Good morning, good afternoon, and good evening, everyone. Thank you for joining today's Morgan Stanley Biotech Without Borders series webcast. Aries Medicines, Travier partner Sivore Brutinib, Renal Disease Strategy, and mRNA Platform Innovation. This is Jacqueline, China biotech slash Taiwan healthcare analyst at Morgan Stanley. Also joining me today is our series co-host, Shang Lamen, who is the head of U.S. MCAT 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 forward slash research disclosures. So today's discussion will focus on Everett's global partnership with Travere Therapeutics for Siviributinin, or Ever001, and its broader strategy across immune-mediated kidney diseases. will also talk about their next wave of programs coming from its proprietary AI-enabled MRM platform and discuss Manchin's perspective on global development and partnership opportunities for China origin innovation. So we're very pleased to have Mr. Ian Wu, President and Chief Financial Officer of Everest Medicine joining us today. Hi, Ian. Hi, Jack. Hi, Sean. And with that, yeah, 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 dialling 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 two companies divide development responsibilities, indication prioritisation, and decision-making from here?

Great. Thank you for the question. And, you know, it really is a pleasure to join this call and, you know, share our perspectives on the Ever001 Silver Reboot Nib collaboration with Trevier. So, you know, so why do we think, you know, Trevier is the right partner? I think, you know, first and foremost, we really believe Trevier, there is a very strong strategic fit with Everest. Trevier is a recognized leader in rare kidney disease. You know, they have very established clinical development, regulatory and commercial capabilities focused specifically on nephrology. You know, I think, you know, as part of our interactions and due diligence on Trivia, we noticed that they have the number of people that they have 100% focused on nephrology is really not that different from, you know, on an FTE basis at a large pharma company. So we really feel comfortable with their specific expertise in this space. You know, obviously, also, they demonstrated with sparsantan or filspari, you know, 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 SIVO. So, you know, I think because of their expertise in nephrology, they really view the C. borobutinib not just as a PMN asset, but a potential pipeline in the product, right? You know, across multiple immune-mediated kidney diseases, you know, 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 approval concept in PMN, and Trivia Brewing's Thank you very much. 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. 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, you know, 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. 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 ultimately, our shared objective is really quite straightforward, right? You know, we want to move quickly to generate high-quality clinical data and to realize the full potential of SIVO RebootNIP across multiple immune-mediated kidney diseases for patients around the world.

Wonderful. Thank you, Ian. Maybe just to, you know, double-click on the pipeline in a product opportunity, which where you're positioning SIVO. 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 its selective reversible covalent BTK profile offer the clearest differentiation versus existing immunosuppressive and Emerging B-Cell Directed Approaches.

Yeah, 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? You know, the common biological thread is that dysregulated immune signaling can drive podocyte injury, disruption of the glomerulus filtration barrier, and proteinuria, right? So, you know, B-cell activation and pathogenic antibody production are, that's very clear for PMN, you know, but these are, these, you know, abnormal signaling are also implicated in FSGS and MCD. So in PMM, we have seen SIBO produce very rapid and substantial reduction in anti-PLA2R autoantibodies. And this is followed by meaningful reduction in proteinuria, improvements in serine albumin, and the stabilization of kidney function. This sequence is very important because it shows that SIBO is first Thank you very much. But, you know, the proteinuria decline got to about 80% by week 36, right? So, you know, 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, you know, 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. All right. So, yeah, I think the differentiation of SIVO versus, you know, other BTK inhibitors is really, I mean, it's a covalent reversible, you know, binder of, you know, BTK. And I think that's very important because what it means is that binds very tightly and potently. Thank you very much. Thank you very much. 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, Thank you very much. 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 that we think is suitable for chronic use. So this is really the basis of the pipeline in a product thesis. So PMM provides the Initial validation and FSGS and MCD offers, you know, potential compelling upside. You know, honestly, as we generate more supportive clinical data, why will we stop at the kidney disease, right? You know, we will certainly work with, you know, Travere to maximize the potential of SIBO, you know, and potentially across autoimmune diseases.

