Hello there. This is Jonathan Aschoff, senior biotechnology analyst at Roth Capital Partners, and I'm here with Serina Therapeutics, with CEO Steve Ledger and CFO Gregory Curhan. Steve and Greg, welcome. Thank you. I'm a guy who gets right into the questions. I would love it if you guys could explain to me your POZ platform technology in pretty simple terms and why it's unique. In very simple terms, Jonathan, the POZ is a next generation drug delivery, drug product optimization platform that we've targeted initially as a core strategic focus at the vast universe of small molecules that have challenges in their current form factors, whether that's oral delivery, where you have low bioavailability and solubility issues, or they have to be delivered at a volume that requires an infusion-based treatment. Patient goes into infusion center once a week, once a month, and gets treated in that fashion. Our technology is optimized to take these challenging small molecules and deliver them as a once-a-week injection. That is our near zero order PK profile that we've built with this biocompatible polymer called poly(2-oxazoline). Importantly, the scientific founders of Serina, this is not their first rodeo. The scientific founders invented what became the standard half-life extension technology for proteins back 30 years ago. That technology is known as PEGylation, and it became a standard for protein drug delivery. Think about POZ as the PEG of small molecules. The universe of small molecules is vastly bigger than the universe of biologics that PEG was working with. Great. Thank you. You mentioned three platform programs, or you have three platform programs, small molecules, RNA therapeutics, and ADC/AOC. Expand on that little definition there for folks. What is the strategic focus of these three programs? Our primary focus and where we've focused the investor conversations is the small molecule platform. Specifically, the therapeutic area that we're first working in is CNS, where we have three programs advancing, two announced, one in stealth mode. SER-252 is the lead program for the treatment of advanced Parkinson's disease. That is in a phase I-B registrational study. We've dosed first patient in that study. The second program is a POZylated version of the molecule known as valbenazine or tetrabenazine. That's the active moiety in the tardive dyskinesia drugs from Teva, AUSTEDO, and Neurocrine's INGREZZA. That is a significant market that we're going after with our next small molecule program. We've got a third program that we hope to have a lead candidate identified in the next nine months or so that we think is as exciting or more exciting than the unmet needs in these other indications. The other modalities have been a bit starved for capital recently because of the nature of being an orphan small-cap biotech company and under-capitalized, which we are solving for as we speak, and announced a deal last week that is part of the capital stack of where we need to go. Both of those programs, we expect to have data. Those are preclinical programs, proof of principle programs, but these modalities are very exciting. The RNA therapeutic space has thousands of active drug development programs targeting gene editors and various oligos. Our ADC program has some exciting early data around creating the ability to use novel payloads in an ADC because of what our polymer can bring to the ADC construct. Thanks. What is the regulatory advantage of the 505(b)(2) pathway you're pursuing? The pathway has been around forever, and it's typically a pathway that accelerates the development process because it allows sponsors to rely on the data that they don't own, data from an already approved drug. There has to be a listed drug that you can leverage data from, and if you can create a better product from that active moiety that's an already approved drug, then you're eligible for this pathway. The devil's in the details as to whether you would want to pursue that pathway. You aren't able to make any efficacy label claims of superiority to the listed drug. If real-world use of your product will tease that out and you feel that your data package is really robust in terms of proving that this is a best-in-class asset, the advantage of going on that pathway is twofold. You don't have to run a bunch of different randomized controlled trials. You can often go from a phase I-B registrational study to an open label safety study and get an NDA submission out of that. You can pull forward the NDA submission and approval process by years, and of course, that means the burn rate of your company is pulled in commensurately, and the clinical trials tend to be smaller in terms of the number of subjects or patients. It is a key aspect of our business model, where we're looking to leverage our POZ platform technology to apply to existing small molecule drugs that are approved, but they are not optimized as products, and there's an unmet need for a once-a-week subQ injection that will get significant share of that opportunity to help those patients where the current standards of care are not Perfect. Yeah, it sounds quite efficient. Why is SER-252, or why do you think it is positioned as potentially a best-in-class for advanced Parkinson's? Well, I'm in no position to say it's best-in-class, but the subject matter experts and the KOLs that we've engaged on the project on the front end, before spending the dollars in the clinic, on the front end to really understand the unmet need and the patient burden with the current therapies, the current standards of care, what the competitive landscape looks like in emerging disease-modifying therapies. Boiling all of that and surrounding ourselves with the best subject matter experts, both in drug development and in clinicians that know these patients, we're pretty comfortable that our target product profile will be considered best-in-class if it's supported by the data we think it could be supported by. The current standard of care in advanced Parkinson's, we define that target market as patients who ultimately get to the point in the journey where their symptoms are inadequately controlled by the current standards of care. They've likely been on levodopa carbidopa in oral form for years. They've moved to adjunct therapies like COMT inhibitors, MAO-B inhibitors, COMT inhibitors, oral and longer-acting versions of the oral formulations. They are now firmly in the category where many of those patients are not responding to those treatments, yet they still have a potentially long life ahead of them, and the quality