Please note that today's conference is being recorded. I will now hand the conference over to your host, Amanda Isacoff from Precision AQ. Please go ahead. Thank you, operator. Good morning, ladies and gentlemen, and welcome to the Terns Pharmaceuticals TERN-701 Phase I CARDINAL Interim Data Conference Call. My name is Amanda Isacoff from Precision AQ. As a reminder, this conference call is being recorded, and a webcast of the call will be archived on the Terns website. Following our presentation, we will open the line for a question-and-answer session. Please turn to slide two of the presentation. We would like to remind you that during this call, Terns management will be making forward-looking statements that are subject to risks and uncertainties. Actual results may differ materially from those described. We encourage you to review the risk factors in the company's most recent quarterly report on Form 10-Q, which can be found on the Terns website. While Terns may elect to update these forward-looking statements in the future, they specifically disclaim any obligation to do so. Terns management joining us on today's call are Amy Burroughs, Chief Executive Officer, Dr. Emil Kuriakose, Chief Medical Officer, and Dr. Mark Vignola, Chief Financial Officer at Terns. With that, let me turn the call over to Amy Burroughs for opening remarks. Please turn to slide three. Amy. Thank you, Amanda, and good morning, everyone. Thank you for joining us today, as we were excited to share our initial positive and highly informative data from the CARDINAL Phase I study of TERN-701 as a treatment for chronic myeloid leukemia. TERN-701 is one of several potentially best-in-class small molecules internally discovered and in development at Terns. For today's call, I will provide opening remarks, and Emil will discuss the trial data and study results. We'll conclude with a question-and-answer period. Please turn to slide four. CML is a well-established indication that has been transformed from a fatal disease into a chronic one with patients living a life that is often significantly impacted by the disease but not shortened in duration. In 2024, CML therapies represented a nearly $5 billion market opportunity. In the U.S., approximately 10,000 new cases are diagnosed annually, and prevalence is expected to triple by 2040. As the majority of CML patients will take a tyrosine kinase inhibitor, or TKI, for life, it is not surprising that CML is characterized by frequent switching of therapy. In fact, nearly 40% of patients switch therapy by year five due to intolerance or resistance. The literature shows that chronic use of prior-generation active-site TKIs is associated with multiple adverse events due to off-target effects, including pleural effusions, cardiovascular events, and GI side effects. asciminib, the first approved allosteric TKI, improves upon the safety and efficacy of active-site TKIs and has been approved for use across all lines of therapy. However, we will discuss in more detail that there remain meaningful opportunities to improve on efficacy, safety, tolerability, and ease of use. Please turn to slide five. To provide some historical context, CML therapies have undergone multiple generations of improvement since 2001 with the introduction of imatinib, the first targeted therapy to impact survival for CML patients. Over the following decade, three second-generation active-site TKIs were approved that improved upon the efficacy of imatinib but were less favorable on safety and tolerability. Each second-generation drug has a unique tolerability profile and has been successful commercially with at least $500 million in sales. The allosteric class is the first novel mechanism of action as it targets the myristoyl pocket of BCR-ABL, enabling exquisite selectivity of the target and leading to meaningful improvements on safety and efficacy. Asciminib has demonstrated superiority in both frontline and previously treated populations and is projected to have sales of over $3 billion. TERN-701 represents an opportunity to continue to shift the allosteric class to the upper right corner of this graph by exploring the potential for an enhanced profile. Please turn to slide six to discuss more about our target profile. TERN-701 exhibits early signs of differentiation from asciminib and has potential to become best-in-class. Preclinically, we have shown that TERN-701 has potency equal to or greater than asciminib across multiple mutational variants. We have also confirmed clinically that TERN-701 can be dosed once daily without food, a key differentiator that is particularly important in a disease where patients are on therapy for life. As we progress in clinical trials, we have a scientific hypothesis that TERN-701 has the potential to demonstrate improved efficacy, safety, and ease of use. This is supported by our own preclinical potency data as well as learnings from asciminib's development and long-term clinical data, which together suggest that 701, through better dose optimization, could not only potentially outperform on efficacy while maintaining good safety but also allow for unified dosing across all CML patients. This is not something that can be established within the first year of clinical study, but our early data is encouraging and supports our aspiration for TERN-701 as a best-in-class agent. With that, I'll turn it over to Emil to discuss the data and tell you more about TERN-701 's potential. Emil. Thank you, Amy. Turning now to slide eight, which provides a high-level summary of the data that we've seen to date. As Amy mentioned, we're excited about these initial data for TERN-701, which shows the molecule to be highly active in heavily pretreated patients with refractory disease and an encouraging emerging safety profile. As of the data cutoff of October 28, 2024, the CARDINAL study enrolled 15 patients across three of four planned dose cohorts of 160 mg, 320 mg, and 400 mg. Already at the lowest dose levels of 160 mg and 320 mg, we're seeing decreases in BCR-ABL transcripts in the majority of efficacy-valuable patients and compelling molecular response shifts in patients with high baseline transcript levels with an encouraging cumulative MMR rate of 50% at three months. In addition, TERN-701 has demonstrated a highly encouraging safety and tolerability profile with no dose-limiting toxicities, dose reductions, or adverse event-related treatment discontinuations at any dose tested to date. The PKPD data show robust and continuous coverage over target efficacious concentrations at all dose levels evaluated thus far, which combined with the safety and early activity support a wide therapeutic index for this molecule. While the remainder of the slides will review all data pertaining to the data cutoff date of October 28, I'm pleased to report that as of today's date, 19 patients have been enrolled in the study, inclusive of the final dose level of 500 mg, with at least three patients enrolled now to each dose level in escalation. As a result, we're on track to initiate dose expansion in the first half of 2025, in which two doses from escalation will be selected for further evaluation. Next slide, please. This slide shows the study design. The CARDINAL study is a multicenter global Phase I study of TERN-701 in patients with relapse refractory chronic phase CML. As shown on the left, the study enrolls second-line or later patients with chronic phase CML. To be eligible, patients must have had treatment failure or suboptimal response to at least one prior second-generation or 2G TKI, or failure, suboptimal response, or intolerance to any two active-site TKIs. As noted, the study also allows patients previously treated with asciminib, the only other currently approved allosteric inhibitor. The