Good day, and thank you for standing by. Welcome to the Terns Pharmaceuticals conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Amanda Isacoff, with Precision AQ. Please go ahead. Thank you, operator. Good morning, ladies and gentlemen, and welcome to the Terns Pharmaceuticals TERN-601 Top Line Results 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. At this time, all participants are in listen-only mode. Following the presentation, we will be opening 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. With that, I will now turn the call over to Amy Burroughs, Chief Executive Officer of Terns Pharmaceuticals. Also on today's call are Dr. Emil Kuriakose, Chief Medical Officer, and Dr. Mark Vignola, Chief Financial Officer at Terns. Amy? Thank you, Amanda, and good morning, everyone. I am Amy Burroughs, Chief Executive Officer of Terns Pharmaceuticals. On behalf of the Terns team, I thank you for joining us today, as we are excited to share our positive and highly informative data from our phase I study of TERN-601 for obesity. TERN-601 is one of several potentially best-in-class assets 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. I'd like to start with a few words about Terns. We focus exclusively on small molecules with validated mechanisms of action in areas of high unmet need. All molecules in our current pipeline are internally discovered. We have been working in the metabolic field for over seven years and have an R&D team with deep metabolic experience and a track record of successfully executing clinical trials. I'm thrilled to say that record continues with today's exciting readout of TERN-601. We are also in the clinic with TERN-701, our potential best-in-class therapy for chronic myeloid leukemia, which we will not discuss today, except to say that we are incredibly excited about the value of that potential class-leading drug. In both oncology and metabolics, we are leveraging learnings from the strengths and weaknesses of competitor programs to apply innovative thinking to our work. As we will see today with TERN-601, our team discovered a molecule with differentiated properties and applied novel approaches to our phase I trial design, which has translated to a compelling clinical profile and a highly informative readout. We are excited to share this data with you today and look forward to sharing additional clinically meaningful readouts across our metabolic and oncology franchises in the months and years ahead. Please turn to slide five for a review of the results from our phase I trial of TERN-601. The study met all objective success metrics that we set out for the trial. We observed weight loss at the higher end of the expected range for a 28-day study, the ability to escalate to higher doses than other oral GLP-1 receptor agonists, and a strong dose response as measured by weight loss and other markers of clinical activity. TERN-601 was well tolerated at high doses, despite a particularly fast titration schedule. Our use of rapid dose escalations was designed to push the limits of titration and will allow us to move more efficiently through future studies. Emil will take you through the clinical data in greater detail, so I'll leave that to him. I would like to highlight that TERN-601 has distinct properties that enable sustained target coverage and a flat PK curve, which allowed us to administer tolerable high doses once per day in this trial. We believe the distinct properties of TERN-601 could lead to an even more differentiated profile in subsequent studies. In terms of manufacturing, TERN-601 is highly scalable with low cost of goods to serve the many millions of patients around the world suffering with obesity. Based on these results, we are quickly moving to phase II development and expect to initiate the trial in 2025. Our team has been preparing for phase II for many months. We are actively evaluating multiple options for a phase II trial based on the data and emerging regulatory environment to enable us to advance to a pivotal trial as quickly as possible. We look forward to coming back to you with further details. With that, I will turn it over to Emil Kuriakose, our Chief Medical Officer, to walk you through the data. Emil? Thank you, Amy. Please turn to slide seven. The compelling clinical data from our first-in-human phase I study of TERN-601 and several distinct properties of the molecule that Amy alluded to, support a competitive and differentiated profile in the oral GLP-1 receptor agonist landscape. So let's start with a high-level summary of the data from the phase I study. TERN-601 dosed once daily over 28 days, showed statistically significant mean weight loss of up to 5.5% from baseline, or 4.9% when placebo adjusted. 