of that life will deteriorate without some way to provide continuous dopaminergic stimulation. The products that have emerged to do that are infusion products. Imagine our target product profile, which is a twice-a-week injection of a powerful dopamine agonist, apomorphine, versus the infused version of that product today, where the patient wears an electronic pump 16 hours a day, takes it off at night, patient wakes up in a functionally off state, needs to be rescued, rinse and repeat. The injection site creates skin reactions that has to be moved around the infusion site, rather. Our product profile, the KOLs think that it will be, if we can get there, the best-in-class continuous dopaminergic stimulation therapy for what we estimate just in the U.S. and EU plus for U.K., 250,000 patients is sort of the target market. You slice that up by major market where you can find these patients. They're in major movement disorder centers, you have a significant commercial opportunity and a significant opportunity to help these patients. That sounds promising. Can you walk us through the clinical design, the clinical trial design for SER-252 and especially focus on the key endpoints? We had an extraordinary outcome at our Type B meeting, pre-IND meeting with FDA back in August of 2025, where we went for an aggressive ask with the agency. Supernus' product, APOKYN, had been approved in February of 2025, and we now had a listed drug to be a comparator in a 505(b)(2) NDA pathway. We completely modified the design of our clinical trial to ultimately end up with a head-to-head with that approved drug. We went into the meeting with the agency, and they saluted our trial design and the registrational pathway that our one study would be viewed as a registrational study. No need for a confirmatory phase III study, just an open label safety study those patients could roll into and an NDA submission. That was an extraordinary outcome. The clinical trial design is a SAD arm in advanced patients. That trial has begun dosing. The first sites have been activated in Australia, where we're taking advanced Parkinson's patients into a phase I unit and dosing them with our commercial product versus placebo. The trial design of the SAD is five dosing cohorts of eight patients. Those eight patients are randomized to active and placebo in a six to two ratio. Again, that's a single ascending dose study. We will learn a lot about our PK profile and the safety tolerability of how a polymer conjugate of apomorphine behaves versus the naive version of apomorphine that is infused as the current standard of care. The second leg of the study is, of course, a MAD, multiple ascending dose study, where we'll have teased out hopefully the three commercial doses we want to take into that study. That'll be an N of 48, three cohorts of 16, 12 active, four placebo, and we hope that will support the conversation with the agency around NDA submission, what we have to do in terms of open label safety study, how long we have to run that, what's the number of patients, et cetera. Do you actually expect there to be any difference in the injection site reaction, placebo versus 252? We actually don't. That's because apomorphine in its naive form is very toxic to the subQ compartment. It's like poison oak or poison ivy. Patients react poorly to it if it's released in the subQ compartment. Our polymer protects the active moiety apomorphine in the subQ compartment, doesn't begin to release it from the polymer until it hits the plasma. We don't expect to see any skin reaction from the apomorphine in humans. We've never seen any skin reactions or burst effect of the active moiety coming off the polymer in the 200 plus monkey studies that we've done to support the IND filing and the clinical trial design. It's important that it's understood that the enzymatic release mechanism is exactly the same in monkeys and humans. The enzyme is called butyrylcholinesterase. It has very little variability between subjects. It's produced exactly in the monkey as it is in humans from a biology standpoint. It's proven to be a robust translation model for us as well from our preclinical studies to our human studies and our proof of principle molecule, which was called POZ-rotigotine back several years ago. We don't expect to see that issue that apomorphine has had as an infused product where many patients go off the product because it's too toxic to their skin. Why it hasn't been a successful commercial product in Europe where it's been approved as an infusion therapy for years, reaching $300 million or $400 million peak sales because of that side effect alone. It's pretty well understood by clinicians that the active moiety apomorphine is a good molecule for these patients. It's controlling that molecule that's been the challenge. It sounds like a universal benefit to whatever extent you can conjugate a small molecule to it to get rid of an ISR. Yeah. It really is. When you look at our discovery model or our discovery algorithm, we really are looking for those small molecules that we believe may have a Cmax related side effect or an under-treatment side effect because of the phasic peak and trough nature of many small molecules in terms of the therapeutic window. If we can level that out and avoid the Cmax and the under-treated side effects, there's a chance that we have a solution. Yeah. We have to solve for the chemistry. Can you maybe give us some specifics as to how you get to the roughly $2 billion market for 252? Great question. The analyst projections that we've seen. We can't rely on guys like us. Yeah. They're all over the map, right? On the front end, again, of the development of this asset, we relied heavily on folks who know a lot more about how to model the commercial potential of an asset like this, right? Had some detailed reports built, subject matter and KOL interviews. The PIs that were the PIs on all of the continuous dopamine stimulation products in the market today have all sort of kicked the tires on our TPP. When you model that, starting with that number I threw out earlier of 250,000 patients in those two major markets, and cut it in half and say half of those have access to care, right? They're in major markets where there are movement disorder centers and clinicians who are looking to innovate with the best and latest and greatest products. You assume we can get some healthy share of that, and then you assume some pricing that is not a stretch versus the current payor supported models for the current standards of care like VYALEV, AbbVie's VYALEV, and