Good morning, and welcome to the Saniona Virtual R&D webinar. At this time, all attendees are in a listen-only mode, and a question- and- answer session will follow the formal presentations. If you'd like to ask a question, please use the written Q&A text box at the bottom of the webcast player. As a reminder, this call is being recorded, and a replay will be made available on the Saniona website following the conclusion of the event. I'd now like to turn the call over to Thomas Feldthus, Chief Executive Officer at Saniona. Please go ahead, Thomas. Thank you, Char, and welcome everyone, and thank you for joining us today. This webinar is the first in a series where we will introduce Saniona's internal development program as they advance toward clinical development. We are starting with SAN2668, our lead development program, which is being developed for severe pediatric epilepsies, including developmental and epileptic encephalopathies, or DEEs. DEEs represents one of the areas of highest unmet medical need in neurology. Benzodiazepines remain among one of the most effective antiseizure medications available today, and they continue to play an important role in treatment of many severe pediatric epilepsies. However, their long-term use is limited by side effects including sedation, cognitive impairment, motor impairment, and tolerance. SAN2668 is designed to address this challenge by maintaining the powerful antiseizure activity associated with benzodiazepines while reducing the side effects that limit their chronic use. Later in this webinar, we will review the clinical data supporting this approach and our plans for clinical development. Before discussing SAN2668, it is important to understand the disease area we are aiming to address. Turning to this agenda, I'm delighted to welcome Dr. Nicola Specchio, Head of the Rare and Complex Epilepsy Unit at Bambino Gesù Children's Hospital in Rome. Please, next slide. Dr. Specchio is a global recognized expert in pediatric epilepsy and has served as a principal investigator on numerous clinical studies in DEEs and other severe childhood epilepsies. Following Nicola's presentation, our Chief Scientific Officer, Karin Sandager Nielsen, will review the mechanism of action of SAN2668 and present the key prediction data supporting the program. Our Chief Medical Officer, Pierandrea Muglia, will then discuss our clinical development strategy and the market opportunity for SAN2668. Following the presentation, we will open the session for questions and answers. With that, Nicola, thank you again for joining us today and for sharing your expertise with us. The floor is yours. Thank you very much, Thomas, and good day, ladies and gentlemen. It's a great pleasure be part of this meeting today. My topic is developmental and epileptic encephalopathies landscape and unmet needs. 15 minutes, I will try to explain and I will try to summarize what are the major medical needs and the unmet needs that we do have in this specific condition. What DEE is, this is here the summary in one slide. We're talking about a condition in which we do have patients which can be pediatric, but also adolescents, but also time to time adults, that they do present with epileptic seizures and/or epileptiform EEG activities together with developmental slowing or regression. Putting together these two concepts, so the slowing of development and the epilepsy, is part of the definition. What we do have is that we have one etiology, so the cause of epilepsy and developmental slowing and regression is exactly the same. One etiology responsible for both situations. This is exactly what we do mean with DEE. Moving forward, what we have in patients with DEE, we have, as I just mentioned, epilepsy, which is usually severe epilepsy and a lot of epileptiform EEG abnormalities. There are other non-seizure clinical manifestations around the single patients, and the single individual may present with, other than developmental delay, behavioral problems, psychiatric problems, speech impairment, sleep problems, and other issues, including GI, gastrointestinal issues. High risk of more complex condition in which we do have so many morbidities in a single given patient. You see here from this review of different papers, you have here the evaluation of what are the most frequent and severe disability in different domains, including mobility, hand use, feeding, and communication. You have here listed four different DEEs, which are Dravet syndrome, KCNB1, KCNQ2, and Lennox-Gastaut syndrome. You can appreciate that there is a high need of support for those patients in sense of disability. You have huge communication issues. Feeding issues also are very relevant, and also mobility. There are some differences in between the different diseases. Overall, it's something that is affecting all patients diagnosed with the DEE. One point that I want to make is, again, just summarizing one concept which may help understanding how much is important having a proper treatment for those patients. This is the normal development of a given child. When this child is affected by a given etiology, let's hypothesize genetic etiology, so a genetic mutation, the development, it goes down due to etiology, due to genetic mutation. When, on top of this genetic variant, you have a difficult to treat epilepsy, still, you're losing much more in terms of development. One step is due to the genetic variant, the second one is due to the epilepsy per se. Therefore, we have to think about how to interfere with this process. We