study comprises two parts. Part one is a dose escalation of TERN-701 dosed once daily, evaluating four dose levels of 160 mg, 320 mg, 400 mg, and 500 mg. The primary endpoints for part one are safety and tolerability, with secondary endpoints including PK and efficacy. The dose escalation follows a Bayesian optimal interval design with a minimum of at least three patients per dose level to conduct safety assessments guiding dose escalation based primarily on incidents of DLTs in the first cycle. Dose levels at completed DLT evaluation may have additional patients enrolled via optional backfill cohorts up to a maximum of 15 total patients per dose level. As of the data cutoff, dose escalation was completed through the first three dose levels, including backfill cohorts with seven patients at 160, five at 320, and three at 400 milligrams. As of today's date, the study has enrolled 19 patients, including three at the 500 mg dose level, which is currently undergoing safety evaluation. Upon the completion of dose escalation, two doses will be selected to evaluate further in the randomized dose expansion part of the study, in which the primary endpoint is efficacy. Turn to the next slide, please. This slide shows the key assessments for both efficacy and safety in the CARDINAL study. The primary efficacy measure essentially assesses molecular response, which measures the change in BCR-ABL transcript relative to baseline and is assessed approximately monthly for the first six months and every three months thereafter. As shown in the figure on the right, molecular response is standardized on an International Scale, or IS, and follows the ratio of BCR-ABL fusion transcript to a control housekeeping gene, in this case, ABL1, with the value reported as a percentage. While changes in the BCR-ABL transcript are followed on a continuous scale, response categories are defined based on the logarithmic categorical shifts on the IS. For example, MR2 is defined as achieving BCR-ABL less than 1% on IS, while MR3, or major molecular response, is BCR-ABL less than 0.1%. MR4 or higher is defined as deep molecular response. Transcript levels generally correlate with tumor burden in the marrow, with each log decrease on the IS representing exponential decreases in leukemic cells. In addition to molecular response, hematologic response achievement in patients with hematologic relapse at baseline is also a meaningful early indicator of efficacy. The CARDINAL study uses standard assessments of safety typical for CML Phase I studies, including incidents of DLTs in the first cycle of treatment, treatment-emerging hematologic and non-hematologic AEs, as well as serious adverse events, dose discontinuations, and reductions. Turning now to slide 11. This next slide shows the baseline demographics of patients enrolled as of the data cutoff. In general, patients are heavily pretreated and have high baseline transcript levels, indicating a high leukemic burden. Of the 15 patients enrolled, 60% have a baseline transcript greater than 1%, 73% don't have MMR at baseline, and 20% of patients have a BCR-ABL resistance mutation. The median number of prior TKIs is four, with 80% having received three or more prior therapies. 47% of patients had prior ponatinib, and 40% of patients were previously treated with asciminib. Taking a closer look at the patients who previously received asciminib, we see both treatment failure and intolerance as reasons for discontinuation of asciminib. Of the six asciminib pretreated patients, one patient received it in a remote prior line and had treatment failure. Five patients received asciminib as their immediately preceding therapy to TERN-701, of whom one had treatment failure, one had suboptimal response and intolerance, and three had intolerance. The reasons for intolerance to asciminib were all non-hematologic adverse events, including headache, skin rash, hypertriglyceridemia, and elevated LFTs. Next slide, please. The swimmer plot on slide 12 shows the time on treatment for all 15 patients dosed in this study as of the data cutoff, separated by dose level. The top light blue lanes show the seven patients at 160 mg. The middle darker blue lanes show the five patients at 320 mg, and the bottom dark blue lanes show the three patients dosed at the 400 mg dose level. The median duration of treatment as of the data cutoff is three months, with a range of 0.79- 7.5 months. The table to the left of the plot shows important baseline characteristics for each patient. Starting on the left, with each patient's number of prior TKIs, whether they previously received asciminib, their baseline BCR-ABL transcript category, and any BCR-ABL resistance mutation. As of the data cutoff, all 15 patients dosed are evaluable for safety, as shown in the left vertical text box. The 12 patients dosed in the 160 mg and 320 mg cohorts are efficacy evaluable. In order to be efficacy evaluable, patients must have had a baseline BCR-ABL transcript and at least two on-treatment BCR-ABL assessments performed centrally. As shown in the table, the majority of efficacy evaluable patients have had more than three prior TKIs, and eight of 12 patients have a baseline transcript greater than 1%, including six with a baseline of greater than 10%, demonstrating how refractory and heavily pretreated these patients are. Despite that, it's noteworthy that 14 of 15 patients remain on treatment with compelling molecular and hematologic responses in several of these patients. As shown in the swim lanes, notable molecular responses include an MR2 after four and a half months at the 160 mg dose and a deep molecular response at 320 mg within three months in a fifth-line patient exposed to all approved 2G TKIs. I'll go over the details of these patients in later slides. We also see an early complete hematologic response attainment at 160 mg in a patient who failed 3G TKIs and asciminib, who had hematologic relapse at baseline. There were four efficacy-evaluable patients with baseline MMR or better who switched to TERN-701 due to intolerance to their preceding TKI, all of whom are maintaining their deep response on TERN-701 and continue on therapy with good tolerability. Finally, there was one discontinuation due to loss of response in a patient with T315I mutation who had an initial 50% decline in the BCR-ABL transcript. To summarize this figure, at a relatively short median duration of follow-up in this Phase I study, we're already seeing important and meaningful signals of clinical activity at the lower dose levels without any safety-related discontinuations. Please move to the next slide. On slide 13 is a shift table of categorical molecular response shifts showing the cumulative MMR rate at three months. This table includes patients without the T315I mutation who, at data cutoff, had at least three months of treatment or had a response of MMR or better at baseline. Of 10 patients meeting these criteria, five are in MMR or better at three months for a cumulative MMR rate of 50%, which is promising at this early time point, given how heavily pretreated and refractory these patients are. You can see that the patients with the highest baseline disease burden with BCR-ABL transcripts in the 1%-10% and greater than 10% categories have molecular response shifts to lower transcript levels, shown in the cells with black outline. One of four patients with baseline greater than 10% achieved a deep molecular response within three months, while one of two patients with a baseline of 1%-10% achieved MR2. No patients have had categorical shifts to a worse response category compared to baseline. Turn to the next slide, please. The waterfall plot shown on this slide shows the best percent change in BCR-ABL transcript levels from baseline for all