Good morning or good evening. Welcome to Everest Medicines 2025 Interim Financial Results Conference Call. Please be advised that today's conference call is being recorded. During the Q&A session, for participants who join the call through PC or app, please click the raise hand button at the bottom of the screen to queue up for voice questions or text your questions as messages. For participants who dialed in, please press star one to queue up for questions. Joining us today are Mr. Rogers Luo, our Chief Executive Officer; Mr. Ian Woo, President and Chief Financial Officer; Mr. Rico Liang, our Chief Product Officer; Dr. Jennifer Yang, our Chief Scientific Officer; and Sandra Zeng, our Chief Medical Officer.
Before we get started, I'd like to remind you that the speakers of this conference call may make statements that constitute forward-looking statements, including descriptions regarding the intent, beliefs, or current expectations of the company or its officers with respect to the business operations and financial condition of the company, which can be identified by terminology such as will, expect, anticipate, future, intent, plans, beliefs, estimates, confidence, and such similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and actual results may differ from those in the forward-looking statements as a result of various factors and assumptions. The company or any officers, affiliates, directors, officers, advisors, or representatives have no obligation and do not undertake to revise forward-looking statements to reflect new information, future events, or circumstances after the date of this conference call, except as required by law.
I will turn over the call to President and CFO, Ian Woo, to provide you with more details on our business updates and the 2025 mid-year results.
Thank you, operator. Let me first start by saying thank you to everyone for joining today's call. Our interim results presentation will begin with me providing an overview of the company's overall business performance since the beginning of 2025, including business achievements, financial results, and full-year performance guidance. Following that, Mr. Rogers Luo, our Chief Executive Officer, and Mr. Rico Liang, our Chief Product Officer, will highlight the progress and future plans for our commercialized product. Next, Sandra Zeng, our Chief Medical Officer, and Jennifer Yang, our Chief Scientific Officer, will jointly present the latest developments in our platform. Finally, Mr. Luo will conclude with a summary and outlook on the company's future development. We'll follow that up with a Q&A session. Looking at this slide, which is a snapshot of our major achievements in 2025, I'm very proud to share with everybody.
First, on commercialization, execution was exceedingly strong, and we rapidly advanced the development of a broad portfolio of innovative pipeline assets that we expect to have tremendous global value creation potential. Let me begin with Nefecon. We generated CNY 825 million of revenue between January and August. We achieved this very strong result in spite of a supply constraint that some of you may have heard of, that was really rooted in both strong market demand and a delay in regulatory approval of a supplemental application for production scale-up designed to ensure supply stability. Since our supplemental application was approved by the CDE early in August and Nefecon's availability was fully restored across China, we've seen very robust uptick in sales this month. We will give 2025 full-year and 2026 sales guidance in the next slide.
With respect to reimbursement, Nefecon achieved NRDL coverage in 29 provinces so far, which is essentially all of the country. We also received full approvals in all licensed territories, including Greater China, Singapore, and South Korea. Finally, Nefecon was recommended by China's first IDN guideline as a first-line disease-modifying treatment. Next, I will talk about our autoimmune disease franchise. For VELSIPITY, I think we're very happy with the progress of the NDA review. The non-clinical, clinical, and statistical sections of the VELSIPITY NDA application are complete, so we are into the final stretch of the NDA review process. Our base case remains early 2026 approval, but we are now hopeful that this timeline can be accelerated. We have initiated pre-launch activities, including building up a commercial team, and are advancing a project to localize manufacturing of VELSIPITY in Jiashan, China, with trial productions to begin in December of this year.
We're thrilled to announce that VELSIPITY's multi-center Asia phase III trial data has been accepted for publication in The Lancet Gastroenterology & Hepatology Journal. Additionally, VELSIPITY's maintenance data was presented at the European Crohn's and Colitis Organization Conference in February. VELSIPITY was also strongly recommended as a first-line therapy in the updated American College of Gastroenterology guidelines for the treatment of ulcerative colitis in adults. On the regulatory front, outside of mainland China, we received NDA approvals for VELSIPITY in Hong Kong and have submitted NDAs in South Korea and Taiwan. For XERAVA in our anti-infective franchise, we're very pleased that the Chinese clinical breakpoints were accepted by the China CDE and reflected in the product label. We're also working to localize production of this product and getting prepared for potential NRDL negotiations next year. Let me move on to our platform.
For SIBO, also known as EVER001, we continue to disclose positive data from the ongoing phase I-B/II-A trial. The March data cut was presented in the European Renal Association ERA meeting in June, and we will be disclosing the June data cuts later today. We made significant progress in our proprietary mRNA in vivo CAR T platform as we generated proof of concept, B-cell situation, and safety data in non-human primates and completed clinical candidate selection. We expect to launch clinical development by the end of 2025. We have three programs in our mRNA cancer vaccines platform, and let me review these one by one. First, EVM-16, our personalized cancer vaccine. Our investigator-initiated clinical study is ongoing, and dose escalation has been complete for the low and medium dose cohort, and we're dose escalating into the high dose now.