Wonderful. Thank you, Ian. I'll pass it over to Jack.

Yeah, absolutely. Thanks, Sean. And yeah, 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, you know, our collaboration with kind of 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 gear shift here to kind of discuss a bit more in terms of, you know, what other opportunities and many more. first in human immunogenicity efficacy signals. And I think we also have moved the EVM-14 to get anti-clearance in US and China. So I want to learn a bit more about both of these pipelines as well as the platform. And I think a key question I have here is really, how do you see the respective roles of personalized versus off-the-shelf cancer vaccines? And when should we expect a 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, I also talked about what's next. And I think what's next, clearly, you know, we have our own discovery platform that we have set up. And today it's very much focused on mRNA therapeutics. And I will answer your question, you know, on the cancer vaccines. But I think we are also looking for the next SIVO-Rebutinib, right? So as you may know, SIVO-Rebutinib was a, you know, Asset from a Chinese biotech company that we licensed in. We did the, you know, we saw the potential to develop this in autoimmune renal diseases. We ran the clinical proof of concept study that led to the Trevear collaboration, right? And, you know, ultimately, I think the realization of the global value for that asset, right? And that was three or four years ago. Arguably, there's a lot more substrate that we can, you know, partner with. And, you know, we've really expanded our BD focus, right? And, you know, I would, you know, say that, you know, we would look for additional opportunities to repeat, you know, what we did with, you know, Ever 001 or Civil Reboot, right? And, you know, at the same time, of course, right, you know, another, you know, opportunity is, you know, are the assets from our own discovery platform, right? And so, you know, sort of commenting on your questions on the cancer vaccines. We do have two different kinds of cancer vaccines in the clinic. We have a third cancer vaccine program that's still preclinical. It's an immunomodulatory cancer vaccine. So the difference between TAA and PCV is pretty compelling. So speaking about the TAA first, TAA-based vaccines are developed against specific tumor types. So they have relatively well-defined indications. The significant advantage of TAAs is that they are off the shelf. 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 advanced stage cancers could be addressable with TAA vaccines. They're low cost Essentially, you should think about them as traditional biologics or with the profile of the traditional biologics. So it's very, very compelling. But we need to generate the proof of concept data with the TAAs. And our first program is EVM-14 is... has five tumor-associated antigens against the squamous cell carcinomas. And 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. 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. So we are taking that into the next IIT study. We're calling that a Phase 1b IIT that's We're 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. and we're expecting data readout in 2027. So the strategies there in terms of selecting the indication is one that relatively allows for a faster data readout, but also in a earlier line setting. And 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, right? But we need to, you know, sort of more quickly demonstrate clinical proof of concept rather than waiting five years in an adjuvant or... Thank you very much.

So quite exciting times later this year and also early next year for this platform and this part of the portfolio. So in terms of time, I want to really quickly touch on this relatively earlier part of our portfolio, but a very hot area, especially recently nonetheless, is our effort in the in vivo CAR-T development. So I think really two, I guess it's kind of two questions in one. So one is in terms of trying to understand what is the central technology or technical advantage of our LMP target approach relative to kind of conventional technology. and also I think the second one is you know we are seeing a lot more I think especially with Sean's companies especially when the broader team right there's a lot of focus on the in vivo car team so you know in terms of our platform technology which specific hurdles you know from cell specificity, transfection, efficiency, expression, duration, safety or reducing or any anything any other matching which one do you see is kind of the most Thank you for the question.

