Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab First Quarter 2023 Financial Results Conference Call. [Operator Instructions] As a reminder, today's call is being recorded. It is now my pleasure to turn the floor over to Billy Cho, Chief Financial Officer of Zai Lab, who will make introductory comments..

Thank you, operator. Good morning, good evening, and welcome, everyone. Zai Lab recently issued a press release providing the details of the company's first quarter 2023 financial results, as well as some recent product highlights and corporate update.

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. She will be joined by Josh Smiley, President and Chief Operating Officer. Dr.

Rafael Amado, President and Head of Global Development Oncology and Research and Develop 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’ve made in those three therapeutic areas.

And I will discuss the performance of our market products and conclude the comments on our first quarter 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.

Such 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..

Thank you Billy. Hello everyone. Thank you all for joining us today. Our first quarter results and progress continue to demonstrate Zai Lab’s potential global best-in-class portfolio and track record of execution, despite challenges from China’s re-opening at the beginning of the year.

The positive top line readout from the Phase 3 EMERGENT-3 trial of KarXT in schizophrenia and the positive analysis from the Phase 2 innova TV 207 study from TIVDAK in head and neck cancer further support our belief that these products provide important treatment options for patients in China and globally.

We are very excited by the unanimous recommendation of the U.S. Food and Drug Administration Advisory Committee’s in support of approval of sulbactam-durlobactam, the first pathogen-targeted therapy for patients with severe and life-threatening infections caused by Acinetobacter.

Recently, we expanded our lung cancer franchise and enriched our global oncology pipeline with a next generation DLL3 antibody-drug conjugate or ADC program, ZL-1310. This global ADC program demonstrates our continued focus on the ADC space and our extension to the global market.

This product complements our lung cancer franchise, and we will leverage our strong capabilities to develop ZL-1310, and look forward to seeing results in patients. I look forward to leading Zai into its next transformational stage of growth, productivity, and global opportunities.

To better support me and help meet the strategic and operational needs of our business during this next stage of growth, we are happy to announce that we have promoted Josh Smiley to President and Chief Operating Officer.

Josh’s rich experience and strategic vision will help us further grow as a leading global biopharmaceutical company and deliver on our mission to improve human health and on our corporate strategic goals for driving innovation in China and beyond. I would like now to turn the call over to Josh.

Josh?.

Thank you Samantha. I look forward to taking on this new role for the company and continue to work with Samantha and the rest of our team to move our company forward. I’m very excited about what is in store for us for the next few years that positions Zai Lab to be a leader in bio pharma innovation.

We’re pleased with the overall environment this year in China for companies like Zai Lab with innovative therapies that meet significant unmet medical needs. As Samantha mentioned, as a result of the proactive steps taken by our team, Zai Lab has established a good foundation for future commercial execution and strong financial performance.

Despite challenges from the COVID-19 reopening in China during the first two months of the quarter, Zai Lab continues to deliver solid growth and overall financial results. Our net loss in the first quarter of 2023 decreased 40% compared to the same period last year, primarily attributable to the increase in product revenue and non-operating income.

And we expect strong growth momentum to continue throughout the remainder of this year. ZEJULA continues to perform well with increased sales for ovarian cancer and we believe ZEJULA remains on track to become the leader in its asset class for ovarian cancer in China starting this year.

For Optune, our team continued to improve market access by expanding commercial insurance and supplemental insurance coverage. As of March 31, 2023, Optune was covered by 96 municipal or provincial supplemental insurance plans, up from 37 as of March 31, 2022.

We're pleased to have added QINLOCK and NUZYRA to China's National Reimbursement Drug List, effective in March 2023. As discussed earlier, we expect a strong revenue ramp-up for these products as a result of their NRDL inclusion. For efgartigimod, the first and only U.S approved FcRn blocker with pipeline and a product potential.

We're getting ready for the commercial launch later this year. As we communicated earlier, we plan to have specialized and experienced team for efgar with approximately 100 employees at launch. We are excited about its potential in China.

With respect to our 2023 strategic priorities, we've made progress towards the BLA approval of efgartigimod for generalized myasthenia gravis, or gMG and the BLA submission for the subcutaneous efgartigimod for gMG in China.

The initiation of a bridging study for KarXT and schizophrenia in Greater China, the initiation of a registrational study for Bemarituzumab in first-line gastric cancer in Greater China, and a full data readout of the tumor-treating field's LUNAR Phase 3 study in non-small-cell lung cancer.

