Zai Lab - Q1 2023

Transcript

Operator (participant)

Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab's Q1 2023 financial results conference call. At this time, all participants are in listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. 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.

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 Q1 of 2023 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. She'll be joined by Josh Smiley, president and chief operating officer. Dr. Rafael Amado, president and head of Global Oncology Research and Development, will discuss advances with our oncology product candidates. Dr. Harald Reinhart, president and head of Global Development, Neuroscience, Autoimmune and Infectious Diseases, who 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 Q1 financial results.

Additional executives will also 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. Our Q1 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 reopening at the beginning of the year. The positive top-line results from the phase III EMERGENT trial of KarXT in schizophrenia, and the positive interim analysis from the phase II innovaTV 207 study from tisotumab vedotin in head and neck cancer, further support our belief that these products provide important treatment options for patients in China and globally. We're very excited about the unanimous recommendation of the US Food and Drug Administration's advisory committee in support 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 continuous focus on the ADC space and our expansion to the global market. This product complements our lung cancer franchise and will leverage our strong capabilities to develop ZL-1310. We 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 the next phase 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 of driving innovation in China and beyond. I would like now turn the call over to Josh. Josh?

Josh Smiley (President and COO)

Thank you, Samantha. I look forward to taking on this new role for the company and continuing 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 position Zai Lab to be a leader in biopharma 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 2 months of the quarter, Zai Lab continues to deliver solid growth and overall financial results.

Our net loss in the Q1 of 2023 decreased 40% compared to the same period last year, primarily attributable to the increase in product revenue and non-operating income. We expect strong growth momentum to continue out throughout the remainder of this year. ZEJULA continues to perform well with increased PARP 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 31st, 2023, Optune was covered by 96 municipal or provincial supplemental insurance plans, up from 37 as of March 31st, 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 a pipeline and a product potential, we're getting ready for commercial launch later this year. As we communicated earlier, we plan to have a specialized and experienced team for efgartigimod, with approximately 100 employees at launch. We're 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 subcutaneous efgartigimod for GMG in China.

The initiation of a bridging study for KarXT in 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 Fields LUNAR phase III study in NSCLC. We're also advancing our proprietary pipeline with global rights, including by initiating a global phase I study for ZL-1218 or CCR8, and moving ZL-1102, our IL-17 antibody 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. 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 8 additional products as we take the steps to achieve overall corporate profitability by the end of 2025 and reach 1 million patients by 2030. Now I will turn the call over to Dr. Amado. Rafael?

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

Thank you, Josh. In the Q1 of 2023, Zai Lab's oncology franchise continued to make progress on all fronts, we expect to have a very productive year. Recall that earlier this year, our partner, Novocure, announced that the LUNAR clinical trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival when TTFields 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, at 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. 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 TTFields 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 II innovaTV 207 study of TIVDAK in patients with treatment-refractory head and neck cancer at the 2023 ASCO annual meeting.

At the data cut-off, 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 these results, 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 KRAZATI or adagrasib.

Our partner, Mirati, presented updated phase II data on the KRYSTAL-1 study in patients with pancreatic adenocarcinoma, biliary tract cancer, and other solid tumor harboring KRAS G12C mutations at the plenary series program of the April session of ASCO. 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 pre-treated 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. We are very pleased to see the results of this phase II study, which demonstrate a marked improvement on the current standard of care for patients with unresectable or metastatic KRAS G12C mutated solid tumors, including gastrointestinal cancers, where huge 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 KRAS G12C mutations. Moving to our internal global research and development programs, we presented new translation on clinical biomarker data from our global oncology program, ZL-1211, an anti-CLDN18.2 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 TIVDAK, we're expanding our pipeline into the antibody drug conjugate, or ADC space, 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 DLL3 ADC discovered by using MediLinx's proprietary TumLinx platform. TumLinx 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 other 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. 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 and Head of Global Development, Neuroscience, Autoimmune and Infectious Diseases)

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 3rd 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 five. KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative Marder factor subscales, which are secondary endpoints in the trial. Karuna plans to submit a new drug application to the FDA in the Q3 of 2023, with launch in the 2nd half of 2024, if approved.

