Immunic, Inc. (IMUX) Earnings Call Transcript & Summary

Good morning to everyone on the call. I would like to welcome you to Immunic's webcast to discuss exciting new clinical and preclinical data from our IMU-856 development program. My name is Jessica Breu, Vice President, Investor Relations and Communications at Immunic, and I will be the moderator for today's webcast. Speaking on the call are Dr. Daniel Vitt, our Chief Executive Officer; Dr. Hella Kohlhof, our Chief Scientific Officer; and Dr. Andreas Muehler, our Chief Medical Officer. [Operator Instructions] And this event is being recorded. [Operator Instructions]. Before we begin, I would like to remind you that this presentation may contain forward-looking statements. Such statements can be identified by words such as may, will, expect, anticipate, estimate or words with a similar meaning, and such statements involve a number of risks and uncertainties that could cause Immunic's actual results to differ materially from those discussed here. Please note that these forward-looking statements reflect Immunic's opinions only as of the date of this presentation, and it undertakes no obligation to revise or publicly release the result of any revision to these forward-looking statements in light of new information or future events. Please refer to Immunic's SEC filings for a more detailed description of the risk factors that may affect Immunic's results and these forward-looking statements. I would now like to turn the call over to our CEO, Dr. Daniel Vitt, to begin the presentation. Daniel?

Yes. Thank you, Jessica. I'm very pleased to be able to present interesting news from our second clinical project, IMU-856 today. IMU-856 has already been successfully tested by Immunic in a Phase I clinical trial in patients with celiac disease. This medicine is particularly interesting due to its unique mode of action. By modulating Sirtuin 6, the renewal of epithelial cells in the intestine is activated. In this clinical study, IMU-856 has already been shown to have a positive effect on the histology of the intestine as well as improving the function of intestinal cells. This makes IMU-856 a completely new approach for a whole range of gastrointestinal diseases. With this mode of action, the drug targets physiological intestinal renewal, including gut hormone-producing cells, and all of this without immunosuppression. During our recent investigations into the mechanism of action and preparations for further clinical studies, we have now come across a very interesting and surprising result, which we'd like to present in today's call. I would now like to hand over and ask my colleague and Chief Scientific Officer, Dr. Hella Kohlhof, to present the preclinical data. Hella, please go ahead.

Thank you, Daniel. So let me talk about GLP-1 and its role in the body first. The hormone, glucagon-like peptide-1 or shortly GLP-1 is quite famous nowadays, because it mediates effects on body weight. And for people suffering from diabetes, GLP-1 receptor agonists are approved as medications to control their blood sugar, metabolism and as well comorbidities like high blood pressure, lipid profiles and inflammation. And in addition to this, these GLP-1 receptor agonists are approved as subcutaneous injections for weight control in people suffering from obesity and the related comorbidities. So GLP-1 is a peptide hormone, which is generated from proglucagon. It is produced by specific cells in the intestine, so in the small and in the large intestine. And the cells are so-called enteroendocrine L-cells. The production happens upon nutrient or food intake and the physiological or normal increase after food intake is around two to threefold. The GLP-1 increase impacts digestion and satiety. So it means that it slows down gut motility, lowers the food intake, increases satiety, and induces insulin secretion. And what you see on the right-hand side is that GLP-1 impacts different organs either directly or indirectly by having an effect on the brain, on the pancreas, different cells in the body, on the heart, liver, and on the stomach. So in our studies with IMU-856, we detected effects on body weight in preclinical testing and effects on blood GLP-1 levels in our Phase Ib celiac disease clinical trial. And as you can see on the left, the 6-month rat study was part of the regulatory relevant studies for further clinical development. So we tested 3 different doses of IMU-856, namely 10, 25 and 75 mg/kg. It was a daily oral treatment over 6 months and with a weekly body weight measurement. On the right, you see the design of the Phase Ib clinical study. Besides the Phase I SAD and MAD testing in healthy volunteers, we also performed this Phase Ib trial in celiac disease patients. In total, 43 patients were enrolled. We had 2 dose levels of IMU-856, namely 80 milligrams and 160 milligrams versus placebo, and all of the patients were on gluten-free diet. It was a double-blind study. We treated over 28 days, and the first 13 days were without gluten. And then it was followed by 15 days of 6 gram gluten challenge per day, which resembles around 2 slices of bread per day. In addition to safety and celiac-related outcome, we read out blood plasma GLP-1 levels in these patients in a post-hoc analysis. And let's walk through our new preclinical in vivo findings. On the left, you see the body weight curves of the rats that were tested. As a reminder, we treated the rats with 3 different doses over 6 months. And what we clearly can see is that we saw a dose-dependent reduction of body weight gain in these rats. And this was linked to reduced food consumption. So the effects were similar in males and females, and you see on the left the combined curve here. And importantly, there was no effect on general health in these animals. So overall, we saw that IMU-856 reduced the body weight gain in a dose-dependent fashion up to 40% compared to vehicle control. And with this, let me hand over to Andreas, who will continue with our new clinical findings.

