Good day, and thank you for standing by. Welcome to the TERN-701 investor and educational webinar. At this time, all participants are in a listen-only mode. Please be advised that today's conference is being recorded and that slides available on today's webinar need to be self-advanced by the viewer. After the speaker's presentation, there will be a question and answer session. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. I would now like to hand the conference over to your speaker today, Amy Burroughs, Chief Executive Officer. Good afternoon, everyone. I'm Amy Burroughs, Chief Executive Officer of Terns Pharmaceuticals. On behalf of the Terns team, I thank you for joining us today for our educational webinar on TERN-701, our investigational next-generation oral allosteric BCR-ABL inhibitor that is being evaluated for the treatment of chronic myeloid leukemia, or CML. Today, we will touch upon TERN-701's potential best-in-class profile, relevant benchmarks for assessing our upcoming phase I data expected next quarter, and potential position of TERN-701 in an evolving treatment landscape for CML. Before we begin, let me draw your attention to the fact that throughout the course of today's program, we will be making forward-looking statements. I invite you to our SEC quarterly and annual filings to review our forward-looking statements, disclaimers, and important risk factors. Finally, please note this webinar event is for informational and educational purposes only and is not intended for the media. So let's begin on page three. We're excited to focus today's discussion on why we believe TERN-701 has best-in-class potential for the treatment of CML and how to assess and benchmark CML data sets in the context of the phase I trial. We will also share our thoughts on how the treatment landscape is evolving with the rapid uptake of the first allosteric TKI to market, how TERN-701 may potentially fit into a treatment paradigm as the second marketed allosteric, and the development path required for TERN-701 to gain FDA approval. Importantly, our primary goal today is to equip you with the knowledge needed to calibrate and thoughtfully assess TERN-701's profile versus asciminib and other therapeutic agents in development for CML. Finally, we will open the event to Q&A with our analysts. Joining me on today's call are Emil Kuriakose, Chief Medical Officer, and Scott Harris, Chief Development Officer at Terns. I would like to quickly acknowledge Emil, Scott, and their teams for rapidly progressing TERN-701 in the CARDINAL study. Thanks to their efforts, we've made meaningful progress towards our ultimate goal of bringing this new therapy to patients who need it. Moving on to page four, CML is a chronic disease where there is meaningful unmet medical need, and most patients require therapy for the rest of their lives. In 2001, the introduction of imatinib, a first-generation active site tyrosine kinase inhibitor, also called TKI, transformed CML from a life-threatening cancer to a chronic disease. Yet despite the impact of imatinib and the subsequent approval of multiple improved second-generation active site TKIs, there remains a significant unmet need for better efficacy, safety, and tolerability. Approximately 40% of CML patients on these active site TKIs switch therapy within five years due to lack of sufficient treatment response or side effects. We've also learned that chronic use of active site TKIs is associated with a variety of serious adverse events due to off-target effects, including pleural effusion and life-threatening cardiovascular issues. Emerging scientific and real-world evidence supports that allosteric TKIs offer the opportunity to once again transform the CML standard of care. Novartis's asciminib is the first allosteric BCR-ABL inhibitor approved to treat CML and has demonstrated significant improvements on efficacy, safety, and tolerability over the active site TKIs. Asciminib has had substantial and rapid uptake in the market since gaining approval in all lines of therapy, including achieving 15% share in frontline, two quarters after frontline approval, and 35% of new-to-brand share across all lines of treatment. Novartis has expressed confidence in $3 billion in peak sales potential for asciminib, with some analysts projecting even higher. On page five, although asciminib is better than any other approved CML therapy today as the first-in-class allosteric, there remains meaningful opportunity for TERN-701 as a next-generation agent to improve across efficacy, safety, and convenience. To assess efficacy in CML, we look at major molecular response or MMR, a measure of improvement in disease burden that is the primary endpoint in CML clinical trials. In the asciminib frontline trial, 32% of patients do not reach MMR at 48 weeks. In the trials in the second and third-line settings, 57% and 75% of patients do not reach MMR at twenty-four weeks, respectively. From a safety AE standpoint, the warnings and precautions section of the label highlights the risk of pancreatic toxicity and hypertension. Lastly, another issue specific to asciminib is that dosing with food drives a 60% reduction in AUC plasma exposure, thereby requiring patients to fast for 3 hours around dosing. This fasting requirement is both a challenge for many patients and a potential risk to efficacy in the case of non-compliance. We already know that TERN-701 is more convenient, as it can be taken once per day without regard to food.... Moving on to page six. The founders of Terns understood the science of allosteric BCR-ABL inhibitors well and sought to design a better allosteric that could lead to meaningful improvements for people living with CML. We believe that our next-generation allosteric BCR-ABL inhibitor, TERN-701, has potential to provide meaningful improvements to efficacy, safety, and convenience, overcoming some of the limitations of asciminib. With that, I'm going to ask Emil to describe our preclinical and clinical rationale, supporting TERN-701's best-in-class profile, and to outline how to calibrate and benchmark our upcoming data in the fourth quarter. Emil? Thanks, Amy. Shown here on page eight is the study schema for the CARDINAL phase I study of TERN-701 in patients with chronic phase CML. This two-part study enrolls patients who have had failure or intolerance to at least one prior TKI, including prior asciminib. Once-daily doses of 160 milligrams up to 500 milligrams were evaluated in escalation using a BOIN design for initial safety