For EVM-14, our tumor-associated antigen cancer vaccine, we received IND clearance in the U.S. with first patient enrollment scheduled for September. Our IND in China has been accepted for review. We expect approval shortly. Lastly, for EVM-15, our immunomodulatory cancer vaccine, we have completed preclinical POC and are advancing with our pre-IND work. Financially, we are on solid ground after completing a placement on August 1, 2025, with net proceeds of approximately CNY 1.6 billion. We had CNY 1.6 billion in as of June 30, 2025, so we have a strong balance sheet for the rest of the year and going into 2026. We also made a $30.9 million strategic investment into NASDAQ-listed I-Mab and are now the largest shareholder of the company with a 16.1% ownership stake. On this slide, let me give you a snapshot of where we are financially.
In the first half of 2025, revenue was CNY 446 million , which grew 48% year-over-year. However, as discussed previously, the first half revenue was artificially low due to Nefecon's supply constraints, which have been fully resolved. Consequently, you can see that we recorded CNY 520 million of Nefecon revenue in August alone in order to meet the pent-up market demand. Therefore, our revenue from January to August is expected to be over CNY 960 million. These are unaudited numbers, but we wanted to give a picture of where we are from the beginning of the year until now because of the supply constraints with Nefecon in the first half. Given the visibility we now have on 2025, we are prepared to give full-year 2025 revenue guidance, and this is going to be CNY 1.6 billion-CNY 1.8 billion , of which CNY 1.2 billion-CNY 1.4 billion will be
Nefecon sales. We believe that Nefecon may be the first ever non-oncology drug to achieve more than CNY 1 billion of sales in the first year of commercialization after NRDL inclusion. Gross margin on a cash basis remains strong at 76.4% for the first half of 2025. This is backing out non-cash amortization of intangible assets as we have always done in the past. Due to the price reduction of Nefecon after NRDL inclusion, the gross margin was slightly lower compared to 2024. However, with cost reductions driven by increased production capacity and scale, we believe that the gross margin will restore to above 80% in the long run. Our non-IFRS net loss was approximately CNY 147 million . This is down 31% year-over-year. We have consistently provided non-IFRS disclosure, which backs out one-time items and non-cash charges, and believe that this is a better measure of the company's ongoing operation.
Our cash balance of CNY 1.6 billion at the end of June 2025 now adds CNY 1.6 billion from our recent financing. Last but not least, we target to achieve operational profitability in the second half of 2025. We have previously guided to achieving this milestone in Q4, but now believe that we can do this earlier than expected. On this slide, there are a lot of numbers there, and I won't be going through everything. I think I will just highlight a few items that I did not touch upon on the previous slide. I think the key takeaway here is that we have been able to grow revenue while increasing operating leverage. The G&A expense increased slightly to CNY 110.8 million , primarily associated with an increase in headcount needed to expand our launch efforts and develop new products.
expense decreased to CNY 195.2 million as we optimized spending to focus on core pipeline programs, which are in earlier stages of development and not as capital intensive. Distribution of selling expenses increased by CNY 114.4 million to CNY 314.7 million . This increase was primarily driven by broader marketing and sales efforts of Nefecon following its inclusion in the NRDL and its full approval across the Asia region, as well as expanded promotion of XERAVA. With that, let me turn over to Rico Liang, our Chief Product Officer, to talk about commercial achievements.
Thank you, Ian. Now let's turn to the key driver of our revenue growth, Nefecon. Following NRDL implementation this year, Nefecon generated CNY 825 million sales from January through August. You know, patient demand has been robust across China after NRDL implementation. To the point, we experienced the supply constraints in certain regions in June and July. The approval of production scale-up has already enabled us to increase supply quickly. In six months, more than 130,000 bottles of Nefecon were delivered to the market across China. On the other hand, we have built a lean and highly efficient commercial model. In the second half of 2025, we will continue to expand the market coverage to 1,000 hospitals nationwide with more than 80% market potential. We expect about 30,000 new IgAN patients will be treated with Nefecon.
Altogether, this performance underscores both the significant unmet need in the IgAN market and the average ability to gradually scale Nefecon into a leading renal function therapy in China. Looking ahead, we see most drivers holding sustained and accelerated growth for Nefecon in 2025 and 2026. As Ian discussed in the early slides, we are going to get from CNY 1.2 billion- CNY 1.4 billion sales from Nefecon in this year, which is expected to further double to CNY 2.4 billion- CNY 2.6 billion in 2026. We believe this forecast is well-supported and highly visible due to the following drivers. First, huge market potential. China has an estimated 5 million IgAN patients, with about 1 million confirmed by the renal biopsy and about 100,000 new confirmed cases each year.
From the second half of this year, we will expand the coverage to 1,000 hospitals, equivalent to more than 80% of the market potential. Secondly, Nefecon remains the first and only IgAN therapy fully approved in China and the EU through the NRDL, which ensures exclusivity in this market. The full approval for China NDA in April expands treatment to all adult patients with primary IgAN at risk of progression without limitation of the proteinuria, substantially improving the eligible population. On the other hand, we expect Nefecon to be included in the updated global KDIGO guidelines, as well as the first china IgAN guidelines in the second half of this year. Also, our supplement expectations for the production expansion were approved, ensuring reliable and sufficient supply to meet robust market demand. Complementary to Nefecon, we are developing a DDIG-1 diagnostic tool.