Thank you, Hella, and good morning, everyone. I'm happy to take over from here and guide you through the clinical results and potential clinical utility given our new results regarding GLP-1. This slide summarizes the findings for blood plasma concentrations for GLP-1 from our Phase Ib study of IMU-856. As you remember, a total of 43 celiac disease patients were enrolled and randomized to either placebo, 80 milligrams or 160 milligrams of IMU-856. The patients were treated in this trial for 28 days. The first 13 days without gluten challenge, the remainder with gluten challenge once a day. Blood samples were analyzed in the morning of day 1 before the first study dosing on day 13, before start of the gluten challenge, and on day 29, the day after the last dose. The samples were taken in a standardized way with patients having fasted without food for at least 8 hours and before taking their study medication that morning. In a post-hoc analysis of the trial, we have analyzed these samples for GLP-1 levels. As you can see, the data show a dose linear increase in GLP-1 plasma levels as compared to baseline with the highest dose of 160 milligrams IMU-856 showing an approximate 250% increase of GLP-1 on day 29 as compared to baseline. This is remarkable as it's known that GLP-1 levels increase about 2 to 3x physiologically following a meal. These pre-meal GLP-1 levels after oral administration of 160 milligrams IMU-856 are therefore well within the range of a natural post-meal increase of GLP-1 in healthy humans that trigger the relevant effects of this hormone, which we will discuss later. We also conducted a post-hoc statistical analysis of the GLP-1 data and found that they are highly statistically significant. The data in our mind provide initial evidence that IMU-856 has the ability to affect GLP-1 levels in humans. Next slide, please. I would like to go back to the histological results of the Phase Ib trial data. These same celiac disease patients showed an increase in villus height on the right, showing regrowth of the bowel epithelial architecture, and an increase of nutrient absorption on the left, showing an increase in vitamin B12 uptake. These data underline, from our point of view, that SIRT6 modulation with IMU-856 not only regenerates epithelial cells in the gut, but also IMU-856 strengthens their function. Next slide. When we go back to the gene map, we can see that SIRT6, the target for IMU-856, is highly expressed in bowel epithelial cells, the left purple circle on this slide, including the epithelial cells lining the bowel wall called enterocytes. The regeneration of these enterocytes presumably is the main source for the improvement in villus height observed in our celiac disease trial. However, the SIRT6 target is also expressed in other epithelial cells, the right green circle there, which includes enteroendocrine cells and their subpopulation of so-called L-cells that produce gastrointestinal hormones such as GLP-1. Given these gene map data of SIRT6, it makes sense that IMU-856 not only have an effect on the bowel architecture, but could also have an effect on gut hormones such as GLP-1. Next slide. Let's look now at the main epithelial cell types in the gut other than the enterocytes lining the gut. Both goblet cells, producing a protective mucus layer on top of the bowel wall, and Paneth cells, which secrete antimicrobial peptides, are known to be important components protecting the bowel wall and its immune cells from assault by and interaction with the microbiome within the gut. Strengthening the function of these 2 cell types has been implicated as potential therapeutic strategies in diseases such as ulcerative colitis and Crohn's disease. A third cell type are enteroendocrine cells, which, in different subtypes, are located throughout the gut. These enteroendocrine cells secrete a multitude of highly active hormones that influence digestion of food, motility of the gut, and regulate blood sugar, but also have effects on the brain, influencing hunger and satiety. Several of these peptide hormones have been shown to be effective therapeutic strategies for indications such as type 2 diabetes and obesity for GLP-1 and GIP, as well as inflammatory bowel disease, short bowel syndrome, and graft-versus-host disease for GLP-2. All these 3 mentioned hormones are secreted by the subtype of L-cells. This brings me to the potential clinical utility that may arise from the finding that IMU-856 increases GLP-1 levels in human blood. First of all, and given that IMU-856 seems to increase function of L-cells, we hypothesized that the hormonal effect of IMU-856 may expand beyond GLP-1 to GLP-2 and GIP and possibly even to other subtypes of enteroendocrine cells. This is planned to be further investigated. This potential multifaceted hormonal effects of IMU-856 would well differentiate our drug from current peptide mimetics being used in diabetes and obesity that mimic 1 or maximum of 2 hormones. A recent head-to-head study in obese patients confirmed that a 2-hormone mimetic outperformed a 1-hormone mimetic. We believe that a new mechanism of action such as SIRT6 modulation may be a potential attractive addition to the therapeutic armamentarium in these indications. In addition, the convenient once-daily oral administration of IMU-856 may also help to expand the current uses for enteroendocrine hormones. I will now hand over to Daniel for further remarks and the summary statement.