efficacy-evaluable patients who had a baseline transcript greater than 1%. Since these are the patients with the highest leukemic burden, seeing decreases in transcripts in such patients is a good early indicator of a drug's activity. As shown in the plot, 88% or seven out of eight patients have decreases in BCR-ABL on treatment, including the patients with molecular response shifts and CHR who were pointed out on the previous slides. The baseline characteristics for each patient, shown in the corresponding table below the plot, show that the majority of these patients had baseline transcript greater than 10%, with several having transcripts greater than 50%, indicating very high leukemic burden, which makes the decreases in BCR-ABL all the more clinically meaningful at this early time point. Importantly, we see decreases in transcripts in patients with T315I mutations, as well as in patients who previously failed 3G TKIs and asciminib. Overall, this highlights the broad clinical benefit seen with TERN-701 in these patients with difficult-to-treat disease and explains why the majority of patients remain on therapy, including those who have not achieved categorical molecular response shifts at data cutoff. Next slide, please. Heavily pretreated patients with relapsed refractory CML, particularly those with baseline transcripts of 1%-10% and greater than 10%, have historically slower response kinetics and a lower MMR rate, as shown with several TKIs, including asciminib. The figure on the right is data from the Phase I study of asciminib, showing the MMR achievement rate over time in patients without the T315I mutation, broken down by their baseline transcript levels. It shows that the patients with greater than 10% transcripts at baseline have the poorest responses, with less than 5% achieving MMR at three months and less than 40% achieving MMR at five years. In the group with a baseline of 1%-10%, the MMR at three months is less than 10%. While the number of patients and duration of follow-up in CARDINAL is currently insufficient to make definitive comparisons to the completed asciminib Phase I study, the asciminib data provide a loose benchmark by which to assess the early activity of TERN-701 within these patient subsets. At three months, TERN-701 shows encouraging trends in MMR achievement, with one out of four patients with a baseline greater than 10% achieving deep molecular response, with the remaining three having decreases in transcripts and continuing treatment. In relation to the asciminib Phase I data, the early data from CARDINAL are certainly encouraging with regard to MMR achievement and molecular responses in general, considering that CARDINAL currently has a more heavily pretreated population, including asciminib pretreated patients. Next slide. On these next two slides, we take a closer look at the two patients who achieve categorical molecular response shifts on TERN-701. Shown here on slide 16 is the first patient dosed at the 160 mg dose of TERN-701, as this is a nice example of TERN-701 deepening response in a fourth-line patient with suboptimal response and intolerance to asciminib. This is a 35-year-old male who has an eight-year history of CML, as detailed in the timeline shown at the top. His disease responded to initial therapy with dasatinib, on which he remained for six years before losing the response. At this point, his TKI was switched to ponatinib, a 3G TKI, with transcript changes over time shown in the plot starting at the point where he switched to ponatinib. He had a suboptimal response to ponatinib over the course of a year, with only a transient decrease in transcript to below 10%. He was then switched to asciminib 80 mg once daily. On asciminib, he achieved MR1, or a transcript of 1%- 10%, but his response plateaued, with the transcript remaining greater than 1% after a year. Despite good compliance on asciminib, his labs started to show hypertriglyceridemia and elevated LFTs. The suboptimal response and abnormal lab values were the reasons why he was then switched to TERN-701 160 mg. On TERN-701, his response deepened to MR2, which is a transcript less than 1%, and he continues on TERN-701 with good tolerability after more than six months on treatment. This patient vignette is a nice demonstration that TERN-701 can improve responses after poor response to both ponatinib and asciminib. Furthermore, the deepening response on 160 mg of TERN-701 after a suboptimal response to 80 mg of asciminib suggests that this dose of TERN-701 may be achieving more effective target coverage than asciminib 80 mg. Turn to the next slide, please. The second patient vignette here on slide 17 shows a rapid deep molecular response being achieved with TERN-701 in a fifth-line patient previously treated with all 2G TKIs and ponatinib. This is a 52-year-old female enrolled at the 320 mg dose level who had treatment failure and intolerance on bosutinib, with baseline transcript greater than 10% at study entry. The patient has over a 10-year history of CML, as shown in the timeline. Over the prolonged course of her treatment, she cycled through all three 2G TKIs, starting with dasatinib and nilotinib over the first two years, after which she achieved MMR but discontinued both due to intolerance. She was then switched to bosutinib, which she remained on for the next approximately eight years, with an initial slow and steady decline in transcripts over four and a half years to the level of deep molecular response. However, after nearly two years with DMR, she had loss of response with a relatively rapid rise in transcript level to greater than 10%. The loss of response was accompanied by intolerance to bosutinib, with elevated LFTs and gastroenteritis. It's at this point that she was switched to TERN-701, on which she rapidly achieved a deep molecular response with a greater than three log reduction in transcript levels within the first three months, with substantially faster response kinetics compared to her initial response to bosutinib. A few important takeaways from this second patient vignette. First, this is a good real-world example of frequent switching of the currently available active site TKIs due to intolerance, highlighting this unmet need in CML. Second, the achievement of a rapid deep molecular response in a patient previously treated with all approved 2G TKIs and ponatinib has promising read-through to how TERN-701 could perform in a second-line or newly diagnosed disease setting. Finally, taken together, both these clinical vignettes demonstrate that TERN-701 can deepen responses in patients with poor response to dasatinib, 2G TKIs, 3G TKIs, and asciminib. Next slide, please. Slide 18 shows the PK data from the CARDINAL study. As of the data cutoff date, steady-state PK was available for the 160 mg and 320 mg cohorts. As shown on the left, TERN-701 has linear PK with approximately proportional increases in exposure with dose. On the right is a radar plot with a dotted blue line showing the in vitro IC90 values of TERN-701 against CML cell lines harboring both mutated and not mutated variants of BCR-ABL. The solid lines on the plot show the average plasma-free drug concentration of TERN-701 at the 160 mg and 320 mg doses from the clinical PK data. As you can see, the majority of points on the dotted line fall inside one or both solid lines, indicating that the average free drug concentrations of TERN-701 achieved at these doses substantially exceed the IC90 for CML without BCR-ABL mutations, while meeting or exceeding the IC90 for multiple mutational variants that are encountered in the clinical setting. Next slide, please. Moving to safety on slide 19. This is a summary of the highly encouraging safety profile we've seen to date in the CARDINAL dose escalation. There