Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab's third quarter 2021 financial results conference call. At this time, all participants are in a 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 Mr. Billy Cho, Chief Financial Officer of Zai Lab, who will make introductory comments.
Thank you, operator. Good morning and welcome, everyone. Zai Lab recently issued a press release providing the details of the company's financial results for the third quarter ended September 30, 2021, as well as product highlights and corporate updates. The press release is available in the investor relations section of the company's corporate website at ir.zailaboratory.com. Today's call will be led by Dr. Samantha Du, Zai Lab's Founder, Chairperson, and Chief Executive Officer. She'll be joined by Jonathan Wang, Head of Business Development, to discuss our recent collaboration for three new potentially transformative medicines. Dr. Alan Sandler, President and Head of Global Development, Oncology, who will discuss advances with our oncology product candidates. Dr. Harald Reinhart, Chief Medical Officer, Autoimmune and Infectious Diseases, who will speak about progress we've made in two therapeutic areas.
Tao Fu, Chief Strategy Officer, who will discuss the performance of our market products, and I will conclude with comments on our financial results in the quarter. We'll all 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 our business plans and objectives in timing success of our clinical trials, 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 that could cause actual results to differ materially from what we expect.
I refer you to our SEC filings for a discussion of risk factors that could cause our actual results to differ materially from those discussed today. At this time, it is my pleasure to turn the call over to Zai Lab's Founder, Chairperson, and Chief Executive Officer, Dr. Samantha Du.
Thank you, Billy. Hello, everyone, and thank you all for joining us. On this call, I'll discuss highlights from our third quarter, including two exciting new deals we announced yesterday, and give you the latest update for what we expect to accomplish in the fourth quarter and beyond. We're continuing to deliver strong growth and performance across our entire business. We made important advances across our innovative portfolio, which we continue to differentiate in terms of its depth and breadth. I'm very pleased to share with you that we expanded our product portfolio both vertically and horizontally by establishing partnerships for three new potentially first-in-class or best-in-class products. Our agreement with Blueprint Medicines for two promising lung cancer compounds, BLU-945 and BLU-701, present opportunities to further expand our world-class lung cancer franchise.
Our deal with Karuna Therapeutics allows us to enter a whole new therapeutic area, neuroscience, with an exciting anchor asset, KarXT. Jonathan Wang will provide additional details about these products. In the third quarter of 2021, Zai Lab made significant progress across all fronts, R&D, BD, regulatory, and commercial. We continue to generate strong revenue growth from ZEJULA, Optune, and QINLOCK. We had a positive meeting with the NMPA on efgartigimod, which suggests the potential for an accelerated pathway for its regulatory approval for gMG in China. Subject to the FDA approval and further discussion with the NMPA, we expect to file the NDA in China by the first half of 2022. We announced exciting data from the ATTACK clinical trial for sulbactam, durlobactam, and we will now proceed to prepare regulatory filing.
We achieved clinical proof of concept for ZL-1102, our IL-17A novel VH antibody fragment for topical treatment of mild to moderate plaque psoriasis. Demonstrating proof of concept for ZL-1102 is an important milestone for Zai Lab in our effort to discover and develop a pipeline of internally developed products with global rights, and to expand to as many indications as possible worldwide. In addition, several of our innovative product candidates had exciting data updates at recent medical meetings. Alan, Harald, and Tao will elaborate on those positive developments in a few minutes. We continue to expect approval of NUZYRA for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection by the NMPA in the fourth quarter.
We are making progress in preparing regulatory filings for Tumor Treating Fields unique to glioma and margetuximab in breast cancer. We expect to enroll patients in China for numerous global clinical trials over the next several quarters. We now have 28 globally innovative assets in our pipeline, and the quality, depth, and breadth of our pipeline continues to go from strength to strength. 13 products are in late-stage development, of which five have already been approved in the U.S., and four have received FDA breakthrough therapy designation. In addition, our growing pipeline includes 11 early-stage programs with worldwide rights, including three in global clinical trials and one that achieved proof of concept and is advancing into full development. We have had a very productive year so far for 2021, and we expect our fourth quarter and 2022 to be rich in milestones to unlock significant value in our business.
With that, I'll now ask Jonathan to speak about our two collaborations. Jonathan?
Thank you, Samantha. As Samantha mentioned, yesterday we announced two strategic collaborations that further strengthen and broaden our pipeline. Our agreement with Blueprint Medicines partnering on the two next-generation EGFR inhibitors, BLU-945 and BLU-701, will significantly strengthen our established lung cancer franchise and precision medicine portfolio, one of our most important focus areas where we have multiple late-stage assets that are complementary with each other. You'll recall that lung cancer is the most commonly diagnosed cancer type and is a leading cause of cancer death in China. The annual incidence of lung cancer in China is more than 800,000 cases, of which non-small cell lung cancer accounts for approximately 85%. EGFR mutations are more common in China than in the United States, occurring in 40%-50% of non-small cell lung cancer patients here.
These two compounds target the largest subpopulation in lung cancer for China. Third-generation EGFR TKIs, such as osimertinib, are commonly prescribed and have emerged as a standard of care for the first-line setting. However, resistance inevitably emerges, leading to disease progression. There are no approved therapies for patients with disease progression following third-generation EGFR treatment. These two compounds from Blueprint are potentially first and/or best-in-class fourth-generation EGFR inhibitors. Together with our other lung cancer products, will enable Zai to cover nearly all the different patient populations for this deadly disease. BLU-945 is a potential first-in-class inhibitor of triple mutant EGFR harboring either the activating L858R or exon 19 deletion mutations, combined with the acquired T790M and C797S mutations. It is potent and has demonstrated high wild-type EGFR selectivity to enable its use in combination.
