Everest Medicines Limited (6HN.F) Earnings Call Transcript & Summary

Good morning or good evening. Welcome to the Everest Medicines business update call on results from EVER001 Phase Ib/IIa clinical study and Primary Membranous Nephropathy. If you are a Chinese speaker, there is a simultaneous stream with instant translation happening in parallel with this call. Please be advised that today's conference is being recorded. Joining us today are Dr. Richard Lafayette, Professor of Medicine, Stanford University Medical Center and a preeminent nephrologist. Mr. Rogers Luo, Chief Executive Officer of Everest Medicines, Mr. Ian Woo, President and Chief Financial Officer; and Ms. Sandra Zeng, Chief Medical Officer. Before we get started, I would like to remind you that speakers on this conference call may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the company or of its officers with respect to the business operations and financial condition of the company, which can be identified by terminology such as will, expects, anticipates, future, intends, plans, believes, estimates, confident and 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 of its affiliates, directors, officers, advisers or representatives has no obligation and does 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. Let me now walk you through our planned event today that is discussing Primary Membranous Nephropathy or pMN and the strong data Everest has generated to date. Ian Woo will briefly introduce Everest Medicines as well as talk about its leadership strategy in the renal space. Dr. Richard Lafayette, Everest's esteemed key opinion leader, will then provide an overview of pMN, its epidemiology and treatment landscape. He will then turn the call over to Ms. Sandra Zhang, Chief Medical Officer, who will share the latest data from the ongoing Phase Ib/IIa study of EVER001, the responsible BTK inhibitor in pMN. Finally, Ian will wrap up the call, and we'll open it up for your questions. We are privileged today to have a preeminent nephrologist with us on the call who can share his knowledge of pMN and lack of suitable therapeutic agents. Dr. Richard Lafayette is the Founder and Director of the Stanford glomerular disease center and its fellowship training program and has led a number of important glomerular disease trials. He has more than 30 years of clinical experience and has more than 200 publications, including more than 150 peer-reviewed papers. Dr. Lafayette will also be available during the Q&A portion of the call to take your questions. I would now like to hand the conference over to your first speaker today, Mr. Ian Woo, President and Chief Financial Officer for Everest Medicines. Please go ahead, Ian.

Thank you very much, and welcome, everybody, for joining this call. Let me start by giving everyone a quick snapshot of Everest Medicines, especially for those who may be less familiar with the company. We're founded in 2017, and we have grown into a fully integrated biopharma company with over 700 employees across discovery, development, manufacturing and commercialization. We have built a diversified and innovative portfolio with 3 launched products across our core therapeutic areas, including renal disease. We are listed on the Hong Kong Stock Exchange and currently have a market capitalization of over USD 2.5 billion. Our growth strategy is powered by a dual-engine strategy. On one side, we have built a focused and increasingly efficient commercial platform that is growing in scale and profitability and supported by 3 launched products to date. NEFECON is also known as TARPEYO in the U.S., XERAVA and BELZIBIDI. On the other side, we have developed deep in-house R&D capabilities. Our growing pipeline includes programs like EVER001 for our primary membranous nephropathy, which is the focus of today's discussion as well as a discovery platform that spans from in vivo CAR-T to both personalized and off-the-shelf cancer vaccines, addressing significant unmet needs in oncology and autoimmune diseases. Renal disease is a core focus at Everest, and this slide summarizes investments in the space. Autoimmune renal diseases like IgA nephropathy and primary membrane nephropathy are considered rare in the U.S., but they affect millions of patients in China, underscoring a major unmet need in our region. We've already made significant progress with the approval and launch of NEFECON for IgAN, and we've secured NRDL reimbursement. We're actively building our nephrology franchise through multiple avenues, clinical development of EVER001, diagnostic tools like our Gd-IgA1 immunohistochemistry assay, business development efforts and new discovery programs, all aimed at reinforcing our leadership in this important space. With that, we get over to Sandra Zeng, our -- with that, let me turn it over to Richard, Dr. Lafayette to go over the pMN overview and treatment landscape.