DDIG-1 is a biomarker highly correlated with the root cause and the progression of ATEM. With DDIG-1 test harmonization, we could establish an integrated diagnosis and treatment ecosystem to improve compliance and the treatment duration of Nefecon. We also aim to improve the detection rate of ATEM through non-invasive early screening. Our DDIG-1 IC has demonstrated up to 95% specificity compared to the gold standard renal biopsy, with low cost and faster result delivery. With the pivotal trial enrollment and the complement, we expect regulatory approval in the second quarter of 2026. Also, I want to draw your attention to our antibacterial business. The enrollments continue to demonstrate steady growth in the first half of 2025. Revenue reached CNY 143 million, up to six years of over a year, with 37% in-market sales growth.
In China, antibiotic resistance is a major issue, but there are limited available treatment options prior to the enrollment. Each visit gets its downside. Consequently, there is a strong demand for new applications and the safe treatment options like XERAVA are already clear. Proposition XERAVA for early land use and the continual increased penetration in the cold hospitals. As we explore the second growth curve for XERAVA, we are actively advancing its local production to aim to participate in 2026 NRDL negotiations. It may pave the way for substantial sales growth in 2025. Yeah, in addition to the XERAVA, we are building a strong and complementary antibacterial portfolio. XERAVA provides broad spectrum coverage across the resistant bacteria.
Succinctines, Chinese Bactrim, offer the best in-class inhibition of both the renin and beta-lactam lactase, and ER206, a novel formatting in relative significantly reduced renal toxicity, which will estimate deep cell potential for all CNY 1 billion-CNY 1.6 billion , positioning us as a leader in the multi-resistant infection treatment market. Yeah, thank you. Now I pass the microphone to Rogers.
Thanks, Rico. I'm going to talk about ulcerative colitis. Along our anti-infectious portfolio, we are also advancing our autoimmune portfolio with a focus on ulcerative colitis, which we see hosts a $14 billion unit market size and is still growing. Both IgAN and UC have huge unmet medical needs with poor prognosis and limited effective treatment available. That's why we believe VELSIPITY has the potential to become the next Nefecon's epitope for the cure. Like IgAN, UC is a highly prevalent, high-burden disease with both clinical and societal impacts. Currently, we see 450,000 patients on treatment in China each year, which is expected to double to 900,000 by 2031. Patients suffer frequent flares and over 40% relapse within one year, while quality of life is severely impaired, with steady symptoms affecting both health and social functions.
In the long term, up to 30% require surgery and nearly one in five face colorectal cancer risk. This underscores the urgent need for therapies that deliver deep and durable disease control. Next slide. Mucosal healing is now recognized globally as the long-term treatment goal in UC. It's not only restoring quality of life but has minimal impact on outcomes. Patients who achieve mucosal healing within the first year of the diagnosis reduce their recurrence rate by 50% and the risk of surgery by 66%. They also experience significantly lower risk of developing into cancer. Yet, despite being recognized, only about 24% of the patients actually achieve mucosal healing on the current therapy. This treatment gap highlights the urgent need for next-generation therapies capable of achieving deep, durable healing. Next slide. VELSIPITY is designed to go beyond symptom control to achieve post and deep healing.
You can see from the case here in the slide. In the picture here, we see clearly that patients progress from severe mucosal inflammation and ulceration to full mucosal healing up to 52 weeks of treatment with VELSIPITY. This case actually is from our phase III trial. This kind of deep and durable response may help reduce relapses and lower long-term cancer risk, highlighting VELSIPITY's potential as the best in disease treatment. Next slide. Global guidelines recognize mucosal healing as a key treatment endpoint. During the maintenance period, VELSIPITY demonstrates a robust rate of mucosal healing, with nearly 52% of patients achieving deep mucosal healing. When compared with the studies' results for other current treatments, whether it is biologics or JAK inhibitors, VELSIPITY showed a comparative rate, including 61% achieving endoscopic mucosal improvements higher than recently in marketed orders.
It is important to note that they are not app to app studies. VELSIPITY employs the most stringent evaluation criteria, and this data suggests VELSIPITY has strong potential to meet established treatment goals in UC. As we discussed in earlier slides, VELSIPITY offers rapid onset of action and deep mucosal healing. From a safety perspective, VELSIPITY has a favorable profile, showing no increased risk of serious infections compared with placebo. Most adverse events were mild to moderate, and the discontinuation rate was low. This convenience of one steady oral pill with no titration requires further support for patient compliance. Finally, VELSIPITY is strongly recommended by global medical guidelines, including the ACA and ACG, as a first-line therapy. These clinical and safety advantages position VELSIPITY as a robust, battling disease therapy for UC with six cells expected to reach CNY 5 billion.
On the operational side, VELSIPITY is on track for NDA approval in mainland China in the first half of 2026. NDA approvals have already been secured in Hong Kong, Macau, Singapore, Taiwan, and South Korea. Pre-commercial activities, including real-world studies and the commercial team build-up, are ongoing, with local production projects well underway. At Everest, our success is built around three complementary value-creating platforms that together form a differentiated and sustained growth engine. First, our commercial platform is already generating significant revenue growth led by two robust Nefecon and VELSIPITY, which address high-needs areas in renal and autoimmune disease, each with six cells, CNY 400 million. This strong commercialization capabilities enable us to invest in in-house platforms to unlock long-term value creation.