have anti-seizure medications, and with anti-seizure medications, we can definitely improve the epileptiform EEG abnormalities, and we can improve epilepsy. What we're doing with precision treatment and disease-modifying treatment is acting on the cause of the situation. The treatment goal for those patients, we have two major goals. One is treating the seizures. The second one is treating and improving multimorbidities. You see that when we choose a drug for seizure control, we have to look at type of seizures, type of epilepsy syndrome, EEG abnormalities, very relevant, we have also etiology, again, and tolerability. We need to choose a medication which can really improve the seizure control, not only in terms of number, but in terms of EEG abnormalities, and a medication that should be well-tolerated because those patients, they do need almost long life treatment. They do have chronic conditions. What is the potential of impact? If I have a drug that is able to modify the epileptiform discharges and reduce seizures, I'm definitely improving cognitions. Why? Because in the mechanisms of epileptic discharges, you can see here, via different pathways, it affects cognition. It acts on the brain, disrupting the function, it acts on cells, making alteration of neuron development, and it acts on the processing of information. Epileptiform discharges are very bad for the brain of our patients. The question is: What are we really treating? The seizures, the encephalopathy, or both? Definitely, I was mentioning a little bit earlier before, controlling the seizures does not mean controlling the full disease. Morbidities often are very relevant for the quality of life of those patients. We need to think about shifting from the anti-seizures to the disease-modifying approaches, even if the definition, and there is a discussion around what is a disease modification and how we should address the underlying neurobiological process, which is something that is not actually happening right now. All those patients, they do have a polytherapy. Drugs are used in combination because of different type of seizures, because most of them, they do have drug-resistant epilepsy. They're used quite early in the disease progression and quite aggressively because we need to stop seizures. We need to reduce epileptiform abnormalities. However, time to time, if we use too many drugs, if we use those drugs not appropriately, we may even worsen the developmental outcome because the side effects for some medications are heavy, and we need to protect our patients. Using many medications together, many, two, three medications together, is fine, but very carefully. We accept polytherapy, as I mentioned, because those patients, they do have uncontrolled seizures. I'm mentioning here, time-limited and regularly reviewed. We don't want to have effects which are against the development of our patients. Trying to use anti-seizure medications with different mechanism of actions, with innovative mechanisms of action, and with the less possible side effects. I give you here a quick example of a condition in which we do have an increase of epileptiform abnormalities during sleep, which is, this is called developmental and epileptic encephalopathy with spike-and- wave activation during sleep. What the spike-and- wave activation during sleep, which was previously called ESES, electrical status epilepticus, what does in the brain of our patients? Cognitive disturbances, you have language regression or regression of cognitions. ADHD, irritability. Some patients, they do present with autism spectrum disorder. What we can do? We have to look at the modifiers. We have to look at how to improve the outcome of those patients. You see that the prognosis definitely is related to the etiology, but a delayed treatment or ineffective treatment, it will give a poorer outcome in terms of cognition. Therefore, the intervention should be rapid, should be with proper medication. What are the best medications for these conditions? With this review, we look at the different results of studies. For this DEE with spike in wave activation, the first-line treatment is corticosteroids and benzodiazepine. It's in the same group, being corticosteroids a little bit earlier than given than benzos, but the great majority of those patients, they are on benzos. Nowadays, what we use is clobazam. Those medications can be effective on the SWI is the spike- and- wave index. Still we have limited cognitive effects. Also, a very relevant risk is the tolerance. Patients, they start to not respond anymore to benzos and steroids after a while. Then there are the possibility of utilizing adjunctive treatment with other anti-seizure medication, depending upon the number of seizures, avoiding polypharmacy when possible. The last point is that some of those patients, they can be treated with surgery, but very few of them. Really, we have few options for those patients. Goal number two, morbidity management. This is, again, the list of some DEEs due to genetic mutations. You can see here that the top priorities for families are the expressive communication, the blue bar, the gross motor function, the orange one, and at the end, you have the receptive communication, behavior, and other issues. You can see here that in several of those DEEs, we do have similar issues for our patients. We do have some unmet needs for those patients, for patients with developmental and epileptic encephalopathies. This is the job that we're trying to do, is trying to fulfill these