Okay, I think we can go ahead and get started. Hi everyone, my name is Nicole Martucci. I am an associate here at TD Cowen. Thank you all for joining us this afternoon. Right now, we have Amy Burroughs, CEO, who's going to be giving us a corporate presentation on Terns Pharmaceuticals. Following the presentation, we'll have a question-and-answer session from both Amy and Emil sitting here right next to me. Why don't you take it away? Great. Thanks so much, Nicole, and thanks to the entire TD Cowen team and to all of you who are in the room and those who are joining us on the webcast. I will be making forward-looking statements today, and we'll refer you to the disclosures on our website. I really want to talk about how important the work that we do at Terns is to us, to really make revolutionary medicines that make a difference in people's health. Like many of you, I've been impacted in my family by cancer and other serious diseases. I lost an uncle to CML in the late 1990s when many of these therapies were developed. We often, at Terns, invite patients in to tell us about their perspective and why the work that we're doing is important. The other day, we had a woman named Joanie, who's about the same age that my uncle would be today, and actually reminds me of my mother. She really has spent her life battling CML and really fighting for better care and therapies for patients. She was so nervous about coming to talk to us. She really put herself out there because she cares so much about developing better therapies. She's excited about TERN-701 and what we could potentially do. She really came to let us know about the challenges and the burdens of the disease and the therapies, and that patients can't wait. It is really our vision to deliver revolutionary therapies to patients like Joanie. Before this conference, we announced some updates on our two clinical programs where you're going to see data readouts in the second half of this year. We have two clinically validated molecules with large indications where we have these readouts towards the end of the year. In CML, we put out our first clinical data in December. We said before this conference that trial enrollment data continues to look good, and we had an update around just another point of differentiation for TERN-701 in terms of drug-drug interaction profile. I will tell you about that today. We really expect TERN-701 to be a best-in-class, really the best treatment for CML. You will see data in the fourth quarter of this year that reads through to the registrational endpoint. For TERN-601, our oral small-molecule GLP-1 receptor agonist, we released differentiated data in September. Before this conference, we released data on our trial design and really our bar for success and how we see this drug as being competitive in terms of weight loss, but really differentiating on tolerability, which we see as an unmet need in the market. You will see data from that phase two trial in the second half of this year. I will also say that we have cash in our balance sheet through into 2028 that gives us the runway to continue to interrogate and generate this clinical data. I'm not going to talk too much today about the rest of our pipeline just due to time constraints. I will say that all of our assets at Terns were developed internally. We have two other programs that are meant to be used in combination with GLP-1 receptor agonists to enhance weight loss and provide additional metabolic benefits. Let's dig into CML. CML used to be a fatal disease, and therapies for BCR-ABL inhibition have transformed it into a chronic disease. Imatinib or Gleevec was revolutionary when it came out in 2001, and additional second-generation active-site tyrosine kinase inhibitors came out in the 10 years after that that improved on efficacy, but still had significant tolerability concerns. SCEMBLIX, or Asciminib, was approved and is an allosteric inhibitor, which means that it binds to a different pocket, the myristate pocket, and the allosterics are more selective than the active-site inhibitors. Really moving efficacy and safety to the upper right quadrant on this slide, we see an opportunity for TERN-701 to continue to move that to the upper right in a meaningful way for patients. I'm going to talk to you today about how TERN-701 could be a better therapy in terms of efficacy, safety, and convenience, all important for these patients living with this disease for life. On efficacy, we have preclinical data that shows potency greater than SCEMBLIX, and we also see improved PK in our human studies and the ability to have better target coverage. In our initial data that we released in December, we showed you a rescue of patients who had failed SCEMBLIX. On the safety front, it's quite remarkable. We saw no dose-limiting toxicities in our phase one, no dose reductions or AE-related discontinuations. We're excited about the possibility of better safety. We also, just before this conference, released data about important drug-drug interactions that you see commonly with TKIs and that you see with Asciminib that we do not see with TERN-701, which offers both improved safety and improved convenience when you do not have to think about changing a patient's chronic medication such as a statin. We also know that we have improved convenience. Asciminib is dosed in many patients twice a day and requires a three-hour fasting window, which twice a day becomes six hours of fasting, quite challenging. We have once-a-day dosing for all patients and dosing without regard to food. To go over our phase one trial that is going on now, we have completed dose escalation, and we are continuing to enroll patients in the backfill cohorts as we move to dose expansion. We allow for the enrollment of second-line patients and also