schizophrenia. Zai Lab's proposed development plan for China has been accepted by the NMPA. We expect to start a clinical bridging study in mid-2023. As you recall, results from Karuna's EMERGENT-2 trial were released in August 2022. This pivotal trial made its primary endpoint, with KarXT demonstrating a statistically significant 9.6-point reduction in PANSS total score compared to placebo at week five. Karuna expects top-line data results from the phase III EMERGENT-3 trial in schizophrenia in Q1 of 2023. An NDA submission to the FDA for KarXT in schizophrenia in mid-2023.

Regarding our infectious diseases portfolio, we have several noteworthy developments. For sulbactam-durlobactam or SUL-DUR, we submitted the NDA for the treatment of carbapenem-resistant Acinetobacter baumannii infection to the NMPA in December 2022. We were granted priority review one month later in January 2023, and in February, the NDA was officially accepted by the NMPA. We look forward to bringing this novel drug to China and Asia Pacific, where severe CRAB infections are frequent and often can no longer be adequately treated because of multi-drug resistance. For omadacycline, NUZYRA, as Samantha mentioned earlier, we are happy to report that it was successfully listed in China's NRDL as of January 2023. Lastly, our internally developed to pical IL-17 product, PL-1102, continues to progress towards initiation of a phase II study for chronic plaque psoriasis in later 2023.

Now Billy will speak about progress with our commercial products and financial results. Billy?

Billy Cho (CFO)

Thank you, Harald. Our full market of products, ZEJULA, Optune, QINLOCK, and NUZYRA, continue to achieve solid revenue growth driven by strong demand and commercial execution. ZEJULA continues to perform well and increase its share of PARP sales for ovarian cancer during the Q4 of 2022. We expect ZEJULA to become the sales leader in China this year. For Optune, we are starting to see a strong recovery given the COVID situation throughout last year, achieving solid revenue growth in the Q4. During 2022, our team focused on continuing to improve market access by expanding commercial and supplemental insurance coverage for Optune and educating physicians about its potentially significant clinical benefits, including survival. As of December 31, 2022, Optune was covered by 87 municipal or provincial supplemental insurance plans, up from 33 such plans the prior year.

We're pleased to have added QINLOCK and NUZYRA to China's National Reimbursement Drug List in January 2023, and implementation starts this month. As discussed earlier, we expect strong revenue ramp-up for these products as a result of their NRDL inclusion. For efgartigimod, the first and only US-approved FcRn blocker with pipeline and product potential, we're getting ready for the commercial launch later this year. We plan to have specialized and experienced team for Efgar with about 100 employees at launch. We are quite excited about its blockbuster potential in China. Now I will discuss our full year and Q4 of 2022 financial results compared to the prior year periods. Total revenues for the full year of 2022 were $215 million, compared to $144.3 million in 2021, representing a 49% year-over-year growth.

Total revenues for the Q4 of 2022 were $62.6 million, compared to $44.2 million in the prior year, representing a 41.7% year-over-year growth.

Product revenues for the full year of 2022 were $145.2 million for ZEJULA, compared to $93.6 million in 2021, representing a 55.2% year-over-year growth. $47.3 million for Optune compared to $38.9 million for 2021, a 21.6% year-over-year growth. $15 million for QINLOCK compared to $11.6 million in 2021, a 28.7% year-over-year growth. $5.2 million for NUZYRA compared to close to zero in 2021.

R&D expenses were $286.4 million for 2022 compared to $573.3 million for the same period in 2021. The decrease in R&D expenses in 2022 was primarily due to lower upfront payments for new licensing agreements. Excluding upfront payments for new licensing agreements, R&D expenses were $256.4 million in 2022 compared to $252 million in 2021. SG&A expenses were $259 million for 2022 compared to $218.8 million for the same period in 2021.