And again, you know, for those who are not familiar with the Everest, you know, approach to in vivo CAR T, I mean, we are focused on, you know, antibodies conjugated to LNP to deliver, you know, mRNA coding, you know, and many more. Thank you. and we are targeting a broader subset of T cells. And our initial program is mRNA coding CD19 CAR. So I think the advantage is pretty clear. If you can move and sort of autologous personalized CAR T therapy into something that's off the shelf, that does not require lympho depletion and is scalable and that's cell-free and controllable in terms of quality, that will be extremely compelling. And so we certainly think that this is why a lot of large pharma companies and biotechs are Thank you very much. There's an active piece with the antibody targeting. There's the passive piece with the right LNPs. So we have our own library of LNPs, and we have different profiles of LNPs. The one that we've selected for in vivo CAR-T is one that deselects the liver and more preferentially goes to the spleen. We have also engineered different sequences and modifications into the mRNA that further results in the silencing of any expressions for any molecules that that's getting to the liver. And so I think there are a lot of innovation that we have to ensure In terms of, you know, transfection, you know, efficiency, look, I mean, I'm not sure if there's, you know, there is a clear goal or threshold that you have to get to. to produce the same type of response as a certain amount of autologous CAR T cells, right? I tell you that we have gotten to levels of anywhere between 40% to 80% transfection of T cells to CAR T cells in non-human primates, right? And I think even at 40%, it produces very compelling B cell depletion. You know, I think ultimately it is going to be you don't need to get to 100 percent. That is that is for sure. Right. But, you know, we will we will optimize and generate more clinical data and be able to get to get to the optimal level a little bit better, you know, as you know, 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? And if If there are, if B cells, diseased B cells do come back, right, can you read those patients to drive efficacy, right? And I think this is, you know, we're in the middle of a number of IIT studies. Hopefully, we will have the answers to some of these, you know, questions in the next six to 12 months, right? We are also working with, working on our US IND filing package. We have guided this before and we'll confirm that we're still looking to file in the US IND before the end of this year. So the combination of clinical data from China IAT studies and an open US IND, I think will put a lot of, hopefully a lot of attention on this asset, both from investors and strategic partners.

Thanks for sharing, Ian. I think the interest of time, I'm going to pass it really quick back to Sean for some final questions.

Thank you, Jack, and great talking to you, Ian. Maybe just to take the discussion a bit broader, and we note the relationship with Travere, but from your perspective, what has changed most in how Global Pharma evaluates China-originated innovation?

Oh, how they have changed in how they evaluate? Well, first, I mean, you know, they've really increased their presence in China, right? Yeah, I know about the trivia doesn't have anybody there, but the large pharma community all have, you know, Some of them have, like, you know, 20 people, over 20 people, right? But I think at a minimum, they probably have at least one search and evaluation person for each of the therapeutic areas that they focus on. That's probably a minimum. Some of them have, you know, transaction people. So they're spending a lot of, you know, they're building local presence. There's a lot of global commitment. I remember a couple weeks ago, I was in Shanghai, and in the same day, there was a... 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. And that same day, there was also a reception by one of the large venture capital firms that was looking for to be part of the ecosystem there. So there's a lot of global commitment as well. I think they want to be plugged into the ecosystem as much for sourcing as it is for competitive intelligence. But I think beyond that, it's really the same. It's all about differentiation and genuine differentiation. So Right. You know, why this asset? Why now? You know, why is it better than, you know, everything else? And how does it fit commercially? So I think, you know, with our asset, you know, we believe that, you know, trivia looked at, you know, the the data that we have generated in PMN and and the profile of this asset is a, you know, because, you know, Thank you very much. I think, you know, beyond that, I mean, it's really the same things in terms of, you know, clean and strong IP, you know, CMC and, you know, manufacturability, right? And the very solid, you know, translational package, right? And then, you know, finally, I would say it's also important for the management team, right? Right. And, you know, especially one is that, you know, they want to make sure that there is credibility right in the people who have developed this asset and generated the data to date. And two, if it's a partnership, then you're getting into a marriage. Right. You really need to make sure that you can work with and trust the people across the table. Right. And so I think those are all very important elements here. In terms of how global companies look at China, evaluate a partner, a potential partner, and how these partnerships could work going forward.

Wonderful. Well, Ian, with that, we've just gone past time, and it's been wonderful speaking to you, and thank you for participating in this series that Jack's been a genius to put together. So we look forward to continuing the dialogue. So thank you, Ian, and thank you, Jack, and thank you, everyone, for listening. Well, thank you very much. Thanks, Ian. Everyone, you may now disconnect, but thank you.