Good morning, ladies and gentlemen, welcome to the Terns Pharmaceuticals conference call. My name is Justin Ng, Director of Corporate Development and Investor Relations. As a reminder, this conference call is being recorded, and a webcast of this call will be archived on the Terns website. At this time, all participants are in listen-only mode. Following our presentation, we will open the line for a question and answer session. We would like to remind you that during this call, we will be making forward-looking statements that are subject to risks and uncertainties. Our actual results may differ materially from those described. We encourage you to review our risk factors in our most recent quarterly report on Form 10-Q, which can be found on our website. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so. Now, I'll turn the call over to Erin Quirk, President and Head of R&D. Thanks, Justin. Here is the agenda for our call today. We'll begin with an introduction and overview of the Terns pipeline, an overview of TERN-601 and the GLP-1 mechanism, the opportunity within obesity. I'll turn it over to Dr. Olivia Osborn for the presentation of non-clinical 601 data that was recently presented as a poster presentation at the 83rd Annual American Diabetes Association Congress earlier this week. I'm also pleased to welcome Dr. Marcus Hompesch, an internationally renowned expert in the field of bariatric medicine research and obesity translational development. I'll come back and describe Terns' obesity franchise overview, including our extensive non-clinical pipeline for different mechanisms of action for the treatment of obesity. We will conclude the event with a brief question and answer session. As we are dedicating today's call to our obesity pipeline, we'll be limiting our questions to those topics discussed today. Terns is a publicly traded biopharma company with a strong discovery effort that has resulted in the discovery of three internally discovered and developed clinical or near clinical stage programs, which we've advanced in our five years of existence. TERN-701 is an allosteric BCR-ABL inhibitor, which is in Phase 1 for the treatment of chronic myeloid leukemia. We are planning a US Phase 1 initiation in CML patients later this year, with interim top-line readouts from initial cohorts expected in 2024. TERN-501 is a thyroid hormone receptor beta agonist, currently in Phase 2 development for NASH. We have fully enrolled our Phase 2 DUET study as of February of this year and are expecting top-line week 12 data in the third quarter of this year, including liver fat content reduction and sex hormone-binding globulin changes from baseline. Today, we will discuss TERN-601, Terns' oral small molecule glucagon-like peptide 1 receptor agonist, or GLP-1, which is currently in the preclinical phase. Terns plans to advance the molecule into a Phase 1 study in the second half of this year. We anticipate having multiple ascending dose 28-day weight loss data for TERN-601 in the 2024 timeframe. Looking at our development stage pipeline, there are three characteristics that all of these molecules have in common. They are small molecules and for oral administration that were internally discovered and are based on clinically validated mechanisms of action, where we see room for improvement. In addition to the three molecules highlighted in our overall pipeline, we also have candidates from Terns' discovery efforts, which have been very productive over the past several years and continue to be put to work to augment our obesity pipeline. We have continued our medicinal chemistry efforts and are continuing to work on the next generation TERN-600 series, in which we envision structurally distinct, next generation, oral small molecule GLP-1 receptor agonists. We are currently in the lead identification phase and believe that the TERN-600 series has the potential for multiple oral GLP-1 receptor agonist candidates coming forward in the future. We were also very excited to announce in late 2022, the initiation of discovery efforts for the TERN-800 series. This is a multi-pronged discovery series aiming to discover and develop modulators of glucose-dependent insulinotropic polypeptide receptor activity, or GIPR. Here, we envision the discovery and development of small molecule agonists and antagonists of the GIPR receptor that could be used in combination with an oral GLP-1 receptor to potentially develop highly potent and well-tolerated combination oral treatments for obesity. Lead optimization efforts are underway for our antagonist and agonist GIPR scaffolds. I'll now give a brief overview of the GLP-1 mechanism, our discovery approach, and the opportunity we see in the obesity space. GLP-1 agonism is a well-established mechanism of action for the treatment of type 2 diabetes, where this mechanism has become a mainstay of therapy. It is well understood that GLP-1 receptor agonists have a multitude of functions in various organ systems that lead not only to improved glycemic control and improvements in insulin resistance, but uniformly across the class, various degrees of weight loss have been observed. The main mechanisms of weight loss, in addition to correction of metabolic perturbations, are thought to be central nervous system effects on appetite suppression and delayed gastric emptying, leading to decreased signaling in the gut and decreased hunger signaling overall. Terns' GLP-1 discovery efforts began shortly after the company was founded in 2017, and were initiated following publication of the crystal structure of danuglipron, a small molecule, non-peptidic GLP-1 agonist bound to the GLP-1 receptor. This was the inspiration for the discovery chemistry for Terns' GLP-1 program, where we instituted a bioinformatics approach and virtual screening methodology, looking at various different binding hotspots for engagement within the GLP-1 receptor agonist. Our aim was to discover an oral, small molecule, non-peptidic agonist that could be administered once daily. Since then, oral small molecule GLP-1 agonists have demonstrated efficacy on weight loss and on hemoglobin A1C decreases in as short as 28 days. These first-generation molecules, however, have inconvenient dosing schedules, such as twice daily dosing, and limitations in