We're also advancing our proprietary pipeline with global rights, including by initiating a global Phase 1 study for ZL-1218, or CCR8, and moving ZL-1102, our IL-17 Humabody, into full global development. We recently released our 2022 ESG report that details our ESG strategy, which we call Trust for Life. It has three commitments.

First, improve human health. Second, create better outcomes. And third, act right now. We're benchmarking ourselves against commonly accepted standards and major indexes.

We're continuing to reach more patients with our existing commercial products and are preparing to launch eight additional products as we take the steps to achieve overall corporate profitability by the end of 2025 and reach 1 million patients by 2030. And now I will turn the call over to Dr. Amado.

Rafael?.

Thank you, Josh. In the first quarter of 2023, Zai Lab’s oncology franchise continue to make progress on all fronts, and we expect to have a productive year.

Recall that earlier this year, our partner, NovoCure, announced that the LUNAR clinical trial met its primary end point, demonstrating a statistically significant and clinically meaningful improvement in overall survival when DT field therapy was added to standard therapies compared to standard therapies alone in patients with platinum-resistant non-small-cell lung cancer.

We recently announced that the LUNAR data will be presented on the morning of Tuesday, June 6, as a late-breaking abstract in ASCO’s metastatic, non-small cell lung cancer session. We are pleased to have contributed and be part of the LUNAR study.

In China, the incidence of non-small-cell lung cancer is well over 700,000 new cancers per year, or 37% of all non-small-cell lung cancer diagnosed worldwide, and it accounts for 39% of global deaths due to non-small-cell lung cancer each year.

We look forward to the presentation of the data at ASCO and are excited about the potential PPCO [Ph] to address such enormous unmet needs for patients with lung cancer, as well as for patients with other tumor types, as subsequent results read out.

As Samantha mentioned, in April, our partner Seagen presented encouraging efficacy results from the Phase 2 innovaTV 207 study in TIVDAK in patients with treatment-refractory head and neck cancer at the 2023 AACR annual meeting. At data cutoff the confirmed overall response rate was 40% with 1 complete response and 5 partial responses.

The safety profile was generally consistent with that observed across TIVDAK monotherapy clinical studies. Treatments for head and neck cancer remain a significant unmet need in China, with approximately 71,000 new cancers annually. Following progression on first-line standard therapy, there are limited treatment options.

Immunotherapy and chemotherapy have low objective response rates with poor outcomes. While more data are required to expand on this result, we believe TIVDAK could be a promising treatment option for patients with recurrent and or metastatic head and neck cancer, and we are planning to pursue this indication in China in collaboration with Seagen.

Moving now to KRASG12C or adagrasib, our partner Mirati presented updated Phase 2 data on the KRYSTAL-1study in patients with pancreatic adenocarcinoma, biliary tract cancer, and other solid tumor, heart, brain, KRASG12C mutations at the plenary series program of the April session of ASCO, and subsequently published the results as a rapid communication in the Journal of Clinical Oncology.

Results showed an objective response rate of 35% for the overall cohort. In patients with pancreatic cancer, the objective response rate was 33%, and for patients with biliary tract cancer, it was 42%.

Notably, the safety profile of adagrasib was aligned with that previously reported in patients with pretreated non-small cell lung cancer and colorectal cancer.

These findings demonstrate a meaningful improvement relative to the historically reported standard-of-care for these cancers, and we are very pleased to see the results of this Phase 2 study, which demonstrate a marked improvement on the current standard-of-care for patients with unreceptible or metastatic KRASG12C mutated solid tumors, including gastrointestinal cancers, where few treatment options exist.

We look forward to closely working with Mirati to advance adagrasib as a potential best-in-class treatment option for patients with tumors harboring KRASG12C mutations.

Moving to our internal global research and development programs, we presented new translational and clinical biomarker data from our Global Oncology Program, ZL-1211, and articulated a pinpoint to specific antibody at AACR, showing that ZL-1211 as monotherapy seemed to be tolerated well and showed early signs of anti-tumor activity.

In addition to TIFGAC, we're expanding our pipeline into the antibody drug conjugate or ADC phase and building a portfolio of potential first and or best-in-class ADCs through both internal discovery and external collaboration.

Last month, we increased our lung cancer franchise and enriched our Global Oncology Pipeline with a next-generation ADC program, ZL-1310. This compound is an innovative DLL3ADC discovered by using MediLink's proprietary TAMLIN platform..