The increase was primarily due to higher payroll and payroll-related expenses from the increased headcount as Zai Lab continue to expand and invest in its commercial operations in China and infrastructure in the United States in anticipation of substantial growth over the next few years. Zai Lab reported a net loss of $443.3 million or a loss per share attributable to common stockholders of $0.46 for 2022, compared to a net loss of $704.5 million or a loss per share attributable to common stockholders of $0.76 for 2021. The decrease in the net loss was primarily attributable to lower payments related to new business development activities and continued growth in product sales.

As of December 31, 2022, cash and cash equivalents, short term investments and restricted cash totaled $1 billion compared to $1.4 billion as of December 31, 2021. We would now like to turn the call back over to the operator to open up the line for questions. Operator?

Operator (participant)

Ladies and gentlemen, we now begin the question and answer session. If you wish to ask a question, please press star one one on your telephone. Please keep your question to maximum of two. Star one one to ask a question. We are now taking the first question. Please stand by. The first question from Michael Yee from Jefferies. Please go ahead.

Michael Yee (Managing Director and Senior Biotech Analyst)

Hey, guys. Thanks. Good morning from our side. We had two questions. One was, maybe you could just give us sort of a real-time update with how things are going in China as opposed as regards to opening up as Covid evolves there, both from a commercial execution standpoint but also from a clinical trial execution standpoint for all the partners. How is that progressing sort of relative to pre-Covid? Second is obviously with TTF and lung cancer, that was a big announcement recently. Appreciating that needs to probably get filed first, et cetera. How are you thinking about that launch and opportunity relative to GBM and particularly on the reimbursement side, how to think about that opportunity? Thank you.

Billy Cho (CFO)

Hey, thanks Mike for your questions. Maybe I'll get started and other colleagues can chime in. Some on the ground reporting from COVID kind of opening. I think everyone is quite familiar with the, with the challenges that everyone faced in 2022. The impact of course in, you know, even all the way through end of 2022 as well as early this year. We're clearly monitoring the situation very closely and we'll continue to do that. So far so good. It looks like, you know, as we kind of enter right now in March and wrapping up the Q1, it looks and we're being optimistic going into the spring and beyond and getting back into some semblance of normalcy. Pretty energized.

If you are here and, I'm in Shanghai right now, the activity is quite active and buzzing, so it's great to see that, traffic not so much. On the commercial side and the R&D side. On the R&D piece, I think we've really learned with our team in the, in the clinical development, clinical ops team has done a terrific job of navigating the challenges, you know, with Covid in the past. You've, you've seen us, you know, consistently execute and have a very resilient performance and not slipping up in any of our commitments, to the patients, to the, you know, to the, you know, physician community, to our partners, et cetera.

You know, I think for us, you know, we managed it quite smoothly, so quite proud of that. As well as commercial, you would have seen, you know, consistent growth. You know, I think Q4 came in, given what happened, you know, even through the end of December and parts of early this year, you know, I think relatively speaking, quite happy with the outcome, and looking forward to, you know, a more normal environment. We expect 2023 to, you know, to be a strong year for growth. On the Tumor Treating Fields, I think your question was really more towards on the commercial opportunity part and reimbursement part.

You've probably heard us say before that like an NRDL, a national reimbursement policy, for a technology like Tumor Treating Fields, we think that there's a possibility it could be, it could be formalized as early as this year. We'll all sort of be on standby for that, and if we hear something, we'll kind of upstream to everybody else. And the significance of it's subject to data of course for LUNAR, but the opportunity is quite significant. I think Rafael said that there's. And people know there's 700,000 new cases per year for non-small cell lung cancer, half of whom are gonna be in stage 4, and about 30% in stage 3.

Despite treatment options available, the significant unmet medical need and at that type of quantum number is pretty dire. Again, substitute data that should be coming out sometime this year. The opportunity is quite significant and it could be a blockbuster program opportunity for us.

Michael Yee (Managing Director and Senior Biotech Analyst)

Good. Thank you.

Operator (participant)

Thank you for your question. We are now taking the next question. Please stand by. The next question from Anupam Rama from J.P. Morgan. Please go ahead. Your line is open.