Hello, everybody. It's great to be with you. We're going to just take a look at membranous nephropathy because it is such an important category of disease for patients with kidney disease, and it is an important cause of suffering and progressive kidney disease and [indiscernible] the need for dialysis or transplant. As you can see in the slide, membranous nephropathy is among the most common cause of nephrotic syndrome in nondiabetic adults and the idiopathic form, which is about 80% of all cases, really needs direct attention. There are secondary forms related to other issues such as infections, drugs, auto-immunity or cancers, but still the bulk of patients have this idiopathic type, which is caused by antibodies. Again, the annual incidence of membranous nephropathy are estimated to be about 10 to 12 per every million patients in North America, similar with a broader range in Europe at 2 to 17 per million, and it's estimated as about 180,000 patients in Western countries. And as you heard before, likely around 2 million patients in China. And as the population ages, we tend to see more and more disease. So this incidence and prevalence is growing. Among patients who have this disease, they generally present with what we call nephrotic syndrome, that's clinical evidence of very high protein losing in the urine usually with urine protein losses more than 10 to 20x normal. So in this range of 3.5 grams to as high as 20 grams per day, which leads to lower blood albumin levels and very profound salt retention, which leads to swelling. Some of the patients can have blood in the urine as well. This is typically a disease of middle-aged to older adults and generally affects men more often than women around 2:1 predominance. Again, even among those patients with more mild disease, the majority of them, about 60% of those who start with more mild symptoms and more mild proteinuria will indeed progress to the full nephrotic syndrome with symptomatic disease and a substantial risk of prevention to chronic kidney disease and to kidney failure. Natural history studies have demonstrated that kidney failure will develop in up to half of these patients in a period of about 10 years and presently we're using standard of care therapy that's not approved medications. Again, novel treatments that aim to achieve remission early and sustain them, prevent disease progression and minimize the risk of side effects are still desperately needed. Next slide, please. So again, bear with me as we talk about the pathogenesis here. As we discussed, sometimes membranous nephropathy, which is a disease of antibody deposition in the kidney filter in the capillaries that lead to dysfunction and the ability to filter large amounts of salt from water, but retain protein in the blood. In this idiopathic form, we've now identified a predominant antibody called phospholipase A2, which binds to the phospholipase A2 receptor that is in the kidney in a very specialized cell that maintains the ability to allow filtration to occur, but maintain protein in the blood. So antibodies to this phospholipase A2 receptor can cause injury to the capillary leading to proteinuria, hematuria and eventually post progression to kidney failure is PLA2R receptor is expressed on podocytes where these antibodies, the anti-PLA2R antibodies bind and can form immune deposits. We've seen that anti-PLA2R titers can actually define the disease and show patients at risk for the diagnosis. It's been used in some patients who are too dangerous to biopsy to make a diagnosis, but the level themselves can be prognostic and response to treatment is often seen by an early reduction in these PLA2R antibody titers and you can guide treatment decisions when you see those responses or don't see the responses. Again, we know that patients who present with very high levels of these antibodies correlate with 4 responses to therapy and take a longer time to come to response and the higher the level, the more likely they have a severe type of membranous nephropathy with a higher risk of nephrotic syndrome, a greater chance of renal function deterioration as mentioned. And in the cartoon, you can sort of see that what happens that circulating antibodies can be made, antibodies are created by B-cells that are exposed to antigen, and then become activated and class switch to make immunoglobulins to that specific antigen and that antibody response is maintained by memory cells such that you can have short- and long-term plasma cells making antibodies, in this case, the best example would be the antibody to the PLA2R protein, which is in the kidney cell and leads to destruction of the kidney cell and injury from there. And again, this B-cell