We are advancing a next-generation AI-enabled mRNA platform to develop a pipeline of therapeutic vaccines for autoimmune and cancer disease, including our in vivo CAR T platform and our mRNA cancer vaccine platform. That are powerful engines of internal innovation. Together, these platforms give Everest a unique balance of near-term revenue, mid-term high growth, and long-term transformational potential. Now, I'll pass the microphone to our Chief Medical Officer, Sandra Zeng.
Thank you, Rogers. Now I'm going to share with you the most updated data from the ongoing 615-628 study of EVER001, also called SIBO, in primary membranous nephropathy. SIBO is a reversible covalent BTK inhibitor that we are developing for autoimmune renal indications, the first one being the TMM. SIBO selectively forms a reversible covalent bond with Cys481 for AD1 in the BTK kinase domain. It differentiates from other BTK inhibitors currently marketed for other indications, which are either irreversible covalent BTK inhibitors or non-covalent reversible BTK inhibitors. The covalent binding mechanism of SIBO ensures ongoing single-insulin strong BTK inhibition, while its reversibility and high flexibility seem to be where we need to map off-target toxicity. As shown on the slide, the table at the bottom left side shows the IC50 of SIBO versus ibrutinib against a panel of kinases.
Compared to ibrutinib, SIBO has similar potencies against the BTK but has much better selectivity against the off-target kinases, such as EGFR, ITK, and TEC family, which are thought to be associated with undesirable safety profiles. Furthermore, as shown on the table at the bottom right side, even compared to the more selective BTK inhibitors, such as zanubrutinib, orelabrutinib, and acalabrutinib, SIBO demonstrated differentiated selectivity. We also believe that relative best off-rate for SIBO combined with its high selectivity may further benefit the safety profile of this compound. Here is the most updated data from the ongoing EVER001, also SIBO, 615-628 study in TMM with a cutoff date of June 12, 2025. Just want to refresh memory. The study is conducted in Chinese TMM patients with quasi-anti-PLA2R antibodies. I choose those numbers. The subject in cohort one started with 100 mg q.d. for four weeks, followed by 100 mg b.i.d.
for 32 weeks, with a total of 36 weeks of treatment. The subject in cohort two received 200 mg b.i.d. for a total of 36 weeks of treatment. By the data cutoff, a total of 31 subjects were enrolled. In cohort one, 11 subjects completed 42-week visits. In cohort two, 16 subjects completed 36-week treatment and nine subjects completed the 52-week visit. As shown on the slide, the left graph represents the immunological response, while the right one represents the clinical response. As we shared previously, as early as 12 weeks, SIBO induced more than 60% reduction of anti-PLA2R autoantibody level in both cohorts. By week 24, the autoantibody reduction deepened, reaching more than 93% in both cohorts. Here, I want to highlight that during the off-treatment follow-up period up to 52 weeks, the green zone shown on the slide, the anti-PLA2R autoantibody reduction remains.
Following the immunological response, we observed a remarkable 24-hour proteinuria reduction during the treatment period in both cohorts as shown on the right side. By week 36, the 24-hour proteinuria decreases by 67% in cohort one and 80% in cohort two compared to the baseline. Also, I want to highlight that further reduction was shown during the off-treatment follow-up period up to week 52. In addition, consistently with the immunological response trait, more rapid and deep reduction of 24-hour proteinuria was observed. With the encouraging and exciting data from this 615 and 628 study in TMM trial, we are claiming the pivotal trial for registration pathway, which is projected to be initiated in 2026. In addition, as we know, BDK is an essential component of BCR receptor signaling pathway.
The inhibition of BDK is an attractive approach for the treatment of a wide variety of autoimmune disease that involves dysregulation of BCR function. Therefore, we are going to develop M001 in other autoimmune renal diseases besides TMA, such as ADAM, FSCS, MDD, and so on. A basket trial will be initiated in early 2026. With the potential of SIBO for multiple indications across the autoimmune renal diseases, we project the peak scale of SIBO will reach CNY 10 billion globally. Now I'm going to pass to our Chief Scientific Officer, Jennifer .
All right. Thank you, Sandra. Now, mRNA as a new class of drug revolutionized the traditional drug discovery paradigm, shifting from a screening-based approach to an information design approach. By simply altering the nucleic acid sequence, different drugs can be produced very efficiently. mRNA drug has its own unique advantages. First of all, its modular design can greatly accelerate drug discovery speeds. Second, the manufacturing is basically a universal platform base. Therefore, it can shorten production cycles and lower overall costs. Last but not least, it has the potential to be applicable across multiple therapeutic areas. Next one. Now, at Everest , we have a fully integrated and clinically validated AI-enabled mRNA technology platform and have built end-to-end capabilities across the whole value chain of this platform.
From upstream protein or antigen design to our proprietary LNP delivery system and our in-house DMC process development and self-owned manufacturing facility can ensure high-quality production of DSDT and different sizes of the GMP material to support clinical trials as well as future commercialization. Due to founding this platform, we've established a pipeline of mRNA products. Our pipeline centers around two types of products. One is utilizing targeted delivery through our in vivo mRNA CAR T. The first program, EVM-18, just generated impressive NHP POC data, and we already selected a clinical candidate and moved towards the clinical POC. Another part of our pipeline centers around therapeutic cancer vaccines. We have three programs in this category. First one is EVM-16, which is a personalized cancer vaccine program, which is in IT trial. The second is a tumor-associated antigen cancer vaccine, EVM-14. For this program, we just received U.S.
