Good day, everyone. My name is Ryan, and I will be your conference operator today. At this time, I would like to welcome you to the Kura Oncology and Caspian Therapeutics investors call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, and if you have joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. To allow everyone the opportunity to participate, we ask that you please limit yourself to one question and one follow-up, and then re-enter the queue for any additional questions. At this time, I would like to turn the call over to Greg Mann, Senior Vice President, Investor Relations and Corporate Affairs.
Good afternoon, and welcome to the Kura Oncology and Caspian Therapeutics investor call on KO-7246 and diabetes. We remind you that today's discussion will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. I'll now turn the call over to Dr. Troy Wilson, President, Chief Executive Officer of Kura Oncology, and Executive Chairman of Caspian Therapeutics. Troy, please go ahead.
Thank you, Greg, and good afternoon, everyone. Today, we'll discuss why we created Caspian Therapeutics and how the KO-7246 data presented at EASD support our plans to develop menin inhibitors in diabetes. Joining me on today's call are Dr. Francis Burrows, Kura's Chief Scientific Officer, who led our research into menin inhibitors in diabetes, and who leads the team who discovered KO-7246, as well as Dr. Rob Spencer, Caspian's President and Chief Operating Officer. Francis will review the science behind menin inhibition in diabetes, and Rob's going to discuss how Caspian intends to translate those findings into a clinical development program. Caspian grew out of more than a decade of work in menin inhibition at Kura. We've pioneered menin inhibition, and that experience gave us the scientific foundation to investigate whether this biology could help restore the body's own insulin-producing capacity.
As the data developed, we saw an opportunity that warranted a focused development effort as well as a dedicated investment. Diabetes requires specialized capabilities and a development strategy tailored to metabolic disease. Caspian gives this program the dedicated leadership and financing while Kura remains focused on its oncology business. Kura contributed KO-7246 and related intellectual property and know-how to Caspian. The $50 million financing was led by BVF Partners with participation from the T1D Fund, Invus, Montanova, Eli Lilly and Company, Kura Oncology, and other investors. The proceeds are expected to support KO-7246 through IND-enabling development and initial clinical proof of concept, as well as to support advancement of a second menin inhibitor candidate. Caspian can access Kura's research, development, and corporate capabilities through an intercompany services agreement. This gives Rob and his team access to established expertise and infrastructure while directing more of Caspian's resources toward development.
Caspian has responsibility for advancing the program with oversight from its board of directors. Kura retains approximately 50% ownership, giving Kura stockholders meaningful participation in potential future value. We believe this structure puts the program in a position to advance efficiently with capital aligned to a specific clinical objective. The scientific basis for the investment is the focus of today's call. Francis, if you could please take us through the EASD slides.
Thank you, Troy. Our starting point is the loss of functional beta cell capacity in diabetes. Beta cells are the cells of the islets of the pancreas that make insulin. We're investigating whether we can help the body rebuild that insulin-producing capacity by inhibiting a protein called menin. Menin controls expression of CDK inhibitor genes in beta cells, thus acting as a brake on beta cell division. Studies of how the pancreas adapts to increased insulin demand, such as during pregnancy, suggest that menin inhibition can release that brake and allow beta cells to multiply. We're investigating whether a drug can harness this natural capacity for adaptation to help restore insulin-producing capacity in diabetes. KO-7246 is a potent, selective oral menin inhibitor developed with metabolic disease in mind.
At EASD, we reported data related to beta cell expansion, insulin production, blood sugar control, and durability after treatment stops using mouse, rat, and human models. We also compared KO-7246 with other compounds to understand where its activity and selectivity differ. Next one. Let's begin with the mouse model of type 2 diabetes. In this experiment, these animals had very, very high blood sugar when the treatment began, and as you can see in the light blue line, semaglutide lowered it rapidly, but that effect weakened over time. With KO-7246, on the other hand, blood sugar fell more gradually over seven weeks, while insulin levels concomitantly increased, shown on the right. That slower response is consistent with the process that takes time to build beta cell capacity.