biology, as you will see, is very dependent on multiple cytokines, multiple interactions, including with protein BTK. So if there is unrelenting antibody deposition into the kidney filter, this will lead to progressive inflammation, complement activation and replacement of kidney cells with fibrosis leading to chronic kidney disease. Next slide. So what we have also learned that in patients who are treated with immunomodulatory or immunosuppressive therapy that what we like to see in patients with PLA2R-mediated disease is that this anti-PLA2R autoantibody is depleted. And this happens early in patients who are having successful responses to therapy, as you can see in the orange bar in this slide that was published almost 10 years ago that patients who achieve early and eventually complete antibody depletion are far more likely to have clinical response, reduction of proteinuria, improvement of symptoms and stability of their kidney function early, as you can see, it is 6 to 12 months. The majority of patients are clinically improved, while patients who do not have their autoantibody depleted effectively will generally not see clinical responses. And if they see it, they see it much later, perhaps when other therapies are deployed or if their immune system decides to get better through its own methods. So again, the ability of what we call immunology response in the case of PLA2R antibody mediated disease, the disappearance of those antibodies is incredibly important and effective at predicting clinical responses. Next slide. So again, in the natural history of patients with primary membranous nephropathy and with good follow-up, it's been clearly defined that patients are at risk. And the figure on the right, patients who do not have a reduction in their proteinuria of a significant fashion will go on and will frequently develop kidney failure, you can see in 10 years, more than half of the patients who do not respond to treatment or have a reduction in their proteinuria that's substantial, will develop kidney failure. Both partial responses, which are defined by at least a 50% reduction in proteinuria to less than 3.5 grams per day will indicate a better prognosis and nearly perfect outcomes occur in patients who have a complete remission getting to normal levels of proteinuria with stable kidney function. So it's very important to try to achieve responses. The problem with partial remission is that patients who achieved partial remission with longer follow-up, sometimes can have relapse and need recurrent therapy. Patients who achieved complete remission do very well, and therefore there's a continued need for therapies that can achieve more complete remission and maintain those remissions long-term. Next slide. Again, presently, our international guidelines can classify patients from low to very high risk of progression to kidney disease, low risk is really determined by patients whose kidney function is intact. Their proteinuria is low grade. Their blood protein levels, or serum albumin are also close to normal. And in general, these patients have -- if they have PLA2R-mediated disease, low or absent levels. Moderate risk or will be patients who still have intact kidney function, but heavier proteinuria that does not respond to 6 months of just observation and would be those patients who don't fulfill the high-risk criteria. And again, higher levels of PLA2R antibodies will leave patients at higher risk as well patients who have lower kidney function at presentation, higher degrees of proteinuria, greater than 3.5 grams per day, again, without a decrease after 6 months of observation for those patients who have very high-grade proteinuria, very low levels of blood proteins, high levels of these PLA2R antibodies. And there are other markers that are used internationally that are listed on the slide, very high-risk patients are those who present right away with life-threatening nephrotic syndrome, which sometimes leads immediately to infections that can be life-threatening or clotting with deep vein thrombosis or pulmonary embolism or when there's obvious deterioration of kidney function month-by-month, those are higher-risk patients. And these risk criteria are important to guide patient care. Right now, the international guidelines are that low-risk patients generally can do well over many years of follow-up. So we just wait and see how they do. usually giving them RAS inhibitors just to make sure their proteinuria is maintained as low as possible. For moderate risk, sometimes we can follow them a little bit longer or give them therapies that seem to be effective, such as rituximab or calcineurin inhibitors with low-dose corticosteroids. For