Good morning, good evening and welcome everyone to Zai Lab's 2021 R and D Day. Today, we will take a deep dive into Zai Lab's broad, deep and truly differentiated product portfolio and pipeline, our organization and operational infrastructure and our strategy for fast growth. We have come a long way in our 7 years of operations and the best is yet to come. 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 and timing and success of our clinical trials, regulatory applications, and commercial launches. Such forward looking statements are not guarantees of future performance, and therefore, you should not put undue reliance upon them.
These statements are subject to numerous risks and uncertainties 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. I will now introduce our speakers. Today's presentation will be led by Doctor. Samantha Du, Zai Lab's Founder, Chairperson and Chief Executive Officer.
She will be followed by Tao Fu, Chief Strategy Officer William Leung, Chief Commercial Officer Doctor. Alan Sandler, President and Head of Global Development, Oncology Doctor. Harold Reinhart, Chief Medical Officer, Autoimmune and Infectious Diseases Jonathan Wong, Executive Vice President and Head of Business Development and I will conclude our event. Here is our agenda for the day. With all the material that we have to cover, our event will take about 3 hours.
Samantha will begin by presenting her vision for Zai Lab. Tao will follow and describe Zai Lab today and the capabilities that will enable our company to achieve that vision. William will discuss our commercial capabilities and our 3 successful product launches to date. Alan will follow-up by walking us through Zai Lab's potential best in class pipeline in lung cancer, followed by what we believe to be a world class pipeline in gastric cancer. We will then take a short break.
When we resume, Alan will discuss our other oncology products. Then Harold will take us through the we're building in autoimmune diseases. He will continue with the discussion of our innovative medicines in infectious diseases. Alan will return to describe our strategy for developing our internal pipeline, including overviews of several key assets. Jonathan will discuss our successful and sustainable business development strategy.
I will conclude by speaking about how we can unlock Zai Lab's true value. We will then open up with a Q and A session involving all of the presenters, which we will handle just like the Q and A on our quarterly earnings conference calls. I'd also like to point out that the 2 leading oncologists in China, Doctor. Xun Liu of Shanghai Chest Hospital, Shanghai Jiaotong University and Doctor. Tianxu Liu of Zhongshan Hospital, Fudan University have provided videos with their perspectives on unmet needs in lung cancer and GI cancer in China.
You can find these videos on the marker site for this event. So with no further ado, it's my pleasure to turn our event over to Zai Lab's Founder, Chairperson and Chief Executive Officer, Doctor. Samantha Du. Samantha?
Thank you, Billy. Good morning and good evening, everyone. Welcome to Zen Life's R and D Day, and thank you for joining us. It has nearly two and a half years since we last had an R and D Day, So we very much look forward to spending the next few hours with you doing a deep dive into our extensive product portfolio and pipeline, Zai Lab has become a fully integrated biopharmaceutical company with many important medicines presentation is to help you better understand the full potential we see for these products and for our company as a whole. Although you may be mainly interested in Zai Lab's future, that future is rooted in our present.
So let me begin with a snap shot of our company today. Zai Lab is an innovative, research based, commercial stage biopharma company focused on bringing transformative medicines to patients in China and around the world. We aim to address significant unmet medical needs in large fast growing segments of the pharmaceutical market where we see the greatest opportunity to help as many patients as possible. We focus on 3 therapeutic areas: cancer, autoimmune disorders and infectious diseases. Within oncology, we have 5 disease area of strongholds: women's cancer, lung cancer, gastric cancer, brain cancer and hematological malignancies.
We already have launched 3 market products in Greater China, Zazula for ovarian cancer, Optune for GBM and Qinglock for GIST. We expect all of them to become leaders in their therapeutic areas. We have a pipeline of more than 25 assets with 12 assets in late stage clinical development. Our industry defining business development team has secured partnerships with leading global biopharma companies that generate a broad pipeline and innovative market products and product candidates. Compounds, we have an unsurpassed track record in advancing them through clinical development to accelerate their global timeline in gaining regulatory approval in Greater China and in marketing them effectively to reach the patients who will benefit most.
For the last 5 years, we have also built an in house team with strong drug discovery and translational research capabilities and have established a pipeline of 11 proprietary drug candidates later today. With the portfolio and pipeline of such breadth, depth and quality, it's easy to forget that our company is just 7 years old. By 2017, we had become a preferred partner for launching innovative products in Greater China. And today, we are a commercial stage biopharma company and preferred global partner. We have built a fully integrated R and D platform with more than 1600 employees globally, and we are only at the beginning of our journey.
We aspire to become a leading global biopharma company. To get there, we are becoming increasingly well positioned in the 2 most important global markets, China and the United States. China is already the 2nd largest pharma market in the world and one of the fastest growing ones. The 55 innovative drugs approved in China in 2020 represent 7 times the number approved in 2016. And we have an emerging presence in the United States.
We have positioned our operations at the heart of the U. S. Biotech ecosystem with discovery labs and development team in the San Francisco Bay Area and the new clinical development and business facility in Cambridge, Massachusetts. We have built a strong foundation for growth with a pipeline, platform and people necessary to drive our success for the remainder of the decade and beyond. We have an innovative, diversified portfolio of best in class and 1st in class assets that address the greatest unmet medical needs in numerous DG's areas.
We have built an open innovation model, sourcing our products, both from internal discovery and from global collaborations, whereas the science is strongest. We have an excellent clinical team advancing more than a dozen products at one time through development and regulatory approval with unparalleled quality and speed. Our best in class business development team supported by our strong R and D team has established us as the clear partner of choice and provided us with a pipeline that represents a sustainable pillar of growth. Our commercial operations are driven by our strategy of building world class disease franchises, which over time will allow us to achieve considerable operational synergies. And as you will hear from our presenters today, we have built global expertise, proven leadership and a deep talent pool across all functions in both China and the U.
S. What will Zai Lab look like in 2020 5? We have big aspirations. We aspire to be one of the leading global biopharma companies. We will have more than 50 marketed products across more than 35 indications.
We will have a leading portfolio and science driven commercial platform. We will have a broad innovative pipeline in late stage development, which we will have built by expanding both vertically within our current therapeutic areas and horizontally into our new therapeutic areas to unlock orthogonal synergies through proprietary combinations. Our internal discovery, Zhenjun, is already generating 1 global IND per year, and we expect to do at least that many by 2025, producing a sustainable product pipeline. We will have globally leading franchises in multiple disease areas, including the franchises in lung and gastric cancers that are visible today. And in addition to doing well, we aim to do good.
This has always been part of our identity and mission. We expect to become a leading global biopharma company that serves and impacts many patients around the world. We take our role of the emerging global leader seriously. With that in mind, we recently published our first environmental, social and governance report. Zai Lab is committed to becoming a biopharma leader in ESD performance and reporting by 2025.
And before I introduce to our next speakers, I would like to tell you why we chose the mountain climbing picture for our slides today. Many of you know that Zai Lab in Chinese means to once again reach the top of mountain. All the hard work over the past 7 years has equipped, energized, and committed us to confidently leave the base camp and start climbing to the top of mountain. We're excited to have you on this journey with us. And now I'll ask the other presenters to speak to how we expect to achieve our vision of Zai Lab 2025, starting with Tao Fu, our Chief Strategy Officer.
Tao?
Thank you, Samantha, and good morning or good evening, everyone. Today, I'd like to talk to you about Zai Lab's disease franchise and innovation strategy, and our growing global infrastructure and capabilities. On my first slide, I highlight our disease area stronghold strategy to build our pipeline. As you can see, within oncology, we focus on 5 common tumor types that are highly prevalent in China. Altogether, these disease areas cover more than 3,000,000 new cancer patients per year in China.
Outside oncology, we focus on autoimmune disorders and infectious disease, two areas that have significant and unique unmet medical needs in China. For example, the newly diagnosed cases of community acquired bacterial pneumonia in China total more than 10,000,000 annually. And the prevalence of the various severe autoimmune diseases that efgartigimod is addressing total well over 500,000. We believe this strategy will provide great operational synergies in both clinical development and commercial relation and allow us to maximize combination opportunities. This model will allow us to scale up our business quickly and build the deepest innovative pipeline in China.
Tsai's unique business model and our ability to work with the best companies in the world and their allow us to build a largely de risked highly innovative pipeline and sets us apart from competitors. 5 of our products have already been approved in the U. S. For our partners and the 6th is pending FDA review. 3 have been designated breakthrough therapies by the FDA.
The rest of our assets are mostly 1st in class or best in class, and many have achieved clinical proof of concept already. This portfolio, combined with our exceptional execution capabilities, allow us to advance our pipeline rapidly with a high success rate. We received 3 oncology approvals in China in the past 16 months, all under accelerated regulatory pathways. Importantly, our pipeline expects to produce 10 to 15 approvals over the next 3 to 5 years, which provides a highly visible path to significant near term growth. As Samantha mentioned, Zai Lab is still very early in our growth trajectory and will be a very different company by 2025.
At Zai, we follow the science. Building a proprietary and competitive discovery pipeline where we own global rights to balance our late stage in licensed pipeline in China is a key pillar of our growth strategy. Over the last few years, we have built strong in house drug discovery and translational research capabilities within our focused areas in oncology and autoimmune disease, and our effort has started to bear fruit. Alan will speak to our discovery strategy and pipeline later in today's meeting. We believe that our 11 early stage molecules with global rights and our discovery effort could create significant value for Tsai and our shareholders.
Importantly, we have an open innovation model that seizes the best opportunities wherever we can find them, internally or externally. Let me discuss this model in the next slide. Our open innovation discovery model is trying to harness the power of the entire biotech ecosystem in order to source Broadly speaking, our pipeline comes from a range of sources. We have collaborated with some of the leading academic institutions for novel targets and translational science. We have selectively built our internal discovery platforms, such as a best in class fully humanized transgenic mouth platform and a proprietary way to generate novel antibody epitopes.
We spread our discovery capabilities across our 4 campuses in the U. S. And China, taking advantage of local talent and expertise. Importantly, we formed collaborations with leading biotech companies to tap into their platform capabilities and expand our global pipeline. For example, we're working with MacroGenics to build CD3 and CD47 based bispecifics and multi specifics.
We're working with Schrodinger on a promising DDR target using their industry leading computational chemistry platform. We plan to continue executing our open innovation discovery strategy to achieve sustainable productivity over the next several years. This slide is a snapshot of our growing global footprint. We currently have over 1600 talented and hardworking employees, split roughly half and half between R and D and commercial. We have a large clinical development and operations team handling about 50 ongoing or planned clinical trials.
We do these clinical trials ourselves and don't rely on CROs to ensure speed and quality. We have a growing commercial presence with over 8 30 employees in Mainland China, Hong Kong, Taiwan and Macau. We have 2 GMP manufacturing facilities, 1 for small molecules and one for biologics, and a new R and D center and manufacturing facility at our Suzhou campus are under development. Our planned 37000 Square Meter R and D campus in Suzhou is included in China's National Strategic Emerging Industry Development Plan and supported by the government of Jiangsu province. The first phase of construction will be completed by 2023.
We're also planning a significant expansion of our existing biologics manufacturing plant, a small molecule production site, and a major distribution center. Above all, Zai Lab is all about people. Our global R and D teams are led by Doctor. Alan Sandler and Doctor. Harold Reinhart, whom you will hear from shortly.
Alan brings to Tsai nearly 30 years of oncology and drug development experience across industry and academia. Previously, he was the Senior Vice President and Global Head of Product Development Oncology at Genentech, where he led all late stage development for solid tumors and was responsible for the global development and regulatory approval of several innovative medicines, most recently, Tecentriq. Previously, he was professor and chief the faculty of the medical schools of Vanderbilt University and Indiana University. Harold is an adjunct professor of infectious disease at Yale School of Medicine. He has had a distinguished industry career with Novartis, Bayer and Shinogi in the areas of infectious disease, autoimmunity and renal disease among others.
He was personally responsible for the development and approvals of numerous important medicines, such as Corterm, Sebivo, Cubicin, and Cipofloxacin. Tsai has built a strong leadership team, shown here, to support Alan and Harold. Our business development, manufacturing and G and A functions are also exceptionally strong. As you can see, our leaders such as Tai and myself came from the leading biopharmaceutical companies such as Johnson and Johnson, Bristol Myers Squibb and Biogen with significant executive leadership experience. Our Business Development Leader, Jonathan Wang, worked at prominent investment and strategic consulting firms such as Worbimet, Goldman Sachs and Boston Consulting Group prior to Zai.
Our leaders are supported by our very strong teams. Our commercial team is led by Chief Commercial Officer, William Lang. William is a trained medical doctor and one of the well recognized commercial leaders in China. Before he joined Zai Lab, he was the Head of Oncology Business Unit for AstraZeneca, and prior to that he was head of oncology for Roche. These are 2 of the best performing oncology commercial organizations in China.
We have built a science driven commercial team with a proven track record of success. And now I would like
to introduce William so he can tell you more about our commercial capabilities. William? Thanks, Tao. Good morning and good evening, everyone. It's great pleasure to share with you our commercial progress at ZLab and our winning strategy for the future.