TAMLIN is a next-generation ADC platform designed to leverage the tumor microenvironment to overcome the challenges in current ADC drugs. DLL3 is an inhibitor of the Notch ligand that is overexpressed in small cell lung cancer and neuroendocrine tumors. We will leverage our global development capabilities to advance this product into clinical studies.

We are on track to meet all the milestones this year, including the initiation of the bemarituzumab gastric cancer trial in China and the filing of Repotrectinib for ROS1 mutated non-small cell lung cancer with an abundance of potentially best-in-class and first-in-class products, both in China and globally, we are very excited about our expanding oncology pipeline at Zai lab.

And 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?.

Thank you, Rafael. I'm excited for the opportunity to share with you today progress across our autoimmune, infectious diseases, and neuroscience therapeutic areas. Let's start with KarXT, the combination of xanomeline and trospium, which we are developing with our partner Karuna in acute schizophrenia.

Results from Karuna’s EMERGENT-3 trial were released in March 2023. This is now the third positive registration trial that has met its primary endpoint, with KarXT demonstrating a reduction of 8.4 points in PANSS total score compared to placebo at week 5.

KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative factor subscales, which are secondary endpoints in the trial. Karuna plans to submit a new drug application to the FDA in the third quarter of 2023, with launch in the second half of 2024 if approved.

As Samantha mentioned, KarXT could be a very important treatment option as a new class of medicine for schizophrenia patients in China and globally. Our proposed development plan for China has been accepted by the NMPA, and we are on track to start a clinical bridging trial in June.

Regarding our infectious diseases portfolio, the FDA Advisory Committee recently unanimously voted in favor of approval of Sulbactam-Durlobactam or SUL-DUR. We are excited about the committee's strong vote of confidence.

We submitted an NDA for the treatment of Carbapenem-Resistant Acinetobacter Infection to the NMPA in December 2022, with priority review granted one month later. And in February, the NDA was officially accepted by the NMPA.

We look forward to bringing this novel drug to China and to Asia-Pacific, where severe crab infections are frequent and often can no longer be adequately treated because of multidrug resistance. Much progress was made this past quarter in VYVGART or efgatigamot.

We submitted the BLA for efgatigamot IV for the treatment of patients with generalized myasthenia gravis, or GMG, in China in the second quarter of 2022 and expect approval and commercial launch this year. We also expect to submit a BLA for efgatigamot SC subq for GMG in mid-2023.

We continue to support our partner GenX on indication expansion in China and worldwide. Last but not least, for our internally developed topical IL-17 product CL-1102, we are moving forward with preclinical and regulatory activities in preparation for our global Phase 2 trial.

Let me now hand over to Billy, who will speak about progress with our commercial products and financial results.

Billy?.

Thank you, Harald. Now I will discuss our first quarter of 2023 financial results compared to the prior year period. Total net product revenues for the first quarter of 2022 for the first quarter of 2023 were $62.8 million compared to $46.1 million for the same period in 2022, representing 36% year-over-year growth.

This included a net product revenue of $42.7 million for ZEJULA, compared to $29.6 million for the same period in 2022, representing a 44.2% year-over-year growth; $13.3 million for Optune, compared to $12.8 million for the same period in 2022, representing.

$1.3 million for QINLOCK, compared to $3 million for the same period in 2022; and $5.5 million for NUZYRA, compared to $0.7 million for the same period last year.

Note that product revenue in the first quarter of 2023 included a negative $3.9 million non-recurring adjustment to compensate distributors for sales of QINLOCK and NUZYRA at prices prior to the price reductions made in connection with their initial inclusion in the NRDL.

Such sales rebates to distributors on previously purchased products are customary in our industry to compensate those distributors for the new NRDL selling price. Research and Development expenses were $48.5 million for the first quarter of 2023, compared to $53.9 million for the same period last year.

The decrease in R&D expenses was primarily due to cost-sharing compensation from collaboration partners related to our clinical trials, partly offset by higher payroll and payroll-related expenses from increased R&D headcount. SG&A expenses were $62.5 million for the first quarter of 2023, compared to $57 million for the same period in 2022.

The increase was primarily due to higher professional service fees and in connection with sales of our products in Greater China and higher payroll and payroll-related expenses with increased commercial headcount.

As Zai Lab continued to 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 $49.1 million, or a loss per share attributable to common stockholders of $0.05 for the first quarter of 2023, compared to a net loss of $82.4 million for the same period in 2022, or a loss per share attributable to common stockholders of $0.09.