It has shown antitumor activity both alone and in combination with osimertinib pre-clinically. It entered a phase I/II clinical trial early this year. BLU-701 is a selective EGFR double mutant inhibitor, providing potential best-in-class coverage of activating EGFR mutations, plus coverage of the major on-target resistance mutation for osimertinib, which is the C797S mutation. It is also highly potent and crosses the blood-brain barrier, which is important because in EGFR mutant non-small cell lung cancer patients with baseline brain metastasis, up to 40% of disease progression involves CNS metastasis. BLU-701 is expected to begin phase I clinical trials before the end of the year. The development strategy for these two compounds is either as monotherapy or in combination together or with other agents to overcome or prevent on-target resistance across multiple lines of treatment.
In addition, this collaboration enables opportunities to combine BLU-945 or BLU-701 with other Zai Lab lung cancer drug candidates to address on-target resistance mutation. Yesterday, we also announced an exciting collaboration with Karuna to exclusively develop and commercialize KarXT for schizophrenia and dementia-related psychosis in Greater China. We already have several products in neurology, including efgartigimod, so this is an adjacent expansion for Zai, and KarXT can leverage our existing infrastructure to create synergy. Just as efgartigimod gave Zai Lab an anchor asset in autoimmune disorders, we believe KarXT will do the same for us in neuroscience. It is a late-stage asset with first-in-class potential in a disease area with a large patient population and significant unmet medical needs. There are an estimated eight million schizophrenia patients in China, and the target population for dementia-related psychosis in China is about two million patients.
KarXT is a phase III asset with strong phase II data and significant differentiation from existing treatment. In the phase II EMERGENT-1 clinical trial, it showed good efficacy in PANSS scores, particularly in negative symptoms of schizophrenia such as apathy, lethargy, lack of pleasure, reduced speech, and withdrawal. It also was well-tolerated and demonstrated a favorable safety profile compared to existing therapies. Overall, these two collaborations vertically and horizontally expanded our pipeline, and we look forward to bringing in more deals for innovative and differentiated products such as these. Now, I'll turn the floor over to Dr. Alan Sandler.
Thank you, Jonathan. We and our partners had several encouraging data updates for our oncology product candidates in the third quarter, and we anticipate further progress in the fourth quarter. Our partner, Mirati, presented exciting data on adagrasib in colorectal cancer and non-small cell lung cancer at ESMO. In the phase II KRYSTAL-1 trial in patients harboring the KRAS G12C mutation for the adagrasib monotherapy arm, Mirati reported a response rate of 22% and a disease control rate of 87% in 45 colorectal cancer patients treated with single-agent adagrasib who received at least two prior lines of systemic anticancer therapies. In 28 colorectal cancer patients treated with at least two prior lines of systemic anticancer therapies who received the combination of adagrasib and cetuximab, they reported a response rate of 43% and a disease control rate of 100%.
In the lung cancer portion of KRYSTAL-1, which is potentially registration enabling, Mirati reported an objective response rate of 43% and a disease control rate of 80% for adagrasib monotherapy while demonstrating a safety and tolerability profile consistent with previously reported findings for adagrasib in non-small cell lung cancer patients, importantly, 98.3% of patients receiving adagrasib following treatment with immunotherapy and chemotherapy. Adagrasib has the potential to be a first-in-class and best-in-class KRAS G12C inhibitor in China. We plan to join global phase III studies in second-line plus non-small cell lung cancer and second-line colorectal cancer in the first half of 2022.
Moving to margetuximab, Zai's bridging study of the compound in combination with chemotherapy in advanced previously treated HER2-positive breast cancer met its primary endpoint of median progression-free survival, as defined by achievement of at least 50% of the efficacy of margetuximab plus chemotherapy in the SOPHIA study. The safety profile of margetuximab plus chemotherapy was acceptable and consistent with that seen in the SOPHIA trial. Based on these positive results, Zai Lab expects to file a BLA in China for this indication around year-end. Our partner, Turning Point, provided positive data updates for repotrectinib and elzovantinib at the AACR-NCI-EORTC triple meeting. In addition, repotrectinib received breakthrough therapy designation by the FDA in the quarter for the treatment of patients with advanced solid tumors that have an NTRK gene fusion, which is the second breakthrough therapy designation and seventh overall regulatory designation for repotrectinib.
We plan to join the global phase II portion of the SHIELD-1 study for elzovantinib in 2022. For Tumor Treating Fields, we completed enrollment of our pilot phase II clinical trial of Tumor Treating Fields in gastric cancer in China during this quarter. We plan to join global phase III pivotal trials in pancreatic cancer and ovarian cancer and to submit a regulatory filing in malignant pleural mesothelioma. Bemarituzumab was granted breakthrough therapy designation for first-line treatment for patients with FGFR2b-overexpressing and HER2-negative metastatic and locally advanced gastric and GEJ cancers in combination with modified FOLFOX6. Amgen initiated a global phase III trial of bemarituzumab in gastric cancer in the fourth quarter. I'm sure you're aware that last Friday, Deciphera announced that QINLOCK failed to meet its primary endpoint in the INTRIGUE trial.