1st, I'd like to give you a brief overview of China market to help you better understand our growth strategy. 2nd, I will discuss strengths of our people and our promotional strategy. Then, I will describe the performance of our individual brands, and I will congru with our bold ambition. We are leaders in several large therapeutic areas in China, oncology, autoimmune disorders, and anti infectives. Oncology and autoimmune are the fast growing markets with plenty of room for further growth.
Based on the speed of innovation and huge unmet patient needs, which Alan and Harold will discuss, There's been a sharp rebound in demand in 2021 after soft performance in 2020 due to COVID. It may surprise you to know that the anti effective market is quite large in China from the point of view of the West. It's the 2nd largest therapeutical area, behind only traditional Chinese medicine, and the patients are in dire need of new therapies. As Harold will discuss, there's an urgent need for novel antibiotics to overcome multi drug resistance. So Zai portfolio strategy fits in well with the current and the future needs of patients in the Chinese market.
The COVID pandemic is reshaping the payer landscape in China. Prior to COVID, commercial health insurance premium totaled about $100,000,000,000 Now according to McKinsey report, the premium is expected to reach about $300,000,000,000 in 2025. Citi Supplemental Insurance is an emerging new form of commercial health insurance. To supplement NIDL, supplemental insurance provided by province and the cities is playing a more important role in patient coverage. Since 2015, more than 100 cities and 26 provinces launched Citi Supplemental Insurance, with the majority being added in 2021.
Back in October 2020, more than 20,000,000 people enrolled for Citi's supplemental insurance scheme in just 9 months. As of July 2021, more than 60,000,000 people are enrolled. We believe this number will be over 100,000,000 in 2025. This represents a tremendous growth opportunity to reach more patients with coverage. It's an important development for oncology brands like Zejula.
We have a strong NIDL team in place and we are expanding capabilities in our commercial insurance team. Since I became the 1st commercial employee at ZLF in June 2018, I'm very proud that we have built our organization to become the only China biopharma with a commercial footprint in all regions, Mainland China, Taiwan, Hong Kong and Macau. Our field force cover about 2,500 hospitals in 300 cities, representing 90% of the market potential for oncology market. We have successfully launched Zejula, Optune, Kinglog cross regions. We believe we have built the best biopharma sales team in China.
These sales leaders are very experienced and science driven with backgrounds at multinational companies. They have a proven track record of selling top brands in China. We have grown our team rapidly. Today, we have over 800 people in our commercial organization, which we expect to grow more and more than 1,000,000 by year end. Our sales and marketing teams are organized by therapeutical area.
1 of our key strategy is to focus on building disease area strongholds. With a portfolio driven strategy, the same sales force can detail multiple products and achieve operational synergies. For tumor treating fields, we created a single sales team across multiple tumor types. Because of its unique business model as a medical device. The shared functions serve all the therapeutical areas.
We believe this kind of organization will maximize our efficiency and effectiveness. It positions us very well to maximize the evolving landscape in China and reach more patients. Our commercial patient model has evolved in response to market dynamics. We are shifting from a product driven to a patient driven model, particularly to improve market access for patients. In order to differentiate ZLab from competitors, we are not only striving for innovation in our own R and D work.
We are also being innovative in our commercial business model. For example, we have established a diagnostic team, a data management team and a digital team. Our industry leading market access team has made tremendous contribution to all three of our product launches. Zejura had the best hospital listing performance post the NIDL among Chinese biotech companies, even including some multinational companies. KingLoc is the first product in a named patient program in which patient can take the drug outside the high net.
Optune is the only medical device listed in supplemental insurance. With our industry leading strategy and our team's ordering execution, We have successfully launched 3 products in just 16 months. Our first half revenue of $57,000,000 was nearly triple that in same period of last year. In terms of highlights for each product, Lejula, the number of hospitals this King has increased 7 fold to more than 800 from the data when NIDL implementation to end of June. For Optune, it's the 1st and only innovative medical device supported by supplemental insurance.
More importantly, China has become the number 3 marketer after U. S. And Europe in 1 year since launch. Despite being in the private paying market. For Kinglog, we are very proud that Kinglog has been approved across all Greater China regions within 6 months.
Now let's dive into products. Starting with Zejula. As I already mentioned, Zejula is ranked number 1 among China Biotechs in NRDL lending performance. It's actually a long road from NRDL publication to patients receiving a treatment. This picture shows you the critical steps in NRDL lending.
After NRDL negotiation, the central government published a drug list and the provincial city and the county government updates their reimbursement procedures. Most provinces only allowed hospital list drugs to be reimbursed. So hospital listing is another important test for a company's capability. Within hospitals, you must be approved by the drug formulary committee, which takes 1 to 6 months. Hospital purchasing then takes an additional 1 to 2 months.
Zejula outperformed others because we created several dedicated teams, including a central government affairs team, a local government affairs team, a hospital management team and a distribution team to focus on each step. We did this with a comprehensive plan and flawless execution. This was a remarkable accomplishment, and I'm so proud of our team. In addition, we continue to maximize the Jira's business potential by penetrating into emerging markets. We have a hybrid sales and marketing strategy for this market, which we believe is more cost effective for us at this stage.
Our core market is about 600 hospitals in so called Tier 1 and Tier 2 cities, representing about 2 thirds of the market. And we have assigned the majority of our sales reps to the core market. For the emerging markets, we also have established a partnership with distributors in a program called Xilinx to further penetrate lower tier cities. Our investment in emerging markets will support all future product launches. Let's move on to Optune.
We are succeeding in shaping the market through building centers of excellence in the top 20 hospitals. Since launch, Optune has been established as the standard of care driven by guidelines CME programs. As a result, we have more than doubled number of HCPs who have recommend or prescribe TTFields to patients. As we discussed, supplemental insurance is an emerging form of coverage within China Payer System. We have a private insurance team focused on partnering with commercial health insurance companies in order to help improve patient access.
Optune was the 2nd most reimbursed treatment in supplemental insurance in first half of twenty twenty one, second only to KEYTRUDA with many major indications. Going forward, we will build upon our early success for supplemental insurance inclusion to benefit more patients. Moving to Kinglock. We had a successful launch campaign in the spring. By end of June, we have expanded our dedicated sales force to more than 100 employees.
Since approval, we have hired very successful road shows. And despite the COVID challenges, we have reached thousands of HCPs online and offline. We are also well positioned in guideline inclusion. KingLog has been listed in the Cisco treatment guideline as the only agent with 1A level evidence in 4th largest. KingLoc is also leading in supplemental insurance coverage, now covering 2 provinces and 10 cities.
To conclude, we are looking to the future with bold ambitions. In the near term, we aim to become the market leader for Zejula, Optune and Kinloch and set a solid foundation for future success. In mid term, we're ready for 10 additional product launch in Greater China. And in the long term, we want to establish therapeutic area leadership in both China and the U. S.
As we're emerging as a leading global biopharma company. Finally, I would like to emphasize it's all about execution. It's all about teamwork. Let's all in for patience. Thank you.
And now I'd like to introduce Doctor. Alan Sandler. Alan? Alan
Sandler:] Thank you, William. I'd like to begin by providing you with some background about lung cancer and its treatment in China. My colleague, Doctor. Shun Liu of Shanghai Chest Hospital and Shanghai Xiaotong University has provided us with a more in-depth discussion of the subject in a video that we've included in the microsite for this meeting and that you may access. After my brief introduction to lung cancer in China, I will discuss the exciting potentially best in class franchise of drug candidates in lung cancer that we are developing.
Lung cancer is the most common cancer type and the leading cause of cancer deaths in China, and I've given you several visuals here to support that. Over 800,000 new cases in China, 4 times as high as you see in the US. The challenge with lung cancer is that the majority of patients are diagnosed at an advanced stage. Almost half of patients are diagnosed at stage IIIB or IV, which is locally advanced, unresectable or metastatic. As a result, many patients have a poor prognosis with a 5 year survival of 82% at 1a, stage 1a, but only 6% in stage 4 or metastatic disease.
5 year overall survival across all stages averages only about 20% and has not improved much in recent years. Let's see what treatment advances we've achieved, though, in lung cancer in the past several years. I will start with precision medicine. Here's a slide that takes you from where we've been on the far left when the diagnosis was made under the microscope and we did not even distinguish small from non small cell lung cancer and patients were treated in the same way with cisplatin based chemotherapy. Over time, we've been better able to define the histologic approach and then using molecular pathology, we were able to determine various genetic aberrations and resulting targets like EGFR and ALK.
In addition, as we went beyond that and cancer immunotherapy began to play a role, other means of differentiating patients, such as PD L1 expression or tumor mutational burden, have come into play. This next slide illustrates that although there are many choices available for various driver mutations in the United States, patients in China do not typically have the same choices. What we've shown you here in blue are those agents that are FDA approved, but not NMPA approved. Importantly, there are numerous agents that Tsai is developing to address this lag in approved medicines in China, including repotrectinib, TPX-twenty two, CLN-eighty one, and adagracib. This slide here illustrates the continued growth of biomarker testing in China.
The graph on the left shows that molecular testing has increased quite dramatically over the past 10 years based on a survey of 49 hospitals. This is reflective of the greater availability of targeted agents over this 10 year period. As all physicians were taught in medical school, there's no reason to do a test unless you're going to do something with the results. So testing for mutation makes far more sense when you have something to treat the patient with following that news. Testing is going to continue to increase in China as more and more targeted therapies are approved and with the use of NGS.
Again, the key element is you see very high testing for patients in ROS, ALK and EGFR because those drugs are available to patients. For those mutations or abnormalities where there is not effective therapy, the testing is less frequent now, but we expect those to continue to increase. Here we show you our broad based and differentiated portfolio, including several targeted therapies in lung cancer that we have at Zai Lab. Targeted therapy is a very important aspect of our portfolio in general, and of course, lung cancer specifically. Our portfolio looking at ROS1 and NTRK, EGFR exon 20 mutations, MET alterations, and KRAS G12C represents nearly a quarter of all newly diagnosed non small cell lung cancer patients in China.
In addition to our targeted approach, we also have a checkpoint inhibitor backbone therapy for IO, retefanilumab, along with very unique therapeutic entity, tumor treating Let's begin with repotrectinib which we are partnering with Turning Point Therapeutics. Repotrectinib could very well be a best in class ROS1 and entrec therapeutic agent. It has already shown efficacy in both TKI naive and TKI pretreated patients. This first slide demonstrates the mechanism of action for repotrectinib, and I'll highlight a few interesting points. It is highly potent, as noted in the table below, and preclinically, it has already demonstrated high potency against fusion ROS1 and TRK ABC an emerging resistant mutations that you can see below.
It's designed to bind completely inside the ATP pocket, as you can see on the right, and this provides it with the potential to address resistance from prior lines of TKI therapy. When used in the frontline setting, it may help to prevent or delay emergence of new resistant mutations. From a clinical perspective, here's a slide that shows you a waterfall plot preliminary phase 1, phase 2 data of reprotrectinib and ROS1 the is downward, showing tumor shrinkage in virtually all patients and a confirmed overall response rate in the phase 1 and 2 portion of 91% out of 22 patients. Although the data is relatively early, you see there is also evidence for a considerable duration of response. In the pretreated population exhibited here, again you see the waterfall plot on the left showing considerable clinical activity in 27 patients.
And on the right in the table, you'll see the specific data. The confirmed overall response rate in the combined studies for previously treated patients is 50%, that is 6 out of 12 patients. Again, limited numbers of patients, but you're already beginning to see clear evidence of activity in ongoing studies. In addition to the activity seen in ROS1, there's activity in limited numbers of patients in NTRK advanced solid tumors. These are TKI pretreated solid tumors in the TRIDENT-one study.
You'll see 3 out of 7 patients responded, corresponding to patients, total of 185 patients from the combined phase 1 and 2 trials, repotrectinib has been very well tolerated. Majority of treatment related AEs are grade 1 or 2 and in fact, there were no grade 4 or 5 treatment related adverse events. And the most commonly reported treatment emergent adverse event was low grade dizziness. We're very excited about the opportunity of repertrectinib. An additional 1.5% of patients in both non small cell lung cancer and other solid tumors with NTRK abnormalities.
Repotrectinib has exhibited both efficacy and safety in these patient populations. The timeline is shown here, the first patient was enrolled in TRIDENT-one in the first half of twenty twenty one. Let's move to CLN08 1 from our partner, oral agent with a unique scaffold which is a oral agent with a unique scaffold which is a pyrrolopyrimidine highly selective for exon 20. It has limited activity for the HER2 wild type and exon 20 wild type being selective for the activating mutations. As a result, it's great potential to differentiate both with respect to clinical activity as well as safety, given the limited impact on the wild type.
Therefore, you would anticipate fewer toxicities in terms of skin and GI events. On the lower portion of the slide, you'll see 2 graphics supporting these concepts. On the left, the dotted area shows the higher selectivity for the exon 20 mutations when compared to other inhibitors. And on the right, you see that the selectivity supports utility in traditional sensitizing mutations such as exon19 deletion, L858R, and T790M mutations as well. From a clinical perspective, there certainly is encouraging preliminary antitumor activity illustrated in this table.
