Good morning, ladies and gentlemen, and welcome to the Coya Therapeutics conference call, results from an investigator-initiated phase two trial of low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease. All participants will be in a listen-only mode to begin the call. Participants of this call are advised that the audio of this conference call is being broadcast live over the internet and also being recorded for playback purposes. A webcast replay of this call will be available approximately one hour after the end of the call through October 29th of 2025. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may click the link on the webcast. Once connected, you will see that you will press the number one on your telephone keypad. To withdraw your question, please press star, then two. I would now like to turn the conference over to Mr. Joey Delahoussaye of CoreIR, the investor relations agency working with the company. Please go ahead, sir. Thank you, Chuck. Good morning, and thank you for participating in today's conference call. Earlier this morning, the company issued a press release highlighting clinical results from a recently completed investigator-initiated phase two trial evaluating low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease. A copy of that press release can be found on the company's website at www.coyatherapeutics.com under the investors tab. I would like to remind all listeners that remarks made on today's call may include forward-looking statements about Coya. Such statements may include, but are not limited to, those related to Coya and its product candidates and their clinical development, financial forecast, development programs, and related anticipated milestones, collaborations, finances, or regulatory matters. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Coya's filings with the SEC, including its Form 10-K for the year ended December 31st, 2023, which was filed with the SEC on March 19th, 2024, and its Form 10-Q for the quarter ended June 30th, 2024, which was filed with the SEC on August 12th, 2024. We encourage you to review the company's past and future filings with the SEC, which identify specific factors that may cause the actual results or events to differ materially from those described in the forward-looking statements. You can find the SEC filings in the EDGAR database at www.sec.gov or in the investor relations section of the company's website at www.coyatherapeutics.com. Please note that any comments made on today's call speak only as of today, October 29th, 2024, and may not be accurate at the time of any replay or transcript rereading. Coya does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. It is now my pleasure to turn the call over to Tom Schrader, senior biotech analyst from BTIG, who will moderate the call. Tom? Thanks, Joey, and good morning to everyone on the call. Welcome to today's event to discuss the data being presented at CTED. The presentation describes the effects of low-dose IL-2 in the treatment of Alzheimer's disease. As I suspect you know, Coya is developing a proprietary low-dose IL-2 named Coya 301. I'm Tom Schrader, one of the biotechnology analysts at BTIG, and we cover Coya. As an analyst, I need to remind you that my disclosures are found on the BTIG website at btig.com, including the fact that in the last 12 months and going forward, we seek to do investment banking business with Coya. To update us on the CTED data, I'm joined by Dr. Arun Swaminathan from Coya and Dr. Alireza Faridar from Houston Methodist, so in broad brush strokes, today's presentation will focus on correcting CNS inflammation in the treatment of Alzheimer's disease. We see this approach as promising as we're positive on the A- beta antibodies and think they represent an attractive backbone for AD treatment, particularly in patients identified early in disease. So, it's a nice backbone. However, even optimally identified patients don't see their disease reversed, and they don't even see it frozen by the therapeutic antibodies. As a result, we, and probably most others, see a second drug with additive effects to be key in establishing truly transformational treatments for Alzheimer's patients, treatments where the patients could live out the last 10-20 years of their lives without the cognitive decline of Alzheimer's. Along these lines, we see no approach with greater promise than treating the inflammatory side of Alzheimer's disease and possibly all neurodegenerative diseases. We cover several companies in the space, including Denali, Alector, INmune Bio. As I said, we like the approach, and we're intrigued by Coya's Treg approach and its potential to treat inflammation in a more targeted and antigen-specific way. Just to paraphrase, you want broad immunomodulatory effects, but you don't want infections. And we think Tregs are an exciting way to approach that general dichotomy. So, to introduce our speakers and outline today's event, Dr. Arun Swaminathan will assume the role of Coya CEO effective November 1st and will succeed Howard Berman, who will continue as Chief Executive