Welcome, everyone, to the J.P. Morgan Healthcare Conference. We are pleased to have with us today Terns' management team, Amy Burroughs, CEO, Emil Kuriakose, CMO, and Scott Harris, CDO. With that, we'll let Amy have the stage. For logistical purposes, please hold your questions till the end of the presentation.
Thank you so much, Sanjibita and the whole J.P. Morgan team. It is lovely to see many familiar faces in the room. Thank you all for a lot of great support this year, as we've had a fantastic year. I will start by saying that we will be making forward-looking statements, and I would refer you to our SEC filings and our website for more information. So, as I said, 2025 has been a fantastic year for Terns, and 2026 is going to be just as exciting. We have the potential to be at best in disease therapy, and we're going to be putting out additional data in 2026 that reaffirms that position in the CML market. We've seen really unprecedented efficacy and equally important and encouraging safety and tolerability profile that sets us up for really the next generation of CML therapies.
In 2026, we have patients in our trial today that will provide us with data to select a dose to move into pivotals. We'll have an interaction with the FDA to discuss our trial design and look to move quickly to our 2L+ trial initiation and follow that up quickly by a first-line trial initiation. We have cash of $1 billion on our balance sheet, which really removes any financing overhang for Terns between now and commercial launch, so we're quite excited about that, and again, thanks to many of you for your support and your belief in us. It's really quite a privilege to work on a special drug like TERN- 701, so for those of you who may not be as familiar with CML, we'll start with a bit of an overview.
So, CML was a fatal disease, a fatal cancer, until BCR-ABL inhibitors came along, and it was really Gleevec i matinib in 2001 that changed the disease. But there are efficacy and safety and tolerability limitations with the imatinib, which led to the development of second-generation tyrosine kinase inhibitors and third-generation that provided better efficacy, however, had more significant safety and tolerability limitations. The first allosteric inhibitor, asciminib, was originally approved in 2021 and got a front-line label for really all lines of therapy in 2024 and has been shown to be both more effective and safer and more tolerable than the first and second-generation agents. We have seen since the front-line approval in November 2024, after only three quarters, that asciminib has 22% market share in the front line. For those of you who know anything about commercial launches, that is a fast uptake.
They also have a dominant share in the second-line plus market, and Novartis recently upped their guidance to $4+ billion for sales for asciminib. However, asciminib has some limitations where we think there's opportunities for improvement for a next-generation allosteric inhibitor such as TERN- 701. So, on the efficacy front, in the patient population that we're currently studying in third-line plus, 75% of patients did not reach the primary efficacy endpoint of MMR at 24 weeks, and through the lines of first and second line, also significant numbers of patients who did not reach that MMR achievement. We think that TERN- 701, based on the data we're going to talk about in a minute, has the potential to meaningfully improve on that. In terms of adverse event profile and off-target toxicities, in their label, we see pancreatic toxicity of 20%.
This is something that asciminib saw early in clinical trials, even in dose escalation, and hypertension of 18%. Asciminib also has a food effect, so it must be taken with a three-hour fasting, so without regard to food. And their studies show that if it is taken with food, there's a 60% reduction in AUC, so it could have a meaningful impact on efficacy for patients who are not able to adhere to that regimen, and it's very inconvenient for many patients. So, let's talk a bit about really the data that positions TERN- 701 to be a best-in-disease therapy in CML. On the efficacy front, we're going to talk a bit more today about the improved efficacy we see at our recommended phase II dose range of 320 milligrams and above, MMR achievement in a highly refractory patient population of 75%.
This is really unprecedented in this disease, and I would say, you know, in talking to a lot of the KOLs and investors, folks in the community, really above expectations for what people expected to be able to see in this difficult-to-treat patient population. We also see a deep molecular response rate of 36% at these doses, which is also quite impressive, and really, the importance there is it reads through to what we could see in our front-line trial, where deep molecular response is an important endpoint when thinking about potential curative outcomes for patients with CML, and we also see in our trial clinical responses in patients who have failed asciminib, a proxy for this really being a more effective and different drug than asciminib.
