Good morning, everybody. Thank you for dialing in today's conference call. My name is Sean Wu. I cover Greater China Healthcare. Today, it's my great pleasure to host this earnings conference call for CStone to talk about their interim results and provide their company outlook. Management attending today's conference include Dr. Jianxin Yang, Chief Executive Officer, Dr. Archie Tse, Chief Scientific Officer, Dr. Josh Zhou, the Greater China General Manager, Mr. Michael Choi, Chief Business Officer, Mr. Jun Cheng, VP Finance, and the last but not least, Ms. Nicky Ni, VP Board Secretary. Today's conference call will be conducted in English, there may be, like, a replay audio after work.
During the call, there will be after the call, there will be Q&A, and you can put your question into the left side box. Without further ado, I'm gonna pass the call over to Nicky.
Thank you, Sean, thanks, everyone, for joining us at this time. We will start the call by letting Jianxin give us an update on the financials and the operations, then have plenty of time for Q&A. Jianxin?
That's great. Again, thanks, Sean. Good morning, good evening. It's, it's my pleasure, actually, to share with you, I think it's a very solid performance for the first half of today, for CStone. First, let me give you a quick overview, introduction of CStone. CStone was founded in 2015, 2016. Right now, CStone is actually a full, fully integrated biopharma with end-to-end capability. It really only took five and five years from inception, from the company inception to first commercial launch. Over the years, we have accomplished in research, development, and also commercialization. If you look at the numbers, we have received more than 45 IND approvals across the globe, and we currently have 10 plus discovery projects ongoing.
For development and regulatory, we have had 11 NDA approvals, and we have presented data at international conference and also very prestigious scientific journals. We have more than 40, 40. Commercial-wise, we have four commercial product launched in three territories, so that's mainland China, Taiwan, Hong Kong, and covering seven indications. I will go over. Next slide, please. Let me just go over some of the key achievement for first half of 2023. For financial, our total revenue for the first six months is RMB 261.5 million. For the. All of those are commercial revenue, so no revenue from BD in the first half.
This commercial revenue representing a increase of 53% year-over-year, and our net loss, this is now IR- IFRS. Net loss is significantly decreased, year-over-year, it's RMB 183 million. That's representing 29% year-over-year. If we including the share-based cost, that's decrease is actually more than 40%. As our financial head will give more details of analysis later. If you go to the RD part, for the first six months, we have had two NDA approval, all for pralsetinib. The most important approval is actually for first-line non-small cell lung cancer in mainland China. That's the largest indication for pralsetinib.
Of course, we also have non-small cell lung cancer, both first line and second line, as well as MTC, TC across lines approved in Taiwan. For the... We also have 5 NDA currently under review. Those 5 NDA divided in two parts. One is actually in UK and Europe, so that's for stage 4 non-small cell lung cancer. In mainland China, we have three major indications that's currently under review. As I will show with you, under the approval timeline, is going to be in the second half of this year and the first half of next year. We have multiple data publication, including ASCO and ESMO, initial cancer.
We have, again, we have 10 plus discovery project, and some of these project are for a partnership. I think we can cover a little bit more on that. Now, most importantly, we have the ROR1 ADC. That's we have major progress for this for the first six months, especially for the last, last quarter, Q2. I will go over a little more, more detail. For the lorlatinib ROS1 indication, that's a co-development with Pfizer. We completed patient enrollment, and we expect top line readout and the NDA submission in first half of 2024. Then finally, but most importantly, we are actively progress the domestic supply for imported drug, for licensing drug....
For the our partner, that's the GIST indication, our tech transfer application has been accepted by CDE, we expect a domestic supply in 2024. For the tech transfer for pralsetinib, that's a RET inhibitor, that's ongoing, the BE study already initiated, we expect the domestic supply in 2025. Next slide. Let me share with you a key pipeline update. Again, I want to emphasize that for our, for our company's next stage, we have Pipeline 2.0. The most important value driver in the Pipeline 2.0 is our ROR1 ADC. That has global rights, except for South Korea. I will talk more about this molecule.
I will give you some update on our commercial stage program. There's three precision medicine plus PD-L1. I will talk a little bit on our other program, that's including our PD-L1 in global phase III study, and also a few other molecules in the preclinical stage. First thing, the ROR1 ADC. As you can see, that ROR1, ROR1 is a very, very interesting molecule because it's overexpressed in a lot of tumors, especially in the B-cell lymphoma. It's almost all, it's almost universally overexpressed in B-cell lymphoma, but it's almost absent from normal tissues.