Officer. Arun has spent most of his career as a chief business officer and was involved at Coya in establishing the broad relationship with Dr. Reddy's lab. This relationship includes the development of low-dose IL-2 combinations, specifically CTLA-4 activators. Prior to Coya, Dr. Swaminathan held roles at Actinium and BMS and received a PhD in the pharmaceutical sciences. Our KOL today is Dr. Alireza Faridar. Dr. Faridar is the Stanley H. Appel Chair of Translational Neuroscience at Houston Methodist. He trained at UCSF and has a long-standing interest in the role of inflammation in Alzheimer's disease, our topic today. For reference, Houston Methodist is a hotbed of activity in the inflammatory field, and we have interviewed Dr. Appel himself in previous conversations, but on the role of inflammation in ALS, not Alzheimer's disease. Dr. Faridar is leading the translational effort at Houston Methodist in Alzheimer's disease. He's published important direct imaging studies, for instance, showing that inflammation in the Alzheimer's brain overlaps with regions of tau pathology much more than regions of A- beta plaque. These are key studies in kind of defining what we all have come to appreciate, that tau pathology is probably more important in understanding disease progression. Dr. Faridar is also the primary author on the phase one study of low-dose IL-2 in Alzheimer's, the trial being followed by today's phase two data, as well as the phase one study of low-dose IL-2 plus CTLA-4 fusions in ALS. So, today's format, we'll have some background on the Coya approach by Dr. Swaminathan, followed by the presentation by Dr. Faridar on the IL-2 that is being presented at CTED. After the presentation, we'll open the call to audience questions. And with that, gentlemen, welcome. And Arun, why don't you get started? Why don't you get us started on the Coya story? Thank you, Tom, for the introduction. Good morning and good afternoon, everyone. Dr. Faridar and I look forward to the presentation. We at Coya are focused on advancing innovative therapies to address significant unmet needs for patients who are suffering from serious neurodegenerative diseases. Our approach to address these diseases is to really get after the underlying neuroinflammation that is at the core of all these diseases. And how do we do that? We do that by modulating regulatory T cells, commonly referred to as Tregs. What the Tregs do is the Tregs modulate the immune system, but they also play a key role in maintaining immune tolerance and homeostasis. And this basically leads to the prevention of neurodegenerative diseases and also autoimmune diseases. While our focus at Coya has been primarily on neurodegenerative diseases, this mechanism has a lot of potential in autoimmune diseases as well. Dysfunctional Tregs essentially leads to neuroinflammation, and this in turn leads to the progress of these neurodegenerative diseases. Our therapies focus on improving the number and the function of these Tregs. Our pipeline assets are focused on this approach. Coya 301 is our pipeline product, which is a proprietary low-dose recombinant human IL-2. We also have Coya 302, which is our proprietary biologic combination of the low-dose interleukin-2 with the CTLA-4 Ig. We at Coya and many in the field, many experts in the field, believe that combination approaches that target multiple inflammatory pathways are likely to be more effective and also more durable in the management of these complex neurodegenerative diseases. To that end, we have partnered with Dr. Reddy's Laboratories, a deal with a potential value of $700 million to advance our combination asset, Coya 302, in amyotrophic lateral sclerosis, commonly referred to as ALS or Lou Gehrig's disease. We do anticipate initiating a phase two trial in patients with ALS. We also plan to follow this with a phase two trial in patients with frontotemporal dementia, a disease that is devastating with really no available therapies to date, supported by a $5 million investment from the Alzheimer's Drug Discovery Foundation. I will spend the next couple of minutes talking a little bit about what our pipeline assets, Coya 301 and 302, are. Coya 301, as I mentioned before, is a proprietary recombinant human low-dose interleukin-2. As previously mentioned, dysfunctional Tregs are associated with neuroinflammation, and this is promoted by activated T effector cells. People who are familiar with oncology probably understand that T effectors work in oncology. In addition, activated innate myeloid cells are also associated with neuroinflammation. So, we have two different things that drive neuroinflammation. What we know is that low-dose interleukin-2 has a robust effect on Treg expansion as well as suppressive function. What we also know from extensive literature and clinical practice, including experience in oncology, is that as you increase the interleukin-2 doses, interleukin-2 tends to do the exact opposite of what we want low-dose IL-2 to do, which is to increase the T effector and the TH17. This leads to actually a reduced Treg function. Dr. Faridar will