Importantly, combining KO-7246 with semaglutide brought together both the rapid initial reduction in blood sugar and a sustained effect due to the menin inhibition. Despite increased insulin production, we observed no hypoglycemia, that is abnormally low blood sugar, in any KO-7246 treated mice, including in the combination group where insulin levels reach quite high. That matters. The aim is to restore glucose control without driving blood sugar too low, and it's encouraging evidence of integrated physiologic regulation of menin in this model. As they say, a picture is worth a thousand words, and I feel like this really captures the power of the approach of menin inhibition here. After only 28 days of exposure, we can see that the islets, the tissues containing the beta cells, have grown substantially and are staining positive for insulin. Improved blood sugar control accompanied expansion of the insulin-producing cell population. Next one.
We next studied rats given STZ, a chemical that destroys beta cells and causes severe insulin insufficiency. This model tests whether generating new beta cells can restore blood sugar control, although it does not reproduce type 1 diabetes autoimmune attack. The positive control exogenous insulin lowered blood sugar quickly. KO-7246 took longer, but a substantial effect developed over eight weeks. Some animals responded strongly, and others did not. Responders regained normal blood sugar control. In the same experiment, icovamenib, also known as BMF-219, did not reduce fasting blood glucose or increase beta cell mass under the conditions tested. Let's take a closer look at this response in the next slide. This binary response, complete recovery in some animals and little or none in others, is consistent with how KO-7246 is intended to work.
It helps existing beta cells multiply, so there must be a sufficient surviving population to build upon. Our interpretation of these data is that animals with enough remaining beta cells could rebuild the insulin-producing capacity needed to restore glucose control, while those with too few lack the starting population needed for a meaningful response in this model. Among the KO-7246 responders, islets recovered to between 40% and 90% of healthy control levels by day 56. In other words, partial recovery was enough to restore normal blood sugar control. This combination of tissue recovery and functional benefit clearly distinguished KO-7246 from icovamenib in this experiment. We then stopped treatment and followed the animals for another month. As you can see, in responders, blood sugar control was fully maintained. Next slide.
Stimulated C-peptide, a marker of the body's own insulin production, also remained significantly elevated after that month, as shown in the chart here. No further treatment, but at the same time, very little cell division remained at this point. In other words, functional benefit persisted after active proliferation had ended, supporting the possibility that treatment can rebuild insulin-producing capacity that continues working after drug withdrawal. We then tested human islet microtissues, which contain the appropriate proportions of the different cell types found in a pancreatic islet. KO-7246 increased beta cell proliferation in multiple donor samples. Under high glucose conditions that stress these cells and exist in diabetic patients, increasing the dose increased both beta cell proliferation and ultimately the proportion of beta cells in the islets. KO-7246 selectively stimulated beta cell proliferation without increasing proliferation of other cell types in these experiments.
The research compound harmine, a DYRK1A inhibitor, stimulated non-beta cells as well as beta cells, ultimately actually reducing the overall proportion of beta cells. KO-7246, therefore, expanded the cell population that we want to restore without stimulating broader cell growth in the microtissues. This selectivity matters because our goal is to rebuild the insulin-producing cell population without encouraging growth of surrounding cells. The results are consistent across complementary systems. Beta cell expansion with improved glucose control in rodent models of both type 1 and type 2 diabetes and selective beta cell proliferation in human islet microtissues. The human findings strengthen the case that the underlying biology extends beyond mice and rats. Finally, the direct comparisons help explain KO-7246's pharmacologic profile.
