Moderna at Bernstein Forum: mRNA Oncology Innovations

On Thursday, 25 September 2025, Moderna Inc. (NASDAQ:MRNA) presented its strategic insights at the Bernstein Insights: Healthcare Leaders and Disruptors - 2nd Annual Healthcare Forum. The company showcased its innovative mRNA technology in oncology, focusing on a diverse portfolio that aims to transform cancer treatment. While Moderna’s approach offers promising safety and efficacy, challenges remain in balancing personalized and off-the-shelf therapies.

Key Takeaways

• Moderna’s oncology strategy leverages mRNA technology for diverse cancer therapies, including individualized and off-the-shelf treatments.
• The company emphasizes the potential of its INT program, showing a 49% reduction in cancer recurrence risk when combined with Keytruda.
• Partnerships, such as with Merck, are vital for accelerating development and commercialization.
• Upcoming data releases are anticipated at ESMO 2024 and in 2026 for key programs.
• Safety and tolerability remain central to Moderna’s therapeutic approach.

Operational Updates

• INT Phase 3 Enrollment: The Phase 3 study in adjuvant melanoma with INT and Keytruda completed enrollment at the end of 2024.
• INT Expansion: The development program for INT is expanding across multiple tumor types, including non-small cell lung cancer, small cell lung cancer, high-risk muscle-invasive bladder cancer, renal cell cancer, and non-muscle-invasive bladder cancer.
• mRNA-4106 Phase 1: This study focuses on safety and tolerability.
• mRNA-2808 Phase 1: Currently in relapsed multiple myeloma patients, examining safety and efficacy.

Future Outlook

• ESMO 2024: Moderna plans to share ARM1B data from mRNA-4359.
• 2026: Data from the pivotal study of INT combined with Keytruda in adjuvant melanoma is expected, along with a five-year follow-up from the phase two randomized study.
• INT Adjuvant Renal Cell Carcinoma: Fully enrolled and next in line for data release.

Q&A Highlights

• Off-the-shelf vs. Personalized Therapies: The company acknowledges that data will determine the superior approach, with off-the-shelf therapies potentially being more accessible.
• Cell Therapy Enhancers: These could benefit areas with limited antigen access or immune suppression, particularly in solid tumor settings.
• Competitive Landscape: Moderna views similar biological explorations by competitors as opportunities for de-risking.

In conclusion, Moderna’s strategic focus on mRNA technology in oncology highlights its commitment to advancing cancer treatment. For more details, readers are invited to refer to the full transcript below.

Full transcript - Bernstein Insights: Healthcare Leaders and Disruptors - 2nd Annual Healthcare Forum:

Courtney Breen, Analyst, Bernstein: Fantastic. Hi, everyone. It’s great to have you here today. Thank you so much for joining us. I am privileged to be sharing the stage with Rose McLaughlin here from Moderna. For those of you who do not know me, my name is Courtney Breen. I cover the U.S. large-cap names here at Bernstein. We’re hoping to have a bit of a conversation, particularly into the oncology portfolio at Moderna today. We’re going to start first with a bit of a presentation to get some context around this part of the business, because I think it hasn’t necessarily been front and center over the last five to ten years of the Moderna story. This will be a great opportunity to perhaps dive into that a little bit better. We will shift to Q&A. As a reminder for everyone in the room, please feel free to use the Pigeonhole app.

You can put through some questions if there’s something that’s burning that you really want answered. I’ll work to integrate those into the question set that I already have. With that, I’ll perhaps hand over to you, Rose, to walk us through the presentation and any other opening comments that you have.

Rose McLaughlin, Moderna: Fantastic. Thank you very much for having us. We, of course, are incredibly excited about the work that we’re doing in oncology and recognize that we want to share that more broadly. Today we want to share... Oh, let’s see.

Courtney Breen, Analyst, Bernstein: Sure.