It's overexpressed in a high percentage of solid tumors, for example, TNBC, the non-squamous cell lung, non-squamous cells, non-small cell lung cancer, and also some ovarian cancer and other cancers that we are, we've been looking at. Very importantly, this molecule is not very busy, so it's not very competitive so far. We actually right now rank in a number two position globally as to clinical development stage. The first one, as you know, is the one that Merck acquired for 2.5, $2.75 billion. That molecule is conducting registration trial in DLBCL, right? The diffuse large B-cell lymphoma. Another important thing to keep in mind is ADC, even if you address certain targets, ADC has a lot more places to differentiate.
That means even if you are second in class, you might have differentiation factors that put you into your best-in-class or potentially even first-in-class-in indication, right? Let me walk you through the differentiations in our molecule. The first one and the second one may not be that dramatic. First one is that specific conjugation, and the DAR is DAR of 2, because this payload is very, very potent, right? PBD is very potent. It can be a 100 to 1,000-fold more potent than DXd. The DAR is small, is a low DAR. Now, second thing, it's important, but most people probably don't pay too much attention to that. This is a fully human, fully human sequence IgG1 mAb. Fully human is important because it really avoid quite a bit of ADA, right?
Because that's gonna compromise your antibody concentration, and those are potentially causing, well, it cause a loss of efficacy, of course, and also potentially cause some side effects. We learned that from our PD-L1. Our PD-L1, the sugemalimab, has very low ADA, and those are very, much, much better safety profile than, than some others, because it's a full human, sequence there. This is the second part. The third part, of course, is a potentially, wider therapeutic window. This is very important. This attribute attributed to two parts. One is our linker, is tumor-specific or cell-specific cleavage linker, right? It's very stable outside of the cell, so in the bloodstream, it's very stable, and we have seen that in our phase I study. The second thing, more importantly, is the payload per se.
The PBD is a prodrug, it has a cap. The cap keep the PBD intact, inactive until it's cleared, the cap is cleared inside the cell, and then the PBD dimer becoming very, very potent, very active. This make this drug potent but has a very high therapeutic window. Next slide. Now, let me just show you some of the preclinical data. There's a lot of preclinical data. We actually presented some of the data in agent, in our ADC early this year. Let me just show you some of the data. The first slide on the left, the first figure on the left, is a monotherapy efficacy, in vivo efficacy comparison with VelosBio's, with Merck's molecule.
If you look at the last two line, those red line, those are the ROR1 ADC at a 0.5 milligram per kg or 1 milligram per kg, and 1 times dosing is pretty much wipe out the tumors, whereas the other lines are our competitor. you can and also the other competitors much higher dose and multiple dosing. The efficacy monotherapy is very outstanding right there. The second, the middle figure is very important because as you expect, for solid tumor, we cannot, we will not be able to avoid PD-1. We are planning, of course, PD-1 combination. In our pre-clinical study, we're already showing that when combining with our internal PD-1, so our PD-1 cross-react with the human and mouse. The pre-clinical study is actually very convenient. This is a very convenient study.
If you look at the 2 solid line in the bottom, 1 is blue, 1 is black. Those are the 2 doses of ROR1 ADC 0.5 or 1 milligram per kg. Combined with our PD-1, 5 milligram per kg, and you can see that you can bring the tumor shrinkage to really to the baseline, whereas the middle line is showing the efficacy of PD-1, monotherapy dose, of course. This is, you, you can see that there's very good synergy between ROR1 ADC and the PD-1. Now, the last figure here is actually important because ROR1 ADCs are relatively new. In this field, there has not been a very good monoclonal antibody or antibody for immunohistochemistry or for patient identification for solid tumor. And we actually generated a proprietary IHC antibody. We just filed a patent.
This IHC antibody, we worked with Ventana and other diagnostic company, and it turned out that this is the best antibody for IHC, and they actually want to license our monoclonal antibody for commercial purpose. So far, we have not agreed to that, you know, because we, for competitive reason, we don't want to do that right now. This is very striking. Next slide. Now I want to give you a quick update on the clinical trial, clinical part. We, right now, let's go to as of today. We have had multiple doses of exploration. Right now, we are at the predicted efficacious dose based on our pre-clinical study.