those who have failed asciminib. We will be guiding shortly as we begin the expansion trial in the second quarter of this year to the doses that have been chosen. I will say that since we've seen such a good safety profile and no DLTs in dose escalation, this allows us to move to a higher end of the dose range in expansion. CML is measured in terms of BCR-ABL transcript levels, which is a measure of disease burden in the blood. This is a logarithmic scale that is on an international standard. You see at the top, as you go down, decreases on a logarithmic scale in terms of those transcript levels. We're getting down to a 0.1% or lower is called a major molecular response or MR3, and lower than that is considered a deep molecular response. Major molecular response is the registrational endpoint in this indication. Our data cutoff was in October of last year. We put this data out in early December. We had 15 patients enrolled in the trial as of the data cutoff. The top two are the first two doses. Those are both efficacy and safety evaluable, and patients at the 400 milligram dose, the three are safety evaluable. They were not on the trial long enough to be efficacy evaluable. We provide you on the left side with the fact that we have a median prior lines of four. Many of these patients are highly refractory and start with high baseline transcript levels for BCR-ABL, and many of them have also seen Asciminib or Ponatinib. On the shift table, we have a highly encouraging major molecular response rate of 50%. This shows you if we had that patients in the green are those that improved their category. From that chart that I showed you, they had a log change in their BCR-ABL transcript level to change categories. Those in the blue had a stable category, and we did not have any patients in the red that moved down in terms of their MMR category. Because it's early data, we're also showing you for patients that started with a high disease burden, meaning more than 1% transcript, we're showing you the best decrease in their transcript level over time. Seven of eight patients had a decrease in transcript, which is quite encouraging given the high baseline transcripts that you see at the bottom, the fact that three of these patients had mutations and many of them had seen Asciminib or Ponatinib. Let me show you two patient case studies. This is a patient with an eight-year history of CML who lost their response to a second-gen TKI, Dasatinib, went on arguably the most effective second-gen TKI, Ponatinib, had a suboptimal response, was transitioned to Asciminib, also a suboptimal response, but also intolerance due to elevated liver function tests and lipids. They were enrolled in the trial and put on TERN-701 at our lowest dose of 160 milligrams. After three cycles, deepened their response and did not have the tolerability issues that we saw with Asciminib. This is another patient that has a 10-year history of CML and has seen every second-generation TKI, had tolerability issues to all of them that you see along the top. I will also point out that it took them over four years to get to a deep molecular response on Bosutinib. They eventually lost that response and were put on to the second dose of TERN-701 at 320 and had an incredibly rapid response to deep molecular response, which is better than major molecular response. This is the type of response that we might expect to see as we move to earlier line patients. This is not a response you would typically see in such a refractory patient. On the safety data, we talked initially about a remarkable safety profile here where we do not see dose-limiting toxicities or treatment-related discontinuations. Also, of note, something you see frequently with Asciminib is elevations in amylase, lipase that we did not see, or changes in blood pressure. We'll also talk in a minute about the drug-drug interaction profile. A way to compare across studies is to look at dose escalation and the incidence of dose-limiting toxicities, which are measured in a standard way over 28 days. For TERN-701, we did not have any dose-limiting toxicities. You see on the right the dose-limiting toxicities for Asciminib or SCEMBLIX. This is new data in advance of the Cowen Conference. Here is data from our Healthy Volunteer study with these two pathways where we see about more than 60% of small molecules are metabolized in this pathway. It is an interaction listed in the label with SCEMBLIX and many other TKIs. With these two pathways, you also have an impact on most statins, which impact about one in three patients. This is going to allow us to further accelerate our clinical trial enrollment and make it safer and easier for physicians to prescribe TERN-701. This is our PK profile from our healthy volunteer study where you see dose-proportional increases in exposure in a linear way. You also see an 8-14 hour half-life, which compares to 5-9 with Asciminib. You also see no clinically significant difference in exposure with food, and you see a 60% decrease in AUC with Asciminib. I will just note here that we have multiple clinical studies ongoing. We have a partner in China that has an ongoing phase one study. We also have our Healthy Volunteer study and the phase I Cardinal trial that we've been talking about that's moving to expansion, which is starting here in the second quarter. We expect after expansion to be able to move quickly to a pivotal trial. We're looking at a second-line plus trial similar to what SCEMBLIX did in a third-line plus population. We are also looking at, we believe, that we can move quickly to a front-line trial. Both of these trials are well within the capabilities of a biotech company. Just to be clear in terms of the opportunity that we see here for patients, it's really to be used as a front-line