Okay, I think we're at 8:45 A.M. Are we good to go? Okay. Good morning, everyone. I'm Ellie Merle, one of the biotech analysts here at UBS. Very happy to have Terns Pharma here with us this morning for a fireside chat. Also joining me from UBS is my colleague, Jasmine Fels. From Terns, we have Scott Harris, Chief Development Officer, and Justin, the Head of IR. Did I get your title correctly? You got it. Okay, awesome. Well, thank you guys so much for joining us. I know we always guess around which we should focus more on, CML or obesity. I think we'll start with CML just given the data's coming up, but I do think it's interesting that you have got two very different programs where we've seen some interesting clinical data. So starting with CML, maybe just you know, high level, where do you see the role for another allosteric inhibitor, given sort of the you know, use of Scemblix to date? Great. Well, thanks first of all to Ellie and Jas and the whole UBS team for the opportunity to participate in your conference today. And so if we're starting with 701, I think it's an exciting program for us at Terns. And just to give a little bit of background on the indication, CML is a chronic indication. It's approximately 9,000 new patients in the U.S. annually, and it is a lifelong disease and lifelong therapy that manifests in a decades-long treatment for patients with CML. So, allosterics represent a novel and exciting class of therapeutics for CML. Traditionally, the prior standard of care has been active sites, and we view that the allosteric class is an interesting mechanism, novel mechanism that can deliver both improved efficacy and safety for patients through the binding of the myristoyl pocket. We've seen a couple of interesting studies from asciminib, Scemblix, and both third line as well as front line showing improved efficacy as well as safety in terms of MMR and MMR response rates. We're happy to be with TERN-701, the second potential allosteric to market right behind asciminib. Mm-hmm. Great. And one of the questions that I get most from investors, around your CML program is just what the unmet need is still in CML, particularly, I mean, given Scemblix as well as, you know, many generics. Sure. So I'll start with the active site generics. And I think as we look at those, prior generation therapies, chronic use, as I mentioned, decades-long use of those therapies, because of the off-target effects with some of those, active sites can lead to adverse events. And indeed, we are seeing a good amount of switching, patients who are on active sites traditionally to switch for intolerance or resistance, etc. And as we speak with physicians and patients, there remains a need for improved therapies, both improving on safety as well as efficacy. We believe that allosterics do represent that option for patients. As we think about, of course, we see Scemblix having achieved approval in newly diagnosed CML patients as well as previously treated CML patients. We see a couple of different options for TERN-701 to be a value, a valuable option within the treatment paradigm. So I think there are a few things we're working on with respect to TERN-701. I think the first and most important is potential optimized dosing. So we think about dosing higher. We think we can drive even better efficacy responses in patients, with TERN-701, dosing higher. There's also an opportunity for us to have a single dose of TERN-701 to cover a broad mutational spectrum. So we think about having a single dose of 701 at a higher dose that can cover both wild type as well as different mutational variants of CML. We also think that we can potentially see a differentiated safety and DDI profile that, of course, will need to go into later stage studies to evaluate that, but that remains also an opportunity for us. And as we've shown earlier this year, we do see a lack of food effect with respect to 701. So we think having a lack of food effect where we can avoid the fasting requirement that asciminib has can be a nice benefit for patients with respect to compliance and also convenience with respect to their quality of life. So I think those in aggregate together represent multiple ways of TERN-701 being able to be competitive within the allosteric space. Mm-hmm. Great. Makes sense. And so you're guiding for initial data from your phase I, in December. First, can you go over the trial design and, you know, how the inclusion criteria inform the potential opportunity, across different lines? Yeah. So the CARDINAL phase I study design is a typical phase I oncology design. It consists of a dose escalation phase followed by a dose expansion phase of the study, and as you're aware, we do have a partnership with a company in China, Hansoh, that's developing the molecule for the Chinese market, and so as far as a starting dose in the CARDINAL study, we were able to leverage the body of data that Hansoh had generated with the FDA to allow us to actually start at a higher dose than we had initially planned, and that was based on the safety and tolerability profile that we saw at that dose, as well as signs of pharmacologic activity, so we're really starting the study at a really good dose level. As we dose escalate and complete dose escalation, we will select at least two doses from the dose escalation to move into dose expansion and increase the N at each of those dose levels. As far as the inclusion/exclusion criteria, the population is really going to be a second-line plus population. We are having patients that have at least seen one second gen TKI. We are also allowing the use of prior asciminib. But as you would expect from a phase I oncology study, there's gonna be a wide range of patient profiles coming into the study. A wide range as far as number of prior lines of treatment, years of treatment, as well as baseline