dosing and tolerability, which is true both of the initial oral GLP-1s and injectable GLP-1s overall. Terns' GLP-1 agonist program target product profile was focused on discovering a potent, safe, and effective small molecule that is non-peptidic and could be suitable for oral once daily dosing. We also sought a molecule that had the potential for combination and co-formulation with other agents, with applicable to obesity, NASH, and potentially other metabolic indications. The obesity market is significant. Based on recent studies, the estimated aggregate cost of obesity and its incumbent health problems is $260 billion annually in the U.S. To date, only about 2% of adults are taking medicine for weight loss, despite almost half of Americans meeting the medical criteria for pharmacotherapy. New generations of weight loss drugs are gaining approval and commercial uptake, particularly in the GLP-1 space. We expect the market to expand. Indeed, 75% of patients starting Wegovy are new to anti-obesity treatments. We believe oral therapies may play a unique role in overcoming the limitations of injectable GLP-1s and support that expansion. Approved GLP-1s for obesity are peptidic molecules, almost all of which require subcutaneous injection. Despite their early success, we do see a number of limitations for patients, including frequent injections, challenging tolerability profiles, and cumbersome titration schedules, amongst others. We think developing oral small molecule GLP-1 receptor agonists may address each of these shortcomings. With that, I'll now turn it over to Dr. Olivia Osborn to take us through the recently presented non-clinical data for TERN-601, our first oral small molecule GLP-1 candidate. Thanks, Erin. Good morning, everyone. My name is Olivia Osborn. I'm the Director of Biology at Tern. Yeah, I'm excited to present to you today our data related to TERN-601 that we recently presented at the American Diabetes Association just a couple of days ago. This data is related to the action of TERN-601, which is our novel oral GLP-1 receptor agonist, where we show this suppresses food intake, improves glucose tolerance in this transgenic mouse that expresses the human GLP-1 receptor. GLP-1 agonism is a well-validated mechanism of action in metabolic disease. GLP-1 agonists interact with the GLP-1 receptor to induce broad metabolic benefits. In this diagram here, I'm showing some of the tissues of the dominant actions of GLP-1. GLP-1 acts on the pancreas to stimulate insulin secretion in response to glucose. GLP-1 also acts upon the brain, whereby in multiple centers, it interacts with the GLP-1 receptor to decrease food intake and decrease appetite. In the last diagram here, I'm showing the stomach and the gut. This is whereby GLP-1 acts in this area to delay gastric emptying. The effect of this is to delay the processing of nutrients through the gut, this increases the feeling of fullness for longer, otherwise known as increasing postprandial satiety. The data I'm going to show today is related to TERN-601 and the action on these various target tissues. As I've said, TERN-601 is our novel, potent, oral, small molecule GLP-1 receptor agonist that's currently in preclinical development here at Tern. The first piece of data I'm going to show is related to the potency of TERN-601. Here, we show TERN-601 has nanomolar potency in cells expressing the human GLP-1 receptor. On the left-hand side, this table reflects this data. This table is showing you the in vitro potency of TERN-601 at the human GLP-1 receptor and the mouse, utilizing an assay measuring cyclic AMP. This is a downstream action when the GLP-1 receptor is engaged, we can see the downstream signaling of cyclic AMP. These numbers reflect the very high potency of TERN-601 at the human GLP-1 receptor, but notably, this is almost inactive at the mouse receptor. This is actually very much expected and is very well described by scientific methods. In the middle of the slide, I'm showing you the human GLP-1 receptor binding pocket. In the middle of the diagram, the human receptor is shown in yellow, and in the middle of the diagram, you can see a green molecule, which is a GLP-1 receptor, small molecule agonist, interacting with this binding pocket. Importantly, there's a red residue, which is shown as W33, tryptophan at amino acid position 33. While this might appear very complicated, it's shown much more clearly in the multiple sequence alignment on the right-hand side. What we're showing here is the essential importance of this tryptophan residue with the interaction of the small molecule. It's essential to have a tryptophan in the position for the activity to be measured of a GLP-1 agonist. As you can see, the tryptophan is only present in a human and a monkey GLP-1 receptor. In species lower than that, such as the mouse, you can see that there's an S in that position, which is a serine residue, and that's the same in many other species below a primate. The message for this is that small molecules only bind to the primate GLP-1 receptor, and hence, it's necessary to either use cells of human origin or a mouse model that contains the human GLP-1 receptor. In the data I'm gonna show in following slides, it's gonna be utilizing this human GLP-1 receptor mice to assess the activity of small molecule GLP-1 receptor agonists. What this mouse is essentially a normal wild-type mouse, but with just a single change of changing the mouse GLP-1 receptor for the human form, that enables us to measure the activity of GLP-1 receptor agonist small molecules at this receptor. As I've said, we can also measure GLP-1 activity in cells derived from human origin. Here, this is presenting data of TERN-601 that enhances glucose-stimulated insulin secretion, or GSIS, in human pancreatic islet microtissues. These are cells derived from human origin, and the first thing we did to ensure that these are actually GLP-1 responsive is in data not presented in this slide, but as an important control. We assessed the activity of liraglutide, a peptidic control, to ensure that this human donor was indeed GLP-1 responsive. Having passed that quality control test, we moved on to this assay, which is to determine the activity of small molecule TERN-601 in this assay. What this assay measures is