Okay, good morning and good evening. This is Chen Chen from UBS. Welcome to InnoCare 2024 interim results earnings call, co-hosted by UBS and Morgan Stanley. Well, first of all, please allow me to introduce the management team joining today's call. They are Co-founder, Chairwoman, CEO, Dr. Jasmine Cui, CFO, Mr. Xin Fu, and IR Director, Ms. Bonnie Yuan. So after the business update from management team, we will open Q&A. If you have any questions, please feel free to raise your hand. And now I will pass the time to Jasmine. Thanks.
Thank you, Chen Chen. Good morning, good evening, everyone. Thank you for attending InnoCare 2024 interim results earnings call. So InnoCare is a high-tech drug innovation company. Our mission is science drives innovation for the benefit of patients. Our vision is to become a global pharmaceutical leader that develops and delivers innovative therapies for patients worldwide. Our drug innovation focus on oncology and autoimmune diseases, two large therapeutic areas that with a lot of unmet medical needs. Last Friday, InnoCare celebrated its nine years anniversary. During the nine years, we have been through an exciting journey of innovation and development.
From concrete milestone, the company was founded in August eighteenth, 2015, and we got successful IPO in Hong Kong, 2020, and IPO in STAR board in mainland China by 2022. We have been through. We did five rounds fundraising from beginning of the company to now, two private rounds and three public rounds, raised a total of $1.3 billion. And among that, we still have around $1.1 billion in hand. InnoCare, the biggest advantage, I think, is our ability for internal discovery. By now, we have over 10 products in the clinical stage, and the majority of that discovered by InnoCare team internally.
And our first product, orelabrutinib, got launched in mainland China by 2020, and by now, we have three indications approved for hemato-oncology treatment in mainland China. These are RR-CLL/SLL, RR-MCL, and RR-MZL, and all three indications covered by NRDL. We also get approval, market approval in Singapore for RR-MCL. Besides that, this first half year, we submitted two NDA packages and for orelabrutinib. Besides orelabrutinib, we also have a number of other assets for hemato-oncology, autoimmune disease, and solid cancers. Those products mostly are in phase II and phase III clinical studies, and we anticipate drug launch in the next two to three to four years and to the market.
The company also stepped into 2.0 stage and from 1.0, which is a fast development of the company. The 2.0 objective is to provide more innovative drugs to patients worldwide. It includes launch of at least six commercial products and become a recognized leader in hemato-oncology, and a strong competitor in autoimmune disease and solid tumor. We are looking to by end of 2028. Besides the clinical asset now, we will add additional five to 10 well-positioned differentiation assets into our clinical pipeline, and will further strengthen our unique research platform. We will have a three- to four-product globalization that includes out-licensing, partnership, and et cetera. By then, our sales revenue will increase significantly, and we will further strengthen our R&D, PD manufacturing, and commercialization platforms, and further strengthen our operational excellence.
We have a strong confidence to reach our two point zero objective by end of 2028. This is because we do have a robust portfolio in short to mid-term. Just to mention that we have, you know, number of asset will be launched commercially and in mid to long term and our innovation platform will generate more assets to benefit patients worldwide. Here listed our business highlights in first half of 2024. Basically, in summary, we have a pretty outstanding performance which underpins foundations for future sustained growth. In the commercial side, orelabrutinib revenue reached CNY 417 million with a 30% year-to-year increase in the first half, and specifically 49% year-to-year increase in the second quarter of 2024.
So in this year, we expect that orelabrutinib revenue will continue to grow because, you know, orelabrutinib is the first and the only BTK inhibitors launched for MCL in China. MCL has great actually market space. We see a lot of potential with that. And right now, it is recommended like a customer option for the M, RR MCL treatment in CSCO guidance of malignant lymphoma twenty twenty-four. And just imagine, all three indications already being covered by NRDL, actually, started a new term from this year, and all three indications with the same price as a couple of years ago, no price cut. So that is quite actually beneficial for our commercialization.
Most importantly, early this year, we have strengthened our commercial team and organization with a clear market strategy and new team with a strong ability to execute and with effective, efficient approaches. In the financial aspect, our total revenue first half year is CNY 419.7 million, and our gross profit margin continued to increase in the past three years. By first half, we already reached to 85.7%. Due to the increased revenue and actually improved operational efficiency, our loss for the period decreased by 37.6% compared to last year. Our cash balance and et cetera, we still have CNY 8 billion in hand.
That providing long-term, strong basis for our, long-term future development and the flexibility of our business. In the clinical trial, on trial, and we also made significant progress in the first half of the year. In the hemato-oncology, orelabrutinib, but we just mentioned we accelerated the first-line trials, first-line approvals. We have submitted two NDAs in this first half of the year, and we also started the first-line treatment of CLL/SLL in combination with our BCL-2 inhibitor, ICP-248. And we have finished the patient enrollment for the phase II trial. Our second product, tafasitamab, plus, lenalidomide, and we, in mainland China, we submit the BLA, in May and then accepted, in June with a priority review. And for our third product, ICP-248, is a BCL-2 inhibitor.