We were surprised and disappointed with this result and are waiting for further analysis. We will collaborate with our partner, Deciphera, to determine next steps going forward, including a possible combination strategy. Note that QINLOCK is still the standard of care for fourth-line GIST patients and addresses major unmet medical needs. It remains the only product that has demonstrated significant benefits, including a survival benefit, in this setting. We continue to have a world-class GI cancer portfolio and multiple products in development. GI cancer is a key area of strength for Zai, and we are fully committed to working with the gastric cancer medical community in China and globally. In hematology, we recently announced that we had enrolled the first patient in China in our partner Regeneron's global, potentially registrational phase II trial of odronextamab in non-Hodgkin's lymphoma.
With so many potentially best-in-class and first-in-class products on schedule, we are very excited about our oncology pipeline at Zai Lab. Now I will turn the floor over to Harald.
Thank you, Alan. The third quarter brought several very encouraging new developments, clinical and regulatory, in our autoimmune and infectious diseases franchise. They stand to surely advance our pipeline to the next stage. Recently, our partner, Entasis, announced top-line results from the ATTACK trial. This is a global phase III registrational trial evaluating the safety and efficacy of sulbactam-durlobactam, comparing it to colistin in patients with serious infections caused by Acinetobacter baumannii. Sulbactam-durlobactam, or SUL-DUR for short, met the primary endpoint of statistical non-inferiority in 28-day all-cause mortality. The patients had mainly pulmonary infections with carbapenem-resistant Acinetobacter baumannii, known as CRAB. At test of cure, there was a statistically higher clinical response with SUL-DUR. In addition, SUL-DUR met the primary safety objective of the study, achieving a statistically significant reduction in nephrotoxicity versus colistin.
SUL-DUR is the first investigational drug to demonstrate efficacy against CRAB in a prospective, well-controlled clinical trial. CRAB infections are among the worst bacterial infections known to man. Safe and effective treatment options are almost non-existent. As a narrow-spectrum antibiotic, SUL-DUR targets CRAB bacteria preferentially, thus potentially avoiding the collateral damage associated with broad-spectrum antibiotics. We look forward to bringing this drug to China, where severe CRAB infections are frequently seen in ICUs and result in high mortality. As Samantha noted, we are actively preparing to file SUL-DUR with regulators in China. Moving on to ZL-1102. This is our internally developed anti-IL-17A novel human VH antibody fragment. We are developing it for topical treatment of plaque psoriasis. We recently achieved proof of concept with this novel compound and formulation in the first-in-human phase I(b) study.
In the study, a psoriatic target lesion was treated for four weeks with ZL-1102 versus placebo in a double-blind fashion. ZL-1102 showed a 45% relative improvement compared to placebo in the local psoriasis area severity index, or PASI. This clinical benefit was maintained after the end of treatment for a prolonged time, observed for up to six weeks. two key PASI components, erythema and scaling, showed clear improvement. There was also a reduction in target lesion size with ZL-1102, in contrast to an increase in lesion size in the placebo arm. In a responder analysis, ZL-1102 had higher responder rates compared to placebo at all time points after week one. These patients had a 45% or greater reduction in local PASI score to qualify as responders.
The safety and tolerability profile of ZL-1102 was indistinguishable from placebo. Pharmacokinetic studies confirmed a lack of systemic absorption, which explains its benign safety profile. There are about 125 million cases of psoriasis worldwide, and 80%-90% of these have plaque psoriasis. 70%-80% of plaque psoriasis patients have mild to moderate disease. We are developing ZL-1102 as the first IL-17-directed topical treatment for chronic plaque psoriasis, concentrating on those with mild to moderate disease. Currently approved IL-17 inhibitors for psoriasis are effective, but they are administered subcutaneously and absorbed systemically. Because they are immunosuppressive, they carry various warnings and precautions in their labels and are therefore approved for moderate to severe psoriasis only. On the other hand, existing topical treatments for psoriasis are lacking in efficacy or create safety concerns with long-term use.
ZL-1102 is a unique IL-17 inhibitor that can be applied topically to the psoriatic plaque without being absorbed systemically. We look forward to advancing this compound into full development, including registrational studies. We also achieved important regulatory progress for efgartigimod, which we partner with argenx. As you know, our partner expects a decision by the FDA on the regulatory filing of efgartigimod for generalized myasthenia gravis during the fourth quarter of 2021. As Samantha mentioned, we had a positive meeting with the NMPA on efgartigimod, which suggests the potential for an accelerated pathway for regulatory approval of gMG in China. Subject to U.S. FDA approval and further discussion with the NMPA, we expect to file the NDA in China by the first half of 2022.
Lastly, we expect approval of omadacycline for community-acquired bacterial pneumonia and acute bacterial skin structure infections in China by the end of this year. Now, my colleague, Tao Fu, will speak about progress with our commercial products.
Thank you, Harald. The third quarter marks our continuing progress in ramping up our three commercial products, all launched within a period of 16 months. Despite the COVID-19 flare-up in certain regions in China, which presented access difficulties, our commercial team did a great job overcoming these challenges and delivering a strong sales performance. ZEJULA continued to perform well, building on the momentum from the last quarter, when the second line ovarian cancer indication was included in the NRDL. Our team executed two key strategies to grow ZEJULA brand. First, our team has been laser-focused on increasing hospital listings as a result of our NRDL landing. As of September 30, 2021, ZEJULA was listed in nearly 1,100 hospitals in China.