assessment, with subsequent enrollment to backfill cohorts at each dose to obtain additional safety and efficacy. The dose escalation enrolled rapidly, with completion of initial safety evaluation of all doses by January 2025. Based on the totality of data from escalation, we selected the higher doses of 500 milligrams and 320 milligrams for randomized dose expansion, which commenced in April and can enroll up to 80 patients. The study is currently enrolling to part two as well as to part one backfill cohorts. Since both parts enroll essentially the same patient population, the upcoming data in the fourth quarter will include all patients dosed in escalation and expansion in a pooled fashion. Moving to page nine. This page summarizes the three reasons we believe TERN-701 has the potential to achieve best-in-class efficacy and safety based on preclinical data and early clinical data from the CARDINAL study that was disclosed last year. First, preclinical data demonstrate that TERN-701 has not only very high target selectivity consistent with allosteric inhibition, but also numerically greater potency than asciminib against multiple BCR-ABL variants. Second, clinical PK data demonstrate that all doses of TERN-701 appear to achieve higher target coverage than the approved dose of asciminib, which we hypothesized could support rescue of clinical response in the setting of asciminib failure and rapid deep molecular response in 2G TKI failures, as we observed anecdotally in our early clinical data reported last year. Third, TERN-701 may have a wider therapeutic index, allowing us to reach clinical doses that achieve higher target coverage than asciminib, as evidenced by the lack of DLTs in dose escalation and the totality of data from escalation supporting selection of the higher-end doses for dose expansion. We believe these three properties support the potential for best-in-class MMR achievement rates and safety. Please turn to page 10. CML is driven by the abnormal fusion of two proteins, BCR and ABL. Slide 10 illustrates how allosteric inhibitors achieve selective inhibition of BCR-ABL. A highly selective BCR-ABL inhibitor inhibits the disease-causing BCR-ABL fusion protein without interfering with the activity of hundreds of normal kinases. All kinases, including BCR-ABL, have highly similar active site domains, where ATP binds to facilitate phosphate transfer to other proteins. Active site inhibitors block this interaction in BCR-ABL, as well as multiple normal kinases due to the similarity of their active site domains, which can drive toxicity. Allosteric inhibitors bind to a different site on the kinase domain that is unique to ABL kinases, called the myristate pocket. It's normally occupied by a myristoyl group located at the N-terminus of the protein. As shown on the left side of the slide, binding of the myristoyl group in this pocket acts like a key that locks ABL kinase in an inactive state until it is recruited for cell signaling by other proteins. In the BCR-ABL fusion protein, the myristoyl group of ABL is replaced by BCR, as shown on the right, leaving the myristate pocket open. With no key to enter the lock and inactivate the kinase, BCR-ABL kinase activity goes unchecked, resulting in uncontrolled cell growth and CML. Allosteric inhibitors like TERN-701 enter the unoccupied myristate pocket of BCR-ABL, essentially replacing the function of the missing key, and inactivate the kinase. Importantly, because the myristate pocket in BCR-ABL is always open and there's nothing else in the cell that competes for binding to the pocket, allosteric inhibitors are able to inhibit BCR-ABL at very low concentrations, resulting in high potency. In contrast, the intact myristoyl group in wild-type ABL effectively blocks the drug's access to the myristate pocket. As a result, wild-type ABL inhibition requires drug concentrations several orders of magnitude higher than those needed for BCR-ABL inhibition that are well beyond concentrations achieved at clinically relevant doses. This is the biological mechanism behind the exquisite selectivity of the allosteric class for BCR-ABL over wild-type ABL and other kinases. And the next slide shows data from experiments that quantifies how much more selective allosterics are versus active site inhibitors. Inhibition of wild-type ABL1, ABL2, and other kinases has been shown to increase the risk of cardiovascular and other toxicities. Slide 11 illustrates the sheer magnitude of the difference in target selectivity between allosteric versus active site inhibitors for BCR-ABL over wild-type ABL1 and ABL2. In biochemical kinase inhibition assays, both TERN-701 and asciminib had over 10,000 times weaker potency against wild-type ABL1, ABL2, and over 450 normal kinases compared to their potency against BCR-ABL. In contrast, the active site inhibitors are, by design, equally potent against wild-type ABL1 and BCR-ABL, and at best, only thirty times weaker against wild-type ABL2 compared to BCR-ABL. Higher target selectivity of allosteric inhibitors is a key driver of the improved safety profile of asciminib compared to active site drugs, as shown in randomized phase III clinical trials. Additionally, there's now over 10 years of long-term safety data on asciminib from clinical trials and real-world evidence that further corroborates this improved safety profile relative to active site drugs. Moving to slide 12. While TERN-701 and asciminib show similar target selectivity in preclinical assays, TERN-701 differentiates from asciminib on the important parameters of potency, target coverage, and therapeutic index, as I'll cover in these next few slides. In cellular cytotoxicity assays, TERN-701 showed numerically greater potency than asciminib across multiple BCR-ABL resistance mutations in the kinase and other domains. Moreover, early data from dose escalation showed that TERN-701 free drug concentrations, particularly at doses of 320 milligrams and above, exceeded the in vitro IC90 for most of the BCR-ABL mutations shown here on this plot. Although BCR-ABL resistance mutations occur in fewer than a third of CML patients, these data support 701's potential to show better clinical responses than asciminib in the setting of specific resistant mutations, particularly in mutations other than T315I and in non-mutated BCR-ABL, for which TERN-701 may have another key advantage over asciminib on the parameter of target coverage, as shown on the next slide. Moving to slide 13. Target coverage roughly quantifies how effectively a