higher-risk patients, we certainly need to treat them because these patients do have a high risk of progressive kidney disease and will often end up needing dialysis in 6 to 10 years without intervention. So there, we often use rituximab, but we may also use cyclophosphamide with glucocorticoids and more rarely calcineurin inhibitors or calcineurin inhibitors together with rituximab. And for the very high-risk patients, the guidelines recommend aggressive therapy with chemotherapy in the form of cyclophosphamide and glucocorticoids as the best choice. But these nonapproved therapies still have their basis of recommendations on limited data and still leave clinicians uncertain, which therapy is actually ideal even in these different categories of disease. Next slide. And again, that leaves us with the point that there's still a highly significant unmet medical need in membranous nephropathy. First, no treatment has been approved, so getting patients to their treatment requires a lot of work with insurance, with having patients understand that this is appropriate for their condition. All the current treatment options are used off-label. Furthermore, there's a range of responses depending on the baseline risk of the patient. That is certainly incomplete. In general, across these therapies, only between 60% and 75% of patients will respond to treatment and failure to respond, as I pointed out earlier, leaves the patient at a high risk of progression to kidney failure. Furthermore, the current treatment options that we have are each associated with substantial side effects. For chemotherapy, major infections and myelosuppression, secondary cancers or calcineurin inhibitors, nephrotoxicity and metabolic disorders. And for rituximab, there are still risks of infusion reactions and serious infections. Furthermore, even among those patients who respond, relapses are well known to occur. They're expected in patients who get calcineurin inhibitors with up to 70% of patients in some studies having relapsed within 3 to 6 months of stopping therapy. And even for rituximab or for cyclophosphamide-based therapies, relapse have been reported in 20% to 30% of patients who seemingly had good responses. And this significant unmet need has left to the present search for more specific targeted and safer and better tolerated immunomodulatory drugs aiming at improving the presently unacceptable clinical outcomes that our patients face. So thanks for your attention. I will just mention again that Bruton tyrosine kinase inhibitors really sit in the right place to be a targeted therapy in the pathogenesis of membranous nephropathy. As I mentioned, membranous nephropathy is a classical antibody-mediated disease, where antibody deposits in the kidney filter after today's complement and leads to target organ damage. And BTK is an incredibly important enzyme to the healthy B-cells, allowing activated B-cells to fulfill their process of maturation into functional plasma cells. And so it's really very, very important that BTK inhibitors have been shown to have broad immunomodulatory effects on these B-cells. They have additional effects on other immune cells, which differs from the mechanism of very specific B-cell depleting agents such as rituximab and other anti-CD20 antibodies compared to these anti-CD20 antibodies, the oral formulation as a pill, allows for more rapid recovery of B-cell function when it is stopped and is a more tolerable delivery mechanism. So we still have the ability to halt specific antibody production to lead to less immunosuppression, not to B-cell depletion, but to have B-cells behave better, and therefore, to get rid of target antibodies, such as this PLA2R antibody that's so important to membranous nephropathy in a well-tolerated and safe fashion. Next slide. And now I can turn it over. Thanks again for your attention.

Thank you, Dr. Lafayette. I'm going to give you the update today from our ongoing EVER001 Phase Ib/Phase IIa study in pMN patients. EVER001 is a reversible covalent BTK inhibitor that we are developing for autoimmune renal indications. The first one being the primary membranous nephropathy. EVER001 selectively forms a reversible covalent bond resistent 481 in the BTK kinase domain, but it differentiates from other BTK inhibitors currently marketed for other indications, which are either covalent in reversible BTK inhibitors or noncovalent reversible BTK inhibitors. The covalent binding mechanism of EVER001 ensures strong BTK inhibition, while its reversibility presumably will lead to less off-target toxicity. If you look at the bottom left side table compared to the ibrutinib, EVER001 has similar potency against BTK, but has much better selectivity