have been no dose-limiting toxicities in dose escalation through the 400 mg dose level, no AE-related treatment discontinuations or dose reductions, and no grade 3 treatment-related AEs or serious adverse events. Additionally, we've not seen any clinically meaningful changes in LFTs, amylase, lipase, or cardiac parameters, including blood pressure, ECGs, and other vitals. Next slide. Slide 20 shows the treatment-emergent hematologic adverse events as of a data cutoff. TERN-701 appears to have a favorable hematologic safety profile, with no hematologic DLTs seen across three dose levels and a notably low incidence of grade three or higher cytopenias in this heavily pretreated refractory patient population that's typically predisposed to cytopenias given their poor marrow reserve. The majority of treatment-emergent hematologic AEs have been low-grade, with only two instances of grade three or higher cytopenias, as shown in the table, neither of which were considered related to TERN-701 by the investigator. Next slide, please. On slide 21, we see an emerging non-hematologic safety profile that's also highly encouraging. The table shows all treatment-emergent non-hematologic AEs occurring in more than one patient. The majority of these treatment-emergent AEs were grade one or two, with no treatment-related AEs more than grade two in severity. Importantly, there were no clinically meaningful changes in pancreatic enzymes, LFTs, vital signs, or ECGs. Next slide. While we currently don't have sufficiently long follow-up to make robust comparisons of long-term safety tolerability to asciminib, one parameter that can be compared early on is the incidence of dose-limiting toxicities in dose escalation, which is the initial assessment of safety in dose escalation that's based primarily on incidence of treatment-related grade 3 or higher AEs during the first cycle of treatment. Both the CARDINAL and the asciminib Phase I study use similar DLT criteria and assess DLTs during the first 28 days of treatment. As shown in the tables on the slide, the incidence of DLTs for TERN-701 is trending lower than the asciminib Phase I study, with TERN-701 having no DLTs through 75% of the planned dose range in escalation, while asciminib had multiple non-hematologic dose-limiting toxicities across the dose range up to the maximum dose of 200 mg b.i.d., including pancreatic enzyme elevations and clinical pancreatitis. While a maximum tolerated dose or MTD has not been identified for either molecule, the lower rates of DLTs with TERN-701 are encouraging with regard to the potential for it to have a differentiated safety profile. Next slide, please. In summary, the emerging Phase I data support a potential best-in-class profile for TERN-701. After completing three out of four planned dose levels in escalation, we see that clinically effective exposures are achieved at the starting dose of 160 mg and above. We see compelling responses in heavily pretreated patients with high disease burden at baseline who had poor responses on prior 2G TKIs, 3G TKIs, and asciminib, and an encouraging cumulative MMR rate of 50%. Deepening molecular responses in patients with poor response to asciminib suggest that TERN-701 at current doses may achieve more effective target coverage than the approved dose of asciminib, which has promising implications for its efficacy in second-line and front-line patients, where we foresee potential future development of TERN-701. These data also show a highly encouraging safety profile with no DLTs, no dose reductions or AE-related discontinuations across all dose levels evaluated to date, and no concerning safety signals with regard to hematologic and non-hematologic adverse events. Finally, the excellent progress we've made through the dose escalation part of this study in less than a year positions us well to initiate dose expansion in the first half of 2025 and generate more mature efficacy and safety data, including longer-term MMR rates. Next slide, please. Before passing the call back to Amy, I'd like to acknowledge and thank all of our study investigators, site staff, and patients participating in the CARDINAL study, and also recognize the continued clinical and operational excellence of the Terns team as we look forward to continuing the positive momentum of the TERN-701 program as we advance it to next steps. I'll now pass the call back to Amy for closing remarks. Thanks, Emil. Today's exciting data provides proof of concept that TERN-701 is highly active and has potential to be best-in-class. These encouraging safety and efficacy data in difficult-to-treat patients compare favorably to asciminib Phase I results at similar time points. The rapid completion of dose escalation enrollment highlights strong interest from physicians and patients to participate in the TERN-701 study. I will now move to slide 26. Taking a step back to the broader development program, I'd like to remind you that TERN-701 has multiple ongoing Phase I studies underway that are each generating important clinical data to inform our Phase III registrational trial. Our partner Hansoh's Phase I trial in China remains ongoing, and we continue to work closely with them. The data from China is invaluable as we move forward our program, not only to compress timelines, but also to contribute to the growing dataset for TERN-701 as we advance the program globally and engage with regulators. Secondly, Terns has an ongoing healthy volunteer study that has shown consistent PK across different populations, as well as a lack of food effect. We shared top-line data from that study with you in April and at a medical meeting in September. Importantly, Terns has our global Phase I CARDINAL study in the U.S., Europe, Australia, and Korea. Today's initial data update has provided early, yet encouraging safety and efficacy signals in difficult-to-treat patients. As Emil noted, we anticipate dose expansion to begin in the first half of 2025 and expect to provide additional efficacy data, including MMR data with a larger number of patients treated for a longer duration in the fourth quarter of 2025. These trials continue to accrue an important safety database, which will inform and potentially accelerate a Phase III registrational pathway. We continue to evaluate multiple options for our registrational trials, including a monotherapy front-line trial and/or monotherapy for previously treated CML patients. Of course, we don't need to make these decisions now, and we'll be informed by emerging clinical data and feedback from regulatory agencies before making final decisions on registrational trial design. Turn to slide 27, please. With the flexibility that we see in our registrational approaches for TERN-701, I want to briefly look a little more at patient numbers for CML. We believe TERN-701 has broad market opportunity across all lines of therapy. In the G7 nations, almost 100,000 people are receiving treatment for CML. Today, that represents an approximate $5 billion market opportunity. In the front-line setting, 17,000 patients are newly diagnosed each year. Novartis has stated they will target 75% of front-line patients with their recent label expansion. We believe TERN-701 will have a competitive profile to target those newly diagnosed patients. Beyond the front line, it is estimated that approximately 15,000 patients are switching from a prior line of therapy. Many of these patients will be switching from a generic first or second-generation TKI, where an allosteric will likely become the standard of care. As with the front line, we believe that a differentiated profile will make TERN-701 a compelling option for these second-line patients. As allosterics become widely adopted and the market triples, TERN-701 has the potential to be