Good morning, and Welcome to ImmunoGen's PVEK Program Update Conference Call. Today's conference is being recorded. At this time, I'd like to turn the call over to Anabel Chan, Head of Investor Relations. Please go ahead. Good morning, and thank you for joining today's call. Earlier today, we issued a press release announcing an update to our pivotal phase II CADENZA study of pivekimab sunirine in BPDCN. This press release and a recording of this call can be found under the Investors and Media section of our website at immunogen.com. With me today are Mark Enyedy, our President and CEO, and Anna Berkenblit, our Chief Medical Officer. Theresa Wingrove, our Head of Regulatory Affairs and Quality, Kristen Harrington-Smith, our Chief Commercial Officer, and Susan Altschuller, our Chief Financial Officer, will also join us for Q&A. We will be making forward-looking statements based on our current expectations and beliefs. These statements include those related to the progression of our CADENZA study and the timing of top-line data and are subject to risks and uncertainties and our actual results may differ materially. Please consult the risks outlined in our press release issued this morning in the risk factor section of our most recent annual report on Form 10-K and in our subsequent quarterly reports on Form 10-Q and in our other SEC filings, which are available at sec.gov and immunogen.com. With that, I'll turn the call over to Mark. Thanks, Anabel. Good morning, and thank you for joining us today to discuss updates to our pivotal program with PVEK in patients with BPDCN. We recently undertook an analysis of data from the first 10 frontline BPDCN patients enrolled in our pivotal study, which we call CADENZA. These included patients with de novo disease and those who presented with a prior or concomitant hematologic malignancy or what we call PCHM. Anna will describe in more detail in a moment, but what we saw was significant activity and favorable tolerability in both de novo and PCHM patients, which further reinforce our view that PVEK could be an important new treatment option for patients with frontline BPDCN. Earlier this month, we met with FDA to review these data. As part of that discussion, we aligned with FDA that the efficacy of evaluable patient population will be the de novo BPDCN patients with CR/CRC as the primary endpoint and duration of CR/CRC as the key secondary endpoint for the study. Based upon this guidance, we will enroll up to an additional 14 de novo patients in CADENZA for purposes of the primary efficacy analysis. Given that this is an ultra-rare disease, we now anticipate top-line data in 2024. In addition, FDA has encouraged us to generate data to support assessing CRH as an endpoint in this population. Accordingly, we will continue to enroll BPDCN patients with PCHM in CADENZA to further explore the potential benefits of PVEK in this population. With that, I'll turn the call over to Anna to provide more color on these promising initial data and our discussions with FDA. Thanks, Mark. BPDCN is an aggressive cancer that is characterized by poor overall survival and limited therapeutic options. Incidence is 500-1,000 patients per year in the U.S., with similar numbers in Europe. In 2020, we aligned with FDA on a pivotal frontline cohort of up to 20 patients in our phase II CADENZA study as a path to full approval with CR/CRC as the primary endpoint and duration of complete response as a key secondary endpoint. Initial enrollment in CADENZA did not distinguish between de novo BPDCN patients and those with PCHM. In conjunction with our analysis of the first 10 frontline patients enrolled in this study, we found that more than half had PCHM, with significant activity in both patient groups. Specifically, two of the four de novo patients achieved a CR/CRC, and four of six PCHM patients achieved CR, CRC, or CRH, which is defined as a CR with partial hematologic recovery and is a measure we believe is important. Additionally, a fifth PCHM patient achieved a CRI, and a sixth had a robust enough response to PVEK to bridge to transplant with a CRH. In addition to those 10 CADENZA patients, recall that we enrolled three frontline patients prior to opening the pivotal cohort, of which two were de novo and one had PCHM. All three patients achieved a CR or CRC. Overall, we are very encouraged with the activity we're seeing across de novo and PCHM patients, with 11 of 13 or roughly 85% of patients achieving some form of complete response. Our understanding of BPDCN continues to evolve. At ASH in 2019, Dr. Pemmaraju presented data showing approximately one-quarter of BPDCN patients may have an underlying hematologic malignancy, with myelodysplastic syndrome or chronic myelomonocytic leukemia being the most frequently observed