Mersana Therapeutics, Inc.

Good morning, and welcome to Mursana Therapeutics' fourth quarter and year-end 2024 conference call. Currently, all participants are in a listen-only mode. There will be a question-and-answer session at the end of this call. I would now like to turn the conference over to Jason Fredet, Senior Vice President, Investor Relations and Corporate Communications. Please proceed.

Thank you, Operator, and good morning, everyone. Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws. These statements may include, but are not limited to, those related to the potential clinical benefits of our product candidates and platforms, our clinical trial progress and designs, dosing and patient management strategies, addressable market opportunities, anticipated milestones and data disclosures, and cash runway. Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. These risks and uncertainties are discussed in our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on November 13, 2024, and in subsequent SEC filings. Our filings are available at sec.gov and on our website, mursana.com. Except as required by law, we assume no obligation to update forward-looking statements publicly, even if new information becomes available in the future. On today's call, we have Mursana's Chief Executive Officer, Dr. Marty Huber, and our Chief Operating Officer and Chief Financial Officer, Brian Descheitner. With that, let me turn the call over to Marty to begin the discussion.

Thank you, Jason, and good morning, everyone. Over the past several months, we have accomplished a great deal here at Mursana. Most notably, with our lead dolosynthin ADC, Emily, we reported positive initial clinical data, started the expansion portion of our Phase I trial, and were granted an additional fast-track designation for a growing portion of the breast cancer population that has previously been treated with a topoisomerase I inhibitor, or topo-1 ADC. At the same time, we advanced Phase I dose escalation with XMT2056, our lead immunosynthin ADC, while also supporting our collaborators. Let's focus first on Emily, Marsana's ADC targeting B7H4. In January, we reported initial clinical data from 130 patients who were enrolled in dose escalation and backfill cohorts as of December 13, 2024 data cutoff. From a safety and tolerability standpoint, EMILY was observed to be highly differentiated within the ADC space. The most common treatment-related adverse events of any grade were transient increases in AST, generally asymptomatic and reversible proteinuria, generally low-grade nausea, and low-grade fatigue. Importantly, unlike many other ADCs, we did not see dose-limiting neutropenia, neuropathy, ocular toxicity, interstitial lung disease, or thrombocytopenia. This provides us with the confidence that Emily could have an attractive monotherapy profile. Just as importantly, we believe it also could enable combinations with standards of care like platinum chemotherapy and other ADCs that our competitors would be challenged to pursue. From a clinical activity standpoint, confirmed objective responses were observed in all enrolled tumor types. These included patients with triple negative and hormone receptor positive breast cancer, endometrial cancer, ovarian cancer, and adenoid cystic carcinoma type 1, otherwise known as ACC1. At intermediate doses, which ranged from about 38 to 67 milligrams per meter squared, or about 1 to 2 milligrams per kilogram, The confirmed objective response rate was 23% across all tumor types with high B7H4 expression, which we defined as an IHC score of 70% or more. Focusing specifically on the evaluable patients in this dose range with B7H4 high triple negative breast cancer, the confirmed ORR was also 23%. At the end of 2024, we initiated the expansion portion of our trial in patients with TNBC who have previously been treated with at least one topo 180C, a population with a very high unmet need. We believe we are positioned for success for a few key reasons. The first is the dose we're utilizing. The second is our inclusion criteria. Third is the standard of care for these patients today. And the final factor is the competitive environment in which we are operating. Let's begin with the dose. Generally speaking, as you might expect, we have seen that clinical activity tends to increase along with Emily's dose. As I mentioned, the 23% ORR we observed was generated across a range of doses from about 38 to 67 milligrams per meter squared. we have brought the top dose from this range, specifically 67.4 milligrams per meter squared every four weeks, into expansion. As we previously reported, this particular dose was well tolerated. Additionally, each of the four B7H4 high patients who received this dose achieved target lesion reductions, and each also remained on treatment for durations of approximately 16 weeks or more as of the data cutoff. A second factor that can influence response is prior treatment. This is well established in oncology, and specifically in triple negative breast cancer. As a reminder, the 23% ORR that we observed with Emily in TNBC was generated in a population of 13 evaluable patients. 12 of these patients received more than three lines of prior therapy, and all had received at least one TOCO-180C. These data compare favorably to historical benchmarks. For instance, a 23% ORR was also seen with Tredelby and TMBC patients who received more than three prior lines of therapy in the phase three assent study. But of course, this was in a topo-naive setting. Tredelby's ORR increased to nearly 40% in patients who received only two or three prior lines of therapy. In expansion, we are limiting enrollment to patients with a maximum of four prior lines, while also mandating that at least one prior treatment must have been a TOPA-180C. It is also important to keep in mind what the standard of care is in TMBC today. In ascent, the control arm, which was single agent chemo, had an ORR of only about 5%. And finally, there is the competitive environment. we view recent developments within the B7H4 ADC landscape as favorable for Emily. Most notably, the company that we have viewed as our primary would-be competitor within the breast cancer space, Pfizer, recently announced that it had discontinued development of its B7H4 ADC candidate. The other B7H4 ADCs that are at a similar stage of clinical development as us all have topo1 payloads. As a result, unlike Emily, we believe they are subject to topo1 resistance mechanisms. In fact, some of these companies appear to be excluding patients who have received prior topo1 therapies from their clinical trials. This positions Emily as the most advanced or statin ADC in the class, which provides us with a significant opportunity in breast cancer. We are pleased with the level of investigator interest and engagement we are seeing. And while TMBC is our immediate focus, given the clinical activity we have seen across all tumor types, we are excited by Emily's potential in other indications as well. And so, enrollment continues at our initial expansion dose of 67.4 milligrams per meter squared. We also continue to investigate doses up to 95 milligrams per meter squared in escalation of backfill cohorts delays. We're pleased to report that we officially amended our clinical trial protocol in late January as we seek to mitigate the proteinuria-related dose that we were seeing at high doses. We expect these efforts will help us identify a second dose for our second expansion cohort in post-TOPO1 TNBC later this year, and we plan to present additional data from dose escalation and backfill later this year as well. Moving on to other areas, we also have advanced the dose escalation portion of our Phase 1 clinical trial of XMT2056 in recent months. 2056 is our immunosynthin sting agonist ADC targeting a novel epitope of HER2. Later in 2025, we plan to present initial pharmacodynamic data from this clinical trial that helps to characterize this candidate's ability to selectively activate the sting pathway in HER2-expressing tumors. And finally, I would like to note that we continue to make solid progress in our dolosynthin research collaboration with J&J and our immunosynthin research collaboration with Merck KGA. With that, let's turn things over to Brian for some color on our financials.