a blockbuster product. Moving to slide 28, I would like to recap our key points of differentiation for TERN-701. TERN-701 has shown early signs of differentiation from asciminib and possesses the potential to become best-in-class. In preclinical studies, TERN-701 demonstrated equal or greater potency compared to asciminib across various mutational variants. Clinically, it's been confirmed that TERN-701 can be administered once daily without food. As we advance through clinical trials, our scientific hypothesis suggests that TERN-701 may exhibit enhanced efficacy, safety, and ease of use. This hypothesis is supported by our preclinical potency data, as well as insights gained from asciminib's development and longer-term clinical data. Collectively, these findings indicate that through optimized dosing, TERN-701 could potentially deliver superior efficacy while maintaining a favorable safety profile and enable uniform dosing for all CML patients. Turning to slide 29, let me close by recapping our exciting pipeline and progress in 2024, as it has been a highly productive year for Terns. In September, we read out top-line Phase I data for our oral small molecule GLP-1 agonist, showing a highly promising and competitive profile for TERN-601. We plan to initiate a Phase II study for TERN-601 early in the second quarter of 2025. We also continue to advance our discovery efforts for our GIPR modulator program and are making exciting progress there as we work on lead optimization for our oral GIPR antagonist. For TERN-701, we expect to report additional, more mature data in the fourth quarter of 2025 as we get the dose expansion portion of the trial underway in the first half of next year and collect data on a larger number of patients with longer treatment durations. Overall, I could not be more excited about the work that we are doing at Terns and can't wait to share additional data in 2025. With that, I'd like to turn things back to the operator to open the line for Q&A. Operator. Thank you. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Silvan Tuerkcan with Citizens JMP. Your line is now open. Good morning and congratulations on this great dataset. Maybe a big picture question here, and I think you summarized that really nicely on slide 28, where you already checked several boxes. As we look at the data that you have to date, what will be your potential improved efficacy over the competition here for your update next year? Would that be only against asciminib, and how would you make the call to go into front line versus second line? And then I have a follow-up. Silvan, thanks so much for your question. I'll let Emil take that. Yeah, thanks, Silvan, for the question. I mean, I think these data are as good as we could have expected from this molecule for early data. And I think the key point here is that in regards to benchmarking, we're already seeing early trends showing that this can have best-in-class potential, specifically with regard to even efficacy as well as safety, based on the fact that we're seeing deepening responses in patients coming directly off of asciminib, as well as 3G TKIs and 2G TKIs. So going forward, that really argues that the safety profile allows us to really leverage the wide therapeutic index. So going forward, we have really good optionality to pick within this dose range that's, again, showing very linear PK to be able to get to doses that achieve, ideally, the most optimal target coverage of any class, including asciminib or compared to asciminib and other 2G TKIs, to get maximal target coverage while maintaining good safety tolerability. And so I wouldn't think of next year's dataset as a head-to-head comparison. Again, it's still going to be a single, it's not going to be a randomized study versus standard of care and dose expansion. But nevertheless, it'll be very informative in terms of seeing how the potential randomized design could perform versus asciminib and other 2G TKIs compared to historical data. The second question you asked is about front line versus second line. Now, see, we don't see any reason why this molecule can't have the exact same broad indication that asciminib currently has, which is front line and everything after front line. And we think there's clear optionality here to get to front line in a very efficient way, again, based on historical precedent in terms of how asciminib was developed and the differentiation early on that we're seeing with the molecule. Great. Thank you. And then, obviously, important to point out in the efficacy data here, you're not at your top dose yet. Given the PKPD data that you collected to date, what can we expect from the 500 mg dose? Yeah, I mean, again, we're seeing linearity of the PK across the dose range so far. And so the dose escalation follows a modified Fibonacci sequence, and that's more of a regulatory requirement because typically, as you escalate, you typically can't maintain the same increment as you go to the higher doses. But that being said, we're still seeing incrementally better target coverage as we get higher in dose. And the safety profile looks pretty good. Even at the higher doses, the safety doesn't look any different than the lower dose of 160 mg. And again, to my point earlier, that gives us really good optionality to get to the potential aspirational goal of can we get to a single dose across all CML patients, including the mutational patients. Again, that's the whole idea of the wide therapeutic index of these allosteric inhibitors. Great. Thank you. Thanks for taking my questions and congrats on the data. Thank you. Thanks, Silvan. Thank you. Now, our next question coming from the line of Akash Tewari with Jefferies. Your line is now open. Hey, this is Akash. Thanks so much for taking my question. So you previously alluded to curative combos. Given this data, are you considering combo studies for 701 with second-gen T KI? No, we're not. And the reason is, again, we're seeing really good single-agent data here. And we know that combinations have a place potentially in CML, but we think that's probably better reserved for those very difficult-to-treat diseases, including things like compound mutations and such when you get to multiple relapse refractory patients. We've all seen that in the front-line setting, asciminib has shown a very robust efficacy differential versus the active site drugs and with a very good safety profile. Again, allosterics as a class have shown superiority in both efficacy and safety tolerability. And so given that, again, we're seeing this drug seems to be deepening responses post-asciminib, that just has more promising read-through into how it can perform as a single agent without the need for combinations in early line patients. Okay. Great. Thanks so much. Thank you. And our next question coming from the line of Etzer Darout with BMO Capital Markets. Your line is now open. Great. Thank you. And congrats on the data today. Just the first question. Given the safety results to date, are you able to potentially amend the protocol to move beyond 500 mg doses if you wanted to do so? And then I have a follow-up. Sure. I mean, you're right. From a safety standpoint, there's no reason why we wouldn't be able to do that. Apparently, so far, we don't see any major concerns from a safety standpoint. But that being said, again, we're seeing very robust target coverage at these doses. If you look at that radar plot slide, even at the 320 mg, we're approaching the IC90 for multiple mutational variants, including T315I mutations. And so I think the 400 mg and 500 mg doses, provided the linearity is maintained, will continue to incrementally improve coverage. And the argument is, if you're already getting good coverage over those mutations, and that's being