needs, to give answers. Firstly, we need to have much better biomarkers of progression of the disease. What I mean is that some of those patients, they may worsen over time if we're not able to control their epilepsy and their EEG epileptiform abnormalities. This is through the evaluation of the complexity of EEG, CSF markers, and so on. We need to have better predictors of who are the responders to some given medications. This is the job that we're doing to using the genotype-phenotype correlation and the deep phenotyping for those patients. Inclusion on non-seizure endpoints in clinical trials. Again, this is another relevant point. Equity of, and access. There is a quite global disparities in the access in targeted therapies around the world. Last but not least, of course, the transition from pediatric to adult medicine. Take home messages. Definitely, seizure control is necessary in developmental and epileptic encephalopathy, but not really sufficient. We need to look behind seizures. We need to look at multi-morbidities as far as they do drive the lifelong disability burden. We're now in the age of trying to have a precision medicines, which is shifting the care from seizures to non-seizure outcome. Also to treat the non-seizure count, to evaluate the non-seizure outcome, we need to develop good measurement tools. The treatment definitely evolves with the child, evolves while the child is growing up. This is a moving target. The success is a moving target, depending upon the age of the patients. This closes my talk. I thank you very much for your kind attention. Good morning, good afternoon. My name is Karin Sandager Nielsen. I am the Chief Science Officer of Saniona, and it's a great pleasure for me to walk you through the mode of action and the preclinical data we have generated on 2668. Next slide, please. The GABA-A receptor is the molecular target for 2668. The GABA-A receptor is a ligand-gated ion channel that is activated by GABA. GABA is the main inhibitory transmitter in the brain. When GABA binds to the receptor, that opens up the channel, and that allows chloride ions to flow in. That hyperpolarizes the neuron and results in inhibition of neuronal activity. That's believed to be the reason why drugs that potentiate the effects of GABA, such as the benzodiazepines and our own 2668, so robustly abort diseases. 2668 binds at the site where the benzodiazepine also binds, and this site is distant from where GABA binds, and that allows for positive allosteric modulation of the inhibitory action of GABA without having any intrinsic activity. This is a concept of a PAM, a positive allosteric modulator. The ion channel consists of five subunits that's normally composed of two alpha subunits, which can be one of either alpha-1, alpha-2, alpha-3, or alpha-5, two beta subunits, and one gamma subunit. It's the identity of the alpha subunit, which is either alpha-1, alpha-2, alpha-3, and alpha-5, that determines the function of each receptor. Next slide. Benzodiazepines non-selectively potentiate the effect of GABA at receptors containing either alpha-1, alpha-2, alpha-3, and alpha-5 subtypes. Benzodiazepines are really, really effective medicines in general and in particular, antiepileptics. Their non-selective action leads to side effects like sedation, cognitive dulling, falls, in particular in the elderly, addiction. We know that all these adverse effects are primarily driven by too much alpha-1 modulation, while most of the beneficial effects are mediated through GABA alpha-2 and alpha-3 modulation. Subtypes activity is very, very critical in order to obtain or maintain benzodiazepine-like seizure control while avoiding the benzodiazepine-like limitations. Next slide, please. The differentiated pharmacology of 2668 is exactly designed to preserve the benzodiazepine class efficacy without the benzodiazepine class adverse effects. The schematic you see in this slide outlines the relative functional activity of 2668 on the separate GABA- A receptors. The strongest modulation is on alpha-3-containing receptors, targeting the thalamocortical circuits that are implicated in spike wave pathology in DEEs, followed by robust alpha-2 modulation for potent control of convulsive seizures, both generalized and focal seizures. Then we have introduced a moderate, or you can call it a balanced alpha-1 modulation, and it's intended to be high enough to preserve the benzodiazepine class anti-seizure efficacy, but low enough to minimize the limitations. So with this profile, we anticipate the 2668 is able to maintain the strong seizure control while avoiding the limitations of the benzodiazepines. I will show you the preclinical data we have generated to demonstrate this in the next few slides. Next slide, please. This slide demonstrates in mice that 2668 results in improved seizure control versus a benzodiazepine. Here we've chosen clobazam. As Nicola alluded to, it's actually used in pediatric epilepsies, and it's likely due to achievement of higher receptor occupancy by 2668. The animal model we have used here is the PTZ threshold test, where higher numbers on the Y-axis corresponds to increased seizure threshold and accordingly, an increased seizure prevention. We've selected a dose of 2668 that targets approximately 30% receptor occupancy, assuming that we'll be able to dose up to that and beyond in humans. We have compared that to a human equivalent dose of clobazam that results in approximately 40% receptor occupancy. As you can readily see here on the graph, the seizure