Mersana Therapeutics at TD Cowen Summit: Strategic Updates on Oncology Innovations

On Tuesday, 27 May 2025, Mersana Therapeutics (NASDAQ:MRSN) took the stage at TD Cowen’s 6th Annual Oncology Innovation Summit. The conference call, led by Tara Bancroft of TD Cowen, highlighted Mersana’s recent advancements and future strategies in oncology, particularly focusing on their EMILI drug for treating B7-H4 expressing tumors. The discussion was a mix of promising developments and ongoing challenges, as the company navigates its pivotal trials and operational enhancements.

Key Takeaways

• Mersana’s EMILI drug showed a 31% overall response rate (ORR) across all tumor types in the intermediate dose range.
• The company is implementing Protocol Amendment 5 to mitigate proteinuria, a common side effect, allowing treatment continuation if patients remain asymptomatic.
• Future pivotal trials will likely favor a randomized design to expedite time-to-event analysis and include a control arm.
• The ASCO presentation will provide further data on non-breast cancer patients and high-dose regimen efficacy.
• Mersana aims for a response rate above 20% in upcoming trials to demonstrate clinical benefits.

Operational Updates

• Proteinuria Mitigation Protocol: Mersana has introduced Protocol Amendment 5, which uses ACE inhibitors and ARBs to manage proteinuria without interrupting treatment for asymptomatic patients. Early feedback from physicians indicates the protocol is effective.
• Dose Expansion: The focus remains on both intermediate and high-dose regimens to maximize drug exposure while managing side effects like proteinuria.
• Biomarker Assay: Adjustments to the B7-H4 expression assay aim to establish it as a commercial standard, enhancing the precision of patient selection in trials.

Future Outlook

• Pivotal Trial Design: Mersana plans to conduct a randomized trial to leverage quicker time-to-event analysis and include a control arm, pending FDA approval. This approach could eliminate the need for a second confirmatory trial.
• Patient Population: The trials will target TNBC patients with one to four lines of prior therapy, including those previously treated with topo-based ADCs.
• Response Rate Target: The company is setting a goal for a response rate exceeding 20%, compared to a 5% rate in the control arm, to validate the clinical benefit of EMILI.

Q&A Highlights

• ASCO Presentation Focus: The upcoming ASCO presentation will extend data from the ESMO breast presentation, focusing on non-breast cancer patients. The data cutoff remains consistent with ESMO.
• High-Dose Data: Additional data in the second half of the year will clarify the efficacy of proteinuria mitigation strategies at high doses.

For more detailed insights, readers are encouraged to refer to the full transcript below.

Full transcript - TD Cowen’s 6th Annual Oncology Innovation Summit:

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Good afternoon, everyone. I’m Tara Bancroft. I’m one of the senior biotech analysts here at TD Cowen. And thank you so much for joining our sixth Annual Oncology Innovation Summit. And for our next session, we have a Q and A with Mersana Therapeutics.

And it’s my pleasure to introduce Marty Huber, president and CEO, and Brian Deschuytner, COO and CFO. So it’s a privilege to have you both here, and thank you so much for joining me and us. So before I get started with the questions for those in the audience, I just want to note that you can feel free to email me any questions at terra.bankroft@tdsecurities.com, and I’ll make sure to to get it asked. So I guess a good place to start, Marty, would be, you know, you guys have had these two data updates since January. So maybe we could start with a review of that and what we’ve learned about Emily from the, you know, the phase one data that you guys have presented so far, both, in January and at ESMO breast.

Marty Huber, President and CEO, Mersana Therapeutics: Thank you, Tara. And we’re really excited to catch everybody kinda up to date on where we are, and answer your questions. Just at a kind of a higher level, we were we’ve set out to be innovators in scaffolding or payload. So part of our thing was trying to address some of the challenges. So we were very excited about the initial dataset and then the update that the March data cut that we used for our ESMO breast presentation and we’ll be using for ASCO presentation and and kind of summarize a few areas.

