Good day, and welcome to the Tango Therapeutics conference call. At this time, all participants are in listen only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question, you'll need to press star one one on your touchtone telephone. Please note this call is being recorded. I'd like to turn the call over to Elizabeth Hickin, Vice President, Investor Relations and Corporate Communications. Please go ahead. Thank you, and good morning, everyone, and thank you for joining us on today's call. This morning we issued a press release on the data which can be found on the Investors and Media section of our website, www.tangotx.com. Before we begin, let me review our safe harbor statement. We will be making forward-looking statements on this call that are subject to risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. This call is being recorded, and a replay will be available on our website. The agenda for this morning's call is as follows. Malte Peters, Tango's President and CEO, will share some introductory remarks. We are pleased to be joined today by Dr. Brian Wolpin, Director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute, who will present the clinical data. Adam Crystal, our President of R&D, will discuss our development strategy for vopimetostat. Matthew Gall, CFO, will share some financial highlights and provide an overview of important upcoming events. Malte will then conclude the call and we will open it up to Q&A. I will now turn the call over to Malte. Thank you, Liz, and good morning, everyone. Today is a very important moment and a critical inflection point for Tango and the pancreatic cancer community. This morning, for the first time, we reported data from our ongoing trial for our PRMT5 inhibitor, vopimetostat, in combination with Revolution Medicines' pan-RAS inhibitors, daraxonrasib and zoldonrasib, in people with MTAP-deleted pancreatic cancer, which is an exceptionally difficult to treat malignancy. These data are the culmination of years of research in PRMT5 inhibition, with Tango leading the development of potentially best-in-class molecules and advancing the scientific understanding of this approach in patients with MTAP-deleted cancer. The results from our ongoing combination trial dramatically exceeded our expectations. As of May 28, 2026, in efficacy-evaluable patients with second and third-line pancreatic cancer, vopimetostat with daraxonrasib demonstrated a 92% objective response rate, six-month PFS rate of 90%, and a 100% disease control rate in heavily pretreated patients. This represents a clinical activity that is meaningfully greater than previously reported data for either agent alone or in combination with standard of care chemotherapy, both in second and first-line treatment. In addition, as we will describe on subsequent slides, the combination was generally well-tolerated, and no patients discontinued due to adverse events. We believe these data are extremely promising and have the potential to change the course of pancreatic cancer treatment and provide a path to development of potential chemo-free regimen in first-line pancreatic cancer. The RASolute 302 data presented by Dr. Brian Wolpin in the plenary session at ASCO are extraordinary, and we heard that the data were the beginning of a new era for patients with pancreatic cancer, as well as a call to action to continue to build upon this data. We feel that the combination data we are presenting today can be a meaningful part of that next step for many patients with pancreatic cancer. When I started my role as CEO in January, the mandate was to accelerate the transformation of Tango from a research and early development-focused company to one with the capabilities to successfully move programs through a registration and to commercialization. At that time, we were seeing some early clinical signals that were validating strong preclinical studies, and the data have continued to progress in a very positive way. We are at a point now where we feel vopimetostat is ready to move to registrational trials, and we have an internal infrastructure ready to deliver. MTAP-deleted pancreatic cancer represents a potential blockbuster opportunity for vopimetostat. There are 60,000 patients with MTAP-deleted cancer, including approximately 20,000 pancreatic cancer patients. Of the pancreatic cancer patients, almost all harbor RAS mutation. Additionally, we see meaningful development opportunities in indications beyond pancreatic cancer, with large patient populations and unmet medical need in areas such as lung cancer and glioblastoma, where we have ongoing clinical work and will be sharing data later this year. On the call today, we will provide a look at the very promising vopimetostat combination data, discuss our updated strategy for developing the combination in frontline pancreatic cancer, and highlight our capital allocation priorities and recent financial results. We are very pleased to have Dr. Brian Wolpin of Dana-Farber Cancer Institute join us today to present the first clinical data which demonstrated the potential of PRMT5 RAS combination therapy. Dr. Wolpin is the director of the Gastrointestinal Cancer Center at Dana-Farber and one of the investigators on our phase I trial. In addition to being an experienced drug developer, he treats a large number of patients in his clinic, and he brings important perspective on the devastating disease burden and the evolving treatment landscape. With that, I'll turn over to Dr. Wolpin. Thank you, Malte. Thanks for the opportunity to be here and the opportunity to share some of the data of both metostat and RAS inhibitors, particularly in patients with pancreatic cancer. I think as folks on this call know, traditionally, and now for many years, we have treated pancreatic cancer with multi-agent chemotherapy. This is true particularly in metastatic disease, where most of what we've been able to use so far has been chemotherapy. However, we have known for some time that over 90% of pancreatic cancers harbor a mutation in RAS, particularly in KRAS, and particularly in codons 12 of KRAS with G12D, G12V, and G12R being the most common. We have wanted for many years to want to target RAS, and RAS that is mutated in pancreatic cancer, and this is