Rose McLaughlin, Moderna: All right. We’ll start the clicker up. Maybe we can swap that guy and... Thank you. Thank you. We want to share an overview. Perfect. Thank you. That power helps. An overview of our oncology portfolio. As we look to establish ourselves in the field of oncology, we are advancing a portfolio that takes multiple different therapeutic approaches and uses multiple parts of our platform technology. In doing this, it’s letting us address multiple different types of cancer, as well as different stages of cancer. We’ll walk through the different parts of the portfolio and give you a sense of where we are. We’ll start with Entismaran autogene, which is also known as INT, or Individualized Neoantigen Therapy, or mRNA-4157. This is a truly individualized therapy. For every patient, we take a sample from their blood, which we consider healthy tissue, and from their tumor.

We sequence those samples and compare them so we can identify mutations that are present only in their tumor. Those mutations are specific to that patient. We refer to those as neoantigens. We then use our own proprietary algorithms to select neoantigens and design this therapeutic just for that patient. We then manufacture it and get it back to that patient within weeks so that they can start their therapy. We have previously shared last year results from the three-year follow-up of a phase two randomized study where we combined INT with Keytruda and compared that to Keytruda alone. In that study, the primary endpoint was recurrence-free survival, and we’ll walk through the three-year data. We also want to highlight that we’ll have that final five-year follow-up available in 2026. We look forward to sharing that as well. What we saw in our three-year follow-up has been very encouraging.

I think you’ll see it’s driven substantial investment in expanding the settings in which we are testing INT. When we look at recurrence-free survival, what we saw was that by combining INT with Keytruda, we could reduce the risk of a patient having their cancer recur or death by 49% versus Keytruda alone. When we look at some of our secondary endpoints, such as that risk that a patient might develop a distant metastasis, we see that we can reduce the risk of that by 62% by combining INT versus Keytruda alone. Importantly, for a large portion of our oncology portfolio, we see a safety and tolerability profile that is, we believe, differentiating. When you combine INT with Keytruda, you see a well-tolerated profile. You do not see, we believe, enhanced safety or tolerability events on top of Keytruda alone.

For patients, particularly in these early settings where they’re thinking about that risk-benefit equation, we think being able to offer clinical benefit with no additional safety or tolerability issues is particularly differentiating. We are currently in a phase three study in the adjuvant melanoma setting where we are combining INT with Keytruda. This study completed its enrollment at the end of 2024. The design of the study is again looking at recurrence-free survival. We actually will need to accrue a certain number of cases before we are able to look at those data. We have gone, of course, as we look at that case accrual and modeled it based on our phase two study, as well as other Keytruda studies. We are cautiously optimistic that we’ll be able to share data from this study in 2026.

In addition to this pivotal study in adjuvant melanoma, we’ve started a development program for INT that expands across multiple different tumor types. For example, you’ll see we have two additional pivotal studies running in non-small cell lung cancer and SCLC. We have studies that are phase two randomized studies in high-risk muscle-invasive bladder cancer, renal cell cancer, and non-muscle-invasive bladder cancer. As you look through these studies, in addition to testing different cancer types, we have the opportunity to test INT in different combinations. For example, in the non-muscle-invasive bladder cancer setting, we’re able to test INT on top of BCG, which is standard of care there, as opposed to Keytruda, and also as a monotherapy. We’re excited to see those data.

Finally, we most recently announced that we’ve started a study in a late-stage setting, first-line metastatic melanoma, to really understand what INT’s potential is in those more advanced patients. Based on the data that we saw in INT, we’ve been very encouraged about this therapeutic approach for oncology. We’ve expanded our pipeline of cancer antigen therapies. As you can see from the small graphic there, where INT is individualized, our other cancer antigen therapies, we actually refer to them as off-the-shelf. They target antigens that are shared among many patients. They do not need to be individualized. They can be manufactured once and available when that patient appears and their clinician is ready to treat. There are two flavors of our cancer antigen therapies that we’ll talk through. The first is mRNA-4359.

mRNA-4359 is designed to encode antigens from the PD-L1 and IDO proteins and to train your immune system to kill the cells that overexpress those proteins. There are two types of cells that do that. One are cancer cells. You can imagine simply training your immune system to kill the tumor. The second are immunosuppressive cells. We think this is an important aspect of the mechanism of action of mRNA-4359. You can think about T-regulatory cells, myeloid-derived suppressor cells, the types of cells that create that environment that makes it hard for your immune system to recognize and then get activated as it’s finding antigens on tumor cells. You think of that as taking the brakes off of the immune system. Because this is such a central mechanism in cancer, we believe mRNA-4359 will be applicable in multiple different types of cancer.