protection by 2668 is increased versus that of clobazam, and that's likely due to the achievement of higher receptor occupancy by 2668. Next slide. Spike wave discharges are aberrant electrical activity in the brain that arises from pathological oscillations in part of the brain that is called the cortico-thalamic system. There's a lot of converging evidence that links GABA- A alpha-3 containing receptor dysfunction to the generation of these spike wave discharges. GABA alpha-3 containing receptors are the dominant GABA- A receptor here in this part of the brain. Also benzodiazepines such as clonazepam, that is active against absence seizure suppresses spike wave discharges. This suppressing is actually absent in alpha-3 point mutated mice that are rendered insensitive for benzodiazepines. Finally, we have shown with our own SAN711, it's now called ACP-711, and as it was the molecule that was out licensed to Acadia. SAN711 is a subtype selective GABA alpha-3 PAM, and that markedly suppresses spike wave discharges in a rodent model called the GAERS rats, finally confirming the alpha-3 mode of action pharmacologically. As I will show you in the next slide, 2668, which demonstrates a very high level of alpha-3 modulation, also strongly suppresses spike wave discharges. Next slide, please. So this is the slide that depicts the very potent efficacy of 2668 against the generalized spike wave discharges. They can be studied in GAERS rats, which is an inbred rat strain that presents with numerous spontaneous generalized spike wave discharges. On the left-hand side is actually an example of such a spike wave discharges taken from the study from one of the rats that are enrolled in the study. On your right-hand side of the slide, that shows the effect of 2668 on the spike wave discharges. The Y-axis depicts the cumulative duration of spike wave discharges, while the X-axis represents the time course after dosing. As you can see by the black line, which is GAERS rats, that has been dosed with vehicle right after a baseline session, they show a very prolonged time spent in spike wave discharges. In contrast, the yellow lines, which represent increasing doses of 2668, you can see they demonstrate a very potent and robust suppression of spike waves with a minimal efficacious dose of 0.3 mg/kg and the highest dose of 0.1 mg/kg fully suppressing the spike wave discharges. You actually get a full normalization of this aberrant electrical activity by the highest dose of 2668. If you go to the next slide. We've also tested the effect of 2668 on another seizure type, namely focal seizures, which arises in one part of the brain and can generalize to the entire brain. The benchmark chronic model for focal seizures is the amygdala kindling model, which replicates progressive epileptogenesis and also seizure propagation up to the cortex. It's known to have a very strong predictive validity for clinical anti-seizure efficacy. The seizures in this model are measured by recording of the after discharges, in seconds, you see that on your left-hand side. After discharges are abnormally prolonged electrical activity in the brain caused by the kindling. It's also assessed by the seizure severity, done by visual observations using a behavioral score. You see that on your right-hand side. The white bars on this figure represents measurements during baseline sessions where the rats are not treated with 2668, while the blue bars represents measurements after the rats have been dosed with increasing doses of 2668 or diazepam, that's the dark blue bar. I think what is readily evident here is that 2668 results in a very potent suppression of focal seizures, monitored as after discharges on your left-hand side. This marked suppression is also evidenced by a comparable reduction of the seizure severity seen on your right-hand side. In both instances, the suppression is comparable to that of the non-selective benzodiazepine, the active comparator in this study, which is diazepam. Next slide. Several of the DEEs are genetically defined, and rodent models of many of those are difficult to get hold of and not necessarily developed. We have turned to zebrafish, which constitute a validated and very rapid way of assessing in vivo activity on genetically defined disease models. This slide shows a snapshot of some of the data we have generated on the effect of 2668 in one of the monogenetic DEEs called syngap1b. The data shows the strong effects of 2668 on seizure events on your left-hand side, aggressive behaviors in the middle, and also on cognitive impairments caused by introduction of the syngap1b mutation in the zebrafish. In each of the figures, the gray bar represents mutated zebrafish without any treatment, and the black bar is the active comparator, clobazam, while the blue bars represents increasing concentration of 2668. I think the data quite clearly shows that 2668 fully suppresses the number of seizure events on your left-hand side, also markedly reduces aggressive behaviors in the mid figure. In both instances, the effect size are comparable to or may even be improved as compared to clobazam. What I think is really interesting is when you look at the right-hand figure that shows the 2668 also seems to rescue the cognitive deficits that is induced by this mutation. In this instance, the comparator clobazam was non-efficacious suggesting a potential benefit of 2668 over clobazam. In conclusion, based on this slide, 2668 not only demonstrates efficacy against the seizures in this model of monogenetic epilepsy, but