Good morning, good afternoon, and good evening, everyone. Thank you for joining today's Morgan Stanley Biotech Without Borders series webcast, Everest Medicines, Travere Partner civorebrutinib Renal Disease Strategy and mRNA Platform Innovation. This is Jack Lin, China Biotech/Taiwan Healthcare Analyst at Morgan Stanley. Also joining today is our series co-host, Sean Laaman, who is the head of U.S. Midcap 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. Today's discussion will focus on Everest's global partnership with Travere Therapeutics for civorebrutinib or EVER001, 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. We're very pleased to have Mr. Ian Woo, President and Chief Financial Officer of Everest Medicines, joining us today. Hi, Ian.
Hi, Jack. Hi, Sean.
With that, 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. First question, Ian, on the partnership rationale and the operating model. With the Travere transaction now closed, what made Travere the right global partner for this asset, and how will the two 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 EVER001 civorebrutinib collaboration with Travere. 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 the number of people that they have 100% focused on nephrology is really not that different from on an FTE basis as a large pharma company. 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 Sevo. I think because of their expertise in nephrology, they really view the civorebrutinib not just as a PMN asset, but a potential pipeline of product, right?
Across multiple immune-mediated kidney diseases, which is exactly how we think about this opportunity. 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 longstanding relationships with investigators and regulators, and an existing commercial infrastructure serving nephrologists, right? That's also exceedingly important.
Combining those strengths, we believe gives Sevo the best opportunity to become a global therapy. From a development perspective, Travere will lead the development and commercialization in the licensed territories. Those are 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.
With respect to indication prioritization. PMN clearly is the lead indication as we have demonstrated compelling proof of concept. Beyond that, I think we both share the view that immune-mediated FSGS, minimal 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. To really allow each company to leverage our own strengths while being very coordinated globally. Ultimately, our shared objective is really quite straightforward, right? We want to move quickly to generate high-quality clinical data, to realize the full potential of civorebrutinib across multiple immune-mediated kidney diseases for patients around the world.
Wonderful. Thank you, Ian. Maybe just to double-click on the pipeline in a product opportunity where you're positioning Sevo. Then just to go back on the proof of concept data. Just your confidence in that proof of concept in primary membranous nephropathy translating into FSGS, minimal change disease, and potentially other renal indications. Where does its selective reversible covalent BTK profile offer the clearest differentiation versus existing immunosuppressive and emerging B-cell-directed approaches?
Yeah, great questions. 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. Across PMN, immune-mediated FSGS and MCD, and IgA nephropathy as well, right? The common biological thread is that dysregulated immune signaling can drive podocyte injury, disruption of the glomerular filtration barrier, and proteinuria. B-cell activation and pathogenic antibody production are, that's very clear for PMN.
But these abnormal signaling are also implicated in FSGS and MCD. In PMN, we have seen Sevo 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 Sevo is first acting on the underlying immune disease activity, and that the clinical response follows, right?
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 Chugai. 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. This gives us a lot of confidence that BTK is a clinically relevant target in immune-mediated glomerular diseases. We've initiated in China a basket study in FSGS, MCD, and IgA nephropathy. Part of the rationale for that is to test the broader mechanistic hypothesis. I think the differentiation of Sevo versus other BTK inhibitors is really, it's a covalently reversible binder of BTK.
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, the reversibility is that binding is not permanent. Right? BTK does come off. I think that's important versus some of the irreversible covalent binders, right? Because we believe it confers some of the safety benefits that we have seen with civorebrutinib.
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 Sevo is an oral agent is also important, because it offers tremendous convenience. It improves compliance, right? It 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 that we think is suitable for chronic use.
So this is really the basis of the pipeline in a product thesis. So PMN provides the initial validation, and FSGS and MCD offers potential compelling upside. Honestly, as we generate more supportive clinical data, why would we stop at the kidney disease, right? We will certainly work with Travere to maximize the potential of Sevo and potentially across autoimmune diseases.
Wonderful. Thank you, Ian. I'll pass it over to Jack.
Yeah, absolutely. Thanks, Sean. Yeah, Ian, I'm very excited about the opportunity with Travere Therapeutics. I think it's also quite inspiring. I mean, this is kind of our first, well, many, I hope, our collaboration with global partners and the first proof of concept in terms of our portfolio and pipeline quality. So maybe I want to take a bit of a steer shift here to discuss a bit more in terms of what are other rising stars within your portfolio. I think one thing that the company has in shared with the investor and with the market, and we're starting to see more and more proof of concept data and signals from, is about the personalized cancer vaccines, right?