We think of it more like the pipeline and a product type of concept. We’ve previously shared data from the ARM1A shown here, the dose escalation at ESMO last year, I believe. That is looking at mRNA-4359 as a monotherapy in advanced metastatic patients. We are looking forward in October of this year at ESMO to sharing additional data from the ARM1B of this study, where we are looking at mRNA-4359 in combination with Keytruda and looking in melanoma and NSCLC patients who are again advanced in metastatic and checkpoint inhibitor refractory. These are very heavily pretreated patients that we’re going into. We’re excited to be able to share those data shortly. In addition, we are planning phase two ARMs. We’re expanding into different indications, including first-line NSCLC with PD-L1 high, as well as first-line melanoma.

As we think again about that mechanism of action, we’ve been excited to see, as we think about some of our translational data, that we’re seeing those regulatory T cells and those myeloid-derived suppressor cells being depleted from the periphery in our studies. We’re actually seeing less T cell exhaustion. We’re starting to see that the therapy is creating that much more permissive immune environment for your body to identify and tackle a cancer. In doing that, we’re still seeing that safety and tolerability profile that’s pretty similar to what we saw with INT. Quite favorable, well-tolerated. Your adverse events are very low-grade. Coming back to our off-the-shelf therapies, we have another flavor that is specifically tumor-targeted. The antigens that it encodes are present in those tumor cells. Our lead program there is mRNA-4106. There we go. For mRNA-4106, this therapy encodes for multiple tumor targets.

We have designed this therapy such that when you look at an indication within cancer, we expect a broad population to have these antigens present in their tumors. We do not need to go and sequence their tumors. We do not need to go and look and see if their tumors are expressing these proteins. In addition to covering a broad set of patients within a type of cancer, if you look at a single patient, we anticipate their tumor will also be expressing multiple antigens within our design for this therapeutic. As it turns out, when you look at the different types of cancer, many of them actually share underlying biology. Even though this is not going after a central immune pathway, it is going after antigens present in cancer cells. They’re actually shared across quite a number of different types of cancer.

We do believe that mRNA-4106 and the cancer vaccines we’re developing in this space will be broadly applicable as well. 4106 is currently in a phase one study where our primary objective is safety and tolerability. We’re looking at it as a monotherapy and in combination with checkpoint inhibitor therapy. Now we’ll take a bit of a pivot in the portfolio in terms of the therapeutic approach that we’re taking on oncology. As opposed to our cancer antigen therapies, which we think of as really training the immune system to identify and kill cells, we think of T cell engagers as actually guiding your immune system toward the cells that you want to eliminate. We have two flavors of T cell engagers that we are developing. The first is focused on targeting what we call surface antigens, proteins on the surface of cancer cells.

The T cell engager is a secreted protein, and it will bind to CD3 on any T cell. It will bind to this protein on the surface of a cancer cell, hold those two in proximity, help activate that T cell, and help that T cell kill that cancer cell. Now, as we think about developing T cell engagers with our mRNA platform, we have two key advantages in this space that we believe are differentiating versus recombinant protein approaches. The first is what we refer to as multiplexing. We specifically use that vocabulary as opposed to combination because from a regulatory perspective, our products are a single product. Within one product, not a combination, we are able to encode for T cell engagers that can identify three different surface antigens. We believe this is important as you’re thinking about antigen escape when you’re treating different types of cancers.