insulin secretion, and as you can see, in a glucose-stimulated state, insulin secretion is enhanced in the DMSO control. We then include the danuglipron, this is the Pfizer small molecule agonist, you can see an enhanced effect on glucose-stimulated insulin secretion in these tissues. Most importantly, what we're able to show here is TERN-601 has a dose-dependent effect of increasing glucose-stimulated insulin secretion in this model. To point out that the high dose that we see on the right-hand side of TERN-601 is equivalent to the danuglipron dose presented as a control. In summary, this slide shows us that TERN-601 indeed has on-target action in the pancreas to cause glucose-stimulated insulin secretion in this model. I'm gonna present data related to the in vivo activity of TERN-601 in the mouse model. In this first assay, we're showing that TERN-601 shows similar activity to a peptide control on glucose tolerance in the mice. Essentially, this assay involves administering the test articles 30 minutes before the start of this experiment. We then use an intraperitoneal injection of glucose into the mice, and we then measure the amount of glucose in the blood for a period of a few hours afterwards. In the vehicle control, as you would expect, when you inject glucose into the mouse, you can measure high levels of glucose in the blood for the few hours following the injection. Notably and importantly, GLP-1 receptor agonism has an impact to reduce the glucose excursion in this model. Here, we're using three different doses of TERN-601 and including a positive control liraglutide in this experiment. What this shows is that any of these GLP-1 agonists have a potent effect to reduce the glucose excursion across this model over these few hours of study. This is summarized also in the graph on the right-hand side, that reflects the area under the curve in this assay. I should say also here that we selected liraglutide as a control 'cause we think this relatively short half-life of this peptide is a good control to use to compare for a small molecule agonist, such as TERN-601, and has been used in many other equivalent assays from similar types of experiments. I'm now gonna present data related to another important action of GLP-1, which is its effect on food intake. Here in our humanized mouse, we do this experiment to show a dose-dependent effect of TERN-601 on food intake. How this assay works is that the mice are fasted overnight and then administered with the various test compounds, and then given the food back, so we can measure the quantity of food eaten in the subsequent hours. In the vehicle-treated group, shown here in gray, you can see that the quantity of food eaten increases over the hours and the refeeding response. You can see the various doses of TERN-601, represented by increasing darkness of the blue color, show that at the higher doses of TERN-601, we're suppressing food intake to a similar level as the peptide control used here, liraglutide. This slide shows us very conclusively that TERN-601 reduces food intake in a very strong dose-dependent manner in this humanized mouse model. The final piece of data I'm gonna show you related to TERN-601 is its impact on gastric emptying. This is a fairly novel assay, but kind of exciting in the fact that it's also used in human patients in a very similar manner. What this involves is essentially administering Tylenol or acetaminophen to the mouse by gavage, and then measuring the impact on how we can then establish the quantity of acetaminophen in the blood over the course of the following hour, which is a proxy for the rate of gastric emptying. In this experiment, it's clear to see that when we inject acetaminophen by gavage and then measure in the blood, you can see a high amount of acetaminophen in the blood in the vehicle-treated groups after just 10 minutes, that continues for the subsequent hour. Here we're showing TERN-601, and in this case, we use semaglutide as a control. The reason for semaglutide was that this assay has recently been published by other groups, and in those experiments, they've also used semaglutide. We wanted to replicate this assay in a similar manner that's previously been published recently. We have no reason to assume liraglutide wouldn't act exactly the same in this type of control. What this is showing us is both semaglutide and TERN-601 have a very potent effect here to reduce gastric emptying. The physiological output of this would be to enhance postprandial satiety in this kind of model. In conclusion, I've shown today that TERN-601 is a novel, potent, oral small molecule agonist of the human GLP-1 receptor. TERN-601 enhanced glucose-stimulated insulin secretion in the human pancreatic islet microtissues. These are the tissues derived from human origin. In the mouse data, I show single oral doses of TERN-601 significantly improve glucose tolerance, suppress food intake, and slow gastric emptying in these mice that importantly express the human GLP-1 receptor. We believe these results support the continued development of TERN-601 for the treatment of obesity, and as mentioned earlier, the phase 1 trial of TERN-601 is expected to initiate in the second half of this year in participants with elevated body mass index. With that, thank you, and I'm gonna turn the call over now to Dr. Marcus Hompesch for his thoughts on the presented data. Dr. Hompesch. Thank you very much, Olivia. Thank you very much, Erin and Terns' team. Let me start with congrats, that I think are in order for what you've been able to achieve from discovery to now, early preclinical development, getting ready for the clinic with your small molecule GLP-1 receptor agonist. I only want to comment here on your development program from two perspectives. One, from the perspective of the clinician physician, who I still am, and then second, from the perspective of the translational clinical researcher. Comments from both, I can start again with congrats. I think in looking at what you've already mentioned, Erin, in particular, the pandemic of metabolic diseases, there is a steep unmet need, and it's only growing on us with regards to patients that require novel treatments that are easily accessible and are convenient to use. If you look at the existing GLP-1 receptor agonist