therapy or a second-line therapy when an allosteric is chosen after a generic first or second-generation TKI. We are not looking as our primary market to go after allosteric or Ponatinib or other failures. We're really looking at, there are 100,000 patients in the G7. This population is expected to triple by 2040. We think that TERN-701 will best serve patients by being used in the front line and where for cost reasons, a first or second-generation drug, which are good drugs, could be used in the front line that when about half of those may need another treatment option, that they are moved to TERN-701 as the best allosteric. From that, I'd love to move to telling you more about TERN-601, our oral GLP-1 receptor agonist for obesity. This is new information for the Cowen Conference. If you look across the landscape here of molecules that have 12-week or further data, we really see the efficacy is fairly comparable across the different molecules in development. What we also see is there are multiple titration steps to get to the target dose and pretty large fold changes. For example, starting at 5 milligrams and going up to 120 milligrams in 12 weeks and beyond in further studies. This is really because these drugs are difficult to tolerate. Despite those steps that are taken, we also see incredibly high rates of GI adverse events, particularly nausea and vomiting, which in such a primary care population is less than ideal. We see the next generation of GLP-1s really coming along and being able to improve on that. We think that's a great opportunity for TERN-601. Let me talk a little bit about why. In our 28-day study, we had about a seven-fold change. We went from 100 milligrams to 740 milligrams, and we got there very quickly in five steps. We already have a simpler titration regimen. We also saw really good weight loss. In most of these studies, you see about 3-5% weight loss. We saw at the higher end of that range at 5.5% and also good weight loss at the 500 milligram dose. We saw a competitive safety profile despite having titrated at the two highest doses every three days. We had no AE-related discontinuations, interruptions, or dose reductions, and the majority of GI-related events were mild. Just looking at the curves for a minute, you also see a linear and dose-related response in terms of weight loss. I will note that at the 240 milligram dose, we had no GI AEs, no nausea, no vomiting. At the 500 milligram dose, we saw all GI events were mild. We're looking at what will happen to these curves as we go out to 12 weeks because we don't see a plateauing of the curve. I'll also mention that we saw good PD effects at all doses. We told you when we came out with the data that we were going to explore all of these doses in phase II due to these PD effects and weight loss effects that we saw. Why is that? Why is TERN-601 different from other oral GLP-1 receptor agonists? It's about the pharmaceutical properties. The pharmaceutical properties translate to prolonged absorption at doses above 240 milligrams and a much flatter PK curve than what you see with other molecules. We also have low refraction. We have a lower overall exposure in the plasma. Yet with that, we get 24-hour target coverage, and we get competitive weight loss. Why do we think that is? We think that it's with these effective drug levels in the plasma. We also get higher levels in the gut because of the higher dose. We see preclinically 5x exposure in the gut. You have GLP-1 receptors in the gut that stimulate the vagus nerve and affect satiety. We have really designed the phase II study to interrogate these questions and to look at tolerability and weight loss over a 12-week period of time. We are looking at non-diabetics and looking at the% change in body weight and the exploratory endpoints of tolerability. This is a U.S. multicenter study. We get asked a lot about these being higher doses than what you see with other GLP-1 receptor agonists. In terms of pill burden, it is not a pill burden. We have 100 mg and 250 mg tablets. Patients are taking their drug once a day with one to three pills. We also do not have a food effect with TERN-601, so they can be taken without regard to food. In terms of the titration regimen, we're interested in this first cohort where we go very quickly from 100 mg to 250 mg, which we know was tolerable in our 28-day study. We're interested to see the level of weight loss and tolerability that we see. We're particularly interested in the 500 mg dose, which is why we have two different titration schemes. We think that could be a good balance between efficacy and tolerability. You'll also note the slower titration regimen is also something that we heard from physicians that they would really like, something where they can say, "Here's a bottle of pills. Take this for a month. Here's another bottle. Take that for a month. It's a very simple titration scheme. For the 500, take two of these for the next month, and then you're done. Much simpler than a complex titration scheme where you might have to have a blister pack or something like that. It's also very easy for patients if they need to to titrate down. Of course, we're also exploring the high end of the dose range given the weight loss that we saw and also a fairly simple titration scheme there. In summary, with TERN-601, we're really looking to have competitive efficacy and superior tolerability with this simplified titration scheme that we've looked at. We already have, you know, at most four steps to the top dose in this trial and a much smaller fold change. This is really due to the pharmaceutical properties of the drug and the higher dose. I will wrap up by saying at the end of the third quarter, we had $373 million in cash, which gives us runway into 2028. As I said