finally now coming to fruition with now good data, including from RASolute 302, showing that RAS inhibitors can be an effective therapy in patients with advanced pancreatic cancer and now showing in the second-line setting with RASolute 302 that it actually can be more effective and more tolerable than multi-agent chemotherapy. We also know that that will not be the answer by itself, right? Tumors will develop resistance to RAS inhibitors, and really the next wave of studies that will be coming will really be needing to combine second agents together with RAS inhibitors in order to really give our patients durable long-term responses that they deserve. What we'll talk about today is a promising combination to do that, which is RAS inhibitors plus PRMT5 inhibitors. A basic slide on mechanism of action for why a PRMT5 inhibitor is appropriate in pancreatic cancer and actually in a number of other cancers. As Malte discussed, there's a host of different cancers that have biallelic deletion in MTAP. When this gene is deleted, there's a buildup of its substrate MTA, and when there's a buildup of the substrate, that substrate displaces on PRMT5 the normal substrate that is used, which is SAM. The goal or the function of PRMT5 is as a methyltransferase serving a number of different functions in the cell. When MTA binds to PRMT5, you get a partial inhibition of PRMT5 function that is specific to tumor cells and not seen then in normal cells because normal cells do not have the MTAP deletion. This is a perfect opportunity then to bring in a drug that completes the inhibition of PRMT5, sparing normal cells and treating tumor cells. When drugs like vopimetostat then bind to PRMT5, you get a number of downstream consequences, including changes in RNA splicing and DNA repair that lead to cell death. This is then the biologic basis for using a drug like vopimetostat in pancreatic cancer, where 35%-40% of the time we see biallelic MTAP deletion. Here's some data. The plots you see are data from Tango, suggesting that there is a synergy between the use of RAS inhibitors and PRMT5 inhibitors in pancreatic cancer. I would also direct you to two independently done studies, both of which were published in "Cancer Research" last year, that show a similar phenomenon, suggesting that this may be, based on the preclinical data, a very promising combination to take forward in pancreatic cancer. We'll now show you today some of the first clinical data that suggests this to be true. There's two drugs that we'll talk about today in combination with vopimetostat. You can see to the left is vopimetostat plus daraxonrasib. As Malte mentioned, this is a RAS(ON) multi inhibitor. It binds to and inhibits the function of mutant RAS and wild type RAS across a whole range of mutant alleles, including the main mutant alleles that we see in pancreatic cancer, with the goal being inhibition of PRMT5 with vopimetostat, disrupting the methylation that the cell requires for normal function, and daraxonrasib inhibiting RAS, leading to a synergistic effect in cell killing in pancreatic cancer. You can see to the right, data we will also show for vopimetostat, but in this case, plus zoldonrasib. Zoldonrasib is also a RAS(ON) inhibitor from Revolution Medicines. This is a KRAS G12D specific inhibitor with substantially less wild type binding. This may also lead to synergy, but there is data preclinically that using a PRMT5 inhibitor in a RAS mutant background within cancer cells can actually lead to compensatory upregulation of wild type RAS. It may be, and this we will have to see, but it may be that having a drug that also inhibits wild type RAS, such as what daraxonrasib does, may even have greater synergy than a mutant allele specific inhibitor. Here's the design of the study and the data that we'll talk about today. As we discussed, there are two arms to this study, vopimetostat and daraxonrasib. This arm allowed patients with any RAS mutation because daraxonrasib is a multi-selective inhibitor, or vopimetostat plus zoldonrasib. In this case, patients were required to have a KRAS G12D mutation because this is a G12D specific inhibitor. You can see the key inclusion criteria. They must have had MTAP loss. This could be by NGS or immunohistochemistry. They must have had one or two prior lines of therapy in the metastatic setting. This is almost entirely chemotherapy in patients with pancreatic cancer. ECOG performance status of zero or one, and no prior exposure to either a PRMT5 or a RAS inhibitor. These patients all had metastatic pancreatic cancer, or as we'll see, a smaller number that had metastatic non-small cell lung cancer. If we look to the right of the slide, you can see the dose escalation plan. Patients received either 200 mg or 250 mg of vopimetostat orally once daily, in addition to 100 mg of daraxonrasib orally once daily. There was a prediction that was done prior to initiating this study that suggested with the addition of vopimetostat to daraxonrasib, 100 mg of daraxonrasib would actually lead to a similar exposure for the patient of 300 mg of daraxonrasib. For reference, 300 mg of daraxonrasib is what was used in RASolute 302, so it would be considered a standard dose in patients with metastatic pancreatic cancer. As we'll discuss, there are 25 patients evaluable for safety, 15 evaluable for efficacy. The ability to be evaluated for efficacy required that patients had at least 14 weeks since the start of their treatment, such that they would have had at least two CT scans to evaluate for efficacy. As you can see in the bottom right, patients were evaluated for MTAP loss, either by NGS or by IHC, although these measures are highly concordant. Here are the baseline characteristics of the patients who are enrolled. You can see three columns. In the first column is vopimetostat, daraxonrasib, and patients with pancreatic cancer. The second is vopimetostat, daraxonrasib in non-small cell lung cancer. The third is vopimetostat and zoldonrasib, the G12D specific inhibitor. Focusing a bit more on the pancreatic cancer patients, median age in the mid-60s. The majority of patients received two therapies before they were treated on this trial. 