against off-target kinase. For EGFR, ITK and the TEC family kinases, which are thought to be associated with undesirable safety profiles, EVER001 demonstrated a superior selectivity even compared to the more selective BTK inhibitors such as zanubrutinib and [indiscernible]. We also believe that a relatively fast off-rate for EVER001 combined with its high selectivity may further benefited the safety profile. So here, I just want to briefly describe the study design of the ongoing Phase I, Phase IIa study. So this is a Phase Ib and the Phase IIa study in Chinese pMN patients with positive anti-PLA2R antibody. The trial is being conducted in 2-dose cohort. The subject in the dose Cohort 1 started with 100-milligram QD for 4 weeks, followed by 100-milligram BID for 32 weeks with a total of 36 weeks of treatment. The subject in cohort 2 received a 200-milligram BID dose for a total of 36 weeks of treatment. The primary endpoint of the study is the safety and the tolerability, the second endpoint due for the efficacy including the percentage change from baseline in 24-hour proteinuria and anti-PLA2R antibody levels, UPCR, EGFR as well as clinical remission and the immunological remission. By the date cutoff March 21, 2025, total 31 subjects were enrolled with 30 subjects in the Cohort 1 and 18 subjects in Cohort 2. So in the Cohort 1, 11 subjects completed the 52-week visit, and in the Cohort 2, 12 subjects completed 36 weeks of treatment. Now I'm pleased to report the encouraging results from this analysis. So first, let's look at the immune response. The blue curve represent the Cohort 1, the red curve represented Cohort 2. As early as 12 weeks, EVER001 induced a more than 60% reduction of -- 60% -- more than 60% reduction of anti-PLA2R antibody levels in both Cohorts. By week 24, the antibody reduction depend reached over 93% in both Cohorts. Even during the off-treatment period, the reduction remains within a range of 89% to 96%. If you look at the curves obviously, we observed a more rapid reduction in Cohort 2. Clinically speaking, anti-PLA2R antibody is a specific pMN diagnostic biomarker. Not only that, it also has an important prognostic value. As Dr. Lafayette just presented a moment ago, completely antibody depletion at 6 months during the treatment is a strong, independent prognostic predictor of clinical outcome. So in our study, we observed as early as week 4 to 8, the immunological complete remission was induced by EVER001. In Cohort 1, actually represented by the blue bars, 77% of subjects experienced immunological complete remission at week 24 to week 36. In Cohort 2, represented by the red bars and all the subjects have reached the immunological complete remission from week 36 onwards, even including the off-treatment follow-up period. Here are the workforce clause of individual anti-PLA2R antibody, percentage change from the baseline by visits at week 12 with 24 and 36. Again, these plots clear show rapid and completely reduction in most subjects during the treatment period. And of course, and then also another thing I want to point out, the immunological response depend over the treatment course because we have different pain points. Next slide, please. So now let's look at the clinical response. As we know, the clinical response always follows that the immunological response. In this study, we observed a remarkable 24-hour proteinuria reduction and during the treatment period in both Cohorts. By week 36, the proteinuria decreases by 37% in Cohort 1 and 80% in Cohort 2 compared to the baseline. And the further reduction was shown during the off-treatment follow-up period because the treatment only lasted for 36 weeks. And with large geometrical Least Square mean reduction by 78% at week 44 in Cohort 1 and 83% at week 52 in Cohort 2. Consistent with the immunological response trend, more rapid and deep reduction of proteinuria was observed in Cohort 2. Next slide, please. Therein further, we look at the proteinuria remission, which is the clinical remission. So the clinical remission was achieved in over 40%, 50% of projects within 20 to 28 weeks in both Cohorts. By week 36, clinical remission was achieved in 69% of subject in Cohort 1 with 2 CR. While in Cohort 2, clinical remission rates was 91.7% with 5 CR. Even during the off-treatment follow-up period, 100% subject in Cohort 2 show clinical remission. Although we have to take into consideration only 7 subjects have reached to 52 weeks visit. So again, here is the workflow clause of individual subject of proteinuria reduction and visited week 24, 36 and 52. Apparently, early and sustained 24-hour proteinuria reduction was observed in most subjects in Cohort 2. After the immunological