Good morning or good evening. Welcome to the Everest Medicines Business Update Call on results from EVER001, phase I-B/II-A clinical study in 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, advisors, 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 Zeng, Chief Medical Officer, who will share the latest data from the ongoing phase I-B/II-A study of EVER001, the responsible BTK inhibitor in PMN. Finally, Ian will wrap up the call, and we will 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 were 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 three launched products across our core therapeutic areas, including renal disease. We're listed on the Hong Kong Stock Exchange and currently have a market capitalization of over $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 three launched products to date: NEFECON, which is also known as TARPEYO in the U.S., XERAVA, and VELSIPITY.
On the other side, we have developed deep in-house R&D capabilities. Our growing pipeline includes programs like EVER001 for 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 our investments in the space.
Autoimmune renal diseases like IgA nephropathy and primary membranous 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, let me turn it over to Sandra Zeng. Oh, let me turn it over to Dr. Richard Lafayette, to go over the PMN overview and treatment landscape.
Yes. 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 ultimately 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 non-diabetic adults.
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, autoimmunity, or cancers. Still, the bulk of patients have this idiopathic type, which is caused by antibodies. 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 is estimated there is about 180,000 patients in Western countries, and as you heard before, likely around 2 million patients in China. 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 is clinical evidence of very high protein losing in the urine, usually with urine protein losses more than 10 to 20 times 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 two to one predominance. 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 whole nephrotic syndrome with symptomatic disease and a substantial risk of progression 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. Presently, we are using a standard of care therapy that is not approved medications. 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 in the ability to filter large amounts of salt and water, but retaining protein in the blood. In this idiopathic form, we have 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 cause progression to kidney failure. This 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.
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 poorer responses to therapy and take a longer time to come to response. 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.
In the cartoon, you can sort of see that what happens is that circulating antibodies can be made. Antibodies are created by these 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 disruption of the kidney cell and injury from there. Again, this B cell biology, as you will see, is very dependent on multiple cytokines, multiple interactions, including this protein BTK. If there's 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. What we have also learned that in patients who are treated with immunomodulatory or immunosuppressive therapy, what we like to see in patients with PLA2R-mediated disease is that this anti-PLA2R autoantibody is depleted. 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, 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, the 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. 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. Again, the ability of what we call immunologic 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. 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. In 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. Nearly perfect outcomes occur in patients who have a complete remission, getting to normal levels of proteinuria with stable kidney function. It is very important to try to achieve responses. The problem with partial remission is that patients who achieve partial remission with longer follow-up sometimes can have relapse and need recurrent therapy.
Patients who achieve complete remission do very well. Therefore there is 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. In general, these patients have, if they have PLA2R-mediated disease, low or absent levels.
Moderate risk will be patients who still have intact kidney function, but heavier proteinuria that does not respond to six months of just observation, and would be those patients who do not fulfill the high risk criteria and who get higher levels of PLA2R antibodies will leave patients at higher risk, as will patients who have lower kidney function at presentation, higher degrees of proteinuria greater than 3.5 grams per day, again, without a decrease after six months of observation. Or those patients who have very high-grade proteinuria, very low levels of blood proteins, high levels of these PLA2R antibodies.
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 is obvious deterioration in kidney function month by month. Those are the higher risk patients.
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.
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 non-approved 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. Again, that leaves us with the point that there is 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 is 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. For calcineurin inhibitors, nephrotoxicity and metabolic disorders. 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 are expected in patients who get calcineurin inhibitors, with up to 70% of patients in some studies having relapse within three to six months of stopping therapy. Even for rituximab or for cyclophosphamide-based therapies, relapses have been reported in 20%-30% of patients who seemingly had good responses. 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.
Thanks for your attention. I will just mention again that Bruton's 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 activates complement and leads to target organ damage.
BTK is an incredibly important enzyme to the health of B cells, allowing activated B cells to fulfill their process of maturation into functional plasma cells. So it is 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 is so important in membranous nephropathy in a well-tolerated, safe fashion. Next slide. Now I can turn it over. Thanks again for your attention.