present the results of the study in a few minutes, and you will see that this biologic effect plays out in this study as well. Now, low-dose IL-2 does have modest effects on innate immunity, but does not have a robust effect. You see about 20%-30% suppression of the innate myeloid cells with low-dose IL-2 alone, which is why we believe in combinations. Combining with an agent that also has a robust effect on the suppression of innate myeloid cells has promising clinical potential. And this is precisely what we do with our combination product, Coya 302, which is a combination of the low-dose interleukin-2 with CTLA-4 Ig. The CTLA-4 Ig converts the pro-inflammatory macrophages to anti-inflammatory macrophages. And when you combine this with the low-dose IL-2, which increases Treg function, one can see strong or one can provide synergistic neuro protection. This is why we call Coya 302 a pipeline within a product because of its potential across multiple neurodegenerative diseases, including ALS, FTD, Alzheimer's, and Parkinson's. The study that Dr. Faridar will present today, and he was the primary investigator on. It is a randomized double-blind study, investigator-initiated, that only studied the low-dose IL-2. Before I turn it over to Dr. Faridar, I want to say from a Coya perspective, we are excited and encouraged by these results as they further validate our approach. At a very high level, what was remarkable about this five-month study with low-dose IL-2 was that in five months, this study showed cognitive stabilization, although it was an exploratory endpoint as measured by the usual markers, including things like ADAS-Cog, which is a measure that is commonly used to measure cognitive function. What was demonstrated in this study is that in the every four-week arm, ADAS-Cog numerically increased in the treatment arm, and compared to placebo, the delta was approximately five, which is a very clinically meaningful difference in cognitive stabilization and function. The study also showed that low-dose interleukin-2 was safe and well tolerated, and subcutaneous administration of low-dose IL-2 expanded Treg numbers and function, did what we expected it to do without any off-target effect in other peripheral lymphocytes. This also was associated with movements in the CSF markers. Particularly remarkable was the statistically significant increase in amyloid beta 42, A- beta 42, which is when it is increased, increased A- beta 42 levels are known to be independently associated with slowing cognitive impairment and clinical decline. Basically, it is a surrogate for plaque reduction in the brain, and we saw the studies showed that A- beta 42 was increased. Dr. Faridar will present additional biomarkers that were studied as well. So, in summary, from a Coya perspective, this gives us a lot of confidence and validation in our approach. What we are seeing is that addressing Treg function does translate into efficacy, and in this particular study, as measured by the cognitive effects and biomarkers. With that, I'd like to invite Dr. Faridar to walk through the design of the trial as well as the results. Dr. Faridar? Thank you, Arun. Good morning, everyone. As mentioned earlier, this is a phase 2 randomized double-blind placebo-controlled trial to evaluate two different dosing frequencies of IL-2 treatments in 38 Alzheimer's patients. Of 38 enrolled participants, nine received IL-2 treatment every four weeks, 10 received IL-2 every two weeks, and 19 received placebo. The primary objective of this study was safety and tolerability. The secondary objective was the impact of IL-2 treatment on blood Tregs, and the exploratory objectives were the changes in CSF Alzheimer's biomarkers and clinical scales. Next slide. The average age of enrolled patients was 70 years. About 60% of them were women, and the baseline MMSE score was about 18, which means that patients were mainly in the latest. Next slide. All enrolled subjects tolerated and completed the treatment phase. There were no serious adverse events, and the most common adverse events were increased eosinophil count and redness or erythema at injection sites that were transient and resolved. Next slide. Next, we evaluated the impact of this treatment strategy on Treg population. The green line is IL-2 every four weeks, yellow is IL-2 every two weeks, and red is placebo. Figure A on the left up. Figure A shows the percentage of Tregs at baseline during the treatment phase and eight weeks after stopping the treatment on day 204. Administering IL-2 every four weeks led to a robust and sustained increase in the Treg percentage that was associated with enhanced Treg transcription factor FOXP3 in figure B and amplified IL-2 receptor CD25 in figure C. Suppressive function of Tregs shown in figure D was also improved following IL-2 administration. Interestingly, increasing the frequency of IL-2 administration to every two weeks had less effect on Treg expansion and the maintenance of FOXP3 expression, particularly toward the end of treatment phase. This is probably secondary to a biologic mechanism that repeated