Anupam Rama (Managing Director and Senior Equity Analyst)

Hey, guys. Thanks so much for taking the question. Maybe a broader question, actually. You guys have talked a lot about private pay and supplemental insurance. What portion of revenues are currently reimbursed with this mechanism? What does that look like as you model out to 2025 and 2030 timeframe? Which products do you see with the greatest portion being reimbursed by private pay and supplemental insurance? Thanks so much.

Billy Cho (CFO)

Hey, Anupam. Josh, do you wanna take this one?

Josh Smiley (COO)

Sure. Hi, Anupam. Thanks for the question. I'd say first, you know, we're pleased with the overall reimbursement environment in China and its development over the last few years. You know, certainly on the supplemental insurance side, we've seen a number of people covered grow from about 40 million at the end of 2020 to 150 million at the end of 2022. We expect that number to grow over the next few years to, you know, somewhere between 200 million-300 million. A quite sizable population if you start to look at that compared to other, you know, countries around the world. That's certainly positive, and we see the benefits of that, you know, most directly now in Optune.

You know, in terms of percentages, while we don't break it out, you know, I think just looking at our 2022 results, ZEJULA is covered through NRDL, the other three products weren't. Just at a very macro level, you know about 70% or so of our sales were through some NRDL mechanism, the rest through a combination of, you know, commercial supplemental insurance and private pay. I think as we look forward, though, certainly with the growth in supplemental insurance, that provides a really important option at launch for our innovative products for a sizable number of patients to have access to the innovation and for physicians to get experience.

Our strategy is going forward for the kind of drugs that we are developing, either in our internal pipeline or with partners, you know, we think they are ultimately gonna be NRDL opportunities. Billy alluded earlier that even on the medical device side, we see some really, you know, important progress there. I think, Anupam, really our strategy is to, you know, bring great innovation, as it relates to China, great innovation to Chinese patients, and we wanna do that as broadly as possible. Our lead strategy will be to leverage NRDL opportunities. We're quite pleased with the 3 products we now have on NRDL and the economics associated with them. In other words, the net price we now have relative to the patient opportunities.

We'll continue to pursue that for innovative drugs like efgartigimod this year. Certainly the multilayered system we're seeing now in China develop in a robust way provides a lot more flexibility and a lot more options for early access for some sizable amount of patients, over time. Thanks for the question.

Anupam Rama (Managing Director and Senior Equity Analyst)

Thanks so much.

Operator (participant)

Thank you for your question. We are now taking the next question. The next question from Yigal Nochomovitz from Citi. Please go ahead. Your line is open.

Yigal Nochomovitz (Director of Biotech Equity Research)

Hi. Thank you for taking the question. Billy, I think you said that you're basically flat year-on-year on R&D, OpEx up-fronts and maybe marginally higher year-on-year on SG&A. Just if you could just clarify, is the spend basically gonna be flattish going forward to drive to overall corporate pro-profitability with the top line growth by the year-end 2025? Or might you have some flexibility to accelerate OpEx and still navigate to profitability with the top line growth by the end of 2025? Thanks.

Billy Cho (CFO)

Yeah. Hey, Yigal. You're right. You heard that correctly. In terms of core R&D, it was pretty much at the 250 level, roughly flat year-over-year, 2021, 2022. This year, you can expect a very modest increase. As you know, we have a pretty active development calendar, given the anticipated approvals and launches over the next 2, 3 years. I think we have around 8 at least in the queue. I think you should expect that to be at that range.

For SG&A, the S portion, you know, we have said that this year we're going to be commercially profitable, or we target to be commercially profitable, even as we build a new sales team for efgartigimod launch. That's a great place to be. You can expect to see that, you know, operating leverage continue to increase as the revenue increases, and as we launch additional products. There is, you know, a lot of flexibility that we have, and that's, I think, you know, a kind of a great place to be.

You know, when you have kind of a growing and relevant scale, a strong balance sheet, and sort of all the engines are firing on all cylinders, you can establish a good baseline and preserve some optionality.