Thank you, Dr. Lafayette. I am going to share with you the updated data from our ongoing EVER001 phase I and phase II-A 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 with Cys481 in the BTK kinase domain. But it differentiates from other BTK inhibitors currently marketed for other indications, which are either covalent and reversible BTK inhibitors or non-covalent 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 ibrutinib, EVER001 has similar potency against the BTK, but has much better selectivity against the 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 acalabrutinib.
We also believe the relatively fast off-rate for EVER001, combined with its high selectivity, may further benefit the safety profile. Here I just want to briefly describe the study design of the ongoing phase I, phase II-A study. This is a phase I-B and a phase II-A study in Chinese PMN patients with positive anti-PLA2R autoantibody. The trial is being conducted in two dose cohorts.
The subject in the dose cohort 1 started with 100 mg QD for four weeks, followed by 100 mg BID for 32 weeks, with a total of 36 weeks of treatment. The subject in cohort 2 received a 200 mg 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 looks for the efficacy, including the percentage change from baseline in 24-hour proteinuria and anti-PLA2R autoantibody levels, UPCR, EGFR, as well as clinical remission and immunological remission.
By the date cut-off March 21st, 2025, total 31 subjects were enrolled, with 30 subjects in the cohort 1 and 18 subjects in cohort 2. In the cohort 1, 11 subjects completed 52 week visit, and in the cohort 2, 12 subjects completed 36 weeks of treatment.
Now I am pleased to report the encouraging result from this analysis. First, let's look at the immune response. The blue curve represent the cohort 1 and the red curve represent the cohort 2. As early as 12 weeks, EVER001 induced more than 60% reduction of anti-PLA2R autoantibody level in both cohorts. By week 24, the antibody reduction deepened, reached over 93% in both cohorts.
Even during the off-treatment period, the reduction remains within range of 89%-96%. If you look at the curves upwards, we observe the 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, complete antibody depletion at six months during the treatment is a strong independent prognostic predictor of clinical outcome.
In our study, we observed as early as week four to eight, the immunological complete remission was induced by EVER001. In cohort 1, actually represented by the blue bars, 77% of subjects experienced immunological complete remission by the week 24 to week 36. In cohort 2, represented by the red bars, all the subjects reached the immunological complete remission from week 36 onwards, even including the off-treatment follow-up period.
Here are the waterfall plots of individual anti-PLA2R antibody percentage change from the baseline by visits at week 12, week 24, and 36. Again, this plot clearly shows rapid and complete reduction in most subjects during the treatment period. Also another thing I want to point out, the immunological response deepened over the treatment course because we have different time points. Next one, please. Now let's look at the clinical response.
As we know, the clinical response always follows the immunological response. In this study, we observed a remarkable 24-hour proteinuria reduction 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. The further reduction was shown during the off-treatment follow-up period because the treatment only lasted for 36 weeks.
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 deeper reduction of proteinuria was observed in cohort 2. Delving further, we look at the proteinuria remission, which is a clinical remission. The clinical remission was achieved in over 40%, 50% of subjects within 20 to 28 weeks in both cohort.
By week 36, clinical remission was achieved in 69% of subjects in cohort 1 with two CR. While in cohort 2, clinical remission rate was 91.7% with five 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 seven subjects can reach the 52 weeks we did. Again, here is the waterfall plot of individual subjects' proteinuria reduction at visit 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 clinical remission, now let's look at the serum albumin change. As we know, the decrease in serum albumin with associated swelling are important symptom and sign in PMN patients.
As shown here, with reduction of 24-hour proteinuria over the treatment course, the serum albumin increased gradually and returned to the normal at week 36 in both cohort. By the date, cut-off date, eGFR was stable. So far, we did observe the limited relapse case up to 52 weeks. In subjects achieved complete remission by week 36, two subjects in cohort 1 relapsed, and no subject in cohort 2 relapsed by week 52. But being aware of only seven 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 we come with the safety and tolerability. Consistent with previous we reported data, most subjects experience Grade one or two 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. We did do some comparison, compare some of the key measures of efficacy to the historical data from the current standard of care, including rituximab or cyclosporine, cyclophosphamide. Of course, this is cross-clinical trials.