TKI inhibits the BCR-ABL target in patients at clinical doses. As shown on the left, a commonly used method to assess target coverage is to compare the exposure at a dose in patients to exposures in a mouse model at which the drug showed robust tumor growth inhibition by simply calculating the full difference between the two exposures. The approved dose of asciminib in non-T315I mutated CML is 80 milligrams once daily. The selection of this dose was supported by the observation that exposures at this dose in patients exceeded the maximally effective exposure in a KCL-22 cell line xenograft. Based on clinical PK data for asciminib reported from the phase I study, the average plasma concentration, or Cavg, at 80 milligrams once daily, is approximately twofold higher than the reported effective concentration in the KCL-22 xenograft. Calculating target coverage at clinical doses of TERN-701 using the same reference mouse model shows that the average plasma concentration in patients exceeds the maximally efficacious concentration in the KCL-22 xenograft by approximately four- to 14-fold as you go from the 160-milligrams to 500-milligram dose of TERN-701, as shown on the right. This is roughly two- to seven-fold higher than the target coverage we calculate for asciminib 80 milligrams based on the previously reported clinical and preclinical data. This led us to hypothesize that the clinical doses of 701 may drive higher response rates than asciminib 80 milligrams, since improved target coverage has been shown to correlate with higher clinical response based on studies with other TKIs. Turning to slide 14. A good clinical test of the higher target coverage hypothesis would be to see if TERN-701 can rescue response in a patient who has treatment failure on asciminib 80 milligrams. This is indeed what we observed with our very first patient enrolled in the clinical trial at the lowest dose of 160 milligrams. This thirty-five-year-old male was previously treated with dasatinib, ponatinib, and asciminib 80 milligrams. The patient's BCR-ABL transcript levels had not decreased to below 1% after a year on asciminib 80 milligrams, thereby meeting criteria for treatment failure as defined by the ELN guidelines. On TERN-701, the patient deepened his response to less than 1% within five cycles, supporting the hypothesis that TERN-701 is achieving more effective target coverage than asciminib at TERN-701 doses of 160 milligrams QD and above. Moving to page 15. Doses with superior target coverage would not be clinically viable unless they're supported by a safety and tolerability profile that allows patients to stay on these doses long term. The early safety data from TERN-701 dose escalation on slide fifteen showed no dose-limiting toxicities all the way up to the maximum dose of five hundred milligrams. In contrast, multiple DLTs were seen with asciminib in dose escalation, and in clinical studies, there was a notable trend towards increased AEs, including pancreatic toxicity and hypertension at higher doses of asciminib with longer term follow-up. These data support TERN-701 having a potentially wider therapeutic index than asciminib, which would enable doses that achieve higher target coverage to drive improved efficacy without compromising safety and tolerability. Early data from TERN-701's dose escalation showed no clinically meaningful changes in pancreatic enzymes, LFTs, or vital signs. Additional safety data with more patients and longer follow-up could further support a differentiated safety profile if these trends continue to hold. That takes us to the next section on how to assess our upcoming, more mature CML phase I data set. Please go to slide 17. This slide shows an overview of how molecular response is assessed in CML and defines some key terms. First, as shown on the left, molecular response is defined as a decrease in the levels of BCR-ABL mRNA assessed by RT-qPCR in peripheral blood, measured as a percentage on a standardized log scale.... BCR-ABL, less than 0.1% is major molecular response, or MR3, which is a regulatory approval endpoint in pivotal studies. In phase III studies, only patients without MMR at baseline are allowed to enroll based on regulatory precedent, whereas in phase I studies, patients with or without baseline MMR can enroll. Patients without baseline MMR enroll because of treatment failure or intolerance to their TKI, and those with MMR or better enroll due to TKI intolerance. The treatment goal in patients without MMR is to achieve MMR, while the goal in those with MMR is to maintain a durable MMR. Accordingly, there are three defined clinical endpoints to assess MMR in phase I studies, as shown on the right: MMR achieved, MMR maintained, and the sum of the two, which is the overall or cumulative MMR. Importantly, the MMR achievement rate at six months is the approval endpoint for pivotal studies in relapsed/refractory CML. The next few slides provide a guide for assessing and benchmarking data in CML phase I study, particularly considering the shifting treatment landscape with asciminib's recent approval in frontline. On page 18, the table outlines key questions to ask within the broad categories of baseline demographics, efficacy, and safety, and comparing a mature data set from a single-arm phase I study to other contemporaneous or historical phase I studies. First, one must appropriately calibrate the baseline demographics to ensure that the patient populations are comparable. The two axes on which this calibration is done are CML treatment history and baseline disease characteristics, measured by BCR-ABL transcript levels and mutation status. Second, when assessing MMR, the key parameter to look at is achievement of MMR by six months in all evaluable patients, as well as achievement in key subgroups with more refractory disease. Finally, longer-term safety data in more patients with longer duration of treatment provides clarity on the safety profile of the molecule relative to other TKIs. Moving to page nineteen. The key parameters to compare when calibrating baseline disease characteristics of a phase I study population are shown in this table. They can broadly be divided into baseline leukemic burden, response to last TKI, and resistance mutations. Baseline disease characteristics of patients in CML phase I studies over the past decade have remained fairly consistent. More than 50% of patients in phase I studies have high leukemic burden, delineated historically as baseline transcripts greater than 1%, and generally, less