70%-80% of patients with pancreatic cancer had liver metastases. This is very common and what we generally see in trials of patients with metastatic pancreatic cancer. Here we can see the waterfall plot that provides some of the efficacy data for vopimetostat plus daraxonrasib in patients with metastatic pancreatic cancer. We can see on the top line an objective response rate of 92% in 12 patients. If we look at the plot, what you can see is the line of therapy in the first row across. Just to highlight, many of these patients had received two prior lines of therapy prior to enrolling on this study. You can see the different dose levels, dose level 1 and 2, with the dose levels described below. The other thing I would call your attention to is the rightward arrow at the bottom of each bar. These patients, almost all of these patients, continue on therapy, so continue to have the opportunity for longer durability and deeper responses as they are followed on trial. To the right, you can see the objective response rate was 92%. Disease control rate was 100%. There were nine confirmed partial responses and two unconfirmed partial responses. These patients remain on treatment, so still have the potential to become confirmed with future scans. This is a similar waterfall plot. Again, vopimetostat and daraxonrasib. The main difference here is that the eligible patients for efficacy for non-small cell lung cancer are also added to the plot. You can see three patients with lung cancer were added to the waterfall plot. These are the darker color. You can see all three of these had partial responses. Again, really emphasizing that this is a relevant combination for pancreatic cancer. It may also be relevant for other cancers, including non-small cell lung cancer, and continues to be a very high objective response rate in the patients evaluated thus far. In addition to looking at objective response rate, it's also important to consider the durability of these responses. Here's a swimmer's plot to describe this. You can see all the way to the left, the indication shows you whether this is a patient with pancreatic cancer or non-small cell lung cancer. Line of therapy, again, emphasizing many of these patients have received two prior lines of therapy already. You can see in terms of durability, the first set of patients now getting out almost 10 months on treatment. Most patients are now beyond six months, and only two patients have had evidence of progression by RECIST criteria thus far. This leaves you, for the pancreatic cancer patients, a 90% six-month progression-free survival rate among these individuals. Would also highlight there are nine additional patients who have not yet met that 14-week criterion for evaluation of efficacy. All are ongoing. No progressive disease events in those patients thus far. This is a clinical example to show you a patient and what we are seeing on imaging studies among the patients that we're treating on the trial. This is a 72-year-old woman. She has MTAP deletion. She has a KRAS G12R mutation, and she has metastatic pancreatic cancer. This is vopimetostat and daraxonrasib in the third line setting, having received two prior lines of therapy before going on trial. We can see in the left, the CT scan representing at the red areas three liver metastases, and on the right and cycle 7, day one, substantial reduction in all three of these liver metastases, with now a confirmed partial response and by RECIST, best response, -52% in the maximal diameter of these lesions, and the response is ongoing. If we now turn to safety and tolerability of the combination for vopimetostat and daraxonrasib. Again, three columns. You can see the column to the left is dose level 1, so 200 mg vopimetostat, 100 mg daraxonrasib. This is in patients with metastatic pancreatic cancer. The middle column, also dose level 1, so the same doses of both vopimetostat and daraxonrasib, but this includes the patients with non-small cell lung cancer. To the right, this is dose level 2. That's 250 mg of vopimetostat, 100 mg of daraxonrasib. If we first focus on dose level 1, we can see that almost all toxicity events are low grade 1 or 2, and there are only a small number of grade 3 events, which were primarily thrombocytopenia in this population. If we move to the column all the way to the right in dose level 2, now a higher dose of vopimetostat, we see a higher rate of grade 3 adverse events, mostly related to rash or mucositis, and also some increase in the lower grade toxicities, so grade 1 or 2. The DLTs in dose level 2 were rash and stomatitis. These are the common toxicities we see with daraxonrasib, not surprising toxicities to see. I would say overall, the safety signals that we're seeing in the patients treated thus far have really been very much within what we would expect based on what we know from vopimetostat and daraxonrasib. Based on these data and the efficacy data that were shown on prior slides, the plan is to advance dose level 1 to further clinical development. If we now take a little bit more of a look and think about, what are the toxicities we know with daraxonrasib, and how do those relate when we give daraxonrasib together with vopimetostat? We'd say very similar toxicities, really the four main toxicities we see with daraxonrasib are the four that are listed at the top of the slide, rash, stomatitis, diarrhea, and nausea. Certainly not an increase. If anything, actually a somewhat reduced incidence of these toxicities compared to what we see with daraxonrasib alone. If you look to the right side of the slide, if we look at the area under the curve using PK measurements from the patients on study for daraxonrasib, this was a very similar area under the curve to what is seen for single agent daraxonrasib at 300 mg. Really emphasizing that the 100 mg that is being used of daraxonrasib in this study, when it is given together with vopimetostat, provides a very similar exposure for the patient to what you see in patients receiving 300 mg daily of daraxonrasib. There is some evidence pre-clinically that PRMT5 inhibition, as we talked about before, alters signaling through the MAP kinase pathway. This may be part of what is to explain the potential for even reduced toxicity when they are used in combination. If we now move on to talk about