As Amanda 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. We're 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're excited about the committee's strong vote of confidence. We submitted an NDA for the treatment of carbapenem-resistant Acinetobacter baumannii infection to the NMPA in December 2022, with priority review granted 1 month later. 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 multi-drug resistance.

Much progress was made this past quarter in VYVGART or efgartigimod. We submitted the BLA for efgartigimod IV for the treatment of patients with generalized myasthenia gravis or 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 SC for gMG in mid-2023. We continue to support our partner, argenx, on indication expansion in China and worldwide. Last but not least, for our internally developed topical IL-17 product, ZL-1102, we are moving forward with preclinical and regulatory activities in preparation for our global phase II trial. Let me now hand over to Billy, who will speak about progress with our commercial products and financial results. Billy?

Billy Cho (CFO)

Thank you, Harald. Now I will discuss our Q1 of 2023 financial results compared to the prior year period. Total net product revenues for the Q1 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 net product revenue of $42.7 million for ZEJULA compared to $29.6 million for the same period in 2022, representing 44% year-over-year growth. $13.3 million for Optune compared to $12.8 million for the same period in 2022. $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 net product revenue in the Q1 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 Q1 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 headcounts. SG&A expenses were $62.5 million for the Q1 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.

Higher payroll and payroll-related expenses with increased commercial headcount as Zai Lab continued 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 Q1 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 equivalents, 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?

Operator (participant)

Thank you. We would now like to open the line for questions. If you have a question, please press star one one at this time. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Michael Yee from Jefferies. Please ask your question, Michael.

Michael Yee (Managing Director and Senior Biotechnology Analyst)

Thanks. Good morning. We have 2 quick questions. One, efgartigimod, I know that you guys are waiting for approval. Can you give us an update on your expected timing and ramifications or your expectations for getting that in for NRDL and what the timelines are for that, and what our expectations should be for NRDL for 2024, and how that would work at the timing of approval? That would be our first question. The second question is, obviously there are 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.

Josh Smiley (President and COO)

Hi, Michael. It's Josh. Good to hear from you. I'm gonna direct the questions to our executives this morning. I'll start on efgartigimod and direct it to me, and then Rafael can talk a little bit about your question on LUNAR. On efgartigimod, you know, as you know, there's not a PDUFA date in China for reviews or approvals. What I can say is we're in discussions with the regulators that they're going well and we're, you know, looking forward to a potential approval. Once we have that, we're prepared to move quickly to launch.

As we mentioned, in my comments, we have a plan to have about 100 sales reps at launch ready to promote the product, and we'll be moving quickly then toward developing packages and strategies for NRDL. You know, we need an approval, you know, sometime over the summer to, I think, to fit into that window. Again, we'll keep you updated as we continue to go through. Everything's going well and, we're excited about the opportunity. Rafael, maybe you could address LUNAR, please.

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

Sure. Hi, Michael. This is about the implications of the data for China. Clearly this is a second line study, so the question is, you know, have most patients receive checkpoint inhibitors in front line and therefore, the data, would the, you know, data that is significant and clinically meaningful, with IO, applicable, if patients have received anything in first line? I think the answer to that is that not every patient actually receives a checkpoint inhibitors in front line, particularly patients with mutations, with EGFR mutations and resistant mutations. Oftentimes, the addition of checkpoints don't tend to add that much benefit, and they may get it in second line.

There is some applicability there. There's also some evidence, I think, which is really demonstrated in this study of a synergy between anti-FGFR2b and checkpoint inhibitors. I think we will be able to corroborate this in the frontline study with this KEYNOTE-B36. I think that study would really establish, you know, this synergy that we believe is observing in LUNAR. As you know, the standard of care non-small cell lung cancer is really evolving. You know, there will be new agents and, you know, different ways of treating patients as new entrants come in. 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 anti-FGFR2b.