than 20% of patients enrolled have a baseline MMR or better. The majority of patients in phase I studies have lack of efficacy to their last TKI, as opposed to intolerance, and about 15%-30% have a BCR-ABL resistance mutation, with the active site gatekeeper T315I mutation being the most common. It's important to point out that historically, T315I mutated and non-T315I mutated patients are separated for efficacy reporting in phase I CML trials, including that for asciminib. Non-T315I mutant patients represent more than 75% of the overall CML patient population. The second parameter to assess when calibrating baseline demographics in a phase I study population is the prior TKI exposure, as outlined on slide 20. The key difference between asciminib phase I studies and the CARDINAL study of TERN-701 is that the CARDINAL study enrolls patients who had treatment failure or intolerance to asciminib, whereas the asciminib trials had an allosteric-naïve patient population, thereby making CARDINAL a more refractory population than the asciminib studies. The similarities between asciminib phase I and CARDINAL are that they both enroll patients with prior failure or intolerance to imatinib, two 2G TKIs, and ponatinib, and both primarily comprise third-line-plus patients. The other contemporaneous phase I study in a Western population that enrolled an asciminib-exposed patient population is the ongoing ENABLE study of ELVN-001, an investigational active site inhibitor. Therefore, it's reasonable to expect that the CARDINAL patient population will be more like the ENABLE population than the asciminib studies with regard to prior TKI exposure. Table on slide 21 shows the six-month MMR rates reported in the asciminib studies and recently reported MMR rates from ENABLE in a post-asciminib patient population. The six-month MMR achievement for asciminib was around 25% and stayed very consistent from phase I to phase III, demonstrating the strong read-through of this endpoint to phase III. The recently reported interim phase I data from ENABLE study showed a 32% MMR achievement by six months in a contemporaneous patient population like that in the CARDINAL study. Overall or cumulative MMR by six months, which includes MMR achievement and maintenance, has ranged from 37%- 47%, respectively, in the asciminib and ENABLE studies. While cumulative MMR is not a regulatory approval endpoint, it still provides a meaningful assessment of efficacy if the drug durably maintains MMR for six months or longer or further improves response to deep molecular response, defined as MR4 or better. While MMR achievement and overall cumulative MMR in all evaluable patients provides the most robust benchmarkable assessment of efficacy relative to other studies, it's important to look at these same endpoints in patient subgroups with more refractory disease, namely those with prior asciminib, ponatinib, and lack of efficacy to their last TKI. While we plan to report data on these subgroups, there's limited data from the listed studies on MMR achievement in these more refractory subgroups. Although seeing MMR achievement in these refractory subgroups is generally a good indicator of meaningful efficacy, subgroup analysis should be interpreted more as informative trends rather than robust benchmarks due to their smaller numbers. Finally, six-month CMR achievement rate in the phase one and three asciminib studies in third-line plus patients was below 15%. Moving to page twenty-two, the other important breakdown of the overall MMR rate is to evaluate the molecular response across the range of BCR, of baseline BCR-ABL transcripts. This is best done using a molecular response shift table, as shown on this slide. The shift table breaks down the response evaluable patient population according to the baseline transcript level category on the top row and captures the best molecular response shift on treatment from baseline in the columns. An improvement from baseline is captured as the number of patients in the cells above the diagonal. As shown in the table, patients without baseline MMR are divided into three categories of greater than 0.1%-1%, greater than 1%-10%, and greater than 10%. Achieving six-month MMR is more challenging with increasing baseline transcript levels. In patients with baselines greater than 10%, transcript levels must decrease by three logs as opposed to just one log in those with the baseline of 0.1%-1%. To put that in perspective, the six-month MMR achievement with asciminib in the phase I study was roughly 8%-10% in patients with a baseline transcript above 10%, compared to approximately 45% achievement in those with a baseline of 0.1%-1%. Therefore, seeing shifts to MMR within all three categories indicates robust efficacy, as does seeing upward shifts across all baseline categories, including those with baseline MMR improving to deep molecular response. That brings us to slide 23, which summarizes the key differences in previously reported early dose escalation data from CARDINAL last December and the upcoming Q4-2025 dataset. Put simply, last year's data showed clinical activity, excellent PK properties, and encouraging safety in a small number of patients, with compelling responses in patients with highly refractory disease and a safety profile that allowed us to select the higher-end doses to take forward to expansion. The upcoming data aims to show benchmarkable efficacy and safety in more than fifty patients with a comparable patient population to ongoing phase I studies, allowing for a more robust assessment of six-month MMR achievement and should also provide meaningful clarity on potential emerging safety differentiators from asciminib. Now, let me turn it over to Scott to discuss the future of CML and our development path ahead. Scott? Thanks, Emil. I'll start on slide 25. As you've heard, we at Terns are excited about the potential for TERN-701 to set a new benchmark for efficacy and safety in CML and move the profile up and to the right on this graph. With Emil's presentation, we hope we have given you the knowledge needed to calibrate and thoughtfully assess TERN-701's profile versus asciminib and other therapeutic agents in development once we release 701 data later this year. Next, I'd like to briefly talk about how the treatment dynamics in CML are poised to change the treatment algorithm with the availability of a second, potentially best-in-class allosteric TKI. Please turn to page 26. Here, I'll step you through how patients in the future might