Second, our commercial team focused on market penetration to drive pull-through by leveraging ZEJULA's differentiated label as the only PARP inhibitor monotherapy approved for all comers in first-line ovarian cancer. By executing these two strategies, we were able to grow ZEJULA's market share in both revenue and the number of new patients treated, and we plan to carry the momentum into the fourth quarter, when we expect to enter into NRDL negotiations for first-line ovarian cancer. We're confident that over time, ZEJULA will be the market-leading PARP inhibitor in China for ovarian cancer. Similarly, the launch of Optune is going well. During the third quarter, our team focused on continuing to improve market access by expanding commercial insurance and supplemental insurance coverage for Optune and educating target physicians about its significant clinical benefits, including survival benefits.
Currently, Optune is covered by 25 municipal or provincial supplemental insurance plans. The implementation of some of the newly added plans in the fourth quarter presents a good opportunity for us to grow Optune. We have also kicked off several important physician education campaigns and plan to establish a GBM patient journey management platform to increase the number of patients treated. As we noted last quarter, we successfully launched QINLOCK for fourth-line GIST in China last May, and we're still very early in our launch process. The key focus of our launch is increasing physician awareness and the number of patients treated by leveraging the INVICTUS trial data and QINLOCK status as the only later line GIST treatment, regardless of the mutation status, as well as the guideline recommendation by the Chinese Society of Clinical Oncology.
In the third quarter, we also received approval for and launched QINLOCK in Taiwan, making it the first-ever product that is available to all parts of the Greater China region during the first year of launch. As Alan mentioned earlier, we're still assessing the impact of the INTRIGUE result. We're committed to establish QINLOCK as the standard treatment for fourth-line GIST based on its compelling product profile, extending patient survival, and we will make appropriate adjustments to our commercial strategy. Now, Billy Cho will discuss our third quarter financial results. Billy?
Thank you, Tao. We saw continued significant growth and strong performance across our business. Today, I'll briefly summarize our financial results for the third quarter as well as year-to-date 2021. Revenues for the third quarter and year-to-date in 2021 were $43.1 million and $100.1 million, respectively. Over the same period last year, revenues were $14.7 million and $33.9 million, respectively. We're still early in our commercialization phase, but we're very pleased with the successful launches and sales trajectory of our first three oncology products. With many more product launches anticipated, our commercial platform over time is expected to generate strong growth and considerable operating leverage. ZEJULA sales for third quarter and year-to-date 2021 were $28.2 million and $64.2 million, respectively.
Over the same period last year, ZEJULA sales were $8.5 million and $22.3 million, respectively. Optune sales for third quarter and year-to-date 2021 were $10.7 million and $27.3 million, respectively. Over the same period last year, Optune sales were $6 million and $11.4 million, respectively. QINLOCK sales for third quarter and year-to-date 2021 were $4.3 million and $8.7 million. Research and development expenses were $55.1 million for the three months ended September 30, 2021, compared to $58.1 million for the same period in 2020. The decrease in R&D expenses was primarily attributable to lower upfront payments for new licensing agreements, partially offset by the increase in expenses related to ongoing and newly initiated late-stage clinical trials and payroll and payroll-related expenses from increased R&D headcount.
Selling, general, and administrative expenses were $59 million for the three months ended September 30, 2021, compared to $27.9 million for the same period in 2020. The increase was primarily due to payroll and payroll-related expenses from increased commercial headcount and expanded commercial activities as Zai Lab continued to expand its commercial operations throughout Greater China. For the three months ended September 30, 2021, Zai Lab reported a net loss of $96.4 million, or a loss per share attributable to common stockholders of $1.01, compared to a net loss of $63.7 million or a loss per share attributable to common stockholders of $0.84 for the same period in 2020.
As of September 30, 2021, cash and cash equivalents, short-term investments, and restricted cash totaled $1.57 billion compared to $1.19 billion as of December 31, 2020. We would now like to turn the call back over to the operator to open up the line for questions. Operator?
Certainly. Ladies and gentlemen, we will now begin the question and answer session. If you wish to ask a question, please press star one on your telephone keypad and wait for your name to be announced. If you wish to cancel your request, you can press the pound or hash key. We would request you to kindly ask two questions per participant to allow everyone a chance. We have the first question, which is coming from the line of Michael Yee from Jefferies. Please go ahead.
Hi. Thank you very much and congrats on a great quarter. We had two questions. The first was obviously on the announcement of the Karuna transaction. This brings you into a pretty big market opportunity in neurology, but also a complex one. Can you just comment on how you're thinking about synergy and being opportunistic in neurology now going forward, and what that means for business development for you? The second question is, you had made some nice comments about efgartigimod, the argenx compound. Can you just remind us about your confidence level in regulatory discussions and the potential faster filing in 2022? And if you could do that would be huge. So I would just love to know if you actually think that's possible. Thank you.
Thanks, Michael, for the question. This is Billy. Sorry about the background noise. We have several members of our management team on, so I'll help direct them like traffic. For your first question on Karuna and our entry into neuroscience, I'll, Jonathan, why don't you take this? I'm sure other colleagues can chime in as needed.
Sure.