Take into account the caution one should have when comparing data across different trials. We believe the result 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, suggest EVER001 compares very favorably to the options currently available in PMN patients. In summary, EVER001 induced early onset and a high rate of immunological response and clinical remission in PMN patient.
Notably, the higher dose cohort 2 induced early, deep, and sustained reduction in both anti-PLA2R antibody level and 24-hour proteinuria. EVER001 is safe and well-tolerated in both dose levels without clinical meaningful adverse events associated with other BTK inhibitors. The safety and efficacy data from the ongoing phase I-B/II-A study continues to support the further global clinical development of EVER001. I'll turn over to Ian Woo.
Thank you very much, Sandra. We are truly excited about the emerging longer-term data from the EVER001 phase I-B/II-A 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. Richard 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 for 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 that 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. 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 will 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 gotten. 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?
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, can work even up to 70% in patients, but carries with it very substantial risks of side effects from the steroids and from the cyclophosphamide, and further risks of long-term cancer risk and short-term infections. 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, we still see up to half the patients having relapse. And there's reasonable fear of these agents because they can also have a lot of metabolic complications 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.
In our best trials, they work about 60% of the time. They, again, once given, their effects on B-cell depletion don't reverse for six to nine months, so there's existing risks there as well for immunocompromised infections that patients need to be monitored closely and rare but worrisome events of leukopenia and neutropenia that need to be treated. 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 an 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. Again, has at this higher dose stadium 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.
Thank you. 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 targets CD38 positive immune cells. Is the BTK inhibitor mechanism more relevant here?
Yeah. There's a lot of exciting things coming in the membranous nephropathy and in the antibody-mediated kidney disease space. 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 mouse trap. 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 delivery is less pleasant and less desirable to our patients. The idea, again, of a drug that can be held in the case of any emergency is 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 in a sustained fashion and serum albumin to come up nicely. These are early days. We need more proof of concept. But yes, this particular mechanism looks 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?
Yeah. I'll leave that a little bit more to the company to answer that question. Again, I'm 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. Again, the data sort of stands alone as looking highly effective, highly tolerable. 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. I'll turn it over to Sandra to add comments to that question.
Sure. 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 because it's covalently binding and then also yet reversible inhibition mechanism. We believe this compound has high potency, also improved the selectivities because of the off-target toxicity is less.
Actually the clinical data already show the evidence, not just preclinical. So definitely, 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 I-B/II-A study show numerically better overall clinical response and the immunological response rate at week 24. Of course, we have to be a little bit careful.
This is a cross-study comparison, but at least all the. Then, so maybe there is difference in study population and then also there is endpoint definition different or maybe statistical methodology. But definitely the data currently give to us very confident this compound deserves to move forward to later development. Then so that is from the development perspective, but I just think the commercial perspective, Ian, do you want to add any things about from commercial perspective?
Well, I think the commercial perspective there is that we do not have anything approved for PMN right now, right? The profile that we are looking at so far shows that it is potentially better than some of the other products on the market. It is oral. I think that is very well. We should highlight the convenience factor of this product. It looks like not just the depth and the durability of the efficacy is impressive, I think the speed of onset of efficacy is also impressive.
It is also important to note that safety has been relatively benign with this product. We have not seen some of the typical BTK-related side effects that you would associate with BTKs. That also gives us confidence. With all of these impacts, it is still early days, but we believe that this compares very well with other BTK inhibitors and other modalities and the mechanisms being developed for PMN. It is also one of the first BTK inhibitors, right, to have this long-term data in PMN, I think that is also very important to highlight.
Thank you, Ian. Here is the next question. To develop EVER001 for PMN in the U.S., what would be the clinical development program, and what would it need to look like? Is there an endpoint that would be widely accepted by U.S. regulators?