On the safety front, we did not see any dose-limiting toxicities in our dose escalation, and the majority of our treatment emergent adverse events were low-grade. We did not see the pancreatic toxicity or clinically significant changes in blood pressure that have been seen with asciminib in their trials and in subsequent treatment, and on the convenience side, it's dosed once a day without regard to food, so at a high level, just to summarize the most important data coming out of this data release that our investigators presented at ASH, again, a 75% MMR achievement rate, the primary endpoint both for a phase I and for a pivotal trial, and when you compare that to the asciminib MMR achievement rates in their phase I and their phase III, we're trending at three times greater.
And I'll show you later the confidence intervals for that, where we do not see an overlap in the confidence intervals, giving us confidence in this being a potential best-in-disease therapy. And on the DMR achievement rate, also trending two to three times higher than what we saw with asciminib. And bottom line, for many of these things we're talking about, an allosteric in CML is not an allosteric, just like for the active site inhibitors. One active site has not had the same profile as others, and we really see this as a next-generation best-in-disease therapy in CML. So, let's go a bit into the data. As I said, we're going to talk about baseline characteristics and what a refractory patient population this is, pretty comparable to other phase I populations. An unprecedented response rate across all doses and 75% at above the 320.
Really, nothing notable in terms of safety: a favorable safety and tolerability profile, where we're encouraged that this will translate to a better safety profile in our label. And we also announced in December accelerated study enrollment. As our investigators saw the emerging data, we had a huge increase in enrollment. We had 85 patients as of December 8th. So, just to briefly go through our phase I/II trial design, we started in dose escalation with a range of 160 milligrams- 500 milligrams, where these patients had received two or more TKIs, where they had suboptimal efficacy or intolerance to their therapy. T315I and non-T315I mutated patients were permitted into the trial. Based on the safety and efficacy data, much of which you've now seen, we chose in April to expand at 500 milligrams and 320 milligrams.
We have this part of the trial, we're having 40 per dose cohort, and only non-T315I mutations are allowed, and it's really treatment failure or suboptimal response to one or more prior TKIs. When we look at the baseline characteristics, the three things that are most important to look at is really the baseline disease burden. So, BCR-ABL transcript levels in the blood, which are the driver of disease in CML, and you'll see that we had a high baseline disease burden for these patients entering in the trial. We also see that patients with lack of efficacy to their last TKI can be more difficult to treat, and we use a very strict ELN 2020 criteria to define lack of efficacy, and that was in 64% of patients.
We also highlight that we had more than 1/3 of patients who'd been treated with asciminib, and 75% of those had had lack of efficacy to asciminib. In terms of patient disposition, the median duration of treatment was six months. 87% of patients remain on study, and we only had one discontinuation due to an adverse event that was due to fatigue, joint pain, and diarrhea, similar symptoms that the patient had on nilotinib and asciminib. As I said, we did not have dose-limiting toxicities in escalation, and an MTD was not reached. We're encouraged by the overall safety and tolerability profile. And then to talk about efficacy evaluable, efficacy evaluable are patients without the T315I mutation or atypical transcripts. As of the September data cut that was presented at ASH, 38 patients were evaluable for MMR at 24 weeks.
And that is patients who've been in the trial for 24 weeks receiving TERN- 701. They achieved an MMR or better prior to 24 weeks. They maintained an MMR over the full 24 weeks or discontinued treatment for any reason. I'm now highlighting the baseline characteristics. I'm not going to step you through this chart. Really, the conclusion here is that the patients at 320 and above that we are going to talk about today had similar baseline characteristics to those that I showed you for all patients in the trial. And if you're interested in all of the data, we have a webinar posted from December 8th that goes through patients at all doses, and I'm going to talk about the patients at 320 and above, which are our go-forward doses in expansion.