Sure. Thanks for the question, Mike. I think, you know, first of all, there's actually a similarity and adjacencies for this expansion to neuroscience. You know, like what we have done in the past, you know, going into sort of severe autoimmune diseases with efgartigimod, going to, you know, hematology, you know, with our Regeneron collaboration, there's been a lot of obvious thought and strategizing as we go into new areas. When we go into new areas, there's always similarities. In this case, the similarity, first of all, is that, you know, especially with this drug, where patients go seek care in China, it's very concentrated. So there's a very limited number of, you know, psychiatric hospitals where patients go get care. There's about 1,000 of them.
In addition, you know, the large Class 3A hospitals, you know, only a very limited number of them have these psychiatric departments within them. So therefore, you know, the amount of sales team that's required to commercialize this is very limited. I mean, if you look at, you know, some of the currently leading companies in China focused in this area, their sales force is somewhere between 100-300 FTEs. I think that brings me to my second point, which is that there's adjacency to our current business because, you know, if you look at efgartigimod, the first indication is within neurology. It's in gMG.
Before we launch, you know, KarXT, hopefully we will already have a commercial team on the ground, selling Invega, and building up the care network in this area. You know, it's been a very slow process as we go into neuroscience. It's a very big market. You know, it's you know right behind oncology and immunology, one of the largest TAs in China. In fact, a very high-growing TA, you know, double-digit growth, even though there's a lack of innovative products. This product being very differentiated, you know, offering both on the efficacy side as well as safety side, clear differentiation compared to the standard of care today. You know, we are very confident about the commercial viability given our presence already in neurology, given the adjacency, a differentiated product.
In terms of the future BD efforts, look, when we get into new area, we bring an anchor product, a de-risked late-stage product. So this is our first product here. You know, we're obviously gonna continue to look for assets that may be synergistic with this, and you know, expand our CNS pipeline, you know, with similar de-risk and late-stage assets, but certainly we'll be on the lookout for those. Yeah.
Mike, for your second question on our
Yeah.
Yeah, Mike, for your second question on efgartigimod, you're right, we did make an announcement just on our third quarter earnings that you know, we have the potential to submit for approval in the first indication by first half of next year. Your question was our confidence level of that. Samantha, would you like to provide some commentary on this?
Sure. Thank you, Michael, for the question. Definitely, we are very optimistic about the potential to accelerate the approval process and submit the application in the first half of 2022 based on our discussion with the NMPA.
Okay. Sounds good. Thank you.
Sure. Thanks.
Thanks, Mike.
We have the next question. This is coming from the line of Yigal Nochomovitz from Citigroup. Please go ahead.
Hi, Billy and team. Thank you very much for taking the questions. I had three. First, I was just wondering about ZEJULA's current market share in second-line ovarian in China and how that market share has been trending since the ZEJULA launch. Second, I'm curious about the distribution of sales for ZEJULA across the 1,100 tier one, two, and three hospitals where ZEJULA is available. Is there a certain tier where you're seeing most sales or are the sales evenly distributed across hospital tiers? Finally, just curious, what are the gating factors for when you will begin to introduce revenue guidance for ZEJULA and also for Optune? Thanks.
All right. Yigal, thank you for your questions. You know, I'll kick it off on all three and invite other colleagues to join if needed. The ZEJULA second line market share, you know, we, you know, are not providing, you know, specific guidance at this point. You know, you can access information, like you do in the U.S., you know, through IQVIA, et cetera, to get views on it.
What I can share with you, Yigal, is that, you know, with the introduction of ZEJULA in the marketplace, in second line, which is a NRDL reimbursed product, and then of course, with first line, as the only all-comer labeled PARP inhibitor in ovarian cancer, clearly we've seen, not only the increasing of the pie of the PARP penetration, but also our market share within it, and that's both within second line and also increasingly so in our first line. We're very optimistic that this trend will continue. Hopefully that helps you.
We could provide additional color as we make further progress, and we're very confident that we're really set up here to have a commanding market share position for ZEJULA in the ovarian cancer space in the not too distant future. Your second question on the distribution of sales with ZEJULA between tier one, two, and three, sort of, you know, hospitals or geographies. Clearly our initial focus was to really, you know, make sure that we penetrate the class three hospitals in the top tier one, two cities, and we have the benefit of that legacy with strong execution. Now, with the second line in NRDL, you know, we have nationwide coverage, but the first line is still private pay.
We're optimistic that we're well-positioned for NRDL negotiation on first line as well, and that's when you're also gonna see not only a dramatic impact of the volume going up, but also a broader distribution as well. In terms of any gating factors for revenue guidance, you know, we're still very much early in our life cycle in terms of commercialization, as we noted on the call. Every month that goes by, clearly, you know, we're getting more momentum, you know, more hard real data, you know, inside Zai Lab, and our commercial platform continues to, you know, execute with strong growth, and productivity.
There will be a point in time, but that point in time is not at this moment.
Gotcha. Thank you very much.
Thanks, Yigal.
The next question comes from the line of Anupam Rama from JPMorgan. Please go ahead.
Hey, guys. Thanks so much for taking the question. I've got two quick ones. Maybe following up on Mike Yee's question on neurology. You talked about business development, but will there also be a build-out of an internal kind of research effort on the neuro side? And then second question, I think there was a mention of NRDL for first-line ZEJULA. Wanted to confirm that QINLOCK is also going to be a NRDL submission and when those pricing effects could take place in 2022? Thanks so much.