First, what we have learned from our phase one, the dose escalation and backfill patients is that EMILI, which is our name for our v seven h four ADC built on this platform, is delivering the differentiated safety profile that the Dolasynthen platform was designed to do. So we’ve achieved effective doses without meaningful neutropenia, neuropathy, or ocular toxicity, which are usually associated with other microtubule targeting ADCs. Think you know, if you think of the orastatin class in general. Second, we learned that EMILY had the potential offer meaningful clinical benefit to the patients whose tumors express b seven h four. This is one of the targets where all of us are, you know, and including our competitors are focused on the b seven h four expressing subset of tumors.

And what we found in this initial dataset is that when we looked at the all the patients we had treated in kind of our intermediate dose range, this one to two milligrams per kilogram, that we observed an overall response rate of twenty three percent in our initial dataset. Those are confirmed objective responses. But in a in our most recent dataset, which we shared at ESMO breast, that’s up to thirty one percent across all tumor types. So we think this is compelling efficacy, especially focused on kind of the third point, which is there’s a lot of topo payloads out there. A lot of and they’re and they’re highly successful.

But one of the unfortunate realities of this is what we’re learning is that if you give another topo inhibitor after the first one, regardless of target, it just doesn’t seem to work. So what we have seen in our dataset is we put and this was really kind of the focus of the ESMO breast presentation that we saw 23 response rate in these are late line, highly refractory TNBC patients, all of which had seen a prior topo payload. This is a setting where our best of response rate’s like five percent. So we’re very excited by the concept of demonstrating efficacy, and we’re the the leading b seven h four for showing efficacy in this post opus setting. And we think we’re we’re and then the kind of the final piece of this, as we see you know, it’s kind of funny to be excited about a competitor’s data, but with Gilead sharing their recent ASCENT three and four trials, which are gonna move Trodelvy into first line breast cancer, we think this, you know, really is gonna increase the number of patients who are this is gonna be this massive unmet need of you’ve gotten a topo.

Now what next? So overall, we think this is good, and then we combine all that is kind of the summarize that is well, if you think about it, we’ve gotten our fast track designations, which are not only in TNBC, but also in certain breast cancer patients who are post topo. So this whole post topo concept in breast cancer is something that we’re now even starting to see recognized by the regulators.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. Awesome. Thank you for that update. So I guess, you know, this is the pre ASCO series, and you guys will have a presentation that that you guys have released an abstract for. So I guess what I’d like to kinda set the stage for is what can we expect in this ASCO presentation?

Is gonna be additional follow-up from the ESMO data or any new patients included? Are there more backfill, more detail on low dose? What can we expect?

Brian Deschuytner, COO and CFO, Mersana Therapeutics: Yeah. Maybe maybe I can take that, and and I’ll I’ll just start by saying, of course, you know we’re under embargo, so I need to be a little bit careful about what we what we reveal about the the presentation content. But I can say that this is the same data cutoff, as the ESMO breast presentation, so more follow-up than what we presented in in January. But here in ASCO, covering all the enrolled tumor types with with more details on the non breast cancer patients. You know, as Marty noted earlier, just to remind you, and this was part of the ESMO breast sort of contextual slides, in in the v seven eight four high evaluable patients treated at intermediate doses across all tumor types, we saw the confirmed ORR improved to to thirty one percent.

So we’ll give more details on the underlying data there.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Yes. Definitely understood. You know, we we really do look forward to to seeing that data. So we can talk a little bit more about the backfill then, you know, without going into the details of of what the data are actually going to be.

So can you tell us or even just review for us how many patients that you enrolled at the high dose that underwent the these new mitigation protocols for proteinuria and those adjustments that were made are so these patients, these are gonna be the additional high dose patients in the second half update, not at ASCO. Right?

