Dr. Anath Shalev - Founder and CSO - TIXiMED

[00:00:00] Rob Howe: Welcome to Diabetes Innovators, a special series from Diabetics Doing Things covering the 85th Scientific Sessions that were held in June 2025 in Chicago, Illinois. You're going to hear interviews from leaders of tech companies, people with diabetes, diabetes creators, researchers, and more on this podcast. If you want to learn more or hear more from this series, visit DiabeticsDoingThings.com slash Diabetes Innovators. Enjoy the episode. Okay, let's talk about our partners who help support this podcast. Today, I'm going to talk about Type Zero, which is typezerohealth.com. It is a business run and founded by a person with type 1 diabetes, John Jensen, who's been on this podcast a couple of times. I've been using this product since 2018. I started training for a half marathon, which I ran in Dallas in December 2018. I was looking for a workout supplement, a pre-workout that I could trust not to spike my blood sugar. 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We've gotten to introduce over 100 campers with type 1 diabetes to diabetes legends like Lauren Cox and Gary Forbes and more. We've got three clinics coming up this year, a very special event at Friends for Life Conference on July 11th. And then later in September, we're going to be returning to Denver. If you're looking for more information on the events themselves, you can visit diabeticsdoingthings.com slash events. And if you're interested in learning more about the Diabetes Legends Foundation, which we formed in 2025, to better support our ongoing initiatives in creating opportunities for kids with diabetes to have a great day with diabetes via one of our clinics, please connect with us and fill out a form on our website, diabeticsdoingthings.com. To get started, why don't you introduce yourself and TIXiMED and what you do at TIXiMED.

[00:04:31] Anath Shalev: Hi, I'm Dr. Shalev. I'm the founder and CSO of TIXiMED, and we're trying to find a new therapy, oral therapy for type 1 diabetes with our compound TIX100.

[00:04:41] Rob Howe: Thank you. And when we last had you on the podcast in 2024, which is episode 282, for those who are listening or want to go back and check out your previous interview, we talked a lot about TIX100 and the potential of TIX100 as a novel oral treatment for diabetes therapy for type 1 diabetes. The great part about this year and the update for our listeners who have been tapping in as part of our Diabetes Innovators series is that prior to ADA scientific sessions this upcoming week in Chicago, we saw the announcement that TIXiMED has announced the successful completion of a Phase I study. So what can you share with our listeners about the study itself and what it means for the next step for TIXiMED?

[00:05:27] Anath Shalev: Sure. So as with any drug, there's always a big step to move it into humans. And so this was really that big step that we took with this first in-human trial. So this was a double-blind, randomized, placebo-controlled trial in just at this point, 28 healthy subjects to check for its safety and tolerability. And we were very happy to see that at all doses tested, there were absolutely no adverse effects. There were no changes in laboratory measurements, in EKG, in anything. And so it was very well tolerated. So in fact, the external medical monitor liked to say that it doesn't get any more squeaky clean than this. And so we were super happy to hear that because that's obviously the first step in moving a new drug into people. And I mean, that really is the whole purpose of a phase one trial is to assess. Exactly. And then we were lucky in a way that in general, you don't expect much else in the study because that's how those studies are defined, that that's what the FDA is requiring us to do. But we were trying to model this study and design it such that maybe, maybe we would also get a little bit of a metabolic signal to show whether ATX-100 has any effects. And we were actually successful in doing so. So we were very excited to see that we did get our initial metabolic signal, even despite the fact that those were healthy subjects and despite the

[00:06:50] Rob Howe: fact that this is a small study. And I saw that, and I know you and I were talking before we started recording. In the release, it talks about the therapy is designed to decrease postprandial blood glucose excursion without hypoglycemia. And obviously, that is not, like in the context of the phase one study, like it's not obviously delivering to patients with diabetes and that'll be part of a future study. But what was it like to be able to not only determine the safety, but also to get those initial results?

[00:07:17] Anath Shalev: Now, that was really super exciting for us because again, in such a small study, we're hoping, but we were obviously realistic not to expect necessarily any metabolic signals at that point. However, actually, the TIX100 is designed to really get to the bottom of the problem of diabetes, namely the beta cell loss and the beta cell dysfunction and the islet dysfunction. So we're really trying to address those problems that are fundamental in the development of the disease. Of course, anything that is symptomatic helps as well. But what we saw in preclinical studies was that those changes, those post-brandial changes, actually went hand-in-hand with the same dose as with the effect, the doses that were necessary for the effect to elicit the anti-diabetic effects, really targeting those beta cells. And so that's what we're hoping we're seeing here as well, that this is just a sign for the ultimate effect on the beta cells. And so seeing that was very exciting to us, especially since it happened at the same doses that we predicted kind of from the animal models that would be effective. We didn't see it at the lower doses, only at the doses that were predicted to be efficacious in humans. That's where we saw the effect. So it seemed to match very well with our preclinical data.