prior or concomitant malignancies. This is similar to what has been seen with myelodysplastic syndrome that can progress to acute myeloid leukemia. BPDCN patients with PCHM are most likely to die of the aggressive BPDCN component, which requires urgent treatment, while the other malignancy is typically chronic and may not even require treatment. What we've observed is that patients with PCHM who've cleared their marrow of BPDCN when treated with PVEK may not fully recover their counts, likely due to the underlying concurrent hematologic malignancy. CRH is a meaningful endpoint in these patients as it may allow these patients to bridge to transplant, which is the only curative option. BPDCN patients with PCHM are increasingly recognized as having significant unmet need given the lack of therapy. With the promising data observed and FDA encouraging us to generate additional data to support CRH as an endpoint, we will continue to enroll patients with PCHM in CADENZA and look forward to further exploring the potential benefits of PVEK in this population. With that, I'll turn the call back over to Mark. Thanks, Anna. As Anna reviewed, we're very pleased with the data that we've generated to date with PVEK in this very difficult to treat population. We look forward to sharing additional data and details of the PVEK in frontline BPDCN at an upcoming medical meeting. As a reminder, we've submitted an initial data abstract for the PVEK triplet expansion cohort in AML for presentation at ASH. With that, we'll open the line for questions. As a reminder, to ask a question, you will need to press star one one on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from Andy Hsieh with William Blair. Please proceed. Good morning, everybody. Thanks for taking the questions. Appreciate the additional color on the kinda the subtypes of BPDCN. I got a three-parter, if you don't mind. You know, first, you know, probably has to do with the FDA interaction. Just wanted to maybe get a sense of the evolution. You know, obviously BPDCN is already really small. Just wondering why, and given the unmet medical need, why the FDA is asking you to further segment an already ultra-orphan population to these two segments. Especially I don't believe ELZONRIS underwent the same process. That's number one. Number two, again, just maybe the FDA realized that, you know, in the study population, a little bit more than half of PCHM, but about a quarter from a 2019 paper, any other retrospective study that would clarify the epidemiology of the breakdown of these two subsegments. The third has to do with the biology. Do we know anything about, you know, PCHM, which is a little bit different from de novo? Should we think about this subsegment kind of like, you know, perhaps secondary AML? Would that be a good analogy? Thanks for taking all my questions. Thanks, Andy. To take your questions in order, in terms of our interactions with FDA, recall that we received Breakthrough Therapy designation, and this gives us the opportunity to interact with them as we did earlier this month. Yes, BPDCN is a very small population. The reason that FDA guided us toward the de novo patients for our pivotal cohort for the primary analysis population is that's the cleanest population where we can demonstrate an efficacy signal. They recognize that the patients with prior or concomitant hematologic malignancies do have this underlying component that makes it a little more challenging to assess not necessarily the response to pivkeimab sunirine because we're seeing clearance of the marrow, but rather the ability to recover blood counts, which is an important component of CR measurement. In terms of ELZONRIS, what we know is in their clinical trial, they specifically excluded patients with an active malignancy, or other cancer history, and they excluded antecedent tumors other than myelodysplastic syndrome. That's what we can say regarding the ELZONRIS population. Moving to your second question. Historically, back in 2019, Dr. Pemmaraju showed from his data that approximately 25% of patients with BPDCN do have some sort of prior or concomitant hematologic malignancy. What you've seen here, for us is that six out of 10 patients we've enrolled in our CADENZA study have PCHM. With that's the limited data that we are aware of. We are not aware of any other retrospective dataset out there, but we certainly look forward to continuing to partner with experts in the field as our collective understanding evolves with BPDCN in general and the patients with a prior concomitant hematologic malignancy, because we're observing very nice responses in both patients, and we believe that a CRH is really meaningful in these patients. Then lastly, regarding your question about the biology, this is fascinating, and we are