We are finishing those expansions, started the U.S. clinical trials, and also just mentioned that we are already finished phase III enrollment for first-line CLL in combo with orelabrutinib. And also we submitted IND for AML and in China and global, we are going to move to clinical stage quickly. In autoimmune disease side, orelabrutinib indication like ITP, phase III, we finished around 50% patient enrollment. This is a registrational trial, and we anticipated to finish the whole clinical study by end of next year and then submit NDA. So we will have autoimmune indications for orelabrutinib. This is efficient lifecycle management. For SLE, we finished the phase II A with a pretty promising result. We started with phase II B right now ongoing.
We finished the patient enrollment of phase IIb, and we are getting interim results by end of this year. We have two TYK2 inhibitors, all made high significant progress. The first one, ICP-332, we started phase III in atopic dermatitis, and we finished the phase II. We disclosed the result, quite exciting result. We are going to talk later. Also, we submit IND for phase II, phase III trials for the second indication, vitiligo indication, and in China. In U.S., we also started the clinical trial. The second TYK2 inhibitor, ICP-488, and we achieved the POC in the phase I psoriasis trial, was one-month study. And for phase II, three-month study, we also finished clinical enrollment in May.
We still supposedly to get a result read out by end of this year, in a couple of months. So in the solid tumor side and the NTRK inhibitor, ICP-723, and we have finished patient enrollment for the registrational study, and we already entered into pre-NDA stage, anticipating to submit the NDA package in six months. ICP- 189 is SHP2 inhibitor, and we have started combo with EGFR, third generation EGFR inhibitor, and we have got, you know, a first few patient results, quite promising. We anticipate to get full proof of concept this year.
- So, next, we'll have our CFO, Ms. Xin Fu, to go over the financial commercial highlights.
Okay, thank you, Jasmine. Hello, everyone. It's my pleasure to share with you our financial and commercialization performance in the first half of twenty twenty-four. Please note that all the financials we present here is based on Hong Kong Financial Reporting Standards. For the financials based on China Accounting Standard, please refer to our announcement in Shanghai Stock Exchange, which is also published on our website. There's no significant financial difference within two accounting standard in the financials, which will be presented in the following pages. So I'm very pleased to report that we have seen strong revenue growth of our flagship products, orelabrutinib. For the first half of this year, the growth of orelabrutinib has blossomed by a 30% increase, reaching to CNY 417 million. Notably, the second quarter growth achieved 49%.
The strong performance of orelabrutinib reflects our expansion into the indication of MZL and the effective market penetration strategies. Based on the progress we have made in the first half, we are confident to raise the full year growth guidance of orelabrutinib to at least 35%, which means the second half year growth rate will be higher than 40%. In addition to our top line growth, we have also made improving our operational efficiency. We have narrowed down our net loss by 37.6%, reducing it from 429 million CNY in the first half of last year to 268 million CNY in the first half of 2024. This significant reduction is attributed to sales growth, operational efficiency improvement, and a reduction in the unrealized foreign exchange loss.
We continually optimize our cost structure. The total expenses, including R and D expenses, SG&A expenses, has also been well controlled, with 5% increase compared to the same period in the last year. Particularly, the selling expenses was decreased by 17.8% to drive, for 30% product revenue growth. The selling expenses saving were driven by improved operations, operational efficiency, and the one-time reduced share-based compensation expenses in the first half of this year. The other key financials also reflect on our effort for sustainable growth. We continually improved our gross margin ratio in the past three period, from 47.5% to 80% to 85.7%. The increase in gross margin ratio attributed to quickly revenue ramp up of, product sales, changing in revenue combination, and also stable, pricing of the product.
Innovation remains the core value of our strategy. The R&D expenses grow by 17.5% to RMB 420 million in the first half of this year, which is within our expectation. We have made significant progress across multiple pipelines with ongoing clinical studies that are crucial to our future growth. We believe these investments are essential to maintaining our competitive advantage and ensuring a steady stream for the innovation therapies in the coming years. Lastly, by the end of the first half of this year, our cash and related account balance stood at around 8 billion RMB, which is equivalent around $1.1 billion. Compared with the beginning year beginning balance, the net cash consumption is around $40 billion.
This robust cash position provides with the flexibility and the security needed to continue investing our pipeline development, accelerate our clinical studies, and exploring strategic opportunities to align with our long-term growth objectives. Based on the good efficacy and the safety profile and the new indication continued approvals which we obtained in the past several years, orelabrutinib has achieved a significant revenue growth, which has been instrumental in driving our financial performance, and it positions us well to deliver at least a 35% growth for this year. One of the key growth driver for orelabrutinib is new indication for MZL. orelabrutinib is the first and only BTK inhibitor for this indication, which is considered to be the second largest indication of NHL in China.
It is also recognized by healthcare professional society, and they recommend it as Class One option, the newly updated CSCO guidelines. This expansion has opened up new market opportunities, and we will continue to work with physicians to enhance the diagnosis to benefit more patients. We are committed to be the market leader of this indication. For the R/R indication for CLL and MCL, we will continue to leverage the advantage of orelabrutinib to further extend the duration of treatment. We will also leverage more real world study to provide clinical evidence to enhance the recommendation of this product. In 2024, we also have expanded our hospital coverage significantly, ensuring that orelabrutinib is accessible to a broader patient population.