67% of subjects lost 5% or more body weight at the top dose of 740 milligrams. TERN-601 was well tolerated, with no dose interruptions, reductions, or discontinuations due to treatment-related adverse events in the entire study. GI adverse events, consistent with the GLP-1 receptor agonist class, were observed, with all being mild to moderate in severity. Importantly, TERN-601 had unremarkable safety findings, with no clinically meaningful changes in liver enzymes, vital signs, or ECGs at any dose. As I will further outline after we go through the clinical data, TERN-601 has distinct drug properties that may enable a wide therapeutic window, allowing us to get to high doses that achieve sustained, robust target coverage while being well tolerated with once daily dosing. As a whole, this study allowed us to efficiently identify a range of pharmacodynamically and clinically active doses to take forward to phase II. Please turn to slide eight. Shown here is the study design. This was a randomized, double-blind, placebo-controlled phase Ib study that comprised both single ascending and multiple ascending dose escalations of TERN-601 dosed once daily. Starting on the left, the study population consisted of non-diabetic, healthy adults with obesity. The study had three parts. Part one was a single ascending dose escalation that evaluated a dose range of thirty milligrams to a thousand milligrams, and randomized eight subjects per cohort in a three-to-one fashion to either TERN-601 or placebo. The overall objective of the SAD portion was to assess PK across a wide dose range to identify doses that achieve sustained target coverage with once daily dosing. Parts two-A and two-B were multiple ascending dose escalations and comprised a fourteen-day non-dose titrated study and a twenty-eight-day titrated study, respectively. The non-titrated MAD study evaluated daily dosing of thirty milligrams or a hundred milligrams for fourteen days in separate cohorts to assess safety, tolerability, and pharmacodynamic effect. The objective of part two-A was to select one of these doses as the starting dose for the twenty-eight-day titration cohort, based on evidence of safety, tolerability, PD effect, and PK. We selected 100 milligrams as the starting dose for the 28-day study based on excellent safety tolerability and on-target PD effect of mild transient decrease in fasting glucose post-dose. Of note, weight loss was not the endpoint of part 2-A. As shown on the bottom, the 28-day MAD study evaluated three titrated dose cohorts, all starting at the 100 milligram dose, with target doses of 240 milligrams, 500 milligrams, and 740 milligrams QD. Both parts 2-A and 2-B comprised separate independent cohorts of 12 subjects, randomized 3 to 1 to either TERN-601 or placebo. Lastly, this phase I study was conducted in the U.S. at a single inpatient phase I center, where all subjects remained at the study site from treatment initiation through completion. Now let's turn to slide 9 for a review of data from the SAD portion of the study. Here, you can see TERN-601 had generally linear PK, with approximately proportional increases in exposure with dose. Interestingly, the PK data show a prolongation of the absorption phase and a delay in the elimination phase with increasing dose. The prolonged absorption results in a flat PK curve, leading to sustained target coverage and is evident starting at the 100 mg dose and above. The 100 mg dose achieves a Cmax exceeding the unbound EC50 for GLP-1 receptor activation and has a flatter tail than the 30-mg dose. At doses of 240 mg QD and above, we see sustained target coverage over the GLP-1 receptor EC50 for 16 to 24 hours, with the absorption phase lasting the full 24 hours at the 500 mg dose and above. These data showed us that TERN-601 can achieve a flat PK curve and meaningful target coverage up to 24 hours with once daily dosing, despite an elimination half-life of 4 to 6 hours. I'll go more into the distinct drug properties that allow for this later. For now, the important point is that these data informed our selection of 240 milligrams and above as potentially efficacious target doses for TERN-601 to evaluate in the 28-day MAD portion. Please turn to slide 10. Moving to the 28-day MAD titration cohorts, shown on this slide are the baseline characteristics of subjects randomized to the 28-day study, with pooled placebo in the left column and the three TERN-601 groups on the right. Baseline characteristics were generally well-balanced across the treatment groups and placebo. Median weight ranged from 90 to 95 kilograms, with BMI ranging from 29 to 31. The vast majority of participants on this study were male, which is worth noting, as we know from literature, that males generally tend to lose less weight on GLP-1 agonists compared to females. Moving on to slide 11, where we have the weight loss data over 28 days. TERN-601 showed compelling and clinically meaningful weight loss of up to 5.5% over 28 days of dosing, or 4.9% when placebo adjusted. On the left is weight loss in kilograms over 28 days, and on the right is percent weight loss from baseline over 28 days. We see a nice dose response from 240 milligrams to 740 milligrams, with approximately 2%, 4%, and 5% placebo-adjusted weight loss as you progress through the dose levels. This shows that all target doses appear to be active in forming various potential future use cases for the drug across the broad disease spectrum of obesity, as we'll discuss later. Please turn to slide 12. Shown here is a responder analysis evaluating the proportion of subjects losing greater than or equal to 3% and 5% body weight, respectively. We see a robust dose-related increase in the magnitude of weight loss as you move through the dose levels. All three dose levels appear to be active, and at the two higher dose levels, a significantly greater proportion of subjects lost more than 3% and 5% body weight, respectively, compared to placebo, with 78% of subjects losing at least 3% body weight at 500 milligrams and 67% losing at least 5% or more body weight at the 740 milligrams. Please turn to slide 13. We also measured changes in patient-reported scores on hunger, appetite, fullness, and satiety over the twenty-eight-day dosing period as additional assessments of pharmacodynamic effect. We were pleased to see meaningful changes in these scores across all doses, with