the efficacy seems to extend beyond the seizures, supporting a potential benefit in behavioral disorders in DEEs where there's a great unmet need. Next slide, please. This slide is just to show you that the differentiated profile of 2668 with this balanced alpha-1 modulation does not lead to the adverse effects such as motoric instability or sedation in pharmacologically relevant dose levels in rodents, as assessed by the rotarod and locomotor activity. The left-hand side of the figure depicts the lack of effect of 2668 on motor performance evaluated by the accelerating rotarod, while the right-hand side of the figure shows that increasing doses of 2668 does not affect locomotor activity of rodents, that's a test that is very sensitive for sedative effects. Next slide, please. The key take-home messages here is that 2668 shows quite strong preclinical efficacy and good tolerability, that supports that it has a differentiated profile. We've demonstrated superior seizure control at high receptor occupancy versus a benzodiazepine versus clobazam. Also importantly, it shows broad efficacy across a number of chronic epilepsy models that displays different seizure types, spike-wave discharges, and focal seizures. The benefit seems to extend to the behavioral comorbidities as well, as evidenced by rescue of aggressive behavior and also amelioration of cognitive deficits. All this is evident without any motor impairment or sedative effects at pharmacologically relevant dose levels. We do believe that those data supports a potential for 2668 as a safe, effective treatment for pediatric DEEs that extends with potential extension beyond the seizure control. With that, I'll hand over the floor to Pierandrea. Thank you, Karin, and good morning, good afternoon to everybody. Pierandrea Muglia, the Chief Medical Officer at Saniona. Dr. Specchio here outlined on the significant unmet need of these severe conditions. Karin has presented this robust, encouraging efficacy profile of the compound. My role is really to show how we plan to translate all these findings into a human proof of concept in patients. We have defined a developmental strategy that, thanks to validated biomarker, it can generate fairly objective evidence of activity and allow a rapid de-risking of the program. The different strategy, importantly, it's also been informed by my and other clinical team members and regulatory team members' experience in DEEs, a recent successful story that we have been all part of. That allow us to kind of anticipate some of the hard dose and put in place measure to minimize the risk of the program. More importantly, I would think, is really to focus on what is important for a patient and family. If we consider, you heard this description of these conditions and from Dr. Specchio here, this is like a multifactorial complex disorder. Our data indicates this robust effect on seizure, but also on non-seizure endpoints. In addition to the non-seizure endpoints, we see this on this pathological EEG electrical activity. Altogether, this efficacy can translate in a kind of a broad disease control. This is why we say that we have a potential disease control that could go beyond seizure. Clearly, seizure is the primary focus, but we can have this additional benefit that we know are very important for patient and for their development. This is like the efficacy side. On the tolerability, on the left side, you see that, as you saw and illustrated by Karin, that the design on the pharmacology and the data support a reduced sedative effect, and also preserved motor function that is quite compromised in this subject, and with the current treatment, particularly benzodiazepine, we further compromise the motor function. For example, induced hypotonia in severely affected hypotonic kids. The other big important differentiating factors that we put in a lot of attention is the fact that all benzodiazepine and all other anti-seizure medication, they have a profound CNS effect, and particularly, they have a cognitive impairment enduring of these kids. We expect less that with our compounds and to a neutral effect on cognition. All this should translate into a potential clinical impact, as you see on the right side. We will have a good chronic use with the reduced tolerability. Reduced tolerance means that we expect to maintain the effect because of the pharmacology and the data, and improve the development of these kids that are compromised by seizure, EEG activity, and all these behavioral issues. In a longer term, as you heard from Dr. Specchio here, these kids that are on polytherapy, that's kind of more a rule than an exception. They take two, three anti-seizure medication, and if you have a new agent that has a robust seizure control. You have the option to reduce this burden that is given by anti-seizure medication, and therefore improve the long-term outcome. That's the ultimate ambition and the opportunity we see ahead of us with the preclinical profile. If you look in this slide, is really the key differentiating feature that we expect based on the pharmacology in the data. When I say the pharmacology, this is a selective GABA pharmacology that Karin and teams are working for a couple of decades. We really understand the nuances on the selectivity and what to expect by all this selectivity. This is the resulting differentiating profile we expect versus benzodiazepine, but also versus most of the anti-seizure medication. They all have a sedative effect, and impair cognition, and have, most of them, motor