You know, based on the pattern of treatment in China, there will be patients that will definitely benefit from this combination.

Michael Yee (Managing Director and Senior Biotechnology Analyst)

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

Josh Smiley (President and COO)

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

Michael Yee (Managing Director and Senior Biotechnology Analyst)

Got it. Thank you guys.

Josh Smiley (President and COO)

Operator, next question please.

Operator (participant)

Thank you. Our next question comes from the line of Igor Nemcovics from CP Group. Please ask your question, Igor.

Igor Nemcovics (CEO)

Hi. Yes, thank you. For Bema, can you just talk about the timelines for running the phase III in first-line gastric? When could that trial read out? What is the current view on when that study, when that drug could launch in China? You also mentioned in the press release that you're joining two global phase III, FORTITUDE-101 and FORTITUDE-102. Can you just explain the differences between those two trials please, both in first-line gastric?

Josh Smiley (President and COO)

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

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

I'll start with the second part of the question, Igor. There are two studies in gastric cancer, the standard of care, it tends to be mFOLFOX6 plus a PD-1 inhibitor, either Opdivo or pembrolizumab. That is really the way that, you know, most patients are treated. You know, some variation of chemotherapy such as XELOX is sometimes used. There has been studies that have not used PD-1 because they started before these results really came about. That's why we have two studies. One, it uses mFOLFOX6 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, both Amgen and ourselves. We obviously have made the decision to participate on that trial. The first approval will be with chemotherapy alone. That trial is ongoing from Amgen. There's been some discussion about the level of expression of FGFR2b. We will enter that study imminently actually. You know, we're just ultimating issues, you know, having to do with the diagnostic, et cetera. The study is ready to start, and it will be shortly after followed by the biggest study which is, you know, normal in China.

With regards to timelines, you know, this study will follow its course and, you know, we'll have a filing in, you know, sometime in 25.

Igor Nemcovics (CEO)

Okay great. Thank you very, very much.

Operator (participant)

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

Josh Smiley (President and COO)

Yeah.

Priyanka Grover (Equity Research Analyst)

Hi, this is Priyanka on for Anupam. We just have one question. Can you give us a preview on what to expect at the Investor Day? If they're gonna 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.

Josh Smiley (President and COO)

Hi, Priyanka. It's Josh, I'll start and then Billy, please jump in. You know, we have not had an in-person Investor Day for quite some time. Thought this was a good time to do it, particularly coming out of ASCO and some of the updates that we'll have there. We will focus on, you know, 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, you know, outlook for the medium term for the firm.

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.

Billy Cho (CFO)

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

Priyanka Grover (Equity Research Analyst)

Thanks so much.

Operator (participant)

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

Jonathan Chang (Senior Research Analyst)

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? 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.

Josh Smiley (President and COO)

Great. Thank you, Jonathan, and thanks for the congratulations. I think on growth drivers, I'll make a couple comments, ask Samantha to weigh in, and then we'll turn it to Rafael to talk about the DLL3. I think on growth drivers, obviously we're, you know, we're quite excited about the launch, upcoming launch, hopefully of efgartigimod. 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, you know, can and should play out in China. You know, 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. As we, you know. NUZYRA and QINLOCK on the 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. You know, we talked a little bit about that as we get a little bit farther out, pembrolizumab, adagrasib, KarXT. You know, there are a lot of growth drivers. I think, again, for this year it's execute on the 4 products that we have in the market and be ready to launch well with efgartigimod. Samantha, I don't know if you want to make any other comments on 2023 and beyond.

Samantha Du (Founder, Chairperson, and CEO)

Oh, you have covered pretty well.

Josh Smiley (President and COO)

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

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

Yeah. Hi, Jonathan. This is ZL-1310. We were pretty impressed with the preclinical activity of this product. As you know, we have TIVDAK, so this is a complement to our ADC pipeline. As you know, ADCs are based on antibody. You know, the specificity and avidity of the antibody are quite good for the target DLL3. Then the payload and linkers, they 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.