the data with zoldonrasib. Again, zoldonrasib is Revolution Medicines' RAS(ON) inhibitor, a G12D-selective inhibitor, much less wild type binding. Very similar eligibility criteria. The only difference really is that require the G12D mutation. If we look to the right, the dose escalation schema, either 2 or 250 mg of vopimetostat orally once a day. Zoldonrasib is given at either 600 or 1,200 mg orally once a day. Available patients for safety were 34, and efficacy for 27. The same criteria being used. You must have been followed for 14 weeks to be eligible for evaluation for efficacy to allow at least two CT scans for evaluation. You can see again in the bottom right, NGS and IHC used for MTAP identification in terms of loss and high concordance between NGS and immunohistochemistry. If we start by looking at the safety and tolerability of vopimetostat and zoldonrasib, again, we can see that most events are low grade, very few grade 3 or higher events. The grade 3 events that we are seeing were primarily due to blood count suppression. In this case, as you can see, most commonly related to anemia. No DLTs were seen. Again, no unexpected toxicity events were identified. To be clear, this plot is actually for all the dose levels combined because the toxicities were quite similar across the different dose levels. If we now look at efficacy for vopimetostat and zoldonrasib. Again, these are patients with MTAP deleted, KRAS G12D mutated, metastatic pancreatic cancer. They may have received one or two prior lines of therapy. We can see on the top line, objective response rate was 52% in 27 patients. Again, you can see on the top line of the plot the number of prior lines of therapy. You can see the dose level in the white print in the bar with the dose level designated below. Then you can see again, many rightward arrows in the bottom of the bars because many patients continue on therapy and therefore even have further opportunities for reduction in disease burden and durability. In the table to the right, you can see 27 patients, objective response rate 52%, disease control rate 96%, 10 patients with confirmed PRs, four with unconfirmed PRs but still receiving treatment, and a 74% six-month PFS rate for the combination. Okay, to finish, this is now the combined waterfall plot for all patients receiving the combination of vopimetostat and a RAS(ON) inhibitor. Again, either zoldonrasib or daraxonrasib. Again, would call your attention to the high response rate, the high disease control rate, and many patients still receiving therapy. Really indicating the durability thus far of this treatment and the promise for really durable responses with the combination. I will pass it over to Adam Crystal, who will give some further information. Thank you, Dr. Wolpin, for joining us this morning and for your leadership on the trial. It's been a remarkable collaboration over the past several years, working with you and our other investigators to bring vopimetostat into the clinic and demonstrate the potential of PRMT5-targeted therapy. As you know, last year we reported the first clinical data for vopimetostat. Those data demonstrated single agent activity and a favorable safety profile. Together with the emerging preclinical data, which demonstrated synergistic activity with RAS inhibitors, these data prompted us to initiate the ongoing combination trial presented today. We believe the data presented today demonstrate that the observed preclinical synergy has indeed translated to the clinic. These combinations have the potential to provide meaningful benefit for many of the nearly 20,000 patients with MTAP-deleted KRAS mutant metastatic pancreatic cancer that die each year in the U.S. alone. Today's results, including the 92% objective response rate and efficacy evaluable patients treated with vopimetostat and daraxonrasib, increase our conviction that the treatment of pancreatic cancer is being dramatically reshaped, and that vopimetostat is well positioned to fundamentally change how this disease is treated. This combination approach may offer a first-line chemo-free option for patients with pancreatic cancer that could be both more active and more tolerable than current standards of care. These results are particularly impressive given the patient population. With more than half of patients receiving this investigational treatment regimen in the third-line setting. Based on the strength of the data and the evolving treatment landscape, we plan to prioritize development of the vopimetostat daraxonrasib combination in the front-line setting, where we believe patient benefit will be maximized. As you can see on this slide, we plan to initiate a phase III randomized controlled trial in first-line patients with MTAP-deleted pancreatic cancer. Additionally, we plan to expand the existing phase I/II study, which generated the data discussed today, to evaluate opportunities for second-line registration. In the coming months, we will share updated data with regulatory authorities and work with them to confirm the details of our development plans as we continue to accrue data to this ongoing study. I'll now turn the call over to Matthew Gall to share financial highlights and review our upcoming milestones. Matthew Gall. Good morning, everyone. It's great to be with you. With approximately $380 million in cash on our balance sheet, we are well positioned to move forward with the planned frontline phase III combination trial in pancreatic cancer, and we continue to expect cash runway into 2028. As we advance development of vopimetostat in pancreatic cancer, we will maintain a focused and disciplined approach to investment across our R&D portfolio, while recognizing that we have several near-term catalysts ahead of us that have the potential to unlock additional meaningful opportunities, both as a monotherapy and potentially with further combinations. We will prioritize our most promising opportunities to impact patients, and our ability to cost effectively generate compelling signals in a short period of time may allow us to efficiently de-risk investment in additional indications for vopimetostat and TNG456 with clinical data. Ultimately, our goal is to realize vopimetostat's blockbuster potential while