impairment, and for sure, tolerance, meaning that the efficacy goes away with time. 2668 is expected to have all improvement on these factors. As you see in this slide, I have delineated here at a high level our development strategy. This has been designed, of course, we will have to measure PK safety in healthy volunteers as a first aim. Thanks to these biomarkers that we can use, and they are a validated biomarker for target engagement and pharmacodynamic readouts, we have defined this program that can objectively determine if this compound is truly differentiated as we hypothesized based on the preclinical data. We will have defined different clinical studies and component that will address key questions that you see listed there. We will have a biomarker for target engagement. Are we engaging the target? Using PET and a selective GABA- A selective tracer, we can say, are we engaging the target, at what doses, and what dose limits we should impose based on this readout? The biomarkers that I'm going to illustrate in a second will tell us if this is truly differentiated versus benzodiazepine. The other key component of the program is the ability to utilize an early inpatient study that rely on a very well-established paradigm that I will illustrate in more details. Basically, this has been used with most of anti-seizure medication in development. If you expose to flickering light a susceptible epileptic individual, you will see an EEG readout. With our compound, we can suppress that effect or test if the compound suppressed that effect, at what doses. We can identify early on doses that are expected to be in the clinical range. Eventually, we will do a phase II study in pediatric to test efficacy. This slide is a fundamental one to understand how sophisticated is going to be our phase I program. First of all, we are partnering with the CHDR, a phase I specialized unit in the Netherlands, has a lot of experience in testing this pharmacology, as defined as a comprehensive battery of tests that you see on the left side, that they are all computerized and used and implemented regularly. What it allows us to do is to define the effect of the drug on motor function, on EEG, and eventually on tolerability issue and cognition. On the right side, for illustrative purpose, I'm showing you what type of output we will generate. You see the red line is the typical benzodiazepine test in all these measures, and you see where it sits on this radar plot. The green dashed line is what we expect for 2668 and how it is different from historical benzodiazepine testing in the same paradigm. This early readouts in phase I will really allow us to tell us the differentiate profile of the compound and its differentiating potential. Now, if the other biomarker that, as I said, we will be able to utilize is this PET tracer that will allow us to test different exposure of the drug and what type of target engagement. This will be very important to define the dose strategy during phase I, but more importantly, to pick up the best and optimal dose to progress into phase II in patients. This information will be matched with this paradigm that we'll be using during the phase I, right after the single ascending dose. In a single dose setting, as traditionally done, we will expose susceptible subjects to this intermittent light stimulation that will generate this EEG trace that you see here indicated. The paradigm is developed so that you can test the condition without drug, and then the effect of our drug in suppressing this EEG activity. This is, as I said, is predictive of anti-seizure efficacy, but also predictive of which dose are expected to give anti-seizure efficacy. This early readout, combined with the PET and all other data, will allow us to rapidly progress in efficient way to the study in patient. This is the pediatric study that we have delineated also based on our experience, as previously said. We will first do an open-label study in few subjects to understand the equivalent dose in pediatric patients that will be modeled up front, and then that study will tell us if the modeling will be correct. That will allow us to move into the randomized placebo-controlled study, phase II of the study, where we will measure seizure effect on EEG and effect on non-seizure endpoint. What is the size of the problem? We have consensus figures that are coming from the field that everybody accept and adopt based on a number of epidemiological study and treatment rate, and we have quite precise numbers. With that, we define our potential revenue. I think everybody has those numbers, and they have the validity of whatever forecast as a validity. What I think is most important to the value of the program is just to illustrate recent transaction in this phase, because they clearly illustrate the pharma companies that acquired this single asset for single disorder, single DEE, or group of DEE, as for the recent acquisition, the value that they've been given. Those are all multi-billion transactions for compounds that have some differentiating features that can manage seizure in these difficult conditions. That speaks by itself on the potential value of such programs. We are really enthusiastic about embarking on this program, we are really planning to get in human later this year, with the submission and potentially dosing first human subject early next year. In that sense, what we have for 2668. We have a robust preclinical data, not only on seizure, on non-seizure endpoint. They are critical for patient