We saw, as a consequence, very good efficacy and tolerability, in preclinical studies, you know, as opposed to other ADCs that have less stable linkers that are not covalent. This is again, a covalent linker, and it actually releases in the tumor microenvironment. There are other linkers that actually don't allow, you know, the payload to remain bound, and therefore, you know, are fraught with toxicity such as high toxicity, rash, immunosuppression, et cetera. Here we could see a very stable PK and be able to increase the doses to a relatively higher level. Because of that, and also because, you know, this company also has a more advanced product, you know, that they're also moving ahead with.

You know, it seems, it seemed like it was a technology that was superior to many other ADC technologies that we've seen out there. That's how we chose it. We could have chosen perhaps a bispecific, you know, Amgen has biotechnology there, and they have demonstrated actually impressive activity in, you know, difficult settings such as refractory or second line small cell lung cancer. We have our own bispecific in the CD20 space with Regeneron. Here, because of the potency and the potential higher benefit risk, given the stability of the linker, and, you know, trying to affect the avoidance of CRS and other IO type toxicities from bispecific, we opted to use an ADC.

In terms of why we chose DLL3, well it's a target that's been validated by Amgen's data. It's a real unmet medical need. 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. I think this, you know, this is the collection of information that led us to really choose this product as our next ADC to move into IND.

Priyanka Grover (Equity Research Analyst)

You know, in the near future.

Igor Nemcovics (CEO)

Got it. Thank you.

Operator (participant)

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

Ziyi Chen (Head of Asia Healthcare Research)

Hey, thank you. Thank you for taking my questions. A couple questions. Number one is, you know, now you're running more than 15 assets in a clinical stage, while based on Q1 and also Q3, Q4, you have been controlling the budget pretty tight. We're trying to understand how would you allocate the resources properly to make sure the programs, the progress of those programs could, you know, potentially make you ahead of peers in competition, and how you're gonna 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?

You know, 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 as partnering with one of the local players licensing their assets. 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.

Josh Smiley (President and COO)

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. Jonathan, maybe you can provide some, you know, broader context around our business development strategy. I'll start with Billy.

Billy Cho (CFO)

Hey, Zhi, thanks for the question. I think at this point in Zai Lab's sort of what I would say relevant scale and organization's life cycle, you know, we think that we have turned a corner whereby we're gonna be able to make sure that, you know, we achieve our strategic priorities, i.e., you know, we have about eight anticipated drug launches over the next two and a half years or so. Very important to us, clearly. While, you know, maintaining, you know, kind of a level of growth and productivity at the same time. You saw a snapshot of that in our quarterly results, where they get from some non-operating items such as interest income and foreign currency gain.

If you actually see the operating line items, you would also see, you know, improving profile, namely that revenue is growing faster than expenses, and you should expect that to continue from here on out. Year after year from here on out, we expect to see our financial profile on operating basis, look better and better. That gave us the confidence, and it felt like the time early on this year to make a commentary to the public that, you know, we target to reach commercial profitability this year and overall profitability by end of 25. This was something that we expected and something that we're starting to see from here on out.

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

Josh Smiley (President and COO)

Rafael, maybe you could cover adagrasib.

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

Sure. Yeah. We obviously are pretty excited about adagrasib. You know, the data in second-line on small cell lung cancer, the data in colorectal, which we referred to at the prior, previous earnings call, and the data that I alluded to today, in pancreatic as well as biliary tract. This is across, you know, solid tumors with G12C, is performing exceedingly well. We are very eager to get this product approved as soon as possible, obviously. We are participating on a number of clinical trials, and in lung cancer, we are on K-12, which is the second line study against docetaxel, and we will participate in the front line, and we're also in the colorectal cancer study as well.