we continue to sustainably invest in additional compelling growth opportunities. We remain on track to generate multiple potentially impactful catalysts for the company, including sharing vopimetostat data in lung cancer and initial TNG456 data in glioblastoma in the second half of the year. I'll turn the call back over to Malte for closing remarks. Thank you, Matthew Gall. In closing, I want to highlight how we are positioning Tango to seize on these important data to deliver value to patients and our shareholders. Building on our scientific leadership pioneering PRMT5 targeted therapy for cancer, we are reorienting ourselves to focus on late stage development for vopimetostat. With the addition of highly experienced talent and enhanced operational capability, we are ready to efficiently execute a global pivotal trial in a competitive space. With promising combination data in hand and a de-risked path in frontline pancreatic cancer, we believe vopimetostat's first-in-best-in-class potential has been strengthened. The optionality we have intentionally created to combine with other RAS targeted therapies in development further enhances vopimetostat's strong competitive positioning for the long term. While the anticipated need for transformative therapies in pancreatic cancer alone represents a potential blockbuster opportunity for Tango, we also have significant upside potential in lung cancer and glioblastoma. In these indications, we believe we can also deliver important therapeutic benefit to patients with vopimetostat and our next generation PRMT5 inhibitor, TNG456, and we look forward to sharing additional updates to these programs later this year. Before we wrap up our prepared remarks, please allow me a personal reflection. As an oncologist who has treated many patients with gastrointestinal cancers during my academic career, I know firsthand how devastating pancreatic cancer is and how difficult it is to treat. The fact that Tango is one of the companies advancing the field into what may be a fundamentally new paradigm with a potentially safe and effective chemo-free treatment is personally very gratifying to me. I want to close by thanking the patients and their families who participated in the studies, clinical investigators, as well as employees and partners who have worked tirelessly to get us to this inflection point. This is an exceptionally exciting time for Tango, and all of us at the company are united in our mission to bring life-changing treatments to patients. With that, operator, let's begin the Q&A. Thank you. As a reminder, if you'd like to ask a question, please press star 11. If your question has been answered and you'd like to remove yourself from the queue, please press star 11 again. Our first question comes from Eric Schmidt with Cantor. Your line is open. Thanks, and congrats on these remarkable data. Truly game-changing. Adam, I'm wondering if you had any opportunity yet to talk to regulators about the path forward in the frontline setting. Do you think you're going to require some experience in frontline patients before kicking off that study? How do you think about establishing contribution of parts in the frontline, if at all? I'm also curious how we should think about potential role for Revolution Medicines in running a future study. Thank you. Absolutely. I would point to the data cut of May 28th, only about a week or so ago, which has not given us an opportunity to discuss these data with either the FDA or other regulatory bodies. We are preparing to do so and look forward to doing exactly that over the coming summer to define exactly what our regulatory path forward will be. It's absolutely critical that we align with them. It is a changing landscape with a lot of open questions. Once we have done so and have a clear path forward into a phase III first line study with the study design at that point, we will bring it forward knowing that we have the endorsement of the FDA under our belt. For you or Malte Peters on the collaboration with Revolution Medicines and their role here. I spoke to our collaboration many times. We have a very good collaboration. The project goes very well. We speak all the time between the two companies at all levels. Both companies have started discussions of how to continue development of both the drugs as a joint effort. We believe that this joint opportunity is a very attractive and tremendous impactful situation for patients and also for both companies. I think that's how I would describe the situation with RevMed. At the same time, we spoke at the beginning of the year that we like the optionality we have built into our company here with the supply agreement that we started with Erasca. That interaction was also followed very well. At the moment, here at Tango, we like the fact that we work probably with the two best RAS inhibitors out there in clinical development. Great. Thanks and congrats again on some amazing data. Yeah. Thank you. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open. Hey, guys. Good morning and yeah, congrats on the data from me as well. Obviously very impressive response rates and duration. I noticed that almost 2/3 of the patients were actually third-line PDAC patients, and I was just wondering if you had a chance to look at the efficacy data in second-line patients only. Just curious, especially for the 12D cohort. Just on dose selection, it sounds like you said you're moving forward with the 200 mg Vopi combination dose and daraxonrasib. Maybe for Dr. Wolpin, do you feel that you have enough data to make that decision yet? And I know there are only a handful of patients treated at 240 mg, 250 mg combination dose. Yeah, just curious how the tolerability compares to the daraxonrasib monotherapy since a lot of the AEs were actually known AEs that have been seen with daraxonrasib. Thanks so much. Sure. Thank you for the question. Regarding efficacy in the second versus third-line setting, the numbers get quite small when we start subdividing. Our conclusion when we compare, for example, second-line to third-line patients in the daraxonrasib treated population, is that there is no meaningful difference in activity. Perhaps the simplest way to say that, of the 12 efficacy evaluable