We have found a very good safety profile, most of the AE we found right now is grade 1. There's only a few grade 2 AE, and there's no drug-related grade 3 AE. Of course, there's no DLT observed. MTD is not, is not reached either. This is, this is important, because for ADC, the most important thing is, is the safety, right? Because after all, it's a very potent chemo attached to a monoclonal antibody. The second part is your PK. For ADC, you don't want to have accumulating a dose effect. Right now, we see a very good linear PK without accumulation when dosed once every 3 week. And also, the half-life is very good. We have, very importantly, we have seen a very good ADC stability.
That means when we look at the total antibody, we look at ADC, the concentration overlapping, and then when we look at the linker payload by mass spec, we have not been able to detect the free payload. That's very good stability. The most promising one, of course, is that we already observed tumor response by tumor assessment. That's objective tumor response. We always observe that. Going forward, by end of this year, we will be able to report more data, more patient data. Right now, we have those, about 20 to 30 patients. By the end of the year, we will have more data to report on safety and the also efficacy, and those data will be disclosed in a coming conference.
It could be AACR or ASCO in the first year or the first half of next year. Also, I want to remind people that when we do phase I study, we are not just looking at a RP2D or MTD or DLT, right? As you guys remember that when we do our PD-L1, when we get our PD-L1 phase I done, we pretty much, pretty much know what indication we can pursue, right? That's why when we, that's why we actually got a first phase III trial in non-small cell lung cancer, couple of years within 3 years from the phase I start.
What that tell, tell you is that when we finish the dose exploration and expansion, we will be able to start a pivotal study, hopefully, in the second half of next year. Okay? The for the CDP, clinical development plan, we are already working on clinical development plan. The plan, of course, is to have faster market approach plus a randomized phase III trials in most attractive tumor types. Hopefully, we can have a market approval sooner, as, you know, as well as our PD-L1, for example. Then let me quickly go over the other precision medicines that's already commercialized. Of course, the most important one is our RET inhibitor. Just to remind you that RET is a RET mutation or alteration-...
It's not just in non-small cell lung cancer or thyroid cancer, it's actually across all kind of solid tumors, right? The total addressable patient population annually can be 70,000. This is getting better and better as our country, our country is actually pushing very hard, early detection of tumor, right, for genetic screening. There, there will be more patients are detected by this approach. For the first half, I think a very important advance is our first line non-small cell lung cancer approval. With that, we have actually 4 indications all approved in mainland China. That means that if we want to go to NRDL, we've got all the indications covered.
Another important thing is we are doing tech transfer, so that our costs will be reduced significantly, so the profit margin will be much, much higher so when this achieved. Commercial-wise, we are continuing to make progress on market access, affordability, and RET testing, as well as scientific advances, so that we can have more indication, including in the national guidelines. The other drug is avapritinib. This is a KIT PDGFRalpha inhibitor. It's actually the first in class, because none of the other drug has identical profile as this one as to efficacy, right? The key indication, of course, is the PDGFRA exon 18- mutated GIST.
As you can see from the left side, there are multiple indications that either approved outside of China or has shown very impressive clinical efficacy by other means, either real-world study, RG, or some POC study. I think this year we demonstrated that our inhibitor not only is efficacious in PDGFRA exon 18, but also in KIT D 816, KIT N 822, as well as in KIT 17/18 exon mutant patients, and this has been published. Outside of China, very importantly, the non-advanced or intermediate SM as approved, and that's going to be a big indication for this molecule.
Now, the other important thing is, as I mentioned before, that tech transfer right now is moving along very well in China, and the NDA approval expected early next year. For commercial-wise, right now, we have, you know, major improvement, again, in the four category. For this drug, it's very interesting, 'cause, you know, you can find out that commercial-wise, it's actually covered multiple disciplines, right? It has solid tumor, it has, also leukemia, and also it has, like, skin disease, respiratory disease, and others. Commercial-wise, we actually need a much larger team to cover this drug. You don't need a lot of people, but you just need to have expertise to cover different disciplines. This is also a drug that we are actively looking for partners, right?
Because this is more complicated than, than, for example, the, the RET inhibitor, because those, those drugs are mostly concentrated on solid tumor department. This is the avapritinib. For our IDH1 inhibitors, so ivosidenib is the first in class globally. It has... In China, again, the drugs they approved for, in R/R AML, but it has either been proved or have shown efficacy in first-line ML, in cholangiocarcinoma, and most importantly, recently in glioma. Glioma, as you know, that in grade 2 glioma, the IDH1 mutation actually occurred in about 70% of tumors. It's a huge addressable patient population. It has also shown activities in MDS and cholangiocarcinoma. Now, again, commercial-wise, we are pushing these drugs into different indications.