I think our pipeline, EVM16, it has generated initial first in human immunogenicity efficacy signals. I think we also have moved the EVM14 to get IND clearance in U.S. and China. I want to learn a bit more about both of these pipelines as well as the platform. I think a key question I have is really, how do you see the respective roles of personalized versus off-the-shelf cancer vaccines? When should we expect the next clinical readout to constitute meaningful validation of your overall underlying AI-enabled mRNA platform?
Yeah. Great. 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, you also talked about what is next. I think what is next, clearly, we have our own discovery platform that we have set up and today it is 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. As you may know, civorebrutinib was an asset from a Chinese biotech company that we licensed in. 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. Ultimately, I think the realization of the global value for that asset.
That was three or four years ago. Arguably, there is a lot more substrate that we can partner with. We have really expanded our DD focus. I would say that we would look for additional opportunities to repeat what we did with EVER001 or civorebrutinib. At the same time, of course, another opportunity are the assets from our own discovery platform. Commenting on your questions on the cancer vaccines, we do have two different types of cancer vaccines. In the clinic, we have a third cancer vaccine program that is still preclinical. It is an immunomodulatory cancer vaccine. The difference between TAA and PCV is pretty compelling. Speaking about the TAA first, TAA-based vaccines are developed against specific tumor types. They have relatively well-defined indications. The significant advantage of TAAs is that they are off the shelf.
They offer immediate treatment, which really, I think, translates into the potential for broader populations of patients both with earlier or more advanced stage cancers. Could be addressable with TAA vaccines. They are low cost. Essentially, you should think about them as traditional biologics, or with the profile of the traditional biologics. So it is very compelling, but we need to generate the proof-of-concept data with the TAAs.
Our first program is EVM14 has five tumor-associated antigens against the squamous cell carcinomas. If that were successful, we will develop additional TAAs for additional cancer types. PCVs have generated probably more clinical validation than TAA vaccines. So we are very excited about that. We also have more data from our own PCV programs. As you mentioned, the EVM16, we have completed an IIT study in China in solid tumors.
We have disclosed the first batch of data at this April's AACR. We have seen very compelling immunogenicity and even some efficacy signals. We are taking that into the next IIT study. We are calling that a phase I-B IIT. We are working on the launch preparation right now. It will definitely initiate in the second half of this year. The focus of that is a lot more specific. It will be in the first-line non-small cell lung cancer maintenance setting. It will be in combinations with PD-1s. We are expecting data readout in 2027. The strategies there in terms of selecting the indication is one that relatively allows for a faster data readout, but also in an earlier line setting. We thought that the first-line maintenance setting is a good balance of these two objectives.
We do think ultimately, the commercial potential of PCVs are going to be in earlier lines. But we need to more quickly demonstrate clinical proof of concept rather than waiting five years in an adjuvant or a neo-adjuvant 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.
Got it. Quite exciting times later this year and also early next year for this platform and this part of the portfolio. In the interest of time, I want to really quickly touch on this a bit. Relatively earlier part of our portfolio, but very hot area especially recently nonetheless, is our effort in the in vivo CAR T development. I think really, I guess this is kind of two questions in one. One is in terms of trying to understand what is the central technology or technical advantage of our LNP targeted approach relative to kind of conventional ex vivo CAR T.
Also, I think the second one is we are seeing a lot more, I think especially with Sean's companies, especially when the broader team, there is a lot of focus on in vivo CAR T. In terms of our platform technology, which specific hurdles, from cell specificity, transfection efficiency, expression duration, safety, or re-dosing, or any other metric, which one do you see as kind of the most key hurdles that you guys are able to clear and become a clinical differentiator? If you can just touch with us on this area.
Sure. Thank you for the question. For those who are not familiar with the Everest approach to in vivo CAR T, I mean, we are focused on antibodies conjugated to LNPs to deliver mRNA coding therapies, in a cell type-specific way. The platform is actually broader than just in vivo CAR T, because we can target different tissue types and cell types and deliver different kinds of mRNA. But for our in vivo CAR T programs it is a T cell surface receptor that we are targeting, and we are targeting a broader subset of T cells.
