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

Good day, and thank you for standing by. Welcome to Everest Medicines Conference Call for Nefecon Latest Update. Please be advised that today's conference is being recorded. [Operator Instructions] At this time, I would like to hand the conference over to your speaker today, Ms. Leah Liu, VP of Corporate Affairs. Please go ahead.

Thank you, operator, and thank you, everyone, on the line for joining us on this conference call to discuss more details on our flagship drug, Nefecon's China approval and future commercial plans. Joining us today are Mr. Roger Luo, our Chief Executive Officer; Mr. Ian Woo, our President and Chief Financial Officer; Ms. Jennifer Yang, our Chief Scientific Officer; and Ms. Bei Wang, VP of Clinical Development. Before we get started, I'd like to remind you that the speakers of this conference call may make statements that consist forward-looking statements, including descriptions regarding the intent, belief or current expectations of the company or its officers with respect to the business, operations and financial conditions of the company, which can be identified by terminology such as will, expects, anticipates, future, intends, plans, believes, estimates, confident and such statement. 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 have no obligation, does not undertake to revise forward-looking statements or to reflect new information, future events or circumstances after the date of this conference call, except as required by law. And now I will turn over the call to our CFO, Ian, to discuss the latest update of Nefecon. Ian?

Great. Thank you, Leah. Let's move on to the first slide. So we are thrilled at Everest to talk about the approval of Nefecon in China for the treatment of primary IgA nephropathy in adult patients. The approval was received on November 21 and we expect to be able to commercially launch Nefecon in China in the first quarter of 2024. The approval of Nefecon in China, this is the first of a targeted medication for IgA nephropathy in China. This is a product that -- in China, there are millions of patients and Nefecon is able to delay the deterioration of kidney function by about 50% in the global patient population. And in the Chinese patient population, I'll show you some data later, we're able to delay the deterioration of kidney function by about 66%. Next slide. So first, let's talk about the mechanism of action of IgA nephropathy. The prevailing theory is that the origin of IgA nephropathy actually starts in the gut. There is the abnormal production of Gd-IgA1 in the intestinal mucosal cells is the -- is believed to be the origin of IgA nephropathy. And these aberrant forms of IgA1 molecules, promotes the production of auto antibodies against these Gd-IgA1 molecules, and the Gd-IgA1 molecules and the immune complex forms an abnormal complex that deposits in the glomeruli cells and triggers additional inflammatory and autoimmune cascades that leads to the destruction of kidney glomeruli cells and reduces the ability of kidneys to clear the toxins from the blood, okay? And the innovation of Nefecon is that it is -- it has an enteric-coated delayed-release formulation that coats the active ingredient, budesonide, with 3 coatings that leads to the release of Nefecon when it's taken orally, directly to the small intestine around the peyer's patches where Gd-IgA1 is produced. Locally releases the active ingredient budesonide and shuts down the Gd-IgA1 production in the peyer's patches. Most of the budesonide is released locally and does not get into systemic circulation. And what small amounts of budesonide that does get into systemic circulation is cleared rapidly through first-pass metabolism in the liver. So therefore, we believe Nefecon acts locally at the origin of IgA nephropathy and has a very benign safety profile because it is mostly not systemically absorbed and what is in the systemic circulation is cleared from the body very rapidly. Okay. Next slide, please. So why is IgA nephropathy such a severe disease, especially in aging population? So if you look at the chart on the bottom left, you can see that almost all patients are at risk of progression to kidney failure within their expected life -- lifetime, especially if you are diagnosed with IgA nephropathy when you are less than 50 years old and most of the patients are diagnosed with IgA nephropathy when you are young, okay? If your IgA nephropathy leads to a rate of eGFR loss of greater than 1 ml per year. And again, most of the patients do lose more than 1 ml per year of kidney function. Most of them actually lose a lot more than that, okay? And we have seen that in our Phase III studies. Your chances of developing kidney failure is almost 100%. This is a sort of study that have -- a number of studies that have been done in China and globally. The chart in the middle shows that patients of East Asian origin have significantly increased risk of developing ESRD compared to other patients globally with a hazard ratio of 1.56, which means a 56% increase in risk, okay? And again, we have seen that in our Phase III study. Okay. And why is that? And I think it's partly because the disease origins and the causes of ESRD in China versus the West is actually quite different, and we can see that clearly in the chart on the bottom right. Most of the ESRD patients in the West are caused by a -- it's a result of their diabetes or hypertension. But in China, most of the patients develop ESRD because of primary glomerular diseases such as IgA nephropathy. Okay. Next slide, please. So here, I would like to review the results from the China subpopulation of 62 patients. And most of these patients are part of the Phase III NefIgArd global Phase III study that we ran together with Calliditas. And the results from the China subpopulation, obviously, that's most relevant to the territories that Everest Medicines has shows numerically greater Nefecon treatment effect on kidney function, on proteinuria and on micro haematuria compared with global data. So first, EGFR. You can see that in the chart on the bottom left, that at 24 months, eGFR reduction was about 21 mls per year over the -- 21 mls over the course of 2 years. Whereas in the global population over 2 years on placebo, you only saw a 12 ml per year -- only saw a 12 ml reduction in kidney function. The treatment effects for Nefecon is comparable between China and the global about 6 to 7 mls of a reduction over 24 months. And this demonstrates that in the China population, there is a 66% savings of kidney function on Nefecon treatment versus placebo. Whereas in the global population, the savings of kidney function was about 50%, okay? The chart in the middle shows the reductions in proteinuria. You can see that at months 9 Nefecon versus placebo in Chinese patients was