mutational status coming onto the study. We will get to see how the drug you know plays out in a variety of different patient profiles. Mm-hmm. Great. And in terms of specifics around number of patients and, you know, follow-up time, what should we be expecting from this data set in December? Yeah. So I think we guided to. We did a webinar back in August with our chief medical officer and one of our KOLs from Germany. And at that time, we were stating to expect about 10-20 patients enrolled in the study, as well as five to 10 evaluable patients. We're still on track to present that next month. You know, this will be probably the earliest data set that has been presented in the CML space. And so that was one of the rationale behind doing that webinar back in August was really to set the expectations on what an early data set in CML looks like. Mm-hmm, and sorry, how much follow-up do these patients have? It's gonna vary. Mm-hmm. And so we may see in the 5-10 evaluable patients, we may see patients, a subset of that that have seen three months of follow-up, a subset that have seen more, and then a subset that have seen less. So it's gonna be wide range. Mm-hmm, and you alluded to it, but you did host a webinar that helped us understand how to evaluate early data in CML. Yep. What should we be looking for at this update? What is good data here and what you're looking to see? So obviously the phase I study, the primary endpoint is safety and tolerability, so that is the first thing that we'd be looking at, but because this is an early data set, we're not talking about MMR rates or comparative MMR rates to other products, and so as far as what we'd expect to see encouraging in this is really signs of activity in the way of movement in BCR-ABL levels. And so you know we'll because of the wide range of patient characteristics that will be enrolled in this. Really context matters when you're looking at what we're seeing. And so, you know, as an example, if your hypothetical patient comes into the study having four or five lines prior treatment, with a baseline, BCR-ABL transcript level of 50%, you know, taking that patient down to 25%, which is a 50% reduction, in their transcript, even though it's not a one log reduction, that is a really encouraging sign of activity in this patient population. And there's really not a direct correlation between the activity that you would see in a patient like that, and the activity that you would expect to see in an earlier stage, like a second line. So there's not a direct translation between that. So seeing activity like that, in this data set, would give us encouragement that in, as we move into earlier lines of therapy, we'd see even greater activity. Makes sense. And I guess just looking forward, so if we do see, you know, this reduction, and sort of deepening of response in these patients, what are the next steps for the program? Yeah. So we think both second line and first line indications are of great interest to us. You know, we are always looking for ways to accelerate development to really get drugs to the patients that need them as quickly as possible. You know, I did mention the Hansoh collaboration that we have. You know, as that body of data continues to grow, we will continue to leverage that in our drug development pathway. You know, as far as front line indication goes, I think our expectation is that we'd be able to run a similar study to what Novartis did with asciminib. Mm-hmm. Absolutely. And maybe just, you know, thinking longer term, are there any scenarios where you would run a head-to-head study? With asciminib? Yeah, or. No. Any of the standard of care? Yeah. Ultimately, a standard of care head-to-head would be required for approval. Mm-hmm. But, we do not expect that a head-to-head with asciminib would be required for approval, because I think that the, you know, that the second gen and the first gen active site TKIs are still gonna remain a standard of care. So our expectation is that that would not be required and we're not planning on doing one. Mm-hmm. What are the most common causes of switching in the real world between sort of, you know, lack of response versus tolerability, safety, DDIs? Yeah. And then, I mean, the reason I'm asking that is also in part in thinking about the patients that we'll be seeing data from in December. So it varies. You see patients switching for a variety of reasons. You see clonal evolution of the CML, and so you see resistance mutations that pop up. And so that's one reason to switch. You do have tolerability issues that come up. You've got heme tox as well as non-heme tox that pops up. And so, you know, it's not, not uncommon for a patient that's on lifetime therapy to go through multiple cycles of different TKIs. Mm-hmm. Great. Makes sense. And, maybe just last one on CML, and feel free to ignore this question and dodge it, but the latest commentary on when we might see more from Hansoh? I cannot answer that question, you know. Hansoh is their own company and it'll be up to them to when they release data. Mm-hmm. Sorry, with that, maybe we'll pivot to the obesity program and Jasmine, I'll pass it to you. Absolutely. So, switching over to obesity, I guess let's just start with the data. So you recently reported phase I data in the third quarter. So can you kind of just highlight what you saw for us? And are there any particular aspects of the data that you think deserve more focus or are important? Sure, so I'll do a recap, so we announced positive phase I topline data in September. We saw statistically significant and dose-dependent weight loss across our doses up to 4.9% placebo-adjusted. TERN-601 appeared very well tolerated with unremarkable safety profile despite a very rapid titration scheme that we intentionally ran in phase I, so I think the things that we are excited to highlight