Marty Huber, President and CEO, Mersana Therapeutics: Right. The well, yes. The folk just to kinda step back a little bit. The focus for this initial data this March data cut for the ESMO breast and for the ASCO is gonna be really primarily focused on patients in this intermediate dose range, this thirty eight to sixty seven. However, I I do wanna point out there are some high dose backfill patients which will be included in these in that are in this data cut, and then will be included in the presentation.

But I would like to note that these are still patients who primarily were treated under the original kind of approach to proteinuria. So we and I and let me step back a little bit. What we’ve observed, and I think this was part of our our back on escalation, our initial dataset was one of the treatment related adverse events we’re observing, especially at the high doses, was proteinuria that led to treatment interruption. And we’re kinda learning that this is a forstatin payload phenomenon. We see this with other ADCs.

And what we observed was the problem wasn’t so much that this was leading to renal failure or nephrotic syndrome, etcetera. The challenge was is per protocol, the physicians had to stop the treatment. And, you know, one of the disappointments of our initial dataset was we saw at these high doses, the majority of patients would get to thirty percent or more reduction, which would have been a PR, but then they would get a treatment interruption weren’t able to. In January, we announced that we had put in protocol amendment five, as we affectionately refer to it, where we have put in additional mitigation efforts as well as, you know, based on the advice our investigators and oncologists were giving, that you can treat through that as long as you’re not seeing symptoms or any type of effect on on on, granted clearance. And so that if you think about it, those patients being treated starting in January, by the March cutoff, you’re not gonna get that.

So to kinda answer your question is the the data that’s really gonna give us a good handle on how well this proteinuria mitigation works in the high dose and does that translate into superior efficacy is gonna be the second half dataset. That’s that’s not gonna be here at ASCO.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Perfect. Yes. Thank you for clearing that up because I definitely talked to a lot of folks since the ESMO breast update, and I I wanna make sure that that is exceedingly clear to people what what we can expect in at ASCO and in the second half. So, you know, since that the focus of ASCO is not necessarily that, can you maybe tell us a little bit of the early feedback that you’ve been getting from physicians that are using this this adjusted protocol?

How do you know? What are they saying about it? Are they noticing differences?

Marty Huber, President and CEO, Mersana Therapeutics: I mean, it’s we wanna be a little careful about getting too far ahead of the data, but I do think this is where this was one of these nice partnerships with the investigators. To be frank, they started the the the desire for this amendment because they were the ones calling us up very frustrated because I have a I have a patient who’s responding. Clinically, they’re feeling fine. I look at their labs, and other than their urine and their protein, their labs are okay. So why do I have to hold the treatment?

And we said, well, that’s what we have in our protocol. They said we’ll fix that, and so we amended it. And so now they’re they’re doing, mitigation efforts with, like, start patients early on, even before they you know, at the beginning of treatment with ACE inhibitors and ARBs to try to slow down the proteinuria. But most importantly, it’s the ability to if the patients asymptomatic, continue dosing. So I think maybe the best way is we’re not getting those angry phone calls anymore, as the physicians seem to be adapting.

The sites The the the FDA reviewed the amendment, said fine with it. You know, the IRBs have put it in place at these sites, and things seem to be chugging along. I I just wanna be a little cautious. We’re still a little early in the experiment, but we we are excited about the potential.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Awesome. Yeah. So we will definitely look forward to that in the second half, not at ASCO.

Marty Huber, President and CEO, Mersana Therapeutics: Second half.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. So, alright, one thing that you said in your previous answer was that it’s the proteinuria you think is is an effect of the payload, and you’ve seen it with other payloads in this type of class. And so how do you how do you know that it’s due to the payload? Is it just based on that precedent, or is there any risk of it being a platform effect at all for you guys?

Marty Huber, President and CEO, Mersana Therapeutics: Well, I think as long I mean, well, first of all, we’ve done renal biopsies on multiple patients as well doing preclinical work. And I think this this concept of a toxic podocytopathy is observed with this class. So there’s been and it makes sense because the podocyte requires microtubules to function. So if you get an or a statin or an antitubulin payload in sufficient concentration into a podocyte, you’re gonna have this dysfunction. But what’s one of the positives about this is podocytes are a terminally differentiated cell.