about -- on Nefecon demonstrated about a 31% greater proteinuria reduction, whereas by 24 months, that treatment effect was about 43% between Nefecon and placebo, again, demonstrating that overall, Nefecon is highly efficacious in reducing proteinuria, but especially so in Chinese patients. In the chart on the bottom right, this shows that in Chinese patients, the number of -- the percentage of patients without microhematuria during the 24 months increased from 26.9% to 57.7%, almost a doubling of patients without hematuria. Again, this is highly clinically relevant. And if you look at in the placebo arm, there is no such increase in the number of patients that are -- that have no blood in the urine, okay? From a safety perspective, the population in the data that we have seen in Chinese patient population is generally consistent with the global study, okay? So from all of these data, we surmise that the disease progression in Chinese patients is more rapid than patients in the global population. And we have seen early signs of that in clinical studies, but also, we think this will translate into Chinese patients' ability and willingness to treat because their disease progresses quite rapidly from diagnosis. Okay. Next slide. So in the next 2 slides, I will review data that you already know. These are the data that Calliditas disclosed in their -- in the global Phase III NefIgArd study, okay? And we'll add a little bit of data that Calliditas has as well as other principal investigators have recently disclosed in the ASN conference. Okay. So you'll see that in this chart, again, as a reminder, the trial design is over 24 months, but dosing with Nefecon or placebo plus a background therapy of RAS inhibitors, okay? So it's Nefecon plus RAS or placebo plus RAS for 9 months and then observe on the background therapies for another 15 months. You can see that at month 9, eGFR for the -- for Nefecon, which is the orange line, is stable above the baseline. But of course, after treatment was stopped, there is a deterioration of kidney function. But if you look at the gray line, which is placebo, you can see that even during the 9 months treatment period, there is a significant decline in kidney function, and that continued throughout the 24 month period, okay? So at month 24, you see a -- that on placebo the kidney function eGFR has declined by 12 mls per minute, whereas Nefecon saw a 6.11 ml per minute decline. This is a -- why we say there's a 50% less loss of kidney function with Nefecon treatment. And [ Dr. Jonathan Barrett ] has done some meta analysis and have demonstrated that this level of decline that actually implies is equivalent to a 12.8 years delay of disease progression to ESRD. Clearly, highly clinically relevant. We have also seen that Nefecon treatment is able to lead to a significant reduction in Gd-IgA1 in these patients. And this is also very important because it validates the prevailing theory on the ideology of IgA nephropathy. And it also demonstrates that Nefecon is potentially a disease-modifying drug with a direct effect on the origin of the IgA nephropathy. Next slide. So let's take a look at proteinuria. This is quite interesting to us because after treating these patients for 9 months, we saw a 33.6% reduction in proteinuria, but that effect deepened to 51.3% by month 12. Okay. Of course, after that, there is a bit of a reversion in proteinuria. So by month 24, the magnitude of proteinuria reduction on Nefecon was 30.7%. But if you see the placebo line, the gray line, it's flat. There is no reduction in proteinuria, okay? We think this is quite important. And again, the fact that proteinuria continues to decline from month 9 to month 12 after Nefecon has stopped speaks to the potential disease-modifying effect of Nefecon and its sustained effect on IgA nephropathy. Again, in the safety findings, generally well tolerated, and quite benign. Now this does raise the question of -- if you look at this slide and the previous slide that the treatment effect was quite significant, especially during the 9 months dosing period. There are questions as to what if Nefecon was continued after 9 months and was not stopped at that point? Could we see even better effects? There are also questions on what if we -- after 24 months that we continue to -- that we give another dose of Nefecon? Could that kind of an interval treatment help manage disease even better than what we have seen in these 24 months. Now we will test these theories and questions together with Calliditas. And there will be real-world evidence data that will come out over time over long-term use of Nefecon, and there are patients who are already on Nefecon long-term in the U.S. because the product has been approved for about 2 years now. And we and Calliditas are working on an open-label extension study that looks at the theory of -- at the end of 24 months, we give another 9 months of Nefecon and could that lead to better treatment effects for these patients? Next slide. So let me go into a little bit about the commercialization plan for Nefecon. So Nefecon, as most of you already know, was successfully launched in the EAP program in the Boao in the Hainan province in China. This was -- this program was initiated in April of 2023. And over the last 7 months, we have had over 700 patients from Mainland China register for this program. And we have -- we're only able to process a number of these patients every month. And so far, we have over about 150 patients that have flown over to Hainan. And each time they were able to get 3 bottles of Nefecon at a price of RMB 23,600 per month gross. There is a reimbursement program that takes that price down to a net price of RMB 18,600 per month per bottle. And what we are really happy to see is that almost all of the patients who have gotten their 3 months of Nefecon and have used those 3 bottles have flown back to Hainan to get their second 3 months of treatment. This indicates to us that clearly, these patients are -- view Nefecon to be helpful to their disease, right? And we also feel that this is a good indication of Nefecon's potential when we more broadly make the product available to Chinese patients. So you can see that after the EAP program has been initiated, we have received 2 approvals in our territories. That Nefecon was approved in Macau in October and obviously in Mainland China last week. We will be initiating the second phase of our EAP program in Macau. And we believe that the commercial launch in Macau will start next month, so December of 2023. We will be treating patients in Macau and other early access patients from China, which I will talk about on the next slide. Formal commercial launch in Mainland China will be in the first quarter of next year, probably in the March or April timeframe. And we also expect the -- to launch Nefecon in other territories