Mersana Therapeutics, Inc. (0M40.F) Earnings Call Transcript & Summary

Hey, everyone. Good morning, and welcome to day 2 of the 2023 BofA Healthcare Conference. Thanks for joining this session with Mersana. My name is Alec Stranahan, I'm Vice President and Senior Biotech Analyst at BofA. And I'm pleased to be joined by Anna Protopapas, President and Chief Executive Officer of Mersana as well as Mohan Bala, Senior Vice President and Strategic Product Planning Program Leadership at Mersana. Thanks for joining, guys.

Well, thanks for having us.

Great. So we're just going to jump into Q&A. We've got 15 minutes. But if anyone in the audience has a question, feel free just to raise your hand throughout, and we'll bring you a mic and you can ask your question. But Anna, maybe just to start for those newer to the story, could you give us an overview of Mersana? How are you differentiated from other ADC players?

So Mersana is an ADC company, launched about a decade ago with a real mission to come up with next-generation ADC platforms that address the limitations of first-generation technologies and really expand the application of ADCs. Today, we have 3 platforms. We believe are highly innovative and differentiated all in the clinic, and we have a pipeline, including our lead asset in 2 registration-enabling studies. And we have a number of validating partnerships where our partners are leveraging these platforms to take forward programs in their own pipeline. So it's a very exciting time to be in the ADC field, and we're very excited with the data we're generating around our differentiated platforms.

Great. Well, maybe we can dive into the pipeline. Could you talk a bit about the NaPi2b in your development program in ovarian cancer?

So a lead asset, we call UpRi is an ADC using our Dolaflexin platform against a target called NaPi2b. This is a sodium phosphate transporter that is overexpressed in ovarian cancer patients. We have done an extensive expansion cohort, almost 100 patients, to understand the profile of the agent. We were very excited with that data. And as a result of that, we started 2 registration-enabling studies that are ongoing as well as a Phase I/II study. And let me tell you a little bit about the registration trial. I should also mention that NaPi2b is expressed in about 60% of ovarian cancer patients. I'll start with the first registration trial, which is expected to read out midyear. So this registration trial is in platinum-resistant ovarian cancer patients. These are women at the last stages of their disease who have very limited options. The standard of care for these patients is single-agent chemotherapy with a response rate of, at best, 12%. These patients have a median survival of less than a year. Our -- after discussions with the FDA, we designed a single-arm study where we are enrolling all patients, all ovarian cancer patients with up to -- having had up to 4 prior lines of therapy that are platinum-resistant and we have a primary endpoint will be the overall response rate in the NaPi2b high patients. That's the 60% patients I mentioned. And the secondary endpoint will be the overall -- the response rate in the overall population. This trial will read out midyear with top line data and that a positive puts us on a time line for a BLA filing around year-end. We have a second trial, which will service a confirmatory trial that is ongoing called UP-NEXT. And maybe my colleague here, Mohan, can describe the design of UP-NEXT and the unmet medical need we seek to address with UP-NEXT.

Yes. Thank you, Anna. So UP-NEXT is really designed to expand the indication of UpRi. The first indication, as Anna said, will be based on UPLIFT will be for platinum-resistant ovarian cancer patients. UP-NEXT actually allows us to expand into the platinum-sensitive recurrence setting. So it's a trial that is designed in patients who have either stable disease or response to recurrent platinum treatment. These patients today have very limited treatment options because the maintenance treatments, which are primarily bevacizumab and PARP are primarily being used in the first-line setting. So there are really a lack of maintenance options in the recurrent setting, and we really believe that there's a high unmet need that we can meet with UpRi in the setting. So these patients who are either in response or stable disease, to recurrent platinum treatment, we are randomizing them either to UpRi maintenance or placebo in a 2:1 fashion. So that study really not only allows us to confirm the accelerated approval, but also potentially expand into the platinum setting -- a platinum-sensitive setting and allow us to register the drug globally.

Great. So you're checking the boxes for what the FDA has said that they want to see for accelerated approval. Maybe circling back on UPLIFT. Data coming middle of this year is probably the next data catalysts. So what do you view as sort of the minimum efficacy hurdle for accelerated approval?

So from a regulatory standpoint, the FDA would require that we exclude the lower bound of the 95th percentile, which is 20% response rate. But really, what's important is what is clinically meaningful and what have we seen in the expansion cohort. In terms of clinically meaningful, I think we believe that if we double the standard of care, remember these patients mostly have 1 option, single-agent chemotherapy, 12% response rate and all the toxicities that come with chemotherapy. So if we double that, I think that would be a clinically meaningful agent for these patients. And of course, if we do better than that, as we saw in our own expansion cohort, that would be a very important agent for women suffering with ovarian cancer.

Great. And obviously, there's others developing drugs in this space. Are there any read-throughs to you or implications from ImmunoGen's recent MIRASOL readout?