learning more and more. As has been shown probably in the last five to 10 years, elderly patients often have what's called clonal hematopoiesis of indeterminate potential. We know that there are patients; if you look, you will find and see clonality of hematologic progenitors. I don't think anybody really understands how that is linked to what we're seeing. I think your point around the connection between MDS and AML is probably the most relevant analog, if you will, to what we're seeing in BPDCN, where not just MDS, but also CMML can be seen underlying in the context of an aggressive BPDCN malignancy. Thanks. Next question. Please stand by for our next question. Our next question comes from Kelly Shi with Jefferies. Your line is now open. Thank you for taking my questions. I'm wondering, during the discussion with FDA, have you talked on the bar on ORR and what would be the clinical benefit bar on duration? Also, would you be able to estimate the enrollment pace for de novo patient population? Thank you. The bar for efficacy has not changed. The study design that FDA guided us toward for the pivotal cohort is unchanged, where we are enrolling up to 20 patients. What we think in terms of meaningfulness is we understand ELZONRIS is the only approved drug for this disease. We would anticipate we would need similar or superior activity to what has been observed with ELZONRIS. They saw seven out of 13 patients with a CR or CRC in the front line setting. Regarding clinical benefit duration, an important component of treatment in the front line setting is bridging patients to transplant. FDA acknowledges that, and therefore, as we look at duration of complete response, the patients who are transplanted are to be followed, and that is a component of the duration of complete response. Moving to your second question around enrollment pace, we anticipate at this point top line data in 2024. The reason we anticipate this is based on historical data that we now have from enrollment in the CADENZA study, in addition to us opening additional sites. Thirdly, now that investigators have an understanding how active our drug is in BPDCN patients, we recognize that it is an attractive option for patients to participate in our clinical trial when considering available therapies, including high dose therapy and ELZONRIS. Thank you. Please stand by for our next question. Our next question comes from Daniel Welch with JP Morgan. Your line is now open. Good morning, everyone. Thanks for taking our question. Given that you will continue to enroll PCHM patients and you've outlined the meaningful nature of the CRH endpoint, is there potential at some point for the primary endpoint to shift to that, allowing you to submit a registration that will encompass both segment populations? Second, is there any way for you guys to refine the 2024 timeline for us? And last, is enrollment in any way affected by the presence of ELZONRIS already in the marketplace? Thank you. We are continuing to enroll PCHM patients and gather additional data on CRH. FDA indicated they were interested in additional data. I think what I would point out is there is a precedent, specifically in BPDCN patients, for CRC to become a regulatorily accepted primary endpoint during the context of enrollment of a pivotal study where it was not previously seen as an approvable endpoint. That was based on the ELZONRIS experience and Stemline's interactions with FDA. Moving to your question about refining the 2024 timeline, we're premature to say at this point it's an ultra-rare indication, and at this point we're guiding toward top-line data in 2024. Lastly, regarding the use of ELZONRIS, we are monitoring that closely in terms of understanding at our investigational sites when patients who are potentially eligible elect not to proceed with our trial. There are some patients who elect or some physicians who elect to treat their patients with ELZONRIS. I would remind folks that ELZONRIS is a challenging medication to give. It requires hospitalization for at least five days for the first cycle and can be associated with you know, potentially fatal capillary leak syndrome, hepatotoxicity, infusion reactions and such. Our drug, in the context of the clinical trial, is an attractive option because of the activity we're seeing, the brief outpatient IV infusion given once every three weeks. Great. Thank you. Please stand by for our next question. Our next question comes from Swayampakula Ramakanth with H.C.W. Your line is now open. Thank you. Thank you folks for giving us this additional details on the study, and glad to see, you know, that you're refining the study to get a better understanding of not only the disease but also what the drug can do. In terms of patients, you know, can you tell us what percent of