We also believe that this is important to address tumor heterogeneity. Not every cancer cell is identical. They don’t all express all of the same targets. By being able to go for multiple targets at the same time, you have a better chance of getting that deep and durable response. The second differentiating factor for us is that we can also encode for proteins that can provide some of those important co-stimulatory signals, which can both increase your T cell activation and increase your specificity. You wouldn’t just want to increase T cell activation without giving it that specificity. We have the ability to do that with our mRNA platform. I’ll come back to mRNA-2808 in a second. The second flavor of T cell engagers that we’re developing are in combination with our collaboration partner Immatics.

These, rather than targeting proteins on the surface of a cancer cell, actually target intracellular antigens that are presented on that cancer cell. What’s important for us in this aspect is that it allows us to open up that antigen space. There are more targets available to us to pursue. In addition, some of these proteins that only appear inside cancer cells are very, very specific to those cancer cells. They are not appearing. They are not expressed or presented in your healthy tissue. You’re broadening that therapeutic index and being able to offer a potentially safer and more tolerable therapeutic. Coming to our lead program in this space, mRNA-2808 is in a phase one study now in relapsed multiple myeloma patients who have been triple class exposed. Our primary endpoints are safety in this study.

We are quite keen to see the translational and clinical outcomes of this study, for example, looking at impacts on different B cell populations in these patients. Moving to the final portion of our oncology portfolio, we have what we refer to as our cell therapy enhancers and our in vivo cell therapies. I’ll start on the top here, but I’m actually going to do a bit of an aside to talk about ex vivo cell therapy. We are not developing ex vivo cell therapies. However, we do believe that we can improve the performance of them. For those who are familiar with ex vivo CAR-T or ex vivo TCRT, these have been truly transformative therapies for the hematological malignancies. In solid tumors, they have shown some pretty interesting effects, but they haven’t shown the same level of effect as in those heme malignancies.

We believe, based on clinical data, that you continue to see this correlation between the persistence of those engineered T cells and the state, the health, if you want to think of it that way, of those engineered T cells in a patient and clinical outcomes. Our cell therapy enhancers are designed to improve those two things in the patient. In collaboration with Immatics, who’s developing an ex vivo TCRT, you can imagine ex vivo cell therapy. What you first do is you take the cells out of the patient, you activate them, you proliferate them, you engineer them. You have to lymphodeplete the patient, so killing a bunch of their remaining immune cells. You infuse those cells back into the patient. You have the engineered T cells back into the patient. It’s an extremely arduous and individualized process.

We can then administer our cell therapy enhancer, which is designed to encode the exact antigen that the engineered T cells recognize. We can actually boost the T cell response of the engineered T cells in the patient’s body. We can do this over time. They only get those cells infused once, but we can boost as often as is needed. We currently are in a phase one study where we are combining our mRNA-4203, which, as I mentioned, was designed explicitly to activate the engineered T cells of our partner Immatics and their IMA203 therapy. This is in patients with cutaneous melanoma or synovial sarcoma. Our primary endpoints are safety, but the translational and clinical data from the study that we’ll be watching closely. I’m going to come back actually to the bottom half of this slide, which is in vivo cell therapy.

As I described ex vivo cell therapy, I think you can start to imagine some of the hurdles both that patients go through, that clinicians go through, that your manufacturers go through in providing that drug. We think if you’re able to have cell therapy that uses an mRNA LNP-based approach, you could eliminate many of those barriers. Our first approach is what we refer to as CAR-M. You can think of the M as standing for monocyte. Using mRNA LNPs, we transfect monocytes and macrophages within the patient’s body and encode a CAR, just like you would imagine in CAR-T. Now, with that CAR expressed on these monocytes, they are going to traffic to the tumor. Within the tumor, that CAR finds its antigen, binds to it. That monocyte or macrophage will then get activated. It will start secreting immune stimulatory cytokines around it.

It will start phagocytosing and eating those cancer cells around it. Perhaps most importantly, in doing that, what it does is start to present even more antigens from those cancer cells to the rest of your immune system. It actually broadens the response well beyond the CAR that was originally encoded in the therapy. Once it gets into the tumor, it’s showing many, many, many different antigens to your immune system. In vivo CAR-T, similarly, uses LNP technology to transfect T cells so that they express a CAR. Once they recognize that antigen on the tumor through the CAR, they will directly kill those cancer cells. Thank you again for the opportunity to share some of our oncology portfolio with you. We are really excited about the diversity of therapeutic approaches that we are able to take.

