Everest Medicines Limited (1952) Earnings Call Transcript & Summary

Good morning, good afternoon, and good evening, everyone. Thank you for joining today's Morgan Stanley Biotech without Border Series webcast. Everest Medicines, Travere-Partnered Civorebrutinib, Renal Disease Strategy and mRNA platform Innovation. This is Jack Lin, China Biotech/Taiwan Healthcare Analyst at Morgan Stanley. Also joining me today is our series co-host, Sean Laaman, who is the Head of U.S. SMID-Cap Biotech Research. Before we begin, please note, this call is intended for Morgan Stanley clients and not for members of the press. If you are a member of the press, please reach out separately. For important disclosures, please see www.morganstanley.com/researchdisclosures. So today's discussion will focus on Everest global partnership with Civorebrutinib Therapeutics for Civorebrutinib or EVER-001 and its broader strategy across immune-mediated kidney diseases. We'll also talk about their next wave of programs coming from its proprietary AI-enabled mRNA platform and discuss management's perspective on global development and partnership opportunities for China origin innovation. So we're very pleased to have Mr. Ian Woo, President and Chief Financial Officer of Everest Medicine, joining us today. Hi, Ian.

Hi, Jack. Hi Sean.

And with that, yes, let me turn the discussion over to Sean and Ian to kick us off on the fireside chat. Sean, please go ahead.

Thank you, Jack, and welcome, Ian, and welcome, everyone, and thanks for dialing in. So first question, Ian, on the partnership rationale and the operating model. So with the Travere transaction now closed, what made Travere the right global partner for this asset? And how will the 2 companies divide development responsibilities, indication prioritization and decision-making from here?

Great. Thank you for the question. And it really is a pleasure to join this call and share our perspectives on the EVER-001 Civorebrutinib collaboration with Travere. So why do we think Travere is the right partner? I think, first and foremost, we really believe Travere, there is a very strong strategic fit with Everest. Travere is a recognized leader in rare kidney disease. They have very established clinical development, regulatory and commercial capabilities focused specifically on nephrology. I think as part of our interactions and due diligence on Travere, we noticed that they have -- the number of people that they have 100% focused on nephrology is really not that different from -- on an FTE basis at a large pharma company. So we really feel comfortable with their specific expertise in this space. Obviously, also, they demonstrated with sparsentan or Filspari, how they were able to get this product through clinical development and the regulatory approval as the first ever FDA-approved treatment for FSGS and the second FDA-approved treatment for IgA nephropathy. We just have an enormous amount of confidence in their ability to both speed up and maximize the value of Civo. So I think because of their expertise in nephrology, they really view the Civorebrutinib, not just as a pMN asset, but a potential pipeline in the product, right, across multiple immune-mediated kidney diseases, which is exactly how we think about this opportunity. So this transaction, I think, really creates a very complementary partnership. Everest has generated the initial clinical proof of concept in pMN. And Travere brings extensive global nephrology expertise, very long-standing relationships with investigators and regulators and an existing commercial infrastructure serving nephrologists, right? That's also exceedingly important. So combining those strengths, we believe, gives Civo the best opportunity to become a global therapy. Now from a development perspective, Travere will lead the development and commercialization in the licensed territories. So those are sort of outside of Greater China and a few APAC markets, and we'll continue to work in our territories. We're already working closely on development strategy, clinical execution and the regulatory interactions, and we will ensure seamless development globally. So with respect to indication prioritization, so pMN clearly is the lead indication as we have demonstrated compelling proof of concept. Beyond that, I think the companies will -- I think we both share the view that immune-mediated FSGS, minimum change disease and potentially other renal indications represent attractive opportunities. But the sequence and the pace of development will ultimately be guided by data, scientific rationale and discussions with regulators, okay? In terms of how we work together, as is typical for a partnership of this nature, we have established joint governance structures to coordinate all aspects of this partnership and to really allow each company to leverage our own strength while being very coordinated globally. So our -- ultimately, our shared objective is really quite straightforward, right? We want to move quickly to generate high-quality clinical data and to realize the full potential of Civorebrutinib across multiple immune-mediated kidney diseases for patients around the world.