The decrease in net loss was primarily due to product revenue growing faster than operational expenses, and the increase in non-operating income, including interest income and foreign currency gains.

As of March 31, 2023, cash and cash equivalent, short-term investments, and restricted cash totaled $931.4 million, compared to $1 billion as of December 31, 2022. We would now like to turn the call back over to the operator to open up the line for questions.

Operator?.

Thank you. [Operator Instructions] Our question comes from the line of Michael Yee from Jefferies. Please ask your question, Michael..

Thanks. Good morning and we had two quick questions. On efgartigimod, I know that you guys are waiting for approval.

Can you give us an update on your expected timing and ramifications and your expectations for getting that in for NRDL, what the timelines are for that, and what our expectations should be for NRDL for 2024 and how that would work with the timing of approval? That would be our first question.

And the second question is, obviously, there is a lot of focus on the TTF lung cancer data coming up at ASCO. You mentioned that in your prepared remarks.

Can you help us understand the ramifications of that result for China, particularly as it relates to the strength of the data with combination PD-1 but not docetaxel, and the use of PD-1 in second line and how you expect that to be important for China? Thank you..

Hi, Michael. It is Josh. Good to hear from you. I am going to direct the questions to our executives this morning. So, I will start on efgartigimod directed to me, and then Rafael can talk a little bit about your question on LUNAR. On efgartigimod, as you know, there is not a PDUFA date in China for reviews or approvals.

What I can say is we are in discussions with the regulators that they are going well, and we are looking forward to a potential approval. Once we have that, we are prepared to move quickly to launch, as we mentioned.

In my comments, we have planned to have about 100 sales reps at launch ready to promote the product, and we will be moving quickly then toward developing packages and strategies for NRDL. We need an approval sometime over the summer to, I think, fit into that window, but again, we will keep you updated as we continue to go through.

Everything is going well, and we are excited about the opportunity. Rafael, maybe you could address LUNAR, please..

Sure. Hi, Michael. So, this is about the implications of the data for China.

Clearly, this is a second-line study, so the question is, have most patients received checkpoint inhibitors in the front line, and therefore, the data that is significant, clinically meaningful with IO applicable if patients have received it in first line? I think the answer to that is that not every patient actually receives checkpoint inhibitors in front line, particularly patients with mutations, with EGFR mutations and resistant mutations.

Often times, the addition of checkpoints don't tend to add that much benefit, and they may get it in second line, so there is some applicability there.

There's also some evidence, I think, which is really demonstrated in the study of a synergy between a PT field and checkpoint inhibitors, and I think we will be able to corroborate this in the front-line study, which is keynote B36.

I think that that study would really establish, this synergy that we believe is observing in LUNAR, and as you know, the standard-of-care in non-small cell lung cancer is really evolving, and there will be new agents and different ways of treating patients as new entrants come in.

So I think we are pretty excited and share the enthusiasm of NovoCure on this data set that really shows particularly this synergy with ICIs and PT fields, and based on the pattern of treatment in China, there will be patients that will definitely benefit from this combination..

Thank you. Just to be clear for Josh, we acknowledge that we do want to get approval by summer and that there's a deadline that we need to hit for NRDL.

That's correct?.

Yes, I mean, we would like approval as quickly as possible for sure, and as I say, we're at – reviews are going well. Yes, I think to be eligible for a 2024 negotiation, we would need to have an approval over the summer, and again, things are going well, but we don't know until we get it, so we'll keep everybody updated..

Got it. Thank you, guys..

Operator, next question, please..

Thank you. Our next question comes from the line of Yigal Nochomovitz from Citi Group. Please ask your question, Yigal..

Oh, hi. Yes, thank you. For Bema, can you just talk about the timelines for running the Phase 3 and first-line gastric? When could that trial read out, and what is the current view on when that drug could launch in China? And then you also mentioned in the press release that you're joining two global Phase 3s, FORTITUDE-101 and FORTITUDE-102.

Can you just explain the differences between those 2 trials, please, both in first-line gastric?.

Sure, yes. Thanks for the question. I think, Rafael, these are both for you..

Yes, so I'll start with the second part of the question, Yigal. There are two studies in gastric cancer, the standard-of-care, and it tends to be 446 plus a PD-1 inhibitor, either TIVO or pembrolizumab. That is really the way that most patients are treated. Some variation of chemotherapy, such as XELOX, is sometimes used.

There have been studies that have not used PD-1 because this started before these results really came about. So that's why we have two studies. One, it uses 446 with pembrolizumab, and the other uses pembrolizumab with chemotherapy plus PD-1. The second one hasn't started.