Hey, Anupam. I'll address your second question and then, tee it up for the team on your first question. Yeah, you heard it right. You know, first line, for NRDL negotiation for ZEJULA and first line, you know, will be happening. We're well prepared, and we're optimistic, that we're well prepared for a good outcome. You know, that's to be determined. What you will hear in the public domain will be very similar to last year and previous years, where the drugs that made it, the companies and drugs who've made it on the NRDL and accepted will be made public, by the NRDL, you know, a few weeks after, the negotiation finalized, which you know is happening in very near term.
The, you know, most of the companies will be signing NDA, so you will not hear about the price thereof until the implementation date, which will be, you know, likely January of next year, early next year, this year, not like, you know, March last, like in 2021, where implementation date was March. Next year is expected to be happening the usual January cycle. That's the cadence, and so there'll be more to come. You know, again, we're optimistic that, you know, ZEJULA will be a very important drug for many more patients. And we'll have a dominating or commanding market share position in the PARP class for ovarian cancer patients. Now, for QINLOCK, we were eligible.
We launched the advanced GIST label in October 20 this year, which means we were eligible to be included in the NRDL negotiation. We've elected not to because we have an ability to drive adoption, and as the only really, you know, we've established this drug as a standard of care, as Alan mentioned, in advanced GIST. You know, we have another opportunity next year to do so. You know, we have good optionality there. Your first question on neurology, where we're gonna build out, you know, our internal research capabilities there. As you know, Anupam, you know, we really dedicated our energy towards oncology and autoimmunity.
In terms of neurology, I mean, this, we just signed this deal, so it's hot off the press, you know, yesterday. In terms of building that out, I don't know if other, you know, Samantha, you know, Alan, Harald, if you have additional comments on that, or Samantha or Harald.
Yeah, if I can just,
Yeah. Thanks. Go ahead, Harald.
Samantha.
Go ahead.
Yeah. Hi. Thank you for the question. Will there be a build-out in neurosciences? The answer is yes. This is a big new addition to our current franchise. It does require extra work, it will require extra dedication, and it has huge potential. This is a big new market for us, but it's not an unknown market because we have had already experience in the neuroscience world, and as mentioned before, we have, on the efgartigimod side, at least two programs that are in neurology, and that is gMG, obviously, and CIDP. Yes, there will be a build-out in clinical and also in the sales team. It will be, you know, for commercialization in those hospitals in China that have psychiatric units, which actually is not too much, but it will not require a large team. We think it's worthwhile.
One point maybe in addition to your question, why do we go into this area? Because we understand the mechanism. This is a well-thought-out mechanism of an antagonist and an agonist working on the M1 and M4 muscarinic receptor. That's a very well-established approach. It's one that hasn't been really tried yet because everybody else has looked in other areas with other antagonists that look at dopamine and serotonin. There's also a lot of data in support of this. With all this, it gives us confidence together with the EMERGENT-1 trial data that this is something we can really sprint full, you know, full press forward. Thank you.
Yeah. I think, thanks, Anupam. Thanks, Harald. I think Harald brought a good, very good point about we branch out into this area with a lot of information. But in terms of discovery, Anupam, we're not interested in building our own research. We still remain focused on oncology and autoimmune.
Thanks for taking our question.
Take care, Anupam.
Thank you. We have the next question. This is coming from the line of Jonathan Chang. Please go ahead.
Hi, guys. Thanks for taking the questions. First question, can you discuss your gastric cancer strategy following the recent INTRIGUE study results? Can you provide any color around how you're thinking about potential next steps?
We'll pass that to Alan.
Great. Thanks. Thanks very much for the question. I think for next steps at this particular point, you know, we believe very strongly in our world-class GI cancer portfolio, and specifically for QINLOCK in the fourth line setting, which again, as has been noted in a randomized study, showed a significant overall survival benefit. We'll continue to look and work in that particular area, continue to build upon that. In addition, of course, we're looking forward to working with Deciphera to evaluate the data from the original study and see what sort of opportunities we have moving forward, which potentially could include combinatorial approaches as well. That's the approach we'll be taking at this point. Thank you so much for the question.
Got it. Thank you. Second question, can you provide any color around how the Optune LUNAR study is progressing? Are you able to provide any more granular color or when the study could read out? Thank you.
Alan, would you like to comment on this one as well?
Yes. Again, thanks for the question. This is something that, of course, is a study that's been accruing and is run, of course, by our partner, Novocure, and we're still working with them on this and participating in that study and waiting again for the accrual to finish. As you know, given the recommendations by the DMC, the follow-up for the study has been reduced from 18 months to 12 months in terms of the minimal follow-up. That might provide you with a little bit of guidance as to when we'll start to see data potentially after completion of accrual. Thank you again.
Yeah. Yeah, Jonathan, you know, Novocure also been saying now, I don't think that they've only said that that's the 2022 milestone, you know, final data to be read out. So I don't think they've guided to, you know, whether it's gonna be first half or second half, but you know, it's gonna be an anticipated milestone for next year.
Got it. Thanks for taking the questions.
Thanks, Jonathan.
We have the next question. This is coming from the line of Seamus Fernandez from Guggenheim Securities. Please go ahead.