Our initial program is mRNA coding CD19 CAR. I think the advantage is pretty clear. If you can move an autologous personalized CAR T therapy into something that is off the shelf that does not require lethal depletion, and is scalable and that is cell-free and controllable in terms of quality, that will be extremely compelling. We certainly think that this is why a lot of large pharma companies and biotechs are focused on this space.
I think the technical hurdles, I think cell specificity, I think you mentioned cell specificity. That is. We can get to the right cells pretty easily. We have also. There is an active piece with the antibody targeting. There is a passive piece with the right LNPs. So we have our own library of LNPs, and we have different profiles of LNPs. The ones that we have selected for in vivo CAR T is one that deselects the liver and will preferentially go to the spleen. We have also put in engineered different sequences and modifications into the mRNA that further results in the silencing of any expressions for any molecules that does get into the liver.
I think there are a lot of innovation that we have to ensure specificity. In terms of transfection efficiency. Look, I am not sure if there is a clear goal or a threshold that you have to get to produce the same type of response as a certain amount of autologous CAR T cells. I tell you that we have gotten to levels of anywhere between 40%-80% transfection of T cells to CAR T cells in non-human primates. I think even at 40%, it produces very compelling B-cell depletion. I think ultimately you do not need to get to 100%. That is for sure. But we will optimize and generate more clinical data and be able to get to the optimal level, a little bit better in the future.
In terms of duration and safety and redosing, I think that is the key hurdle or the key challenge that industry have to solve. Can an in vivo CAR T molecule produce complete and durable B-cell depletion in a safe way? If diseased B cells do come back, can you redose those patients to drive efficacy? I think we're in the middle of a number of IIT studies.
Hopefully, we will have the answers to some of these questions in the next 6 to 12 months. We are also working on our U.S. IND filing package. We have guided this before, and we'll confirm that we're still looking to file in the U.S. IND before the end of this year. The combination of clinical data from China IIT studies and an open U.S. IND, I think will put hopefully a lot of attention on this asset, both from investors and strategic partners.
Got it. Thanks for sharing, Ian. I think in the interest of time, let me pass it really quick back to Sean for some final questions. Back to you.
Okay. Thank you, Jack, and great talking to you, Ian. Maybe just to take the discussion a bit broader, we note the relationship with Travere, but from your perspective, what has changed most in how global pharma evaluates China-originated innovation?
How they have changed in how they evaluate? Well, first, I mean, they have really increased their presence in China. Travere doesn't have anybody there, but the large pharma community, some of them have over 20 people. But I think at a minimal, they probably have at least one search and evaluation person for each of the therapeutic areas that they focus on. That's probably a minimal. Some of them have transaction people.
They are building local presence. There is a lot of global commitment. I remember a couple weeks ago I was in Shanghai, and in the same day, there was a large pharma company that was doing a global partnering day and another large pharma that's doing an R&D day in a particular therapeutic area, which in itself is also pretty interesting. In the past, they will have maybe one R&D day for the entire company.
Now it's divided by therapeutic areas. That same day, there was also a reception by one of the large venture capital firms that was looking to be part of the ecosystem there. There is a lot of global commitment as well. I think they want to be plugged into the ecosystem. I think as much for sourcing as it is for competitive intelligence. But I think beyond that, it's really the same. I mean, it's all about differentiation and genuine differentiation. Why this asset? Why now? Why is it better than everything else? How does it fit commercially?
I think with our asset, we believe that Travere looked at the data that we have generated in PMN, and the profile of this asset as an oral product and the safety margins, and really said, "Hey, this is a product that could be differentiated in the U.S. if we develop this aggressively." I think beyond that, it's really the same things in terms of clean and strong IP, CMC, and manufacturability, and the very solid translational package. Finally, I would say, it's also important for the management team.
One is that they want to make sure that there is credibility in the people who have developed this asset and generated the data to date. Two, if it's a partnership, then you're getting into a marriage. You really need to make sure that you can work with and trust the people across the table. I think those are all very important elements in terms of how global companies look at China, evaluate a potential partner, and how these partnerships could work going forward.
Wonderful. Well, Ian, with that, we have just gone past time, and it has been wonderful speaking to you. Thank you for participating in this series that Jack has been a genius to put together. We look forward to continuing the dialogue. Thank you, Ian, and thank you, Jack, and thank you everyone for listening.
Well, thank you very much.
Thanks, everyone.
You may now disconnect. Thank you.