IND approval early this year, and we anticipate that in the fourth quarter of this year, we should receive China IND approval. Our immune modulatory cancer vaccine program, EVM-15, just finished a preclinical proof of concept. We've selected a clinical candidate and will move towards IND-enabling studies. In the next few minutes or for the next few slides, I will give a brief update of progress made for each of these programs. First one is EVM-18, our mRNA in vivo CAR T. The left side graph sort of explains how mRNA in vivo CAR T works. Basically, we have CAR-encoding mRNA encapsulated in LNP. On the surface of this LNP, we conjugated a T-cell targeting enzyme.
Once introduced in patients or in vivo, this TLNP will bind to T cells, and CAR protein can be produced in T cell and expressed on the surface of T cell, therefore transform a regular T into a CAR T that can kill a target cell. We think in vivo CAR T can address many of the challenges encountered with the autologous CAR T. First of all, it's off the shelf, so easily scalable, and the production cost is very low. For the patient, there is no lymphodepletion needed, therefore reduced the risk of infection. The PKPD is predictable and tunable. Because it's cell-free production, the quality can be better controlled. We all know there is a new modality called T cell invasion, TCE, that's been very actively developed in both oncology as well as autoimmune disease.
We believe that CAR T versus TCE has the advantage of CAR T can really elicit very deep depletion of pathogenic B cells in tissue, therefore allowing the patient to achieve immune reset and reduce future recurrence risk. Currently, there are two technology platforms to enable in vivo CAR T. One platform is viral vector-based, represented by EsoBiotec and Interius. Their products just entered phase I clinical trials. Very early or preliminary data from EsoBiotec provided clinical proof of concept of this approach, both in terms of efficacy as well as safety. The other platform is mRNA LNP-based. The front runner is Capstan. Because mRNA will not integrate into genome, therefore this platform presumably offers better safety profiles and is especially suitable for disease-like autoimmune indications. Our Everest EVM-18 actually utilizes a similar platform as Capstan. We just finished a preclinical proof of concept study.
Our non-human primate data actually is very comparable to what was published by Capstan, both in terms of level of B cell depletion as well as overall safety. Because of the great potential for this technology, we've seen BD activities being very active. Only this year, we've seen three high-profile BDs. AstraZeneca announced the acquisition of EsoBiotec for $2.1 billion. Just last week, Acilio's subsidiary TICE also announced the acquisition of Interius. In June this year, AbbVie announced the acquisition of Capstan. These high-profile BD deals actually reflect the great potential for this approach. Next one. For our EVM-18 program, we would like to accelerate to provide clinical proof of concept data. We are taking a parallel approach. While accelerating to clinical proof of concept by launching multiple IAT studies, we are also conducting IND-enabling studies in preparation for IND submission. Next one.
Now I'm going to switch gears to talk about programs in the cancer vaccine pipeline. The first one is our personalized cancer vaccine program, EVM-16, which has completed dose escalation for the low and mid-dose, and we are now in the high-dose cohort. Overall, we see a favorable safety profile, and we also see robust immunogenicity even at very low exposure. Next one. Here is a case report for a patient with metastatic stage IV non-small cell lung cancer who had failed three lines of therapy when entered into our study. As you can see from the right side graph, even with vaccine monotherapy, we start to see good immunogenicity. The immunogenicity continues to increase with repeated dosing. After cycle five, we see very high immunogenicity in this patient. These data actually validated our self-developed new antigen prediction algorithm, EVER-NEO-1. Next slide.
The second program is a tumor-associated antigen vaccine, EVM-14. There are certain advantages of a TAA cancer vaccine. First of all, it has good tumor specificity. Second, it has more T cell epitopes. Therefore, we don't need to select patients based on HLA. This can really expand its reach. Compared to a personalized cancer vaccine, it is off the shelf. Therefore, it's well-suited for advanced disease. Manufacturing cost is also quite low compared to PCV. For this program, we obtained U.S. IND approval in March, and we anticipate China IND approval in the fourth quarter of this year. Next slide. Now, our phase I clinical design for the EVM-14 is an intracohort staggered dose escalation design. This will enable us to quickly identify RP2D for both the mono as well as combo cohorts.
Patients that will enter into this phase I trial would be those with squamous non-small cell lung cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma. This is based on their high expression of at least one of the five TAAs encoded in the vac. The primary endpoint for this study is safety and tolerability, but we will also explore other endpoints, including ORR, PFS, and immunogenicity. Next one. As I said, we obtained U.S. IND approval, and currently, U.S. site initiation is being launched, and we are on track to enroll first patients next month. Towards this goal, our Jiaxin manufacturing facility has successfully generated GMP batch, and it's been shipped to all the U.S. clinical sites.
We are glad that many of the top cancer hospitals, including MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, as well as Shanghai Changhai Hospitals, are all participating in this trial. Next one. We also have a highly innovative immune modulatory cancer vaccine program in our pipeline, EVM-15, targeting both PD-L1 and IDO. This vaccine actually has a dual mechanism of action, so it can kill two birds with one stone. I want to explain a little bit. If you focus on the left side of the figure, this vaccine can elicit direct tumor cell killing to kill those tumors that express PD-L1. At the same time, this vaccine can also change suppressor tumor microenvironment by revitalization of M1 macrophage as well as reducing suppressor Tregs population in the microenvironment. This dual mechanism of action gives advantages to this vaccine.