Oh, thanks, guys. Just a couple of quick questions. You know, first, AstraZeneca in its filing documents has noted a patent expiration for Lynparza in 2024. Just wanted to get a little bit more color on how you guys are assessing the patent landscape in China. You know, are you anticipating the entry of Lynparza generics in 2024 or shortly thereafter? And if not, why not? Have you assessed the patent landscape and feel that Lynparza is likely to be protected longer? If there are generics that are introduced in 2024, what's your expectation for the evolution of the market from that point in time?
My second question really relates to, you know, the expansion and earlier stage opportunity for Optune. What are you guys doing at this point to prepare for a potential expansion, should the phase II or the trial, the LUNAR trial read out positively, to basically prepare for uptake and demand?
Hey, Seamus. Thank you for your questions. I think the first one, Jon, would you like to take it, and then I'll take the second one?
Sure. Thanks for the question, Seamus. You know, let me first say that we have a very strong patent position for niraparib. You know, we have a strong composition of matter patent that lasts almost to the end of this decade. And we have a very differentiated product. So even if there is a generic that comes to the market after Lynparza patent expiration, we have very differentiated assets. In particular, we're the only asset that has the all-comer monotherapy label in first line. And we're rapidly gaining market share, you know, as we're being on the second-line NRDL as we have, you know, a better product. Now, as we have NRDL negotiations that's currently ongoing, you know, if we're successful to get onto the first line for NRDL, we will have a even stronger market position.
We will solidify, you know, our broader label. Therefore, I think with a differentiated product, with a strong patent position, we can dominate the market for a very long time, with that.
Seamus, for your second question on Tumor Treating Fields. Optune obviously, we have it in the market since, you know, second half of last year. Our dedicated, you know, commercial team has doing a great job, covering the top hospitals, you know, in Optune for GBM. You know, there's about top 250 hospitals and, in fact, great coverage to neurology, to radiotherapy departments. We have a dedicated DSS team, that, you know, who continue to provide patient care and education. They've also done a great job, with the supplemental insurance. You saw from our earnings release that, we have up to about 25, you know, supplemental insurance plans signed up.
This is gonna bode well for not only Optune, but really positioning and building awareness for Tumor Treating Fields in the future across indications. Now, next year, obviously, you know, the LUNAR readout is gonna be an important milestone. But ahead of that, there's a lot of things we'll be doing. In addition to other indications in global phase III trials and we just wrapped up a China-only phase II trial, and we'll have data out for that, you know, by possible first half of next year. We're also been preparing to submit the second indication in mesothelioma. As you know, it just gives us a strategic opportunity to engage with the lung cancer community ahead of a possible positive outcome for LUNAR trial, so we can really optimize, you know, that event if it was positive.
We remain optimistic on all those fronts and continue to be big believers, you know, in the potential Tumor Treating Fields to serve many, many more patients than, you know, what we're doing right now. Thanks again for your questions. I think we can move on to the next question. Operator?
Certainly. The next question comes from Ziyi Chen from Goldman Sachs. Please go ahead.
Thanks for taking my questions. A couple of questions on the recent deals. Number one is on the Blueprint Medicines' EGFR assets. I'm trying to understand a bit more about the two molecules' preclinical data, you know, how's the therapeutic window look like? And also for their clinical strategy in China, 'cause, you know, the third-generation EGFR, including Tagrisso, and some of the domestic brands gonna potentially becoming the standard care in China in the first-line, second-line setting. And some of them also show a decent the blood-brain barrier penetration. So, will the BLU-945 and BLU-701 mainly targeting the patients who failed the third-generation EGFR? Or if we try to move into earlier lines, I guess head-to-head study will be inevitable.
Any chance that the combo could potentially beat the third generation EGFR in the survival benefits to patients? You know, trying to understand a bit more about your thoughts here. Also for KarXT, while we understand there's a large population of schizophrenia patients in China, you know, six million plus. However, a lot of them actually are in a poor financial condition. Affordability might be a big challenge, you know, particularly given available standard care now are super cheap. What could potentially be the pricing strategy here in China and how we should look at the commercial potential? Thank you.
Thank you for your questions. Alan, would you like to take these questions around the EGFR?
Sure. Thanks, Chen. Thanks, Billy, and thanks for the question. A couple aspects, I think I can probably lump those together. The initial one was more sort of the toxicity. You know, for these two agents, there's wonderful preclinical data that shows exceptional wild type sparing effects. That is the main cause for toxicity with these types of agents. By limiting the effects on the wild type, there should be fewer toxicity such as dermatologic and diarrhea. That's one potential advantage. It also, what it does is it allows for the potential for combination of these two agents.
That's a very key element for this because by combining these two agents based on preclinical data, you not only have limited wild type, you also impact those original mutations in EGFR, and then also the resistance such as again the T790M and the C797S. That allows for coverage that is actually in some ways similar to that of Tagrisso and then superior because it also can potentially overcome the escape mechanism, the resistance mechanisms.
Although the initial study of these agents will be in resistance because that's a faster path to approval, ultimately, moving and looking at this combination in a frontline setting is certainly a logical approach, and we're confident along with our partners at Blueprint that there is an opportunity to be superior to Tagrisso in this area. Thank you so much for the question.
Ziyi, for your second question.
Oh, one last thing.
You know...
I'm sorry. There was one last question.
Oh, please. Please.
They also have excellent blood-brain barrier penetration as well. Resistance that occurs in the CNS will be overcome by these agents as well. Thank you. Sorry.