for the investors, not just that profile, but as well, unique properties that we discovered with TERN-601, which include low solubility and high permeability, which we believe represent a pretty unique approach amongst GLP-1 receptor agonists, so I think as we step through phase I with that dose ranging in hand, we're very excited to move forward to phase II and explore different titration profiles, which may continue to improve our tolerability for TERN-601. Yeah. Absolutely, and I think just we've seen so much in the obesity space. Recently, we've seen orals and duals and triples. Yep. And so kind of can you talk about how you think that your data is early, but how it kind of compares and fits in with other early data that we've seen? Sure. So we've been very consistent in saying that 28-day data is early data, right? I think it's good enough to show that we have an active GLP-1 oral GLP-1 that's competitive. We've always thought about the benchmark of activity for a drug like this to be 3%-5% with placebo-adjusted weight loss. And we're happy to be on the upper end of that. But again, there's only so much we want to read into a 28-day phase I study. So we're really excited to move forward to phase II and look into what we can continue to learn there. But with 28-day, I think we've checked that box. We're ready to move on to phase II. Yeah. Absolutely. And I think the tolerability is obviously a really important aspect here. And so can you talk about kind of the unique properties of 601 and kind of how you think that impacts your tolerability, maybe go over your titration scheme that you did in phase I and, what you're planning on doing in the future to kind of improve the tolerability that you see? Sure. I'll start off, and maybe Scott, you can add in. But I think what's interesting about TERN-601 is, as we mentioned, the unique sort of profile of having low solubility and high permeability. We think that gives you a prolonged coverage of target in 601 while being an immediate release formulation. We intentionally titrated very quickly across phase I. If you look at the 500 mg and 740 mg cohorts, we up-titrated over a span of three days to really, we stepped up every three days to really get to that high dose and in that short amount of timeframe. So I think we've seen at the lower doses, being able to slow down that titration did lead to improved tolerability profiles. So that's an interesting thesis that we'll prosecute in the next study. Yeah. And I'd say that even with the extremely rapid titration that we did in the phase I study, the tolerability profile was as good or better as others have seen in the context of a 28-day study, so obviously, as we move the program forward into longer-term studies, we will slow down that titration, and you know, expect to see an even better tolerability profile. Yeah. Absolutely. And so you very recently announced plans to initiate a phase II. So can you go over kind of that design and how you settled on that specific design for your next step? Yeah, so in earnings yesterday, we did guide to initiating a phase II study in early Q2 of next year. That study will initially be looking at cohorts of 12 weeks duration, and we will use that data to inform subsequent cohorts. As far as the actual study design goes, we're not guiding to that right now, but we do plan to come back and release more information on the study design before we start that study. Right. Okay. That makes sense. And, data, I think you said later in 2025? We would have data second half of 2025. That's exciting. Yeah, it is. Wonderful. I guess how are you thinking about kind of taking a step back and thinking about the broader landscape, you know, where an oral GLP-1 fits among all the other mechanisms? Are you thinking about kind of initiation of therapy, maintenance therapy? Where do you think the specific place is for orals? I mean, I think the exciting thing about the obesity space is I think there is a lot of optionality, and you know, as we move the program forward in development, and learn more about the molecule, I think there's a lot of options for us to pursue. Maintenance therapy is one of those options. Combination therapy is another one. I think we will continue to you know monitor the space and the evolving landscape, and really see where our oral can fit in and differentiate itself. Right. Absolutely. That makes sense. Thinking about future development, you know, as a small company, kind of how are you thinking about long-term your plans for this program, whether this is something that you think having a partner would be valuable for of your strategy going forward in these larger indications like obesity? Yeah, it's a good question. We've talked about our strategy underlying the company. I think the best way to characterize that is we'll look for ways to get drugs to patients as quickly as possible. As we think about obesity and the vastness of the indication, right, I think it makes sense to consider partnering and thinking about ways we can accelerate and find the right partner with resources to help push drugs through, especially late-stage development. We're always open to that. But I think as we sit here, we are capable and excited to run the immediate next step, which is a phase II. Right. In the phase II, is it too early kind of to ask, you know, what you would be looking to see to give you some confidence from a 12-week study? I mean, I think continuing to see, you know, weight loss on top of what we saw in the 28-day study, as well as an improved tolerability profile, the two aspects to take a look at. Again, you know, these clinical trials in the obesity space, there are artificial constructs, if you will, you know, 28-day study, the 12-day study. And so really the design of these studies is really to optimize maximum weight loss and tolerability at