Like I said, it can directly kill tumor cells, but at the same time, can reverse or change the suppressor TME into a more immune-supportive TME. It will have strong synergistic effects with checkpoint inhibitors such as PD-1. Early this year, IO Biotech, who has an immune modulatory vaccine targeting both PD-L1 and IDO, just announced their phase III clinical trial results. In this trial, they compared vaccine plus KEYTRUDA versus KEYTRUDA monotherapy in first-line metastatic melanoma patients. If you look at the median PFS in this trial, we can see the combination group achieved great benefits compared to the KEYTRUDA monotherapy group, especially for those patients with PD-L1 negative. If you focus on the bottom sort of figure, PD-L1 negative subgroup, the combo achieved the median PFS of 16.6 months versus KEYTRUDA monotherapy is only 3.0 months PFS.
Next one. IO Biotech's vaccine utilized the traditional peptide technology, and we actually used mRNA LNP technology for this immune modulatory vaccine. Preclinically, we can see that our vaccine can really break self-tolerance, elicit very strong immunogenicity in transgenic mouse. It can also give very impressive anti-tumor efficacy. If you focus on the middle panel, two graphs, both prophylactic as well as therapeutic dosing can lead to significant anti-tumor activity. The bottom graph is actually a survival curve. As expected, mice receiving vaccines actually have prolonged survival compared to PBS groups. Now, preclinically, we also provided evidence or data to support this dual mechanism of action for this vaccine. As shown on the right side, we can see that the group that received EVM-14, there was an increase of CD8 to Tregs ratio as well as M1 to M2 macrophage ratio.
Now, both Tregs and M2 macrophage contribute to the suppressor tumor microenvironment. Therefore, by lowering these two populations, we can turn the TME into a more immune-permissive condition. This program just achieved preclinical POC and will move ahead to IND-enabling study next year. With that, I'll hand over to Rogers to give a summary.
Okay, thank you. We recently announced a strategic equity investment of $30.9 million in Nasdaq-listed I-Mab shares, increasing Everest Medicines' ownership to 16.1%. The two companies have complementary oncology platforms, with I-Mab's differentiated 4-1BB platform and bispecific antibody pipeline pairing well with Everest 's existing mRNA cancer vaccine and in vivo CAR T platform. Through collaboration, we have the potential to create future synergies in both global clinical development and commercial access in Asian markets. Additionally, we have been impressed by I-Mab's data recently presented at the 2024 ASCO GI conference, which demonstrated an ORR of 83% in combination with immunotherapies in phase I-B trial of first-line gastric cancers. We look forward to the next key data readout in the first quarter of 2025. As of August 28, the latest closing price of I-Mab was $4.25, representing an increase of approximately 118% growth compared to the placement price of $1.95.
Next slide. As we look ahead, our growth will be powered by two complementary engines: commercialization and in-house discovery. On the commercial side, we are entering an exciting phase with multiple new trending catalysts. Nefecon continues to expand, supported by upcoming updates of global and china IgANN treatment guidelines, and we are preparing commercial launches across China, Taiwan, and South Korea. VELSIPITY is also moving rapidly towards markets with NDA approvals expected across several regions, including mainland China, Taiwan, and South Korea. Local manufacturing projects in Jiaxing are on track to complete the trial run to support our NRDL negotiation plans in 2025. Meanwhile, XERAVA will advance its own localization projects while initiating NRDL negotiations next year. At the same time, our in-house discovery platforms are beginning to deliver meaningful clinical and preclinical milestones.
EVER001 will soon report important one-year follow-up data, while our in vivo CAR T platform is on track to launch clinical drugs. From the mRNA cancer vaccine pipeline, EVM-14 is advancing into U.S. and China clinical trials, with initial readouts as early as the first half of next year, and the immunomodulatory program aiming to finish IND-enabling studies next year. Taken together, this dual-engine strategy of commercial execution and discovery innovation positions us to both expand near-term revenues and unlock transformative long-term growth. Next, now I would like to lay out our long-term vision of the company to become a leading global biopharma by 2030. The first is our commercial portfolio of four foster drugs, Nefecon and VELSIPITY. We believe that each of these products could grow to over CNY 5 billion in sales at peak. These are two key commercial pillars in the near term.
They are also supported by the high-potential portfolio consisting of XERAVA in our anti-infective segment, which we believe can contribute CNY 1.5 billion in peak sales and is nearly on the mark. These commercial segments will also include a cephalosporin cannibal vaccine, which similarly has CNY 1.5 billion in peak sales. We also believe we can derive significant value from SIBO, which recently reported strong results in PMN and can be studied across other autoimmune and renal conditions. SIBO, previously called EVER001, is truly a pipeline in a product, and we believe it has the potential to deliver CNY 10 billion in peak sales globally across its different indications. We are also planning the leverage of RMB mobilization to in-licensing other development stage assets, which we believe could contribute another CNY 2 billion in sales over time.