We're in the process of getting it going on both Amgen and ourselves, but we obviously have made the decision to participate in that trial. So the first approval will be with chemotherapy alone, and that trial is on-going from Amgen.

There's been some discussion about the level of expression of FGFR2 alpha, and we will enter that study imminently, actually. We're just automating issues, having to do with a diagnostic, etcetera, but the study is ready to start, and it will be shortly after, followed by the biggest study, which is normal in China.

So with regards to timelines, this study will follow its course, and we'll have a filing in, sometime in 2025..

Okay, great. Thank you very, very much..

Thank you. Well, our next question comes from the line of Anupam Rama from JPMorgan. Please ask your question, Anupam..

Hi, this is Priyanka [Ph] on for Anupam. We just have one question. Can you give us a preview on what to expect at the Investor Day, and if they're going to be more of a pipeline or development-focused, or is it more focused on commercial dynamics and potential for the pipeline products in China? Thanks..

Hi, Priyanka. It's Josh. I'll start, and then, Billy, please jump in. But we have not had an in-person Investor Day for quite some time and thought this was a good time to do it, particularly coming out of ASCO and some of the updates that we'll have there.

So we will focus on certainly on the pipeline, on the eight launches that are coming, as well as a look into our discovery strategy and some of our earlier global developments. We will talk about commercial dynamics and outlook for the medium term for the firm.

But really, I think our primary goal here is to give investors a little bit deeper insight into the breadth and depth of our pipeline and the things that are coming sometime soon. Billy, if you have anything to add, please do..

No, that was well covered, Josh. We'll be sending out a phase of date to all of our investors and sell side probably sometime this month, followed by, some more details around the agenda. So stay tuned..

Thanks so much..

Great. Thank you. Our next question comes from the line of Jonathan Chang from SVB Securities. Please go ahead, Jonathan..

Hi, guys. Thanks for taking my questions and congrats to Josh and Christine.

First question, in the context of a broad and expanding pipeline of commercial and clinical stage assets, what do you see as the most meaningful growth drivers for the company in 2023 and beyond? And my second question, can you tell us more about ZL-1310, the construct itself and the timelines associated with the program? And discuss your thoughts on pursuing DLL3 with an ADC versus a bispecific T-cell engager.

Thank you..

Great. Thank you, Jonathan. Thanks for the congratulations. I think on growth drivers, I'll make a couple of comments, ask Samantha to weigh in, and then we'll turn it to Raphael to talk about the DLL3. I think on growth drivers, obviously, we're quite excited about the launch, upcoming launch, hopefully, of an efgartigimod.

And as I mentioned, we're well-prepared to hit the ground running there. We've learned, I think, a lot from the very successful launch in the U.S. And I think a lot of the dynamics that led to success in the U.S. actually can and should play out in China. So, certainly, we're looking forward to that as a new growth driver.

ZEJULA continues to perform well, and we would expect, as we mentioned up front, to continue to grow share in that class, secure a place as the market leader, and continue to drive penetration, particularly in the first-line setting.

And, of course, NUZYRA and QINLOCK on NRDL, beginning in March, will drive good volume and good revenue growth for the remainder of 2023. I think as we get into 2024, then, looking forward to the next wave of potential launches in that period, which could include TTFields for lung cancer, Repotrectinib.

And then, we've talked a little bit about that as we get a little bit farther out bemarituzumab, adagrasib, KarXT. So, there are a lot of growth drivers. I think, again, for this year, it's execute on the four products that we have in the market and be ready to launch well with Cartagena.

Samantha, I don't know if you want to make any other comments on 2023 and beyond..

Oh, you have covered pretty well..

Maybe we can go to Rafael to talk a little about our most recent deal with DLL3..

Yes, hi Jonathan. So yes, this is ZL-1310. We were pretty impressed with the clinical activity of this product and as we have feedback so this is a complement to our ADC pipeline. And as you know, ADCs are based on antibody, the specificity and ability of the antibody are quite good for the target DLL3.

And then the payloads and linters tend to dictate the benefit-risk of the product. This payload is a topoisomerase inhibitor and it has really high potency and high clearance and better permeability.

So we saw as a consequence very good efficacy and tolerability in preclinical studies, as opposed to other ADCs that have less stable linkers that are not covalent. So this is again a covalent linker and it actually releases in the tumor microenvironment.