I'd like to emphasize the box in green. There are 13 patients noted, with all patients showing stable or better disease and an overall response rate of 54%. It's important to mention that this is a heavily pretreated patient patient population and in fact more than 2 thirds of the patients were treated with at least 2 prior lines of therapy. On the far right, we've provided you with a summary in 42 patients in multiple doses ranging from 30 to 150 mg, again showing a consistent response rate of 50%, in this case 21 out of 42 patients and a 98% control rate. The safety profile shows acceptable overall safety and tolerability and in particular, the GI toxicity profile is quite encouraging with no Grade 3 treatment related AEs for diarrhea and doses below 150 mg and no Grade 3 rashes.
So our key takeaways for exon 20 insertions, there are no improved targeted therapies in China at this time. There's an annual incidence of approximately 30,000 patients with this mutation in China and these are patients who clearly don't do nearly as well on approved EGFR therapies as those patients with the more traditional EGFR mutations. We've shown you a response rate of 46%. The compound has a favorable tolerability profile. It's been challenging in this area to find a highly selective agent that does not impact the EGFR wild type with resultant toxicities.
We believe that CLN-eighty one does in fact meet that need. China timeline is for anticipated enrollment of the first patient in the Phase 2b study in Greater China next year and plans for future studies may include select pivotal studies such as monotherapy in frontline, combinations also in first line, second line, and beyond. Let's move to TPX-twenty two from our partner TurningPoint. This is a potent inhibitor of MET, Src, and CSF1R tyrosine kinases as supported by both biochemical and cellular assays, with its inhibition measured in nanomolar concentrations. On the right, you see the screen of 373 kinases and you'll note that TPX-twenty two is highly selective as it's only in the very distal branches of the kinase tree shown here.
Although designed as a potent MET inhibitor, there was also the targeting of Src and CSF1R, which may improve clinical efficacy as Src is a downstream MET effector that's involved in malignant transformation, metastasis and drug resistance. CSF1R plays an important role in the regulation of tumor associated macrophages. Therefore, we see a 3 pronged approach and all three should favorably impact efficacy in this patient population. We have Phase I data to suggest evidence of activity in patients with various MET genetic alterations such as exon 14 deletion, amplification, fusion or oncogenic kinase domain mutations. This activity was seen in a range of diseases including gastric and colorectal cancer, which I'll discuss later in another presentation.
For MET positive lung cancer, we had 1 out of 3 patients in the TKI naive achieve a PR. 3 out of 5 of those were previously treated with a TKI and had stable disease. The compound was well tolerated with no treatment related grade 3 or greater ALT or AST elevations and no ILD or pneumonitis of any grade. On the right, you'll note the traditional approach to the Phase 1 study with dose escalation across multiple diseases involved with MET genetic alterations, as I mentioned. And then you'll also note the activity in the waterfall plot on the right.
So to summarize, there are approximately 83,000 patients annually in China with MET alterations in non small cell lung cancer. And this comes from about 20% of patients having some sort of MET derived abnormality, whether it be exon 14 deletions, amplification or association with EGFR TKI resistance. There is only one MET TKI currently approved in China and that's specific to the MET exon 14 skipping non small cell lung cancer. There are no approved targeted therapies for MET amplification following frontline EGFR TKI therapy. This is especially important because of the large population noted in China.
The encouraging preliminary Phase I data suggest a pan MET potential. And we anticipate enrollment of the 1st patient in the phase 2 portion in Greater China in the first half of next year. Moving on to adegrasib from our partner, Mirati, we believe it is a potential best in class KRAS G12C inhibitor. And as a thoracic medical oncologist, I can say that KRAS has been a target that many people have attempted to address for many, many years. It's certainly exciting to see an agent with the level of activity seen with adagracib.
To review, adagracib irreversibly locks the mutant protein in its inactive state and is designed to fully inhibit KRAS G12C for the entire dosing interval. This is an important point to mitigate against potential escape mechanisms. Some additional key characteristics that I'd like to highlight from preclinical studies are shown here. Adagracisib is potent with nanomolar potency, has a long half life, is highly selective with a very wide therapeutic index and achieves extensive and broad tissue distribution. So let's move to the clinical efficacy in pretreated patients with non small cell lung cancer.
This will be data pooled from a set of Phase 1, 1b studies with 600 milligram BID dosing. In the first 14 clinically evaluable patients, there were 6 responses noted. Looking at that dataset, in combination with early data from the Phase 2 study at the same dose, we now have a total of 51 clinically evaluable patients. We see 23 patients for an overall response rate of 45%. The safety profile is in 110 patients, showing only 4.5% of those with treatment related AEs leading to discontinuation of treatment and only 7.3% of all AEs leading to discontinuation of treatment represent a very tolerable safety profile.
I think it's quite apparent that the KRAS mutation is certainly an unmet medical need. It represents 43,000 patients annually in China when you look at non are no currently approved targeted therapies in China. Patients with KRAS mutations respond poorly to other standard therapies such as chemotherapy. We believe the differentiation for adagracib is both its clinical efficacy and a very favorable tolerability profile. Later during my presentation on GI malignancies, I will show you data for colorectal cancer.
With respect to the China timeline, we'll be participating in multiple mono and combination therapy global trials next year and beyond. In addition, we'll also be running exploratory local studies in combination with our own assets. So now let's take a look at a very interesting and intriguing therapeutic endeavor, tumor treating fields from our partner Novocure. It provides electric fields at frequencies tuned to target dividing cancer cells. This slide shows the frequency band from low frequency used in cardiac defibrillators and pacemakers all the way to the far right for ionizing radiation and resulting DNA damage.
You'll note within the intermediate frequencies is where tumor treating fields has its impact on those malignancies that have a higher rate of replication and also have a higher differentiated frequency. This allows for the potential a therapeutic index and resultant safety that you've seen. Currently, there are now 3 approved FDA indications, 2 of which are NMPA approved for newly diagnosed and recurrent glioblastoma with 5 additional indications in late stage development. The global phase 3 pivotal LUNAR trial in non small cell lung cancer following platinum failure is ongoing and I'll discuss this further on the next slide. Please note Novocure is also working with Merck on a phase 2 study in the frontline non small cell lung cancer TFI, TT fields in combination with pembrolizumab.
Here is the Phase 3 LUNAR pivotal trial in which there was an an interim analysis earlier this year. The rationale for conducting LUNAR trial is based on the efficacy seen in a pilot Phase II study, revealing a 13.8 month median survival, comparing quite favorably to a pemetrexed historical control. The original LUNAR study was designed to have 534 patients with 18 month follow-up and the anticipated final data sometime in 2023 using a primary endpoint of overall survival. However, following evaluation by the DMC, the DMC recommended and the FDA accepted an adjustment to the protocol to reduce the number of patients to 276 and the follow-up period reduced from 18 months to 12 months, with the final data now anticipated sometime in 2022. It's well known that non small cell lung cancer is an important unmet medical need globally and in China specifically with an annual incidence of nearly 700,000 patients.
Tumor treating fields with its safety profile has the potential to combine with multiple therapies moving forward. Its differentiation relates to its unique mechanism of action and tolerability. We'll be submitting an MAA for malignant pleural mesothelioma sometime later this year. You'll also can see key milestones that our partner Novocure is anticipating. And now I'd like to move from lung cancer to GI cancers, whereas in lung cancer, we have a very well differentiated and targeted portfolio and a potential world class franchise.
GI cancers consist of gastric, liver, pancreatic, and colorectal cancers. My colleague, Doctor. Tanshu Liu of Songshan Hospital, Fudan University, has recorded a video with an in-depth discussion of GI cancers in China that we've included in the microsite for this meeting and that you'll be able to access. As with lung cancer, I'll begin with an overview of these diseases in China. The prevalence of GI malignancies in China is the highest in the world.
The incidence of GI cancers is significantly higher than that the US. Also very concerning, GI malignancies in China are associated with an extremely poor prognosis, generally worse than in the U. S. And Japan. Of note, the 5 year survival rate for gastric cancer is only 36% and for liver China accounts for almost half of the world's deaths from the disease.
China accounts for almost half of the world's deaths from the disease. It is mainly caused by unhealthy dietary habits, as well as high incidence of H. Pylori infection and smoking. The early diagnosis rate for gastric cancer and the rate of gastroscopic evaluation in China are much lower than that in Japan. More than 60% of Chinese gastric cancer patients are diagnosed at advanced stage when compared to 12% in Japan.
For advanced stage gastric cancer, the prognosis remains poor, with a very low 5 year survival. Thus, gastric cancer represents a significant burden for China, the Previously, gastric cancer was one disease and chemotherapy was the only treatment for advanced gastric cancer with modest impact. In the past decade, HER2 has emerged as the first target for gastric cancer. Now, more genomic alterations alterations are identified as therapeutic targets and more therapeutic agents are under development. The table on the right shows examples of gastric cancer genomic alterations and the respective prevalence rate.
I would like to point out that Zai Lab's current gastric cancer portfolio covers 3 highly prevalent alterations shown here, HER2, MET, and FGFR2, as well as KIT and KRAS, not shown in this table. So let's move to our Xi will actually cover about 50% of all gastric cancer patients, Xi will actually cover about 50% of all gastric cancer patients in China. Our targeted therapies in GI cancer include bemrituzumab in FGFR2b, margetuximab in HER2, TPX-twenty two in MET alterations, repretinib and C KIT and PDGF R alpha and adagrassib and KRAS. We also have additional opportunities in immuno oncology with tibotelumab in combination with niraparib, our PARP inhibitor, in gastric cancer. We're also studying tumor treating fields in gastric, pancreatic and liver cancer using electric fields to inhibit malignant cells from dividing.
Let's start with bemerituzumab from our partner Amgen. Bemrituzumab is an IgG antibody that is specific to the FGFR2B receptor. We think in class in China. It was engineered to enhance tumor cell killing via ADCC and it also selectively avoids many of the problems associated with electrolyte abnormalities seen with the TKIs in this setting. The mechanism of action is shown on the right, blocking the FGFR2B receptor and also the ability to activate ADCC, both of these events leading to tumor cell death.
Clinically, there was anti tumor activity of 18% seen in late line FGFR 2b positive gastroesophageal cancer with bemrituzumab monotherapy, prompting an evaluation of combination therapy. The FIGHT Phase 2 study was initiated by 5 Prime Therapeutics, later acquired by Amgen. This study looked at a combination of FOLFOX6 plus bemrituzumab or placebo in 155 patients. The Kaplan Meier curve on the right shows a remarkable difference in overall survival with the addition of bemarituzumab to chemotherapy, revealing a hazard ratio of 0.6 and an improvement in median overall survival from 13.5 to 19.2 months. With respect to safety signals, overall TAEs were balanced between the two arms, despite an arm that contains more therapeutic agents.
There were some corneal and stomatitis adverse events more frequent in the bemratuzumab arm which were expected based on the mechanism of action. However, they were reversible, and no adverse events of retinal detachment or hyper phospatemia were identified in the bemrituzumab and chemotherapy arm. So, to summarize, bemrituzumab is 1st in class FGFR2b inhibitor with a sizable market opportunity in Greater China. There are significant unmet medical needs in China for gastric cancer in general and patients with tumors that FGFR2b represent about 1 third of those gastric cancer including squamous cell carcinoma in the lung, breast cancer, ovarian, and other organs. Zai contributed to the phase 2 FIGHT study and our plan is to initiate the confirmatory phase 3 study with our new partner Amgen.
There also remains the potential for us to explore other indications. So, let's now move to TPX-twenty two, which we're partnering with Turning Point in the phase 1 SHIELD 1 study in gastric and colorectal cancer. TPX-twenty two is a small molecule MET inhibitor. Patients are defined by their MET alterations, which include exon 14 deletion, amplification, fusion, or oncogenic kinase domain mutations. The schema for this study is shown in the upper right as a monotherapy escalation with subsequent dose expansions in the various cohorts in either non small cell lung cancer, which I discussed earlier, and GI cancers.
We have early efficacy data in the MET positive gastric and colorectal cancers. 4 of the 7 TKI naive patients, which include all 3 in gastric cancer and 1 out of 4 in colorectal cancer, achieved a partial remission, illustrated in the waterfall plot on the lower right. The compound has been generally well tolerated. Most of the treatment emergent adverse events were grade 1 or 2 and the most common T EAE was dizziness. There were no related grade 3 liver abnormalities, no ILD or pneumonitis of any grade.
MET amplified gastric cancer represents about 3% to 5% of gastric cancer cases. There are no approved targeted therapies for MET amplified gastric cancer, so this is one of the largest potential market opportunities for MET inhibitors. There's encouraging preliminary phase 1 data in both gastric and colorectal cancers suggesting that TPX-twenty two may be useful in MET abnormalities in a tumor agnostic approach. We anticipate enrolling the 1st patient in the phase 2 portion of SHIELD-1 in Greater China in the first half of twenty twenty two. Now I'd like to move to margetuximab, which we are partnering with MacroGenics.
This is a novel immuno optimized anti HER2 monoclonal antibody. It was designed to increase its antitumor effectiveness through Fc engineering using MacroGenics' proprietary optimization platform. There was increased binding to CD16A as well as decreased binding to CD32B, thereby increasing the activation and decreasing any opportunity for inhibitory As a result, margetuximab inhibits tumor cell proliferation and reduces shedding in the HER2 extracellular domain. Importantly, there's also enhanced antibody dependent cellular cytoxicity via immune cell mediated antitumor activity and NK cell activation. We have seen encouraging data in advanced previously treated gastric cancer patients shown on this slide.