and families, as you heard. Irritability, aggressivity, they need to be managed, and there is a potential here for some of the preclinical data. We have then defined this developmental strategy that based on established biomarker will do early de-risking, early objective readout and differentiation. You see here the key listed value inflection point we will see in the program, the early programs that will be, as I said, starting early next year. With that, I complete my part, over to Thomas for his wrap-up of the session. Thank you, Pierandrea. Before we open up for questions, I would like to briefly summarize key messages from this webinar. First, development in epileptic encephalopathies remains among the areas of highest unmet medical need in neurology. Despite the availability of treatment options, many patients continue to experience severe seizures, development impairment, behavior issues, and there's a substantial burden on both patients and their families. Second, while benzodiazepines remain among the most effective antiseizure medications available today, their long-term use is limited by side effects such as sedation, cognitive impairment, motor impairment, and tolerance. Third, SAN2668 has been specifically designed to maintain the powerful antiseizure efficacy associated with benzodiazepines while reducing the side effects that limit their chronic use. The preclinical data presented today demonstrate robust seizure control across multiple models, activity against spike-wave discharges with potential to increase cognition, efficacy in behavioral endpoints, and a differentiated tolerability profile. Finally, we have outlined a clinical development strategy designed to rapidly generate human data through the use of translational biomarkers, PET imaging, and an early proof of mechanism study in photosensitive epilepsy. Before we advance into patients with DEEs, we believe SAN2668 represents this exciting opportunity to address a significant unmet medical need, and we look forward to advance the program into clinical development around year-end this year. With that, we will be happy to take your questions. Thank you. We open up for Q&A now. Yes, Thomas. Just pull on some questions that have come in through the audience here. First question that's come in, can you talk about why SAN2668 is ultimately the right focus for Saniona's next chapter? Yeah, I would take that one. SAN2668 is an excellent fit with our strategy. It combines, in our view, a relative attractive risk profile with significant commercial potential in an area with high unmet medical need. The biology is well understood in this case, and we believe SAN2668 is differentiated both from benzodiazepine and previous subtypes selective GABA moderators. The goal here is to retain the benzodiazepine class efficacy while we reduce the side effects that limit the chronic use. The clinical data support this. We now focus on severe pediatric epilepsies, which represents a substantial commercial opportunity in an area where we potentially have the opportunity to take the program significant further ourselves. Therefore, we believe that this program that could fit very well into our strategy of advancing selected assets through late-stage development and potential commercialization allowing us to retain substantially more value than just in traditional partnering model. This is why we are so happy with this program. Awesome. Thank you, Thomas. The next question from the audience is, can you talk about what is the most promising aspects of 2668, in respect to the DEE opportunity? Would you like me to take this one, guys? Yeah. Yeah, sure. Nicola go on, if you feel you had enough then. Okay. Yeah. What I've explained to you guys about DEE is, this drug, it seems is addressing network dysfunction and developmental burden also behind the seizure reduction. What is really exciting for us as a clinician is that targeting the spike in wave pathology, as Pierandrea just showed a little bit, it's something that is very interesting in terms of clinical output. As far as what we do actually know, and we're very sure about this, is that many DEEs are characterized by persistent epileptic form activity that contribute definitely to cognitive and behavioral impairment. Therefore, if we're able to have a complete suppression of the spike in wave discharges, through the mechanism of action via the alpha-3 subunit, this is going to improve definitely several aspects, including reducing the sleep-related epileptic form activities, because these receptors are very highly expressed in the thalamus, and the thalamus is relevant for the sleep. It's relevant for the spreading the seizures from one hemisphere to the other. The epileptic form activities in some seizures are really mediated by thalamus. This is a really potential impact not only on seizures, but there is a potential impact on behavioral communications very high. Awesome. Thank you. The next question is, can you talk about what does 2668 selectivity profile enable that earlier alpha-2 or alpha-3 selective positive allosteric modulators couldn't achieve? Yeah, I think I should take that one. As I said in the presentation, this entire field and this program rests on the shoulders of more than 30 years of scientific discovery. When it was discovered back then that the majority of the adverse effects of the benzodiazepines was mediated by too high alpha-1 modulating, most of the companies, including the one that I was working at at the moment, NeuroSearch, tried to dial out