[00:08:36] Rob Howe: Let's talk a little bit about that, because I think, you know, as you guys are designing these studies, like me as a patient and as a person who is not a researcher, How does that data influence maybe how you're designing the next phase of the study? Does that add another layer? Do you then try to push forward further or add more detail to that study? Like what has that done for you and your team, at least initially, and how you're planning to move forward?

[00:09:03] Anath Shalev: That's a great question. In fact, no, it's been very exciting in the sense that we feel that now that we have seen already a signal, we can move faster and get faster to people with type 1 diabetes. So we're going to try to get the second part of the multiple ascending dose done more quickly and then move faster into people with recent onset type 1 diabetes, which is ultimately the cohort that we want to have this drug work and to show its efficacy.

[00:09:30] Rob Howe: Right. You know, like you're talking about, for those who are recently diagnosed or, you know, in the sort of screened or like pre-diagnosis moments, like that's where the real impact could potentially happen for TIX100, right?

[00:09:47] Anath Shalev: It would have the most beneficial effects the more beta cells are still remaining because that's what it's acting on. So we would have, you know, the protection of those remaining beta cells. Having said that, again, seeing this metabolic effect that happened, even aside from any beta cell preservation, we anticipate those beneficial effects in terms of glucose control, even in those that have lost a significant amount of beta cells already.

[00:10:11] Rob Howe: So that's great news as well for people like me who've had diabetes for quite some time, where there's still going to be some of that efficacy of the drug as part of the diabetes

[00:10:19] Anath Shalev: toolkit. Absolutely. And again, we know now, and I have to kind of repeat that over and over again, because it is a myth that people, that at the time of diagnosis, people have lost all the beta cells. We know, as a matter of fact, that people have still a significant amount of beta cells left even decades after the diagnosis. It's not enough to maintain normal blood sugar. But if we create an environment for those beta cells to maybe function better or even replicate and expand a little bit, we can have a major impact on the overall outcome and the control of the patient in terms of their blood sugar control with their own insulin rather than being dependent always on an exogenous insulin.

[00:10:55] Rob Howe: it. Exactly. And I think that was also you were talking about in the study. This helps you without hypoglycemia, right? Because you're not adding more exogenous insulin. That's exactly right. So just so that, because I think you're right, it is a myth. And I think it's interesting how widespread it seemingly is, is that, you know, at diagnosis, your body doesn't make insulin anymore and your beta cells are all gone. Is that, is what you're describing and, you know, forgive me if I'm just kind of jumping to try to interpret this on the fly, but the honeymoon period is something I think is that is widely discussed and like known among patients as like the period, maybe after diagnosis could be six months, could be two years where there still are instances where your body is creating some insulin or, you know, makes your diabetes management change, you know, or fluctuate during the first few years of your diagnosis because of those beta cells that are still lingering there and are still maybe creating insulin. So, you know, in a world where TIX100 is part of the diabetes toolkit, is that something that would potentially extend like a longer phased

[00:12:00] Anath Shalev: honeymoon phase? Absolutely. And in fact, you know, this would describe as the honeymoon that is typically very limited in time and in diabetes and what we've kind of known as such is actually probably a lot longer and can be extended and can be actually recreated if you want to. Because I think what we also know now is that some of the cells, they may not beta cells, they may not produce insulin, but they may still be alive. Or they may even slightly end differentiated. But if you can, if you create the environment to push them back into functioning, becoming functioning beta cells, you can kind of regenerate cells that produce insulin. That doesn't mean that they have to be in a new cells. They can't be cells that just have are stunned kind of by the disease and are not functioning properly, but you kind of trigger them to start up function again. And so that's what we're hoping that we could elicit some of that with TIX100 and those approaches. And we have some initial data that may suggest that that might be.

[00:13:00] Rob Howe: That's fascinating. It seems like just as a result of the study, we're learning a whole lot more about beta cells and how they function.

[00:13:07] Anath Shalev: That's right.

[00:13:08] Rob Howe: So in our last conversation, you had touched on what we know as patients is that diabetes is such a complex disease. It's the disease with too many inputs. And then it was unlikely that ever we would get to one single therapy that would solve all the problems for all patients, right? Like that sort of wonder drug type of approach. And that the end game might be more of a mix of an approach with therapies from multiple angles. And that would likely be the answer. So how do the results from the phase one and your plans as you and the team continue to the next phases, like, make you see TIX100 as part of that long-term diabetes treatment tool?