Again, this drug is facing the same commercial challenge with, that is, you need to have cell reps cover multiple different disciplines, including hematological and the solid tumor, and also even as you can see that glioma is mostly in the CNS surgery department, so these are some challenges. Again, for this drug, we are also looking for commercial partners. Next slide. This is for sugemalimab, just a summary of the regulatory progress. The dark green color is showing that its NDA already approved, it's already launched. That's stage three and stage four non-small cell lung cancer already launched in mainland China. The blue color is the NDA currently under review. You can see that three in mainland China, and then stage four non-small cell lung cancer in UK and EU.
The light green is the expected NDA approval time. It will be end of this year, but in the second half of this year and early next year for all these five indications. Okay? For U.S.-... Let me just go back to the EU part. The EU part right now is the registration process is going smoothly. We received, according to schedule, the day 80 and day 120 question, question, question list, and none of those questions are not addressable. Also, we received a formal GCP inspection notification, and that will be conducted by end of the year and early next year. It will be three inspection, two on clinical sites and one on the clinical CRO. Did not say our EU. We are preparing for GCP inspection. Okay?
This is for the ex-China part. For U.S. this is for European part. For U.S., we have had a top three meeting with U.S. FDA on our ENK lymphoma. U.S. FDA accept our ENK lymphoma pivotal trial as a phase II single trial based in China. They accept that as a registration trial, they have no problem with that. The only thing they want is that they want us to extend enrollment in U.S. or South America. 20 or 30 patients that are more representative of the U.S. demographic. We are right now, of course, working with a partner, and we are going to proceed that, not on our own, but working with a partner. What that tells is this, there is a registration pathways for ENK lymphoma in U.S. This is number one.
Number two is that our gastric cancer and esophageal cancer in the first-line setting is often standard in U.S., right? We are planning to conduct a regulatory discussion with U.S. FDA on these two indications for potential regulatory pathway. Based on our discussion, on our PD-1 in first-line HCC, we expect U.S. will grant, will recognize the phase III trial as a registration trial, meaning they don't want you to repeat a trial, they might again want us to extend a single-arm, enroll, say, 50 to 60 patients in a U.S. patient population. That's my expectation. Again, we will do that when we find a partner for our PD-1, you know, in the next couple of months. Okay? This is for PD-1.
Next slide. I just mentioned our PD-1. Our PD-1, we have only one global phase III trial that's ongoing. We know it's late, as you can see that we are picking a very, very important indication to pursue. This is actually the first-line HCC. And also this particular trial is a combination with best TKIs in the liver cancer, that's lenvatinib. We have a very strong POC data. That POC data, if you across trial comparison, is better than the pembrolizumab plus lenvatinib, right? You know, if you look at ORR, DCR or PFS, it's, it's better. Our trial design is different from the Merck trial, and our demographic is slightly different. Of course, our OS endpoint and statistical analysis is all different.
We are highly hopeful that the top line read out in the first quarter of next year will be positive. As you know, that OS read out time is dependent on the accumulation of OS events, essentially accumulation of death events. Our best expectation is the Q1-2024, the data will be mature, and the top line will be read out. If this is successful, it will be superior to all the first-line combo that are approved for first-line HCC. In several aspects, of course, one is efficacy, the second one is potentially a safety profile 'cause we don't have Avastin, right? The third one is potentially the cost. We have one antibody, but another one is a small molecule that's already off pattern.
We think this is a very attractive clinical trial, and we're looking forward to top-line readout. Next slide. Just quickly go over the preclinical assets. We currently have most advanced, we have 3 molecules in the preclinical development stage. One is the, a tri-specific antibody, a multi-specific antibody. That's targeting PD-1, our own PD-1, VEGF, and also another IO target that we have not disclosed because of competition sensitivity, okay? We have very good data right now in the preclinical stage. We expect IND, and also we have very good CMC developability data, 'cause this is important, 'cause when you're dealing with a bispecific or tri-specific molecule antibody, sometimes you don't get good CMC, right? Your yield is too low, or your stability, all kind of things.