earlier, runway to really interrogate these molecules. We are excited to be here. Thanks to everybody. Thanks, Nicole. I will turn it back to you for questions. Okay, great. Thank you so much. Let's start off the questions on your 701 program in CML first. You guys are going to have data later this year in Q4, I believe, that encompasses longer-term efficacy data. What are the general expectations for that? How do you plan on presenting it? Will it be patient-specific like you did the earlier data that you presented, or will it be just overall MMR rates? I can take that. Yeah, thanks for the question. Yes, it'll be a larger data set and more an aggregate data set that includes patients from, you know, both escalation and expansion, which we aim to start in the second quarter. With respect to the type of data, it is really going to, we intend it to give both us and the external stakeholders sort of a clear idea of what a six-month MMR could look like for the molecule in terms of making that as strong a read-through into what a randomized study could look like versus a standard of care 2G TKI control arm. That's the goal. At the end of this year, we really see effectively phase II proof of concept that then informs the development path for a pivotal. Moving, once you guys move forward, you have plans to evaluate it. Well, you're evaluating the path forward for it to be either second line or potentially a first line. Is there an option for both of those trials happening at the same time? Yeah. What is the kind of path of that look like? What are FDA expectations for that path forward? Yeah, so we very much see this as a front-line drug. To have a label similar to Asciminib or SCEMBLIX, we see the ability from a regulatory standpoint that this is a well-trodden path and that will likely start with a second-line trial, but move potentially quickly and in parallel to a front-line trial to have that broader label and that that is not doing something that has not been done before. In fact, given the use of first and second-generation drugs in the front line, from a regulatory standpoint, we do not have to go up against Asciminib, that we do a similar trial to what Asciminib did for Ask for First. Great. There are a lot of different medications, you know, on the market for first line, second line, even third line. What drives, what is the biological reasoning that patients are not responsive to some therapies? How do you think Terns 701 can really kind of differentiate themselves and potentially be, you know, both a second-line and first-line therapy? I'll let Emil, as the oncologist, take that one. I guess my mic is working out. Yeah, it's a great question. Regarding your first question around what's the biological rationale? I mean, look, BCR-ABL is fundamentally the primary driver of this disease for the duration, the majority of its duration. You know, the remaining sort of the main sort of next paradigm shift in CML is getting patients to the deep molecular response, right? We talk about MMR, which is critical, obviously. For patients to get to sort of a cure state, you want to get to even deeper molecular responses like the response Amy just showed in that patient who got to rapid DMR. Why is that? Because studies have shown over and over again that the faster you get those responses and the longer you maintain those responses, the more likely it is that the disease won't come back. What is preventing that from happening today? It's really not the biology, it's tolerability. When you look at the active site drugs, you consider that 50% of patients will have to switch therapy over the course of the first five years. When you aren't able to maintain that dose intensity due to tolerability issues, that not only limits the dose intensity, but also limits, because of their limited therapeutic index, the degree to which you can cover the target. The stronger you cover the target, the better you get those deep responses. That's exactly what allosterics can do. We know that asciminib has clearly shown that already in terms of the phase III data in both third line and front line that it showed better efficacy than certainly Gleevec and then numerically better efficacy than the 2G TKIs. We think there's still an opportunity to further leverage the wide therapeutic index of this class with 701, specifically by dosing higher to attain multiples of target coverage higher than even what asciminib achieves at the 80 milligram while maintaining that excellent safety profile. That's really the unmet need that we think the front line patients still need to get to that 701 can achieve. Great. Thank you. Just kind of a follow-up on the molecular responses that you guys have seen. A deep molecular response encompasses both an MR4 and an MR5, correct? Correct. Is there a big clinically meaningful difference between those two? Like, is the ultimate goal an MR5, or is it just in general a deep molecular response? In general, a deep molecular response. No study has shown that if you're MR5 versus 4.5 versus 4 that you get to. It is more of a categorical achievement. The thing is, at least, you know, we have data from sort of the stop TKI studies that were done in the 2010s or so where they've shown that, you know, if a patient generally can maintain a deep molecular response for at least two to three years, you can do a trial of stopping the TKI. Obviously, you have to monitor for those. The main reason, the impetus to stop TKI is patients do not have tolerability issues. Arguably, if you have a TKI that they have essentially no tolerability issues and they can take it like any other medication they take, you know, you might argue that that might not be a need, right? That is really why DMR is an important milestone. We think that the profile of 701 is probably