seen and manifested with responses in the clinic in these mutated patients, we may not need to go that high above 500 mg easily. Right. Great. Thank you. And the benefit post-asciminib was a bit of a surprise to us. And I guess the potential front line would be straightforward. But I guess, does this maybe change your thinking around potential second-line setting to potentially include patients with prior asciminib? I know we had talked a little bit about before whether or not this is a population that you could potentially exclude in the second line. But given the efficacy, could you sort of see a broader approach where you include patients post-asciminib? Thanks. Yeah. And yes to both. I mean, we've never considered this molecule or considered the development as requiring exclusion of patients who had prior asciminib. I mean, that would be unrealistic. I mean, asciminib is now approved across all lines of therapy. And we knew going in that we would have post-asciminib treated patients, which is exactly why we really want to focus on the dose optimization piece because we think there's headroom there for improvements. But to your point, I think, like I said earlier, we don't see any reason why this drug can't have the same exact broad indication that asciminib currently has, including both front-line and beyond. And I think there's efficient ways to get there very quickly to the front-line based on historical playbooks of development. Right. So congrats again. Thank you. Thank you. Thank you. Now, our next question coming from the line of Ritu Baral with TD Cowen. Your line is now open. Hey, guys. Congratulations on this. I wanted to dig in a little further on sort of the differential activity and tolerability in your second- and third-line patients. If we're looking at slide 12, and that's Swimmer's plot, looking at that first patient and the efficacy-evaluable patient, the one that discontinued, and going back to your comment on increased or better potency or efficacy, can you go over what either in the binding or the kinetics in the preclinical data support this now clinical signal that some patients are responding better to 701 than Scemblix? And then, well, I'll let you answer that, and then I have follow-ups around those two specifics. Thanks. Yeah. Thank you. That's a great question. I mean, preclinically, we knew that this molecule from a potency standpoint was more potent than asciminib in several contexts, including both wild-type BCR or native BCR, as well as several mutations. And so going into this, especially in the non-mutated patients, we're already seeing that from an exposure-to-exposure standpoint, even with equivalent exposures at any given dose, the higher potency that we saw in the preclinical data appears to be translating in the clinic in terms of deepening those responses. The other piece I'll add is that as, when we'll post these slides up in the appendix, there's some pharmacodynamic data showing how the exposures that we achieve at these doses compare to in vivo exposures, where we saw really potent tumor cell kill in a KCL-22 model, accompanied by prolonged exposure in the tumor for the molecule compared to plasma. That was accompanied by very robust inhibition of phospho-BCR-ABL and phospho-CrkL, which are the PD markers that are typically followed. At these doses in the clinic, we're already four-fold and eight-fold higher than those exposures in the mouse model, where we saw very robust tumor exposure and very robust tumor target inhibition. So we do think that the pharmacology of this molecule is also playing a role in t erms of that rescue effect. Got it. And then that first question. I'm sorry. That first patient in the Swimmer's plot, I believe that was also the patient featured in slide 16. And you mentioned there were some lipid abnormalities on asciminib. Were those lipid abnormalities maintained? Were they improved after the switch to 701? Can you comment on that? Yeah. So as I mentioned, the patient remains on 701 for over seven months now with no tolerability issues, and we have not seen any reports of adverse changes in the lipid profile. Okay. But can you say whether that lipid profile has improved on 701, or is that something we'll find later? We'll report on that later. But yeah, we're collecting that data. Got it. And then final question, that last patient, the one who discontinued, was there anything unique about that patient versus the others that did show responses? I mean, this was a T315I mutated patient. He had five prior TKIs, including ponatinib, asciminib, as well as other 3G TKIs. This is a very heavily pretreated patient with a lot of disease. And what we saw was a rapid 50% decline initially in the transcript levels, and the patient was doing well. But then he had a sudden increase in the transcript, and the investigator thinks that it was probably a clonal escape due to a probable different clone with T315I plus another mutation, again, illustrating that these very heavily pretreated patients have multi-clonal disease. And the drug is very active. But in certain contexts, for example, these compound mutations, no drug is really sufficient as a single agent in that context to rescue those patients. But these are the types of patients you typically get in a dose escalation study. Got it. Thank you. That's helpful. And I'm sorry, I have one more question because apparently today I have all the questions. In your next data update, will that include - will we get anything ahead of that, including which doses you're moving for dose expansion? And at least the next data update, will that include the dose expansion data along with continuing data and backfill patients? Yes, to everything that you asked. And we will update externally on sort of which doses we take as we move forward. Great. Thanks so much. Thank you. Now, next question coming from the line of Eliana Merle with UBS. Your line is now open. Hey, guys. Thanks so much for taking the question, and congratulations on the data. Can you just elaborate a little bit on what the different potential scenarios for your Phase III strategy could look like? You mentioned the potential for a front-line study. Can you just talk a little bit about what the different potential designs could be and maybe what you're looking for in the data to inform this? Thanks. Yeah, for sure. I think in the front line, as we've mentioned before in several contexts, it's very feasible for us to do a very similar study to ASC4FIRST, where you compare 701 versus a standard control arm of 2G TKI plus Gleevec. We know that that's likely going to be feasible going forward, even with asciminib approved as front line because the expectation is that at least half of front line patients will still get a generic 2G TKI or imatinib, making the feasibility of running such a study pretty high, and again, seeing the data that we're seeing here early on, the PTS for a very strong efficacy differential between current 701 and a standard 2G TKI control arm is pretty high, knowing what we know about asciminib and knowing what we know now about this molecule. And I think that's why we have confidence that this molecule can be very competitive in the front line setting. I think the path to front line also may potentially require coverage of second line, which is important as well because, again, we want to have a broad label for this molecule. And the second line setting, we already have a playbook for that design as well in terms of a standard 2G TKI switch arm as a control. And we've seen at least a preview of that with asciminib in the third line setting, where it performed really well versus bosutinib. And we think that if this allosteric can perform that well in a third line setting, that would incrementally even