Finally, you have heard us speak exclusively about our two internally developed oncology platforms, which continue to grow and advance. Here, we are ongoing programs in in vivo CAR T as well as monoclonal mRNA cancer vaccines, which are either in IND or advancing into the clinic in the coming years. These are high-valued programs with global rights that we should also honor to boost the overall goals of the company as we execute on our vision to become a leading global biopharma company. Thank you. Now let's start our Q&A session.
Thanks a lot. We are now open for the Q&A session. For participants joining through PC or app, please click the raise hand button at the bottom of the screen to queue up for voice questions or text your questions as messages. For participants who joined through Douyin, please press star one to queue up for questions. The first question comes from Goldman Sachs, Lin hai Zhao. Please go ahead.
Good morning. Thanks for taking my question. I'm Lin hai from Goldman. Congrats on the very exciting results. I have three questions. One is for VELSIPITY, and the second is for EVER001. The third, if time permitting, I would like to know more about the mRNA platform. For the first question, I noticed that we raised the peak sales for VELSIPITY to CNY 5 billion. I just want to understand a bit more about what gave us the confidence for the raise and what are the key assumptions underlying the current peak sales estimate. Given the product is expected to get approval in early 2026, what have been the commercial preparations? What's the overall commercial strategy for this asset? For example, what patients would be our priority? Any thoughts on how we increase the penetration in the longer -term? That's the first question. I'll follow up later.
Sorry, I take your first question. Thank you for your question. I think the potential of VELSIPITY is higher than we previously stated. There are several reasons. One is that the data is pretty strong. As Jeff mentioned, our Asian study data is already accepted by Lancet . You will see the data, especially on the mucosal healing rate. As we apply percentage in our slides, it's nearly 62% in endoscopic healing and 52% of the deep mucosal healing. Very high numbers. If we compare with other currently widely used biologics, small molecules, I think we are at the, I would say, potentially best in the disease treatment. Of course, as I mentioned before, it's not a head-to-head comparison. If you're looking into the phase III data, we use the most strict criteria to evaluate the clinical outcome of up to 52 weeks treatment.
This is number one. I think this market is previously underdeveloped because the available choice is not as good as patients expect in terms of efficacy, in terms of safety profile. You know, second inhibitors have black box warning. Biologics have, you know, I would say, not inconvenience. It's infusion. They have kind of secondary value of watching the drugs at the second year and other considerations. If this market is underdeveloped, if you're only looking at how many patients treated and how many patients actually diagnosed. Currently, nearly half a million patients have been treated. If you're looking at the compliance rate, it's very low. The conclusion is this market is underdeveloped. If you're taking this nearly half a million patients being treated and times with their annual treatment cost, it's nearly, let's say, CNY 40,000- CNY 50,000 per year. As reimbursed, then you can clearly calculate the market potential.
The market size is about CNY 15 billion- CNY 40 billion- CNY 50 billion. If we take, you know, as the market is also growing year by year, right? In five years or go to 1 million patients, then you can clearly calculate. If we only take about, let's say, 30% or 20% of the growth market, then you can clearly figure out the peak sales can be CNY 5 billion. I think that's a major reason. To the second part of your question, what's the preparation? The most important thing is, you know, getting prepared for the market, prepare the market, the brand, and our own, you know, sales team buildup starting from this year. There are some milestones. Number one is that, you know, most importantly, we are planning to get the, we're entering into NRDL negotiation next year. Before that, currently, we are building our own pivotal team.
For next year, we are planning to hire about 120- 150 sales reps on the ground with strong medical and marketing support, mostly working with KOLs on the guideline promotion. As you know, VELSIPITY is strongly recommended by global guidelines. We have a lot of things to do in China to convince the KOLs and as well as our physicians to support our proficient in, you know, our track for the first-line pivotal choice over others, especially because the deep mucosal healing rate is very high. On the other side, you know, medical market access is also important. Next year, we will have, I would say, sampling programs to gain the experience of patients for both patients and physicians to prepare the market. Basically, that's the preparation for next year.
Of course, on the production side, we are now doing a tech transfer from Pfizer to the production capacity in our Jiaxin site. Make sure once we get a reimbursement in 2027, then we can have enough supply to fill the, you know, our peak sales. Those are the things we are doing now for the preparation for VELSIPITY to the CNY 5 billion peak sale. Thank you.
Thank you, Rogers. Very comprehensive and helpful answers. My second question regarding the EVER001, I found that we have a more detailed clinical development plan for 2026 with a phase II basket trial for 1Q and also the potential pivotal trial also planned in 2026 in EMN. I just want to direct your thoughts on how we are planning for the next steps, particularly. Given I understand that we are still undergoing potential BD negotiations during the same time, and how prepared are we to launch this 2026 trials, and how convicted we are in terms of finding a partner to do the pivotal trial or versus we're doing it independently in-house? Thank you.
Of course. And Ying et al.
Yes, sure. Thank you for the question. Wonderful. As we just presented, yes, we did it in, actually, let me talk about the first where we did it in the design stage. Actually, we currently have an IND with MSCB. We may just do a current amendment of the IND or either the protocol amendment just as a basket trial for our current, you know, H1B, H2A studies. It could be, should be, used, you know, regular pathways. The study design is almost at finalization. After the interaction with the health authority, only expect that the trial can be initiated in early next year. That's for a basket trial. For the typical study, we also need the finalization of the development plan stage. Our first step probably is, we plan to do our global typical studies.