stimulation of Tregs without sufficient rest period following IL-2 every two weeks administration resulted in exhausted and unstable Treg population. Next slide. In the next step, we evaluated the impact of IL-2 therapy on CSF Alzheimer's biomarkers. Figure A shows level of CSF amyloid beta 42. As a reminder, higher level of CSF amyloid beta 42 indicates reduced amyloid beta pathology in the brain. Low-dose IL-2 administration every four weeks significantly improves CSF amyloid beta 42 levels. NfL in Figure B is a biomarker of neurodegeneration, and GFAP in Figure C indicates glial activation or neuroinflammation. In contrast to amyloid beta 42 levels, increased level of NfL or GFAP indicates worsening of the pathology. We observed a trend toward stabilization of CSF NfL and GFAP levels following IL-2 every four weeks administration, and there were no changes in the tau biomarker of p-tau181 in these three arms. The CSF biomarker data suggests that IL-2 immunotherapy has a potential positive impact on modifying Alzheimer's pathology in the brain. Next slide. And finally, clinical scales, including ADAS-Cog, CDR-SB, and ADCS-CGIC, were assessed at baseline in the middle of the treatment on day 64, and at the end of the treatment phase on day 148. In Figure A, ADAS-Cog scores on day 148 showed a slight improvement following IL-2 every four weeks administration, while scores worsened in the placebo group by 4.9 points. In figure B, the changes from baseline in CDR-SB were 27% less in IL-2 every four weeks arm compared to placebo, and the trend toward reduced worsening of ADCS-CGIC scores was observed following IL-2 administration. However, due to a small sample size, they did not reach statistically significant points. In conclusion, IL-2 treatment was safe and well tolerated. Administering IL-2 every four weeks effectively and specifically expanded and restored Treg population, and the positive signals of modifying AD pathology and reducing cognitive decline were observed following IL-2 administration, which needs to be confirmed in a larger clinical trial. I will wrap up my presentation here and pass it back to Arun. Well, thank you, Dr. Faridar, for that wonderful presentation. So what does this mean for us at Coya for Coya 301 and Coya 302 programs? We're obviously excited by these results. As I previously mentioned, we believe it validates our scientific approach. Dr. Faridar is expecting additional data from this study that will include CNS plasma markers as well as PET brain imaging, and we're looking forward to seeing those results that will further refine our strategy moving forward. We'll also continue to advance our discussions for other combination strategies with Coya 301 in larger cohorts of Alzheimer's disease patients that include other modalities, as well as look at the path forward for our combination asset, Coya 302, as well. In addition to that, Coya continues to plan and will execute on the clinical trials for Coya 302 in patients with ALS and in patients with FTD. The key takeaways for us, firstly, is that this study validates the hypothesis that restoring the number and function of Tregs targets neuroinflammation successfully. Second, the results also suggest that administering low-dose IL-2 systemically mediates significant disease-modifying pathology in the CNS. Third, the results from this study increase our confidence in Coya 302's outcomes in the neurodegenerative diseases, including our planned trials in ALS and FTD. Number four, this also gives us the opportunity and confidence to combine Coya 301 with other complementary modalities targeting Alzheimer's disease, for example, amyloid or tau targeting agents. And lastly, from a business perspective, that increases our confidence to pursue additional value-creating strategic partnership opportunities for Coya 301. With that, I will now like to turn the call over to the operator to begin the Q&A session and Tom to help moderate the Q&A. Thank you. We will now begin the question and answer session by phone. To ask a question, please click the link on the webcast or dial in by phone as indicated. Once connected by the operator, you will press stars and one on your telephone keypad, and to withdraw your question, you will press stars and two. And at this time, we'll pause momentarily to assemble our roster. Okay, thank you, Arun. I'll probably jump in and ask a couple of questions before we get to the queue. So Dr. Faridar, most of us know IL-2 from the cancer world, where it's one of the most difficult drugs to deliver. Can you just give us a sense of low-dose IL-2? How different is it? Is this like cancer IL-2, or is it closer to just delivering an antibody? How tricky will this be for hospitals to adopt if it becomes exciting? The dose is 15-30 times higher than the dose that we applied in our current trial. That's why we call it low-dose IL-2. Yep. High-dose IL-2 will activate the whole immune system. But the dose that we applied, that is 15 or 30 times lower than the cancer dose, is sensitive and specific to only bind to Treg population, not other immune cells, that