such as Hong Kong, Singapore and receive approvals in Taiwan and South Korea as well in 2024. Let's look at the next slide, please. So just to go into a little bit on the market dynamics in China. First of all, I think you've heard this from us many times now, a lot of patients in China. There are about 5 million patients, about 1 million are biopsy-confirmed IgA nephropathy patients. And each year, there are about 100,000 newly diagnosed through biopsy of IgA nephropathy patients. This is a huge population in China alone. And as I mentioned before, most of the diagnosed patients are diagnosed when they are young and at the peak of their working hour and very, we believe, have a high willingness to treat. Part of the reason why is that this is not a light disease. And especially in Chinese patients, we have seen some data before that this could progress very rapidly to end-stage renal disease, which leads to either dialysis or kidney transplantation. The current treatment options leave a lot to be desired. They are really adjuvant therapies or supportive therapies. They treat symptoms without getting to the core of the disease. And we believe that Nefecon is the first treatment that has the IgA nephropathy indication but also is the first drug that treats the origin of the disease. And we talked about the EAP program pricing already at about RMB 23,800 per month but on a net price basis RMB 18,600 for these patients. Now if we look at the commercialization plan that we will be executing on this year. So first of all, Everest is already commercial. We already have a commercial team of about 180 people. About 100 of those are for our first product, Xerava, but about 80 are in the sort of the central commercial team of channel, [ KA ], marketing, strategy, medical, so on and so forth. These 80 people, together with the 200 new people that we will be hiring specifically for Nefecon, will be responsible for the commercialization of the product in China. And we believe this organization is able to help us cover about 600 hospitals which represents about 60% of the addressable patient population or about 60% of the hospitals in China that can do kidney biopsies, okay? And we've chosen these hospitals because we -- these are -- this will allow us to be able to get to a significant portion of the patients without building a very large commercial organization. So it's a very efficient way of launching Nefecon. The other effort that we have been working on throughout the course of 2023, is to work with a charitable -- charity foundation on a patient registry. This registry is -- now has over 5,000 patients. They know about Nefecon. They use the charity foundation program to help manage their IgA nephropathy, and we intend to turn these -- this pool of patients into the first prescribers for Nefecon in Macau and in Mainland China. Because of our confidence in Nefecon's potential in China and in our territories, we are reaffirming our revenue guidance for 2024 of RMB 700 million. And of that, we believe RMB 400 million to RMB 500 million will be from Nefecon and RMB 200 million to RMB 300 million will be from Xerava. And as a reminder, we are already almost in December. And you'll hear every time we talk about this, we are reaffirming our 2023 revenue guidance of RMB 70 million to RMB 100 million. And our confidence is higher as we get closer to the end of the year. In addition, I think we will be pursuing a number of innovative commercialization efforts as a way to better manage patients but also as a way to help us go to market in a more efficient way because this fundamentally is a chronic treatment, and there are a number of different ways online and off-line that we can use to better engage with these patients. And we will be working on accessibility for patients because that is key for us. We want to make sure that every patient that have IgA nephropathy has access to this product through a number of programs such as [ PAP ], private commercial insurance plans and eventually, of course, we want to provide the broadest coverage access possible through listings in the NRDL. Next slide, please. Next slide. Doesn't look like the slides are advancing. Okay, here we go. Okay. So around Nefecon, we really view Nefecon as an anchor product to our renal franchise. And this is a snapshot of what we intend to build for the renal disease platform, okay? So first of all, primary glomerular diseases in China, there's just a huge number of patients, which indicates significant unmet medical need. IgA nephropathy is the largest with about 5 million patients but other diseases listed here also have a significant number of patients, much larger than the global population. This slide used to say that no available therapies for all of these indications, but that's changed since last week. Now we have Nefecon approved in China. But many of these other diseases still do not have any therapies approved for them. And we hope to change that. We have a covalent reversible BTK inhibitor that we are developing for primary glomerular diseases. We should have Phase Ib data that we can share with everybody in the -- in 2024, hopefully, in the first half of 2024. You have seen that a couple of months ago, we brought in zetomipzomib from Kezar in the U.S. We're super-excited about this product, which has demonstrated some very promising or early data in lupus nephritis, and we are working with Kezar on a -- we hope a pivotal Phase IIb study in lupus nephritis patients. We will be filing the IND and start to enroll in China in 2024. And we intend to continue to build our renal franchise through a combination of internal discovery and in licensing. Next slide. Okay. So finally, maybe just to touch upon some of the catalysts. We're already almost at the end of 2023, but look for us to provide some updates on some of our other programs before the end of the year. So other than Nefecon, which we have talked about. A few of the things that we are really excited about include the submission of the NDA for cefepime-taniborbactam in complicated UTI. This will -- we hope to submit the NDA in China before the end of 2023. This product is already approved -- already submitted by our partner, Venatorx in the U.S. with a PDUFA date of February of next year. And once the product is approved in the U.S., we will submit the NDA in Macau for approval there. We're also very excited about etrasimod approved by Pfizer in ulcerative colitis with the brand name of Velsipity. We have run, as most of you know, a fully powered Asia Phase III study for etrasimod in UC. We have guided that we will be disclosing the 12-week induction of remission data before the end of 2023. So you should be looking for that as well. and we intend to submit the NDA for etrasimod in UC in 2024 as well. Okay. So let me wrap up and turn it back to Leah for questions.

