Conference Transcript - TERN 2026-03-02

Speaker 4

Good afternoon, everybody, and thank you once again for joining us for the 46th annual TD Cowan Healthcare Conference. I'm Jeroen Werber from the biotech team, and it's really a great pleasure to moderate my first fireside chat with Terence Pharma. To my left really needs no introduction, Amy Burrows, a CEO, and to her left also needs no introduction, Andrew Gengos, Chief Financial Officer. So, team, thanks so much for joining us. Well, we appreciate it.

Speaker 1

Thank you so much for having us, Jeroen.

Speaker 4

So there's a lot going on in CML. We'll dive into 701. The data really looks super promising and interesting And it's obviously drawn a lot of attention But let's maybe just zoom out Quickly and kind of talk about CML in general. There's a lot of Both innovation going on not not as much innovation going in the stamp area, which is specifically what you're going after But there's a lot of options in frontline There's the historical first-generation GLEVAC, there's a second-generation compounds as well, obviously more tangible talks. More competition now in terms of Semblix moving into second line, moving into frontline. And at the same time, physicians are beginning to try to really figure out TFR. And at what point do you stop therapy and based on potentially DMR. So can you talk about the shifting landscape a little bit and you know, because that's gonna weave into your data and then how you think about clinical development.

Speaker 1

For sure. And thanks again, Yaron, for having us and to the TD Cowan team. I will also say that we will be making forward-looking statements and to refer to our website and our filings for more information. So, CML is a really interesting area in oncology and different from many other indications. It became a chronic disease with the approval of GLEVAC in 2001, and there are multiple approved therapies as a first-generation, second-generation, now Allosterix, also a third-generation active site. In the front line, it's really the first and second-generation active site TKIs and Asiminib. And despite all of these options, there remains tremendous unmet need. And this is not just in the area of efficacy, but also in the area of safety, particularly if you think about a young CML patient, perhaps diagnosed in their 20s or 30s, they could be on these TKIs for life. And so safety, whether it be rates of arterial occlusive events or pleural effusion, other things that you can see with these TKIs, that's a big concern. One of the big areas of excitement with allosteric is that they're much more selective, therefore leading to a better safety profile. And we have already shown an even better selectivity and better safety profile than others. I will also say that really the dream in oncology is to offer functional cures and that's possible in CML and we know that there's data that says that if you drive faster and deeper responses that you can get higher rates of what they call treatment-free remission. This means that a patient gets to a deep molecular response practically undetectable levels of the BCR able fusion protein and if they stay there for three to five years they can be taken off of drug and you see if their transfer levels come back if they don't come back for about a year most patients are effectively cured for life and that would be a dream and that's a goal particularly for young patients in the frontline setting and we don't see enough treatment free remission today and if a drug that gets faster deeper responses could do that that is that

Speaker 4

would again be the holy grail do you have any sense what percentage of patients these days get to DMR and then are taken off therapy in that setting I

Speaker 1

know that about 15 to 20 percent of patients get to a treatment free remission I'm not sure we have the data around how many attempt that and once

Speaker 4

you get to DMR you're then therapy stopped and you're monitored initially every three months is it every six months for about is it for about a year and then you go to an annual follow-up what's the latest standard I'm not I'm

Speaker 1

not sure actually if you get to a deep molecular response you're still monitored for that three to five years if you go off therapy I believe you're monitored very closely and if those levels start to come back you immediately go back on the therapy that was working for you. Okay. When physicians are now,

Speaker 4

a seminary is now moving to frontline, it's got as much as a 15% share, potentially even 20% share now. About 25. 25. And what's driving that option against other kind of older,

Speaker 1

even generic options? Yeah, it's really because it's been shown to be a better drug. safety is a huge driver because when we went from imatinib to the second gen tkis you were trading off safety for efficacy and often the higher risk younger patients were getting the second gen tkis and older patients were getting imatinib and then also just patients who are more cost sensitive and may not be able to be on the branded therapy but you know the allosterics and the simonib are really bringing the opportunity to get safer than both and better efficacy than imatinib and you know they have not been shown to be more effective than second generation TKIs and there's more and more data coming out that people believe that efficacy is in the same ballpark but we believe that they are getting this kind of uptake because you can get the second gen level of efficacy without, you know, things like a 30% rate of pleural effusion with the satinib.