so far the best profile to improve the probability of patients getting there. Absolutely. The tolerability issues with the currently approved therapies that you keep mentioning, I guess, is that the discontinuations off of those therapies, is that mainly due to the food effect that you guys do not see? Or is it, what exactly is the reasoning behind patients? If I were to break that 50% down into the reasons, approximately half of that is treatment failure, meaning, you know, loss of response or suboptimal response. The other half is intolerability. That anecdote was a great example. You saw the patient cycle through Gleevec and all three 2G TKIs. They were only able to remain on each of those drugs for about a year before they got to some AE that caused them to switch. Those are sort of the two big categories. In the category of treatment failure, given the allosterics are now available as a new class, most likely we think the paradigm is going to be a class switch. That speaks to that second line population that we talked about where, you know, we expect still half of front line patients to get the 2G TKIs, which are great drugs. They're going to be generic. If 50% of those patients have to switch, they would likely want to switch to an allosteric. They would want to pick the best allosteric. Therefore, both of those opportunities are really good for us. Regarding food effect, it's certainly not convenient for patients to fast around dosing, but we don't see that as a major reason for discontinuation. Patients would much rather prefer a drug where they didn't need to do that. We have a question from the audience. If you're not seeing any of the liver problems that you mentioned for 701, what are the most common side effects for your drug? I think the first question is, what is the average time to relapse? That's not a one sort of number answer there. I could tell you that we could look at it as median duration of therapy. You know, in the context of patients who do not meet the response milestones that are set by sort of the European Leukemia Net or other things like NCCN, patients should in general be at at least a two log reduction by 12 months, ideally a three log reduction by 12 months. The percent of patients who do not get there with the current 2G TKIs and Gleevec is about 15%-20%. That is what I mentioned, that, you know, that 50%, approximately half of that is that lack of response. Therefore, you know, that is about, you could argue one year to two year timeframe for those patients who will not. Now, tolerability plays a part in that too, because one reason why patients might not get to that deep response is because they keep having to interrupt a drug during that critical first year because of tolerability issues, right? The median duration of therapy in a patient who cannot tolerate their drug is about 12 months. The median duration of therapy who has zero tolerability issues as a front line therapy is five years. That is a huge difference. That gives us an opportunity to take that 50% that is currently the problem with 2G TKIs and shrink that to maybe 10%, to maybe 15%. That is a huge impact in terms of getting that many more patients to tolerate their therapy to where they can get to those response milestones. Your second question was, what are the AEs that we see with our drug? Right now, we do not really see a signal in terms of an AE that is emerging as sort of a drug-related effect in our safety data so far. We are very encouraged by that. Great. Thank you. Just with the last minute that we have here, I really want to get in a question about the 601 GLP program. Okay. I would really love both your thoughts on maintenance dosing for patients, you know, that struggle with obesity and need to lose weight. How do orals kind of fit into that paradigm and specifically 601? Yeah. I'll start with a comment on that and then turn it over to Emil. You know, I think orals are a great therapy for maintenance for lots of reasons, right? From, you know, ease of manufacturing, being able to take it long term, not having to store it in a fridge, sort of things like that. Also just ease of administration. With Terns 601 in particular, that's part of the reason that we think tolerability is important and titration is important. Some people do not know, but if you are on a GLP-1 receptor agonist, regardless whether injectable or oral, if you go off of that drug for sort of more than a cycle, you may have to start titrating all over again. Titration is not something that somebody only has to go through once. There may be times that people do not want to be on their drug because their daughter's getting married or something like that and having to go back. You know, we see orals as a very important therapy for maintenance. In that, tolerability and ease of use is going to be really important. Emil, anything to add to that? No, I think I totally agree with everything you said around the maintenance piece. I will just add that maintenance is just one use case, right? We think that, you know, the use of orals as a starting therapy is probably going to be the most commonly used approach. We think that, you know, there's a large segment of this population that do not need to lose 20% of their weight in a year. That sort of mild to moderate obese BMI group, they do not, you know, need fancy combinations. They want a drug that they can take without complex titrations, get to a target dose with excellent tolerability, and have a steady pace of weight loss. That's exactly what TERN-601 showed. We think that that's where the drug is probably the most useful. Great. With that, we are slightly over time. Thank you guys so much for the presentation. Thanks, Nicole. Yeah, absolutely. Enjoy the rest of the conference, everyone. Thanks. Thanks.