What that means is they’re not actively dividing. And the thing that gets you really kind of nervous with an antitubulin agent, if a cell’s actively dividing with an antitubulin, that’s when you get cell death. So what we’re observing at this point in time or and and is reassuring is that you get dysfunction. The podocyte gets a little disfigured. It doesn’t work quite as well.

But once the drug goes away, it’s functioning quite well. And that this does not, in fact, decrease the ability for for kidneys to clear the the toxins. I mean, basically, you still maintain your creatinine clearance. So we’re and I think the fact that we’re seeing others now report this, like AZ has a clot in 18.2, that has a meaningful rate of proteinuria, and, it’s it’s it’s another orostatin payload that they licensed in, and that’s in phase three. So we you know, the fact that AZ is taking a a product that has a similar pathophysiology into phase three is reassuring to us.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Great. So let’s go into dose expansion a little bit more. So, you know, you’ve said intermediate dose, you’re taking the sixty seven milligrams, and then the high dose, you have this really interesting dose schedule that you have with forty four grams up to eighty. But can you walk us through how and why you selected these doses out of out of the dose escalation.

Marty Huber, President and CEO, Mersana Therapeutics: Right. And thank you, Tara. And and this is one and I I wanna be quick. We’re not trying to come up with the most complicated doses and schedules here. I know sometimes it seems that’s what we do, but but there is actually some logic here, and so I I appreciate the opportunity to kinda walk people through this, is one of the things we observed, and why why do we even care about the high dose, is in that initial dataset, the majority of patients were treated with a high dose of the b seven hundred forty five thousand would get into these we’d see these tumor reductions, and they were dramatic.

They were week six scan. You’d start seeing these tumors. And it was a much it was at a higher rate than we observed with the intermediate and lower doses. So there’s a strong efficacy signal there that we want to pursue. Once you so what’s kind of the next dose level up from sixty seven, which is what we think of as the upper end?

So we our intermediate dose now that we’re taking forward is sixty seven every four weeks. Well, the next meaningful increase in dose is going from sixty seven to eighty, about a 20% increase. That will increase your exposure, give more drug to patients. So we’re thinking eighty milligrams per meter squared is a way to explore the high And interestingly enough, other than proteinuria, eighty milligrams per meter squared is very well tolerated. So this idea of next dose up, proteinuria mitigation, we can basically should be able to give eighty.

But was one more piece of data that we looked at really that kinda got us very excited was when we went we as we had told people before, we were exploring this kind of alternative regimen, day one, day eight, the idea of spreading out the exposure over more time. Interestingly, we had in the high dose kind of expansion backfill, we had four patients who were treated with forty five or forty four point five day one, day eight every four weeks. All four of those achieved a more than 30% reduction tumor at their first scan. And so it’s like four for four. Problem with doing the split dose at these higher doses, which we unfortunately ran into, was it’s just very hard to keep a cancer patient on a day one, day eight schedule, especially with these higher doses.

So we stepped back and we looked at and go, well, in these it’s really aggressive tumor like TNBC, let’s just load them and, you know, people do this in hematologic tumors all the time. So this forty four point five day one day to load them, and then after that, eighty as a single dose every single week. And that was kind of the rationale for this.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. That definitely makes sense. And so then, I guess, you you touched on something there, which, you know, was really interesting about the initial data. So I’m wondering, to what extent do you have expectations for further improved response rates at the high dose than with with this improved protocol? Like, what proportion of of the high dose patients that interrupted looked like Yep.