Speaker 4

And how important is it, the nice element to the allosteric inhibition at the stem site is really shutting down potentially the emergence of resistance? How important is that in front line? Or is it still very much a safety question to your point? And you reserve that activity in immune population for a later line.

Speaker 1

Yeah, I think it's that in CML, resistance mutations are not the biggest driver. of patients becoming refractory to their therapy so we don't really have data across you know active sites versus a seminib and emergence of of mutations but mutations are not the big driver in CML and the big unmet need for patients we know in the front line say for mirror state pocket mutations that's about four to seven percent in the front line over a three to four year period

Speaker 4

So it's a slow, slow emergence.

Speaker 1

Yeah. You know, our ability, and we've already shown in a simonib resistance mutation, F317L, we've shown a patient that was resistant to a simonib and responded to TURN701, and we think, you know, a different molecule with higher target coverage could, and we see pre-clinically too, more potency on some of these mutations.

Speaker 4

And so, and by the way, for the audience, if you have any questions at any point, feel free to raise your hands, and happy to take them. So let's maybe talk about a little bit about your cardinal data in phase one. It was a dose-finding regimen. At this point, you're expanding at 320 and 500, and I think you went 160, 320, 400, and 500. Correct. I think we saw about 63 patients, right, at ASH. The data looked really good, including, to your point, you had data obviously in prior first-line, sorry, first-generation, second-generation failures, and even in patients who had acetaminib. And they failed either for tolerability or for efficacy, including some data now in the mutations. And looked really good, an achieved MMR was 75%. The achieved DMR was 36% at the expansion cohorts. And MR2 actually looked very, very good at 62% as well. I think you said at ASH that you had 85 patients or so enrolled, or more, or at least 85 patients?

Speaker 1

As of early December, we had 85.

Speaker 4

As of early December. So as you think about the stage in development that you are now with 701, and maybe what we should see this year in terms of data, maybe kind of walk us through your thinking.

Speaker 1

Sure. based on those 85 patients that we had enrolled in December, we knew that we would have the data to submit to the FDA and speak to them in the middle of the year about our dose, so to pick a dose, we need to look at exposure safety and exposure efficacy. We've already seen that safety looks pretty good and we don't see an issue with the higher doses in the ASH data that you saw, so assuming that holds, what we'll really be looking for do we see a benefit on efficacy at the higher dose we also want to see at least 20 patients at each of the 320 and 500 for six months so we were able to you know calculate that and that's how we're able to guide to meeting with the FDA mid-year and we will talk to the FDA about our pivotal trial designs and plans we hope to gain their alignment to move directly into a second line plus pivotal we do not need to finish everything in the cardinal one to phase one to to do that and we're also going to talk to them about our first line pivotal and how quickly we can move to first line okay and I think I think the

Speaker 4

data and I'm just going through memory of the 63 patients at ash I think 10 were at the 160 so essentially 53 were higher and 320 was already like 21 patients and I can do the math to get how many 500 but if you need 20 at six months I mean you're getting there pretty quickly while you continue to enroll correct so you should be in a in pretty good shape what drives the decision as to which dose to take forward is it MMR is a DMR what's more

Speaker 1

important to you it's really much it's it's about looking at the different subgroups normalizing across different covariates and really looking at what kind of efficacy response we see in terms of categorical shifts it's not so much you know MMR is more about the regulatory endpoint and we're really looking at categorical shifts in transcripts and we do do we see something

Speaker 4

different at 500 and we see at 320 so in parallel you're now doing the study in the 20 patients or at least 20 patients are going to be who are mutants and for you're actually using the 500. Yes. Two questions on that, is that potentially down-the-line label enabling or is that sort of what, because Asimonyme did the same, roughly you know patient numbers, and then secondly you're choosing 500 so it sounds like you're fairly comfortable with the safety, so why not even decide if things look good to take the 500 forward to a pivotal? For all

Speaker 1

all patients for all patients yeah if we see that if we see that efficacy response at 500 we would like to go to 500 and have that dose for all patients you were asking about the mutation cohort whether that's label enabling the 20 patients we're looking at really is signal seeking these are rare patients we're not sure how long it will take us to enroll we think you know every patient will actually be informative like the F317L patient that you saw in to date in the escalation and we'll take that and expand it so a simonib got their label with 45 patients and so we'll expand the cohort from there based on what we see initially to enable putting that into the label and

Speaker 4

at that point that goes into the clinical section of the label I believe

Speaker 1

so yes I don't think it will be at first approval okay so that's something that

Speaker 4

you do in parallel so it sounds like based on the initial 20 patients you then potentially decide to expand yes and so you have a few years to continue

Speaker 1

to do that in parallel yes can't guide the timing on that we can say that would not expect to see data from that cohort this year just based on it will enroll fairly slowly these patients are difficult to find yeah and so the data I

Speaker 4

I think typically you release data at medical meetings, right? So the natural ones are probably ASCO, EHA, and probably ASH. As you think about different subgroups that we might see data from, sort of what comes to mind and what's important?