landscape, it was mentioned they consist mainly of injectables, peptides. That comes with some inconvenience. It comes with access restrictions. Most of those compounds that are approved will require refrigeration. There's a limitation in terms of access, usability, and convenience. The next frontier, truly, I believe, in the GLP-1 receptor agonist space, incretin space, is developing small molecules that are effective and convenient to use for a growing population of patients with metabolic diseases. Your commitment in that regard is commendable and very much appreciated by certainly clinicians and patients alike. In looking at the data that you've been able to show us today, in looking at the development path that you've taken and are committed to continue, again, congrats are in order, all my commentary comes from the translational researcher point of view. For context, the GLP-1 receptor family is part of the GPCR receptor family. It's a highly complex, highly preserved across species, throughout the evolution receptor family. Several hundreds of receptors are known to be coded on the human genome. Highly complex receptor family that's regulating most of our biology, a sort of all drugs approved are addressing GPCR receptors. For all sorts of reasons, cardiac, vascular, health, metabolic health, and the GLP-1 receptor is part of that family. It's a highly complex receptor to address as a small molecule. Very intelligent drug design is needed, and structure activity research is needed to come up with a compound that will trigger the desired efficacy and effects on that receptor. There are, to my current knowledge, only really five active development programs, three in the clinic right now. Terns would enter the clinic shortly and are designed to kind of really address a significant unmet need. If I look at the preclinical data that's been generated by other programs, I think I can say what you've done at Terns really makes me very optimistic and excited about the future of the compound. A, you've I think, chosen the right cell models here. You've chosen the right preclinical animal models with humanized mouse humanized receptors, GLP-1 receptors, being involved. If I look at all the reference data that's out there, one thing seems to be a common theme. If you've been able to show efficacy and safety using this type of development approach, humanized receptors in in that mouse model, those data have beautifully translated into clinical data along the path, and I think that's very encouraging. Obviously, proof's in the pudding in terms of how the dose response relationship will translate into a magnitude of effect on the clinical human side. I have little doubt, knowing the data from competitive programs, that we'll have very good reason. We have very good reason to be very optimistic about that step for Terns. That will obviously help to address this next frontier of new therapeutics in the interchange GLP-1 receptor agonist space that we need to kind of go towards, where we need to break down the walls of inconvenience and accessibility. That's my commentary here. I'm happy to see this program move forward, and want to wish everyone all the best. Thank you so much, Marcus, for that very interesting commentary. I'll now resume with an overview of Terns' obesity franchise, including TERN-601 and beyond. As we mentioned at the beginning of this call, Terns' discovery efforts are continuing to work on enhancing our obesity pipeline. You just heard about non-clinical data for TERN-601. I'd now like to spend a few minutes on next steps for TERN-601, and then introduce you to our next generation oral GLP-1 program, the TERN-600 series, as well as our oral GIPR modulator discovery program, which we call the TERN-800 series. To remind you, the next step for TERN-601 is to initiate a phase I clinical trial in the second half of this year. We're making great progress towards that goal. We've completed initial drug product manufacturing to support the phase I program. We've now presented preclinical data from a transgenic mouse model evaluating TERN-601, and we're in the late stages of completing routine IND enabling work. Therefore, we are on track to initiate a clinical trial later this year. Our planned first-in-human phase I clinical study includes a single ascending dose phase Ia portion in healthy volunteers, followed by multiple ascending dose proof of concept phase Ib trial in patients with overweight or obesity. Planned endpoints in the multiple ascending dose portion of the study include safety measures, body weight change through 28 days of dosing, as well as the potential to look at glycemic control parameters in parallel. Our iterative medicinal chemistry efforts have been ongoing for some time now in the GLP-1 receptor target and are priming the next generation of oral GLP-1 receptor agonists for obesity. A few years ago, when we initiated the GLP-1 program, we set out to discover GLP-1 molecules with once-daily dosing potential, suitability for combination, and ease of manufacture. That is and remains our core target product profile for our GLP-1 discovery efforts. In our first generation oral GLP-1 candidate molecules, we sought out small molecules with activity to danuglipron, with once-daily dosing potential based on preclinical work, and that were suitable for combination with other agents. Those efforts were fruitful at the end of 2021, when we nominated our lead candidate, TERN-601, for development. We began the IND enabling work to bring that molecule forward. Terns has now continued these medicinal chemistry efforts, and we're now working on next-generation GLP-1 small molecule receptor agonists. The target product profile for this generation series, which we call the TERN-600 series, is to discover new, potent, and structurally distinct scaffolds that also have the potential for once-daily dosing, ease of manufacturing, and suitability for combination with other agents. We have made significant progress along these lines. We have discovered some interesting new scaffolds, which we think could meet this target product profile. We hope to nominate new TERN-600 compounds, which could be the next generation of oral once-daily agonists and have the potential of being part of fixed-dose combination regimens