It's not easy to do this, and we got a very good data so far, and we expect IND next year. Now, the others, we have two ADC, and these two ADC, we are addressing either... Let's just say one of the targeting has not been known, so this is a completely novel target discovered by our AI platform, okay? Another target is a known target. It's a validated kind of target, but it has no approved or successful ADCs. Both of these, we can consider they are best-in-class and first-in-class, first-in-class, sorry. Again, we expect IND next year or early 2025. This is really we're trying to build up our pipeline, okay?
Now, the third one is we got a cell-penetrating therapeutic platform, and this one can bring a lot of treatment modality into the cell to target the undruggable intracellular targets. For this platform, we are also actively, actively looking for partner in China and also ex-China. With that, let me just summarize our pipeline. As you can see that our pipeline, either generation one or generation two, eventually will cover a broad indication and with rapidly growing commercial value. We understand that the commercialization in the first one or two years is not easy, it's not smooth, as you can see for our PD-L1. Our PD-L1 commercialized by Pfizer, the first year we have, you know, drug supply issue, right? The performance is miserable. I mean, for this year, the first quarter is also miserable because there's no drug essentially supply.
The drug supply issue is resolved in the second half, and it's resolved for next years, next couple of years. We expect, we fully expect the PD-L1 commercialization, revenue-wise, will pick up very quickly, especially with the pending approval of gastric cancer, esophageal cancers in first-line setting in China, because those are large indications. Okay. Now, of course, most important for us is our Pipeline 2.0. With ROR1 ADC, we are highly hopeful and optimistic that it will be test applications in multiple tumor types, including both B-cell lymphoma and the solid tumors. Then, our other molecule, like tri-specific monoclonal antibody, and the ADC, and other molecules will help, you know, build a very healthy clinical pipeline down the road. Yeah. Thank you.
Let me hand the slides to our financial head, who will walk through the financial results with you. Thank you.
Thanks, Jianxin. Continuing the positive momentum, our operating loss was significantly lower than last year, 2022, and the total group revenue for H1 2023 achieved RMB 261.5 million, and sales of pharmaceutical products rose 53% to RMB 246.9 million. Royalty revenue also grew by double-digit. I would like to highlight here that the commercial gross margin on these fourth products increased from 47% to 59%. No license fee revenue in H1 2023. However, we expect the milestones from GC and the ESCC approvals by the end of this year or early 2024. Loss for H1 2023 decreased by 29% to RMB 183 million.
This is a non-IFRS basis, mainly due to higher margin, lower spending on phase III registering trials and the lower selling, marketing, and adminis- expenses. As you can see, we have booked a one-time milestone revenue in H1 2022. If we exclude this one-time gain and compare to H1 2023, the adjusted loss for H1 2022 would be RMB 344 million. The H1 2023 loss was actually reduced by RMB 163 million or 47%. We ended June 2023, with a strong cash balance of RMB 1 billion, and this significantly reduced the cash burn from our operating activities. Back to Jianxin. Thanks.
Thank you, Jun. Let me just walk you through the key catalyst for the next 12 months. First thing, of course, we expect the R/R ENKTL formal approval soon, actually, definitely by end of this year. Then for the stage four non-small cell lung cancer in EU and the UK, we expect approval in the 1st half of next year. Then the NDA approval for 1st-line GC and essentially gastric cancer, it will be by end of this year or 1st half of next year. That's- it's the same for the esophageal cancer indication. As you know that for both indications, we will receive a significant cash milestone from Pfizer once it's approved.
The other is the, we also are expecting imminent top-line readout for a pre-specified OS analysis of the first-line GC. Now, for lorlatinib, as I mentioned, we expect top line and NDA filing in the first half or middle of 2024. For the PD-1, the phase III, global phase III top line readout, we expect in the first quarter of next year. For the ROR1 ADC, that's the most critical ones, we are expecting to give you a relatively extensive update on clinical safety and efficacy without releasing the detailed data, because it's going to be embargoed, because we want to present those datas in a coming conference, right?
That will be in the first half, because right now, by end of the year, there's no major conference, and also the timing is not appropriate, right? Because you know that you need to clean up data, you need to have data card, and you need to prepare for everything. Also, the submission to a conference is a couple of months before the meeting, so we want to have a more comprehensive presentations in the first half of next year. It does not mean that we will not, not share with you the progress. I know this is important, we will get to share that. Okay. Thank you.