a clear dose relationship in the magnitude of these effects. Hunger and appetite decreased, while fullness and satiety increased in a dose-related manner. Turn now to slide 14, please. Slide 14 shows how we dose titrated in the twenty-eight-day MAD portion. Our goal was to titrate quickly to inform us about the tolerability of the drug. The operating premise behind this strategy was that if we see the drug being well tolerated, despite fast titration to high doses in a short twenty-eight-day study, that would indicate potentially even better tolerability in subsequent studies, where we would slow the titration speed. The study protocol allowed flexible titration and escalation, such that safety tolerability data from completed cohorts would guide the titration speed and target dose in subsequent cohorts. The key measures of tolerability that guided escalation titration decisions were dose interruptions, reductions, or discontinuations, and the severity of GI AEs, such that we would continue to titrate quickly if there were no dose interruptions and the majority of GI AEs were mild in the preceding cohorts. Importantly, GI AEs incidence was not as heavily weighted in decisions on escalation and titration, since we expect an increased incidence of GI AEs with fast titration, and these numbers typically decrease in subsequent studies with slower titration, as has been shown with other GLP-1 receptor agonists. As shown on the right, we were able to titrate much faster using an every three-day titration schedule in the 500-mg cohort based on the excellent tolerability we saw in the 240-mg cohort, and used a similar fast schedule in the 740-mg dose cohort based on the tolerability we saw at 500 mg. We'll cover this in the next few slides on safety and tolerability. Now please turn to slide 15. Shown here is the treatment disposition in the 28-day MAD portion. In total, 37 subjects were randomized across three TERN-601 cohorts or placebo. In the 240-mg cohort, one subject was replaced due to early withdrawal from the study due to an unrelated grade one adverse event of menstrual bleeding. All treatment groups had nine subjects that completed planned study treatment. Importantly, there were no dose interruptions, reductions, or discontinuations due to drug-related adverse events in any subject. Please turn to slide 16. Shown here are the treatment-emergent AEs from the 28-day study. Overall, we see a favorable safety profile, with more than 95% of treatment-emergent AEs on study being mild and no severe or serious adverse events. The majority of observed AEs were consistent with known effects of GLP-1 receptor agonists and were predominantly mild GI AEs. There were no clinically significant changes in liver enzymes, ECGs, heart rate, or blood pressure at any dose. As shown in the table, the maximal AE severity in most subjects on study was mild. Lastly, as expected, we saw a dose-related increase in the incidence of GI AEs with faster titration at the higher dose cohorts. Turning now to slide 17. Looking more closely at the liver function test, TERN-601 appears to have an excellent hepatic safety profile across the wide dose range that we evaluated in this phase I study. Liver enzymes in all subjects remain less than one and a half times the upper limit of normal while on treatment at all doses. In the table showing mean changes in LFTs over time, we see an overall slight decrease in AST, ALT, with bilirubin remaining overall stable during treatment. Moving on to slide 18. This slide dives further into the treatment-emergent GI AEs seen over 28 days. The main takeaways from this table are, first, the majority of GI AEs on study were mild, despite fast titration to high doses.... Second, the rate of GI adverse events increased in latter cohorts that titrated faster on an every three-day schedule to target dose. The increase was most pronounced during the early phase of titration through lower doses that were very well tolerated in the 240-milligram cohort, indicating that titration speed had a big impact on the rate of GI AEs, as we expected. Third, despite such fast titration, GI AEs were tolerable, manageable, and did not lead to dose interruptions or reductions. Please turn to slide 19. When compared at a high level to 28-day data from other orally dosed GLP-1 receptor agonists, the phase I clinical data with TERN-601 looked competitive and differentiated. All the GLP-1 receptor agonists, including injectables and orals, demonstrated a range of approximately 3% to 6% placebo-adjusted weight loss at 28 days over a highly variable spectrum of drug types, doses, and titration schemes. Based on that, we think the right metric of success for a 28-day study is the identification of a tolerable dose range that shows a clear dose response through the 3-6% range of weight loss. TERN-601 showed precisely that, with a clean dose response of weight loss tracking to the top end of that range, with approximately 5% placebo-adjusted weight loss at the 740 mg dose level, indicating that we have successfully identified an optimal range of clinically active doses to take to phase II. Importantly, TERN-601 was well tolerated without dose interruptions, reductions, or discontinuations, despite a very fast titration schedule, which we think is a unique feature of this phase I study compared to others. Altogether, these data provide strong clinical proof of concept and validate TERN-601 as a promising oral GLP-1 receptor agonist. Please turn to slide 20. Shown on this slide are the distinct drug properties of TERN-601 