for the treatment of obesity. To provide a little more background on our vision, we have seen several different injectable peptidic GLP-1 combinations, which included GLP-1 receptor agonists combined with GIPR modulators, with glucagon, or a combination of both, as well as other peptides, including amylin and FGF21. These combinations are very interesting and are producing both enhanced weight loss and, in some cases, improved tolerability when these peptidic mechanisms are added to GLP-1 receptor agonists. These are very exciting advances for the field. Terns, however, is focused on oral regimens for weight loss, and we believe that within our pipeline, we could have the potential for multiple different approaches for oral combinations. One of those could be an oral GLP-1 receptor agonist combined with our oral thyroid hormone beta receptor, TERN-501. We also envision the future potential for an all-oral GLP-1 receptor agonist, GIPR modulator combination. Terns has internal discovery programs that potentially could be brought forward in the future to produce these combinations based on our current internal pipeline activities. I'll now cover some non-clinical data that is interesting regarding the combination of the THR-β agonist with a GLP-1 for weight loss. Non-clinical data now suggests that, in fact, TERN-501, our THR-β agonist, may in fact augment the weight loss effects of a GLP-1 receptor agonist. Terns has been interested in combinations of TERN-501 with our GLP-1 receptor program for some time, and earlier this year, we initiated a non-clinical study in diet-induced obese NASH mouse model. In this model, mice are fed a high caloric, high-fat diet to induce overweight and obesity. The diet also contains components such as fructose, fats, and cholesterol that can lead to liver fibrosis. In this non-clinical study, we had used a lean mouse vehicle control in gray, two doses of TERN-501 THR-β monotherapy in orange, a low and a high dose, which were designed to bracket the TERN-501 exposures that we're currently using in our Phase 2 clinical trial in NASH patients. We used semaglutide in blue as an injectable GLP-1 positive control in this study. Semaglutide was used rather than an oral small molecule because these are wild-type mice that do not express the human GLP-1 receptor. Therefore, a peptidic GLP-1 must be used to induce the pharmacological effects rather than an oral small molecule GLP-1. Finally, in purple, we had two combination arms of the same dose of semaglutide in blue, with either a low or a high dose of TERN-501. Following 10 weeks of treatment in each of these study arms, we have observed quite intriguingly, that while semaglutide alone induced significant body weight loss, semaglutide in combination with TERN-501 significantly enhanced the body weight loss compared to semaglutide monotherapy. The combination arms achieved weight loss in excess of 25% and even 30% when the high dose of TERN-501 was added to semaglutide. This is despite the fact that monotherapy with TERN-501 did not elicit weight loss in this model as monotherapies. The mice in the high-dose TERN-501 co-administered with semaglutide, remarkable bar, in fact, achieved the same mass. Therefore, interesting non-clinical proof of concept data that a THR-β agonist, such as TERN-501, could be combined with a GLP-1, either co-administered with an injectable GLP-1, or perhaps in the future state, co-formulated with an oral GLP-1, to have a regimen that may have enhanced weight loss in the clinic. Turning to our GPCR modulator program, I'd like to spend a moment to discuss why we are pursuing both GPCR agonist and GPCR antagonist programs. Both mechanisms of action, agonism, antagonism, combined with GLP-1, have been shown to produce significant weight loss with improved tolerability in clinical trials. tirzepatide is an injectable GLP-1 GPCR agonist, which is approved for the treatment of Type 2 diabetes. It showed impressive weight loss of greater than 20% at 72 weeks in a phase 3 clinical trial, and had a good safety and tolerability profile that appears may have better GI tolerability than GLP-1 receptor agonist monotherapy treatment for weight loss. We also find it intriguing that AMG 133, which is a large molecule consisting of a peptidic GLP-1 receptor agonist and an antibody GPCR antagonist, also showed significant weight loss up to 150 days following a 3-dose, 1 monthly subcutaneous administration. Therefore, it appears that both GPCR agonism and GPCR antagonism, when combined with the GLP-1 receptor agonist, can produce both enhanced weight loss and perhaps improved tolerability as well. For this reason, we are pursuing, at this point in time, both a small molecule GPCR agonist program and a small molecule GPCR antagonist program, with the division of discovering at least one GPCR modulator that could be moved forward into clinical trials in combination with an oral GLP-1 receptor agonist, such as TERN-601, or perhaps another candidate from the TERN-600 series. The TERN-800 discovery series is well underway, and we have already initiated and made great progress with lead identification, leveraging our internal chemistry expertise to develop the initial set of 800 series compounds. Based on our improving knowledge of our scaffolds, we'll move this into lead optimization. Supplementing our efforts here, we have utilized computational approaches to virtually screen over 9 billion compounds in silico to identify additional GPCR modulators. We are focused on modulators that could be combined with either approved or, in the future, investigational GLP-1 agonists. We're moving through the lead identification phase and would anticipate moving into lead optimization phase, with the potential for a candidate nomination as early as 2024, followed by initiation of IND-enabling studies. I'd like to close by reviewing and summarizing Terns' obesity program, as well as our next steps. Terns' has multiple exciting discovery stage programs and a soon-to-be clinical stage program for obesity with TERN-601, our first-generation oral small molecule GLP-1 receptor agonist, which we anticipate moving into Phase 1 in the second half of this year. We are focused on continued discovery efforts on next generation or on the next generation oral small