Wonderful. Maybe just to double-click on the pipeline and the product opportunity, which -- where you're positioning Civo. And then just to go back on the proof-of-concept data. So just your confidence in that proof of concept in primary membranous nephropathy translating into FSGS, minimal change disease and potentially other renal indications. And where does it selective reversible covalent BTK profile offer the clearest differentiation versus existing immunosuppressive and emerging B-cell-directed approaches?

Yes, great questions. So first with pMN data, we really believe that provides a very strong proof of concept for the underlying mechanism of BTK inhibition in autoimmune renal diseases. So across pMN, immune-mediated FSGS and MCD and IgA nephropathy as well, right? The common biological threat is that dysregulated immune signaling can drive podocyte injury, disruption of the glomerulus filtration barrier and proteinuria, right? So B-cell activation and pathogenic antibody production are -- that's very clear for pMN. But these are -- these abnormal signaling are also implicated in FSGS and MCD, right? So in pMN, we have seen Civo produce very rapid and substantial reduction in anti-PLA2R autoantibodies. And this is followed by meaningful reduction in proteinuria, improvements in serum albumin and the stabilization of kidney function. This sequence is very important because it shows that Civo is first acting on the underlying immune disease activity and that the clinical response follows, right? So for example, if you look at the data, we don't have any slides right now, but I think a lot of this data has been disclosed by both us and by Travere. So at week 12, the autoantibody reduction anti-PLA2R is approximately 80% already, right, especially in the high dose. But the proteinuria decline got to about 80% by week 36, right? So it's delayed, but it's also very substantial. So this gives us a lot of confidence that BTK is a clinically relevant target in immune-mediated glomerular diseases. And we've initiated in China a basket study in FSGS, MCD and IgA nephropathy. And part of the rationale for that is to test the broader mechanistic hypothesis, right? So yes, I think the differentiation of Civo versus other BTK inhibitors is really -- I mean, it's a covalent reversible binder of BTK. And I think that's very important because what it means is it binds very tightly and potently with the BTK receptor. But on the other hand, it's -- the reversibility is that the binding is not permanent, right? And so BTK does come off. And I think that's important versus some of the irreversible covalent binders, right, because we believe it converts some of the safety benefits that we have seen with Civo. The high selectivity is also very important, right, because it reduces off-target effects. So in clinical experience to date, both in patients and in healthy volunteers, we've not seen the platelet neutropenia, cardiac or liver safety signals typically associated with some of the earlier generation BTK inhibitors. Obviously, we still recognize that this is early days. But I think so far, the profile of the product is very interesting to us, right? I think the fact that Civo as an oral agent is also important because it offers tremendous convenience, improves compliance, right? And also offers flexibility in disease management, especially for these more chronic diseases. So if you take all of these together, we see a very differentiated profile, rapid control of immune disease activity, targeted modulation of B cells and an oral selective and reversible treatment, right, that we think is suitable for chronic use, right? So this is really the basis of the pipeline in a product thesis. So pMM provides the initial validation and FSGS and MCD offers potential compelling upside. Honestly, as we generate more supportive clinical data, why will we stop at the kidney disease, right? We will certainly work with Travere to maximize the potential of Civo and potentially across autoimmune diseases.

Wonderful. And I'll pass it over to Jack.