While both KO-7246 and balomenib, another menin inhibitor being advanced in diabetes, were indeed active against menin, KO-7246 was about three times more potent than balomenib in vitro and displayed superior antitumor activity at one-quarter of the dose in a menin-dependent mouse leukemia model. Icovamenib, on the other hand, showed a different profile. Although described as a menin inhibitor, it did not measurably block the menin-MLL interaction in our assay and showed no efficacy in the menin-dependent animal model, even at eight times the dose of KO-7246. Instead, we observed robust inhibition of several kinases, including CDK9, a protein broadly involved in regulating protein synthesis, along with other kinases with reported roles in diabetes, such as c-Kit and ABL. These results do not support menin-MLL inhibition as icovamenib's mechanism, but do identify CDK9 as a distinct pharmacologic activity of this compound.
For KO-7246, the evidence connects potent menin inhibition with beta cell expansion, improved glucose control, and persistence after treatment stops. The consistency across mouse, rats, and human models, together with selective proliferation of beta cells, gives us a strong scientific basis for development. The next steps test whether these findings translate into safe, meaningful improvement in patients own insulin production. Rob will now describe how Caspian intends to build on these findings. Rob?
Thank you, Francis. Caspian's initial development objective is to characterize the safety, tolerability, and pharmacokinetic profile of KO-7246 for chronic administration and to assess its ability to improve endogenous insulin production in people with diabetes. The preclinical package gives us a strong rationale for that work and helps define what we need to learn by translating that into humans. We are advancing KO-7246 through IND-enabling studies to support our initial clinical program. The goals of the ongoing work are to establish the toxicology and exposure information that we need to support clinical dosing, together with the manufacturing and drug supply required for these studies. Our goal is an early clinical assessment that can inform both the potential of the molecule and the design of the subsequent studies.
But safety always comes first, so we need to understand how KO-7246 behaves in people and establish an appropriate basis for evaluating repeated dosing. The clinical program must ultimately establish the tolerability and exposure profile relevant to people with diabetes. Patient selection will be important, and as you heard from the preclinical data that Francis presented at EASD, the biology suggests that residual beta cell capacity may be important, and the results in the STZ model reinforce that point. We are considering how baseline endogenous insulin production and the degree of insulin deficiency may help identify populations in which a treatment effect would be most informative. We believe that both type 1 and type 2 diabetes are relevant to the broader opportunity. For the initial clinical assessment, we want to match the population to the mechanism and select measurements that can detect a meaningful change in function.
For example, one key measure will be stimulated C-peptide, which helps us assess the body's insulin response to a defined challenge. We would interpret that alongside other measures and treatment requirements, looking for trends over time, and those trends could help us to understand the magnitude and timing of the biological response, including glycemic control. For us, initial proof of concept is about establishing a satisfactory safety and exposure profile and looking for evidence that KO-7246 can improve the body's own insulin production. An encouraging signal would be an increase in stimulated C-peptide from baseline, whether during treatment or follow-up, and we would assess that signal alongside the broader set of data. We have a defined scientific hypothesis and a program focused on testing this in the right way in people with diabetes. Troy, I'll turn this back over to you.
Thank you, Rob. Thank you, Francis. The EASD findings explain why we believe this opportunity deserves dedicated development. KO-7246 combines potent selective menin inhibition with evidence of beta cell expansion and durable functional benefit in preclinical models. Caspian's building the leadership and the resources to investigate whether those findings can translate into a meaningful benefit for patients. For Kura stockholders, Caspian provides continued participation in that opportunity through its ownership position while enabling a development strategy focused on diabetes. For Caspian, the next priorities are completing the work needed for clinical entry and conducting the studies to establish initial proof of concept. We'll look forward to sharing progress with you as the program advances. We appreciate your interest, both Caspian and KO-7246. With that, Ryan, we're happy to conclude the prepared remarks and then open it up for Q&A.
Thank you. We will now move to our question-and-answer session. If you have joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. When you are called on, please unmute your line and ask your question. We will now pause a moment to assemble the queue. Again, we ask that you please limit yourself to one question and one follow-up. You're welcome to then reenter the queue for any additional questions. Our first question will come from the line of Roger Song with Jefferies. Please unmute your line and ask your question.