I might respond if they had stayed on because you mentioned, you know, several of them had these tumor reductions. So Yep. Can you quantify that a

Marty Huber, President and CEO, Mersana Therapeutics: little bit? In our initial dataset, that was of, you know, roughly half of the patients who went who had that initial response subsequently had an interruption and did not confirm the response. So the the success rate for getting people to confirm response rate was under fifty percent. And if you compare this to our intermediate dose or for that matter, anticancer agents, especially like the breast cancer, you would expect over half or even two thirds or three quarters of patients who get that initial response to confirm. So the fact that our, you know, clearly less than half, maybe as low I mean, you know, basically, the majority of the patients who had went to a initial response didn’t confirm, and that was clearly associated with a prolonged treatment interruption.

So our hope and and once again, it’s early, is that by putting in place the the protocol MMFY, the proteinuria mitigation and ability to treat and avoid these interruptions, our expectation would be that we should be able to not only maintain getting more patients into initial response, but getting those into a confirmed response. That’s our goal.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Thanks. Yeah. So then let’s briefly also talk about the patient population that you’re looking at in dose expansion. Is this very similar to the ones that you enrolled in dose escalation?

And are these gonna be the patients that you plan on most closely assessing in the pivotal trial? And, like, are you using the same TPS scoring to determine the b seven h four expression in dose expansion?

Marty Huber, President and CEO, Mersana Therapeutics: I’m gonna take the first part of the question, then I’m gonna turn it over to Brian to talk a little bit more about the the the biomarker. Generally, we’re directionally, this is the the where we plan to go for our target population as we think about how we’re going forward. So if you think about TNBC, this is, you know, classic triple negative breast cancer is patients start out that way. But there are now patients who we know who are ER positive, but have now become negative. So there’s a group of patients that don’t come straight down a TNBC channel.

They start off as hormone receptor positive, and then they crossover. So that, if we think about what we’re looking at, it’s patients who get there. They generally had at least one prior chemo, but with the recent Trudelvy approvals from Ascent, maybe they move up a lot. They don’t necessarily have to have gotten chemotherapy. And those, generally today, are getting a TROP two, Trodelvy, or we’ll see now with the new with the other initialations being approved, how many you know?

But they’re gonna get a basically a TOPO based TROP two. And then there’s also these patients who are receiving in HER two because they really have no other options for them. Currently, we’re not they’re you’re probably not gonna require them to have prior systemic therapy, but in in real practice, these patients are getting one or two systemic chemotherapies. So if you think about that population, so it’s one to four lines of prior therapy, triple negative breast cancer, at least one of those prior lines being a an ADC, that actually when we looked at our and this is what we did share at ESMO breast. When we pulled out the patients who met that criteria, our response rate actually went up to twenty nine percent.

So we think that’s interesting. The PFS was four months. And if you look at the control arm from the first ASCENT trials, it’s a chemotherapy response rate of five percent, that PFS is seven weeks. So we think, you know, focusing on that one to four TNBC prior topo, we think we have a really good opportunity compared to the current standard of care. And I’ll turn it over to Brian now to talk about the TPS on that.

Brian Deschuytner, COO and CFO, Mersana Therapeutics: Yeah. With with respect to TPS, we’re partnered with the same company for the b seven h four expression assay between backfill and dose escalation and and expansion. We’ve made some minor tweaks to that assay so that it could conceivably become the commercial assay down the line. You’ll you’ll recall that our preliminary cutoff for backfill and dose escalation identified about the same size patient population as others working on b seven h four, directed assets. You know, it’s frankly really difficult to compare TPS cutoffs and and research assay staining conditions across these different research assays.

It’s really about, you know, does it, identify about the same prevalent population? I will say we’ll use that assay to determine the final TPS cutoff in expansion based on the data that we’re we’re accruing now.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Great. And just one more clarification question that came from Marty’s answer. Can you just confirm for us what currently like, what is the percent of the overall population that that actually now gets two prior to oppos? And and can that evolve significantly by the time you’re running and even completing enrollment in in the pivotal trial the future pivotal trial?

Marty Huber, President and CEO, Mersana Therapeutics: Brian?