Our first step of interest in regulatory interaction first is to go to the U.S. with FDA. We are planning to have, you know, the health authority interaction towards the end of this year, where we follow up with other health authorities like the EMEA or China CDE, that's a plan. That's an instantaneously, you know, probably we are in the CMC optimization stage, we are in sort of correlated with our timeline. Once the, you know, health authority interaction is done, then we can initiate the phase III study. In terms of how to do the studies, I can probably add more, you know, either partnership or in-house use.
Okay. Thank you. Thank you, Sandra. Ling, thanks for the question. I think, you know, let's, let's, I think we have been very consistent from a couple of calls back that, you know, with the EVER001, I think we have received very, very encouraging preliminary data. As a reminder, in September, we will have all 52-week data for all of the phase I-B/II-A study patients. I think that's an important milestone. Our first principles have always been that we want to access the resources, both financial and development capabilities, to accelerate the development of EVER001, or what we are calling SIBO for short. We also want to make sure that if we execute a strategic transaction, it reflects the true value of this asset.
Now, what's changed is the first principles have not changed, but what we have now is much broader capabilities and a much stronger financial position. That is why we are putting in place plans for the next study in primary membranous nephropathy, which we believe is a phase III pivotal study. We are also reminded that this product is a pipeline within a product. Therefore, we want to start to generate some proof-of-concept data in additional autoimmune-driven renal indications. We think that would further unlock the value of SIBO. In that process, we have not stopped talking to potential partners. If there are options that could help us bring in the right expertise, the right resources, accelerate the development, and provide the appropriate value for this asset, we will definitely consider that.
We think that it's important to have an organic plan as an alternative to be able to unlock such a strategic option.
Thank you, Ian. My third question is about our mRNA platform, particularly on the strategic planning in our different programs. Recently, we have seen increasing industry interest in the in vivo CAR T. On the other side, we're seeing the increasing public discharge, particularly in the U.S. for the mRNA vaccines. What is your perspective on the future potential of these two therapeutic areas? One is for the in vivo CAR T, and the other is the mRNA vaccine. From a value maximization perspective for Everest Medicines, do we have a strategic ranking on the current programs?
Yeah, I'll ask you Jennifer's question, then we can lay it out.
Sure. Thank you for the question. As you said, you know we do have two categories of products based on mRNA platform. One is the mRNA LNP CAR T, right? As you can see, we are actually getting a lot of efforts in this area to accelerate further development for our EVM-18. We this year finished all preclinical proof of concept studies in both NAOS and NHP. We believe our data is quite comparable to that published by Capstan. Therefore, we are taking this parallel approach, right? One is to launch several IAT to quickly generate human proof of concept data. At the same time, we do want to file formal IND so that we can follow clinical development to hopefully bring this asset to late-stage development. We anticipate that next year, we're going to see quite a bit of data from this program.
In terms of mRNA therapeutic vaccine, we do have several programs ranging from personalized cancer vaccine all the way to off-the-shelf immunomodulatory or tumor-associated antigen vaccines. We do believe that all of these vaccines or products have their own place in helping cancer patients to achieve long-term survival benefits or to reduce their recurrence risk, right? Our strategy in this area is a certain program. We will do U.S. and China filing. Some other programs, we're going to be more focused in China for China markets. I guess the detailed strategy would depend on each asset characteristic and our company's long-term goal. To your point of current new development of mRNA vaccine in the U.S., we believe that, first of all, we cannot comment too much on that policy, but we believe that this probably will affect more of the prophylaxis, infectious disease vaccine, rather than therapeutic cancer vaccine.
Obviously, we have to wait and see. We know there are several high-profile products such as Moderna's personalized vaccine that will release phase III data next year. Let's see how U.S. regulatory builds these products. Yeah. Rogers and EMC, feel free to chime in.
Okay. Thank you, Jennifer. I think maybe just, you know, I'll add a few points. First, just in terms of these two platforms, we think both are very important and core strategic platforms for the company. I'm talking about the mRNA in vivo CAR T platform and the mRNA therapeutic vaccine platform. There's quite a bit of overlap between the two platforms, but we believe that they are distinct and have significant opportunity in the global market. In terms of the regulatory, I think what we have seen is that this year with the new administration in the U.S., it's anything but stable, right? Things change all the time. I think for us, we truly believe that any regulatory authorities at the end of the day will be making decisions based on science and based on data, right?
If generating those data is going to become more challenging in the U.S., that plays to our advantage to be able to enroll patients and generate those data in China and other territories. Ultimately, I think we feel very good about both of these places because there are a lot of other people working in this area, and they can generate data that provide proof of concept as well and help us guide the direction of where we will explore these assets for differentiation. We're very much focused on generating our own data. At that time, we think we believe the regulatory authorities will see the value of these assets and react appropriately.
Okay, I think I should know. I have no further comments. Thank you.
Thank you, Ian and Jennifer, for the sharing. Definitely looking forward to more data updates from this platform. That's all for me. Thank you.
Thank you. Thanks, Ling hai.
Okay. That's the end of today's investors' call. Thanks, everyone, for your attendance.
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