move through various lines of CML therapy when there are two approved allosteric TKIs and potentially the availability of new active site inhibitors. For simplicity, we think about the treatment selection in each line as either being an allosteric, shown in light green, or an active site, whether branded or generic, in white. For newly diagnosed patients, our research indicates that up to 60% of patients will start on the best available therapy, which may be one of the two allosteric TKIs, namely 701 or asciminib. The remainder in frontline would receive generic active site TKIs due to cost or access reasons. Compared to those who start on active site drugs, patients who start on an allosteric inhibitor in frontline are expected to stay on treatment longer, with a 50% lower chance of needing to switch therapy. This is supported by data from the randomized phase III frontline study of asciminib, which showed that at two years, the discontinuation rate in the active site arm was twice that of the asciminib arm. Based on this, we expect that second-line setting will have a disproportionately higher number of patients who are switching from a generic active site drug than from an allosteric. TERN-701 is expected to launch with a second-line plus indication, given a trial in this population is the fastest path to market. For frontline patients whose CML has progressed on a generic active site drug, our market research indicates that physicians will switch classes to the allosteric with the best efficacy and safety profile. Our research also indicates that for patients whose disease progresses on asciminib in frontline, physicians would prefer a best-in-class allosteric if it has demonstrated rescue of response in asciminib failures. Therefore, we believe TERN-701 will be well-positioned to be the preferred TKI of choice in the second line. When a patient has progressed beyond two allosteric TKIs, they are likely to receive an active site in the third line in later settings. Of course, there may be situations where an allosteric is prescribed in later settings, such as for patients who had active site inhibitors in earlier lines. Finally, with strong pivotal data in a frontline setting, we believe TERN-701 has the opportunity to compete for a significant share of frontline as well. Our goal is to advance TERN-701 quickly through development and generate data to support a label in all lines of CML therapy. Moving to slide 27. We show a high-level overview of our potential full clinical development path. When we have sufficient data from the CARDINAL study to select one of the two expansion doses, we expect to initiate a registrational study in a second-line-plus CML patient population, similar to the one currently enrolling in CARDINAL. We would aim to start a frontline pivotal study in parallel to the second-line-plus study, with a slightly staggered start to maximize speed to a frontline approval. It's worth noting that the CARDINAL study will continue to provide long-term efficacy and safety data for TERN-701 that would serve as additional supportive data for registration and provide meaningful data catalysts as the pivotal studies are ongoing. In summary, on Slide 28, we continue to see a compelling potential opportunity for TERN-701 in CML, including a potentially superior mechanism of action and best-in-class allosteric profile, broad opportunity across all lines of therapy, accelerated development with a clear regulatory pathway, and limited competition within the allosteric class. Now, I'll turn it back to Amy for a few closing comments before we open for Q&A. Amy? Thanks, Scott. We hope today's presentation has been informative on why there is a significant need for better therapies in CML that could potentially be addressed by TERN-701. This is personal for me. CML has affected my family and several close friends. When we released our early data last December, we said it would take until fourth quarter of this year to have enough patients on therapy for a long enough duration to allow for comparison of the performance of TERN-701 to other therapies with phase I data sets. We plan to deliver on that promise and want to thank the patients who've enrolled in the CARDINAL trial and the staff at the dozens of clinical sites around the world who are participating in the study. Without you and our incredible team at Terns, we could not explore the possibility of a better therapy for people living with CML. Now, I'd like to ask the operator to open the line for questions. Operator? Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. One moment for questions. Our first question comes from Ritu Baral with TD Cowen. You may proceed. Good afternoon, guys. Thanks for laying everything out so clearly today for expectations. A couple questions from me. Amy, can you please go over exactly how many patients that we should expect six-month MMR from at essentially six-month evaluable MMR from the 300 mg and the 500 mg dose? In terms of doses, we said that we've been backfilling in dose escalation, and so you will see meaningful data at those higher dose levels. We've also said that we have over 50 enrolled patients across escalation and expansion. I can't guide to a specific number of efficacy evaluable overall or by dose, but I can say that we will have enough to benchmark the data to other phase I data sets. Understood. And then a quick follow-up on that one patient that had the inadequate response to asciminib, but a good response to 701. Was there something about that patient's mutation profile or, I guess, a lesson learned about mutation profiles in general that may set up patients that wouldn't respond to asciminib but would respond to 701? Yeah. Thanks, Ritu. Great question. I'll turn that over to our oncologist, Emil. Yeah, Ritu, no, that patient actually did not have any BCR-ABL resistance mutation, so this is a non-mutated patient. And again, this is... That patient is an example of the patients who comprise the vast majority of patients in CML. And here, again, the approved dose of asciminib is 80 milligrams, and that we think that's a clear demonstration of why target coverage matters, and we think that's the primary reason for the improved response. Got it. Thanks. Thank you. Our next question comes from Graig Suvannavejh with Mizuho. You may proceed. Good afternoon. Thanks for taking my question, and thanks for the presentation. Really helpful. Two questions if I could. My first is, I just wanted to revisit this idea of following frontline