I think that's the end of the presentation, we can start the Q&A session now. I'll just, I think, starting with a quick question. Everybody is talking about anti-corruption. I guess supposedly biotech companies shouldn't be jumping on these kind of things, but of course, you have promotions going on, and also you have to talk with doctors about your new drugs, especially your precision medicines. How do you see your business in the near term and longer term being affected by this anti-corruption campaign? That's my first question. The second question, like, your, I think you are emphasizing this ROR1 product, any opportunities for out-licensing in this sense, for the global rights? I recall, I think I'm talking about one you got from Korea with ex-Korea rights. I, I have these two questions.
Right. Josh, Sean, thank you for the question. The first question, I would ask our commercial head, Josh, to respond, and then I will answer question to this, answer the second question.
Thank you for your question. Regarding this question, I would like to firstly mention that CStone Pharmaceuticals has always been an organization that we make high standard, and all our selling and activities are organized and guided with a high ethical standard. Secondly, precision medicine, unlike many other, I would say, many other different categories, in this category, there's really very strong clinical unmet needs. Meaning that, you know, all, all our scientific-- all our promotions, actually are very scientific oriented, scientific focused. Yeah. Basically, our selling is science-driven selling. You mentioned a very good point. As you, probably the entire industry is now watching, you know, how this kind of, this external circumstances will evolve, and we're also doing closely monitoring. Yeah.
That's what I can share regarding this matter.
Do you think this would also affect somehow the conduct of clinical trials in hospitals? Sometimes you need to work with other hospital chiefs, key opinion leaders, to have those hospitals to help you kind of conduct those clinical trials. Would that be affected to some extent?
Right, Sean, this is a very good question. It really depends on how a company conduct their clinical trial, right? I mean, technically, I mean, theoretically, you don't need to you are not allowed to interact very closely with a trial physician, right? That's by GCP. You are not allowed. You are actually working through a third party, right? You know, I mean, for example, you, you know, for the, you know, patient, bottom line is, the sponsor are not supposed to see patients or to know the patients, right? I don't think that for us, we don't see any impact on our clinical trial, for example, enrollment or other interactions. That's not a concern.
If other companies utilize their commercial capability for patient enrollment or to persuade, you know, investigators, in patient enrollment or in trial conduct, I think that they're going to have an issue. Okay. Sean, I hope that answered your question.
Okay, I think the next question comes from.
The ROR1. Let me just-
ROA1.
Let me try to respond to your ROR1. It's obviously we are going to find global partners for ROR1 ADC at due time. The fact is that there has been a lot of companies interested in ROR1 ADC already. When we goes to ASCO earlier this year and also the Boston BIOs, we have a lot of interaction with our partners. As you also know that this is one of the most important drug in our pipeline, so we are very conservative as to when we should strike a deal, right? Also what type of deal we want to have. Then we want...
If we want to transform the companies into a more like a global or biotech or global bio pharma with our, you know, so-called CStone Pipeline 2.0, including ROR1 ADC. We are very careful with what type of deal we do and what, what kind of evaluations we hope to achieve.
Thank you very much. Next question is from Yi Chen of Goldman Sachs. So 1, expenses have been reduced significantly, meaningfully, admin, down 34% year-over-year, R&D, 30% year-over-year, and even selling expenses are down 10%. Could you elaborate on, 1, where you have cut the headcounts, and what's the future plan? 2, are you going to see operating expenses to be further cut to extend the cash runway? In that case, how are you going to drive sales growth? As the first half of sales were flat year-over-year. That, that's the first question. Another one is, after the tech transfer, which facility you are planning to produce ROR1? Does that require additional CapEx?
Right. This, again, this is very professional questions. I, I, I guess I want to say that we-- when we are cutting down the expenses, it's not purely for cost saving purpose, right? It has other purpose too. One purpose is that since our later stage clinical trial is winding down, so we do have a so-called overcapacity. We have just too much capacity, right? We cut down some of the capacity, just like every company would do, right? Especially when the, the, you know, capital, is actually, not easy to, to get. That's a right thing to do. This is, this is one thing, that's we need to depend on the need.
The second thing is we're trying to streamline, we're trying to increase the efficiency, we're really trying to squeeze and then push for productivity in across the department, including supporting department. By doing that, we also squeeze out some of the cost, right? As you can see that, the total cost cut is not, you know, it's not like you completely just cut the companies away. Then going forward, we will adjust our, for example, FTE leading based on our top line and commercial need, right? We probably don't want to, for example, for our clinical department, right, as the ROR1 ADC is going to expand into like a registration trial, we probably don't want to cut more, right? The existing workforce is, is enough to handle a couple of registration trials, even without a partner, right?