There are other linkers that actually don't allow, the payload to remain bound and therefore, are [Indiscernible] with toxicity such as high toxicity, rash, mitosuppression, etcetera. And here we could see a very stable PK and be able to increase the doses to a relatively higher level.

So because of that and also because, these companies also have more advanced products, that they're also moving ahead with and it seemed like it was a technology that was superior to many other ADC technologies that we've seen out there. So that's how we chose it. We could have chosen perhaps a bi-specific, I'm getting past biotechnology there.

They've demonstrated actually impressive activity in difficult settings such as refractory or second line small cell lung cancer. And we have our own bi-specific in the CD20 space with Regeneron.

But here because of the potency and the potential higher benefit risk given the stability of the linker and, trying to affect the avoidance of CRS and other IL-type toxicity from bi-specific, we opted to use an ADC. And then in terms of why we chose DLL3, well, it's a target that's been validated by Amgen's data.

It's a real medical need and I think also has the opportunity to expand to neuroendocrine tumors, which is an area where there hasn't been really a lot of progress. So I think this, this is a collection of information that led us to really choose this product as our next ADC to move into IMD in the near future..

Got it. Thank you..

Thank you. Our next question comes from the line of Ziyi Chen from Goldman Sachs. Please ask your question, Ziyi..

Hey, thank you. Thank you for taking my questions. A couple questions. Number one is, now you're running more than 15 assets in a clinical stage. While based on first quarter and also third quarter, fourth quarter, you have been controlling the budget pretty tight.

So we're trying to understand that how would you allocate the resources properly to make sure the programs, the progress of those programs could, potentially make you ahead of peers in competition and how you're going to prioritize some of the key assets. Second question is more specific on adagrasib.

Is there any updates on the regulatory timeline for adagrasib in China? When should we expect more visibility on the China filing strategy? Particularly what are the factors that management is considering while trying to determine the filing plan in China? A quick one also on ADC is, this is probably the first time that we saw Zai Lab is partnering with one of the local players licensing their assets.

So does that mean that you have been changing your strategies? You have been more looking into potentially domestic biotech company to collaborate? Those are my three questions. Thank you..

Thanks for the questions and we'll try to cover all three. Billy, maybe you could start on resource allocation. Rafael can talk about adagrasib. You can make any comments, Rafael, about business development. And then Jonathan, maybe you can provide some broader context around our business development strategy. So I'll start with Billy..

Hey Ziyi, thanks for the question.

So I think at this point in Zai Lab's sort of, what I would say, relevant scale and organization's lifecycle, we think that we have turned a corner whereby we're going to be able to make sure that we achieve our strategic priorities, i.e., we have about eight anticipated drug launches over the next two and a half years or so very important to us, clearly.

While, maintaining, kind of a level of growth and productivity at the same time. So therefore, you saw a snapshot of that in our quarterly results where, yes, from some non-operating items, such as interest income and foreign currency gain.

But if you actually see the operating line items, you would also see improving profile, namely that revenue is growing faster than expenses. And you should expect that to continue from here on out. So year after year, from here on out, we expect to see our financial profile and operating basis look better and better.

And that gave us the confidence and it felt like the time early on this year to make a commentary to the public that we expect to, we hope to target, we target to reach commercial profitability this year and overall profitability by end of 2025. So this was something that we expected and that we're starting to see from here on out.

Now there's going to be, of course, some quarterly, quarter per quarter action, but year-over-year, we felt very comfortable that you're going to, we're going to start to see improving financial picture. So that includes, right, that bakes in making sure that we execute on all of our priorities, including, the anticipated launches we talked about..

Raphael, maybe you could cover, adagrasib..

Sure. Yes. So we obviously are pretty excited about adagrasib. The data in second line on small cell lung cancer, the data in colorectal, which we referred to at the previous earnings call and the data that I alluded to today in pancreatic as well as biliary tract. So this is across, solid tumors with G12C is performing exceedingly well.

So we are very eager to get this product approved as soon as possible, obviously. We are participating on a number of feasible trials. And in lung cancer, we are on K12, which is the second line study against docetaxel. And we will participate in the frontline and we're also in the colorectal cancer study as well.

Our filing was based in the getting data from PFS on K12. And that would be something towards the end of 2024. But we are always looking for ways to accelerate filing. Obviously, we can't really control the approval because of lack of PDUFA timelines, but we can control whether or not we can, working with CDE, accelerate the filing.