Supernus' ONAPGO. Our model suggests that in year 10, we can get to peak sales of $1.7 billion-$2.5 billion. There's no real stretch in terms of aggressive market share or moving the evolution of where we can start to impact that patient journey earlier in the curve. We think that's possible as well as real-world evidence unfolds on our version of apomorphine being a best-in-class therapy, not just for advanced patients, but maybe there's a potential to move it forward in the treatment paradigm and stave off levodopa-induced dyskinesias, reset peak dyskinesia thresholds in patients who are suffering from levodopa-induced dyskinesias. All of that, we believe, can be teased out in the real world once we get to the commercial launch, which will likely be with a partner who believes in the commercial opportunity. All right. Which is why we spent a lot of time on the front end before spending money in the clinic on who will care about this asset and get it to patients. Given the work you've done on it almost sounds like the only headwind is price for those who can tolerate the current apomorphine and because I'm assuming you're not going to come in at that price or anywhere near that price. I would say it's a failed commercial product in its current form, right? In Europe, because of its lack of traction and really becoming top of mind with clinicians for these patients, it's got very poor pricing in Europe, right? We look at the European pricing as that's probably only going to drive one third of our market because of the poor pricing. We're not assuming any premium pricing in that market. We believe there is an opportunity to get premium pricing. Again, we're not assuming any premium pricing to Anapco or VYALEV, the two current standard of care in the CDS space that we'd be competing with. It really is going to come down to if we can deliver the PK profile and dial out the skin reaction of apomorphine, clinicians now have something where the much lower patient burden, potentially more efficacious, and certainly competitive with the continuous infusions of levodopa carbidopa. Right. Yeah. That pretty much takes care of a question I was going to ask about, where do you fail? It sounds like you've outlined how you could possibly fail in the clinic, and I know it seems like a pretty long stretch for me to think that that's going to miss in these SAD and MAD trials. What I'm going to ask you, I'm going to move to SER-270, and what's the unmet need in tardive dyskinesia, and how does SER-270 address that? 270 is an interesting program for us. The current standard of care, the only drug class approved for tardive dyskinesia are called VMAT2 inhibitors, and the two incumbents that have successfully gotten those drugs approved and commercially launched, and successfully commercially launched, are Teva and Neurocrine, and AUSTEDO and INGREZZA respectively. That was a nearly $4 billion market between those two drugs in 2024. Tardive dyskinesia is a condition that is drug-induced. It has developed because of the years of use of first and second-generation antipsychotics, and it's been considered a low profile, a low priority comorbidity of the psychosis that is the primary morbidity of those patients. Only recently, in the last three, four, five years, because those two pharmas have done a phenomenal job marketing to psychiatrists and clinicians. We've all seen the commercials. Yeah. There is now a quality-of-life aspect that these patients care about and their clinicians care about. If you look at what happened in the first and second-generation antipsychotic market, the long-acting injectables have taken about 15%-20% share of that market. We believe there is a sub-segment of that $4 billion market today, analysts all have it going to $6 billion in 2030 because of that brilliant marketing job that those two incumbents are doing. If there's a 15% or 20% share of a $6 billion market in 2030 growing at 5%, 6%, 7% from there, we potentially have that product, and both those incumbents should care about that product, and others should as well, as an asset to potentially co-develop or take a little bit further ourselves. We haven't disclosed anything about that study design or what the lead molecule is, but the second half of this year, more data around that will unfold. Okay. Can you give us a little information on the development timeline for SER-270 in tardive? SER-270, we believe that it could follow a 505(b)(2) NDA pathway. We have two listed drugs that potentially could be PK bridged to, that we could demonstrate relative bioequivalence to. There's no reason to believe that the agency wouldn't salute that pathway for this asset. We're using this exact same polymer that we're using with the apomorphine approach. That would be similar. It would be a phase I-B/II-B study, SAD/MAD protocol. We might start in normal healthy volunteers with that to get early PK data. It would be similarly a compressed timeline to an NDA submission, and that would certainly, from a lifecycle management standpoint alone, be appealing to those two incumbent pharmas, one would think. To move to SER-290, what can you tell us about this mysterious program? Not a lot at this point. It's a CNS indication, undisclosed. We think it could be the biggest indication that we will ever find in small molecule therapeutic areas. A lot of work needs to be done around, and it's all new IP for us in solving for the chemistry for the prodrugs that we're building against that potential opportunity. I would just say stay tuned. We're building out an advisory panel that we'll probably start to expose publicly at some point in the second half of the year. Their expertise might tip us off? It might tip us off. Okay. Just looking at the folks involved in the project, our board of directors, advisors, may be an early signal on what that indication might be. If we maybe skip that a little, how do you think about either platform expansion versus focus on your two lead programs? I guess you can count the third one. Sounds like it's a big enough market that you're very excited about even though we don't know what it is. Look, our business model is opportunistic, in that the default model is, can we find small molecules that we can wholly own, we can take all the way through the clinic. Opportunistically, are there co-development partners that could take on that load sooner, right? We have all kinds of conversations going around both those opportunities. Thank you very much, Steve and Greg. We're out of time. Thanks a lot for talking about Serina Therapeutics. Appreciate it, Jonathan.