Again, like I said, we're not expecting to have major cut. Commercial-wise, as I just mentioned it, first thing, important thing is I want to, you know, I want to thank George. I think our productivity per sales rep is very high, right? If you're comparing to the industry benchmark. That's one thing. The second thing is, we also know that if you don't spend money, you don't, you are, you're not going to get a very, very fast growth of your top line, right? That's just a, a matter of mathematics. That's also why I said that for some of the drugs, that requires a lot of investment, especially in FTE.
We are looking at potential commercial partners. By doing that, we are going to increase the revenue without our own investment, right? It will be a fixed cost based on service fee. This is regarding the budget cost. The second part is the tech transfer. Tech transfer, what I can tell you is that, with the completion of tech transfer for those two drugs, the costs will be reduced. For two drugs is different. Will be reduced from 50% to 80%. That way of resulting in a significant, significant, significant increase of a gross margin for those two drugs.
I also want to add one thing to the previous question on sales growth. Just want to point out that our total revenue was flat year-on-year. That's mainly because there's a one-time milestone income in the first half of last year. If you only look at the product sales of our three precision medicines, the year-on-year growth is 53%.
Thank you.
Thank you. Next set of question come from Hayden Zhang of China Merchants Securities, Hong Kong. The first question he's asking: On the technical transfer, any color on how much should we expect the sort of margin improvement, any numerical figure or ballpark you can provide? For PD-L1 subcutaneous version, we see some global and domestic peers are working on that, such as Merck and others. What's your thoughts on this, and do you have plan on that? That's the first two questions. The follow-up is about your PD-L1 supply issue in fiscal 2022 and the 1Q 2023. Can you remind us what's behind the supply shortage? Is that because of the tighter capacity of your CMO provider, and then we know who it is, or like COVID reopening, or s- or there are some other reasons?
Clearly, we, we really don't hear any kind of capacity constraints from, the CDMO, vendor.
Right. Thank, thank you, Hayden. That's a good, good question. I think for the first question, I, as I just mentioned, we're expecting 50%-80% of costs reductions after tech transfer. That will be significant improvement of our gross margin. For the second one, Pfizer is very dedicated to the sugemalimab commercialization. I think going forward, I think the look, the, the indication is going to be big, right? 5 large, 5 indications. I fully expect that they will try to improve either subacute or the cost of good, so that the drug will remain to be competitive, and not just against the imported drug, like pembrolizumab, but also against the domestic competitor.
Just keep in mind, right now, Pfizer is selling this drug after PAP, around RMB 100,000 per year, right? That's significantly higher than the domestic supplier, but still it is, it's very known, it's selling very well, right? This is also, of course, related to the second question, the drug supply. The drug supply issue is typical. That's a issue resulting from a BD deal. When Pfizer licensed our PD-L1 for China market, the CMC issue was discussed but was not completely resolved. 'Cause before this BD, we are supposed to manufacturing, CStone is supposed to manufacture PD-L1 in our Suzhou manufacturing sites. Once Pfizer took over the drug, they want to continue WuXi Biologics to supply, right? Because, of course, it's a much more, a much more credible site.
They want to WuXi Biologics to do that. WuXi Bio did not has no capacity, did not prepare them for this capacity, right? Because they were thinking that the CStone is going to take over. That's causing a capacity was squeezed in the first year of commercialization. After, you know, really after a lot of discussion involved the highest level of two companies, WuXi Biologics and the and the Pfizer, and of course, we also involved, on this issue, is resolved in the first quarter of this year. That's why I say, starting from second quarter, the drug supply is not an issue anymore. It will not be an issue for the next couple of years, while Pfizer is trying to find another resources or more resources to expand drug supply going forward.
I guess, you know, as for sugemalimab, I think that's one thing that, if Pfizer want to do that, I think they have motivation to do that. Thank you.