use of asciminib, whether you believe the practice will adopt a strategy of going with another allosteric or perhaps following a class-switching approach. We've heard various things from KOL that we've spoken to, and so just wanted to get your understanding of what second-line standard of care might look like and the reasons for or against using an allosteric versus an active site TKI. That's my first question. Then my second question really has to do with once you do get the phase I or the next set of phase I data how specifically those data will help you inform of how to design either the second line plus study and also the first-line study? Thanks. Great. I'll take the first one, and I'll turn the second one over to Emil. On your first question, we've also spoken to a lot of KOLs and treating physicians. And, Graig, as with most things in therapeutics, it's really gonna be based on the data. So for many years, physicians have used active site TKIs after active site TKIs. And as we said, allosteric asciminib has shown to be both more effective and safer. And with supportive data, again, showing effective treatment post asciminib, we believe that a second allosteric would be a treatment of choice due to efficacy and safety and demonstration of that in this patient population, which with our trials in second-line plus, we'll have the opportunity to potentially demonstrate. And for the second question, Emil, would you like to take that? Absolutely. So I think your question was around how the data, in terms of the MMR numbers, would inform our design of the second-line plus pivotal. And so, yeah, based on, given that we already said that MMR achievement at six months is the regulatory endpoint, that's the key number to look at. And so based on what that number is relative to historical data with 2G TKIs, which has been sort of the control arm in essentially all second-line, third-line studies that have been done recently, including those with asciminib, that would sort of be the default design, where you take 701 versus that same control arm, where we know that the data on six-month MMR is most robust, and we know that 2G TKIs in a second-line plus patient population perform about a 15%-20% six-month MMR rate. And so based on what our numbers look like, we'd be able to gain confidence in terms of the probability of success of controlling that historical control arm. And then any color on how that might impact how you think about the frontline study? Yeah. So the frontline study, again, we would anticipate doing a very similar design to what asciminib did in ASC4FIRST, which again, was a control arm where you had a blended mix of Gleevec and 2G TKIs, which is very reflective of real-world practice with regard to frontline therapy. As Scott outlined, we think that 50% of patients will still be getting a generic 2G TKI or a Gleevec as their therapy. And that also provides a good benchmark in terms of comparison with asciminib when you use the exact same control arm to be able to rank the drugs against each other. Thank you very much. Thank you. Thanks, Graig. Our next question comes from Jay Olson with Oppenheimer. You may proceed. Oh, hey, thanks for providing this update, and thanks for taking the questions. Since you had no DLTs in dose escalation, does that suggest that you could go to even higher doses with 701 than five hundred milligrams? Emil? So I could take that. Yeah, so we did not reach a maximally tolerated dose, and based on that, yes, it is possible that we could go to higher, but we don't think we need to, again based on the fact that we see the target coverage at 500 is at least estimated to be two- to sevenfold higher than what you achieve with asciminib 80 milligrams. And you know, part of the reason that we were able to select the five hundred milligram dose is, of course, the safety profile, not just DLTs, but overall incidences of adverse events, but also sort of a dose relationship in terms of response rate. And so putting that together, we think that the 500 milligram dose is has excellent PK properties and shows really good target coverage. We don't think we need to go higher than 500 based on the data we have today. Okay, understood. And then when you considered some of the safety advantages for 701 compared to asciminib, what are the most clinically significant safety differentiators that you'll be looking for? You know, asciminib is- Hey, Jay ... the cleanest drug, right? Sorry, go ahead. That's okay. Go ahead, Emil. Okay. Yeah. Asciminib is the cleanest drug in available for the disease today, but it still has issues with regard to safety. And the most common things, at least with asciminib, that you see, are pancreatic enzyme elevations, clinical pancreatitis, hypertension. In fact, these are on the warnings and precautions section of the label. In the phase I study, as you saw on that slide, there were several pancreatic DLTs in cycle 1. But over long-term follow-up, the incidence of pancreatic enzyme elevations, all grade approach 40%-45% in the phase I study, with grade 3 approaching 20%-30%, and there was a dose relationship seen with that. And so we think that that's number one. Number two, hypertension was also in the 20%-30%, all grade, and did show dose relationship as well. Again, we didn't see any evidence in the early data we disclosed last year of any changes in pancreatic enzymes, LFTs, or vital signs. So we think those are important and meaningful differentiators on safety, especially given that patients have to stay on these drugs lifelong. Great. Thank you. That's super helpful. And then maybe one big picture question: How would you define a next-generation allosteric TKI, and what would you like to see from 701 to, to position it as a next-gen allosteric TKI? Yeah. I think as it's been defined, for the active sites, it's really been about a step up, in efficacy, and I think it goes back to kind of Scott's slide 25 about, you know, sort of taking it to the next level on, on efficacy in particular, and safety. Great. Thanks again for hosting this event. Super helpful. Thanks, Jay. Thank you. Our next question comes from Silvan Türkcan with Citizens. You may proceed. Thank you. Thanks for taking my question, and thank you for putting up this clarifying event. My question is also a little bit bigger picture, maybe about the patient population you're looking at here in more near term, in the second line plus setting. What's the principal reason for progression here? Is it tolerability issues, or is it disease