patients presented today, effectively all benefited and most continue to benefit with no difference between the second and third-line patients in how they responded. In terms of the dose level 1, we do have a large number of patients treated in that, in excess of 20, and very much like the profile in terms of PK safety as well as efficacy. The one thing that I would note is that we have begun to explore other dose levels, really to de-risk the path forward. We consider the dose level 1 data we presented today excellent and are very comfortable moving it forward. In order to ensure that we can do so as quickly as possible, we're making sure that we understand possible alternatives so as not to slow things down. Thank you. Thank you. Our next question comes from Laura Prendergast with Stifel. Your line is open. Hey, guys. Congrats on the very exciting data today. In monotherapy, PRMT5 inhibitors have shown about six months median time to respond. Can you comment to how early you're seeing responses and if you're seeing deepening with time? Also, regarding a phase III, as far as inclusion of RAS mutations, is this something that you're going to need to wait to see what the daraxonrasib monotherapy label looks like first? Would you maybe do all comers in PDAC with an MTAP deletion or a specific patient population? Any comments there would be helpful. Perfect. As to the first question, overall, the pace of tumor shrinkage is a little bit faster than with single-agent PRMT5 inhibitors. We look forward to sharing a more full set of those data when we update these data as they mature with more patients later in the year. They do continue to shrink over time. Indeed, most of the patients in this cohort continued to shrink at the time of the data cut. It is fair to say that the velocity of that shrinkage tends to slow by the third or fourth scan. The second part of your question on the phase- III III Mutations testing. Yes, I remember. Testing for RAS. Will we be testing for RAS in a phase III? I think the simple answer for that is that we need to understand the daraxonrasib label as that likely approval comes to pass, and that will impact the discussion we have with FDA and other regulatory bodies as to the relative advantages or disadvantages of pre-screening for KRAS mutation. We know from the RASolute presentation that in each arm, there were only eight or nine RAS wild-type patients respectively. We assume that the label will not include testing, but that's our assumption. Of course, we need to wait for what the label will actually show. Got it. Thank you very much, guys. Congrats again. Thank you. Thank you. Our next question comes from Kelsey Goodwin with Piper Sandler. Your line is open. Hey guys. Congrats on the data this morning. Really impressive. I guess maybe two quick ones from me. First, in terms of the patient numbers for the daraxonrasib combo in PDAC, I'm just wondering, I think we had about 14 you had said, as of December. I'm just wondering why did enrollment kind of not pick up in the H1 of 2026? Then maybe second for Dr. Wolpin, building on the plenary discussant's call to action to really evaluate more RAS inhibitors, more combinations. How do you see the landscape shaping out over the next few years? Thanks so much. Sure. I'll take the first question and then pass the baton to Brian for the second question. The reason is straightforward, is simply that we explored two dose levels with daraxonrasib and analyzed those data before expanding dose level 1. In contrast to with zoldonrasib, where we explored four dose levels, which enabled patients to come on in escalation as well as backfill for a larger number of slots. Brian, would you like to comment on the second question? Sure. Thank you for the question. I think we were all quite impressed with how RAS inhibition in RASolute 302 was able to lead to substantially higher response rates and durability than chemotherapy. I think as we also discussed, and as you said, the discussant also mentioned, that doesn't mean these patients are cured. They will develop resistance to RAS inhibition. What we really need as a field now is to evaluate a number of options to improve the durability of response and increase further the response rate. I think there is a whole host of things out there that could potentially be. I think this, though, in terms of the data presented today, is very much supported by preclinical data and now has a body of clinical data in patients suggesting that this may be one of those high-priority combinations for us to consider. I would consider this one of some high-priority combinations that we as a field need to explore to help our patients. Great. Thanks, guys. Thank you. Our next question comes from Joseph Catanzaro with Mizuho. Your line is open. Hey, everybody. Thanks so much for taking my questions. Let me add my congrats on the data here. Maybe two from me. First, forgive me if this was mentioned in the prepared remarks, was rash prophylaxis implemented in this study? If not, are there any sort of considerations around utilizing that prophylaxis regimen that's being used with daraxonrasib? Second, I think there's some preclinical data out there that would suggest this sort of dual mechanism of RAS inhibition and PRMT5 inhibition could have utility in non-MTAP-deleted tumors. Wondering if you've explored this preclinically, were there any interest in exploring clinically? Any thoughts there would be great. Thanks. Sure. The answer to your first question is yes, we prophylaxed these patients for rash, much in the same manner as was done, for example, on RASolute 302, following the guidelines provided to us by our colleagues at RevMed. We have asked the very fair question of have investigators gotten better at prophylactically managing rash, resulting in what may be a lower incidence here? It is possible, but it is also possible that the absence of Grade 3 events and slightly lower rate of Grade 1/2 events is secondary to the impact on biology affected by the addition of the PRMT5 inhibitor. As to the second part of the question, remind me the second part of the question. I apologize. Yeah. No problem. It's the idea of this sort of combo in non-MTAP deleted tumors and whether you've looked at that