Brian Deschuytner, COO and CFO, Mersana Therapeutics: Yeah. Right. I mean, today, I think in the demo group, it depends which data you’re talking about, but about 27 of patients had had two prior topos. It’s hard to speculate as to whether that number will go or down in the future. One of the drivers might be that increasingly there’s real world data and physician anecdotal experience that suggests that topo after topo simply does not give you a consistent clinical benefit.

And so notably, some of the other b seven h four directed agents that are delivering topos have now actively excluded patients with prior topo from their enrollment criteria. And, you know, in part, we’ve heard from investigators that it’s because very few investigators will enroll a topo after topo. And so whether that number goes up or or down, I I can’t really speculate. The number that exists today is born out of desperation and lack of options, because there’s truly no other targeted therapies available for some of these patients, especially in in TNBC. But I think there’s an increasing dataset that suggests that that’s not really a viable standard of care to try to do these in series.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Makes sense. Okay. So then I I do wanna make sure in the last few minutes that we get the chance to hear your thoughts on single arm versus controlled pivotal trial, like, the the rationale that that you guys are thinking for this, and then really kind of thinking ahead to how you’re strategizing that, what would be, like, the minimum response rate that you’d really wanna see in dose expansion to either select a dose or just have a lot of confidence that that the trial would be successful?

Marty Huber, President and CEO, Mersana Therapeutics: Well well, I’ll take this the first part of that, and then we’ll let’s circle back on the last part is, so first of I do wanna put a disclaimer. We have yet to have the conversation with the FDA on pivotal study design. So this is a theoretical conversation as does not reflect, you know, official FDA guidance. But a a couple things I think we already know from an agency perspective, randomized trials are always preferred to monotherapy. So I think if you’re thinking in terms of a, you know so but are there reasons to do it other than you have to?

And we actually think there are some significant advantages as we go through this kind of thought process to doing a randomized trial as your pivotal study. First of all, TNBC, because it’s so aggressive, the endpoints in a time to event analysis, PFS, and for that matter, overall survival happens so quickly that you’re gonna get the data in a meet you know, fairly fairly quickly. You don’t have to wait years of follow-up to get enough events. And so if you think about it, the timelines for the study are not dramatically longer for a randomized trial than a a single arm. The only driver of it taking longer, in fact, is not the time to event.

It’s the you’re just gonna have a larger sample size because you’re gonna have some control patients. But if you think about the value you get out of that is you now have a control arm, which is critical when you start interpreting your data. You also then get survival data as part of the study. And what this really does also is it avoids the need to do a second confirmatory trial. Because if you look at those settings recently where people have done nonrandomized trial, you have to have your randomized confirmatory trial well underway at the time of the file.

So doing a single randomized study versus doing a nonrandomized and starting the randomized trial at the same time and essentially potentially competing for patients, etcetera, we think the better you know, what’s likely to be, once again, pending regulatory, is that we just do the randomized trial. And and then kind of one last advantage of that is if you’re using a historic control arm, you have to be very, very tight on your patient eligibility rules to kinda match the historic dataset. If you wanna start integrating a few kind of additional patients is on the edge, what the control arm gives you is that opportunity to expand your patient population a little bit because you’ll have an actual control built in, and you don’t have to rely on these very precisely defined historical datasets. So so overall, I think if you were to you know, if we had to put money down on a pivotal study tomorrow, pending regulatory approval, it would probably be a randomized trial. But once again, we’ll see what the final dataset looks like.

Oh, and I owe you a response on the response rate. And just, you know, to to kind of point out is the control arm’s a 5% response rate. So anything north of 20, we think would be interesting that we think higher is always better. Hello?

Brian Deschuytner, COO and CFO, Mersana Therapeutics: We might have lost Tara.

Marty Huber, President and CEO, Mersana Therapeutics: I oh, we hit the time. I guess when you get the time, they literally pull the hook on you.

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