In the first line setting, you'll see the standard of care, chemotherapy plus trasituzumab and in the second line setting, the standard of care of ramasirumab and paclitaxel. We're going to compare those treatments to the phase 2 study of margetuximab and pembrolizumab. In this study, patients were evaluated by expression of HER2 and PD L1. And in both cases, the median overall survival in the first line setting or numerically better than standard of care in the second line setting. In HER2 positive HER2
When you
look at HER2 positivity plus PD L1 expression, you see an impressive response rate of 44% and nearly a doubling of the overall survival to 20.5 months, comparing quite favorably to data seen in first line patients who typically live longer than patients in second line. The incidence of grade 3 adverse events is significantly lower in the combination of margetuximab and pembrolizumab, predominantly due to the absence of chemotherapy in this regimen. The ongoing MHAHOGANY trial in previously untreated patients, which is potentially registrational, has a module A studying a combination of margetuximab and the PD-one inhibitor, ritafanlimab, a chemo free regimen in patients who are PD L1 positive. Module B looks at patients independent of PD L1 and tbotelemab and chemotherapy. So, it's clear that gastric cancer is an important malignancy in China.
About 12% to 13% of these patients will overexpress HER2 positivity. The current standard of care is trasituzumab in chemotherapy, and margetuximab has the potential with its enhanced ADCC to provide additional clinical efficacy, which has been shown in earlier studies. We will continue to evaluate that in pivotal trials moving forward. In terms of the China timeline, we've enrolled the 1st China patient in module B of the global MAHOGANY study and we also plan to submit an NDA in breast cancer toward the end of this year. I'd now like to talk about GI stromal tumors and Kinlok or rupretinib, which we are partnering with DeCYPHRA.
It's a novel switch control kinase inhibitor that blocks the drivers of resistance in this disease. Kinloch has a dual mechanism of action that provides broad spectrum inhibition of KIT as well as PDGF R alpha kinase signaling in vitro, including multiple primary and secondary mutations as well as some wild type GI stromal tumors. The mechanism of action is shown with kinlock binding to the activation switch and switch pocket regardless of mutation, thus locking the kinase in the inactive state. An early phase 1 study was done in multiple cohorts in revealing positive results across all lines of therapy in a pretreated patient population shown here in this table. You see the median progression free survival of 10.7, 8.35.5 months and response rates of 19.4, 14 point 3 and 7.2 percent in the second, third and fourth line plus respectively with prolonged median durations of response across the board.
There was an ongoing Phase III study known as INTRIgue studying rupretinib versus sunitinib, the de facto standard of care in 2nd line GI stromal tumors post imatinib therapy. The primary endpoint is PFS and as there's no crossover, overall survival will be evaluated as well. The GIST market is significantly larger in China than in the U. S. And Europe with about 30,000 newly diagnosed patients annually in China.
There is a clear unmet need, particularly in pretreated patients as well as the frontline setting. This is a potential best in class therapy for advanced GI stromal tumors that have been previously treated regardless of mutation. There are multiple types of mutations, so this could offer a broader spectrum of therapy than other agents currently available. It's the only therapy recommended in the 4th line all comer setting by the NCCN. It's the only drug recommended with level 1a evidence in 4th line GIST setting in the China 2020 Cisco guidelines with a recommendation in second line as well.
The 4th line GIST indication has been launched in mainland China, Hong Kong, and Taiwan. The 2nd line GIST bridging study is currently ongoing and we anticipate the 2nd line GIST supplemental NDA to be submitted next year. Now I'd like to discuss the ZAI sponsored phase II pilot trial of tumor treating fields in gastric cancer. On the left, you'll see the preclinical data showing that TTFields and FOLFOX chemotherapy result in enhanced activity compared to chemotherapy alone. The scheme of the Phase II trial is shown here.
It's a single arm study looking at this combination in 28 patients with 12 months follow-up and final data expected next year. Tsai will be joining Novocure's global phase III studies of tumor treating fields in both pancreatic and liver cancer. In pancreatic cancer, efficacy was suggested in a Phase II pilot study called PANOVA, where TTFields was utilized with chemotherapy, either gemcitabine or gemcitabine plus nab peclitaxol. The median overall survival was not reached, which compared quite favorably with historical controls of 8.5 months seen with the chemotherapy combination previously studied. We anticipate that the first patient in China will be enrolled in this pivotal trial later this year.
For hepatocellular carcinoma, efficacy was suggested in a Phase II pilot study called HEPANOVA with TT fields given concurrently with sorafenib, the VEGF TKI. This was a small pilot study in 21 patients. There was a 9.5% overall response rate in this very difficult to treat malignancy with a 76% disease control rate and PFS of 5.8 months. Notably, 11 patients who were able to complete at least 3 months of therapy had an improved overall response rate of 18% and a 91% disease control rate. A phase III pivotal trial is currently in the planning stage, including determining the appropriate control arm and backbone therapy with TTFields.
Let's now take a look at adagrasib, the KRAS G12C inhibitor that we discussed in non small cell lung cancer. We've seen evidence of activity in previously treated patients with colorectal carcinoma, a very difficult disease to treat in patients with KRAS G12C mutations. In this slide, you see the design of CRISPR1 study including the dose escalation phase that arrived at a recommended dose of 600 mg twice daily and the dose expansion phase. Mirati recently presented data at ESMO for adagracib as monotherapy or in combination with cetuximab in colorectal cancer. Let's take a look.
On this slide, you can see the waterfall plot of the ESMO data for adaggressive monotherapy. Mirati reported a response rate of 22%, that is 10 out of 45 patients, including one unconfirmed partial response. Stable disease was also seen in 64% of patients, 29 out of 45 patients, and an overall clinical benefit in 87% of patients, 39 out of 45. Mirati also revealed evidence of a rapid onset of action and significant duration of response in the monotherapy cohort with a median time to response of 1.4 months and a median duration of response of 4.2 months with 40% of patients remaining on treatment at the time of the data readout. Now, this slide shows the combo data.
Here you see a response rate of 43%, representing 12 out of 28 patients, including 2 unconfirmed partial responses. Stable disease was observed in 57 percent of patients that is 16 out of 28 patients for an overall clinical benefit in 100 percent of patients. The combination also showed evidence of rapid onset and significant duration of response with a median time to response of 1.3 months and 71% of patients remaining on treatment at the time of the data readout. Edagracib has the potential to be a 1st in class and best in class KRAS G12C inhibitor in China. As I mentioned earlier, there are significant number of these patients in China in non small cell lung cancer, colorectal and pancreatic cancers and there are currently no approved therapies for these patients.
Our plan is for broad development in both monotherapy and as combination in both non small cell lung cancer and colorectal cancer that will include several registrational studies, all of which Xi will be participating in, in 2022 and beyond. In addition, Xi will also be able to run exploratory local studies looking at combinations with some of our own pipeline assets. And now, you and I deserve a break. So we will pause and when we resume, I will talk about some of our other disease franchises Welcome back, everyone. I will now discuss products in oncology other than lung cancer and gastric cancer.
I'll begin with odranexamab, our CD3, CD20 bispecific that may prove to be best in class against non Hodgkin's lymphoma. On the left, you'll see both its molecular structure as well as its mechanism of action binding to both CD3 activated T cells as well as to cancer cells expressing CD20. Intriguing data is shown here in relapsed and refractory follicular lymphoma with a complete response rate of 70%. Notably, the strong responses were seen in relapsed and refractory diffuse large B cell lymphoma in both CAR T naive patients with a CR rate of 55% and post CAR T patients with an overall response rate of 33%, including a 21% complete response rate. With respect to safety, there was CRS observed during the step up dosing, but with no CRSs higher than grade 3 in the follicular and diffuse large B cell lymphoma population.
The majority of CRS events being mild or moderate and no discontinuations due to CRS or neurotoxicity. There is certainly a high unmet need in China and there are limited treatment options for Chinese patients beyond rituximab, including the low feasibility of CAR T therapy. Therapy subsequent to rituximab would include chemotherapy with rituximab and or high dose chemotherapy with stem cell transplant, which provide limited benefit. So this allows for an off the shelf cell therapy option for relapsed and refractory non Hodgkin's lymphoma. We have seen durable and complete responses in heavily pretreated patient settings that include some patients post CAR T therapy.
Importantly, subcutaneous formulation is also under development. As for our timelines in China, we anticipate enrolling the 1st patient in China in the Phase II study, B cell non Hodgkin's lymphoma, in the second half of this year. Tibotelimab is a potential 1st in left. It's a tetravalent, bispecific DART molecule designed by our colleagues at Macrogenics. Tibotelimab blocks the binding of T cells expressing PD L1 and LAG3 to their ligands with that tetravalent approach bivalent for each target structure with the IgG4 fraction.
It allows for the reactivation of exhausted T cells and enhancement of immune capacity against tumors. In the graphic on the left, tivotelimab demonstrates synergistic T cell activation in vitro superior to that seen with other PD-one and LAG-three combinations or with PD-one or LAG-three inhibitors by themselves. We've shown in our ongoing phase I study that there is evidence of monotherapy tumor activity in various advanced solid tumors. Here we show further evidence of single agent antitumor activity across multiple tumor types, including patients with previously treated triple negative breast cancer, epithelial ovarian cancer, and non small cell lung cancer. On the bottom left, please note the activity in diffuse large B cell lymphoma is illustrated in the swim lanes.
This includes previously treated patients who are either CAR T experienced or naive. The preliminary response rate was 5 out of 7 for CAR T naive patients and 2 out of 6 CAR T experienced patients. To date, tivotelimab has been well tolerated with a safety profile not much different from other checkpoint inhibitors. After establishing monotherapy, the next step in development is to evaluate tivotelimab in combination and this is being done in multiple solid tumors. Our China clinical development plan is shown on the left where it's being evaluated in monotherapy in second line hepatocellular carcinoma in both checkpoint inhibitor naive and post checkpoint inhibitor cohorts.
We are also utilizing our very strong and broad right, including gastric triple negative breast, biliary tract cancer, as well as endometrial cancer. Tivotelimab is also being evaluated as monotherapy in melanoma and additional indications are being investigated as well. Retefanlimab is a high affinity, humanized anti PD-one monoclonal antibody that we are partnering with In Sight who obtained the rights to the product from macrogenics. Its structure is shown here on the left. Preclinical data reveals an affinity of bound PD L1 that's equal to or exceeding that of other PD-1s such as nivolumab or pembrolizumab.
It also blocks PD-one interactions with PD L1 and PD L2 with potency equal to Specifically, preliminary activity in patients with previously Specifically, preliminary activity in patients with previously treated and recurrent MSI high and MMR deficient endometrial cancer is encouraging and consistent with the known treatment effect of anti PD-one inhibitors in these tumors. Retefanlimab was generally well tolerated and we are moving forward into additional studies in this setting. Retefanlimab remains one of our foundations in immuno oncology. I've discussed our work in endometrial cancer where there are no approved CPIs in China. Ritafanlimab will also continue to help strengthen our lung franchise and serve as an IO backbone therapy.
In Podium-two zero three, ritafanlimab demonstrated antitumor activity in non small cell lung cancer and selected solid tumors comparable with approved checkpoint inhibitors. We'll be looking to explore future combinations with our pipeline assets. I'd like to conclude by summarizing some key elements of our strategy in oncology. We are taking a scientific and disease based mechanistic approach with the intent of building on Dizai's established portfolio and network. We will aim to find global best in class and first in class assets, either through our own internal discovery and development program from in licensing or from co development through collaborations such as those with MacroGenics and Schrodinger.
We will use our expertise in areas such as cancer immunotherapy, DNA damage response and repair and oncogenic signaling. We will explore new therapies as monotherapies, but importantly also in combinatorial approaches such as those seen here within our robust pipeline, which includes IO, tumor treating fields, and other zy assets. And we will look for supplemental indications across our pipeline. And now I would like to introduce my colleague, Doctor. Harold Reinhart.
Harold?
Yeah. Thank you, Alan. Thank you so much for giving me the opportunity to introduce the autoimmune infectious diseases franchise. We have built this franchise up over the last 5 years, and we now have 4 rather unique assets that I will present to you here. All 4 are truly differentiated, innovative products.
None of them is in B2. They are addressing unmet patient needs. Let's talk first about the area of autoimmunity. This is certainly a major growth area in industry and many drugs have become blockbusters, Especially biologicals have been the center of attention ever since a series of anti TNF drugs were approved in the 90s. We at Tsai recognize the immense potential of this area of research, which brings new discoveries every year and often breakthroughs in our understanding of the processes underlying autoimmunity.
However, it is also a somewhat tricky area because we often don't fully understand the pathways central to each autoimmune disease. We often develop drugs that act as non specific immunosuppressants that can expose patients to the risk of serious infectious complications. So while it is an area that holds immense promise, we also realize that there are numerous uncertainties and a risk of failure for drug developers. Therefore, in our selection of compounds, we've tried to mitigate that risk by in licensing drugs that have already shown strong science or proof of concept and for which we also see unrecognized growth potential. How we do this will become clearer as we discuss our programs individually.