response and then also clinical remission. Now let's look at the serum albumin change. As we know, the decrease in serum albumin with associated warning are important symptom and sign in pMN patients. As shown here, with the reduction of 24-hour proteinuria over the treatment course, the serum albumin increased gradually and returned to the normal at week 36 in both Cohorts. By the date -- cutoff date, EGFR was stable. And so far, we did observe that limited relapsed case up to 52 weeks. In subjects achieved a complete remission by week 36, 2 subjects in Cohort 1 relapsed. No subject in Cohort 2 relapsed by week 52, but being aware of only 7 subjects followed up to 52 weeks in Cohort 2. We will need a longer follow-up of more subject to monitor relapse rate, especially for Cohort 2. Here, it comes with the safety and the tolerability. Consistent with previously reported data, most subjects experienced Grade 1 or 2 adverse events. To date, EVER001 treatment in both dose levels are safe and well tolerated without clinical meaningful adverse events associated with other BTK inhibitors. This highlights EVER001's improved selectivity, which is consistent with its mechanism of action. And we did do some comparisons, compared some of the key measures of efficacy to the historical data from the current standard of care, including rituximab or cyclosporin, cyclophosphamide, of course, this is across clinical trials. So taking into account the caution one should have when competing data across different trials, we believe the results we get so far in terms of immunological complete response, complete remission and 24-hour proteinuria remission, especially in the high dose level Cohort 2 suggests EVER001 compares very favorably to the options currently available in pMN patients. So in summary, EVER001 induce the early offset in the high rate of immunological response and clinical remission in pMN patients. Notably, the high dose Cohort 2 induce the early deep and sustained reduction in both anti-PLA2R antibody level and 24-hour proteinuria. EVER001 is safe and that correlated in both dose levels without clinical meaningful adverse events associated with other BTK inhibitors. So the safety and efficacy data from the ongoing Phase Ib/IIa study continues to support a further global clinical development of EVER001. Now I'll turn it over to Ian.

Thank you very much, Sandra. So we are truly excited about the emerging longer-term data from the EVER001 Phase Ib/IIa proof-of-concept study. It is great to see the depth and durability of the effect from 001 without any new safety signals. Let me quickly talk about catalysts. First, we are expecting to disclose full 52-week data from all 31 patients in September of this year. Second, what we have heard from leading renal KOLs, such as Dr. Lafayette and others is that EVER001 should be developed quickly and aggressively, given the strength of the data, ideally straight into a pivotal Phase III trial. Everest Medicines is going to work with regulatory authorities to align on a development program in the U.S. and in China. To make this important therapeutic option available to pMN patients as soon as possible. We will provide further guidance on the clinical development plan when we have this finalized and aligned. Third, it is probably not surprising that a number of companies have approached us to explore ex China collaborations, as they see EVER001 as an attractive late-stage asset complementary to their existing renal and autoimmune portfolios. We're not in a rush, but believe our interest will increase as we disclose more data. We will evaluate opportunities to ensure the right strategic and financial fit. Fourth, we have also heard from physicians and potential partners that we should explore additional B-cell-driven renal indications, given the positive data in pMN. And we're putting together a plan for signal-finding basket study that could significantly expand the potential for EVER001. Finally, thank you for joining our call to learn more about Everest Medicines. In addition to EVER001, we have a number of exciting mRNA cancer vaccine and in vivo CAR-T programs that we'll begin reporting out data in the back half of the year, and a strong commercial business with significant growth ahead. With that, let me turn over to Irina Koffler from LifeSci Advisors to manage the Q&A session.

Good morning, everyone. Please send us questions through the online portal. I will begin with the first one we've got. And there are a lot of off-label treatments for pMN, which include ACE inhibitors, arbs, diuretics and statins, also immunosuppressants like Rituxan or cyclophosphamide may work too. Why are these treatments inadequate?