Last but not least, our experienced commercialization leadership team has played a pivotal role to executing commercial strategy. With focusing on maximizing the potential of orelabrutinib, we have been able to enhance productivity, improve cost efficiency, and deliver strong commercial results. In conclusion, the first half of twenty twenty-four has been a period of strong financial performance and a successful commercialization. Going forward, we are confident to we are confident in our ability to sustain high growth revenue and also deliver long-term value to our shareholders. So with that, I will hand over to Jasmine for the introduction of our key pipeline progress. Thank you.
Sure. Yeah, next page. Great, thank you, Xin. In hemato-oncology, our pipeline strategy is comprehensive coverage in indications and MOAs, from multiple myeloma to non-Hodgkin's lymphoma to leukemia. So, our two cornerstone product, orelabrutinib and the tafasitamab, and in the first half of the year, we got significant progress. We submitted the three NDA packages for these two drugs, and we also made progresses on other drugs listed here, like BCL-2 and antibody and et cetera. So I will quickly review a few assets in addition to orelabrutinib in hemato-oncology. So tafasitamab plus len, and for the treatment of second-line DLBCL, this is asset we licensed in from Incyte. This tafasitamab plus len is an outstanding therapy for the treatment of DLBCL.
From the table below, you can see the therapy demonstrated outstanding efficacy, particularly in duration of response for the 3.9 months, and also overall survival, 33.5 months. This therapy is much more superior than other MOAs and other therapies approved for the treatment of DLBCL, in specifically six to six times better, more efficacious, better than others in terms of length of time. For tafasitamab plus len therapy, we already got highly used in Hainan and Greater Bay Area. We got approval in Hong Kong, and in Taiwan, we have formed a collaboration with the TTY for the development and commercialization in Taiwan.
In mainland China, just said, our BLA package was accepted with a priority review in June this year, and we anticipate approval in the coming year. Our another product just mentioned, ICP-248, is a novel BCL-2 inhibitor with a lot of clinical advantages. As you may know, for BCL-2, it's actually a protein-protein interaction inhibitor and, so far, only venetoclax approved for the in the commercial. In venetoclax, there is a metabolic soft spot that generated actually a major metabolite, M27. Both venetoclax and M27 inhibit CYP enzymes and also P-gp substrate, and also the transporters, BCRP, that generates quite risk for drug-drug interaction, et cetera.
By blockade of the soft spot for metabolic spot, the advantage of 248 includes elimination of major metabolites, reduction of drug-drug interaction risk, and improvement of a PK, and we saw very good efficacy, of course, with a good safety profile. By now, for 248 development, we already expanded, like 40 patient at a 100 mg dose in AHL. We also mentioned combo with orelabrutinib finished the phase II enrollment for the first line therapy, CLL, SLL. The U.S. trial also started, and our dose escalation now is up to 150 mg, will finish very soon. We also submit IND for first-line AML.
This page shows, actually the purpose we develop 248, is for the sequential or combinational treatment with BTK inhibitor orelabrutinib. In the 100 milligram PD expansion, we did enroll patient with BTK naive or BTK-filled patient. In the 40 BTK-filled patient, you can see, we still see the ORR 71.4%, actually, with a very good PFS. And this efficacy is better than venetoclax and other BCL-2 inhibitors. And for on the right-hand side, showing in animal study, we saw robust and significant synergy of 248 with orelabrutinib. This is a scientific basis for us to start the clinical trials for the first-line CLL, SLL combo with orelabrutinib. Our next product is ICP-B02. It's a CD3/CD20 specific antibody co-developed with KeyMed.
From figure on the left, you can see it has outstanding efficacy, no matter by IV dosing or sub-Q dosing. At six milligrams and above, we observed 100% ORR in HL, such as DLBCL, follicular, MZ, and et cetera. On the right-hand side, you can see the sub-Q formulation has excellent PK profile. It avoided the exposure peak caused by IV injection, and then therefore gave a much better improved safety profile and avoidance of CRS and et cetera. Our molecular glue compound, ICP-490, we're still in development for both multiple myeloma as well as NHL. Both trials are progressing. For our solid tumors, we discussed before, we have our strategy is one is precision medicine. It's try to benefit the patient with specific mutations, gene abnormalities, and benefit the patients more.
Second is immuno-oncology, a combo, a combination, try to benefit more patients. We will use two examples, and they exemplify our strategy. The first is precision medicine, ICP-723. It's an NTRK inhibitor. It's a second generation of NTRK inhibitor, and it has very good efficacy in patient carrying NTRK gene abnormalities, including the fusion and the mutation. We have finished the patient enrollment for registrational trial, and we observed a very good efficacy ORR, 80%-90%, and the PFS over 36 months. Not only adult patients, we also did in adolescents and pediatric patients. Also we saw very good safety and efficacy profile in this young population. Our registrational trial includes adult, adolescents, and pediatric patients.
At the bottom, showing the excellent efficacy achieved for ICP-723, not only in the fusion, but also in the mutation caused by first generation of TRK inhibitor. Our next compound is a first-in-class compound, SHP2 inhibitor. It is the phosphatase inhibitor and in the phase II clinical trials now. In monotherapy, where we have been doing dose escalating now to 160 milligrams, there is a very good safety profile, no SEs observed. For efficacy, we observed the single agent efficacy in the dose escalating study. On the right-hand side, we are doing combination therapy with the third EGFR inhibitor furmonertinib. By now, the study has initiated. We also observed the promising result, and those are in patients resistant to the EGFR inhibitor.