that enable what appears to be a wide therapeutic window, where we're able to attain high doses that achieve sustained, robust target coverage while being well tolerated on a once daily dosing schedule. TERN-601 is an immediate-release tablet formulation, and based on the dose range we've identified in phase I, we can manufacture tablet strengths that achieve convenient once daily oral dosing with minimal pill burden. TERN-601 has four distinct properties that we think drive the clinical profile we're seeing. The first two are low solubility and high gut permeability, which results in slow dissolution and prolonged absorption along the length of the GI tract, an effect that becomes more pronounced at higher doses, resulting in the flat PK curve that gets us sustained twenty-four-hour target coverage with once daily dosing, despite a four- to six-hour half-life. The third property that may also be related to low solubility and high permeability is substantially higher drug concentrations and residence time in the gut tissue relative to plasma, as we saw preclinically. Since endogenous GLP-1 primarily acts through GLP-1 receptors in the gut to trigger appetite suppression via neural pathways to the brain, we think the high drug levels in the gut tissue is amplifying this normal physiologic effect to further drive appetite suppression and weight loss. Finally, TERN-601 is highly protein bound in plasma with a low free fraction, which, combined with the flat PK curve, is what we think allows us to titrate fast to high doses with good tolerability and supports the wide therapeutic window. We have put together the following slide to illustrate how these properties may be working synergistically to create a desirable effect. Turn to slide twenty-one, please. First, shown in the left illustration is how prolonged GI absorption, due to the drug's low solubility and high permeability, results in a flat PK curve with sustained target coverage supporting once daily dosing, as shown in the graphic on the right. Second, the high concentration of drug in the gut wall relative to plasma, as shown in the left illustration, may achieve even greater target engagement in the gut tissue. As shown in several preclinical and clinical studies, activation of GLP-1 receptors in the epithelial cells and vagus nerve terminals in the gut wall is known to trigger satiety centers in the brainstem that drive appetite suppression, satiety, and slowing of gastric motility, which act together to drive weight loss. Finally, as also shown in the illustration, TERN-601 has a low free fraction in circulation, which, combined with the flat PK curve, may enable a wide therapeutic window, allowing us to attain tolerable high doses that achieve both gut and systemic target engagement to achieve the full spectrum of clinical benefits associated with GLP-1 agonist, including weight loss, glycemic control, and other benefits. And with that, I'll pass it back to Amy for closing remarks. Please turn to slide 23. Thank you, Emil. As I mentioned at the beginning of the call, this compelling data drives us to move quickly to a phase II study, and we have a team at Terns with deep experience executing phase II studies. We've learned a lot from other GLP-1 trials, and we'll use that, along with the data from our phase I study, to run another insightful study that will support an efficient path to approval. To summarize our takeaways, we have explored a comprehensive dose range and expect no further dose range exploration in subsequent studies. TERN-601 was well tolerated, even with an aggressive titration scheme, and we have evidence from this phase I trial that we can further improve the tolerability by slowing the titration regimen.... We also see an opportunity for robust efficacy with longer durations of treatment, given the sustained target coverage and distinct properties of the molecule that Emil discussed. Finally, given the robust PD responses observed, we see a high degree of optionality to explore the use of TERN-601 across different patient profiles. For example, a lower dose with a high degree of tolerability could be an important option for people seeking weight management. Turning now to slide 24, please. Our operations and manufacturing team has been preparing for many months in anticipation of positive phase I data that would support moving TERN-601 quickly into phase II. Following today's release, our nearest priority will be to solicit additional feedback on this data from key clinical advisors and regulatory agencies to thoughtfully design the right phase II program to advance 601 as quickly as possible to a pivotal trial. Our ongoing preparations and next steps allow us to anticipate initiation of the phase II study for TERN-601 in 2025. Please turn to slide 25. As the obesity market continues to rapidly evolve, it is becoming increasingly clear that the future will be dominated by monotherapies and combination agents, given the diverse patient segments and associated comorbidities within the obese population. To potentially address this wide range of patient needs, we have two oral metabolic assets in our pipeline that can be combined with GLP-1 receptor agonists to enhance their beneficial metabolic effects. TERN-501 is an oral THR-β with preclinical data that demonstrates enhanced weight loss and proportionally greater loss of fat mass versus lean mass when combined with a GLP-1. THR-β is an orthogonal mechanism to a GLP-1 receptor agonist, because it targets the liver and may deliver additional metabolic benefits not seen