Good afternoon, team. Thanks for sharing more color here. Excited to hear about this new development, and then mentioning some of the thesis and what to look for in the future. So these C-peptide levels that you're looking for, if you could provide some more color on what would be a meaningful signal, whether in the follow-up or in the treatment. Thank you.
Yeah, Nabeel, thanks for the question. Rob, do you want to speak in broad strokes what might we be looking for in terms of the markers of activity?
Yeah, absolutely. I think what we're looking for is preservation or enhancement of C-peptide levels as compared to baseline. As I've mentioned, that would be over the course of the treatment period or during the follow-up period. As you heard from Francis, we expect that this rebuilding of the beta cell pool will take time for that to occur, and then for the treatment effect to demonstrate this increase in C-peptide.
Great.
Thank you. I'll go back to the queue. I have a few more questions.
Thanks, Nabeel.
Your next question will come from the line of Priyanka Grover with JP Morgan. Please unmute your line and ask your question.
Hi, guys. Thank you so much for taking our question. How do you think about KO-7246 in positioning it in the diabetes treatment landscape, especially with the possible combination used with GLP-1s?
Yeah, Priyanka, thanks for the question. Francis, maybe you can just talk a little bit about the scientific rationale, and then Rob, if you could talk about potential future combination usage. Maybe Francis, we'll start with you.
Sure. Yeah. Certainly from our perspective, the mechanism that we're engaging here, which enables us to selectively increase beta cell mass, is clearly very complementary with any current standard of care. On the most basic level, GLP-1 agonist for instance, will among its many other positive attributes, will improve the function of pancreatic beta cells. So combining that with increasing the number of pancreatic beta cells gives you a clear opportunity for a synergy that we see in the animal models. There are certain other activities of menin which we don't talk about so much. One of those is upregulation of GLP-1 receptors. So I think that there's a strong basis for expecting that that will translate in the human setting as well. This has certainly engendered a significant amount of interest among the producers of standard of care drugs in diabetes. Rob?
Sure. I think as you said, Francis, I think we see KO-7246 as being complementary to the existing standard of care, in particular the GLP-1 receptor agonist, rather than acting like a typical glucose-lowering agent. As you probably can imagine, there's this unmet need to really have a therapy that can restore endogenous beta cell function and provide that physiologic insulin response. We see this as being important and obviously great to have in addition to GLP-1 agonists.
Yeah.
Thank you so much for taking my question.
Thank you, Priyanka.
Your next question will come from the line of Li Watsek with Cantor Fitzgerald. Please unmute your line and ask your question.
Hey, guys. Thanks for taking my question. Just given the regenerative effect you have seen preclinically, what is the intended dosing paradigm in your clinical trials? Would it be chronic or maybe after a defined period?
Li, that is the million-dollar question. Maybe I will take a quick stab. This is Troy. I will take a quick stab at it, but then I will invite Francis and Rob to comment. Preclinically, you get regeneration of the beta islet cells and restoration of function relatively rapidly, and as Francis showed you do not need full restoration. This is not oncology, so we do not have to get to 100%. I would also say we and others have been treating cancer patients with menin inhibitors for years with no obvious issues with respect to metabolic tolerability. So it is possible one could just keep this on board, and if there are insults to the beta cell mass, they would repair it in situ. At the moment, that is why you have to do the preclinical tox and why you have to start with this sort of first-in-human studies.
I think it is too early to say, do you do it continuously? Do you do it intermittently? What I think is pretty clear is you probably have a large therapeutic window with which to operate based on what we know about ziftomenib and what Francis and his team have designed into KO-7246, as well as successor compounds. And the fun part will be figuring out, is it one? Is it the other? Is it both? Is it different applications for different diseases? But Francis, anything you would add to that?