molecule TERN-600 series, where we are progressing through lead identification and lead optimization efforts. With our TERN-800 series, which is our oral small molecule GPCR modulator program, lead optimization is underway. With that, I thank you very much for your attention, and let's open it up to questions. ... Our first question comes from the line of Akash Tewari of Jefferies. Your question please, Akash. Hi, everyone. This is Amy on for Akash. Thanks so much for taking our question. I guess the first one is, given the backbone of 601 is likely more similar than danu versus loti, do you think this potentially de-risk for the liver tox for 601 that we see with loti? Have you seen anything from your preclinical tox studies? Just a quick second question. I guess, how do we expect this preclinical data to translate to clinic? I know it's really hard to standardize head-to-head, but we are seeing some signs that 601 seems to be doing better on food inhibition compared to danu. That said, you have to standardize for doses. Is there anything that you can talk about 601's property that could either allow it to get to higher exposures, or any points of differentiation versus danu, or even the other oral GLP-1s on bioavailability, half-life, or on extent of bias on cyclic AMP signaling and other factors? Thanks so much. Mary, do you wanna take that? Sure. Hopefully, I will remember most of them. I think the first question was about de-risking of liver toxicity, based on our, the scaffold for TERN-601. Earlier this week, we heard the news that Pfizer has discontinued lotiglipron, due to a number of reasons, including an elevations in liver enzymes. It's our understanding that that may come from the southern half of the lotiglipron molecule, which is not a common motif used in TERN-601. Therefore, we do not anticipate that same read-through to the TERN-601 molecule, if that's helpful. Next, I think you were asking about bioavailability and potential differentiation from danuglipron. I'm glad that you are encouraged also by the food intake data that we presented earlier this week. We're excited about that as well. I think the best answer to your question is that, you know, we've done a number of experiments that show that TERN-601 is engaging the GLP-1 receptor, and therefore, we have the data that we need to move forward in the clinic. With regard to oral bioavailability and tissue distribution and potential differentiation, we think those questions are best answered by clinical data, and we're looking forward to producing those data, you know, over the next 12- 18 months. I've forgotten the last question. Sorry about that. That's all my questions. Thank you so much. All right. Great. Thank you. Thank you. Our next question comes from the line of Ellie Merle of UBS. Your line is open, Ellie. Hi, this is Jasmine on for Ellie. Thanks so much for taking our question. First, can you just give some color on the current thinking for TERN-601 on your development plan and the potential opportunity in type 2 diabetes versus obesity, considering the competitive landscape for both? Secondly, we've seen some data from some other GLP-1 oral agonists recently, so can you maybe give some color on how TERN-601 could be differentiated from those based on the design of the molecule? Thanks. I can tackle those questions as well. Hi, Jasmine. Thanks for the questions. The first question was about the potential for TERN-601 as a therapeutic for type 2 diabetes. We would anticipate, based on the data that Olivia went over today, that TERN-601 could have an impact upon glycemic control. Our plan is to develop it first for obesity, however, given the multitude of treatment options currently available for type 2 diabetes on the market. I think the second question had to do about potential 601 differentiation. Here, I'll just guide you back to the target product profile that we've saw in the discovery of TERN-601, which was activity at least similar to danuglipron, where significant 28-day weight loss was shown in a clinical trial, right? The potential for once-daily oral dosing, ease of manufacture, and combinability with other agents. We've shown some really interesting preclinical data, and Dr. Hompesch, I think, shares our excitement about what this could portend in the clinic. Nonetheless, there are limitations, I think, of these preclinical models, so again, I think we'll be looking towards the clinical data we'll be producing, you know, over the next several quarters to understand potential differentiation. Mainly though, we think that's gonna be important to have different treatment options, you know, out there and available for the many patients, you know, who are in need of pharmacotherapy for obesity. Having something comparable to danuglipron with perhaps improved PK profile, we think could be meaningful. Great. Thank you. Thank you. Our next question comes from the line of Ritu Baral of TD Cowen. Your question please, Ritu. Hi, guys. Thanks for taking the question. Just as a follow-up to Ellie's, actually, I wanted to drill down on the tolerability part of her question. As we look at the humanized mouse models and the preclinical models that you have run, are they good read-throughs? Sorry, are they good sort of models for which to predict tolerability of compounds going forward, and have you generated any data to suggest differential tolerability? A quick second question was, Erin, you mentioned the combination strategy a few times over, one for 601 and one for the 600 series. As you look at that, what are your favorite candidates for combination? Are you thinking about the THR-β combination with TERN-601 in the near term, and are you thinking of mechanisms even beyond the GPBAR and mechanisms that are in-house? Thanks for the questions, Ritu. The first question had to do with the prediction of tolerability based on preclinical in vivo models. Mm-hmm I think I need to acknowledge that there are limitations. Mice can't report nausea, and there are different triggers in the vomiting center with mice, certainly. We've looked to those models primarily for efficacy and activity as pharmacological models. For toxicity, we've, you know, we, as I mentioned, we're on track to start our phase 1 program later this year. That would mean that, you