So let me now introduce Efgartigimod to you. We in licensed China rights from argenx in January this year. It is a compound that reduces circulating autoantibody levels. As you know, autoantibodies are central to the pathology of many autoimmune diseases. It is for that reason we call efgartigimod a pipeline in a product.
It has great potential given its mode of action. I will get more into this later. Next, there is CL-eleven oh two also a highly innovative development stage product. It's a compound for which we have global rights. It is an anti IL-seventeen nanobody, basically just a warhead of an IgG molecule.
In recent years, we have come to know about IL-seventeen as a key pro inflammatory cytokine in various autoimmune diseases, including psoriasis. Several biologicals targeting IL-seventeen are already blockbuster drugs. Hence, proof of concept is fully established for CL-eleven oh two. However, we see great untapped opportunities here for this small sized nanobody. Whatever we do, we always look for differentiation.
Let me start out by saying that efgartigimod fits that bill. It's a drug ahead of the competition and will be the 1st in class FcRn inhibitor once approved. As an FcRn inhibitor and receptor inhibitor, many potential indications could be studied. Actually, the list is longer than what is shown here on the right hand side of this slide. Indeed, any and all autoimmune diseases associated with auto antibodies or which benefit from IgE, IV treatment or plasma exchange or which respond to rituximab would seem to fall within the scope of efgartigimod.
Our partner, argenx, is conducting a large multipronged program, and Zai will support those indications by contributing Chinese patients. As you may know, argenx already submitted a BLA for generalized myasthenia gravis. This dossier is currently under review at the FDA with a PDUFA date in December 2021. Efgartidimod has already established proof of concept in various diseases. It's already shown efficacy in myasthenia gravis, pemphigus and in immune thrombocytopine purpura or ITP.
It's a drug that is differentiated in many ways from other FcRn inhibitors currently in development by chemistry, formulation, target engagement, efficacy, safety tolerability and convenience. Efgartigimod is not a full size monoclonal antibody, but a small Fc fragment construct with high receptor ability. It is the most advanced FcRn inhibitor in development with both an IV and a subcu formulation. Critically important, efgartigimod is a very safe drug. Unlike some other FcRn inhibitors, it does not interfere with the recycling of albumin by the FcRn receptor and does not affect serum albumin levels.
It also has no effect on serum cholesterol or serum LDL levels. Now, I would like to briefly talk about efgartigimod's mode of action shown in these cartoons. Physiologically, serum IgG is taken up by cells and carried inside endosomes for lysosomal degradation just like other proteins. However, IgG is rescued from being broken down by the neonatal Fc receptor in the endosome and shuttled back into the bloodstream. However, as shown on the right, efgartigimod blocks IgG from binding to the FcRn receptor and as a consequence, IgG is no longer recycled, but instead broken down.
Serum levels of IgG decrease and levels of pathologic autoinibodies go down in parallel. This finding was confirmed in many clinical trials of FcRn inhibitors conducted at argenx and elsewhere. Of note, this mechanism selectively affects IgGs, not other immunoglobulins. And as already mentioned, efgartigimod does not block the recycling of albumin at the FcRn receptor. We do believe that there is a significant market opportunity for China.
While rare individually, autoimmune diseases taken together represent a very large patient pool. In China, myasthenia gravis, ITP, CIDP and PV, pemphigus vulgaris, are seen with similar frequency as in other parts of the world. With its large population, China is a huge market opportunity for efgartigimod. It's important to understand that patients with these autoimmune conditions often remain symptomatic despite current standard of care therapy. Many patients can only function when receiving systemic steroids for prolonged periods.
Even then, steroids do not fully control the disease. Other immune suppressive drugs are added, carrying their own toxicity. At the same time, we know that these patients periodically experience exacerbations. In myasthenia gravis, such crises can be dangerous presenting with life threatening episodes of muscle weakness that may then require hospitalization and more aggressive interventions like plasma exchange or high dose IVIG. Such rescue therapies are costly and not always available.
Several newer expensive drugs are not approved in China or just not available. So we believe that efgartigimod will address an unmet medical need for many of these argenx. As already mentioned, the Myocela Gravis indication is currently under review at FDA. In all the other indications, Zai will participate by contributing patients from China. This way, we want to ensure faster study completion and set the stage for China regulatory approval.
While this list comprises 6 different disease indications, Zai plans to investigate other autoimmune diseases in China that even go beyond this list. The next slides will provide snapshots highlighting the activity of efgartigimod in various diseases. Let's start with the results from the myasthenia gravis Phase 3 study. Please note that most patients entering the ADAPT trial were symptomatic despite being on steroids and other immunosuppressive drugs. Efgartigimod was administered in addition to standard of care.
Efgartigimod resulted in major symptomatic improvement. Minimal symptom expression was achieved in 40% and in contrast only in about 11% on placebo by the criteria listed here. Looking at the pyramid on the right hand side, the degree of improvement for patients on efgartigimod is obvious. The average patient started with an average MG MG ADL myceliogravis activities of daily living score of 9 and improved to different degrees over time, but much more so with efgartigimod. Quite a similar picture when looking at the quantitative MG score, Like the MG ADL, it is a validated tool, and both tools showed a highly significant benefit with efgartigimod therapy.
The outcome is pretty much the same for patients with ITP, immune thrombocytopenic purpura shown in a Phase II study. Here, auto antibodies against platelet surface proteins are causing the disease. We saw significant improvement with efgartigimod depending on dose and duration. So in the open label extension, we see a 67% improvement compared to a response rate of only 25% in the control group. ITP patients are at risk of bleeding events that can be dangerous.
Therefore, bringing those platelet counts up with efgartigimod to more than 50,000 is important. As you would expect, efgartigimod prevented bleeding episodes by decreasing auto antibodies and raising platelet counts. Tsai just held an investigator meeting in China to help with recruitment for a Phase III trial. 3rd, I would like to briefly introduce the f.carticimus mold pemphigus data. Pemphigus vulgaris is one of the most dreaded diseases encountered in dermatology.
These patients are like burn patients with blisters all over and open weeping, sloughing skin lesions. The autoimmune attack on the skin is so pronounced that high doses of steroids are needed for survival. In this Phase II trial, efgartigimod provided significantly improved symptoms, reduced antidesmoglein autoantibody levels and allowed more rapid tapering of steroids. Cylab is ready to participate in the Phase III study for which we just had an investigator meeting in Shanghai earlier this month. So key points for efgartigimod are: 1st, it is a drug that will prove useful in multiple diseases, individually rare but quite sizable in the aggregate.
2nd, safe and effective treatments are just not available currently for many autoimmune conditions that can be addressed by efgartigimod. IVIg and plasma exchange are only treatments of last resort, and both ecolizumab and rituximab have problematic safety profiles. I cannot stress safety enough. In the argenx trial program, which comprises more than 600 patients treated with efgartigimod. We did not observe the dark side of immunosuppression such as an increase in bacterioviral infections.
As we learned earlier this year, some FcRn inhibitors reduce albumin and increase serum LDL levels, but not efgartigimod. All this adds up to a well differentiated and much needed product. Preparations for our China studies are well underway, as is our submission planning. We obtained CTA approvals for 5 studies in the last 6 months and will start enrolling patients in China soon. Our second development project is quite unique as well.
CL-eleven oh two is an anti IL-seventeen nanobody derived from Camelid IgG, but further modified. It's a construct that we believe is very well suited for the topical treatment of psoriasis. IL-seventeen is a validated target in psoriasis and several IL-seventeen monoclonal antibodies have already been approved in this indication. So what makes our compound different? All currently approved biologicals are full size monoclonal antibodies for systemic administration.
They are reserved for moderate to severe disease only, given the immunosuppressive tendencies these agents all have in common. However, we see a great market opportunity for a small nanobody that can be applied to the skin directly and avoid systemic toxicity. ZL11002 has some very specific features. 1st, it has very high avidity for the target. 2nd, as a small size molecule, penetration into tissues is much better.
And 3rd, because of their small size, nanobodies can interact with epitopes not accessible to full size monoclonals. Furthermore, nanobodies are very stable compounds. In vitro skin models and animal models of psoriasis suggest that skin penetration of macromolecules the size of CL11 is feasible. We are about to finish our Phase 1 proof of concept first in man study shortly. Here's a list of IL-seventeen monoclonal antibodies currently on the market.
Sacukinumab was the first one approved and is still the standard against which most other drugs are compared. The last approved drug was bimekizumab, which is a bispecific. And a slight variation on the theme is prodolumab, which is a receptor antagonist. Nonetheless, from an efficacy perspective, these drugs all work beautifully and they have really changed the treatment paradigm for psoriasis. But when you look at their labels, you will see that these drugs are only approved for moderate to severe disease and that some of them have black box warnings because they are immunosuppressive and therefore they must be monitored carefully.
Consequently, 70% to 80% of patients are currently not eligible for systemic IL-seventeen antibody treatment. This is the market segment we would like to go after with CL-eleven oh two because we believe that topical treatment can be at least and much safer. To sum it up, CL-eleven oh two is differentiated because it is a nanobody. We see topical application as the best way to treat mild to moderate plaque psoriasis because it works directly on the lesion without much systemic exposure and toxicity. Our study in patients with chronic plaque psoriasis will provide our first data on skin penetration and clinical benefit.
Our Phase I proof of concept trial is a well controlled double blinded PK safety and efficacy study. We will assess biomarkers and the transcriptome in skin biopsies from skin in response to CL-eleven oh two topical treatment. The study is just finished enrolling and hopefully we will have favorable data to share with you later this year. Now let me move on to our other therapeutic area, infectious diseases. It is important to recognize that antibiotics represent a very large segment of the pharma market in China, larger than any other therapeutic category as you see on this slide.
This is a growth area and it is underserved. It's also important to recognize that few new antibiotics have entered the China market in the last 10 years, And those that have entered are mostly old class antibiotics. With the documented high prevalence of resistance in many pathogens, we believe that infection is an area of unmet medical need and great commercial potential in China. These market forces are quite different from the U. S.
Or the EU. The left hand graph shows the various therapeutic areas led by traditional Chinese medicine TCM, which still commands a big chunk of the China medical market. But next comes anti infectives. This is not the same distribution that you would see anywhere else and definitely not in the U. S.
Where oncology and autoimmune are much larger markets. In China, the frequency of multidrug resistant organisms needs to be addressed rather urgently. There is a considerable When you no longer have antibiotics for those resistant infections, you're really back in the last century, the pre antibiotic era and that is a fairly scary proposition. Chinese regulators are acutely aware of the situation and are beginning to address it in the 14th 5 year plan, which calls for special attention to the development of new drugs that control infections caused by multidrug resistant organisms. These patients do not die slowly as in cancer after 2 or 3 years.
They die rapidly within 14 days. So bringing more potent antibiotics to China is a matter of medical need and also a political priority. Let me now talk about multidrug resistant Acinetobacter, which is probably one of the largest biological threats you will ever find in a hospital. It's such a threat that it has made the CDC list of the top 5 organisms that need attention. It is one of the biggest killers in the hospital with mortality anywhere from 40% to 80%.
It is an hospital organism that has become not only MDR, multi drug resistant, but XDR extremely drug resistant. And unfortunately, China has a very large number of patients infected with Acinetobacter 1,000 cases per year. All these Acinetobacters can be presumed multi drug resistant. Worse, the majority have become carbapenem resistant too, giving them the acronym CRAAP, which stands for carbapenem resistant Acinetobacter baumannii. CRAP are also quite prevalent in some other Asian and a few European countries.
So this is a regional phenomenon with China as the epicenter. Therefore, we believe that our drug, zulbactam, durlobactam or ZulDUR is very important for China. This drug has the potential to make a big difference in patients' lives and for the management of these cases. Why is the situation so scary? Well, until recently, we could still treat these organisms with a carbapenem antibiotic, which is both effective and safe.
With CRAP, this drug class no longer works. These CRAB patients are now given colistin or tigecycline drugs that show efficacy in vitro only. However, in real life, they don't work due to issues with pharmacology, toxicology, toxicity, dosing and poor lung penetration. As shown in the table, colistin does not work at labeled doses. And tigecycline and colistin have always been inferior drugs in pneumonia, the most common site of acidobacter infection.
What is most scary is that colistin has predictable nephrotoxicity. And 5 days into treatment, these patients show signs of renal toxicity. So what do we do here? We need a new drug that's efficacious and nontoxic. Therefore, Zaha was excited to co develop durlobactam with our partner Entasis and bring it to China.
Durlobactam in combination with solbactam can overcome the resistance mechanisms found in most Acinetobacter including the crab variety so prevalent in China. This is a more technical slide, but I want to point out to you that the combination of Sulbactam and duralobactam just where the red arrow is brings multidrug resistant acidulobactam down to a susceptible MIC range. Furthermore, in the graph on the right side, you can see how durlobacter moves the microbial kill curves to the left and into the susceptible range. A triple combination of Soldua with imipenem is exceptionally active against these multi drug resistant organisms, the light blue line on top. No other antibiotic regimen even comes close.