So we are, we will try to leverage K12 data from Chinese patients to see whether we can file earlier. Obviously, in all promises, stay tuned and we'll see whether that's the case. But right now, the base case is end of 2024. And hopefully, it will be sooner. And I'll just make the comment that, [Indiscernible] apparently won't be approved in China.

And there are some domestic products that one of them have breakthrough designation and they obviously have Chinese patients, so they have an advantage over Allograft [Ph]. That's why we're eager to leverage K12. But these products really are very early.

They have response rate, they don't have a lot of durability, they don't have a lot of follow-up and or survival. So we don't believe that we are behind in this field. There's really competition, but we will do our very best to try to make this available as soon as possible.

And the last comment I'll make, I don't think we made any comment to this last time, but we did file the BK study, which again is required for the filing, and we finished it already actually. And so when we go to CDE to discuss these timelines, we would have more data, from Chinese patients at BK. So I hope this helps.

Stay tuned and hopefully we'll be able to give you more granular data, as we continue our discussion. Jonathan, I think you can make perhaps a comment about the DLL3..

Yes, thank you for the question on the BD strategy. First of all, it's not a changing strategy. I like to see it as an evolution in our BD strategy. In fact, I think our BD strategy is multi coiled. So there are a couple of elements to it.

Number one, I think we'll continue to do those type of deals, which maybe we are more well known for, the Malavis [Ph] the Escartige Mods, the late stage assets with regional rights. The latest one is our FibDAQ, obviously with Seattle Genetics.

In this DLL3, it's the second part of our strategy, which is to help the company acquire global rights and complement our in-house discovery strategy. I think if you look at the success in BD, it really comes from the rigor in our scientific evaluation. And our scientific team is very good at picking assets.

So we want to leverage the strength and extend these regional rights deals to global rights in selected areas, such as ADCs, synthetic big data and others, where we're already building a portfolio of very synergistic assets.

And today whether those assets come from globally or come from China, in the case of ADCs, I think China is actually making a lot of positive progress. And this particular company, a particular asset, has shown or demonstrated very promising early data. So we're very excited by it.

And I think we may do more deals with these types of profile going forward. And I think as we evolve as a company, certainly BD will continue to evolve and there will be other points and elements. And hopefully, you'll see more of our other types of creative deals that we'll do in the future. Thank you..

Thanks, Jonathan. Next question, operator, please..

Certainly. Our next question comes from the line of Seamus Fernandez from Guggenheim Securities. Please ask your question..

Great. Thanks, everybody. Thanks. Just a couple of quick questions.

So first, just on KarXT, can you just help us understand what kind of commercial presence is likely to be necessary for the launch to really capitalize on the size of the overall market opportunity? Can you just sort of remind us how the sort of relative generic utilization is in country versus kind of the undiagonised patient population, just trying to get a better sense of how we should be thinking about the commercial launch of KarXT post approval/ And then second question is really just on how you are thinking about the opportunity for another topical agent in the treatment of psoriasis, that area has been relatively slow to come on with two new agents in this space.

Those agents have good efficacy but what we continue to see across the board are challenges as it relates to gross to net dynamics in that market and reimbursement coverage, so just how are you thinking about that opportunity for the topical IL-17 and the spend that you will be pursuing associated with it, is it perhaps an opportunity to pursue HS or other potential opportunities outside of purely psoriasis? Thanks..

Thanks Seamus it’s Josh. I’ll make a brief comment on sort of commercialization, but I’ll really want Harald to dive in on both of the topics.

I think as it relates to KarXT and commercialization opportunity our estimates are that about 8 million patients with schizophrenia across China atleast 4 million of whom are speaking actively, taking care in equivalent of psychiatric wings or psychiatric hospitals in major settings.

I think our view at launch is probably somewhere in the range of 200 sales reps or so can cover the heavy treatments, centers, generics are prevalent I think certainly [Indiscernible] are well utilized in China today.

But I think Harald can talk about the opportunity that KarXT presents in terms of beta patients who aren’t responding well the current therapies or the benefits from combined and other – that may come and then Harald you could talk a little bit about why we are excited about ISO [Ph]..

Yes thank you. First Corona and the KarXT compound, it’s so different from existing anti psychotics and schizophrenia treatments so that we really see this is a great opportunity to either compliment existing regimen as a add on or as a standalone. The efficacy was clearly in the lab studies. The E3 is just another own.

We see confirmation of the trial that’s already shown the efficacy of this -- in this patient population with a similar kind of efficacy signal that we have seen in E1 and E2.