Yes. Absolutely And yes, I'm very excited about the opportunity with Travere Therapeutics. And I think it's also quite inspiring. I mean this is kind of our first of many, I hope, our collaboration with kind of global partners and kind of first proof of concept in terms of our portfolio and pipeline quality. So maybe I want to take a bit of a gear shift here to kind of discuss a bit more in terms of what other rising stars within your portfolio. I think one thing that I think the company has been [indiscernible] with the investor and with the market, and we're starting to see more and more proof-of-concept data and signals from is kind of about the personalized cancer vaccines, right? So I think our pipeline, EVM16, it has generated initial first in human immunogenicity efficacy signals. And I think we also have moved the EVM14 to get IND clearance in U.S. and China, right? So I want to learn a bit more about both of these pipelines as well as the platform. And I think the key question I have here is really how do you see the respective roles of personalized and versus kind of off-the-shelf cancer vaccines? And kind of what -- when should we expect the next clinical readout to constitute meaningful validation of your overall underlying AI-enabled mRNA platform?

Yes. Great. I think -- thanks, Jack, for that question. I think the question specifically is on mRNA cancer vaccines. But I think in your preamble to that question, leading up to that question, right, I also talked about what's next. And I think what's next, clearly, we have our own discovery platform that we have set up. And the -- today, it's very much focused on mRNA therapeutics. And I will answer your question on the cancer vaccines. But I think we are also looking for the next Civorebrutinib, right? So as you may know, Civorebrutinib was an asset from a Chinese biotech company that we licensed in. We did the -- we saw the potential to develop this in autoimmune renal diseases. We ran the clinical proof-of-concept study that led to the Travere collaboration, right? And ultimately, I think the realization of the global value for that asset, right? And that was 3 or 4 years ago. Arguably, there's a lot more substrate that we can partner with. And we've really expanded our BD focus, right? And I would say that we would look for additional opportunities to repeat what we did with EVER-001 or Civorebrutinib, right? And at the same time, of course, right, another opportunity is the assets from our own discovery platform, right? And so sort of commenting on your questions on the cancer vaccines, we do have 2 different kinds of cancer vaccines, right, in the clinic. We have a third cancer vaccine program that's still preclinical. It's an immunomodulatory cancer vaccine. So with -- the difference between TAA and PCV is pretty compelling, right? So speaking about the TAA first, TAA-based vaccines are developed against specific tumor types. So they have relatively well-defined indications, right? The significant advantage of TAAs is that they are off the shelf, right? And they offer immediate treatment, which really, I think, translates into the potential for broader populations of patients, those that are both earlier or more -- with earlier or more advanced stage cancers, right, could be addressable with TAA vaccines. They're low cost. Essentially, you should think about them as traditional biologics, right, or with the profile of the traditional biologics. So it's very, very compelling, but we need to generate the proof-of-concept data in -- with the TAAs. And our first program is EVM14 is -- has 5 tumor-associated antigens against the squamous cell carcinomas. And if that were successful, we will develop additional TAAs, right, for additional cancer types. PCVs have generated probably more clinical validation, right -- than TAA vaccines. right? So we are very excited about that, and we also have more data from our own PCV programs. As you mentioned, the EVM16, we've completed an IIT study in China in solid tumors. And we have disclosed the first batch of data at this April's AACR. We've seen very compelling immunogenicity and even some efficacy signals, right? So we are taking that into the next IIT study. We're calling a Phase Ib IIT that's -- we're working on the launch preparation right now. It will definitely initiate in the second half of this year. That will -- the focus of that is a lot more specific. It will be in the first-line non-small cell lung cancer maintenance setting, okay? And it will be sort of in combination with PD-1s. And we're expecting data readout right, in 2027. So the strategy is there in terms of selecting the indication is one that is relatively allows for a faster data readout, but also in an earlier line setting. And we thought that the first-line maintenance setting is a good balance of these 2 objectives. We do think the -- ultimately, the commercial potential of PCVs are going to be in earlier lines, right? But we need to sort of more quickly demonstrate clinical proof of concept rather than waiting 5 years in an adjuvant or neoadjuvant setting. So look for us to -- for the first patient in for the first-line maintenance trial for PCV in the second half of this year with initial data readout in 2027. With TAA, we are in the middle of a U.S. and China Phase I dose escalation study. We expect that to complete before the end of this year with data also expected in 2027.