pre-clinically, any interest in looking at that clinically. We have begun to look at it pre-clinically. I can't say that we've generated any data that I'm ready to share today. I think it is an interesting question. If the data presented today holds up and continues to demonstrate that this drug makes pan-RAS inhibitors more tolerable, if it is the case that even in an MTAP intact patient, we get a little bit of efficacy from this molecule, which is possible given the concentrations we achieve, there may be a path to doing it. I would consider it speculative at this point, but certainly something we are thinking about, primarily in the pre-clinical domain. Okay, great. Thanks so much. Thank you. Our next question comes from Emily Shutman with Leerink Partners. Your line is open. Hey, this is Andrew Berens. I think Emily must have dialed in for me. Congrats on the update. Really a great day for MTAP and PDAC patients. Two from me. You gave some additional insights into the pathophysiology that you're seeing for the activity. Just wondering if you think HRAS or NRAS or cyclophilin play a role. Just wondering if the pan-KRAS agents could possibly benefit from this synergy and have less tox. Maybe if you could give us an update on where you are with this combination effort, versus other efforts like your own with Erasca or, the collaboration of daraxonrasib with Mirati. Just trying to get a sense for how far you are ahead of any fast followers. Thanks, and congrats again on this impressive data set. Sure. Thank you. I'll answer your second question first. Our Erasca study, we are moving as quickly as possible with the intent of getting that study open this year. It is almost the H2, and that will be in the H2. It's worth noting that there are other molecules or other trials combining PRMT5 inhibitor with pan-RAS inhibitors. I think potentially the most interesting one from our perspective is the combination of daraxonrasib with BMS-504, the prior Mirati molecule. My understanding, based on clinicaltrials.gov, is that that study is scheduled to start in July of this year, putting us at least one year ahead. In terms of the role for NRAS and HRAS or cyclophilin, I think that as KRAS wild type may be upregulated by the treatment we've given here today, so too may be the case for HRAS and NRAS. I think more likely KRAS, but it could be important. I think that will be determined over time. In terms of cyclophilin A, I think that data set is emerging, and I don't think I would draw any conclusions on it based on what we've presented today. Okay. Thanks. Appreciate it. Just maybe one addition from my end on your first question. We expect that there will be more than one RAS inhibitor approved, going forward. Our vision here at Tango is that, vopimetostat could ideally be the preferred PRMT5 inhibitor to be combinable with any RAS inhibitor available, right? That's a bit the vision and the dream we have. Great. Thank you. Thank you. Our next question comes from John Newman with Canaccord Genuity. Your line is open. Hi there. Thanks for taking my question. Let me add my congratulations as well. Just curious, obviously, you've got a lot of things going on here, and you've discussed your priorities, just curious about a potential path forward in lung cancer. I'm wondering if at this point, if you just plan to expand the current study, or if there are any thoughts kind of going forward eventually on a randomized study there. Thanks. Sure. I think that there are opportunities in non-small cell lung cancer for vopimetostat. I would guide first to the single-agent data, which we are planning to share this year, which we are optimistic about. The most obvious place to put such a molecule for a short-term approval might be in the second line versus docetaxel. I think for that data, we need mature PFS data which establishes durability sufficiently strong that we would have high confidence that it could beat docetaxel in such a setting. I also think that the overlapping population of MTAP del and RAS mutation is a real population of patients of approximately 5,000 patients a year, similar to the size of the ALK population in non-small cell lung cancer. These preliminary data suggest that this combination could be meaningful there. We are determining the exact paths forward, and we'll look forward to sharing that once we have developed it. I think that there are opportunities, whether it be in the second or first-line setting in that patient population for the combination. Great. Thank you Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open. Hi, good morning. Congrats on the great data. I was just going to ask about the durability that you're seeing so far with the six-month PFS. Seems like you're tracking better than RevMed's monotherapy data. Do you view this early durability signal as superior to daraxonrasib monotherapy? Could you show a PFS update later this year when you do your next data update? I'll start with that. Perfect. I think that here we have 12 patients, and we have a 90% six-month PFS rate. There are confidence intervals in the deck which speak to the likelihood that this may well be better than single-agent daraxonrasib. I'd also point out that ours is in more heavily pretreated patients than RASolute 302. The data remain early, but thus far suggests that it could be better than achieved in RASolute 302. Anything else? That's all I have, I think. Are you planning on doing a durability update later this year? Oh, thank you. I do think that when we present the data, an updated data set later this year, it will include more patients with efficacy. There will be longer-term follow-up for many or most of those patients, and I would expect it would have a similar amount of patient-level data so that a PFS could also be extracted from that data set. We have one here, which is, of course, immature because so few patients have progressed. Got it. Maybe one quick follow-up, just with the data that you're seeing here and the debate around daraxonrasib potentially getting accelerated approval in front line. As you communicate with FDA and figure out your next step plans, do you think you have enough to potentially go head-to-head versus daraxonrasib in a registrational study? We have not