We’re excited about the different parts of our platform technology that we are able to leverage in this space. We really like the opportunity that it offers to be able to treat different types of cancer and different stages of cancer to truly have impact on those patients.

Courtney Breen, Analyst, Bernstein: Absolutely. Thank you so much for taking us through that, because I think there is a lot there.

Rose McLaughlin, Moderna: Yes.

Courtney Breen, Analyst, Bernstein: There’s a lot that sits kind of behind the INT, which has been kind of your leading asset in many ways. Can you talk a little bit about kind of how these pieces fit together? It feels like there’s a lot of different approaches to come at patients, perhaps kind of shifting from individualized, but it’s all built on the backbone of the mRNA. Can you talk about kind of the portfolio strategy?

Rose McLaughlin, Moderna: Yes, absolutely. As we are thinking about it, we are thinking about this as building a toolkit that can engage with the immune system in different ways based on what’s needed in different stages of cancer. For example, if you are thinking about a patient that is in a preventative or precancerous state, you might only need to prime the immune system such that when one of those cancer cells develops, it quickly recognizes it and eliminates it. If you are thinking about an early-stage cancer patient, perhaps they’ve had a resection, you might want to train the immune system with a cancer antigen therapy to prevent recurrence after they’ve had their tumor removed. If you start thinking about some of your more advanced patients that are later line, their immune systems might not be quite as competent. You might want to access a broader population of T cells.

You might think there that in order to really, again, have deep and durable responses, you might want to use something like a T cell engager that is multiplex and can handle a complex heterogeneous tumor. You might want to consider a cell therapy where, instead of just guiding your immune system, you are just engineering it to go and fight that cancer. We think of it as the different ways to leverage the immune system that will be most relevant in those different stages of cancer.

Courtney Breen, Analyst, Bernstein: Absolutely. I think in a couple of different places, you’re doing kind of concept of off-the-shelf versus your own personalized work plus perhaps potentiating other personalized work when it comes to the CAR-T space as well. How do you think about the utilization of those opportunities? Is there the potential that off-the-shelf can perhaps deliver the same types of durable responses as the personalized? How might these things fit together?

Rose McLaughlin, Moderna: Ultimately, the data will determine whether an individualized approach or a sort of off-the-shelf approach may be superior as we go forward. We are seeing similar safety profiles from those two, which we think is encouraging. Ultimately, some of the other differentiators might actually be the availability. When you think about the manufacturing of those individualized therapies, you do need a window to design and manufacture. When we think about some of the off-the-shelf therapies, they may be available as soon as a patient arrives. Those may sit really well together in a sort of complementary way.

Courtney Breen, Analyst, Bernstein: Absolutely. I think it’s about a six-week window or so for your INT therapy.

Rose McLaughlin, Moderna: From our early studies.

Courtney Breen, Analyst, Bernstein: Is that right? One thing that I just wanted to ask about because I think it popped up in the presentation, the mRNA-4203, which is kind of potentiating the cell therapy intervention. As you look at those, I think the early studies are in solid tumors predominantly, where CAR-T hasn’t necessarily had the kind of full, deep, durable effects in the same way as we’ve seen in liquid. Is that the space where you think the most opportunity is? Could these also be used to help increase the response rate or increase the durability of responses or perhaps even reduce the amount of CAR-T that needs to be infused in the heme spaces as well?

Rose McLaughlin, Moderna: We do think any space where you may not have the same access to antigen, or you may be in an immune suppressive environment, we do believe a cell therapy enhancer could have a benefit. Those are perhaps exaggerated in the solid tumor settings, but it’s not that they are not present in some of those other liquid tumors.

Courtney Breen, Analyst, Bernstein: Got it. That’s super helpful. As you walk through that, it feels like there’s a lot going on as we looked at a lot early, as well as some big readouts for the INT program as well.