Thank you. Thank you, Ian. Operator, can you please announce how the audience can make -- ask their questions, please?

[Operator Instructions] The first question comes from Jefferies, please.

Yes. This is Farzin on for Maury. Ian, are there any certain characteristics in Asian patients that could drive faster progression in IgA nephropathy?

Sorry, the question is on faster progression in Chinese patients?

Right.

Are you asking whether -- what kind of support we have for the faster progression in Chinese patients?

Right. And what drives it? Exactly.

Oh, what drives it. Okay. Maybe this is a question that Bei or Jennifer can go into first.

Yes. So yes. Maybe let me take this question first. So yes, you're right, during this study that we have some observations, the Chinese population have more rapid disease progression. So just based on the observations in the placebo, we see large magnitude of UPCR decrease and also the large magnitude of eGFR decline in the placebo arm. So these findings basically is consistent with what was reported in clinical practice and in the previous publications. So regarding the reasons why we can see this high risk -- higher risk of disease progression in Chinese populations seems multiple factors could contribute to it. For example, like the [indiscernible] habit, [ heterogeneity ] of genetic predisposition and fundamental [indiscernible] pathways. But so far, as the pathogenic reasons of IgAN is not completely established yet. So there are a lot of research that is still ongoing to get answers in the future.

Got it. And then the other question is on pricing. Do you expect RMB 18,600 per month net price to be consistent for broader China?

I mean we commercialized the product in China, quarter 1 next year. The price we set for the early access program is RMB 18,600 per bottle. But once we get into the market, we'll be reestablishing the price also with our patient assistant program. So currently, we are still in the discussion to define the final price. As of now, we haven't finalized that kind of research. But of course, we'll continue to increase the patient access through different mechanisms, for example, by the end of next year, we will be entering into a reimbursement discussion or negotiation with the central governments, where we will very likely will get reimbursement because of these products. It has been -- has been regarded as a breakthrough destination and also priority review at the CDE. So very likely, we're getting reimbursement, then the patient access will be increased. And also before we get reimbursement in 2024, we will have a patient assistant program. We will have joined some private health care insurance and many other ways to increase the product access. So that's about our plan.

And the next online question comes from Morgan Stanley. And the question is, what is the manufacturing strategy for Nefecon?