As we know, EGFR inhibitor is, actually, they are huge drugs for treating the non-small cell lung cancer lymphoma, and non-small cell lung cancer. But when patient develop resistance to the EGFR, inhibitor, third generation, there are no approved good therapies by far. So we hope the combo of SHP2, the WNT89 with the EGFR inhibitor, we're providing a promising and, and a novel, treatment therapy for patients develop resistance to third generation of, EGFR inhibitors. For our autoimmune disease, we have been putting effort in both targeting B-cell pathway, such as orelabrutinib, and the T-cell pathway, such as the TYK2 inhibitor, as well as the newly disclosed IL-17 inhibitor, and we have number indications ongoing for that.
orelabrutinib, we in addition to targeting for hemato-oncology, we also try effort to expand the life cycle of and also to expand the market space. For autoimmune disease in China, we have several indications. For ITP the phase III is registrational trial, and we finished around 50% patient enrollment, as mentioned. We hope to finish all the clinical study by end of next year and submit the NDA in 18 months from now. That's once it is approved for ITP, that will significantly expand the market space for orelabrutinib in autoimmune disease. SLE is another indication that we have been putting a lot of effort. We got phase IIA positive, exciting result, and we started much bigger and longer trial.
It's a 48-week trial treatment, and with about 200 patients of phase II trial. We already finished the patient enrollment this month, and then we anticipate the interim result by end of this year. We hope these indications will be approved and in the coming two to three years, hopefully, this will, and this, if it's approved, this will significantly expand the market space of orelabrutinib. So we have two TYK2 inhibitors, and ICP-332 is a TYK2 inhibitor with some minor JAK1 activity and very selective against the JAK2 and JAK3. Another inhibitor, ICP-488, is only inhibit TYK2 without effect on JAK family. This is a phase II result of ICP-332 we disclosed earlier this year. The primary endpoint is the percentage of EASI score change from baseline.
From here, we can see both 80 milligram QD and 120 milligram QD cause the significant change of the EASI score comparing to placebo, right hand showing that the change is time dependent. We look at one week, two week, and week four, and so showing a steady decrease of the EASI score. And here, we also compared three thirty-two with other MOAs and treatment for atopic dermatitis, and either with JAK1-specific inhibitors or pan-JAK inhibitors, as well as larger molecules such as IL-4R and IL-13. So no matter which one, even the treatment was twelve to 16 weeks, and our four-week result are outstanding comparing to all these different MOAs. And actually, for the proof of the drug, upadacitinib is the best.
It's better than the other therapies and the phase III with 53.3% and 46.8% of EASI-75. And even though ours is better than upadacitinib, so we also compared the very difficult endpoint, such as EASI-90 and the itching score, NRS, above that equal and above four. We can see actually three thirty-two showing quite big improvement comparing to upadacitinib. And in addition, we also look at it, the quickness, the how quick the compound responds to, you know, the itching, which is a big problem for atopic dermatitis. And biologics such as IL-4R and IL-13, actually, they have delayed response. Patient get a drug, but there is no response in two weeks, actually, for patient that is very suffering. So we see whether three thirty-two can fill up the space.
And to our [audio distortion], really pleased to see and ICP-332 showing a significant improvement in EASI from day two and until, you know, every day and in the first two weeks, and continuously to improve until week four. And with this big improvement in EASI, we definitely see the very significant improvement of patient quality of life. And then, if you go back, we also started the second indication, vitiligo, and this is also a very big unmet medical need and also a large population of patients in China and worldwide. So for our second TYK2 inhibitor, ICP-488, and in phase I, in addition to healthy volunteers, we also add a cohort of psoriasis, and this is a one-month treatment in the small cohort.
Despite of that, we still see statistical significant change of PASI score from the baseline and comparing 38% with 488 6 milligram QD dose compared to placebo. And we also compare to Takeda 279, and they also did a phase I study, very small patient, and it seems 488 is equivalent or slight better than TAK 279. So we started the phase II early this year, and this is a three-month treatment and with one month, you know, safety follow-up. And also, we, this is a pretty large study with 129 patients. And the patient enrollment finished in May, and we anticipate to see the result in couple of months in end of October to November time frame. Now, we move to the preclinical space.
We do have a number of assets in preclinical space generated from our innovative research platforms, and IL-17 is one of the example. And so this is IL-17 is a small molecule molecule inhibitor for the treatment autoimmune disease. As you know, IL-17 is a proven target. The signaling path pathway is well known, and it's it's already marketed. And but the small molecule so far, there is no, we are still quite ahead in the global market, and there is no proof of the small molecule yet. Small molecule gives a lot of actually convenience for patient, and hopefully, it will have better safety profile as well.
Our small molecule modulator of IL-17 blocks both the homodimer of IL-17A and the heterodimer of IL-17A and F, with quite equivalent potency, and has much more improvement comparing to the reference compound, which in the phase I trial. In the animal models, CIA animal model, we see the compound has excellent efficacy and also has very good exposure since you can see the clearance of the compound much decreased comparing to the reference. In addition to IL-17, we have a number of compounds in the preclinical space targeting autoimmune diseases from our innovative platform.