In summary, right now, we are in a situation where treatments are not available either in China or elsewhere for the worst variety of these organisms. They happen to be fairly frequent in China and that's why Tsai is engaged in this particular area. This is truly a high medical need which Entasis and Zai are trying to address together. Where do we stand in the development of ZULDUR? The ATTCK study is a Phase III registrational study.
It is the largest well conducted, well controlled study ever conducted in MDR, CRAP, Acinetobacter infections, pneumonia and bacteremia. The trial just finished enrollment and we expect to learn the results by the end of this year. This effort was significantly supported by Tsai and we contributed roughly 25% of all patients to that study. Here are key takeaways for SULDUR. This is a drug that addresses an unmet need particularly felt in China.
These are severely ill patients infected with a super resistant organism for which we have run out of good treatment options the world over. What we can offer currently is way too toxic and or does not work. By contrast, ZulDUR is a much safer drug, as we already know from our Phase 1 and 2 studies. Clinical efficacy data will be available soon, and we have good reason to believe that results will be favorable. We also believe that the narrow spectrum activity of Soldua will be welcome as it prevents the collateral damage associated with broad spectrum antibiotics.
Now let's switch to our other antibiotic, omadacycline. Omadacycline belongs to the tetracycline class and is one of the latest broad spectrum and well differentiated antibiotics that have been developed. Our partner, Paratek, conducted a large clinical program with FDA input and guidance. And the potency and safety of omadacycline was tested in 2 indications for adults: community acquired bacterial pneumonia and acute bacterial skin skin structural infections. It has excellent tissue and lung penetration, including a favorable PK profile with low protein binding and much higher free drug levels than any other tetracycline.
Similar exposures are obtained following 300 milligram oral and 100 milligram IV dosing, which allows step down therapy from an IV to an oral formulation of the same antibiotic. Patients can be started on IV omadacycline in a hospital and once stable switch to PO making early discharge possible. It is a very unique and differentiated tetracycline. The next two slides present the results all published of the Phase 3 program. Here we show that omadacycline, is now approved in the United States under the name NOSYRA, is as potent as best standard of care antibiotics in CAP, community acquired pneumonia.
As you know, for CAP, moxifloxacin has become the gold standard antibiotic all over the world, including China And omadacycline has convincingly shown similar efficacy. These are exceptionally good results because the bar for this is so high. Regarding its adverse event profile, omadacycline was safe and This slide shows you a similar panel of graphs for 1 of the 2 Phase III APC studies also conducted by Paratek. Here, the comparator is linezolid, the world's standard for treatment of these kinds of infections, one of the best drugs available for staphylococcal and streptococcal skin infections. Sequential IVPO omadacycline was as potent as sequential IVPO linazolid, the undisputed standard of care for this indication.
As in the CAP trial, safety and tolerability was favorable between comparators. Consistent with studies of tetracyclines, GI related adverse events were the most common events reported. So efficacy wise and safety we have a drug here that is as good as a standard of care, quite an achievement. I don't know of any other antibiotic that has done equally well in a similar set of studies in recent years. There are currently 3 newer generation tetracyclines on the market.
Terecycline was approved some time ago and is a well known and safe drug. It is available in China where it is used predominantly for mild to moderate skin skin structure infections. There's some hesitation to use it in respiratory tract infections as efficacy was subpar in some clinical trials. It is not approved for CAP in the EU. Then there is eravacycline, which was just recently introduced in China.
However, that drug is only available in an IV formulation. It is not indicated for pneumonia, only for inter abdominal infections. Quite surprisingly, it failed in 2 large UTI trials. So in this side by side comparison, omadacycline is truly a standout. 1st, because of the 2 indications for which it has already been approved in the U.
S. These same two indications we also pursued in our China bridging program. 2nd, omadacycline has a favorable safety tolerability profile overall, particularly regarding GI side effects, which can be bothersome with some tetracyclines. 3rd, and most importantly, we have the option of IV2PO step down therapy. I want to stress that no other tetracycline has both formulations.
China's CDE granted priority review for omadacycline last year. Omadacycline is not only at best in the tetracycline class of antibiotics, it also has an excellent differentiated profile when compared to other classes of commonly used antibiotics for CAP and APSI that are already in use in China and abroad. As shown here, it has a broad antimicrobial spectrum including gram positives, gram negatives and atypical pathogens like Legionella, plus several multi drug resistant organisms not covered by other antibiotics. Despite being a broad spectrum antibiotic, there were no reports of clostridium difficile infections during the omadacycline clinical program. The convenience of once daily dosing with oral tablets is an important attribute as it fosters compliance.
These are features that few other antibiotics can match individually or in combination. CAP is a big market anywhere and it's a big market in China as well. As already mentioned, no new antibiotics have been introduced in China for this indication in many years. Acute bacterial skin skin structure infections can also be managed effectively with this drug. Clearly omadacycline fits that bill.
It's a Category 1 drug in China which is important here for caregivers in Chinese hospitals. We expect approval for omadacycline by the end of this year and look very much forward to working with Hanwei, our sales and marketing partner to bring omadacycline to Chinese patients. And now I will turn the presentation back over to my colleague, Doctor. Sandler. Alan?
Hello
again. It's good to be back to tell you about our research strategy and our exciting pipeline of internal products. I'd like to begin by discussing our process. Our methodology for establishing a balanced portfolio is to use an open innovation model. That is, we establish a pipeline of proprietary assets against prioritized targets in areas of extensive internal expertise and modalities of strength based on the available science to date that describe that unmet need.
You can see the open innovation model schematically on the left, showing the integration of our portfolio with that of our targets, pathways and prioritized disease areas. Our focus in internal discovery includes immuno oncology, DNA damage response and synthetic lethality and autoimmunity. Our disease areas in oncology include women's cancer, lung and CNS cancer, GI and GU cancer, hematology and cancer immunotherapy, which works very closely with our autoimmune disorder approach and also infectious diseases. Of course, Harold is our Chief Medical Officer heading up our immunology and infectious diseases therapeutic areas. We have invested to build our internal drug discovery capabilities.
The result is a proven world class biologics drug discovery team led by Peter Brahms who discovering some of the most commercially successful antibodies in discovering some of the most commercially successful antibodies in oncology today. His group has capabilities to perform end to end discovery, engineering and optimization of monoclonal antibodies. This has resulted in 2 INDs and one preclinical candidate of therapeutic monoclonal antibodies for Xi's global development portfolio. We have also recently entered into several collaborations to synergistically enhance our internal capabilities. We partnered with Rubrik to access technology to enhance our antibody discovery platform and our diversity of antibodies.
We also partnered with MacroGenics to use their DART platform to jointly discover and develop bispecific T cell engagers for Xi's proprietary tumor targets. Xi's internal small molecule drug discovery has also been focusing on leveraging preferred CROs to advanced compounds such as ZL2201 and ZL2203 or molecules that will result from the recent Schrodinger partnership in DNA damage response. Response. In order to support the future small molecule portfolio, Xi has made the decision to invest in and build fully integrated small molecule drug discovery capabilities. We will report back to you in future presentations as these capabilities deliver de novo first in class global small molecules in our strategic areas of focus.
Our internal discovery engine has proven that it can take small molecule or biologic drug discovery programs from target validation through to IND filing with fully integrated internal capabilities throughout the discovery value chain. Our world biology and translational sciences groups work seamlessly with the preclinical groups to validate mechanisms of action and develop key biological assays and pharmacology models to support moving the programs forward to IND and generating D pipeline. We have 13 internally discovered assets, 11 of which have global rights. They are listed here. Harold has already discussed our IL-seventeen antibody.
Our CD47 and CDC7 compounds are already in Phase I and our claudin18.2 will be in the clinic shortly. We have multiple other preclinical compounds including a DNA dependent protein kinase. We are collaborating with MacroGenics on up to 4 CD3 or CD47 based bispecific Let me go into a few of our molecules in more depth. Simarosertib's mechanism of action is shown here schematically, where it works in DNA damage response by blocking CDC7, a protein kinase with key roles in DNA replication elongation and in bypassing DNA damage response. This compound has the potential to be the 1st in class oral selective inhibitor of CDC7.
It's shown encouraging preclinical activity including synergy with PARP inhibitors. In solid tumors, it has shown activity in Phase I and II trials as monotherapy and we are also looking into combinatorial approaches. ZL2201 is an IND ready, wholly owned, potent selective DNA PK inhibitor developed with our in house discovery capabilities. DNA PK is a critical kinase activated by double strand DNA breaks induced by radiation or chemotherapy and drives a cascade of events programmed to repair the damage to the DNA. Inhibition of DNA PK has been shown to sensitize cells to killing by DNA damage inducing cancer therapies.
This leads to synergistic and antitumor activity. We aim to translate these encouraging preclinical data to patients undergoing treatment with DNA damage inducing radiation or chemotherapy. We expect to file an IND in the first half of twenty twenty two. ZL-twelve oh one is an inhibitor of CD47 which is a macrophage immune checkpoint. ZL1201 is a humanized IgG4 monoclonal antibody that binds and blocks the function of CD47 expressed on tumor cells, thus activating macrophage induced phagocytosis.
It also may bind to red blood cells, although in this preclinical setting, hemagglutination was not observed. Preclinical data in HL60 tumor cell xenograft models, shown on the left demonstrates considerable activity in combination with 5 azacitidine. Preclinical data also azaacitidine. Preclinical data also support combination with chemotherapy, ADC enhanced antibodies and T cell checkpoint inhibitors. ZL1218 is designed to block ligand binding and to induce ADCC mediated Treg depletion selectively in tumors and not in other tissues.
The compound was discovered on Zai's internal antibody discovery platform and optimized using in house in vitro and in vivo assays. Non clinical development is led by Xi's internal capabilities and our in house cell and process development groups. The team is preparing for GLP tox studies and is in the process of characterizing Tregs from human tumor isolates to develop translational hypotheses. This slide refers back to the topic I mentioned earlier, our partnerships with both Macrogenics and Schrodinger. Our macrogenics collaboration includes 4 compounds.
The first program covers a lead research molecule that incorporates macrogenics' DART platform and binds CD3 in an undisclosed target that is expressed in multiple solid tumors. This next generation CD3 component of the DART bispecific molecule has been designed to minimize cytokine release syndrome while maintaining antitumorcytolytic activity. Tsai receives commercial rights in Greater China, Japan and Korea with an option for fifty-fifty global development. The second collaboration program also binds to CD3 and will cover a target in solid tumors to be designated by macrogenics. Zai receives commercial rights in Greater China, Japan and Korea.
Zai Lab also obtains exclusive global licenses from MacroGenics to develop, manufacture and commercialize 2 additional molecules. In the Schrodinger collaboration, we will tap their best in class physics and AI based drug discovery platform to identify compounds involved in DNA damage response, which is an active area of research for us. The discovery work will be conducted jointly. Zai will then be responsible for the global development, manufacturing and commercialization. The collaboration provides opportunities for combinatorial approaches utilizing molecules within our pipeline as well.
To review, our strategy for our internal research and development program is to prioritize those programs that are synergistic with our portfolio. We will do so by embracing an open innovation model encompassing both internal and external collaborations. We will continue to leverage and invest in our global footprint, further strengthening our R and D capabilities in both China and the U. S. This multi pronged internal R and D strategy will aim to generate at least 1 global IND per year.
And now, I'd like to introduce my colleague, Jonathan Wang. Jonathan?
Thank you, Alan. Our standard has always been to develop and market globally 1st and or best in class assets. Over the last 7 years, Tsai has demonstrated that we are the part of choice for helping Western companies launch such 1st in class and best in class products in China. On this slide, you can see that every year, we have been very consistent in partnering or licensing assets of that standard quality. For us, it's not actually the numbers, it's really the quality of these assets that we're most proud of.
We, more than any other company, have consistently been partnering for the best assets with the best companies like Regeneron, argenx, Novocure, Turning Point, etcetera, many of whom have openly said that if it wasn't for Zai, they probably would not work with any other Chinese company in this region. If we look at 2021, over the last 9 months, we have executed a number of deals shown here and each of them has its own unique strategic and business rationale. In January, we did a deal with argenx, embroiling a very promising asset in efgartigimod. That collaboration essentially extended our therapeutic focus with an anchor asset in severe autoimmune diseases, an area where we have always been looking for great assets. EFCAR has significant potential.
It is really a pipeline and a product opportunity across many rare diseases, actually many of them not so rare in China. Together, the patient prevalence in FCAS targeted patient population is 700,000 patients just in the 6 indications in its current or planned clinical development plan. The lead indication, gMG, has a prevalence of more than 200,000 patients in China. In January, we also did a deal with Turning Point for TPX-twenty 2, further strengthening our lung and GI cancer franchises. Our existing partnership was working very well and both partners clearly were quite happy with it.
So we decided to broaden it. And similarly, for a deal we did with MacroGenics in June, we expanded upon the original deal for 3 clinical assets with China rights with an additional 4 preclinical assets with global rights in our latest deal. And our interest in building our early stage pipeline also led to the deal with Schrodinger. We very much have an open innovation model as we think about early stage products with global rights. We tap into the best platform, the best technologies, working with different partners and it obviously doesn't have to be all in house.