further improve in the second line setting, especially with TERN-701 showing rescue effects post-asciminib. So that's why we feel confident that both those options are very doable for us. Great. Thanks. And I know that you got a lot of questions on the dose selection, but just maybe have your latest thinking on what the two dose levels that you would select for the expansion and any more color on when you'll plan to decide on this, just in terms of I know you said you'll start the dose expansion in the first half of next year, but just any more color on when you would expect to start dosing there. Thanks. Yeah. Like we said, we expect to start the expansion in the first half. We're already evaluating the highest dose in escalation, which is 500 mg which we'll have data on soon. And so the great thing that we see with this molecule is that the safety profile provides us a really strong optionality to pick two doses that meet the current sort of Project Optimus requirements of being sufficiently differentiated in exposure, but also to be able to detect a meaningful dose-response in terms of efficacy. And the real first requirement for that is that your safety profile allows for that. And what we're seeing so far is that, especially with no DLTs, and we saw this live with regard to the treatment-emerging hematologic and non-hematologic AEs, I think we have really strong optionality to select a high dose that really gets optimal target coverage and a low dose that also gets a. We're already seeing very good activity at our lowest dose. And so, like I said, we'll update externally on what those doses are. But right now, our options are looking pretty good. Great. Thanks. Thank you. Our next question is coming from the line of Graig Suvannavejh with Mizuho Group. Your line is now open. Good morning. Thanks for taking my questions and congratulations on the data. I've got two questions, if I could. First, I'm interested in the patients that you've shared data on and by the fact that I think 40% of the patients that you're sharing data on had prior treatment with asciminib. So I was wondering if you have any evolving thoughts around what asciminib is showing in the real world and how that might inform what you're seeing as the opportunity for 701. Clearly, you're seeing a potential in first and second line plus, but asciminib, I think, has gotten off to a great start, but clearly, it's perhaps not the cure-all. So just interested in your thoughts there. And then secondly, maybe bigger picture, maybe this is for Amy. Amy, you've got two really exciting opportunities in 601 for obesity and 701 for CML. So with this in mind, how are you thinking about capital allocation across your R&D pipeline efforts? And strategically, has there been any evolution in your thinking around the assets since you've come on board as CEO? Thanks. Thanks, Graig. I'll let Emil take the first question, and I will take the second. Yeah. Yeah. Thanks, Graig, for the question. And regarding the question regarding asciminib, I think our data are already kind of showing a preview of what's in the real world. I mean, 40% of patients coming on to our study for both intolerance and suboptimal response, I think, is a reflection of the fact that, yes, it's a great drug, but there's a lot of room for improvement. I think we're very encouraged by the fact that TERN-701 is performing very well in that context. And again, this just says that the first-in-class necessarily doesn't have to be best-in-class. And so I think we have a real strong potential for 701 to be the best-in-class allosteric. Yeah. And on your second question, Graig, from a capital allocation perspective, as you know, we have $372 million on our balance sheet, which is runway into 2028. That runway includes all key next steps in that timeframe for all of the programs that we have talked about. And from a capital allocation perspective, where we are with TERN-701 is no different from where we planned in terms of moving to expansion next year. And these are indications of where we are right now. These trials are well within our capabilities internally and also our cash. Even the pivotal for TERN-701 direct cost is under $100 million. So we have to raise more money, obviously, to do the pivotal. However, all the steps that we need to do between now and 2028 are all allocated. And the Phase II for TERN-601 is also within our cash capabilities. And we are not in the realm of obesity, and trials in Phase III are getting to launch. Okay. Thank you. Thank you. And our next question coming from the line of Jay Olson with Oppenheimer. Your line is now open. Oh, hey. Congrats on these impressive results. And thanks for providing the update today. Could you talk about how soon you could start a pivotal trial for 701 and then some of the driving factors and timeline for getting started? Thank you. Emil? Yes. Yeah. We're not guiding specifically to a start timeframe for a pivotal, but I could give you. We know the historical context and the historical playbooks that the average timeframe has been to a five- to six-year timeframe from start of Phase I through the initial approval. That timeline has potential to shrink, especially for classes of drugs with already very robust and very favorable efficacy and safety data. We happen to be in that allosteric class, which, again, with asciminib has shown excellent profiles, arguably the best profile of all TKIs in CML. Those all act as tailwinds for us in terms of being efficient and shortening that timeline to pivotal. The progress we've already made in the Phase I part of this study is already a testament to the excitement that's in the field for allosterics. We all have very motivated investigators, and we're enrolling this study very well globally. This shows that there's a lot of excitement for 701 and the allosteric class in general, which, again, acts as a tailwind. So we're really confident that we could move into expansion and get the expansion done quickly to be able to support the next step to a pivotal within that historical timeframe or even shorter than that. Super helpful. Thanks for taking the question. Congrats again on the results. Thanks. Thank you. Our next question coming from the line of Corinne Jenkins with Goldman Sachs. Your line is now open. Good morning, guys. I guess maybe a couple from us. In terms of the next data update, I guess, what information are you looking to gain from the data that you'll produce as well as sort of the real-world utilization trends for asciminib that will help you make a decision around the pivotal trial strategy here? And then in terms of the asciminib tolerability, I guess, of those patients who had some intolerance, when did those challenges start to emerge? And I guess, how does that compare to kind of less than three months on therapy? Thanks. Yeah. Yeah. So with regard to your first question, I think going forward, essentially, I believe we essentially see the same trends that we're seeing now, and both efficacy and safety continue to play out as we enroll more patients and get longer-term follow-up. I think the data right now, especially for the patients who have been on the study longest, it's at 160 mg dose looks pretty good. We have no discontinuations so far at 160 mg with treatment up to seven and a half months. And so seeing more of the same going forward, and I don't expect there to be, based on what I said around the fact that geographically, we're seeing a very broad distribution of patients that we're getting across. So we're getting patients from the U.S.,, Europe, Australia, Korea, and this is the demographics that we see. And so we don't expect at least there to be any drastic differences going forward in terms of the prior TKI picture as well as the prior asciminib