If you separate that based on the targeted class, biologics like antibodies, a PPI, a protein-protein interaction blocker, and also a small molecule kinase and a phosphatase, et cetera. You can see for small molecule with less than five hundred, we have a number of compounds, you know, in the clinic already. orelabrutinib is ICP-022, and it's a covalent inhibitor. The ICP-332 is also allosteric inhibitor, and ICP-488 is an allosteric inhibitor. Of course, we also have other molecular glue and other molecules for the treatment of autoimmune disease, molecular with less than five hundred. For protein-protein interaction blocker, and is a much larger molecule. It's still small molecule, but the molecule with generally around five hundred to two thousand.
Among that, we have IL-seventeen, just mentioned, and we also have other three or four products in that space. Of course, we also have antibody for autoimmune diseases such as the bispecific antibody CD3/CD20, can readily being used for the treatment of autoimmune diseases. Besides that, we also have mono antibody and a bispecific antibody, even ADC and other combination platforms generated assets for the treatment of autoimmune diseases. We will disclose them gradually in the next few quarters. Just as a note that autoimmune disease has huge unmet medical needs and big market potential. For indication-wise, there are over a hundred and fifty different indications for autoimmune diseases. And the patient-wise, over five hundred million worldwide. In China, also over a few thousand million patients in China.
And autoimmune disease indications can affect different organs and different places, can be categorized, like nephrology, gastroenterology, dermatology, hematology, neurology, rheumatology, and et cetera. Among that, by now, in the clinic, we already covered four categories of the six, and we are also moving to, nephrology, like lupus nephritis, gastroenterology, like, UC, IBD, and et cetera. So we will, continue our effort and hope to get, a comprehensive coverage for different indications of autoimmune diseases to benefit, patients worldwide. I stop here, and I will be happy. Thank you for your listening.
Okay, thank you, management, for the detailed introduction. And right now, we can start the Q&A session. To all the audience online, if you have any questions for management, please feel free to raise your hand. And, before investors are preparing their questions, I have several questions for management. Well, first of all, on orelabrutinib. As we are glad to see that orelabrutinib has strong momentum in the first half, driven by MCL and NRDL coverages. So, what's the current duration of treatment time, and to what extent do you think you may increase the DOT? Also, how do you view the peak sales of orelabrutinib in oncology area in China? Yeah, that's my first question. Thank you.
Okay. Thank you, Tintin. Those are really good questions, so indeed, for hemato-oncology, it's quite different from solid cancer, and actually, the DOT gradually increased with the treatment time, so for the three indications that we proved, the RR-CLL, SLL, MCL, and MZL, actually, the PFS is quite long for all the three indications, particularly for CLL, SLL, and also for MCL, so since the first two indication proved the CLL and MZL, yeah, about three and a half years ago, actually, the DOT and also be covered by NRDL already two and a half years, so actually, the DOT is pretty good. The DOT, I think, for CLL, is close to a year or something, and so because, you know, launched earlier the drug.
For MCL, the PFS is also long, but it's only covered by NRDL from January this year, and you can see our major, the big effort started, and after NRDL launched in first quarter, and the second quarter, the sales increased a lot, so the DOT is still short right now, and still big room to grow because, you know, it's just covered by NRDL. We also anticipated, you know, the DOT increase to over a year, so for R/R, the PFS for MCL as well are several years, so this is almost like a chronic disease.
So for the TigaCell, you mentioned in the past, actually, we also give, we always give a prediction of we will have one-third of market share, and also with the TigaCell, for just oncology, maybe around 3-5 billion CNY. And we still see actually by second quarter, our market share already pretty high, I have to say, and hopefully we reach our goal of one-third market share by coming year. And the sales, we still anticipate a steady increase in the next few years, and we think we will reach the 3-5 B, between 3-5 B, just for oncology, with more indications approved. We still push a lot of first-line indications right now.
Yeah, thank you. That's very exciting. Yeah, and my second question is also about our orelabrutinib. So, we see that BTK as a class, its liver toxicity has been a concern in multiple sclerosis in a few clinical trials. And how do you comment on the toxicity in other potential autoimmune indications such as ITP, SLE? And what's your R&D plan for this drug in autoimmune indications in the overseas market? For example, which indication will you focus on, and are you considering any partnership? Thank you.
Yes, thank you, Chen Chen. There are several questions in here. First of all, for the MS, like you mentioned, for RMS, relapsed MS, there are few companies for RMS, the clinical trials being partially hold and including Sanofi, Merck Serono, Roche, and et cetera, and ours as well. So for us, since we already finished the phase II trial, and for us, we have observed actually one SAE in the MS trial. And because I think experience with other BTK inhibitors, we also got the partial clinical hold. For RMS, as you all know pretty well, in the U.S. market, there are three to four CD20 antibodies approved, and therefore they raise the bar pretty high for the treatment RMS.
But for PMS, progressive MS, including the primary PMS, secondary PMS, and et cetera, by now, there's no good treatment therapy. So those are the patients that's actually much severe, and the primary endpoint is the disability score. And for those, Sanofi already get the partial clinical hold lifted in the first half of this year, and both for primary PPMS and SPMS. So because the huge unmet medical needs for PMS and we believe orelabrutinib also can be used for the treatment of PMS as well. So we are in the middle of also communication with FDA, and hopefully we can start the clinical trials, the phase III for PPMS as well.