So, looking at these doses, we see that of the patients who came in not in major molecular response, three quarters achieved an MMR. 100% of the patients that came in with an MMR maintained their MMR. And 36% of patients who were not in deep molecular response achieved a deep molecular response. And it's important to look when investors first saw our ASH abstract, there were a lot of questions about what's behind this. You know, are you getting these great rates because you have easier-to-treat patients, or are you just seeing shifts in the easier-to-treat patients? So, that's what's important here about the shift table, and I'll take a minute for people who aren't as familiar with CML. The darker blue boxes are patients who have remained stable in terms of their disease transcript category. It's measured in terms of logarithmic shifts in baseline transcripts.
Those on the right, greater than 10%, started with the highest disease burden, and you'll see that no patient had a downward shift in their transcript level. All patients were either stable or improved. And you'll see really the important piece here too is that you'll see that patients improved across all baseline transcript levels. And on the right, those that started at greater than 10%, we even had one that went to a deep molecular response. And we outline in the boxes really how we calculated that 75% and 36% for full transparency. So, how does that compare to asciminib when we look at baseline transcript starting levels? And if you look across the asciminib trial at all doses and the 701 phase I trial at all doses, you'll see that we had a much higher rate of response for those difficult-to-treat patients above 10%.
Again, really across all categories and good response across all categories. So, let me bring this to life a little bit with two patient vignettes. So, this is an elderly male with an F317L mutation. The patient has about a five-year history of CML, started and had lack of efficacy on imatinib, and had intolerance on dasatinib. Went on to asciminib, had an initial response, lost that response, was actually taken to twice the approved dose of 80 milligrams Q D or 40 b.i.d. as the approved dose, was taken to 80 milligrams b.i.d. Despite that, did not have a response. Transcript levels kept rising. And then they were found to have an F317L mutation, which is known to confer resistance to asciminib. They were put into the ELVN- 001 trial, and after nine months, were qualified as a treatment failure due to lack of efficacy.
were put onto the TERN- 701 trial at our highest dose of 500 milligrams after just four cycles, got to a major molecular response, and deepened this response. This is another way in which we have shown that TERN- 701 is a different allosteric inhibitor with a mutation such as F317L that confers resistance to asciminib, where we have seen both preclinically and clinically the ability to address that mutation, and then this is a young patient with actually more than a 20-year history of CML, diagnosed in his 20s. Did well on imatinib for a while, then had lack of efficacy. On dasatinib, developed pulmonary hypertension. Was on asciminib and had dyspnea, so intolerance, and they reduced the dose, which led to even more rising transcript levels. Was put back on imatinib, also had dyspnea. I can't say that word very well.
And then went on to TERN- 701 again at our highest dose, and after six cycles, got to major molecular response, continues to deepen their response, and remain on treatment. This is an example of how safety and efficacy are strongly related in CML and really our ability to get higher target coverage and drive responses in patients who are resistant refractory to asciminib. So, what gives us confidence that this is going to be a best-in-disease therapy? As we talk to our KOLs, they say, "This is not an early data set. This is a compelling data set, and if you look at the confidence intervals, both at the 320 milligrams and higher and at all doses, you'll see that the bottom end of our confidence interval does not overlap with asciminib.
You will also see that the asciminib phase I results are pretty comparable to the phase III results, and this is typical in CML, where we see with a similar endpoint in phase I - phase III, the results often translate. So, that gives us high confidence in this being a best-in-disease therapy on the efficacy front. We announced this week that we are opening a mutation cohort in CML. Typically, mutations are studied in a separate cohort at the highest dose. We will be enrolling in that cohort this year with 20 patients with T315I and other mutations. So, what's next? Why could 2026 be as exciting for Terns as 2025? We anticipate choosing our dose.
We have the patients in our trial now, as I said, to pick that dose in the first half of the year, to have a regulatory interaction with the FDA to propose our dose and our trial design. We expect to do a 2L+ trial versus 2G TKIs and have confidence in our ability to succeed in that trial with an endpoint of MMR achievement at 24 weeks. We'll also discuss with FDA our frontline trial. We would like to move this important therapy to the frontline as quickly as possible, where we expect to do a similar trial to what asciminib did in the frontline in their ASC4FIRST trial, where they did a trial versus stratified imatinib and second-gen TKI. We are seriously considering adding asciminib to that control arm.