with GLP-1s alone. The TERN-501 phase II data showed that the drug was safe and well tolerated in NASH patients without the GI side effects, variable PK, and drug-drug interactions seen with other THR-beta agonists. In addition to TERN-501, TERN is developing a series of oral GIPR modulators, and we are in lead optimization with an oral GIPR antagonist that has an intended use in combination with a GLP-1 receptor agonist. Please turn to slide 26. In closing, we are incredibly enthusiastic about the clinical data from our phase I study of TERN-601 in participants with obesity or overweight. As you have seen from today's presentation, TERN-601 is a distinct oral small molecule GLP-1 receptor agonist with properties that have demonstrated competitive weight loss, safety, and tolerability, and has the potential to be a leading GLP-1 receptor agonist. We are well on our way with phase II preparations and are fortunate to have an experienced and dedicated team ready to continue to flawlessly execute our clinical programs. We will now open the call for Q&A. 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. Our first question comes from the line of Etzer Darout with BMO Capital Markets. Your line is now open. Great, thanks for the question and congrats on the update today. So first question, you think about the dose-dependent 28-day mean weight loss, and you know, at the 500 and the 740 mg doses, you continue to kind of see this sort of improving, right, weight loss over time. And thinking about sort of maybe the phase II trial, have you considered sort of the duration of treatment that you're thinking about for that phase II study in terms of being able to kind of see fully how much weight loss you could ultimately get with the once daily dose? And then also on the safety bit, sort of given what you've kind of learned today, your thoughts around sort of maybe near-term dose combinations with 501 and then or others, given kind of the safety profile that you've identified with 601 to date? Yeah, Etzer, thank you so much for your question. I think your first question was really about phase II design, and your second about combinations. So, I will answer those questions and see if Emil has anything to add. On our phase II design, you know, the FDA has shown flexibility with other sponsors in obesity development, and we think it behooves us to engage with regulators and think creatively about how we can run the most efficient and speedy phase II possible. We have great phase I data here and want to make sure we're exploring all options. So your question was about length of time. As soon as we have more clarity on that, we will come back to you with more details. Does that answer your question? Yeah. And then just because you're continuing to kind of see weight loss through sort of the 28-day process, is sort of ways to kind of maximize sort of the ultimate weight loss that you could sort of see at these higher doses. Because it continues to improve through 28 days, I guess, based on sort of the charts that you show. Emil, would you like to take that question? Sure. Yeah, no, Etzer, that's a great observation, and we were also pleased to see that we don't see any sort of a plateau effect here over 28 days with all these slopes continuing their downward trends. And that's encouraging, and I think that bodes well for phase II. Again, we see very good tolerability with the very fast titration schedule. We're not going to replicate this titration schedule in phase II, and knowing that all these doses are pharmacodynamically active without a plateau effect at 28 days, gives us a lot of optionality in terms of the duration that we may explore in phase II. To your point, you know, Amy's point, the exact phase II design, we're going to be-... Very careful in terms of how we put that together, because we have a lot of optionality to get the most bang for buck from a clinical data standpoint. But as you know, typically, you look at in phase II weight loss at twelve weeks and then followed by weight loss at thirty-six weeks, right? And so, you know, when you think about the optionalities for sort of a twelve-week design in terms of duration of dosing, we think that the fact that even at two fifty and above, we start to see PD effect in weight loss, we could slow the titration, spend more time at these doses, and that gives us ability to potentially simplify titration relative to a lot of other drugs. Because we could think of maybe a two-step or at most a three-step titration with a single dose-strength pill that could be very easy for patients in terms of getting to the top dose. And so, you know, we're excited that we don't see a plateau effect here, and that gives us a lot of room to play with in terms of titration schedule optimization in phase II. Great. Thank you, and congrats again on the data. Thanks. Thank you. Thank you. Our next question comes from the line of Ellie Merle with UBS. Your line is now open. Hey, guys. Thanks so much for taking the question, and congratulations on the data. So you mentioned that you have no new dose exploration planned. I guess, just given the strong tolerability despite the rapid titration, I guess why not explore higher doses, as you do a less rapid titration schedule in phase II? And then just a follow-up question on the combinations. I think it was briefly mentioned in the last question. Yeah. But just, I guess, how are you thinking about potential timelines for potentially studying the combination of your THR-β and GLP-1? Just I think that preclinical data is interesting