Yeah. In the type 2 model, we quadruple beta cell mass in 28 days. In the type 1 model, we essentially were able to get full 100% glucose control by basically increasing the beta cell mass from 20% to 40%, or a little bit more. So the bars are not spectacularly high. There is no doubt that the rodent beta cells proliferate more readily and more quickly than we would expect the human beta cells to do. But if you extrapolate from the numbers in the ex vivo experiment with the islets, that does turn out to be quite a lot of beta cells after a certain period of time. So we think that we will get there. The less you start out with, the longer it will take to get to the finish line.
So there may be variability in response time between individual patients, depending on what their starting position was.
The next question will come from the line of Jason Zemansky with Bank of America. Please unmute your line and ask your question.
Good afternoon. Thank you so much for taking my question and congrats on the good progress. I guess, looking at the balomenib data, I believe that the three weeks of the menin inhibition gave an A1C benefit lasting about three months off drug in type 1 diabetes. So I guess, how does that shape your plan for 7246? I know you mentioned chronic administration, but does the durability here suggest that maybe a short fixed course might work instead? And I guess beyond the in vivo potency, how does 7246 stand apart from the competitor islets moving forward as well? Thanks.
Jason, your audio was breaking up a little bit there, but let me see if I can restate the question in two parts. So the first part, which I am going to ask Francis to speak to, is how does, excuse me, 7246 and balomenib relate? The second part is, given the relatively short course of treatment shown with balomenib, how are we thinking about kind of intermittent dosing versus continuous dosing? If I am reading the question back, and I will ask Rob to speak to that. But Francis, maybe we start with just similarities and differences to balomenib.
Yeah. We are, as you know, very active in the menin chemistry front, and any other compounds that are of interest, we synthesize and try and do as full a workup of comparison as possible to understand where we stand. As I understand it, balomenib is a menin inhibitor that was repurposed from AML. It's changed hands a couple of times. In our hands, as I say, it is a bona fide menin inhibitor that inhibits the menin KMT2A interaction in the biochemical assay. But in looking at menin-dependent cells, we see about a fourfold difference that reflects the difference in the binding affinity in the biochemical assay. In the mice, it's given twice a day, quite rapidly cleared, and again, you end up having to use about four times as much of it. So it looks pretty similar.
Absent comparisons of any other properties, such as safety issues that we're not privy to, it looks as though the two compounds are broadly comparable, but KO-7246 is a little bit more potent. Rob?
Yeah. I think as far as the clinical aspect of it, I think that's where, as you can appreciate, we have to really look at the exposure response to assess both the magnitude of the response, the onset, and then, as you said, looking at that duration of action post-dosing. So I think we have to take all that into consideration, as well as patient population, because we are looking at both type 1 and type 2 patients.
Yeah. It's probably, just to add to that, Jason, to both what Francis and Rob said, the intention, I think, is to start in healthy volunteers next year and really get a good understanding, as Rob said, of what is dose, what is exposure, what is initial tolerability. You really want to understand the drug-like properties of 7246 when you then go into patients, such that you understand as best you can the experiment that you're running. So that's the way we're planning on approaching it. I don't know that all that data's going to get disclosed as we go. I think we're kind of guided to data in late 2028, possibly early 2029.
But that's the way we're going to go about it, is you have a very good compound, but the more one can learn about it, the better we think we can position it in these patient populations.
Great. Thanks for the color.
Sure.
Next up will be Charles Zhu with LifeSci Capital. Please unmute and ask your question.
Hi, this is Peter Green on for Charles. Question for the team. How might this phase I trial or future trials be designed to show KO-7246's potential unique contribution to glycemic control as compared to other background therapies that patients might come in the trial on?
Take that?
Yeah, Peter, thanks for the question. Rob, do you want to—
Yeah.
—share your thoughts with Peter?
Sure. Yeah. I think, what we'd be looking at is that people would be on their standard of care during the course of the study, and then looking at the comparison between that and being on treatment, and obviously looking at that from a dose-response perspective. As I mentioned, C-peptide is going to be one of the main pillars that we're going to focus on. But beyond that, we'll also be looking at HbA1C and other markers as well, looking for other improvements in glycemic control.