Yigal Nochomovitz (Director of Biotech Equity Research)

Got it.

Josh Smiley (COO)

Hey, Billy. I'll just maybe add just one quick point to that, is, you know, really our priorities are to grow the top line and to advance our clinical programs, and we've got, you know, a plethora of them. If we execute on those two priorities, you got all, you know, the profitability is gonna follow. If you look at, you know, products like ZEJULA and our women's health franchise and the expected growth over the next few years, and then add TIVDAK on top of that, those are the things that are gonna drive profitability and give us the flexibility that Billy mentioned to continue to invest in, you know, sales force, to continue to invest in the clinical program. Again, to us, it's more around the portfolio that we built.

If we execute as we expect to along that side, the profitability is gonna come.

Yigal Nochomovitz (Director of Biotech Equity Research)

Just real fast, just one housekeeping on QINLOCK and NUZYRA. Can you say at this point what the discount is for the NRDL? I think you mentioned in the press release you expect significant increase. Just for our modeling purposes, what does that look like? Thanks.

Billy Cho (CFO)

Yeah. The NRDL pricing for QINLOCK is $2,400 a month. For NUZYRA, it's $450 a month. Oh, sorry. For NUZYRA, it would be for the treatment. The $450 for the treatment cost.

Yigal Nochomovitz (Director of Biotech Equity Research)

Okay.

Billy Cho (CFO)

The treatment program.

Yigal Nochomovitz (Director of Biotech Equity Research)

All right.

Billy Cho (CFO)

Yeah.

Yigal Nochomovitz (Director of Biotech Equity Research)

Thanks.

Operator (participant)

Thank you for your question. We are now taking the next question. Please stand by. The next question from Jonathan Chang from SVB Securities. Please go ahead. Your line is open.

Jonathan Chang (Senior Research Analyst)

Hi, guys. Thanks for taking my questions. Can you elaborate more on the assumptions underlying your guidance of achieving corporate profitability by end of 2025 and discuss your level of confidence in this? Second question, can you discuss Zai Lab's current state of compliance with the HFCAA and how you're thinking about the situation going forward? Thank you.

Billy Cho (CFO)

Yeah. Thanks, Jonathan. I'll take these two. Maybe I'll start with the second one. That's got to be a quick point that I want to that I can make. You would have seen that our 10-K that we just filed is with KPMG US. That means that we have filings that are fully accessible by the PCOV. As a result, you know, we have and continue to believe that we are now fully compliant with all the requirements of the HFCAA, that's going to preclude us from, you know, now and future to be off sort of any kind of list or any kind of potential for delisting from the Nasdaq. Very proud of the team that worked hard, you know, to get this done.

It was strategically very important for us. I think, you know, again, a little kudos to the team. Welcoming KPMG US on board. To your first question, on kind of how do we feel about the statement that we made about getting to an overall profitability by end of 2025? Jonathan, we wouldn't make such statements, you know, unless we've carefully thought about it. The best way to think about the... You know, we're not giving guidance, at this time, so we're not gonna kind of give you hard numbers.

If you took your, you know, the number that you had for 2025, whether you, Jonathan, or whether the Street, and I know there's a range out there, but you take that and you assume, even if you assume just today's gross profit, and you know that's gonna continue to improve over, you know, kind of next several years. You know, use that, and then you kind of stick with, sort of the, you know, modest assumptions on sales, marketing, and G&A, especially since we would have already done a lot of heavy lifting infrastructure spend by then, you will be able to get that. I think you should, you know, we feel pretty good about it.

You know, that gives us the confidence to make, you know, a public comment about that.

Jonathan Chang (Senior Research Analyst)

Got it. Thank you.

Operator (participant)

Thank you for your question. We are now taking the next question. Please stand by. The next question from Ziyi Chen from GS. Please go ahead. Your line is open.