And for RMS, besides U.S., and we get approval in China or other regions for initiation of phase III trials, because, you know, the cost doing MS trials, phase III trials, and, you know, the patient population and market potential, and we are still considering whether it's worth to start a phase III outside of the U.S. for just RMS. So we have different options for that. And hopefully we will sort it out in a few months and can give a clear path forward for that, for MS treatment. And we still think orelabrutinib is the best in class for that, based on the brain penetration, based on the peripheral exposure and et cetera, and we do have it has really good chance for the treatment of PMS.
For other indications such as ICP, particularly SLE, is also lack of treatment globally used for small molecules, especially. There's no good drug for the treatment of SLE. orelabrutinib is actually the only BTK inhibitor get to work in the phase II clinical trials for SLE. We're also considering doing global trial, but as you know, SLE, you do any drug, need to be on top of standard of care, and that standard of care is quite different in China, in U.S., and different countries. So perhaps it is very tedious or difficult to do a global trial, including U.S. and et cetera, for the SLE. So we like. You know, for China, we are getting really proof of concept. We have a large phase II study with a large population.
We should have the data this year, and if it is good, and we are also considering a move to the global clinical study, perhaps it should separate from the China study, and that's our plan. Also, for indications like severe indications like lupus nephritis, like we mentioned, PMS and others, we still think orelabrutinib has great hope on those indications with unmet medical needs. Well, thanks. That's very clear, and we are looking forward to the progress. Okay, I will pass time to our co-host, Jack Ming, and to see if Jack has any questions.
Hi, can you hear me?
Yes, very clear.
Hi. Yeah, thanks, Chen Chen, and thanks, management, for taking my question. I have, I think two main questions, and one about orelabrutinib, and I think one about, I think ongoing company operation. So, just kind of going back to Chen Chen's first question regarding orelabrutinib sales in the second quarter, and also trying to wrap my brains around the earlier guidance, you know, for the 35% year-over-year growth. I'm wondering if the management is guiding a bit more on the conservative, conservative side, 'cause if I applied the 35% growth this year, it would suggest that, you know, and taking into account the first half of sales, it would suggest that for third and fourth quarter, we're kind of expecting more or less flat or even some small decline compared to our second quarter sales, which has been very robust.
So in light of that, the question I have is, I'm wondering, for the various drivers that has allowed us to achieve this very strong growth in the second quarter, whether it's increase in DOT, it's MZL, or there are any other major drivers, do we expect any of these drivers to weaken or no longer contribute to drive growth in the third or fourth quarter? If we don't, then should we expect a more robust growth trend in the third and fourth quarter, or be a much higher guidance for the whole year? So that's kind of the first sub-question. If management can also help share, you know, if we have any color in terms of sales breakdown between the indication, what, how much, I mean, specifically, how much did the MZL contribute so far for, I guess, the first half and the second quarter?
That's the first question about orelabrutinib.
Yeah, okay. So, thanks, Jack, for your question. Yes, you have very quick calculation, right? Yeah, in the first half, we have 30% growth, and then we raised to 35% for the full year, and that means the second half is over around 40% growth. So I think we seek guidance, which pretty much safe, 'cause we said the risk, the growth percentage, at least it is at least 35%. We think if we continue, at least with, even we continue with second quarter, we can achieve that target. Because in the last year, if we talk about growth, this actually is this year achievement and the last year base. So in last year-
Mm-hmm.
Our third quarter actually is the lowest because the you know the big environment issues we see the lowest you know contribution in the last in the last year quarter three. So I think we do expect that in the for the growth rate-wise the quarter three will be very very high. And then we gradually going back to normal starting from quarter three and quarter one this year. So I think our growth will continue but you know we don't see our absolute dollar you know the revenue number will not decrease. That means I think 35% is pretty much safe target so we can risk that guidance. That is of course you know for your question.
Secondly, for the contribution with the growth driver, yes, we see that MZL is a new indication and also covered by the NRDL without any price cut. Well, from the volume point of view, the major contribution is still coming from our well-established indication for SLL and MZL, because we already have a market launch for about two and a half years. And the MZL is still grow based on the small basis, but the growth rate, I mean, is very strong. So we see that the MZL actually has very big potential. The question and challenge we now to see have for the diagnosis, because the MZL patient not only coming from the hematology department, it's coming from different departments.
So how to treat it, how to diagnose the patient, actually, we will put a lot of effort in the second half. I think, in the long run, we see that MZL will be becoming the second growth driver for this year and also for next year, several years. So this is, you know, our basic contribution and also- we don't have the exact number because we cannot collect the prescription from the hospital, but we do see some market research data. Well, we see that MZL is contribute a lot of new patients. We do see that, we hope that MZL patient will be have longer DOT than CLL.
So eventually, we think MZL, the contribution will be bigger than the CLL and the MCL.
Yeah, yes, yeah, to answer your question, there's no any factor will be, is weakening in third and the fourth quarter. We'll continue to grow, and, and, our team also play a bigger role. We have upgraded, we're strengthening our commercial team, especially the leadership team. We changed the CCO and head of marketing, head of medical, and also, and sales team. And so, - we will, we expect continuous growth in third and fourth quarter. Yes, 35% is relatively conservative.