Speaker 1

Subgroups of patients in terms of, it's really similar to what we showed you. The things that affect how a patient, what kind of response rates you expect to see, baseline transcripts is is big and you see that even from the assignment of data how much lower they saw in the 10% plus baseline transcripts whether or not they've already seen drugs like a simonib and panatinib is is a big deal what treatment line they're in is so well it will be similar to what you have seen to date and what you saw at ash okay so maybe before we talk about the

Speaker 4

phase two child design in second line and then potentially front line can can you maybe zoom out for us and think or help us understand differentiation of 701 relative to a cinnamon nib on maybe coverage of the stamp site maybe potentially how the exposure relates to then potential music coverage of mutants

Speaker 1

and an overall tolerability yeah so for that you can look at the data that we presented EHA last year we looked at potency on these mutations and in preclinical assays we also talked about this we had a webinar in September which I think people still find informative it was really an educational webinar on how to interpret phase 1 to CML data where we talked about the preclinical data supporting higher target coverage for turn 701 and I think it's important to note too the reason that we're able to get that higher target coverage is not just you know the different drug even even at the same exposures we see higher target coverage it's also the fact that we see such good safety that enables us to go up to 500 and get much higher target coverage and the other piece that we talked to people about is you know there could be a different way it's binding to the pocket and other things that make it a it's it's a different

Speaker 4

drug and from the pharmaceutical properties for the drug can you talk about simonib it does have a food effect and I believe at this point you don't and you're not you're not expecting it can you can maybe discuss that in the PK and what you've seen on the PK of the drug well we're confident that we

Speaker 1

don't have a food effect we are dosing in this trial without regard to food people have asked you know why does that have that with a simonib and I'm told they got unlucky.

Speaker 4

And so at this point, you don't need to do a food effect study? That's not your expectations?

Speaker 1

No. We've done our food effect study.

Speaker 4

Okay. So as you, any questions from the audience by any chance? Renee?

Speaker 1

Yeah, so the question was just for people who may be listening, if resistance mutations are not the primary driver, what is the driver of patients being refractory for efficacy. We think that it could be target coverage, but we don't know for sure what it is.

Speaker 4

I mean, is it also, is there any data on time and therapy in relating to tolerability? And if you're not really getting to the right dose or you've got a dose reduced and you're on therapy for a short period of time, then efficacy is probably not optimal.

Speaker 1

There is a huge, you know, our CMO, Emma will tell you, and I'm sorry you could not be here today. Our CMO, Emma will tell you that there's a big relationship here between tolerability, safety, and efficacy. If you can't get to the right dose, then you won't have the same level of efficacy. And we think that the 80 milligrams of Asimunib is kind of at the bottom range of where they need to be in terms of target coverage. And we are multiple folds higher.

Speaker 4

So one of the questions that I think is out there and we've started getting is the phase one cardinal data that we've seen, again, has been really, really strong. It's still early in development of the drug, and there's been some questions about as you continue to enroll, your level of confidence that that level of efficacy will continue to hold up and really show differentiation, obviously against the seminary, but obviously also against some of the other competitors versus expecting some

Speaker 1

decrement any any thoughts about that yeah absolutely so we've talked a lot about confidence intervals so you know I sitting here today do not know what that you know that magic sort of top line number is going to be the next time we release date and we ultimately get to the end of the trial we are incredibly confident based on the robustness of the data that we showed you at Ash it'll be within that confidence interval which is meaningfully superior to a seminib and

Speaker 4

everything else out there and I think you've said specifically even given your maybe just give us a little bit more thinking and your views on the constant intervals of the data you've seen and what that relates to even a seminibs higher end of their confidence interval I think I believe yeah there's

Speaker 1

no there's no overlap so I think we have a great slide in there whether you're looking at all doses or you know what you really care about is the dose we're going forward with we're showing now 320 and above because it's going to be 320 or 500 ultimately you know when we release data you're going to be interested in you know if you're going forward at 500 if you're going forward to 320 what does the efficacy look like there and you know so far 320 and above are there's no overlap in the confidence interval do you want to add anything to Oh, that's right.