Well, I think we were excited to see the early uptake of the agent and actually not surprised because we were at the Society of Gynecologic Oncology conference just shortly before their quarterly call and talk to a lot of physicians. And I think it confirms what we have been saying, this is an area of huge unmet medical need. Patients and physicians are desperately looking for new options. And it's not surprising that there is a robust uptake. As for the recent MIRASOL data, I think it's encouraging to see that they've confirmed the accelerated path in this setting and more options are really good for patients. It's important to note the differences between the 2 molecules. We obviously have different targets, different payloads. We also have very different prevalence of the biomarkers. In our case, NaPi2b is about 60% of the population. I think based on the FDA approval materials that came out with the approval of Elahere, that's about 29% of the population and the 2 biomarkers are not correlated. So the overlap is expected to be fairly limited. And then, of course, the 2 agents have very different safety and tolerability profile. So more options for patients will ensure that more patients get treated because in this setting, a lot of patients are taking a stay on the sidelines. And this is good for patients.

Right, right. If UpRi does get approved, and you mentioned Elahere, do you see those as competing head-to-head or are those sort of separate baskets?

Maybe Mohan wants to...

Yes. So again, as Anna said, based on what we know so far, the 2 biomarkers don't seem to be correlated. So the proportion of patients who are positive for both, we expect to be pretty small. So I think they can both serve patients. So I don't think it's primarily a head-to-head competing situation.

It's definitely not a zero-sum game.

Yes.

Got it. And Mohan, you talked about the UP-NEXT trial. Where do you think that could be at the time of accelerated approval just in terms of the pace of enrollment so far?

Yes. So our goal and what we expect we will have is for that trial to be substantially enrolled, which is what FDA looks for. So we are well on the way to be there.

Okay. Very good.

It might be worth mentioning that in the UPLIFT trial, the single-arm study, we enrolled approximately 270 patients in 12 months, which is a pretty significant achievement and a reflection of both the unmet medical need as well as the interest of investigators in UpRi. UP-NEXT is in an earlier setting. It's a selected population. So it will be NaPi2b positive, and it's about 350 patients. So that gives you some context as to our confidence that we could be substantially enrolled by the time the FDA has to make a decision on a BLA filing on UPLIFT.

Okay. And one curveball question because this is maybe a broader theme for the sector, which is what's the FDA's stance today on accelerated approval pathway? Do you have any updated view?

So we -- obviously, with our expansion cohort data in hand, we went to the FDA to discuss the UPLIFT trial and asked a number of questions. Is ovarian -- is platinum-resistant ovarian cancer an area of high unmet need that justifies an accelerated approval? And do we agree on what the standard of care is that we will be compared to and had a very constructive discussion. And I think subsequently, we've had subsequent discussions around protocol design and other discussions with the FDA. If you look at the guidance that has just come out a few months ago, the FDA is clear that in areas of high unmet medical need, they are open to accelerated approval. And in fact, the fact that they've been open to accelerated approval has led to a lot of innovation in the oncology field. There are 2 things that are important to them: dose exploration to make sure you have the right dose, what they refer to as Project Optimus. And if you look at our expansion cohort, we studied 2 doses and really selected the dose we thought was optimal to go forward. And then second, they want to make sure the confirmatory trial is well underway. And as Mohan just described, we started that in the second half of the year.

Okay. Great. And you have a third UpRi trial UPGRADE-A. What's your strategy with this study? And what can investors look forward to in the upcoming second half readout?

Yes. So UPGRADE-A is a trial where we are combining in the recurrent platinum-sensitive setting, UpRi, with carboplatin for 6 cycles and then continuing treatment with single-agent UpRi. So our strategy there is to really replace paclitaxel with UpRi. So paclitaxel is a drug that's been around for a long time, but comes with significant toxicities, particularly neuropathy, neutropenia, alopecia. And these are toxicities that have a significant impact on patients. So if we could provide an option that doesn't have those toxicities and meets or exceeds the activity that paclitaxel has and also allows for continuation treatment beyond that initial 6 cycle, that could be a substantial advancement in how we treat ovarian cancer. And that combination, if it's combinable, we have a potential pathway to move that into a front-line setting.

We did see at the beginning of the year that we completed dose escalation. We were initiating expansion with -- and we expect to have interim data in the second half of the year.

Okay. Great. And I do want to talk about something other than UpRi. We've got about a minute left, but maybe you could talk to us about XMT-1660. What makes B7-H4 an exciting target for you guys? And how does your asset compare to other B7-H4 ADCs in development?

So B7-H4 is a great target for an ADC. It's broadly expressed in some tumors with high unmet medical need, breast cancer, triple-negative breast cancer, HR-positive breast cancer, endometrial, ovarian, and we -- 1660 users are Dolasynthen platform. It has the payload, the same payload as UpRi where we've demonstrated, we don't have neutropenia, neuropathy or ocular toxicities and it uses a precise drug-to-antibody ratio optimized design. We believe we are in dose escalation. We expect to complete dose escalation by the end of this year and be in a position to move into expansion cohorts early next year. There are 2 other companies that are at similar stages with B7-H4 ADCs, one is Seagen using their vcMMAE platform. We know that as we compare our platform to theirs, we do not have the dose-limiting neutropenia and neuropathy that is typical of vcMMAE ADCs. AstraZeneca is using a homegrown topoisomerase platform. We don't believe it's gone into the clinic before. We haven't seen any data. So it's hard to know what the profile will be. We understand that they have recently indicated in their quarterly call that they will not have data on that until 2024.

Okay. All right. Very good. Well, I think with that, we're out of time. So we'll have to leave it there. But I really want to thank you guys for the discussion and for participating in the conference.

Thank you very much.

Thank you.