know, toxicity data to date, support going into the clinic. We think that this will be important to monitor in clinical trials, and we're very well aware that these small molecules do require titration, just as injectables do. We'll be very carefully approaching the titration scheme in our clinical studies, to ensure that, you know, there's not an excessive safety signal that merely has to do with administration of the drug rather than anything inherent to the drug itself. Our combination strategy, I think, is very interesting. You asked about what our, what our favorites are. We like all of our ideas, actually. You asked about 501 and 601 specifically, in terms of 501 being our THR-β agonist. Ritu, as you know, 501 is in a phase 2 program right now for NASH, so it's more advanced in our pipeline compared to 601, which is still a preclinical asset. Nonetheless, we, you know, we've shown some interesting data today on 501 combined with an injectable peptidic GLP-1, and that's certainly a program that we think could be initiated in the near future as maybe a first wave combination. We, I think, something like an oral GLP-1, either 601 or something else in the 600 series, plus a GPBAR small molecule agonist or with a THR-β, could be a potential future combination. We'll of course, need to see our GLP-1 program mature into the clinic first, to understand where the GLP-1 anchor drug could be in performance with that regimen. I think you also asked about other mechanisms of action, which are really fascinating. We're seeing an explosion of data in this area. We at Terns are always on the lookout, for opportunities to bring in, new discovery and development programs. We'll be keeping an eye on that space and thinking about, what our internal chemistry efforts might be able to bring forward in the future. Great, thanks. If I could squeeze one quick follow-up in. Erin, as you talked about the 600 series, and distinct scaffolds, what advantage do you see, in approaching the target with alternate scaffolds? Is it from an efficacy perspective, or again, a safety tolerability perspective? Thanks for taking all the questions. Sure. With the differentiated scaffolds that we're pursuing, Ritu, we are looking for increased potency, which we think might give us more flexibility in the clinic ultimately. Great, thanks. Thank you. Our next question comes from the line of Corinne Jenkins of Goldman Sachs. Your question please, Corinne. Thank you. Maybe one for Dr. Hampasch. As you look forward for several years, it does seem possible that you'll have many therapeutic tools available for the treatment of obesity. How do you envision making treatment decisions based on the different clinical profiles of those drugs or based on patient characteristics? I'm just curious how you think this could evolve with, you know, multiple agents on the market. Yeah, treatment decisions, if I want to answer that question first. Certainly it will, to a large extent, depend on who the patient is that I'm working with here, and how he responds to the treatment choices that we can offer to him, and how I can improve health beyond losing weight is certainly a factor in that as well. We know, in particular, the GLP-1 receptor agonist class certainly has an expectational coming with it, that we are impacting not just obesity, body weight, but cardiovascular health in particular. It's a complex decision. It always involves a personal individual assessment, and together with the patient in front of me, before I'm offering a treatment choice. I hope that addresses the question that you had? Yeah, that does. Thank you. Then maybe for Erin, just how should we understand the mechanism of action that underpins the enhanced weight loss we see between 501 and 601, particularly given you don't really see any weight loss in the THR-β agonist on its own? Yeah. This was an unexpected and interesting finding, Corinne. Thanks for the question. We're digging into that mechanism right now. We have some hints just based on the pattern of weight loss in those mice, the NASH diet mouse model. It appears that mice have continued weight loss and perhaps at a faster rate in the additional, in the initial first few weeks of therapy, and they return to normal feeding patterns sooner when the THR-β agonist is added to the GLP-1. We see this as maybe a synergistic effect, where there could be effects of thyromimetics on energy expenditure in a positive fashion, so that as people lose weight just by caloric deprivation or GLP-1 agonism, they reach a metabolic set point where the body burns fuel less efficiently as a way to sort of regain weight. We think that THR-β may be perturbing that mechanism, returning the organism towards a more normal state of energy expenditure, as we see increased food take despite greater weight loss when the THR-β agonist is added to the GLP-1. Helpful and interesting. Thanks, Erin. Thank you. Our next question comes from the line of Sylvan Tuerkcan of JMP Securities. Your question please, Sylvan. Yeah, thank you for taking my question, and thanks for the great presentation here with the details on obesity. Just a big-picture question regarding, you know, building a portfolio of several oral pills that you can maybe mix and match together, and how that compares to maybe, I would call it an arms race with the injectables, where, you know, now we've seen with Lilly, a triple agonist that really reduces weight but may have some baggage on the side effect profile. How do you contrast these two, and why are you so focused on giving this, I guess, oral portfolio? Thank you. Thanks so much for the question, Sylvan. Yeah, all these different injectable peptidic drugs are just really fascinating on how they're changing the field and the amount of weight loss that can be obtained through these different mechanisms. We continue to see an issue with access to these medications. If you're using biologic molecules that have expensive manufacturing processes, mostly require refrigeration, need for injections that patients may have difficulty tolerating over time or may not be able to access over time, and we're also seeing that there may be constraints within the payer space here. Oral small molecules will presumably be much simpler to manufacture, thereby decreasing cost of goods. So