Understood. Thanks so much for the detailed explanation. And I think the second one is, I guess, will be a relatively quicker one. So in the second quarter, we see that, our selling ratio has significantly declined. Well, I guess, the first half altogether. And I think a large driver of that was from the, you know, share-based, payment reversal or reduction, whichever. But once we adjust for that, it seems like the selling ratio or the, the selling cost ratio to product seems to have remained fairly stable, whether compared to the first quarter or I think the second quarter last year. So wondering, in terms of, like, on a cost trend perspective, do we expect this selling trend to have stabilized?
What trend? If we expect to trend down, at what rate do we expect to continue trending down? And how does that impact whether we have an updated timing or guidance on the break-even?
Yeah. I think yeah, you are right. In the second quarter, because there's a one-time stock payment based of the compensation expenses, there's a reversal, and also will reduce a lot, around CNY 30 million impact. So, from dollar to dollar-wise, even we excluded for this impact, I think the total spending compared with last year is quite equal. That is the dollar to dollar. Well, the revenue uses grows very strong. If you divide it by the drug sales, I think our sales percentage is also improved. Traditionally, you know, for the new products launch, the commercial expenses will be high, but we see that InnoCare actually has very strong cost and efficiency spirit.
Our commercialization, the spending percentage, whether we increase or decrease from 17% in 2022, and last year, 56%. This year, first half year is 37%. I think the one-time impact that happened in the first quarter will not continue on the recurring the second quarter. But we do see the OpEx ratio will be further to, you know, to reduce compared with last year ratio. And we foresee that maybe this year the OpEx ratio will be lower than 50%. I think with the our MZL new launch in the market, we still keep a strong investment in the patient education, physician education, and also diagnosis. I think we will still invest in this area and also to drive the top-line revenue.
Anyway, we will continue to reduce the full year the percentage compared with the last year.
Thank you.
And also-
Yeah. Yeah, go ahead.
Break even, yeah. For the break even, we're still a young company, and we have to see that, compared with the several peer company which have already disclosed the anticipated year for the break even. We think the InnoCare entering into this second phase for our company. We do see starting from second quarter, our gross revenue has been, you know, revenue will be continuing with a high growth, leveraged with MZL strengths. In the last year, we will the first line for the sale will be approved, and we will have new products for tafasitamab. For the the solid tumor products will be approved in twenty twenty-five and also in twenty twenty-six.
Starting from 2026, we will have entry into the autoimmune disease, which will ensure for the higher growth, so will be continuous. So we can see that InnoCare entering into the accelerated growth period, starting from this quarter, from the short term, midterm and the long term. For the break even, I think we can anticipate maybe after our entry into the autoimmune diseases commercial launch, we are excited, and we can have the break even. Even that, considering we are establishment starting from 2015, we can break even in 2027 or 2028. We're still very successful biotech companies.
And before that, if there's some BD deal could be completed, and we will accelerate for the break even year.
Understood. Thank you so much for sharing the details. Passing the mic back to Chen Chen.
Thank you, Jack. Okay, we can now accept questions from investors. Sam, you can unmute yourself. Thanks for waiting.
Thank you, Chen Chen. This is Sam Isaly at Exome Asset Management. A couple of questions. We've already spoken a lot about the orelabrutinib situation, so I'll leave that alone unless there's time. On the TYK2 candidates, do you expect those to be licensed out candidates? And have you begun clinical trials in the United States, or when will you begin that? Secondly, you've given a break even scenario, I'll call it, not a projection, of 2027 or 2028. Will you need any external financing to get that far? Last, are there any special financial items, either positive or negative, in this year, or this half year, and last year's half year, that would distort comparisons between the two? If we have time, I'll ask you more about orelabrutinib.
- Okay, Sam, thank you for the question, and it's very, I'm really pleased to hear from you. So for TYK2 inhibitors, we have two TYK2 inhibitors just mentioned. The first one, three thirty-two, since we got the phase II result early this year, and we started the phase III in China. Yes, in U.S., we already started the clinical trial. In the U.S., actually, we need to do a, first of all, in healthy volunteer, a few cohorts. We are doing three-cohort MAD study, and we anticipate to finish it in three months. Then we are going to move to patients in the U.S. We're thinking about, you know, what is, well, what is less competitive in the U.S., and what is unmet medical needs.
Learning from orelabrutinib, you know, FDA's communication, we feel the unmet medical need is really the first important criteria for us to move on. So we're thinking ICP-3 32. Actually, from a scientific background, it is a first-in-class compound. It's an allosteric TYK2 inhibitor with selective activity. And we get, you know, such exciting results in atopic dermatitis. Inspired by that, we want to finish the phase III study of atopic dermatitis in China and collecting more safety, efficacy data. Perhaps in U.S., we are thinking to pursue a new indication, such as IBD, UC, and with a lot of unmet medical needs. That's the current consideration. For ICP-488, it is a purely TYK2 inhibitor, actually.
So far, the only thing approved to work and approved concept is the psoriasis, and that's what we are doing in China. We're finished the phase II, and we will know the result in a couple of months, and then we definitely will start phase III if the result looks good. For the global market, like I said, you know, do we want to repeat the psoriasis study in the global market? We consider it's, you know, the crowdedness and the unmet medical needs. We're thinking to do severe diseases such as SLE. Even as a T-cell therapy, even considering the combo and with B-cell therapy for SLE and other indications. That is the thought, and that's really brand-new ideas. Our team is discussing that.