Peter, to what Rob was saying, what we have heard from clinicians, from strategics, from folks who are knowledgeable in the space is there really is not another mechanism that anyone can name that selectively expands beta islet cells and drives increases in C-peptide without increasing the alpha cells or other cell types. That is the critical proof of concept experiment. If you can do that with acceptable safety and tolerability, the view among the experts is you have something unique and pretty powerful. How you develop it then, I think that is the much longer part of the question. If we can demonstrate that, and the preclinical data suggests that Caspian can, you are going to be doing something that no one else to date has been able to demonstrate. So there is going to be a lot of focus on that C-peptide and then related markers.
I think you would need maybe a little more to interpret the data in type 2 patients.
Agreed.
But in type 1 patients, if you can significantly move the needle on any marker of glycemic control, I think you have got to feel that it has to be due to an increase in beta cell mass.
As we have gone out, now that the company is constituted and financed and Rob is building a team, folks have come forward with some pretty clever ideas on how to answer that question, which we are not going to share because it is a competitive space. But there are some interesting experiments in patient subtypes that one can do to try to get to this answer as quickly as possible. So, more to come.
Excellent. If I may ask a follow-up, are there any incidental findings from the ziftomenib experience demonstrating insulin control in perhaps diabetic patients, that might have influenced the molecular design for the new compound or the development plan?
We wish, Peter, and that's the honest answer is we wish. Two things. As you know, AML patients are frequently transfused, so that complicates your ability to gather the data and to interpret it. I think more to the point, we've yet to meet a hematologist oncologist who's really interested in doing exploratory work in diabetes. Most of them are pretty focused on trying to extend and improve their patients' lives. So the data may be there, but it isn't really the right patient population in which to ask the question. What I can tell you, and folks know both our experience in AML, and we haven't shown the data yet, but we are at higher doses in patients who have GIST in combination with imatinib, is there isn't anything we're seeing from a safety perspective, a tolerability perspective, that would preclude giving this chronically to diabetic patients.
That's reassuring. Because at least one of the companies in this space has reported liver toxicity and some other observations, which, in our experience, that's not menin inhibition. That may be the fact that it's a covalent inhibitor, it's hitting other targets. Menin inhibition appears to be quite clean in a generalized patient population. So that's in contrast to the DYRK1A inhibitor that Francis mentioned. That's a big step in the right direction.
Excellent. Thank you very much, and congrats on the updates.
Thank you.
The next question will come from the line of Phil Nadeau with TD Cowen. Please unmute and ask your question.
Good afternoon. Thanks for taking our question. A question on the patient selection. Can you talk a little bit more about how you will figure out who are the ideal patients in terms of residual beta cell capacity, endogenous insulin production? On a related note, in the recent data that came out from [inaudible], do we know what patients were enrolled in that trial in terms of those parameters? Thanks.
Yeah I'll take the second part of the question. I'll let Rob take the first part. The answer to the second part is no. We don't know. I think those observations are kind of directionally encouraging but there's a lot there that wasn't shared in terms of patient selection. Maybe a bit early but Rob, I'll let you know whatever we can say about patient selection.
Yeah I think obviously as we said before, we're looking for some markers since we obviously can't do a biopsy of the pancreas. We have to use the alternative which is where we come back to the C-peptide because that tells us about endogenous insulin secretion. So we will be looking for patients who demonstrate at least a reasonable amount of C-peptide that would suggest that they have enough beta cell mass to respond to KO-7246. So it is probably utilizing that tool to guide us going forward, and obviously stratifying our patient population in the study so we can understand people who perhaps have more or less C-peptide suggestive of differences in beta cell mass to start.
That's very helpful. Thank you.
Okay. Thanks, Phil.
The next question will come from the line of Reni Benjamin with Citizens. Please unmute and ask your question.