Thanks, Alan. Ziyi, for your second question on KarXT, you know, clearly we've done a lot of work around this as we always do for all of our programs. I'll invite, you know, Jonathan to provide additional color.
Yeah, thanks for the question, Ziyi. Look, I think, first of all, the cheaper prices are due to it's pretty much mostly generics. However, all the products are on the NRDL. In fact, when there's recently a more recent launched product, you know, gone to the NRDL, the price cut was very limited. For example, in Invega, you know, only had a 5%-10% price cut to get onto the NRDL, and its annual treatment cost is about $4,000-$5,000. But it's still very largely undifferentiated asset in the dopamine, you know, 5-HT category.
With this product, a totally new MOA, you know, with first-in-best-in-class attributes, that addresses not only the positive symptoms of schizophrenia, but more importantly, addressing the negative symptoms which currently nothing out there does, and with a much better tolerability profile, you know, for example, weight gain, QT prolongation, you know, these kind of bad side effects KarXT seems to do very well at, we believe it is definitely worth premium pricing. You couple that with, you know, there's about eight million schizophrenia patients in China, these are chronic usage. Because the better tolerability, you can have a much longer DOT potentially.
Beyond schizophrenia, obviously, its potential in dementia-related psychosis, I mean, when there's nothing currently is approved on the market, that is a very large market potential, so I think we should consider as well. Hopefully this answers your question.
Thank you. Just a quick follow-up here. What is the patent status in China for KarXT?
Yeah. Look, it's undergoing the prosecution. Globally, its patent has a pretty broad family of patents. There's two primary major families. The patents are strong. You know, as you know, it includes two APIs. One of the APIs is not approved anywhere in the world, so there's no potential for any off-label usage. Overall in the U.S., you know, we're looking at the patent up to 2039, and we believe we have a good opportunity here in China as well.
Thank you.
Thank you.
Thanks. We have the next question. This is coming from Yang Wang from Credit Suisse. Please go ahead.
Thanks. I have two questions. First one is on the ZEJULA. Can you quickly comment on kind of what's a rough split for the ZEJULA prescription in terms of, you know, ovarian cancer, first line maintenance therapy and the second line maintenance therapy in China right now? Just give us, if you know, just give us some rough idea. That will be great. Then since our ZEJULA is in NRDL negotiation, I think it has, you know, a large chance to be included for first line. If first line included in the NRDL, then in the kind of longer term, what kind of a rough split between first line and the second line prescription for the ZEJULA in the longer term? That's my first question. My second question is about our kind of PD-1 strategy.
Since we see in our portfolio, we don't have a PD-1 approved yet, but quite a few of our drugs. Actually, our partners are doing a combo study for the drug called adagrasib and cetuximab, but they are all doing combo study, and the combo study with PD-1 have seen great efficacy and safety. Can you clarify your PD-1 or PD-L1 kind of development strategy in China? Thanks.
Hey, Yang. Thank you for your questions. For the ZEJULA-related question, you know, first of all, as you've heard on this call, you know, for first line ZEJULA, you know, we have been selected for final negotiation for NRDL inclusion, which will be going into effect early next year. That is the reason for that. Also like to remind you, we are and will be the only all-comer first line monotherapy product in the market, and it's a very differentiated product profile. The inclusion into the NRDL will significantly solidify our market position. Again, we're optimistic on the negotiation and the potential for ZEJULA to be a market share leader in ovarian cancer.
With that, you know, first line, we've always been saying that the first line, you know, indication is where really the battle is gonna be won. We continue to have very much confidence around that. At this time, we're not still giving splits between, you know, first line, second line, you know, kind of market share, and revenue split as well. Just want to remind you, Yang, that, you know, we recently launched first line and it's a private pay product, you know, and it was up against the reimbursed product, although they have a slightly different label.
You know, we'll try to provide additional color, you know, as we go into, as we wrap up our first, you know, it's really 2021 was our first full calendar year of commercialization. You know, we're still very much ramping up. I hope you understand. In terms of your second question on PD-1 strategy, you know, you're right in that, and I'll invite, you know, Alan to also comment here, but we have several combos, and, you know, in the future we'll have additional, what we call orthogonal synergies that we expect to realize, and that'll be quite proprietary. But you already listed a few that are ongoing.
The KRAS, they just had an update, you know, I think a day or two ago, an incremental update on the combo for lung. That was quite interesting. We have, you know, MARGENZA and even ZEJULA, right? There's PD-1 late-stage combo trials, you know, in two very large indications, you know, frontline lung and breast cancer as well. It's great and it'll be strategic for us to have, you know, not only PD-1, but to have a, you know, unencumbered portfolio within immuno-oncology to really, you know, go after and fully realize, you know, those orthogonal synergy opportunities. But Alan, do you want to, you know, provide any additional color?
Actually, Billy, you did a great job, and I don't have too much more to add other than we'll continue with the studies that we're doing to establish our PD-1 retifanlimab as an opportunity for use such that we can then go on to those combinatorial approaches, as you mentioned. Again, you know, the KRAS is certainly an exciting one. There'll be other opportunities of course as well, along with that in second generation IO combinations, as well. Yeah. Thanks very much for the question.
Okay. Thanks.
Thanks, Yang.
Thank you. I'm showing no further questions at this time. I will now turn the call back over to Zai Lab's 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 fourth quarter. Operator, you may now disconnect the call.