many of them are kind of inflammatory, and just restore and expand Treg population. As part of this current trial, we also evaluated the other immune cell population to confirm the specificity of our treatment strategy. In this regard, we evaluated CD4, CD8 cells, natural killer cells that we showed the specificity of our treatment strategy to only target and expand Treg population with no adverse effect on other immune population. Okay. And Tom, if I may add to that, our low-dose proprietary IL-2 will be an aqueous prefill syringe, easy to self-inject or administered by a caregiver. So it's no different than a GLP-1 injection or insulin injection. That'll kind of be the patient experience. Got it. And then something you said, Arun, did you image A- beta plaque? Are we going to see plaque data down the road? And maybe for the company in your animal studies, does this suggest, if you correct inflammation, that you actually clear plaque? Yes. Actually, Arun? In our clinical study that published last year, in Alzheimer's mice model, we evaluated this effective strategy and showed that this Treg expansion strategy cleared amyloid plaque from the brain. In this clinical trial, we didn't do the amyloid beta PET scan, but we did CSF, as I showed the data. We did the CSF at baseline and at the end of the treatment, which showed that this effective IL-2 administration every four weeks improved the level of Aβ42, which indicates that the level of amyloid plaques in the brain reduced after six months of treatment. Okay, got it. Operator, why don't you go to the queue? Yes, sir. Our first question will come from Keay Nakae with Chardan. Please go ahead. Yes, thank you. Just a question for Arun and the investigators. How do these findings inform the design of your next studies in ALS, FTD, and specifically interested in how you might address the phenomena you're seeing in terms of the exhaustion of the Treg cells over time? Yeah, I can start addressing it, and Dr. Faridar can add to it. Key, good speaking to you. Key, as you know, our Coya 302 is the asset that we advance in both ALS and in frontotemporal dementia. And that's precisely why, because it is a combination of the low-dose IL-2 and CTLA4. And we do believe that having the CTLA4, and this is supported by the data of Treg suppression we have seen in our ALS trials, that we can keep that Treg durability longer and more effective and higher suppression as well. So we are pursuing the combinations in those two indications. What is encouraging from this trial for us is that it increases our confidence in the outcome of those indications. In those indications, obviously, we will have to do the studies. As far as design, obviously, we will go back and look at it, but at this point, we plan to do a randomized double-blind study, phase 2 study in ALS as originally planned. Definitely, the clinical team and our experts will look at the data from this study to see if there's something we can learn in terms of adjusting anything in the trial protocol. Dr. Faridar, did you want to add anything to that? Of course. And regarding the exhaustion, I think that for the next step, we will also. We didn't observe exhaustion of Treg in the IL-2 every four weeks administration. But the question is, what about if we extend this treatment? We need to evaluate that. We need to evaluate for the next phase, probably to evaluate in Alzheimer's to see what's the impact if we extend this treatment for a year, if we observe any exhaustion or not. And also, at the addition of CTLA-4 Ig to this treatment strategy, is it effective in reducing the potential exhaustion of Treg? We need to evaluate it and find out the result. Okay, great. And just a second question in terms of safety. You saw a really nice safety here with low-dose IL-2 as monotherapy. So when you combine it with the CTLA-4, again, as monotherapy, that drug in and of itself is fine, but any combined effects in terms of safety that you might be on high alert to look for? Thanks. Yeah, I can answer it quick. Out of court. No, please, Dr. Faridar. Go ahead, Dr. Faridar. I can answer this question. Sure. So far, for the small phase one clinical trial of IL-2 plus abatacept, we didn't observe any major or serious adverse events, but we cannot rule it out. We definitely need to evaluate it in the larger phase two clinical trial and probably to see if there is a potential side effect regarding the following immunomodulation of IL-2 plus CTLA-4 or not. But at this moment, I don't know. We just need to see. Key, as you know, we are planning on initiating clinical trials using Coya 302 in both ALS and FTD in 2025. Very good. Thanks. Again, if you have a question, please press star, then one. This will conclude our question and answer session. I would like to turn the conference back over to Mr. Tom Schrader for any closing remarks. Please go ahead, sir. Okay. Thank you, Operator, and everyone in the audience. Pretty rich data set for a small early trial. I hope you all enjoyed the presentation and enjoy the rest of your day. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.