We're really glad to work with MacroGenics in what we think is world class bispecific platform and with Schrodinger using their cutting edge technology to come up with best in class small molecules. And in June, we announced the partnership with Mirati, again, strengthening our lung and GI cancer franchise with one of the hottest assets in the world today. We certainly think we have an opportunity to make this 1st and or best in class in China, and we'll definitely work hard towards that goal. This is a great asset to further solidify Zai's reputation of being the partner of choice. So as you can see, each one of these collaborations has a different strategic rationale or objective for the company's growth.
We'll continue to execute to achieve these different dimensions that you see at the bottom of the slide from a licensing perspective. Many people ask us how we find our assets, how we evaluate them, what portion of them are inbound versus outbound. Our BD strategy has been an evolution. Initially, it was much more outbound. From the early days, we really have to educate people about China and the Chinese market.
I think today, a lot more interest has been inbound, including some of those that you saw on the previous slide. Our partners came to us. They wanted to find a Chinese partner, and they thought that Zai will be their ideal partner. Of course, we have a very systematic approach to scouting and searching for products across different modalities and TAs. We also look for assets that can complement what we already have and can address significant unmet needs.
Between inbound interest and systematic searches, we look at hundreds of opportunities every year. We have very robust process to evaluate them, a well oiled machine. We're very lucky as I in that because of our prior collaborations, we built a strong in house team across the full breadth of drug development, commercialization and manufacturing to evaluate every opportunity that comes in. We also have built a very strong network of KOLs and external opportunities were actually controversial at the time of licensing. However, soon after deal was struck, those assets had data presentations that proved we were right.
One example I can give will be 5 Prime. When we licensed Beamer, nobody really valued that asset highly. When we licensed that asset, it was really a Phase I product. We did a deal with 5,000,000 upfront back in 2017. And by early this year, Amgen had BroadfiPrime and BIMA with the China rights already partnered to Zai for US1.9 billion dollars So we're really proud of our extended team and it's really because of our development and commercialization colleagues and their expertise in effectively evaluating products and then after the deal, moving the products ahead quickly that we're able to continuously execute in BD.
So I
think this competitive edge, this position of the partner choice is fully cemented and will continue going forward, especially today across our key therapeutic areas where we have great products. And some of these great products can also have combination potential with other assets that we're looking to bring in. One example will be the KRAS, where we're going to look at monotherapy and also combination opportunities potentially with our other lung and gastric cancer franchise products in house. I explained earlier the concept of our BD strategy starting from being the partner of choice, leveraging the Chinese market, already the 2nd largest in the world. And today, we're very proud to build leadership positions in certain areas, for example, in lung and in gastric cancer, 2 of our largest oncology disease areas in China, where China has the largest patient population in the world.
We have also built a very enviable pipeline where these assets cover a large portion of the patient population from a mutation perspective. Many of these can be useful not only as monotherapy but also in combination with each other, not only for Chinese patients but eventually for global patients. And that is one of the key reasons why our partners come to Zai because they want to leverage Zai's expertise in drug development, working with innovative assets to help accelerate our partners' global time line and bring these products to China and to the world. The long term ambition of Zai is really to build a global biopharmaceutical company with a significant presence in China and in the U. S.
I think we are well on that path. BD is going to play a very significant role together with in house discovery to achieve that ambition. So we're really looking forward to further expanding the pipeline through licensing, looking at globally first and or best in class assets for either regional and or global rights and working with different modalities as well. Thank you. And now Billy will conclude our presentation.
Billy?
Thank you, Jonathan. I hope you've been impressed with the breadth, depth and quality of our product portfolio and pipeline with the organization and operational infrastructure that we have built and with our strategy for robust growth and value creation for years to come. Over our 7 year history, we have raised $2,600,000,000 and deployed about $860,000,000 of it to create Zai Lab as you see it today, quite a return on investment. Our future growth will come from continued execution with Zai's speed and quality, enabled by our culture of high performance and relentless focus. We will continue to bring transformative medicines to patients in need, build our product portfolio and pipeline, including our internal pipeline, and synergistically scale up our global operations.
We are already the partner of choice to develop and commercialize products in China with 16 assets in global co development, which truly showcase our status as a global strategic partner of choice. We will continue to expand our product portfolio with new partnerships for 1st in class and best in class medicines, including products with global rights. And we expect to continue to set the industry benchmark for innovation and extend our track record of execution excellence. Of course, we cannot and will not do this alone. Financial results.
We are very pleased with the progress we made in the Q4 of 2018. We are very pleased with the support and we look forward to working with you to achieve our vision of Zai Lab benefiting far more patients in China and around the world. We have no doubt that we will accomplish great things together and unlock significant potential value in Zai.
Hello, everyone. Thank you for sending in to our R and D Day. Thank you for your continued interest and support in our story and we've had quite an update since the last time we did this over 2.5 years ago. So this format was really a way to provide really the only way to provide a comprehensive review. And again, the recording will be available after this.
So we encourage you to refer back to it. On the call, you have all the speakers for this Q and A portion. Samantha Du, Tao Fu, Nguyen Leung, Allen Sandler, Eric Reinhart, Xiaoten Wang and myself, Billy And so before we open up the Q and A, please queue up your questions as we completed our earnings Q and A. There has been some recent activity at ESMO and others. So we want to highlight some exciting results from several of our programs and partners that was recently announced.
So with further ado, I'll turn it over to Alan for some commentary and then we'll proceed to our Q and A. Alan?
Great. Thanks, Billy, and good morning or good evening to everyone. As I'd already mentioned in my presentation, some of the data from our partner Mirate for the colorectal cancer cohorts in the CRISTL-one study. There also were some updated results on Monday, where Mirati had presented results from the Phase II portion of CRISPR1 that evaluated adagrastiv in patients with advanced non small cell lung cancer harboring the KRAS G12C mutation following prior therapy. And then in the intent to treat population as of June 15, 2021, edagracisib demonstrated an objective response rate of 43%, disease control rate of 80% with a safety and tolerability profile that was again consistent with the previously reported findings for adagracisib in these similar patients.
So these lung cancer results in addition to the new data at ESMO relating to colorectal cancer, again, very encouraging and reinforce our view that adagrastin has that potential to be a best in class compound for patients with KRAS G12C mutation. I'd also like to mention our partner, MacroGenics, announcing the results of Mahogany Cohort A at ESMO, evaluating the combination of margetuximab plus rasifanlimab in patients with GE junction cancer. With the data cut off here of July 19, 2021, tumor shrinkage was observed in This included 21 of 40 response evaluable patients for a response rate of 53% with 4 confirmed complete responses. The median duration of response was 10.3 months. Safety analysis of all 43 patients treated with margetuximab plus rituximab as of August suggested the combination was well tolerated with only 9 Grade 3 TRA Es reported and representing 8 patients for a total of 19% of patients seen no Grade 4 TRAEs were observed.
This safety profile compares quite favorably with other chemotherapy based therapy. And lastly, our partner Dasypra presented a long term update from the Phase 3 INVICTUS study of Kinloch, which continues to show clinically meaningful median overall survival of 18.2 months as compared to 6.3 months with placebo. Progression free survival remained unchanged at 6.3 months with TIMLOCK compared to only 1 month with placebo. Safety findings again were consistent with the original primary analysis results. We and our partner, DECIPRA, look forward to the Phase 3 INTRIGUE readout later this year in patients with second line GIST.
Thank you.
Operator, those are some opening remarks that we have to make live before passing over to Q and A. But I can also double check that there are no issues with this audio portion. I believe it should be working out, right? Operator, are you online? You can go ahead and proceed to open the line for questions.
Certainly. We will now like to open the lines for questions. The first question comes from the line of Mike Yee from Jefferies. Please go ahead.
Hi, good morning and good evening if you can hear me.
Hi, Mike.
I appreciate the comprehensive review today. Can you hear me?
Yes, we can.
Okay, perfect. Great. I know that there's a lot of technical things going around and we've got everyone connected around the world. Two questions. One is that there is obviously a lot of uncertainty and a lot of market nervousness around the regulatory developments in China, whether that's in technology or purportedly potential for healthcare.
And obviously, that's got a lot of investors nervous. Is there anything you can say as to your insights with regulators and with the government that can give some comfort to people that the biotech and drug pricing area is something that you think will not be impacted at all and there's not going to be any changes there? Talk to that topic is number 1. And the second question is a more strategic broad question. You can appreciate that in inflammation, it's quite an area that you sound like you want to in license more.
That's a huge area. GMG and psoriasis are totally different sales forces. What generally would you like to do in inflammation? And how can we be assured you will be focused? Thank you.
Yes, Michael, thanks for the yes, please, Samantha.
Yes. Thank you, Michael. For your first question, let me just give me give you some of my personal thinking. I had several discussions with the CDE, especially after July 2, the guidance for industry for oncology draw. And I think that perhaps started the concerns about what does it really mean.
Actually from my own interpretation and also from my own communication, I saw that's a very positive sign because what the whole guidance for inventory on 2nd July 2nd issue is actually is about reaching the bar for innovation in drug development, which is good for Zai Lab and companies like Zai Lab with very differentiated product pipeline. And within this timeline, we saw a very strong signal from the regulatory authority to guide the industry to shift to need first or need better drugs to meet unmet medical needs. As we know how many PD-1s we're having right now. And I think also given Zai Lab has only focused on best in class and first class assets to address unmet medical needs And we really feel like we benefit from this guidance and we of course you won't see that today. But in the long run, we are truly well positioned in China.
But overall and all the other interactions, we just recently had a pre PLA meeting and we saw the meeting went well, very positive and our other applications, INDs and keep going according to the plan. And also from the 14th healthcare planning, even though it's still in the planning stage, all the things IFR has been very positive, especially on innovative healthcare industry.
And Mike, to ask your second question, I'll pass this along to Jonathan Wong, our BD Head. And Jonathan perhaps can comment a little bit about leveraging our BD platform brand network effect to not only look at oncology but other areas of information, etcetera.
Yes. Thanks, Mike, for the question. So autoimmune has always been an area that we've been looking for products. And if you look at the asset that we got in EFCOD, it's mainly focused on severe autoimmune diseases. So in many ways, it's actually like our other oncology products.
So the commercial capabilities will be very focused, targeting large hospitals, very concentrated in terms of the KOLs and where patients go seek for care. And there are many of these severe autoimmune disease. I mean, if you look at just FGART in itself, it addresses several different indications, 6 already announced, addressing something like 850,000 patients currently in China, where there is very large online medical need. So we'll continually look for other assets in the anti inflammation area where there are large unmet medical need like this and where we can adopt a very focused, concentrated commercial efforts, when those products get closer to the market. I hope that answers your question.
Great. Thank you. Appreciate it. And thank you, Samantha, for your answers as well.
Thanks, Michael.
Thank you. The next question comes from the line of
Yes, we can.
Oh, good. Okay. Thanks for taking the questions and congrats on the continued positive momentum, both the partnered pipeline as well as the internally developed pipeline. I had two questions. First, on your high level strategy to build the portfolio, curious what other therapeutic areas would you like to gain exposure to beyond the current solid footprint in oncology, autoimmune and anti infectives?
Or should we expect additional partnering deals to fall within one of these three buckets? And a second more technical question on ZL-eleven oh two, I'm just wondering how you're thinking about the dosing frequency for topical ZL-eleven oh two. Is it expected that this will be a daily Or will the half life of the molecule of the antibody potentially allow for less frequent than daily dosing?
Great. So thanks for your question Yigal. Your first question on therapeutic areas, as you know, to your suggestion, we've been very much focused on the 3 that you're aware of, oncology, autoimmune, infectious disease. And your question is, are we looking to expand beyond that? And if so, what would it be?
Perhaps I can turn it over to Kyle. Do you want to take the question?
Sure. Yigal, it's a very good question. I think certainly from a business development perspective, we have really mentioned before, we're really trying to expand our business both vertically and potentially horizontally. When we say vertically, we mean within our existing area, we're really stronghold. So I think that makes a lot of sense.
But we have also been looking at areas horizontally to see whether we can find any anchor assets in new disease area where there's big unmet medical need, where we can really build a sustainable business. I think Jonathan alluded to what we have done with efgartigimod in severe autoimmune disease as a very good example of how we would consider expanding horizontally. So we're certainly open to those opportunities, but I think we will apply to the criteria I outlined in terms of really whether these opportunities can significantly turbocharge our growth in the future. Hope I answered your question. Yes.
Thank you.
And Yigal, for your 11.02 question, we'll take we'll send it on to Calvin Klein. Thanks.
Yes. Hi. Thank you for the question about 1102 dosing. The current proof of concept trial used BID dosing. And as you know, this is just proof of concept.
The true dosing frequency duration and concentration of the product, all these are variables that will have to be determined with Phase II study that we hope to conduct after we've shown significant penetration to the skin and hopefully also clinical efficacy.
Okay. Thank you.
Thank you. The next question comes from the line of Anupam Dhanma from JPM. Please go ahead.
Hey, guys. Thanks so much for hosting this Analyst Day, and I hope everyone is well. Maybe just a quick question from us.