and shows some synergy. So I guess curious what you're thinking about in terms of that potential development strategy. Thanks. Yeah. Thanks, Ellie, so I'll take the second question, and I'll turn the first question about dose exploration to Emil, so as you pointed out, we have a great portfolio of combinable assets in obesity. TERN-501, as I talked about, is incredibly interesting. Right now, we're focused on taking TERN-601 to phase II, and we're also exploring options for TERN-501 in obesity, and we are not guiding to specific timing or details around combination trials at this time. Emil? Yeah, I'll take that first question on dose exploration. You make another great observation that, again, we have good tolerability. You know, our safety margins preclinically would allow us to go even higher in dose. But as I showed in the data, you know, we're tracking nicely through that 3-5% range over 28 days without a plateau effect at the 740 mg, you know, approximately 740-750 mg dose range. And so we think that's a great starting point in terms of having that dose range, where we track through that weight loss range that pretty much every other drug has shown over 28 days. And I think that gives us, you know, a good dose range that we can definitely play with in phase II without having to do extensive further dose range exploration with the molecule. Got it. Thanks. Thanks, Ellie. Thank you. Our next question comes from the line of Akash Tewari with Jefferies. Your line is now open. Hey, congrats on the data. It seems like the high plasma protein binding is a feature, not a bug here, which is really interesting, so just a couple from me. Given the rate of moderate GI AEs at the 740 dose, did you see the time course of these adverse events change throughout the study? Basically, did patients who had moderate adverse events see them alleviate by the end of the 28-day dosing period, and how concerned is your team about the rates of constipation at the 740 dose? Did you see exposure levels kind of hit a steady state by the end of that 28-day trial, or was there kind of evidence of continued drug accumulation? Thank you. Great question, Akash. Emil? I'll take that. Great question, Akash. And you mentioned the protein binding being a feature, we certainly agree. I mean, with regard to the time course of the GI events, it is, as I mentioned during the presentation, we saw that at the higher dose levels, it was more a function of titration speed. Because essentially, the uptick in GI AEs happened during those first nine to 12 days when we were titrating very quickly through the same low doses that we saw excellent tolerability with at 240. At the 240 mg dose, we saw zero nausea, vomiting, or any GI AEs where we did a weekly titration. And the same doses, when we got there quicker, we saw an increase in onset. To your point, so we did see more of an uptick during the titration phase and sort of more of a plateau after we reached the peak dose. And so I think, again, that informs, as we expected, that titration speed has a big role in the incidence of GI AEs. With regard to exposure, we don't see any accumulation. Again, the drug has a half-life around four to six hours, and so despite the prolonged absorption phase that gets you to the twenty-four-hour target coverage, that doesn't lead to accumulation over time. So yes, the exposures don't seem to increase as you go above, which is again, why we think there's sort of a plateau effect and potential attenuation that we'll see as we dose longer. Does that answer your questions? Yeah, yeah, it does. Thank you so much. Appreciate it. Thanks, Akash. Thank you. Our next question comes from the line of Nicole Martucci with TD Cowen. Your line is now open. Hi, everyone. It's Ritu. Sorry for the delay and mix-up this morning. Thanks for taking the question. Amy, I wanted to ask about sort of your strategy, your and Emil's strategy heading into phase II. As far as the number of doses, it seems like you know sliced through this 3-5% weight loss at 28 days with a couple doses. But just given how the GLP-1 market is evolving and the sort of different needs for potential future maintenance therapies versus just an emphasis on strength in weight loss, how are you thinking about the number of doses that you would take into a phase IIa as a setup for potential pivotal trials? Thanks. Yeah. Great question, Ritu. Thank you. You know, as we said, we're not- we are not looking to explore additional dose ranges, and we also expect to look at this dose range in phase II, given that we saw that all these doses were pharmacodynamically active. These are short trials with a small number of patients, so we think it behooves us to continue to explore this dose range. Emil, would you like to add anything to that? Yeah, no, that's a great point. I'd, I'd just add that, you know, as I mentioned during the presentation, the fact that we see sort of this nice trend of 3% to 5% across these dose levels, that informs potential use cases, as you alluded to in your question, around the different segments of the obesity population that we can explore. And I think that's why we do plan to specifically take all three doses to phase II. You know, an example there could be that, you know, the 740 milligram dose or doses in that range could be more applicable to a much higher BMI subgroup, where they, you know, wanna lose weight quickly. Whereas a more overweight type population, where you don't need to lose that much weight that fast, could do a lower dose, where again, we see that weight loss