the same time. And as you get into longer-term studies, you continue to slow down the titration to improve the tolerability. You know, we are taking forward the full dose range from the 28-day study into the phase II program. And you know, I was just at Obesity Week last week and spoke with a lot of KOLs. You know, a lot, a lot of the feedback we received was really focused on an oral GLP with a really clean tolerability profile. As these orals move it out of specialized, you know, the injectable space where they're administered, prescribed in, you know, specialized clinics into the community setting where you've got primary care practitioners that will be prescribing oral medications, tolerability profile becomes really important to them. And so that is one aspect to keep in mind as we move the program forward. Right. Absolutely. That makes a lot of sense. I think also your point about combinations is interesting. So you do have 501, your THR-β, and then you've presented some interesting preclinical data there showing synergistic effects with the GLP-1. So can you kind of go over, you know, what you saw there and how you think those two mechanisms play together to improve the effects that we see on weight loss and other metabolic parameters? Sure. Yeah, you're right. We released some data over the summer showing that TERN-501, our clinical stage THR-β, paired with the GLP-1 did indeed drive improved weight loss than either agent alone. And we were also pleased to see that there was a relative improvement of lean mass reduction in the combination arm, on a relative basis versus either agent alone. So, we're very excited about TERN-501 as a potential combo agent in obesity. It does not necessarily need to pair with something at Terns. It can pair with really any GLP-1. So we continue to evaluate that, and we're excited to see where 501 can fit in the broader paradigm. But we do see that it brings some exciting value adds to GLP-1 alone. Right. Okay. That makes sense. Have you, can you say anything about kind of your plans going forward? Are those still undecided? I mean, is there any color you can give on potential next steps either for 501 within Terns or externally? Yeah. It's consistent with what we've said before in terms of we're continuing to evaluate TERN-501 application in metabolic and cardiometabolic indications. But that's as far as we've said for now. Right. Okay. That makes sense. And then I guess thinking about other metabolic indications, you obviously have a lot of experience in the NASH, MASH space seen recently, quite a bit of data from GLP-1s in that space. Do you think that there is a place for an oral GLP-1 kind of in that space or in other metabolic indications that down the line you'd be interested in pursuing? So I think we've, with respect to TERN-501, we've said we've paused NASH development on that, and the reason for that is really the current regulatory landscape with respect to at least THR-βs is quite onerous, we think, for late-stage clinical studies. So with respect to at least 501, we've announced halting further development in NASH for GLP-1s. I think that's something that remains to be seen. I think we're currently focused on the obesity effort as we have it currently in plan. Right. Absolutely. And you also have your 800 series, your GIP modulators. So can you talk a little bit about that and where you are in development with those? Sure. Terns, the TERN- 800 series is a GIPR modulator discovery program. We've talked about prioritizing a GIPR antagonist as part of our priority for discovery efforts. That remains a discovery stage asset. We'll have more to say about that as we advance that through the discovery process. Right. And can you go a little bit more into kind of the decision-making about prioritizing the antagonist? Yeah. So I think we looked at both internal and external validation of the biology and the science, as of course it's rapidly evolving. And so we, I think we prioritized an antagonist just based on what we were seeing internally as well as the developing external scientific learnings. Also, as you think about it from a design and chemistry perspective, it's a little bit easier to antagonize the target versus having to agonize it. So I think there are confluence of different factors that led to our decision to prioritize the antagonist first. Okay. Yeah. That makes sense. I guess where does that kind of fit into your combination strategy? And where could you think that would fit with your programs or other things externally you might be interested in? Yeah. I think GIPR modulation fits well with GLP-1. I think that's the probably obvious answer. That's not going to surprise anybody. But we'll have more to say once we continue to develop the pipeline. But right now we think of it as a nice combination option with GLP-1. And not necessarily our own GLP-1, but it could be combined with any other multiple GLP-1s, so. Right. Absolutely. That makes sense across the landscape. Thinking about kind of starting a phase II now in obesity, I guess, have you said how many subjects that is going to enroll? We have not guided to any specifics on the study design right now, other than we'll be starting that in early Q2 of next year, and as I mentioned, prior to initiation of that study, we will release more information on what that study looks like. Okay. That makes sense. Thinking about your current cash runway, I guess, where are you with that, and with your planned study start? You know, how far does that get you down the line? Yeah. So as of September 30th, the cash balance is $373 million. And that takes our runway into 2028. And I think that covers a substantive amount of the catalysts that we've been talking about, especially around, of course, 701 next month and 601 INDs going into next year. So the large bolus of those catalysts