Speaker 4

So we actually went and we did an analysis where we could, because some drugs have kind of lumped all their phase one data together across doses, sometimes it's a little harder to tease everything out. And Semblix, from the early data to the late data, they actually had a gain. So obviously, number one, we know from the data, right, that the longer you're on therapy, the better you do. And two, Semblix actually stepped up from phase one to phase three. response went up incrementally. Basu was flattish, and Eclusec is the only one that actually had a decorant from the phase one that they had to ultimately the phase two, you know, ten years ago. So at least we have two cases out of three where the data was the same or even got better. Now that's not within the same protocol, that's moving from one protocol to another. Yeah, I can't speak so much

Speaker 1

to the Panatinib data, but the Assiminib data actually is relatively consistent. So the phase one data is 24 percent. The phase three data is 25 percent. So we actually think that it's a comparable patient population with the same end point or almost the same end point. It's at 24 weeks and we can calculate that towards the end of our trial. So we think it will translate very well.

Speaker 4

examples in the past. So now moving to the phase three trial design, give us maybe your latest thoughts on second line and do you need to have a simonib as a control, given that they've never actually done a second line study, they've done a third line and front line, and then what that

Speaker 1

means for the front line strategy. Yeah, so I'm actually going to start with the last part of the question, which is based on the data we've seen, we think we should have confidence to compare ourselves to a simonib and win and we think the best place to do that is the front line the front line is frankly the majority of the the market and the way that the the way that the ask for first trial was done with a simonib they had stratifications of second gen tkis and imatinib and our thesis today we haven't decided we're not guiding specifically to it but we're leaning into having a simonib in that control arm of standard of care for the second line plus trial we're still considering it from a regulatory standpoint we don't think either trial will require a simonib being in the control arm in the second line plus will definitely have patients who've been refractory to a simonib and we think that's important especially given how many patients are being put on frontline a simonib today and that's an important proxy not only for being then used in the second line but also for efficacy there could be reasons not to put a simonib in that trial in terms of speed and cost and getting to market but we're still considering it and we'll let you know

Speaker 4

later this year after we talk to the FDA so you know as you think about Semblix's frontline studies to your point it was an all-comers and then they did the primary also against either first generation or second generation to your point what drove the win in the overall population was really the activity against Gleevec they didn't beat the second gen drugs if you also then add Semblix to your first line study and maybe it's too it's too premature to even discuss it is there going to be going to be head-to-head sort of an all-comers and then looking at its subtype excuse me there would likely be

Speaker 1

a primary endpoint similar to theirs where it was a blend of the two as more data has come out you know and they're asked for first trial they did see a a trend in better efficacy there's a trial called ask for start where they see very similar efficacy and closer to 60% or high 50s for a simonib so we're not sure there's a big difference between second-gen TK eyes and a simonib and we're pretty confident fact that we're seeing frontline type of MMR achievement and DMR achievement in these incredibly difficult to treat patients gives us confidence for winning in the front line okay any questions on that yeah just repeat so people can hear it have you thought about combining with an active site molecule so based on the responses that we're seeing we don't see a huge need to do that and add frankly the cost and the toxicity of an active site there could be a small group of patients who have particularly poor prognosis where that could be done in the future whether it be in combination with 701 or with a simonib, but in terms of us getting to market, particularly before we're approved, that's not a priority for us at this point. So we have not guided to EHA. In fact, we've said that dose selection is going to be done sort of mid-summer with the FDA, so we will not be talking about that until we speak to the FDA about it. We had 85 patients in December, we'll continue to enroll rapidly, and we will use all of those patients as we look at the exposure efficacy and exposure safety. As I was saying before, it's not just six-month MMR, it's really looking at categorical shifts. So it should be more than 85 patients included in that analysis.

Speaker 4

Right, it's almost we should think about it as almost like two sets of data, sort of the ASH update in 63 patients, and then another opportunity is to update us on the bigger end.