Ziyi Chen (Equity Research Analyst)

Thank you. Thank you for taking my questions. The first question is, you know, if we're looking at the commercial infrastructure, well, with more drugs expected to be launched in 2023 and next year, including mirvetuximab, Efgar, repotrectinib, and more antibiotics. The therapeutic category is becoming, you know, much bigger compared to what it is now. Trying to understand a bit more about your plan in terms of commercialization team set up in order to achieve the sales efficiency, and of course, maintain the productivity when covering a variety of different therapeutic areas. Secondly, you, since you mentioned about, you know, Optune, now looking forward to the data.

could you elaborate a little bit more about, you know, based on the LUNAR data and what you're gonna planning to communicate to CDE in China and what could potentially be the regulatory pathway and also timetable for the potential indication approval in China? Thank you.

Billy Cho (CFO)

Yeah. Thanks, Dee. I'll give your second question to Rafael. On your first question, you know, people who are familiar with Zai Lab story knows, we've been pretty thoughtful about curating a portfolio that's clustered around specific areas that are very strategic for us. Within that, some of the They're all quite differentiated, and some of the programs are quite large in terms of commercial potential. So potential blockbusters, you know, would be the likes of, let's see, based on the data for LUNAR, the Tumor Treating Fields franchise, bemarituzumab, adagrasib as a pipeline of program. I think that people are underappreciating, you know, drugs like KarXT, et cetera. That's point one. Point two is, it's actually a...

You know, if you look at a snapshot of a quarter, 2 quarter, 3 quarter, you know, you will not see it. If you look at what we have in currently the NDA submissions, and you've already mentioned some of those, and you look at the programs that we have in pivotal stage right now, there's also a lot of clustering effect going on. For women's cancer franchise that we've already built that with ZEJULA, you've threw out, you know, MARGENZA, but we have TIVDAK that Josh, you know, mentioned, and these are pretty substantial operating leverage that kicks in. I believe that we have a slide in our corporate deck that says, "Here's a case study for ZEJULA," which is the first drug in the women's cancer franchise.

You layer TIVDAK on top of that, you know, we're sort of expecting commercial profitability, you know, kind of profit margins for that product to be in the 40% range and even build upon from there. You look at the lung programs in just the near-term stuff, you've got in addition to, of course, LUNAR, which benefits from, of course, a specialized sales force for Tumor Treating Fields and often anyways. The lung itself would have, you know, a, They have LUNAR, they have crizotinib, you know, we've got the ROS1, I'm probably missing one or two more.

We think that we have a lot of, you know, just a great opportunity here to drive productivity as we scale kind of revenue pretty much at the same time. You will not see it in like, you know, from a quarter view, 2 quarter view from within a 1 to 2 year timeframe. You just, you know, really begin to see that.

Rafael Amado (President, Head of Global Oncology Research and Development)

This is Rafael.

Billy Cho (CFO)

Please.

Rafael Amado (President, Head of Global Oncology Research and Development)

Yeah. I wanted to go over the second part of the question. You know, just briefly, Novocure has made public that they expect to submit a PMA or Premarket Approval Application with the US FDA on the second half of this year. That's the equivalent of the NDA for drugs. Our plan is to follow the Healx submission and submit the NDA following the US submission in China. You know, the timing of that is still obviously flocked as we work with our partner for exact timing of the submission in the US. It will follow very closely the US submission.

Then obviously there's no particular timeline in China, but, we will work with the authorities to try to, you know, accelerate the approval, as soon as possible. You know, we expect that, this, you know, potentially, you know, could be approved in the not-too-distant future and the file would be imminent after the, U.S. file.

Ziyi Chen (Equity Research Analyst)

Got it. Thank you.

Rafael Amado (President, Head of Global Oncology Research and Development)

Thank you for your question. We are now taking the next question. Please stand by. The next question from Seamus Fernandez for Guggenheim Partners. Please go ahead. Your line is open.