progression? And within 701, you know, better target coverage or selectivity, what's more important here in the clinic for that compound? The first part of your question, Silvan, I would actually refer you back to the slide where we have lack of efficacy to last TKI. If you look across phase I studies, I think it's on page 19, greater than 60% if you look across the CML studies over the last decade, in these refractory populations, are lack of efficacy to last TKI. And I'll let Emil take the second half of the question. Silvan, can you repeat the second part of that question? Just within the profile that you have, you know, and thanks for the data, you have some better target coverage, and at the same time, you have higher selectivity here versus other compounds out there. Just what is more important in the clinical setting? Yeah, I think it's a combination of all those things because, you know, the selectivity is fundamental to the... It's driven by the biology, the difference in biology in terms of the allosteric versus active sites. And hitting the protein at that pocket, which is very unique to the target, gives you exquisite selectivity, which already gives you an advantage with regard to therapeutic index. And so, you know, technically, all TKIs are able to increase, can increase the dose. They've been primarily limited by toxicity because their therapeutic index is really narrow. We've seen that patients who, for example, sort of plateau their response or stop responding to imatinib at four hundred, when they increase to eight hundred, they can rescue response, and that's been seen with other TKIs. But the extent to which they can do that is extremely limited because as you do that, you get much more toxicity. The benefit of allosterics is that you have a much wider therapeutic index or window, where you have the room to actually get to those higher level exposures, where you can drive better efficacy. But in order to do that, you have to see a clinical safety profile that supports that. Putting all those things together is why we think 701 can be potentially the best-in-class drug in the disease. It's in the allosteric class, which has already shown superiority to the active site class on both efficacy and safety. Within the allosteric class, there's a lot more head room to take advantage of that therapeutic index, which we don't think asciminib can because of the dose-related increase in the toxicities I just talked about, and that's where we think 701 will have the key advantage. Great, thank you. And maybe just one follow-up for the upcoming data set. You know, I think all eyes will be on the shift table. Do you think in what category is it harder to kind of make headway? So the MMR maintaining or the, you know, putting people into MMR, achieve population? What will be, let's say, the biggest surprise or better success for you for this first data set? Thank you. So the toughest patients, if you go look at the shift table on slide 22, is really those ones on the right, those with greater than 10% transcript levels. As Emil had said, even if you look at the data from other trials, those are much harder than, say, the patients in the MR2 category. You also mentioned the MMR maintained. Historically, looking across phase I data sets, that MMR maintained rate is pretty high, almost close to 100%. Great. Thank you. Looking forward to the data. Thanks, Silvan. Thank you. Our next question comes from Ellie Merle with UBS. You may proceed. Hey, guys. Thanks for taking the question. At this upcoming data cut, what proportion of the patients enrolled entered the study not in MMR? And then in terms of the timeframe for the pivotal trial, I guess if you could elaborate on when you think you'll be able to begin the phase III second line study, and whether 2026 is a possibility for that trial start. And just any more color on when you plan to speak to the FDA about the pivotal trial design and when we could get an update on that. Thanks. Thanks, Ellie. So the first one, I would refer you to slide 19, where, you know, we'll have a fairly comparable set with baseline MMR or better at fewer than 20% of patients. And I'll let Scott take the question about timeline of pivotal and speaking to the FDA as our head of regulatory. Hey, Ellie, thanks for the question. So I can't speak to specifics yet on when the pivotal study and second line plus would be initiated, but, you know, we are still currently enrolling in the dose expansion phase of the study. And, you know, as I mentioned during the presentation, once we feel that we have sufficient data at the two doses we're currently looking at to make a dose selection, that would be the time that we'd approach the FDA. So we anticipate that we would have that at some point next year, but whether or not the pivotal study would actually initiate next year, I can't comment on that. Got it. Very helpful. Thanks. ... Thanks, Ellie. Thank you. Our next question comes from Corinne Johnson with Goldman Sachs. You may proceed. Hi, this is Kevin on for Corinne. I had a question about the anticipated patient flow and market share that you shared for CML on slide twenty-six. How quickly do you see the market getting there based on what you've seen so far with the launch of Scemblix? Thanks. Yeah. So as we said, they already have 15% in frontline, you know, two quarters after launch, which is a very fast uptake. And, you know, our projections and what we've heard are pretty consistent with Novartis's. I honestly don't know exactly the timeframe to that 60%. And I would imagine it's probably gonna be over the next several years. Thanks. Thank you. Our next question comes from Evan Seigerman with BMO Capital Markets. You may proceed. Hi, this is Connor on for Evan. Thanks for taking our question and for the really comprehensive presentation today. Maybe just one on us, from us, if you can help us think through the relative importance of 701 convenient dosing and potentially differentiated safety in the context of the chronic treatment of CML. And maybe what are you looking for from a safety perspective to feel comfortable with meaningful differentiation here? Thanks. Yeah. So, you know, CML patients are different, as we talk to treating physicians. There are higher-risk patients. There are patients for which, you know, the convenience of, no fasting requirement is more meaningful, than for others. So it's hard to quantify exactly across, but if you look historically at dasatinib versus nilotinib, a lot of dasatinib share