we think these could be more affordable approaches for patients. Not all patients are interested in injectables, so this gives them another option of orally administered therapy for obesity, should, you know, any one or combinations of our pipeline candidates move forward. Great. Thank you. A quick follow-up, for the TERN-601 trial that you showed a slide on today, are you gonna be testing different dosing regimens, and is there a once-per-day dosing, you know, feasible based on your mouse data? Thank you. Sure. Yes, we will be doing multiple doses, both in the single dose portion of the study and in the multiple ascending dose portion of the study. We'll be very mindful, we think, of titration in the multiple ascending dose portion to just to better understand overall tolerability of the molecule. You know, we selected the molecule, Silvan, TERN-601, based on its potential for once-daily dosing, you know, on the basis of preclinical data overall. Of course, as Marcus mentioned, the proof is in the pudding, we're looking forward to seeing that human PK and the potential for once daily. Great. Thank you so much. Yeah, just to be clear, I think you may have been asking, are we testing multiple dosing schemes, right? I think we will be testing multiple titration schemes, but the intent is to test once-daily dosing here. Thank you. Our next question comes from the line of Eric Joseph of J.P. Morgan. Your question please, Eric. Hi, hi, guys. This is Noah on for Eric. Thanks for taking our question. Our question is regarding the TERN-501 that you showed in combination with semaglutide. Was wondering how you're thinking about the opportunity to improve the responder rate to currently available GLP-1s with the combination of 501. Thank you. Thanks for the question. These are, you know, new sort of, hot off the, hot-off-the-presses data, that we're pretty excited about. We're in the process actually of discussing, both internally and externally with experts about how they would envision, you know, a THR-β being used on top of a GLP-1. I think we could see multiple potential uses here, either increasing, you know, adding a THR-β to patients who may have plateaued on a GLP-1 therapy, maybe, achieving greater weight loss when both are initiated, together, for example. We think there may be excitement for being able to use even maybe lower doses of a GLP-1 combined with a THR-β, and, producing similar weight loss, which would allow potentially more patients to be treated. We're thinking about a number of different options here, and are happy to speak with lots of people out there in the field about how they think this, these data could be applied to the clinic. Yeah, and just adding on to that, right, I think as we think about TERN-501, there are potential benefits beyond purely weight loss, right? As we think about other metabolic factors, right, that are associated with the metabolic syndrome more, generally, right, including everything from lipid and triglyceride elevations, liver fat content, right? Of course, you know, we are very familiar with the NASH market. So I think the nice thing about a THR-β is that when combined with the GLP-1, yeah, great to see additional synergy on or potentially additional synergy on weight loss. I think also being able to present a multitude of benefits here for patients who are likely experiencing, a lot of these symptoms, across the metabolic spectrum will be quite important. Thank you. Our next question comes from the line of Graig Suvannavejh of Mizuho Securities. Your question, please, Greg. Hi, this is Avantika on for Greg. I just had a question about the bar that you're setting internally for yourself for TERN-601 once it enters the clinic. Obviously, there have been a lot of data that's come out this week that has been setting a much higher bar, especially with retatrutide hitting the 24%. Is your internal bar that you're setting closer to the data that's been seen by oral GLP-1s, or are you setting it closer to some of the injectables? Thanks for the question, Avantika. Recall that TERN-601 was selected based on the potential for it to have activity at least as good as danuglipron. We'll be looking for weight loss over 28 days rather than over the course of 6- 12 months, where you're correct, we have seen large amounts of loss, weight lost. I think we'd like to be competitive with the weight loss that's been shown with other oral small molecule GLP-1s that are still in development. Sen, I don't know if you have anything more to add. Yeah, thanks, Erin. You bring up a good question, which is, I think there's an implied question there, which is: Is there gonna be a single solution for all patients, for all people that are overweight or dealing with obesity? I think the answer that we're hearing from a variety of stakeholders is that there will be a multitude of solutions for different populations of people, depending on the extent of weight loss or weight management that's needed and other comorbidities. As I think as we think about what the future of this landscape would look like, I imagine that there will be continue to be injectable therapies, whether we're talking about GLP-1s on their own, GLP plus GIP or maybe even triple Gs. I think You know, but the, some of the potential challenges are that all of the drugs are gonna have to deal with is the balance between efficacy and tolerability. As we think about tolerability, you know, there's sort of the medical tolerability, right? There's also financial toxicity, right, which is which has been a big issue for a multitude of indications. You know, our goal is to try to present solutions that can get to broadest, most appropriate set of people possible. That's trying to deal with everything from manufacturing costs, once-daily dosing, convenience, and things like that. Long answer to your questions, I don't think we or anyone developing orals are necessarily trying to compete with the injectable therapies. I think we're trying to offer solutions to make these mechanisms available to a much broader population in a, in a manner that is safe and appropriate for those patients. Okay. Thank you. Thank you. As there are no further questions in queue, this concludes today's conference call. Thank you for participating. You may now disconnect.