But for ICP-488, we already have IND approved in the U.S.
Okay. Um-
Yeah, this is-
Break even, with break even without financing?
Yeah, break even, as you know, InnoCare is very cautious and careful about spending. And as I mentioned, we total raised $1.34 billion. By now, we still have $1.1 billion in hand. We do have a lot of cash. Based on our spending rate, our cash should last, like, eight, 10 years or something. Other people are predicting for us, it lasts a long time, by the way, beyond the five years. And whatever, you know, despite of that, we still try to, you know, break even. Maybe global, you know, whether break even or not, depend on how much global trials you are doing, right? If you do few phase III trials for autoimmune disease, it eats up a lot of money. And we're considering partnership for the big phase III, especially autoimmune disease studies.
By this way, we can, you know, actually we do the clinical studies by ourselves in China and with really cost-effective way. And the global study, we still try to get a partnership, and we, if we get a partnership sooner, we are going to break even sooner than 2027. And other question about another round of financing, you know, we're getting the market, the global market for healthcare, and there are a lot of cheap assets on the market, and we do have a lot of money. And we are also considering organic growth of the company, looking for MA opportunities and that. So we don't need to raise another round of finance, but if there are good opportunities ahead of us, we are not eliminated of it.
We are not, you know, we keep open for it. But just for ourselves, you know, we cost very little money the first half year and comparing our cash reservoir.
Do you have time for additional thoughts on orelabrutinib?
Sorry, what's the question?
Do you have time to take a question related to orelabrutinib?
Sure, sure. Yeah. For you, always. Yes, please.
Thank you. Look, there's multiple indications, of course, for BTKs, but on a sort of top of the mountain view, on a worldwide basis, BRUKINSA is going great and taking share and Imbruvica looks like it's disappearing. You're somewhere in between. You're at least maintaining share on this global basis, I think. But do you have your own assessment of that?
Yeah, actually, you raise a very good point. For autoimmune disease, hematology oncology, like liquid cancer and et cetera, you are absolutely right. Then, this is Zanubrutinib, right? They are taking a lot of market shares for CLL and MCL and et cetera. And, so for us, actually oncology, since, you know, we are getting into market, getting into global market relatively late, our company established much later. So, now, since orelabrutinib has excellent safety profile, we can do autoimmune disease. Other BTK inhibitors now marketed in China for oncology, they cannot do autoimmune diseases. They are not moving into that direction. So we are thinking for the global market, and autoimmune disease is our major direction.
We are communicating with FDA for MS, just like I said, and also we are considering other indications, as mentioned, SLE, lupus nephritis, et cetera. We think, you know, if we push, we prove a small indication like RR MCL in U.S., and with the IRA, you probably well know, we will launch a drug by certain years, like ibrutinib already decreased the price because it launched more than nine years. We are considering autoimmune disease is our major direction. We are going to compete for that in the global market.
Thank you. Thank you for taking my questions.
Sure. Thank you, Sam.
Thanks, Sam. Next, I think my colleague, Dr. David Gu, has a question for you, Jasmine. Over to you, David.
Sure.
Hi. Thanks. I see it's already over the time, and I will keep it very short to ask a simple question, so I know that the, in the previous Q1, earnings call, that we mentioned about to submit the, the MCL of orelabrutinib- of orelabrutinib in, the U.S. And, I was just wondering, would there be any update of this target and, any more colors to update for its, way out in the commercialization and, and future development? Thank you.
Yeah. Hi, David. And, yes, you mentioned this question just exactly, just discuss with, tie together with Sam's question. RR-MCL, indeed, we finished a single-arm study, and that's eligible for submit for, you know, for the NDA conditional approval. And, and so, but, you know, we're already number four in the market, or number four, even later, number five. So we conducted this global market analysis in the U.S. and in global. It is, the, the potential is not that great. And so also with the newly, you know, the policy in U.S., IRA, if you launch a drug to the market, no matter which indication, and then you have nine years. After that, you get price cut. And so with the IRA, we are discussing the strategy.
Do we want to get first into market, or we want with a larger indication to be launched in the market? Since orelabrutinib has so much potential for autoimmune diseases, just mentioned the very large indications like MS, SLE, lupus nephritis, and et cetera. And we are, next few months, we're considering the strategy. Do we want to first enter market, or do we want to actually launch larger indications first? For autoimmune disease, we'll have a longer lifespan for, you know, to preserve the price. So that's what we're discussing internally, and we'll have some strategy by maybe a quarter from now.
Okay, great. Thank you so much for your answer. Yes, thanks.
Sure. Thank you, David.
Okay, thanks. So Jasmine, we have no more questions from investors. So do you have any concluding remarks?
Thank you, Chen Chen, and everyone for today's conference. Thank you for attending our conference. I saw Sam's face, and so, so nice to see you, your name on the screen, and we look forward to seeing JP Morgan or even earlier than that, and thank you for your support and for your attention to InnoCare. Bye then, you have a good day and a good night.
Cool. Thank you, Jasmine and the management team for your time. And thanks to all the investors for your interest in InnoCare. So see you next time. Bye-bye.
Bye. Bye.