had these discussions in great detail. We are preparing to have the first discussions with regulators around the world, including FDA, but also EMA and the Japanese authorities. Once we have an opportunity of sharing the data and discussing next steps, we are ready to give an update. That's, I think, probably the most realistic answer I want to give at this point. Understood. Congrats again. Thanks for taking my questions. Yeah, thank you. Thank you. Our next question comes from Yuan Zhi with B. Riley. Your line is open. Good morning. Congrats on the unprecedented combination advocacy. Maybe my first question is on the first line setting in PDAC, we don't know if the dara 300 mg will beat the dara 200 mg plus chemo. How will that impact your phase III design if dara plus chemo is better than the dara monotherapy? I think that I would defer to, in part, what Malte said before. Much of the finalization of our study design depends on upcoming interactions with FDA in this changing landscape. We also intend it to be the case that this study is up and running well before that phase III first-line study reads out. The study design will be finalized before those results are known, but certainly account for the scenarios which emerge from that study. Got it. Do you need any dose de-escalation to optimize the dose since the ORR is already at 92% in PDAC before your phase III initiation? Excellent question. We are very comfortable with dose level 1 in terms of PK safety and efficacy, but recognize that there is often interest in dose optimization. For this reason, we have begun to explore other dose levels to ensure that the data package we bring forward supports a final dose determination for the phase III. Got it. Thank you for taking our questions. Congrats again. Thank you. Thank you. Our next question comes from Kalpit Patel with Wolfe Research. Your line is open. Yeah. Hey, good morning, many congrats on the results here today. One for Dr. Wolpin. How do you think about these results presented today versus the Navlimetostat chemo combo data from Bristol-Myers, both from a tolerability and efficacy perspective? Second question on the top-line efficacy here between daraxonrasib combo and the zoldonrasib combo. Any reasons for why there's such a gap in the response rates? Do you plan on prioritizing the daraxonrasib combo going forward? I'm assuming that's the case. Why don't I start with the second question, I'll ask Brian to comment on the first question. I think the second question is very interesting. Effectively, why is the overall response rate higher with daraxonrasib combination rather than zoldonrasib combination? I think that there are two credible explanations in terms of the data. One is what Brian spoke to earlier, the understanding that upregulation of wild-type RAS isoforms may be activating and that daraxonrasib could effectively suppress that, whereas zoldonrasib would be unable to. The second thing I would point out is that the zoldonrasib patients had an inferior ECOG status in the study. It may contribute to the lower overall response rate, but we certainly cannot be sure. Those are the reasons that I would point to. In terms of your first question on comparison to the other study, I'll defer to Brian. Yeah. I would say, it's early days for comparisons across different PRMT5 inhibitors and across other combinations. I would say, focusing on what we saw today, this clearly looks like a promising combination, and I think it will need, over time, further patient enrollment across a number of studies to really show what is truly best. However, this really does look like, and in response to other questions that I've been asked, this really does look like, based on the data that's available so far, like a competitive combination approach, whether that be with chemotherapy, other PRMT5 inhibitors, or other mechanisms of actions of other drugs. This really does look to be a competitive combination for the field to be moving forward with. Okay. One follow-up for the company, how should we think about the other tumor-agnostic indications because of the profound efficacy you've seen here in PDAC? I think that it is something we are interested in. The data we shared towards the end of last year demonstrated a single-agent overall response rate in that histology-selected population of 49%. We believe that is meaningful activity and would highlight that in that population there were some particularly interesting activity. For example, three- of- three patients with head and neck squamous cell carcinoma achieved confirmed PR. We have been adding more patients there. However, we have two primary focuses. One is pancreatic cancer, the second is non-small cell lung cancer. We are finalizing our plans in PDAC as we solidify our plans in non-small cell lung cancer. With those in hand, I do think that there are opportunities in a histology-agnostic population. It's on our long list of questions we are going to discuss with the regulators. Okay, great. Thank you again. Thank you. Thank you. Our last question comes from Robert Driscoll with Wedbush. Your line is open. Thanks. Morning, guys, adding to the congratulations here. Maybe just at a higher level and to follow on maybe a little bit, does the synergy demonstrated here have read-through to how you're thinking about development of 456 in GBM, or how you may think about additional potential combinations outside of KRAS inhibition going forward? Thanks. It's a very interesting question. I do think that it merits thought as to what this data means in other indications and beyond KRAS. I think the preclinical data speaks to this being through the MAP kinase pathway, and there are other targeted therapies which drive their efficacy through inhibition of the MAP kinase pathway. Those may provide opportunities. Specifically in GBM, I don't think that there is an obvious combination play because there are simply no other drugs which are approved or even in advanced investigational development that might be efficacious in doing exactly that. Got it. Super helpful. Congrats again, guys. Thank you. Thank you. This does conclude the question and answer session. Thank you for your participation. You may now disconnect. Everyone, have a great day.