exposure. We'll probably see more of a blend of baseline transcripts as we enroll more patients and a balance there that would allow us to do more of a side-by-side comparison to MMR rates relative to the asciminib data because, again, you need more numbers and a more uniform distribution of the baseline transcript levels to be able to make that assessment. So that's sort of what we expect to show at the next step. And with regard to your second question around the timing of these AEs with asciminib, it's very variable. As you saw, even the types of AEs were very variable, and there was no one emerging theme. I mean, we know that with AEs in general, the timeframe can vary. So for example, hematologic AEs, you see very quickly as you start treatment. Things like amylase lipase also, you see fairly sooner than later, and that can also be variable. Whereas things like cardiovascular arterio-occlusive events typically take a little bit longer. But there are some things like hypertension are potentially indicators of later issues with vascular events, and there's data to support that. And the fact that we're seeing no clinically meaningful changes in blood pressure, I think, is a very good sign on that front. So overall, I think the safety profile that's emerging with this molecule is very helpful. It's very encouraging. Thanks. Thank you. And our next question coming from the line of Eric Joseph with JP Morgan. Your line is now open. Hi. Thanks for taking the questions. Just a question about the data and then one forward-looking question related in regards to a potential pivotal study. Of the six patients that entered the trial here that were in MR at baseline, can you just comment a little bit on what their rationale for switching to 701 was? Just trying to get a sense of whether it was primarily the tolerability or if you saw signs of actually a rise in their transcript level prior to entering the study. No, it was all primarily tolerability for various reasons. Okay. Great. Thank you. And then maybe just picking up on the prior question, can you just clarify what the eligible patient population would be by their baseline transcript level in a potential pivotal trial and maybe just how well represented they are in the data here today? And then if you talk to that, do you expect cumulative MMR potentially to be leverageable as a registration at one point? Thank you. That's a really good question. Yeah. I think that if you look at the historical examples, the asciminib study, which is the Phase III study, initially, the inclusion criteria was that you had to have a transcript greater than 1%. And it was via later protocol amendment that they included patients who were 0.1%-1% who were intolerant. And so typically, in the context of a relapse refractory population, the regulators historically have wanted the study to only enroll patients who are not in MMR. And so MMR achievement rate becomes all the more important as a metric, which is exactly why we focused on those patients so heavily who had the transcript greater than 1%, where this molecule is clearly showing improvements in molecular response categories with one having a three log reduction because that's probably going to be more reflective of the population. Now, we didn't have any patients yet enrolled in the 0.1%-1% category, but as you saw in that asciminib plot, those patients have the lowest threshold to get to MMR, and they also get there the fastest relative to the other two categories of 1%-10% and greater than 10%. and so all in all, I think what we're seeing with this molecule in those higher baseline transcript patients fits really well to what it could potentially do in a realistic sort of Phase III refractory population in a second and third line setting. Now, in the front line, there's really no cutoff. It's everybody, but typically, when patients are newly diagnosed, they also have higher transcript levels, but the kinetics of response is much faster because the disease is biologically much more homogeneous compared to a refractory population. And so all in all, I think these data speak very well to how this drug could perform with regards to MMR achievement. And if you do the math on that in our current data set, it's about 18%. And so we're trending right along where asciminib did on that piece within a more refractory patient population than what asciminib had. That's great. Do you have any ability to enrich for patients with higher transcript levels in your expansion cohorts? 1% or greater? Yeah. I mean, you could, of course, do that, but I don't think it would be a real-world reflection of what the real-world population is, right? So I mean, if we wanted to just in that situation, you'll also miss out on those patients with lower transcripts who are intolerant, which is also an important unmet need. You don't want to ignore the fact that this molecule so far is showing a really compelling safety profile. And that second patient vignette shows that switching due to intolerance is a real problem. And those patients also have a need for new drugs that they can maintain their responses and not have tolerability issues. So that's why you don't want to necessarily focus in on one subset or the other because the unmet need is there across the board. It just happens to be different on that needs. Okay. Thanks for taking the questions. Yeah. Thank you. Our last question is coming from the line of Ed Arce with H.C. Wainwright. Your line is now open. Great. Congrats on the early data here, and thanks for taking my questions. I have two. First, I just wanted to focus again on those 40% of six out of 15 patients with immediately prior asciminib treatment. Obviously, the one patient on slide 16 with a categorical change is quite positive. I'm wondering about the other five. How would you characterize your responses in those? And if there were any other categorical improvements in those patients? And then I have a follow-up. Yeah. Thanks for the question. And the answer to that question is on probably the best answer is on slide 14, which is why I wanted to show that waterfall plot. You can see that the other patients, the evaluable patients who also had asciminib immediately preceding, have decreases in their BCR-ABL transcripts. And again, these are patients with the high baselines. And so that just shows that there's a reason why the majority of these patients remain on treatment is because they have decreases in BCR-ABL, even those who have not gotten to a categorical shift. Great. Thank you. And then just thinking about ahead once you potentially reach the market and obviously as one of two allosteric inhibitors, wondering if you might consider more just for commercial evidence and perspective, a head-to-head study with asciminib, perhaps as a separate study that may not be part of any registrational package. Thanks. Yeah. I mean, again, from a regulatory standpoint, again, we have plenty of historical playbooks to support the idea that we don't need to conduct a head-to-head study versus asciminib to get to approval. But to your point, are there options to conduct such a study? Absolutely. And we'll evaluate those options as we get more data. Great. Thanks again. Thanks for the questions, Ed. Thank you, and I'm showing no further questions at this time. I will now turn the call back over to Amy Burroughs for any final remarks. Great. Thank you, operator. Thank you all for joining us today for a review of these compelling initial Phase I CARDINAL data in CML. For those of you who will be at ASH later this week, the Terns team will be there as well. We're happy to connect with you. Have a great day, and thanks again. This concludes today's conference call. Thank you for your participation, and you may now disconnect.