[00:13:44] Anath Shalev: Absolutely. So it doesn't change, of course. I mean, we're staying realistic. We're excited about the results, but we're still, you know, realistic, not expecting this to solve all the problems. But I think it just highlights, again, that this would become a very powerful and very effective tool within that toolbox. And then in that regard, I need to stress too that I think the beauty of TIX100 is that it functions completely different from anything else that is described currently out there. And so it would lend itself extremely well to combine with any of the current treatments that are out there and that are being studied for type 1 diabetes and others, as well as potentially future approaches that may come down the road, be it pharmacologically, be it cell-based, be it any other way. So I think from that point of view, it's attractive because it lends itself to those different combinations.

[00:14:40] Rob Howe: I think that's really interesting as well, like thinking through what those combinations look like and how from an oral medication perspective, like so much of diabetes management, especially in type 1 diabetes, is either injection or insulin based or invasive from like a continuous glucose monitor base. So to be able to add something that has this impact and is really only an oral medication is particularly exciting.

[00:15:03] Anath Shalev: No, exactly. And again, it's much less of an intrusion, I guess, onto the patient. So you can also imagine that if one wants to ultimately use it as a prevention and as a treatment in the earlier stages of type 1 diabetes, again, it lends itself very well because if the risk is low and it's well-tolerated, it would be very easy to put that into the mix and to help people take it, even if we don't know for sure that there are just, the diabetes development is imminent, even if they have to take it for several years in order to prevent the onset of diabetes. But if it's well-tolerated, then it's kind of no foul in a

[00:15:42] Rob Howe: way. Yeah. I mean, I didn't even consider that. So you're saying like, let's just talk about a scenario like that, where we have a patient maybe who has a family history or goes through a screening process and is identified with the antibodies to develop type 1 diabetes. They start to take the drug, they start to take TIX100, and that maybe prevents their diagnosis from starting, or even when they are diagnosed, it allows them to get onboarded to life with diabetes much simpler than what we're seeing today. It's not as drastic of a start. And it may be prevented

[00:16:15] Anath Shalev: altogether. I mean, that's the thing. I mean, we don't know. We have no data for that, so we have to be very careful. You know, theoretically, if everything works the way we anticipate based on the preclinical studies. And this is really protective of the beta cell since it is not an immunosuppressant. We don't have those issues. We don't have to be at the stage of the autoimmunity where it's active in order to address that, like with teplizumab. And so theoretically, it would offer the beta cell that protection of that shield that we envision this to offer to the beta cell as early as we can and protect them from any autoimmunity or any other stressor that they may encounter in the process of the potential disease development.

[00:16:54] Rob Howe: That's amazing. I think just sitting here like, and, you know, we've had a previous conversation and I've worked with your team, like continuing to follow this very closely. So it's exciting to me. What's it like for you and your team, like in the lab to be able to see like the success of the phase one and, you know, potentially, you know, moving on to the next phase? Like what kind of energy is there?

[00:17:14] Anath Shalev: It's really fantastic. I mean, when we got the results, you know, we were kind of on step nine. So it was very nice. And, you know, you really see decades of work come to fruition. And for lab members who have been with me for ages, I mean, it's very nice for them to see that all their work pans out and that there's some direct connection with helping people. And that's kind of really the exciting thing, I think, for being in that field is that, you know, basic research can be very interesting and rewarding in any case. But, you know, if you see a direct impact and a direct translation for people and to help people with their lives, I think that's a totally different ballpark. And it's really super exciting and keeps people motivated.

[00:17:58] Rob Howe: Yeah, I mean, like the impact of this is dramatic. You know, you're talking about a world where diabetes is either delayed or avoided completely. and the impact that that can have on people's lives, not just short-term, but long-term is incredible. Even just restoring beta cell function, like as you're talking like, hey, we don't know how many beta cells that I have left, maybe there's some in there and they could regenerate or things like that. So that's very, very exciting. For people who are keeping track of TIX100 and the next phases, what do the next steps look like to get to that next trial? And for people who are maybe even interested

[00:18:37] Anath Shalev: in enrolling in that trial? Where can they keep an eye out? So the next trial is what we call a multiple ascending dose trial, MAD trial, that's still considered the phase 1b, that's still in healthy subjects. And then the next one would be the phase 2, and that would be in recent onset type 1 diabetes, where we are going to target recent onset diabetes. So that is still several months away. We have to pass the other ones. And of course, this all depends on the funding situation. So we'll have to garner that in order to move forward. But yeah, I think that those are the next steps that every drug has to go through. But at least now we have the way paved, I guess, with the first step, at least with knowing that it's safe in humans.

[00:19:23] Rob Howe: It's very exciting. And congratulations to you and the team. And I know that this is going to be generating a lot of buzz here at the conference this weekend in Chicago and wishing you and the team the best. And thank you for taking the time to brief us on this amazing diabetes innovation that's taking place right before our eyes. So on behalf of our Diabetics Doing Things community, thank you so much for coming back. And we'll have to have you on again after the results at the phase two. We're going to be following this very closely. Absolutely. Thank you so much for

[00:19:53] Anath Shalev: having me.