Based on this data, we have confidence in our ability to win, and we also think that's important for the label and to show that this is a best-in-disease drug. That trial is the primary endpoint of MMR achievement at 48 weeks. I will say this is a fairly well-trodden path in CML in terms of the trials that it takes to get to approval. Stepping back again, we started a bit with the history in CML, and I'm going to talk about the history a bit from a commercial standpoint. When imatinib came along, it was really revolutionary in CML, and everyone wanted to be on it as there was more experience with imatinib and a need for more effective therapies.
Second-gen TKIs came along, and even in the presence of generic imatinib, managed to capture more than half the share in the frontline, really demonstrating the need for a better therapy for frontline patients, particularly higher-risk patients. As asciminib has come to market, they have demonstrated in the frontline better than imatinib, but similar to second-gen TKIs. However, they've shown better safety than both first and second-gen, really highlighting how important safety is, and I told you in the beginning how well they're doing in their launch, and you know it is projected that they will have greater than 50% market share, really repeating the history that we've seen in CML, and as 701 emerges, we expect history to repeat itself, where we expect with better efficacy, better safety, and tolerability.
We don't even have convenience on this slide, but convenience is important in terms of the once-a-day without food that TERN- 701 could have a majority of the market share in the frontline. It's also important to note that with a safer therapy, there will also be extended duration of treatment. In conclusion, we're often asked about what's exciting in 2026. As I said, our dose selection, our regulatory interactions. I might not have mentioned we will also be sharing additional data in 2026. People will be interested to see data from more patients with longer treatment duration and longer-term safety, and we expect to have guidance around our 2L+ trial design, additional guidance, and specifics around our initiation, which could happen later this year and should happen by early next year at the latest.
In conclusion, we are really excited and feel privileged to have the cash on our balance sheet, $1 billion, to be able to move this drug, this important drug, forward to patients. It gets us through 2021, which includes our first approval and launch of TERN- 701. Thank you, everybody, for coming today, and I will turn it back over to Sanjivita for any questions from the audience.
Okay. I'm going to call on people?
Yeah. Very exciting data. We're obviously thrilled to hear what you're doing for CML patients. You know, interestingly, no question that asciminib is safer, but imatinib has a number of indications beyond CML. Given the lovely safety profile that's emerging with your compound, do you see potential for use outside of CML, myelodysplastic syndrome, or anything else where patients might benefit from its exquisite profile?
Yes.
I actually forgot to introduce Emil Kuriakose, our CMO, and Scott Harris, our Chief Development Officer, and I will let Emil answer that question.
Yeah, no, that was a great question. So, the simple answer would be no, because again, imatinib is in those other indications because of the fact that it has off-target inhibition of other kinases other than ABL1 and BCR-ABL. This drug is exquisitely selective against BCR-ABL, which is really the reason in CML that we see this very nice safety profile, because it has very little to no off-target kinase inhibition. And so, as a result, you know, because of that target selectivity, we think the development will be essentially limited to CML and other diseases where BCR-ABL is a driver. Potentially, ALL is another subset of ALL that has BCR-ABL-driven biology, but it would be limited to that setting.
Thank you very much for sharing.
In terms of the regulatory pathway, is it a must to do a head-to-head comparison with asciminib, or you can do like a single or more old pathway development?
I'll let Scott answer that question.
Yeah. For the 2L+ indication, the expectation is that the control arm would be against a 2G TKI. It would not be a requirement to include asciminib in that control arm. As Amy alluded to, for the frontline study, we could run a study that's very similar to what Novartis did with ASC4FIRST, which would be imatinib or 2G TKI. Again, we don't believe that asciminib would be a requirement to include in that control arm, but for various reasons that Amy outlined, we're strongly considering including that in the control arm.
Thank you, everyone.