Sort of with the breadth of
the pipeline review today and products entering or in the launch phase here,
how are you thinking
about the balance sheet and the cash needs going forward? Thanks so much.
Hey, Bob. Thanks for your question. So as you guys all saw from the presentation, we have a pretty extensive portfolio of 25 assets, half of them are in late stage, 11 of them with global rights are advancing nicely. We have commercial expansion plan for launch products, a robust launch schedule, and we already have a pretty comprehensive business. But we're able to, I think, with the strategy, become a pretty large significant company with a lot of efficiency built in already.
And therefore, we do have a lot of control of how we commit our resources. And we have to commit to you that we'll constantly prioritize these resources, whether it's our capital or time, which are precious to us and you as well. But the bottom line here is that you saw from our Q2 earnings as of July 30, 2021, we had US1.77 billion dollars So it gave us full flexibility and we had no need for any opportunities of fundraising given our strong very strong balance sheet.
Thanks so much for taking our question.
Thank you. The next question comes from the line of Jonathan Chang from SVB Leerink. Please go ahead.
Hi, guys. Thanks for hosting the event and for taking A couple of questions. First one, on the evolving gastric cancer landscape, how does the introduction of IO and triplet combinations and first line gastric impact your development strategy here across the different programs you have?
Hey, Jocelyn, thanks for your question. I think that one's for, Alan Sandler.
Yes. Hi. Again, thanks for the question. I think the important aspect first is that with the advent of checkpoint inhibition, it's great news, of course, for cancer patients. And I think that what we have shown is we have evidence that our own pipeline, there are several agents that have activity across various aspects of patients, patient population, some of which may overlap with those agents PD-one expressors and some may not.
So I think it helps to broaden our opportunities. And there are still areas where we can combine with potentially checkpoint inhibitors and also potentially work towards those patients who may not be benefited by those who don't overexpress PD L1, for example. Have I addressed your question?
Understood. Thank you. Yes, that was helpful. And second question, in terms of different treatment modalities, I'm curious to get your thoughts on other areas like ADCs, cell therapies, etcetera, that are outside the existing modalities, that you're evaluating both in terms of potential business development and internal discovery efforts? Thank you.
Yes. I think Go ahead. Go ahead.
No, I was going to I think, Jonathan yes, Samantha, please.
Sorry about the interruption. Actually, Jonathan, you read a very good question and happy to hear your voice. And as you know, internally, we focus on precision medicine, small molecule, but also large molecule. But we also have through collaborations, very early stage, expand our technology platforms. And whether it's ADC, whether it's cell therapy, whether it's MRA, we'll see.
Whatever to us, this all means to the end. And if they can drive the unmet medical needs they should cope for patients, They can bring synergy with our current portfolio and we'll definitely look into it. But never
Got it. Thanks for taking my questions.
Yes, Josh, and I would also that was great to note that. And I would also refer you back to the presentation of the end of the discussion as you may have thought on sort of the latest internal research capabilities and strategy. And Alan covered some discovery platforms that we have internal, where we continue where we expect to have future expansion, some partner platforms. And then also another session on some of the core expertise that's specific on oncology and immunology across specific modalities and overlapping as well. So we'll refer you back to the presentation and you can let us know if you have any other questions.
The next question comes from the line of Seamus Fernandez from Buckingham Securities. Please go ahead. Great.
Thanks for the question.
Thank you.
So just a question for global clinical studies, kind of the timelines? And if there would be potential assets that your team would consider to start building a commercial presence globally sooner rather than later? I guess that's sort of a blended question, Tau and Jonathan. And Samantha, just love to know know maybe a little bit more your specific thoughts and insights into maybe differentiated approval timelines, perhaps even seeing earlier approvals in China than we might see in the United States or aligned timeline in that regard over time. I think it's particularly poignant for a product like bermarituzumab, where we've seen some pretty impressive Phase 2 survival data?
Thanks.
Hey, David. Thanks for those questions. I think you directly went to Matt for the second one. Your first question, maybe I can just address it. As you referring back to the R and D Day, Samantha mapped out a blueprint for our aspirations from now till next few years, really from still 25.
And the baseline expectation is that we expect to have internally deduct assets near commercial stage by then. And but to your point, there could be opportunities to accelerate and develop TA leadership, commercial TA leadership in both China and U. S. Even before then. So right now, we're expected to grow our U.
S. Presence as we advance our global pipeline and the half full optionality to really unlock true value for our platform and of course for our shareholders. Of course, at the end of the day, it's all about accelerating and having maximum impact for patients. But I'll stop there for that question and turn it over to Samantha for the second for your second question.
Yes. Thanks for the question. And I think, of course, there are facilities based on the filing strategy, it's also based on the where are the majority of patients being recruited, right? We did see several cases where people take the opportunity of FDA's project audit and the data came broadly from China. So we based on the different programs, different patient populations based on the partner agreement will be very even our own pipeline will be really thinking all of those, with all those things in mind, what is most efficient and high quality, timely to get to the patient.
So that's very important. So how to design the Phase 3 class, Phase 3 trial, where to get approval first and that's really what we will be considering over the next 3 years. Thank you.
The next question comes from the line of Ji Yee Chen from Goldman Sachs. Please go ahead.
Thank you for taking my questions. Can you hear me?
Yes, we can. AB.
Okay, great. Yes, thank you. So, well, the first question, I'm really interested into the in house strategy, in house discovery strategy, because we have seen some of the targets, for example, CD47, claudium 10.2 or the interleukin 17. Those targets are relatively crowded. So compared to our license, how to differentiate in terms of MOAs.
So I'm trying to understand a bit more about the rationale to pin those targets, which are relatively crowded. And also we're trying to understand, given the FlyOver's extensive licensing experience and expertise on that. So how you guys are going to leverage your licensing expertise and BD capability to accelerate the in house development? Thank you.
Hey, Zvi. Thanks for your question. So for your first one, we'll break it up into 2 responders. I think for the CD47 and cloud and A2.2, Alan can provide some commentary and IL-17T antibody. Cheryl, I'm sure will have some thoughts as well in terms of the scientific differentiation and rationale with our programs.
So, Alan?
Yes. Thanks, Billy, and thanks again for the question. So for both CD47 and the claudin programs, we're of course designing these with a best in class potential. And we've benchmarked them against our competitor molecules throughout this process and attempting to build a differentiated profile for those to attempt to overcome some of the liabilities that may have been seen in some of the other molecules in the field. In the field.
For CD47, pre clinically, there was a lack of hemagglutination that was seen and no significant adverse hematologic changes seen in monkeys when tested. So the potential there for CD47 was a potential lack of red blood cell phagocytosis in these preclinical studies, which we're looking to see how that translates into the clinic. For the Arcladine program, again based on preclinical data and it was an AIRC poster conclusion, we can efficiently target the claudin18.2 lower expressing tumors with the enhanced ADCC activity. And this potentially will broaden the number of patients who may benefit from this therapy. So I think those are the 2 ways that we were looking or at least one way each of how we were attempting to differentiate these agents.
Thank you for the question, Geoff.
Let me just answer a little bit here, if I may. Is, Zui, we know these are targeted these are very crowded field. However, this is still very early stage and very few compounds has reached later stage, basically, so we say the road run the reason is the risk they were on. However, if we didn't see the preclinical correlation our transitional with our preclinical will stop the program because we have many more innovative programs and in house. And also as we mentioned earlier, we have many discovery programs.
They are innovative. They are more 1st in class. But as a company, we always need to consider a good balance of 1st in class and best in class combination. And because that's whatever address unmet medical needs, that was our end goal.
And Harold, did you want to add on anything for the L17 that is a known target, but our approach is unique?
Yes. Yes. Thank you for the question and thanks for the opportunity to
talk about
IL-seventeen-two as a differentiated product. You're correct, we are targeting IL-seventeen just as the other drugs which are already on the market, but these are all systemic drugs with a systemic approach with the issues of adverse events that come along with a non specific targeting. We believe in contrast that if one could use an established target like IL-seventeen, a proinflammatory cytokine, if you could block that directly in the skin where the disease is after all with psoriasis, it would be a direct way of addressing the pathology and at the same time avoid the systemic side effects. Now you know that the other drugs are full size monoclonals. They cannot be used in topical use for psoriasis.
And here comes the other differentiating feature for 1102. It is a nanobody much, much smaller and possibly able to penetrate into those abnormal skin tissues that represent psoriasis. So we believe that there will be very little systemic absorption. There will be very little of the side effects that you see in the package inserts of all the other IL-seventeen inhibitors. And most importantly, these other IL-seventeen inhibitors are only indicated for moderate to severe psoriasis, which is about 20% of the market.
However, we are targeting the mild to moderate psoriasis population, which represents close to 70% of the market. And again, so we believe there is a great differentiation and possibility for differentiation. Thank you.
And as to your second question about how to leverage our partnership, leadership expertise capability to accelerate our global sort of pipeline effort and how to augment our existing drug and spending drug discovery platforms. I'll pass that to Jonathan Wang. Yes.
Thanks for the question, Lee. Look, I think we are certainly very proud of our scientific team and our commercial team. I think we have built very significant scale actually across all of the different functions from drug development, manufacturing to commercial. And I think through all of the different teams combined effort, we certainly demonstrate track record in how to identify good asset, how to evaluate them and then how to most efficiently and quickly bring them to patients. And so as we do these during that process and it's really a very well oiled machine from a business development point of view.
But during all of these processes, as we go from getting the right product to taking it to the patients and across so many different programs today. We have built very strong capabilities across different technology platforms, different modalities. And also, we really understand certain diseases and markets know where the unmet medical needs are. For example, in gastric cancer, in lung cancer, we have built disease strongholds. I think we can quite proudly say in some of these areas, we probably have one of the most enviable pipeline of products for those diseases.
And in certain areas like target therapy in IO, we have a very enviable pipeline of complementary assets as well. So all of these enable us to have strong capabilities to have know how and so to help us when we come to in house efforts discovery, we know where to go for, we know where the unmet need is and we know how to select the right technology for the right disease. So I think it's certainly very complementary in house together with BD licensing, they go hand in hand. And I think you hopefully will see more about in house programs coming to the clinic very soon. Hopefully that answers your question.
Thank you. Thank you so much.
Thank you. The next question comes from the line of Young Huang from Credit Suisse. Please go ahead.
Yes. Thank you for holding these nice R and D events. I just have a quick question. Trying to understand better understand your long term commercial strategy in China and outside China. For outside China, you mentioned in 2025, you are going to be at or near kind of global commercial stage.
So do you mean you are going to build a commercial team, say, in the U. S. Or other parts of the world? And then for in China, in long term, it seems that you are going to build a very large commercial team since now we already have 800 people commercial team and we only have 3 products. And in total, we currently have 25 in the pipeline.
It seems that we're going to have a lot more. Is that the case that we intend to build, let's say, a few stores on the commercial team comparable to the commercial team to existing China large pharma companies? Thank you.
Hey, Yaron, thanks for your question. So yes, this was partly asked previously, but we'll add more color to it. And it's kind of both of your questions are somewhat integrated from our view, the way we think about it. So yes, it is correct that by 2025, if everything is going to plan, just with what we have right now, we expect to be at or near global commercial launch. For us, we want full flexibility on how to do that organically or inorganically, whatever it is.
But it requires scale to have full flexibility and optionality at our disposal so that we can make the best decision on again really creating a looking value. And that is tied to the scaling up visibility we have in China today. So you saw again from the presentation and all of our prior discussions just with what we have right now in our pipeline and portfolio relatively speaking, we have excellent visibility on how we're going to scale because we have a launch estimated launch schedule on all of these programs. So over the next 3 to 4 years, I mean, you saw some effort in opening remarks, we expect to have about 15 plus, again, if everything goes according to plan, 15 plus new products, not even talking about the indications in the marketplace. That's one of the most intense commercial launch schedules in the next 3, 4 years within the landscape at this level of global innovation that we're talking about.
So again, from a risk reward point of view, we have an unusual level of visibility and economies of scale through China and then get to that relevant level where, again, we could contribute more significantly to the global medical community. Now I'll also refer you to go back to what William has presented during the R and D Day, where we have a pretty unique way to build our commercial infrastructure. And he was mostly focused on China for this presentation, but there is a whole section where we built because of all the things that we just talked about, the launch schedules and the size of our portfolio, late stage innovating, We've built a commercial organization based on therapeutic areas, based on disease areas. And that drives leadership on how we shape the market and also operating synergies, whether they're in the clinical development process or even during commercial execution. So it allows us to have strong execution and productivity at the same time and it's built so that the more products you actually build add into this therapeutic area focused organization, the more operating leverage you can actually realize.
So I think those are the key points that we want to make on your question. So, Young, thanks for answering the question.
Yes, okay. Thank you, Peter.
Thank you. I'm showing no further questions at this time. I will turn the call back over to SAIL Life's CEO, Samantha Du, for closing remarks. Please go ahead. Thank you.
Yes. Good morning and good morning good morning to everyone. And just I know it's a long winded 2.5 hours presentation. And I really appreciate your time and your interest in Zai Life. And together, we think we are building a great company with your support.
Thank you.
Ladies and gentlemen, that concludes Tri Lab's R and D Day. Thank you for your participation. You may all now disconnect.