Yes. Thank you, Andreas, for sharing these very exciting data. So why has this finding a potentially huge impact? On one hand, a substantial unmet medical need still exists to address this rapidly growing medical challenge. Obesity and overweight are among the fastest-growing and most prevalent chronic human conditions in the world, affecting 2.5 billion adults worldwide. The economic impact of obesity and overweight in the United States is estimated to be more than $700 billion, increasing to $2.6 trillion by 2060. GLP-1 receptor agonist class has revolutionized obesity treatment, but there are still unmet needs for novel mode of actions, oral administration, increased tolerability, and greater efficacy. On next slide, IMU-856 has demonstrated both clinical and preclinical consistent effects pointing to its potential as an obesity treatment option with a radically new mode of action. We've seen a substantial dose-dependent reduction of body weight gain of up to 40% in preclinical studies. And in our clinical Phase I study, we've seen a dose-dependent increase of naturally occurring GLP-1 levels of up to 250% versus placebo. This compares favorably to the typical physiological 2x to 3x increase in GLP-1 in healthy humans after a meal, indicating that IMU-856 may replicate the natural effect after eating. While currently available incretin mimetics delivered via a subcutaneous injection are focused on 1 or 2 endocrine hormones, we believe that the SIRT6 modulation approach may result in a broader, more physiologic activation of enteroendocrine hormones, which we plan to further explore. If the effects reported today can be confirmed in further clinical trials, our convenient once-daily small molecule tablet may represent an oral treatment option for obesity, a market with millions of people affected worldwide. Our IMU-856 program offers the potential for immediate Phase Ib or Phase II clinical testing. As such, we will continue to analyze the findings and assess any next steps. We are very pleased with this new data and see it as a further confirmation of our principle that open-minded research can lead to real breakthroughs.

Thank you, Daniel, and also Hella and Andreas for presenting these exciting new findings for IMU-856. It's now time to open the call for questions from the audience. So we will now begin the question-and-answer session. [Operator Instructions] Our first guest today is William Wood from B. Riley.

Really exciting and very interesting results you presented today. So congratulations on that. So just 1 or 2 from us. I'm just curious, the benefits presented in the clinical work today, do you see these as relating to an improved intestine sort of matching what we normally see physiologically? Or do these sort of elevate the GLP-1 levels and provide further benefit above and beyond what we would normally expect? And just remind me, did you see a dose-dependent effect? And was there any weight loss in the patients during the trial? And then I have a follow-up.

I would assume -- William, first of all, thanks for the question. And I assume I would need to answer this. This is Andreas, Chief Medical Officer. So first of all, I think the Phase I trial, of course, was not really meant to look at weight loss. And also when you look at the BMI that these patients were in our trial, they're well below the values that you usually would have for an obesity trial. So these patients were not obese. So I think it's remarkable that we see this GLP-1 increase actually in these patients that are not obese. And therefore, I think -- and it was also limited to 28 days of dosing and they had the gluten challenge in there. So I think it was not expected to see a weight effect in the Phase I trial. And this has to be tested really with the right patient population, with the right BMI inclusion criteria, and with longer treatment periods. And that's certainly on our mind for the future. I think I missed some part of the question, William.

Yes. I was curious, just could you speak to how the GLP levels that you presented sort of -- are those more related to an improved testing sort of matching, as you mentioned, what we normally see? Or did those sort of elevate above and beyond what we would expect? And did you see a dose-dependent effect?

Yes. I mean we saw a dose-dependent effect. Whether that's due to more maybe enteroendocrine cells or better functioning enteroendocrine cells, I think, is still up for investigation. That's why I went back to kind of our histological results that shows actually that we have an increase, of course, in -- or an improvement in the architecture. So actually growing epithelial cells in a normal way, not above the normal, but basically back to normal. But we also saw that these epithelial cells performed better, yes, in terms of the vitamin B12 uptake that very quickly was upregulated during 28 days of dosing for IMU-856. So in a lot of ways, I think both effects are probably possible. But at this time, we cannot say that. We have to explore this a little bit further.

Got it. Very helpful. I guess maybe just one last one and then -- I know this is still very early, but where would you see sort of 856 fitting in to potential weight management? I mean, would this be more in sort of an induction or more for sort of the management maintenance setting? Obviously, there's always a potential for a combination approach, but just with the fixing of the gut in general, I'd love to hear your thoughts there.

Maybe I'll take that question. This is Daniel. I think if you look at the current market situation, there are definitely unmet needs among all these tools for reducing obesity and managing weight. The good thing here is we have a new mode of action, so that could be applied in very different ways. And given that it is a tablet, it's an oral option, it is something you can easily manage, has a couple of other benefits, of course, based on that. So we think that's too early to say if it should be used early or late or in a combination, but we have all the optionality here. And given that this market is still evolving and there is a need for a new approach, I think it nicely comes at the right time. It is already for Phase II testing. So I think this is an exciting contribution to the landscape of potential next-generation obesity treatments.