Our filing was based in the getting data from PFS on K-12. That would be something towards the end of 2024. We are always looking for ways to accelerate the 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. We will try to leverage K-12 data from Chinese patients to see whether we can file earlier. Obviously, no promises. Stay tuned, and we'll see whether that's the case. Right now, the base case is end of 2024 and, you know, hopefully it will be sooner.

I'll just make the comment that, you know, sotorasib apparently won't be approved in China, and there are some domestic products that, you know, one of them have breakthrough designation, and they obviously have Chinese patients, so they have an advantage over adagrasib. That's why we're eager to leverage K-12.

These products really are very early, and they have response rate. They don't have a lot of durability, they don't have a lot of PFS, follow-up, or survival. 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. The last comment I'll make, I don't think we made any comment to this last time, but we did start a PK study, which again, is, it's required for the filing, and we finished it already, actually. When we go to CDE to discuss, these timelines, we would have more data, you know, from Chinese patients, PK.

Hope this helps. Stay tuned, and hopefully we'll be able to give you more granular data, you know, as we continue our discussion. Jonathan, I think you can make perhaps a comment about the deal with three. Yep.

Yeah. 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-pronged. There are a couple of elements to it. Number one, I think, you know, we'll continue to do those type of deals, which maybe we are more well known for. You know, the Mirades, the Efgartigimod, you know, the late-stage assets with regional rights. You know, the latest one is TIVDAK, obviously with Seattle Genetics. In this BL three, you know, it's the second prong of our strategy, which, you know, 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 at Zai, it really comes from the rigor in our scientific evaluation. Our scientific team is very good at picking assets. We want to leverage the strength and extend these regional right deals to global rights in selected areas, you know, such as ADCs, synthetic lethality and others where we're already building a portfolio of very synergistic assets. Today, you know, whether those assets come from globally or come from China, in the case of ADCs, I think China is actually, you know, making a lot of positive progress in this particular company and particular assets, you know, has shown or demonstrated very promising, you know, early data. We're very excited by it.

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

Josh Smiley (President and COO)

Thanks, Jonathan. Next question, operator, please.

Operator (participant)

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

Seamus Fernandez (Senior Managing Director and Senior Analyst)

Great. Thanks everybody. Thanks. Just a couple of quick questions. First, just on KarXT, can you just help us understand what kind of, you know, commercial presence is likely to be necessary, for, you know, the launch to really capitalize on the size of the overall market opportunity? Can you just sort of remind us, how the, you know, sort of, relative, generic utilization is, in country versus kind of the undiagnosed patient population? Just trying to get a better sense of, how we should be thinking about the commercial launch, of, KarXT, post-approval. Then, you know, second question, is really, just on how you're thinking about the opportunity for another, topical agent in the treatment of psoriasis.

you know, that area has been relatively slow to come on with two new agents in the space. you know, those agents have good efficacy, but what we continue to see across the board are challenges as it relates to, you know, growth to net dynamics in that market and reimbursement coverage. Just how are you thinking about that opportunity for the topical IL-17 and the spend that you'll be pursuing associated with it? Is it perhaps an opportunity to pursue HS or other potential opportunities outside of purely psoriasis? Thanks.

Josh Smiley (President and COO)

Thanks, Seamus. It's Josh. I'll make a brief comment on sort of commercialization, but I really want Harold to dive in on both of the topics. I think as it relates to KarXT and the commercialization opportunity, you know, our estimates are there are about 8 million patients with schizophrenia across China, at least 4 million of whom are seeking, you know, actively seeking care in equivalent of psychiatric wings or psychiatric hospitals in major settings. You know, I think our view at launch is probably, you know, somewhere in the range of 200 sales reps or so can cover, you know, that heavy treatment centers. You know, generics are prevalent.

I think, you know, certainly, you know, thinking of like olanzapine and others, I think are well, you know, well utilized in China today. I think Harald can talk about the opportunity that KarXT presents in terms of either patients who aren't responding well to current therapies or the benefits from compliance and otherwise that may come. Then Harald, you can, you can talk a little bit about the why we're excited about IL-17.