slope still not plateauing, and so again, it gives us a lot of long-term optionality in terms of how we could think about the various use cases for this drug with a dose range that's pretty simple. Got it. And if I interpreted your answer to a prior question correctly, it sounds like you are open to speeding up some of the lower doses. Sorry, speeding up the titration of certain lower doses, but also potentially slowing down the seven forty, seven fifty. So you have flexibility depending on dose? Yeah. Emil? Not exactly. I think, you know, what we were saying was that this phase, the fast titration with phase I was really designed to gauge the tolerability profile in a robust way. And like I mentioned, you know, if we see good tolerability with very fast titration, as we did in this study, that just puts us in a better position on the tolerability front as we move to phase II studies, where, again, we will be titrating slower. We don't intend to replicate this very fast schedule in a phase II study, where you have a lot more time to get patients to the target dose and, you know, realize the benefits that we see at these lower doses over a longer period of time. To answer your question, we don't intend to replicate this exact titration schedule, but I think, you know, the fact that we see clinical activity across these dose levels gives us optionality to sort of play with the slower titration schedules and see the optimal one. Understood. Thank you. Yeah. I'll just add to that, Ritu, that if you look at the titration slide, we, for two hundred and forty milligrams, we got there in three days. At the five hundred and seven hundred and fifty milligram cohorts, and at two forty, we got there on day fourteen, fifteen. So, dramatically different titration to two hundred and forty milligrams, and we saw different tolerability. So we learned a lot from that. And we also know from this study and other studies, that tolerability is really more related to titration speed than to absolute dose, and that was evidence for that in our trial. That makes sense. Thanks. Thank you. Our next question comes from the line of Graig Suvannavejh with Mizuho Securities. Your line is now open. Thank you. Good morning. Congrats on the data, and thanks for taking my questions. I had two, if I could. First on, I believe it's slide 12 of your deck, I was very intrigued by the data around the greater than or equal to 3% weight loss and the greater than or equal to 5% weight loss. And, realizing these are relatively small ends or numbers of patients, but any comment on how to put that in context with other competing GLP-1 programs? So that's my first question. And then my second question perhaps is a bit bigger picture, more philosophical, which is just a view, the current view at least, the company has around where an oral GLP-1 might be best positioned. Is there even room for considering use for an oral GLP-1 upfront, versus I think the main view that I think the market has, that an oral GLP-1 is really best suited for just a maintenance therapy? Thanks so much. Yeah, thanks for your questions, Graig. I will start off with the second question and then see what Emil has to add to your big picture question and let him comment on slide 12. You know, our view is that this is a fast-moving market, where there is still a lot of data that's evolving in terms of the potential for oral GLP-1s. You know, using an oral GLP-1 upfront may really depend on the patient segment. As we talked about, we see a variety of patient segments in this market. We do think there's a market here for maintenance, but there could be a market for upfront based on the performance that we see in later stage trials for oral GLP-1s, and that data is really still to evolve. Emil, you may have something to add to that, and if you could also comment on Graig's first question. No, I totally agree with your points there. Graig, with regard to your first question, I think, you know, we were very encouraged to see that responder analysis. I mean, despite the small numbers, you're seeing a very clear trend, and again, we saw statistical significance at those, for that 78% and 67%. You know, the mean weight loss over 28 days gives you one dimension in terms of what the drug can do, and we saw a nice dose response there. But the responder analysis shows you what the overall distribution of the weight loss is. You know, we know from very long-term studies with, like, semaglutide and others, that, you know, the weight loss, when you look at sort of the distribution of weight loss, it's somewhat of a bell curve with there, you know, there's patients who lose a lot of weight, and there's patients who don't lose a lot of weight. So I wanted to look at that, and we're very encouraged to see that a dose response where two-thirds of patients lose more than 5% body weight at the 740 milligram dose, saying that, you know, that mean is not driven by one or two outliers. And that was very encouraging for us to see. As to how to put that in context with the other oral GLP-1s, I don't... I mean, I don't think every other drug has, all of them have shown the data this way, but we're very encouraged to see that both on a responder analysis basis and the mean analysis basis, we're seeing a very good dose response. Thanks for the question, Graig. Thank you. Our next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is now open. Good morning, guys. Maybe a couple strategic questions for me or questions on the forward here. One, obviously, you'd like to move rapidly into a phase II