Speaker 1

Yeah, I mean, I think it's going to, really the bigger end is what you're going to care about, and you're also going to care about, as we said, the go-forward dose and what the efficacy looks like there. We're going to have a lot more than the 63 patients as we go through time with a valuable for efficacy.

Speaker 4

Yeah. And you said data, I believe, in the second half, you said that you'll update?

Speaker 1

We said by the second half, so we haven't guided specifically. Okay.

Speaker 4

Yeah. EHA is straddling FDA communication and decision and update. When you're thinking about, there's two other active site competitors, one's approved in China moving into phase three, and another one is the Enliven compound as well, I think they're planning on potentially starting their pivotal sometime later on this year, second half or so. When you're thinking about differentiation and overall profile, sort of what comes to mind?

Speaker 1

Well, when we think about overall profile, particularly in the front line, they're looking at efficacy and safety primarily and we think on the safety front that an allosteric has been shown to be much more selective and will generally be preferred over an active site for safety the efficacy the the physicians don't think of it so much as sort of what class you're in but really about what is the data support and and what can I what can I expect the data that we saw at ash and that we expect to continue to evolve is really in a different tier from what we're seeing from other therapies in development we think those are good therapies and important to have additional options for patients we see turn 701 really being used primarily in the first and second line where we are going to be competing with the generics in the front line and potentially in

Speaker 4

with a seminum and in terms of the maybe just remind us in terms of tolerability

Speaker 1

what was your most common AE the most common AE was hematologic AEs however they were significantly lower than you see with other therapies and we did not have in terms of non hematologic AEs we didn't have any particular signal or or high degree of A's we only in this data set lost one patient due to an adverse event and it was joint pain and fatigue and do and which dose was that in I'm not sure I don't think we said okay we don't though if you look at the safety

Speaker 4

we don't see a dose relationship yeah in terms of you know pre-clinically your activity are there any mutations where the drug is shown to be kind of have better activity or is it you know equal across all mutations yes particularly

Speaker 1

some of the mutations where you see non mirror state pocket mutations and resistance to a seminim like the f3 1 7 L that we talked about and that when you

Speaker 4

see you see good activity you see good coverage well we see good coverage

Speaker 1

preclinically and now we've seen a response in a highly refractory patient and that patient failed a seminib despite going to double the dose of the seminib and also failed enliven and responded to turn 701 so maybe just to

Speaker 4

remaining one one and a half minutes or so when we've been speaking to a lot of clinicians and some of them even big KOLs have expressed a little surprise how well Asimunib has been doing because some of them you know in academic centers sometimes they want to start with the older drugs a new kind of typical escalation keep the best drug for last the community though is obviously gone on board and using the drug you know fairly routinely what

Speaker 1

do you think really explains that it's funny as a commercial person I find some of this market research and CML to be challenging you know it took Novartis quite a while to start their frontline trial I think because some of what they were saying but yet what they've done are different so and I think there's also a lot of patients I think most people in this room if you got CML and needed a frontline therapy you'd want to pick the best therapy and so I think that there actually is a lot more even in the time that I've been in CML I've seen the KOLs and the academics really change their perspective as they get more experience with a seminative and I expect the trajectory with a simonib to continue to go up and frankly for them to prepare the market for us for an even better therapy because to your point I

Speaker 4

mean if it's it's not so much a music a resistance issue with but it's tolerability and frontline but that also leads to better efficacy now ponatinib is a great drug but the efficacy the tolerability is a real issue right correct so wouldn't you also get too much higher DMR rates if you start with a better drug and then you have a better chance of TFR yeah I mean

Speaker 1

we're seeing DMR rates in the third line plus comparable to what anybody seen in the front line so we definitely think that will translate to faster deeper responses in the front line which yeah at least as we started out with could

Speaker 4

lead to higher rates of functional cure any maybe final last quick question maybe just timeline to some of the earlier pipeline some of it you're potentially looking for a partnership any update on that yeah for our metabolic

Speaker 1

portfolio we've really chosen to focus in oncology so we're looking to license turn 501 THR beta and turn 801 or GIPR antagonist preclinical development candidate and we are working actively on discovery for oncology small molecule

Speaker 4

targets and is that oncology broadly or hematology more we are interested in

Speaker 1

hematology but we're looking more broadly and I assume you haven't given

Speaker 4

any timelines and potentially partnering some of those early assets no great team thank you so much good to see you we appreciate it thank you guys all for

Speaker 1

being here nice to see you thanks everybody thank you