So I can take that. And as I alluded to before, they're mainly inadequate because we already have many, many years' experience of taking patients with substantial risk membranous nephropathy and utilizing agents such as just standard background therapy with diet, exercise and RAS inhibitors and knowing that that's inadequate. Again, the cyclophosphamide and prednisone regimen can work in patients. And as I mentioned, it can work even up to 70% in patients, but carries with it very substantial risk of side effects from the steroids and from cyclophosphamide and further risks of long-term cancer risk and short-term infections. So it's a treatment that we have really tried to move away from. We thought calcineurin inhibitors would be a good choice because they also enjoy a very high response rate. But they need to be maintained because when we withdraw them in less than a year, there's extremely high rates of relapse. And even when we withdraw them at greater than a year, and we still see up to half the patients having relapsed. And there's reasonable fear of these agents because they can also have a lot of metabolic complication such as high blood pressure and diabetes. And they intrinsically can lead to kidney damage in up to 10% of patients treated. The anti-CD20 agents held tremendous promise, and they do indeed work well in some patients, have been in our best trials. They work about 60% of the time. And they, again, once given, their effects on B-cell depletion don't reverse for 6 to 9 months. So there's existing risks there as well for immunocompromised infections that patients need to be monitored closely, and rare but worry some events of leukopenia and neutropenia that need to be treated. So we really still need not only a second-line drug for the patients who don't respond to present therapy and those that relapse. So there's a definite need there. But even first-line having an agent that's easy to administer as a oral medication that you know you can stop if there's any concern for adverse events, particularly infections, but has not shown a tendency to cause adverse events or infections. And again, at this higher dose data you've seen, really remarkable impact on the specific antibodies that cause PLA2R-related membranous nephropathy and rapid and nearly complete response rates. It's just extremely exciting to think about this agent as a replacement to present therapies.

Here's the next one. Can you review the mechanism of action of EVER001 versus other investigational mechanisms being studied, for example, Biogen's felzartamab target CD38 positive immune cells, is the BTK inhibitor mechanism more relevant here?

Yes. So there's a lot of exciting things coming in the membranous nephropathy and in the antibody mediated kidney disease space. And I think that we focus rightfully so on B-cells and trying to stop the mature B-cells, the plasma cells from making the specific antibodies, but you want to have your very finest mousetraps. So you want to, again, inhibit those B-cells in a way that they can recover in case the patient is in danger of infection. You want the delivery mechanism to be convenient, so infusions and subcutaneous deliveries less pleasant and less desirable to our patients. And so the idea, again, of a drug that can be held in the case of any emergency is very, very helpful. The role of BTK not only in the maturing B-cell and plasma cell, but in other cells that may underlie the -- in kidney inflammatory response may further underlie why we are seeing indeed the rapid and nearly complete reduction of antibodies, but also the very beautiful clinical responses to see proteinuria fall rapidly and in sustained fashion and serum albumin to come up nicely. So again, and these are early days, we need more proof of concept. But yes, this particular mechanism looks very, very attractive. And it's nice you can put the genie back in the box when you need to and that you can deliver it at home in an efficient way. So thank you.

Great. Here's the third question. What do you think are some of the potential advantages of EVER001 versus other BTK inhibitors that are commercialized or under development.

Yes, I'll leave that a little bit more to the company to answer that question. Again, I'm very, very impressed by this data. I think, again, the tolerability, the safety aspects, you've heard about its ability to stay on target, making it less likely to have off-target side effects of infection or other symptoms, makes it quite attractive. And again, the data sort of stands alone as looking highly effective, highly tolerable. And so I think that's the main differentiation is where they are in their development program and in the design of the molecule to be more on target and more tolerable. And I'll turn it over to Sandra to add comments to that question.

Yes. Thank you. Dr. Lafayette. Yes, I think we just presented from both data and also mechanism of action. I think EVER001, the key advantage is just like because it's covalent binding and then also get reversible inhibition mechanism. So we believe this compound has high potency also improved the selectivities because of the off-target toxicity is less. And then -- and actually, the clinical data already show some -- the evidence, not just like preclinical. So definitely, we also -- that's the first one. Second, we think compare the data from our available data with other -- we did a comparison table there with other sort of standard of care or in development of the compounds, including other BTK inhibitors. We did see EVER001 Phase Ib/IIa study show numerically better overall clinical response and immunological response rate at week 24. And of course, we have to be a little bit careful. This is a cross-study comparison. But at least all the -- and then so maybe there's a difference in study population, and then also there's endpoint definition different or maybe statistical methodology. But definitely, the data currently gave to us very confident this compound deserves to move forward to later development. And then, so that's from the development perspective, but I just think the commercial perspective, Ian, do you want to add anything about from a commercial perspective?