Okay, I think they will need, need your help with fulfilling the numbers for the second half. If I, I, I guess you can get as much from them as they can survive. In any way, there are some, a couple questions from the investors. One is, like, we all try to register your PD-L1 for refractory kind of request, the ENKTL in the United States. From the same person is asking, "By the end of 2024, looks like your cash will be running out. Do I understand this correctly, or how will you solve that?" I thought that you said that you have, like, $1 billion on your balance sheet, so-
Okay. You're right. First, I want to assure all the investors, we're never going to run out of cash, okay? That's not going to happen under my watch, so, so don't even think about that. The second thing is the PD-L1 registration for ENK and lymphoma in US, as I just mentioned. We have a registration pathway going forward, but we're not going to do that alone, right? We are actively looking for a partner. If the partner want to take this molecule, that actually is the most expedient, right, different ways to US market. Only 20-30 patients expansion without really the efficacy requirement, right? We will not worry about that part.
Maybe I can add more on the cash runway to just put some numbers to it. As Sean mentioned, we have RMB 1 billion on our balance sheet, and if you look at our net loss from last year, it was around RMB 700 million. First half of this year, we continue to shrink the net loss. Just based on that, you can, you can probably estimate cash runway will be 2 years. There will be other ways, especially some non-dilutive ways we are looking at to extend, further extend the cash runway.
Okay, thank you. Could you, management, give a timeline expectations for the application of stage 3 non-small cell lung cancer in UK or EU? Any plan on that?
Right. This is, again, this is Jianxin. The standard procedure for this is that after we received the first approval, which is the stage four non-small cell lung cancer, we are going to bundle other indications like stage three non-small cell lung cancer, the gastric cancer, the esophageal cancer, and potentially ENKT lympomas together, and then file to EU and UK. That's just a typical way that other company doing this.
Okay. His other question is, like, in fiscal 2020, at the earlier discussion, you mentioned about Pfizer increasing their batch orders in 2023 for sugemalimab, but we did not see a strong spike in RoW in first half of 2023. Could you please explain why, why so?
Right. That's, we kind of explained. The first quarter for this year, there's almost no sales to new patients, 'cause the reserve, whatever is available for existing patients, right? There's very little revenue in the first quarter of this year. You could almost say that all the sell and also the royalty we received, coming from mostly from Q2. Even for Q2, it's just a ramp up, right? Because they pretty much stopped commercial activity in the Q1.
Thanks. This question is, could management update the status for CS2006?
Okay, CS2006. Okay, that's good. That's the Numab , the 4-1BB. This, the PD-L 1, 4-1BB project, it was mostly driven to phase I, and phase I extension was driven by Numab . We have not, on our side, we have not seen the clinical data that is promising enough for us to commit to further study on this molecule. Right now, for right now, we are holding or we are pausing our activity on this molecule, we are going to taking it off from our pipeline.
I think for the second time, this will be the last question. This question may be best addressed to Mr. Jun Cheng, the VP of Finance. Could management please elaborate on the account payable being so high at RMB 340 million that are due in 90 days or over? Clearly, payable high is good for you. As well as the RMB 450 million of other payables, what's the impact on your cash positions?
Okay. In this payables, it has a significant portion, is due to accounting treatment, that we need to accrue this R&D expenses based on the progress of the clinical trials, which hasn't been due to pay. That is mainly for the accounting purpose. We make these approvals. When we consider this cash run, runway, we always consider the also include this, the invoice we received and to calculate the cash runway, so no real impact to our cash positions. If you compare with last year, you can see the comparable balance actually reduced more than RMB 100 million.
Okay, thank you very much. Dr. Yang, do you have any concluding remarks?
Well, firstly, I want to add to the response. I think, you know, the account receivable, you know, you know, the way we handle this is, this is actually to cover for future expenses, it's not a cover for, you know, the past expense that's our due, right? That's important. With that, I just want to say that, you know, thanks, for, you know, all your support. I know there's a lot of long-term investors who actually are losing quite a bit of money on payable right now. That's also true for myself, right, as you know that. Again, you know, I am very. Our team, management team and our board is very supportive and very optimistic about CStone. As you can see that, we all take care of the most important thing.
A couple of most important things, of course, one is our business top line and the top line advances, right, and also the BD activities. The second thing is our cash position. We are constantly looking for additional revenue, right, in addition to our commercial revenue. We are very cautious about our cost expenses, right. Without sacrifice, the key project for the company. We don't want to cut the company off from future growth. That's very important. Again, thank you, and, of course, looking forward to talk to you for the next half of years. Yeah. Bye-bye.
Thank you, management. Thank you, everybody, for dialing in. This concludes today's conference call. Have a very good day. [audio distortion]