Rose McLaughlin, Moderna: Yeah.

Courtney Breen, Analyst, Bernstein: Can you talk about some of the big catalysts we should be looking out for? You mentioned some of the data we’re going to get in 2026. Can you talk about expectations on what you might be looking to deliver and the goals there?

Rose McLaughlin, Moderna: Sure. If we go sort of in a chronological order, as I mentioned at ESMO 2024, we are looking forward to sharing ARM1B data from mRNA-4359. As we roll into 2026, we should be able to share the five-year follow-up from INT in that phase two randomized study in adjuvant melanoma, the same setting as the pivotal study that we have ongoing. The pivotal study, we are cautiously optimistic that we will have enough cases to be able to share data over the course of 2026. When you look through the other indications as they are coming, our study in adjuvant renal cell carcinoma with INT has also fully enrolled. That is likely next in line for providing data.

We may also have some smaller, more opportunistic readouts this year because we still have phase one cohorts running with INT in exploratory settings, spaces like pancreatic and gastric, where we’re really going into different cancer types that have very different profiles of their tumor microenvironment and tumor mutational burden.

Courtney Breen, Analyst, Bernstein: Maybe to that point that you just finished on the different types of tumors, the kind of perhaps immune sensitivity of those tumors as well, or as I look through your portfolio, in many ways, it’s about potentiating, enhancing, or directing the immune system to target kind of that particular tumor type. Melanoma is kind of a good place to start always, highly immune sensitive cancer. Some might then say non-small cell lung cancer is another place. Triple negative breast is another place that’s potentially being very responsive to checkpoint inhibitors as well. How do you think about that strategy and your ability to perhaps kind of double down in a place like melanoma or non-small cell lung versus being able to broaden and go across different tumor types?

Rose McLaughlin, Moderna: I think what you’re seeing us do is a very methodical exploration of those different variables because we believe INT has the potential to bring clinical benefit in the different settings. Starting in melanoma, as you pointed out, tends to have high tumor mutational burden, given that many, many years ago when we started INT, thinking about the design, it is required to have sufficient mutations to be able to design it. Starting in an environment where you have that high tumor mutational burden and sensitivity to checkpoint inhibitors and IO therapies makes a lot of sense. Starting out in early settings in adjuvant melanoma, as we proceeded through, you can think through how you walk down on tumor mutational burden. NSCLC often comes next. We then look at things like bladder cancer, renal cell carcinoma as you’re working through.

We’ve also been thinking about things like the tumor microenvironment, what sort of T cell infiltration you have there. How hot is that tumor microenvironment? You can sort of see us walking down that as well. The last variable that we’ve introduced is truly that stage. When you think about that early adjuvant setting, many of these patients, they’ve had a resection. You’re really looking to stop recurrence. You don’t anticipate having a very large tumor bulk as burden. We’re exploring that area first. We are still looking to see if we have the potential for impact in those later line patients that may have more tumor burden and potentially metastatic disease. We’ve sort of explored those in chronological order.

Courtney Breen, Analyst, Bernstein: Fantastic.

Rose McLaughlin, Moderna: Yeah.

Courtney Breen, Analyst, Bernstein: I do want to kind of ask, I mean, there are a few other players out there. We’ll get into kind of some of the read across questions. Even within your own portfolio, as you’re getting scientific questions answered for one of these assets or one of these profiles, how much are you able to feel like that de-risks the others? I think safety is clearly one area where you feel really good. That almost just carried across from COVID and where you began in terms of a commercial product and the safety that you’ve been able to carry through. What other markets are you looking for for success in particular indications or with particular assets that give you confidence for the rest of the portfolio as well?

Rose McLaughlin, Moderna: Sure. As we look at the data coming out of INT, I think you’ve already called out safety as the first piece that we believe translates across our cancer antigen therapies. We also believe, as you look at our ability to drive really strong CD8 and CD4 T cell responses, that we’re understanding a lot about that in the individualized setting and then reinforcing those learnings with mRNA-4359. We do believe that will pull through into the rest of the portfolio. There are also quite a few translational endpoints that shouldn’t be underestimated. As you start to recognize over the course of multiple studies, initially with INT as its most advanced, what those translational signatures are that appear to be correlated with your clinical benefit. Those could be, you think of things as how broad the T cell response is, not just what did we encode in the vaccine.