are covered, and we'll be able to say more as the programs continue to evolve. A question I get from investors, and I'm not really sure I know of a precedent for when a compound hasn't gotten composition of matter, but maybe just the latest in terms of, with 601, where you stand in terms of IP. Yeah. So we continue to feel confident about our ability to gain IP coverage on 601. We are just past phase I. So I know there's been some attention directed to IP around 601. But I think we are at the right stage of IP prosecution relative to where we are in terms of clinical development. And we remain confident in that ability to gain coverage. Mm-hmm. I know this is a tricky one, and feel free to skip it. But how can we think about the timing for when we could get clarity, since this now has become somewhat of an investor question? Yeah. I don't think it's appropriate for us to give guidance on timing for that. Somewhat out of our hands. Yeah. Yeah. Yeah. But maybe just, you know, turning to the structure, there's obviously been changes versus danu, based on what we've seen from the PK/PD. So fair to say that you're quite confident that you will be able to receive composition of matter? I'm allowed to say that the active and ongoing IP efforts at Terns are robust, and we have confidence in our ability to gain coverage for 601. Got it. Good try. It's good. Sorry. I feel like Mark is on the line that is probably wants to kill me. Hi, Mark. Maybe just going back to the conversation around partnering and business development, you have two programs that are in pretty distinct therapeutic areas, and you know, an interesting opportunity in CML and also an interesting opportunity in obesity. How do you think about the prioritization across these two and, you know, where you might see potential for a partner and, you know, priorities between those two? Yeah. So it ties in a little bit with what we talked about before. We think within obesity being large and vast opportunities, it makes sense to potentially partner that with a larger pharma partner that has resources to really accelerate development path and fully prosecute those molecules. I think on the other side of the spectrum, we have CML and TERN-701. That is a program and an indication where we've seen small companies like Terns be able to prosecute that and get those to the finish line on our own. And I think that's within the purview of Terns to advance a molecule like TERN-701 and CML to the finish line. It's possible for us. We saw that last with Ariad, so we know it's possible. I think that's sort of the spectrum of how we look at the different programs. But I think we'll be opportunistic as interest arises. I think we're always guided by the principle of getting patients drugs to patients as quickly as possible. So that's always in the back of our minds as we think about how to advance our molecules as quickly as possible. Mm-hmm. Absolutely. And in terms of, you know, how you can drive the most value and in terms of timing, what do you think makes the most sense in terms of obesity, you know, in thinking about, you know, waiting for further phase II data, and, you know, where you see the key value inflection points? Yeah. I mean, we will have data from the initial 12-week cohorts next year. So that is the next value inflection point that we view with the program. Beyond that, we're still deciding what makes sense. But I think that, you know, in 2025, releasing data on the initial 12-week cohorts from the phase II program would be the next logical step for value. Mm-hmm. And walk us through the steps between now and starting the trial in the second quarter next year? The operational team is in, you know, full operational mode, to select CROs, select sites, manufacture drug. So all of those activities are ongoing. We are on track to initiate that with first patient in early Q2. Mm-hmm. Great, and turning to CML, I know we talked about, you know, potential next steps, but can we talk about timelines a little bit more? So say we see this data in December, and we do see, you know, kind of on these shift tables an improvement, in terms of the deepening of response across these patients. You know, how quickly do you then move forward into potential larger studies? Going from dose escalation to dose expansion, so we expect that dose expansion will start sometime early next year, and then the next logical time to really release data on that program would be probably sometime towards the end of next year. Mm-hmm. So next year, we expect to have two additional data catalysts with our programs, first with the or both with the 701 program and with the 601 program. Mm-hmm. Got it. And, you know, thinking longer term, you know, should we be thinking about 2026, we could be looking towards the start of a pivotal program? That is within the realm of possibility. Yes. Mm-hmm. All right. Great. And with just a couple of minutes left, anything else that, you know, you think that we should hit on in terms of, you know, Terns? You guys have a unique model in terms of your internal chemistry, things that, you think people should be paying more attention to. Yeah. I think it's been an exciting 2024 for us. The execution remains robust at Terns. We turned over the data card for TERN-601. We're very excited about the phase I data there and moving that into phase II in early Q2 next year. And of course, we're looking forward to sharing information, perhaps the earliest readout CML data that has ever been seen with TERN-701 in early December, early next month. So I think the clinical execution remains terrific at Terns. And we're excited to continue sharing exciting data for both patients and the broader community. Mm-hmm. All right. Great. Well, excited to see the data. Yeah. We will too. Thank you both for joining us. Thanks so much. Yes. Yeah. Thank you.