was gained through, the no fasting requirement. So that's really the best proxy that we have, and particularly with a, you know, strong efficacy and safety profile, you know, it's really, it's really a bonus to have the, the no fasting requirement. And, you know, we are, as I think is clear from the presentation, we really think that all three are important. From a safety profile in terms of what we're looking for, Emil, could you address that question as an oncologist? Yeah. I think it's essentially the broad answer is that we would want patients to be able to stay on these doses that achieve higher target coverage than asciminib for long term to derive maximum efficacy. And in terms of the fact that they're already looked to be achieving higher target coverage than the approved dose of asciminib, you know, even at our lowest dose of 160 milligrams and above, the more we can get prolonged dose intensity at those doses, the more likely it is that you will achieve deeper responses. And so effectively, whether it be a differentiating, we currently think we have a meaningful differentiator based on our early data with regard to the specific AEs of pancreatic toxicity hypertension. But regardless of the AE, the bottom line is patients should be able to just stay on treatment without interruption or reduction at doses where you meaningfully cover the target to be able to get to deeper responses, and that's our goal. Great. Thank you. Thank you. And as a reminder, to ask a question, please press star one one on your telephone. Our next question comes from Andy Hsieh with William Blair. You may proceed. Oh, great. Thanks for taking our question. So, maybe one on the relatively understudied asciminib failure patient population. I'm curious if you expect a lower MMR rate in that population compared to, let's say, patients who failed, you know, conventional TKI. So that's part one. Part two is more of a philosophical question. I think at EHA, some research groups suggested that the mutations arise from the myristate pocket is correlated with baseline ASXL1 mutation. And so I'm curious if that could be an interesting subpopulation to study, just to kinda accentuate the differentiation that you mentioned, which is, you know, more of expanded target coverage of 701. Thank you. Emil? Yeah. So maybe I'll start with the second question first. And, you know, the ASXL1 mutation is interesting. There's been a lot of interest on this mutation with regard to it being sort of a co-mutation that occurs that seems to predispose to a higher rate of mutational acquisition on BCR-ABL. So we are actually doing exploratory analyses of all our patients on study, you know, as most phase I studies do, looking at NGS to look at other mutations. Because when you get to these very late line patients, like fourth, fifth-line patients, they get additional mutations outside of BCR-ABL that become primary drivers of the disease, and so it helps to get that data to better inform sort of individual patient profiles as far as response. And so this is an area of exploration, and ASXL1 mutations are not in any guidelines right now as far as CML treatment in terms of guiding which TKI to pick, but it is an evolving area that we're interested in. And sorry, remind me. Your first question was? I'm sorry. Oh, just maybe the biology of asciminib failure patients. Do they, you know, kinda exhibit a more difficult to treat phenotype? And so how do you- Ah, yes. Think about benchmarking that? ... That's that population. Yeah, exactly. Yeah, generally, historically, you know, patients when you look at the subgroups, in patients who have been exposed to the most, the best TKI, so the third-gen TKIs like ponatinib and asciminib, these patients are the most heavily pretreated. They generally tend to have the more refractory disease. Yes, MMR achievement rates typically tend to be lower in those patients, which makes sense because they've been exposed and failed best drugs. The benchmarking in these subgroups is really tough because, again, numbers are usually small in subgroup analyses, and there are other variables that impact response, like baseline BCR-ABL transcripts. That's sort of just a way of saying that seeing MMR achievements in these patients is certainly a sign of a very active drug. But those numbers should be more informative trends than robust benchmarks because subgroup analyses are limited by small numbers and other variables that impact response. That's helpful. Thank you. Thank you. Our next question comes from Graig Suvannavejh with Mizuho. You may proceed. Yeah, thanks so much for taking the follow-up. Just wanted to get back to the benchmarks that you provided on slide 21, where you had 24% for the phase I for asciminib and 32% for Enliven's program. And I'm just curious, while you are providing that those two sets of data as benchmarks, I'm curious as to your thoughts are how whatever number you end up reporting, whether that's in between, whether it's above or below, whether safety tolerability should be considered as a way to assess the competitiveness of your compound, when looking, you know, that that balance between safety and efficacy. Thanks. Yeah. I'll start, Graig, and let Emil add anything that he'd like to add. You know, we think that the whole profile here, and as Emil's been saying, the safety really allows the potentially better target coverage, and that efficacy, as in most therapeutic areas, particularly in oncology, is a huge driver. And so we are, you know, it is really our goal and our hypothesis that we can be better overall on efficacy, and the safety is key to getting that better efficacy. Emil, what would you add to that? No, I agree with what you said. I think it is the whole picture, so you can't, you can't sort of rank everything just based on one number with regard to MMR achievement, and so safety certainly is one of the key components of differentiation. Okay. Thank you again. Thank you. I'm showing no further questions at this time. I would now like to turn it back to Amy Burroughs for any closing remarks. Great. Thank you so much. I just want to thank everyone for joining us for this exciting discussion on TERN-701, for all of the questions from our analysts, and our discussion about how to assess phase one data in CML. For any questions we did not get to on the call, we invite you to reach out to our investor relations team, and thanks and have a great day. Thanks, everybody, for joining us. Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.