Seamus Fernandez (Senior Managing Director and Senior Analyst)

Yeah.

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

Yeah. Thank you. First Karuna and the KarXT compound, it's so different from existing antipsychotics, schizophrenia treatments, that we really see this as a great opportunity to either complement existing regimens as an adjunct or as a standalone. The efficacy was clearly shown in the lab studies. The EMERGENT-3 is just another, we say, confirmational trial that's already shown, the efficacy of this drug in this patient population with a similar kind of efficacy signal that we've seen in EMERGENT-1 and EMERGENT-2. With that said, I think this is, you know, a new area in the market. In China, as we've already told in previous meetings, there is a lot of undiagnosed schizophrenia. There is an effort by the government to activate more schizophrenia treatment in the country. We see this as a great commercial opportunity.

Regarding the second part of your question about ZL-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. I just would like to bring out again the uniqueness of ZL-1102, which is an IL-17 mimetic basically, or a blocker that works similar to the most active drug class for this disease. 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. Our proof of concept study has clearly shown that we achieve penetration and early success in clinical markers of benefit.

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.

Josh Smiley (President and COO)

Thank you, Harald. Next question, please.

Operator (participant)

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

Yang Huang (Head of Asset Management, Asia Pacific and Head of Asset Management, China)

Hi, everyone. Thank you for taking my questions. I have two quick ones. First is, Q1 commercialization progress. We saw year-over-year product revenue increase by 36%. Look pretty strong. Concerning Q1, there are still some, you know, COVID impacts in January and also an NRDL in kind of just effective for one month. My question is, 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 drugs in NRDL potentially should gain more volume momentum? That's first question. Second question is on KarXT. 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 of this bridging study for KarXT? Thanks.

Priyanka Grover (Equity Research Analyst)

Great. 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 things that are going on. Obviously, Harold, you can talk about Karuna or KarXT.

Samantha Du (Founder, Chairperson, and CEO)

Sure. Thanks, Yang, for the question. The first two months in China, we do experience the COVID impact, and also, like you said, an NRDL inclusion, with last month. Going forward, we start from March. We have seen the much lesser COVID effect, and we are very optimistic about to continually to deliver our goals for the rest of the year.

Josh Smiley (President and COO)

Great. Thanks. Harald, do you wanna.

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

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 Karuna. It has the same kind of dose ramping schedule that you've seen there. We'll 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, the 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. I think that was your question, unless I missed some piece.

Josh Smiley (President and COO)

Okay. Thank you, Harald.

Yang Huang (Head of Asset Management, Asia Pacific and Head of Asset Management, China)

When do we expect we can finish that study, bridging study?

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

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. We have certain expectations. We think we have the centers lined up. We do believe this can be done rather expeditiously. I think this will be for a future conference call to get more clarity on.

Yang Huang (Head of Asset Management, Asia Pacific and Head of Asset Management, China)

Okay, great. Thank you.

Operator (participant)

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

Rebecca Liang (Senior Analyst)

Hi. Thanks for taking my question. 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. Even after we adjust for the $3.9 million rebate, there's still a net decline. Could you help me understand better what's actually going on with QINLOCK and when do you expect the volume release effect from the NRDL to take place? Thank you.

Josh Smiley (President and COO)

Thanks, Rebecca. It's Josh. Just to remind everybody that those two products were added effective March first. 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. You should expect to see good QINLOCK volume and net sales growth over the next three quarters. Yeah, as Samantha mentioned, I think across all of our products, we saw a little bit of, you know, challenges in the Q1 just related to COVID. Again, not different than what you're seeing, you know, across China-based, you know, sales and marketing efforts.

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

Operator (participant)

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

Samantha Du (Founder, Chairperson, and CEO)

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 Q2 of 2023. Operator, you may now disconnect this call.

Operator (participant)

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