study. Can you remind us what you've done with respect to the tox studies you'd need to complete in order to move forward with longer trials? And then, two, can you remind us, in terms of the cash runway guidance and the funding that you currently have, where you stand with respect to executing against those studies on your current balance sheet versus, like, looking for additional sources of capital? Thank you. Great. Thanks, Corinne. I'll let Mark Vignola comment on your second question, and then I'll come back to you on the first. Hi, Corinne. $225 million as of the end of last quarter. We're continuing to reiterate guidance into 2026. You know, we have cash to cover next steps on this program, and we continue to think strategically about how we allocate our capital. You know, obviously, we've talked about some different options here on phase II, and you know, we'll have to think about how we are opportunistic with regards to capital markets on bringing in additional capital. Thank you. Then, Corinne, on your first question about our preparations for phase II, as I said, we've been preparing for many, many months, anticipating positive phase I data. We have an experienced team from the CMC, preclinical, and operations standpoint, and we're really evaluating all of our options. We don't comment specifically on the status of our tox studies. Okay, thank you. Thank you. Our next question comes from the line of Eric Joseph with JP Morgan. Your line is now open. Hi, good morning. Thanks for taking the questions. Maybe just a question on the planned phase II trial. I guess, how should we be thinking about the length of that study? I guess you've seen some variation in phase II studies ranging, you know, 12-26 weeks. I guess any sense at this point that you could provide in terms of the duration of the study that you're contemplating? And then secondly, just a housekeeping question, wondering whether there's any additional formulation work to be done here, either going into the phase II or later-stage trials. Thank you. Great. Thanks for your question, Eric. I'll take the second one first, which is, as I've said, our CMC team has been planning for this. I think as Emil may have said, we have 260 milligram tablets that will be ready to go. And so in terms of moving into phase II, there's not additional CMC work that we need to do for that. And in terms of the planned phase II trial, and the length of the study, sort of as I said earlier, we have great phase II or great phase I data here. As we think about phase II, we're not guiding to specific lengths or specifics on that, just because, as we had said, given some of the emerging regulatory environment, it really behooves us to speak to our advisors and regulators about the most efficient and speedy path forward. Okay, got it. Thanks for taking the questions. Thanks, Eric. Thank you. Our next question comes from the line of Jon Wolleben with Citizens JMP. Your line is now open. Hi, thanks for taking my questions, and congratulations on the data. I just wanted to comment on the male and female split observed in this early phase I. So was that something that was intentional, or do you foresee that trend sort of evening out in phase II? And then secondly, could you specifically comment on the diarrhea? I know that's traditionally a difficult adverse event to manage, so how transient was-were those adverse events? Thank you. Thanks for your question, Josh. I'll let Emil take both of those. Yeah, Josh, thanks for the question. So the male-female split is a good observation. Again, like I said, we see predominantly male subjects in this study. That wasn't intentional. Again, this is a randomized, double-blind, placebo-controlled study. And so that just was sort of the way the numbers ended up splitting out at the end. But that does bode well, again, for phase II, where we do expect the numbers to even out more as we go to larger sample sizes and longer study durations. We have more females subjects added to the mix. I think that could potentially or suggest that the weight loss numbers may even improve further, knowing that females lose more weight on GLP-1s. With regard to the diarrhea, again, we saw very low rates of diarrhea across all these doses. All cases were mild and self-limited, and so, you know, the diarrhea does certainly not appear to be a GI signal with this drug. Great. Thank you. And just one more thing. I know we touched on the titration schedule a fair amount, but I just wanted to clarify if there were sort of more optionality in terms of just the three-day schedule and the one-week step up. You mean going forward? Yeah, going forward in the phase II. Yeah. Are there more options than just, you know, those two primary step-ups, or are you guys thinking about other potential timeline or durations between doses? Certainly, there are more options. I mean, we haven't gotten into the very specifics of exactly what those are. But to my earlier point, I don't think we need to replicate an every three-day titration schedule in phase II. Okay, great. Thank you guys so much, and congrats again on the data. Thank you. Thanks, Josh. Thank you. This concludes the Q&A portion. I would now like to turn the call back over to Amy Burroughs for closing remarks. Thank you for joining us as we share this exciting data on TERN-601 for the first time publicly. I want to thank our study participants, clinical advisors, study staff, and dedicated Terns team for their support. Thank you so much, and happy Monday. Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.