alpha-1 activity entirely, that resulted in improved tolerability, but it might have been at the expense of efficacy. What differentiates 2668 is that apart from the fact that we have pretty high modulation on the beneficial alpha-2 and alpha-3 receptors, we have introduced a balanced, or calibrated, or whatever you would like to call it, alpha-1 modulation. That's explicitly designed to preserve the benzodiazepine-like efficacy, in the hope that it's low enough not to cause the adverse effects. I think it's readily evident in our animal models that this balanced alpha-1 modulation contributes to a stronger seizure protection. We might have hit the right balance. That is, of course, to be seen in the clinic. At least we see that the additional alpha-1 activity shows increased seizure prevention. We don't see the benzo-like adverse effects, at least in our rodent models. I think that's the critical point, the critical differentiator for 2668 versus the other two, three PAMs. Awesome. Thank you. The next question is, can you talk about which preclinical data are the most important in supporting 2668's potential in pediatric DEEs and ESES? Should I go for that one as well, or? Yeah. Yeah, I can do that. As Dr. Specchio said, seizure prevention is of essence. That's the most important thing. I think it's quite compelling, the data we have demonstrated, that 2668 very robustly, very potently suppresses, fully suppresses seizures in a range of not only acute seizure models, but also in the chronic epilepsy models that presents with different types of seizures. That's the first thing. I think the preclinical data are quite impressive. The second thing is that there's a great unmet need on the behavioral disturbances in the DEEs. The data we have generated so far actually does suggest that the 2668 may have a benefit beyond seizure protection in that it could ameliorate or rescue some of the behavioral disturbances that are seen, such as aggressive behaviors, cognitive impairments in particular. From my side of the table, I think that's the most compelling data. Thank you. A couple additional questions here that have come in, Can you talk about the significance of using the quantitative EEG biomarkers in the planned phase I study? Yeah, I can take that one. Thank you, because this is like for brevity, I couldn't expand on this very critical aspect of our phase I program. We in the field has quite a bit of experience on what we call pharmaco-EEG. That means understanding what the specific pharmacology does on the EEG trace. We recently completed a phase I of an alpha-3 selective compound that we partnered out to Acadia, We really understand what to expect. This is going to be very helpful biomarker to respond to one critical question. The critical question of the program is: Is 2668 has a sedative effect, and if it does, at what doses? Of course, when you do that as a question, you're going to be asking the patient. Actually, the patient's going to tell you, look, I feel a little bit sleepy, and that you see and you observe it. That's not very objective. The EEG can objectively tell you if the sedative effect is relevant. If you use a benzodiazepine, you have specific waves in the EEG that are called delta waves that are increased because you're sedated, you're sleepy. Basically, just to give you one example, we will be looking for the lack of an increase on delta waves that will be an objective way to demonstrate that the compound is not associated with the sedative effect or is associated with a very reduced sedative effect. That's the utility of the EEG, or pharmaco-EEG, as we call it, during our phase I program. Just to say that we will do that during the single ascending dose, during multiple ascending doses. Multiple dose level will have all the readouts. We will compare effects, doses, and exposure. Awesome. A follow-up here, can you talk about the added value of the photosensitivity study as well? Yeah. This is like, I would say in the CNS, that's what I've been doing, is unique opportunity that you can do a test in patients so early on. The test in patients, as I described, is something that has been extensively used and validated, so has a great predictive value. You see this effect on the EEG and the suppression of this EEG activity, you will expect, and you will see anti-seizure effect. Basically, it's a very early readout of efficacy in patients, that will be tremendously important to correlate that exposure where you see efficacy with everything else we will do in the program in the phase I. Awesome. I think that concludes the Q&A, and it looks like we're at the top of the hour, so I'll turn it back to Thomas for any closing remarks. Thank you. Speaking a little bit about the financing then. Today, based on our current plans, we have funding into the second half of 2028, while advancing our three internal prioritized programs through phase I development and initiating phase II study for at least two of them. For SAN2668, this includes the planned phase I study, the PET study and biomarker work, and the anticipated photosensitivity study, which could provide the early evidence of anti-seizure activity in humans, as Pierandrea just mentioned. A larger phase II study in DEEs would require additional funding, and this could come through partnering, financing or a prioritization of our resources, or a combination of those three. Our focus today is to generate clinical data that will maximize the value of the program and expand our strategic options in this context. Thank you.