Seamus Fernandez (Senior Managing Director and Global Biopharmaceuticals Analyst)

Great. Great. Thanks for the question. Just 2 quick questions. Can you, team, if you could just walk us through how you see the KarXT opportunity evolving. You know, I think, Billy, you specifically stated that you feel this particular program is underappreciated. Just again, from that SG&A spend perspective, what do you think is necessary to really effectively promote KarXT to kind of maximize the opportunity? Just a second quick question. As we think about the Tumor Treating Fields opportunity, obviously manufacturing to support this potential size of that market opportunity is gonna be important. Can you just help us understand how you're going to approach that opportunity from a manufacturing perspective? Thanks.

Billy Cho (CFO)

Hey, Seamus. Thanks for your question. I'll provide the manufacturing question to Josh. For your question on KarXT, Yeah, you're right. I did say, you know, people are underestimating the potential in China, and we believe that, you know, there are more than 8 million people in China living with schizophrenia today. We believe in this product. Yeah, we think that it's got a potential to treat multiple symptom domains as monotherapy or even, you know, adjunctive. Really out of the 8 million people, we know that 4.3 million people are diagnosed with severe forms of schizophrenia in the national database. These are, you know, truly, you know, significant figures.

I think I hear, you know, my colleague, Harald, clearing his throat because I think he may be adding some comments here and there, but, feel free to chime in, Harald, on the potential, you know, impact of KarXT, you know, on a kind of a TAN the size of, you know, in, you know, China.

Harald Reinhart (President, Head of Global Development (Neuroscience, Autoimmune and Infectious Diseases))

Yeah. Thank you for the question, too. It's clear that when we in-licensed KarXT, we were really keen on bringing something to China which is differentiated. We have and see in KarXT in two studies now, in the EMERGENT-1 and in the EMERGENT-2, both are the EMERGENT studies, that this drug is addressing the negative symptoms that are really difficult to treat with existing pharmaceuticals. The second one was the side effect profile. This is a totally different class of drugs, and that alone is an important piece to remember because most of the other antipsychotics for schizophrenia, they do come from the serotonin dopamine series and have a certain side effect profile, which is really problematic. That's one of the reasons why a lot of patients do not continue treatment.

As far as the addressable patient population, there is a significant unmet need in the patients with schizophrenia just because the negative symptoms are not adequately treated at this point in time. We see this as a global issue, but we see it also in China, where there is a need to bring more psychiatric help to patients who are currently underserved. There's a government drive to increase the numbers of psychiatrists and to help patients out with schizophrenia, much more so than in the past. From our perspective, we see a significant market potential in China, and we see it in a patient group that currently has very few options. Thank you.

Billy Cho (CFO)

Yeah. Seamus, to the second part of your question about what kind of infrastructure, the commercial infrastructure is needed. You know, we're not yet in the, you know, we can provide a specific number later on as we're close to the approval and launch. While the prevalence of disease in the neurosciences is quite large, it's pretty concentrated market. We believe that a sales team that's focused and smaller than even an oncology product will be sufficient. On top of that will be to leverage existing capabilities that we have that we've built for example, Efgar, gMG, and CIDP, as you know, that touches neurology.

You know, I think, it will provide specific, you know, details later on, but, it's going to be an efficient build-out.

Josh Smiley (COO)

Thanks. I'll take the manufacturing question on TTFields. Thanks, Seamus. I think first, this is a hopefully a great problem to have. Of course, Novocure's been, you know, focused on the breadth and size of the opportunity for many, many years and have a series of strategies in place to work to bring down manufacturing costs for the, you know, for the device. I think if we look at the China opportunity, of course it's gonna be driven by the data.

If you look at the studies that are underway today across various tumors as well as, you know, where the data could lead us, I think our view is there's probably somewhere in the range of 1.8 billion patients in China who could benefit from, you know, could benefit from the technology over time. The volumes that we're considering and thinking about here could be quite significant. With those volumes, I think there will be very good opportunities to bring down, you know, unit costs, and we're working closely with Novocure on those strategies. Again, they've got the same view as they look at the world, not just China. I think we're excited about the commercial opportunity.