Okay, I'm going to take that one. We just shared the data with you. We are actually very encouraged by the data generated from the study. Based on the current available efficacy and the safety profile of EVER001, we will select and optimize those for later development. For U.S., I would say we will take a global clinical development approach, such as phase III registration studies. This could include in U.S., China, and other territory towards the registration. The second one is, in terms of endpoints, the two-year completed clinical remission is a widely accepted endpoint by health authority and including U.S. regulatory agent. This endpoint has been used in current pivotal trials in PMN. Dr. Lafayette, you want to add something?
No, I think that's well said, and that certainly the company's being encouraged to move rapidly to phase III trials. Again, as mentioned, the classic approach would be looking for two-year efficacy with safety, looking for that complete remission of proteinuria. There are lots of discussions going on, at least in the U.S., with the FDA to try to allow shorter study designs. I think the remarkable impact on the actual cause of the disease, the PLA2R antibody for PLA2R-positive patients, could lead to a much shorter study design. Again, that's speculative as to whether the agency would be ready to accept that. I think the plan would really be looking at your two-year efficacy study, and that's a great starting point.
Great. Here's the next one. Will Everest begin clinical trials in any other indications besides PMN, and where else can EVER001 be appropriate?
Yes, I'm going to take that one. Based on the mechanism of action of EVER001, we believe, beyond the PMN, EVER001 has potential in other autoimmune renal disease, such as IgA nephropathy, lupus nephritis, and then minimal change disease, and FSGS. These are the disease, actually, with highly significant unmet medical needs and with a broad population. I would say in China, probably over 10 million patients with this disease, and then in USA, maybe over 300,000. From company perspective, we are planning to conduct a basket trial for all these other indications. Dr. Lafayette, you can also add something.
Yeah. Again, these are very exciting times. We talk a lot about antibody-mediated kidney disease, and there's still huge unmet needs across those diseases where we have inadequate safety of our therapies, inadequate evidence that they work well, and inadequate efficacy of our present medications. In virtually every autoimmune kidney disease where we now use rituximab or cyclophosphamide, or even mycophenolate, this kind of mechanism could replace that. That could be hundreds of thousands of patients in the U.S. and millions globally. I think this development program must move forward, and I have tremendous excitement that it can prove its worth.
Okay. Next question is, what are Everest's plans for ex-China rights of this drug?
Yeah. All right. Well, maybe I'll take that one. I think, as I mentioned earlier, number one, given the data that we have generated to date, and given the fact that we have global rights on this asset for renal indications, we do want to make sure that we advance this program globally as quickly as possible. We're doing this two different ways. Number one, we are going to engage with the regulatory authorities in the U.S. and in China to put together a viable and expeditious clinical development plan so that we can take this into a pivotal study as quickly as possible. Number two, as I mentioned in the wrap-up, we are on the receiving end of a number of conversations.
If this asset is one that have, number one, generated the clinical proof of concept, and number two, is on track to get into a pivotal phase III study, it is an asset that we believe is going to be strategic and synergistic with a number of companies' existing efforts in renal diseases and the autoimmune diseases. Again, we feel that even though today the data that we generated is in PMN, we do believe that this product could potentially have additional utility across other B cell-driven autoimmune renal diseases. In some ways, this is a pipeline within a product. That's how we feel. That's how our board is looking at this. We are looking to, through perhaps partnerships, to gain expertise and capital to fully develop this as quickly as possible.
Thank you. All right, last question. How durable is the treatment effect expected to be? Would you envision EVER001 to be a chronic therapy or one with the potential for retreatment courses?
I am going to take that one. That is a really good question. We just shared with you the sustainable proteinuria reduction up to 52 weeks, which includes 16 weeks of off-treatment period. Especially in the higher dose cohort, we did see these sustainable effects. We will continue, of course, monitor patient in off-treatment period and generate more long-term data to evaluate the durable effects of EVER001. With the mechanism of EVER001, which is a reversible covalent BTK inhibitor and available clinical data we just shared, which suggested that these medicines, this M001, has a potential to be a chronological therapy. Obviously, we need to generate more data to support this clinical practice.
That concludes our Q&A session. Thank you everyone for joining the Everest Medicines PMN call. You may now log off.