So with that said I think this is a low area in the market and in China as we’ve already told in previous meeting there is a lot of undiagnosed schizophrenia is an effort by the government to activate more schizophrenia treatment in the country. So we see this as a great commercial opportunity.

And regarding the second part of your question about 1102 and the use of topicals in psoriasis, where there are already quite a number of treatment options. Recently, Tapinarof was added and roflumilast. Both of those drugs are quite different from ours.

And I just would like to bring out again the uniqueness of 1102, which is an IL-17 mimetic, basically, or a blocker that works similar to the most active drug class for this disease. So we see this as a way to bring what is currently the best treatment by sub-q treatment or IV treatment directly to the skin.

And our proof of concept study has clearly shown that we achieve penetration and early success in clinical markers of benefit. So we see ourselves as in a very unique situation. One in which, yes, other topical treatments exist, but they have systemic absorption, they have other issues, and the overall results are well documented.

However, they are not IL-17 mimetics that are currently really the leading drug class for psoriasis. I hope I addressed your question..

Thank you, Harold. Next question, please..

Thank you. Our next question comes from the line of Yang Huang from Credit Suisse. Please ask your question, Yang..

Hi, everyone. Thank you for taking my questions. I have two quick ones. First is first quarter commercialization progress. So we saw year-over-year product revenue increase by 36%. Look pretty strong. And considering first quarter, there are still some COVID impacts in January. And also DL kind of just effective for one month.

So my question, first question is for the remaining quarters of the year, should we expect a kind of accelerated kind of commercial progress, given there will be no COVID impact and the two jobs in IDL potentially should gain more volume momentum? That's first question. Second question is on KarXT.

So you mentioned you are going to initiate a bridging study pretty soon this year. Can you give us more color on the design and the scale and the potential kind of timeline when of the office bridging study for KarXT? Thanks..

Thank you for the question, Samantha. If you can cover the first one, which is sort of commercial outlook for the year and COVID impacts and other other things that are going on. And then obviously, Harold, you can talk about KarXT..

Sure. Thanks, Huang for the question. The first two months in China, we do experience the COVID impact. And also, like you said, an RDL inclusion last month. However, going forward, we start from March. We have seen the much lesser COVID effect. We are very optimistic about to continue to deliver our goals for the rest of the year..

Great. Thanks, Harald, you want to add..

Yes, the question was about the clinical study for KarXT in China, which is about to start. It's actually almost imminent to start out with a design. Very similar, almost identical to the emergent program studies that were conducted by Corona. It has the same kind of dose rate ramping schedule that you've seen there.

So we will try to mimic the design, the duration, the details in the same way as it was seen in the global program. As far as the timelines, as I said, this study is about to start. We just finished our PK study, which was also on track, which allows us to feel confident about the clinical trial overall.

And I think that was your question, unless I missed some piece..

Thank you.

So when do we expect that we can finish that project study?.

There is at this point in time no clear understanding how long it will take. This is the first study in a long time with a new drug. So we have certain expectations. We think we have the centers lined up. So we do believe this can be done rather expeditiously. But I think this will be for a future conference call to get more clarity on..

Okay, great. Thank you..

Thank you. Our next question comes from the line of Rebecca Liang from Bernstein. Please ask your question, Rebecca..

Hi, thanks for taking my question. So specifically on the two products that are already covered by NRDL, we saw that NUZYRA had a lot of growth in Q1. But the other one, QINLOCK, had negative growth. And even after we adjust for the $3.9 million rebate, there's still a net decline.

So could you help me understand better what's actually going on with QINLOCK? And when do you expect the volume release effect from NRDL to take place? Thank you..

Thanks, Rebecca. It’s Josh, just to remind everybody that those two products were added effective March 1st. So in Q1, you're really not seeing a real effect of the NRDL listing. We're making good progress in terms of pulling that through to the local hospitals.

So you should expect to see good QINLOCK volume and net sales growth over the next three quarters. As Samantha mentioned, I think across all of our products, we saw a little bit of challenges in the first quarter just related to COVID. Again, not different than what you're seeing across China-based sales and marketing efforts.

But we're quite confident that the volumes will – you'll see them beginning in Q2 from both NUZYRA and QINLOCK. Thank you..

Thank you. I'm showing no further questions at this time. I'll now turn the call back to Zai Lab CEO Samantha Du for closing remarks..

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 second quarter of 2023. Operator, you may now disconnect this call..

Thank you. That concludes today's conference call. Thank you for participating. Goodbye..