We certainly believe that given the potential volumes here and the supply chain and manufacturing strategies that, you know, that Novocure is working on and that we're partnering with them on, that we'll be able to have this be a, you know, very attractive economic proposition as well with both the gross margin as well as at the, you know, at the bottom line. Again, I think the big focus for us, of course, will be to get through the LUNAR data to see the readouts from, you know, the studies in, you know, other tumors.

We're well, you know, we're well-aligned with Novocure and well-prepared to supply the volumes that we think, you know, can benefit Chinese patients and to be able to do that at reasonable gross margins.

Operator (participant)

Thank you for your question. We are now taking the next question. Please stand by. The next question from Yang Huang from Credit Suisse. Please go ahead. Your line is open.

Yang Huang (Equity Research Analyst)

Thanks for taking my questions. I have two. First one is about LUNAR trial. We know that we are going to see LUNAR data in the first half this year. I think people are probably, including us, are more interested in understanding some subgroup analysis for LUNAR, right? Given LUNAR trial enrolled both in first-line people who only receive chemo and the people receive PD-1 plus chemo.

My question is that case that the subgroup analysis for the patient who receive PD-1 plus chemo in the first line is a kind of key to allow us to file and in the worst case, let's assume a worst case scenario, if the subgroup analysis in the PD-1 plus chemo group is not that great considering the treatment landscape is different between U.S. and China, will Zai Lab still consider filing for the indication? That's my first question. Thanks.

Billy Cho (CFO)

Rafael, I think this is, this one's for you.

Rafael Amado (President, Head of Global Oncology Research and Development)

Yeah, I'll take the question. Thanks for this insightful question. I think the most important thing is to understand that the study met its primary endpoint, with both statistically and clinically meaningful results on the primary endpoint. You know, in any study, that's really what matters. It is a randomized trial, and the population being studied is the post platinum population, so prior PD-1 is not an exclusion criteria. The study is randomized, obviously, and stratified as well. Factors are supposed to mitigate for patient imbalances.

The important point I think is that regardless of the makeup of the PD-1 subgroup, there was a statistically significant and clinically meaningful difference in overall survival in the overall population and in the PD-1 subgroup, with the trend in the docetaxel group. The details of the patient characteristics and prior treatment history, will be shared at future data presentations, and the release is owned by Novocure. Rather than speculating on subgroups, I think it's best to just wait for the full analysis of the data set to interpret the results. But, you know, we should be cautious about subgroup analysis and really focus on the primary analysis which had results that were pretty exciting as reported by Novocure.

Yang Huang (Equity Research Analyst)

Okay. Got it. Yeah, my second question is on efgartigimod commercial preparation. As we understand, this is a kind of a rare disease in China as well. Can the company let us know, has company started to try to identify some MG patients, just to, you know, prepare for the launch of the drug? If so, can you let us know, kind of how many MG patients you have identified so far?

Billy Cho (CFO)

Yeah. Hey, Yang, I'll take this one. First of all, the addressable, you know, patient pool is quite large for MG. We're talking about a prevalence, maybe about 200,000. We strongly believe that efgartigimod will become a very important treatment option for these patients. It's early days, but we have started to build awareness ahead of the anticipated approval and launch. As you know, we've launched a program in a part of China where, you know, patients can potentially get access. It was really more for strategic purposes, given travel restrictions up until recently. It really allowed us to engage, you know, with not only the physician, but patients and get some feedback and responses. It's quite encouraged by what we see. No surprise, right?

Given what's been happening outside of China. I believe argenx reported, you know, a pretty strong first-year sales and engagement and, you know, whatever metrics that you follow on the commercial side. I think that's provides a nice read-through for the potential and opportunity in China.

Yang Huang (Equity Research Analyst)

Okay, great. Thank you.

Operator (participant)

Thank you for your question. There are no further question at the moment. I will hand back for closing remarks.

Speaker 13

Thank you, operator. I want to thank everyone for taking the time to join us on the call today. We appreciate your support and look forward to updating you again after the Q1 of 2023. Operator, you may now disconnect the call.