We believe that translational understanding will also inform the rest of the cancer antigen therapies.

Courtney Breen, Analyst, Bernstein: Fantastic. Maybe getting to the competitive kind of BioNTech out there doing some similar things in the mRNA space, what are the read acrosses that you’re looking at from data you see out of them? I think IO Biotech is also doing some work on some of the components that you’re experimenting with, so what data do you look to coming from those players as giving you either positive signals or things that you get worried about?

Rose McLaughlin, Moderna: Sure. I would perhaps make the general statement and then go into the more nuanced. The general statement being where we and our competitors are exploring similar biological hypotheses. I think we look forward to that as potential read through and de-risking for us as well. We, all three of us, utilize slightly different platforms. That is where some of the nuance does come in for us. As we think about BioNTech’s iNEST, their individualized therapy, there are some differences. We can’t necessarily say which one may or may not make a difference, which is why we’re sort of looking to those readouts. For example, they encode 20 neoantigens. We encode 34. We each have our own proprietary algorithm for selecting those neoepitopes and designing those therapies for patients.

They do have an mRNA-based platform, but they actually use a lipoplex that they IV infuse, whereas we use a lipid nanoparticle that we inject intramuscularly. You may have different antigen presentation within the body. There are some of those platform differences that we want to keep in mind as we start to see the different results. As we look at IO Biotech, their lead asset is a peptide-based vaccine for PD-L1 and IDO. This is very similar in concept to what we’re approaching with 4359. They recently released their phase 3 data in first-line melanoma, which, of course, we were watching closely. As we look at those data and the biological hypothesis that we tested, is this the right therapeutic approach? Are those targets relevant? Can they have clinical impact? We feel like they did demonstrate that biological hypothesis.

As the trial read out, they did narrowly miss on the statistical significance. From the what do we read through to our vaccine for mRNA-4359, we feel like that’s helped de-risk it as well and encouraged us to continue aggressively developing in that space. From a platform perspective, they are still a peptide-based platform. We have slightly different antigens that we encode. We’ve chosen to encode slightly broader antigens for broader coverage. We look to the mRNA platform to drive particularly strong CD8 and CD4 T cell responses, which we think are really critical to that mechanism. We do believe that there is still some nuance between a result that would be generated with their vaccine and a result we would generate in the same setting.

Courtney Breen, Analyst, Bernstein: Absolutely. One other area that I did want to touch on was the T cell engagers and the work that this is some of the earliest work that you’re doing in trying to bring, confirmationally, these cells close together and ensure that they can have real impact. Why is that the next place to go after presenting antigens? Why is this the next place for Moderna to begin to advance this technology?

Rose McLaughlin, Moderna: Yeah, absolutely. As we mentioned, as you get into some of these other later lines of cancer, you may not have the same immune competence. You may not be able to take just one T cell population. You may have immune dysfunction. You may not be able to say, I’m going to use a cancer antigen therapy approach in that setting. In that case, if you use a T cell engager, you can actually access any T cell in that patient’s body, and you could administer these repeatedly over time. We also find that the heterogeneity, as you get into those settings, is particularly well addressed by our platform. This has actually been playing out in clinical data in the field.

If we think about multiple myeloma, where some of the earliest T cell engagers have shown their promising data, right now, I believe it’s moving to pivotal now, there is data taking two T cell engagers that were developed separately that look very promising and clinically combining those recombinant proteins in patients. When doing that, the results look like an improvement in your overall response rate, and again, durability of response starts to look even better. You start to see patients that have some of the more complicated disease responding. In a perhaps parallel thought experiment, there are protein engineering approaches that others are taking so that they can actually target both of those antigens. Instead of a clinical combination, they’re designing it all into one protein, which is pretty complex protein engineering, and also seeing similar clinical benefit.