Hey, good afternoon, guys. Thanks for taking the questions, and congrats on the update. I guess one or two for us. Can you talk a little bit about the non-responder animals and maybe what insights you may have learned as to why they aren't responding, maybe outside of residual beta cell reserves, or if that's pretty much the only thing that you've been able to find regarding those non-responders? As a follow-up, and I think it pertains more to T1D, it's a little bit outside my therapeutic area of focus, but how do you think about these newly generated beta cells surviving, like the underlying autoimmune disease process that's leading to this issue? Do you think you'd have to somehow be thinking about combinations that curtail that autoimmune process as well for this to really work?
You want to go, Francis?
Sure. Yeah. The second one, that's not going to go away. There are treatments for that the patients may be on while they're on trial. One thing I would say is that producing the beta cells endogenously one at a time in the pancreas has got to be less immunogenic than giving a bolus transplant of beta cells. That's, I think, a small advantage that we have there. And what was the first part of the question?
The first one was can we explain the non-responder?
Yeah.
Is there anything other than lack of beta cell?
Yeah. I'm going to have to say, in my opinion, I don't think there is. There's not that much we can do in the context of that therapy experiment where by the time you see the outcomes, the animals have sort of moved on, if you like. But what we did notice and one of the little highlight boxes that popped up, and that I used in the EASD talk was that there was a substantial amount of variability in the baseline glucose, FBG, at day zero. You can just see that by looking at the control group. Similarly, when you look at the size of the islets in uninsulted rats, there was a wide variation, 3 to 4x between the largest amount of beta cell area and the smallest.
You could imagine an animal that was particularly well endowed with islets at the beginning would tolerate the STZ better, and so on. You can see how a lot of variability can creep in there. Indeed, in the treatment groups, we did see in several cases, the animals that failed to respond were the ones that had particularly high FBG at the beginning, which presumably reflects a relatively small beta cell pool. Beyond that, there is no real factors that we would bring in. For me, the black and white nature of the response, it either worked perfectly or it did not work at all, really speaks to a threshold, and if you like, a sliding doors moment early on in therapy where you can either beat this thing or it's going to run away from you.
If you look again in the details of the response, you'll see there are some rats that normalize their blood sugar levels in two weeks, but there are others that took six weeks. Again, I would assume that that's because the ones that took longer had a smaller starting point. So that was my earlier comment about how we would expect perhaps different times to response for different patients, that will reflect that. But there are a battery of tests that we can do to throw light on the initial beta cell mass above and beyond what Rob has described. So we're confident that we can stay mostly within that range and or that the first trial will give us clear guidance as to where the cutoffs might be.
Perfect. Thanks for taking the questions.
Thank you, Ren.
As a reminder, if you have joined by the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. When you are called on, please unmute your line and ask your question. Again, we ask that you please limit yourself to one question and one follow-up. You are welcome to then reenter the queue for any additional questions. Next up will be Daniel Brims with Lake Street. Please unmute your line and ask your question.
Hi. Thanks for taking the question. Back to eligible patients, if we look at C-peptide, that could be for patients later on after diagnosis with type 1 diabetes, say the long tail. In general, what do you think the window would be around onset of autoimmune destruction of the pancreas for patients to really have enough beta cells? Then, as I said, probably after that, there is a long tail where you have some patients that continue to have enough over time, whereas others probably don't. To grab that largest chunk, what do you think that window is around diagnosis and onset of type 1 diabetes?
Daniel, it's a good question. I'm going to answer it and not answer it. I'll take a stab at it, and then Rob can add any thoughts he has. I think let's do this stepwise. Stepwise, you want to have patients who are relatively stable. If they're rapidly declining, that's probably not good because it's going to make it difficult to compare relative to benchmarks. If one gets a strong signal there suggesting you move forward, then I think, and this is where Caspian will endeavor to do it, there may need to be more resources. Then you may go in combination with agents that help tamp down the autoimmunity. You may go on top of implants or explants. Anytime you're dealing with beta cells, you could see how a menin inhibitor might play a role.