BPDCN patients get diagnosed at the de novo stage? This is what I can tell you, RK. When Dr. Pemmaraju went back and looked at his data from MD Anderson, about 25% of patients with BPDCN had a prior or concomitant hematologic malignancy. The reason he lumped them together as prior or concomitant was there were some patients who had a known prior malignancy, and then there were others who, when they were diagnosed with the aggressive BPDCN, when the hematopathologist looked under the microscope, they saw a concomitant more indolent tumor there, like CMML, for example, or MDS, but there was no prior documentation thereof. you know, there's even a third wrinkle in that there are some patients who present with BPDCN, and then it's only after their bone marrow is cleared of BPDCN that you can see a small volume of an underlying indolent disease that just previously was not appreciated. What I can tell you is historically 25% in our study, six out of 10. You know, we're really excited to continue working with our experts to understand who these patients really are and how they do with available therapies as well as with PVEK. Okay. Thank you for that, Anna. Then when you're talking about the patients who were in the CADENZA study, I'm just trying to understand, you know, the definition of that patient group. Can we call them de novo? Because you said the patients who had some prior history of hematological disease were not included, but that doesn't mean they are de novo patients, are they? Again, what we have available is what's in the public domain, RK, and the eligibility criteria specifically excluded patients with antecedent cancers that could confound assessment other than antecedent MDS. I don't believe that any of the demographic tables that they've reported went into this level of granularity, frankly, because I think our understanding of the disease when they were doing their pivotal trial was not as advanced as it is now. We're learning along the way. Okay. The last question from me is, you know, based on what you said just a minute ago, how easy or how difficult is it to identify de novo patients? Because it looks like you have to do multiple things before you can classify somebody as a de novo patient. Basically, you need to look at the bone marrow. You know, if a patient has a prior bone marrow, then you can kind of compare. Once a patient is on our study, remember, we're enrolling de novo and PCHM patients, so it doesn't matter. Everybody will get the opportunity to receive PVEK in the context of the clinical trial. When they have a complete response and the marrow has been cleared of the blast, you can go and look and see if you see any small clones of an underlying chronic malignancy like CMML or MDS that may just have not been appreciated on the initial marrow. Okay. No, thank you. Thanks, Anna, for taking all my questions. You bet, RK. Please stand by for our next question. Our next question comes from Jonathan Chang with SVB Securities. Your line is now open. Hi, guys. This is Jessica Shea on for Jonathan. Just wanted to ask about your phrasing of the enrollment target as up to 20 patients. Could you just clarify why that's worded that way and if it's possible that you guys can do less than 20? Sure. When FDA guided us toward the design of the pivotal frontline cohort, they had discussed with us the potential to stop earlier should we see profound activity. We are permitted per the study design and the statistical analysis plan to start doing interim analyses after 13 patients. Remember, it's not just the rate of CR/CRC, but also the duration of complete response or CR/CRC that is important. As we continue to enroll patients over time and monitor their efficacy, you are right, there is an opportunity for us to stop earlier than waiting until we enroll the 20th patient. Got it. Thank you. Great question. I would now like to turn the conference back to the team for closing remarks. Thank you for joining us today, a week before Labor Day. Couple closing points here. The first is we think we've got an important drug with PVEK. We're very encouraged by the activity that we've seen, as Anna mentioned, you know, with some form of complete response in, you know, 85% of the patients that we've enrolled in the frontline setting. Importantly, we are working constructively with FDA to define a clear path to an approval for this drug, first in the de novo population, and then being encouraged to work to generate additional data for these PCHM patients to support CRH as an approval endpoint for this population. We look forward to sharing additional data, more detail at an upcoming medical conference and as the program progresses. Thanks very much. This concludes today's conference call. Thank you for participating. You may now disconnect.