Remarkably, both of these are not seeing additive toxicity, which is fantastic for patients and developers alike. When we look at that data, we see a significant opportunity to expand multiplexing. mRNA-2808, our lead asset in that setting, happens to target three cell surface proteins, but there’s no actual reason that we need to necessarily limit it to three from a platform perspective.

Courtney Breen, Analyst, Bernstein: That’s wonderful. That’s very exciting.

Rose McLaughlin, Moderna: Yeah.

Courtney Breen, Analyst, Bernstein: This is kind of a journey that Moderna has been on for a while. As I said earlier, it hasn’t necessarily been at the front of the conversation or the company story. Through this, you’ve also partnered with a number of other companies along the way, and Merck being one of the big partners when it comes to INT and combinations with Keytruda. As you look to these newer assets coming through, you’ve got a couple of partnerships here and there. What are the capabilities that you’re looking to bring in from the outside? Is it particular assets that you want to combine with? Is it clinical development capabilities? Is it commercial capabilities? What’s going to be important for Moderna to succeed with these assets going forward and building the partnerships and collaborations around the assets?

Rose McLaughlin, Moderna: Sure. And just for those who aren’t familiar, in INT, we are partnered with Merck. It’s a 50/50 cost and profit sharing relationship. We share our costs, including our CapEx. We make our decisions together. It also means that we and Merck together are able to access some pretty substantial development and commercial capabilities that are already in place. That has allowed us to accelerate that development program into so many different settings, which has been fantastic. Now, our partnership with Immatics comes from a very different angle. It’s in a very early space where they brought deep biological expertise in T cell receptors. We were able to combine that with the power of our platform to really start these new concepts early in development. As we think about the rest of our portfolio, we are in a fortunate state where we have many different investment opportunities.

Should a partner be able to bring capability to that that could accelerate a development program or let us explore a broader set of spaces where we believe we may have that type of pipeline in a product opportunity, we would be open to doing that to create even more value.

Courtney Breen, Analyst, Bernstein: Fantastic. Often it is the trade-off of what can I start today, what do I have to wait to start next year and the year after because of those constraints, and de-risking those opportunities while making sure you’re fully investing simultaneously, which can be really, really, really tough. In the last couple of minutes, I do want to hear just a little bit about, as you think about your oncology strategy, and the whole theme of this conference has been leading and disrupting. It feels like you’re on a path to disrupt some of the ways that we have traditionally gone after some of these cancer types. How will you know that you’re on the track before perhaps all these drugs eventually make it to market? How will you know that success is around the corner? What are those disruptive milestones that will de-risk this portfolio for you over time?

Rose McLaughlin, Moderna: Sure. I think for our earlier programs, we are certainly looking at some of those translational data that you can get out of your early clinical studies. As you look across the field, you can start to interpret translational data and translate that into what you would anticipate as clinical effect. I think for INT, as I mentioned, it’s sort of a methodical walk through all of the different settings in which it can work. We’ll be watching that and sort of adjusting and potentially adding to our development program in certain places where we see success and potentially exploring new spaces, depending on what we see in some of those translational data.

Courtney Breen, Analyst, Bernstein: Fantastic.

Rose McLaughlin, Moderna: Yeah.

Courtney Breen, Analyst, Bernstein: Very exciting time ahead. Any final comments on kind of what you hope Moderna to look like when it comes to oncology over the next five to ten years?

Rose McLaughlin, Moderna: I’m obviously very excited about the different therapeutic approaches that we’ve been able to take. It is an incredibly diverse portfolio for a company. For us, it utilizes different parts of our platform technology that we have invested in and de-risked in actually very many different settings, from infectious diseases to rare diseases. For us, this is really fulfilling the mission that we’ve had to have a really significant impact on patients’ lives because it’s opening up just such a vast opportunity space to do that.

Courtney Breen, Analyst, Bernstein: Fantastic. Thank you so much for your time today, Rose. It’s been a pleasure.

Rose McLaughlin, Moderna: Thank you for having me.

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