For these first experiments, whether it is type 1 or type 2, you want them at that part of the curve where they're relatively stable. In talking to clinicians, we think those patient populations can be identified. You want to be careful, but you're looking for that very strong signal that tells you this warrants a much more significant investment. Rob, anything you'd add to that?
No, I think that's perfect. I think you are fighting with T1D, you're fighting the battle on both sides, meaning—
Yeah.
—you're looking at the destruction of the beta cells, but you're also looking at what remains of the functional. We can't obviously treat the patient population as being a single entity. It's going to be on an individual patient basis. I think your point is well taken.
Yeah.
Thanks, guys.
Sure. Thank you.
Your final question will come from the line of Roger Song with Jefferies. Please unmute and ask your question.
Hey, thanks, folks. This is Nabeel on again for Roger. Appreciate the additional questions. Just wanted to ask, your release also references other chronic metabolic diseases, if you could provide any color beyond T1D, T2D, if you're evaluating anything else. And is that also beta cell specific? Or any color there would be great. Then if I could sneak one quick other one, what have you learned about the class? You guys have pioneered menin inhibition in AML, understood on-target toxicities. You guys have a differentiated safety profile versus other menins. If you could kind of share a bit more on how you designed KO-7246 for this chronic population. Thank you.
Yeah. Nabeel, since you're the last question asker, well, you get to sneak the two questions in. Let me ask Francis just briefly to touch on your second question, which is what did we learn and how did we design 7246? I think you covered it in the prepared remarks, but Francis, maybe touch on it, and then I'll hit Nabeel's first question.
Yeah. As you know, how well a drug works is a ratio of two things, how efficacious it is and how toxic it is. We feel that the efficacy bar is a bit lower in diabetes than it is in AML, which is a super aggressive disease where you've got to get every last cell. On the other hand, diabetes patients are not nearly as sick as AML patients, so clearly we would view the tolerability bar as being somewhat higher. So we really focused, as you so kindly said, we are quite experienced at making menin inhibitors, so we had a large library of highly active compounds to choose from. We were able to focus on the safety side for 7246. What we did there was we completely dialed out any interaction with the CYP system, any interaction with the hERG channel.
We also really kind of went the extra mile on the genetox, which is a big delta between oncology and everything else. We can sort of look the other way if things are a bit genetoxic in oncology, but not in this situation. So we did full GLP grade genetox, both flavors, with this compound at millimolar concentrations that mimic the concentration it would achieve potentially in the lumen of the stomach, so very, very high, and found them to be completely clean. These are really what we've focused on. Beyond that, we just wanted to make sure we had a nice clean modern drug which can be given once a day orally, which will block the target for the majority of the dosing interval, but be completely cleared by the time of the next dose.
It's fairly plain vanilla, but I think that's what we really wanted to have here.
Yeah. Nabeel, to your first question, yes, there are other indications, potential indications that the teams, both the Kura and the Caspian teams working together, collaborating, are evaluating. We can't tell you what they are. But menin is sort of hardwired into biology, right? What we're really doing is phenocopying with a small molecule what nature, in some circumstances, does. So I think there's going to be some interesting applications. I'm reminded, when I first got involved in this, all we really thought about was KMT2A rearranged AML with menin. Now we have NPM1, we have FLT3. You'll see other mutations at ASH. We have solid tumor applications. This whole field of epigenetic regulation, I think, is really ripe for drug development, and menin appears to be the gift that just keeps on giving. So, I'll close by thanking all of you on the call.
I want to thank our investors, including Eli Lilly and Company, the T1D Fund. This is the first beta cell regeneration investment that each of those organizations have made. I think that says a lot. We are really excited. Caspian is going to keep a relatively lower profile. A lot of exciting things to come. For those of you who are following Kura, we will have an earnings call here before too long where we will give you an update on the third quarter, and a lot of exciting developments to come. In the meantime, please reach out to me, to Greg, with any questions or any follow-up. With that, we appreciate everybody's time, we appreciate the questions, and we will conclude the call. Thanks very much.