All right, well, good afternoon, everyone. My name is Lolita, and it's my pleasure to introduce Centessa Pharmaceuticals' speaker for this presentation. It's CEO, Dr. Saurabh Saha. With that, I'll turn it over to you. Great. Thank you. I appreciate J.P. Morgan for the invitation to present this year. Before I begin, I will be making some forward-looking statements, so please consult our SEC filings for any risks and uncertainties associated with such statements. 2023 was a fantastic year for Centessa, and given our pipeline of potential blockbuster products, a strong balance sheet, we anticipate the momentum to continue into 2024. This year, we expect major clinical milestones from all our programs. We anticipate that SerpinPC will have a readout with our part one of our PRESent-2 study. We also expect to have healthy volunteer proof of concept data from ORX750, our first molecule from our orexin platform, and we will continue to generate safety and efficacy data with LB101 from our LockBody platform. All of this sets us up for a very catalyst-rich year. So our pipeline continues to mature very rapidly. So we're developing SerpinPC for Hemophilia B, a treatment that's intended to be convenient, given subcutaneously to reduce bleeding, but importantly, with a differentiated safety profile. We're developing ORX750 for narcolepsy, for a treatment that's meant to treat the underlying cause of the disease and restore wakefulness in patients with the potential to expand far beyond narcolepsy into indications where excessive daytime sleepiness is a comorbidity. And in addition, we are pursuing follow-on Orexin molecules for indications outside of narcolepsy in neurodegenerative disorders and other disorders where excessive daytime sleepiness is a component of the disease. And we are developing LB101, our first molecule from our LockBody platform, for solid tumors to address some of the immuno-oncology challenges that exist today. So true to the founding of Centessa and our model based on asset centricity and the specialized teams that are tasked to execute on each of these programs, all of our programs are uncorrelated in nature, so the success and failure of one doesn't determine the success and failure of the other. But should any one of these work, and we certainly hope they all do, this could change medicine and create significant value for stakeholders. Now, in 2023, we made significant advances in our pipeline. Throughout the year, we achieved a number of milestones. For SerpinPC, we commenced dosing in PRESent-2 and PRESent-3. We achieved Fast Track designation status, and we also showcased data at ASH for three years of patient data on SerpinPC in our phase 2 study, and we commenced our dosing with our LockBody molecule, LB101, as well as nominating ORX750 as a development candidate. Now, all of that sets us up for a catalyst-rich 2024. So in 2024, we anticipate the interim readout on our SerpinPC program for our pivotal studies, our registration studies that are ongoing today. We anticipate healthy volunteer proof of concept data with ORX750, which is in, I should specify, healthy volunteers, which is the high bar for showcasing efficacy of an orexin agonist. And then we anticipate generating additional data, both safety and efficacy, with LB101. So let's start with our first program, hemophilia. So it is remarkable that for a market that's $2.6 billion for hemophilia B today, standard of care has not progressed beyond IV factor replacement therapy. So it's our belief that there could exist a product that does three things. The first is to reduce bleeding. The second is a product that can be given conveniently, subcutaneously, self-administered by patients via injection. And three, and most importantly, is a safe product that doesn't have the potential risk of thrombosis. So we believe that SerpinPC could potentially hit on all three of these attributes. So SerpinPC is delivered subcutaneously. We've already shown in phase 2 studies that SerpinPC can reduce bleeding by 96%, and we've shown that in the course of 3+ years of treatment, that we haven't seen any thrombosis or any elevations in D-dimer to date. So how did we achieve this? What's the mechanism of this drug to be able to negotiate this therapeutic index? Well, the brilliant scientists who developed this molecule had an incredible insight, an insight based on human genetics. They noted that patients who have Factor VIII or Factor IX deficiency, or Hemophilia A or Hemophilia B, but also co-inherit a Factor V Leiden mutation, bleed a lot less, and they bleed a lot less because their Activated Protein C, or APC, is rendered ineffective. So they sought to develop a biologic, a first-in-class biologic, that targets APC and depletes it from circulation to phenocopy essentially the mutation of Factor V Leiden, but in a more penetrant way. And what results is Thrombin formation and clot formation. But the mechanism allows for the pool of Protein C to still remain intact, and when that pool is still intact, the feedback loop is present to prevent overclotting from occurring. Now, how does that all translate into human clinical studies? As we showcased at ASH in December, in a very, very difficult to treat population of patients, patients who have both Hemophilia A and Hemophilia B, who are bleeding on average a median of 35 times a year, we were able to bring their bleeding down to one bleed per year, a 96% reduction, by giving SerpinPC subcutaneously once every two weeks at 1.2 mg/kg. Now, more importantly, and this is what differentiates SerpinPC from other hemophilia agents potentially in development today, is that we have not seen any evidence of thrombosis to date, and we have not seen any elevations in D-dimer. Why is that important? D-dimer is a harbinger for potential clot formation, and we haven't seen any sustained or unexplained elevations in D-dimer, which, again, is unique for a panhemophilia agent that's in development today. Based on the totality of safety and efficacy data, we commenced global pivotal studies, our PRESent-2 and PRESent-3 studies, across hem A and hem B patients in 77 sites in 20 countries. Despite being a $2.6 billion market just for hem B today, we anticipate that SerpinPC will be a viable treatment option for hemophilia A and rare bleeding disorders, increasing the potential market of SerpinPC. Moving on to our second program, our orexin agonist. So there is no question that there is a tremendous need today to provide a treatment option for those who suffer from sleep-wake disorders. What's clear to all of us in the field is that the current options that are available do not treat the underlying cause of the, the disease, but rather just treat the symptoms. So patients need a better therapy. So enter ORX750. This is an orexin agonist developed by Centessa, and it's an agonist that was developed through exquisite medicinal chemistry efforts based on a proprietary crystal structure. The chemistry that was required and the bar that we set was to create a small molecule that can phenocopy the orexin A peptide, which is essentially missing in patients with NT1 or Narcolepsy Type 1. The team was able to achieve an incredible feat. They developed a molecule that is almost as potent as the Orexin A peptide itself. They were able to develop a molecule that can lodge into the small pocket in the orexin 2 receptor and agonize this receptor to physiologically recapitulate what the normal Orexin A peptide would be able to achieve. And not only were they optimizing for potency, but they're also optimizing for selectivity. And the ORX750 molecule is 9,800 times more selective for the orexin 2 receptor than the orexin 1 receptor. But that's not all. We didn't stop there. We wanted to set a goal for being potentially a best-in-class molecule. So the team went further to optimize the PK profile of the molecule, to optimize the PK curve, optimizing on brain penetration, on rapid onset of action, as well as the metabolite profile. All attributes which, together, give us a shot at being a very, very competitive molecule in this class. So when we tested ORX750 in data that we showcased at the World Sleep Congress late last year, we tested the molecule at its lowest doses of 0.1 mg/kg. Even at the lowest dose that we tested in a Narcolepsy Type 1 model, we were able to show that ORX750 was able to achieve prolonged wakefulness in these animals, as well as suppress cataplexy. Now, this data is also accompanied by data where we showed in what we call our healthy volunteer mice, these are mice who are wild type with normal orexin levels, we were able to also show in a dose-dependent manner that the mice were able to stay awake. And why is that important? It's important that an orexin agonist can work not only in a narcolepsy type one patient, where the orexin levels are deficient, but can also work in people who have normal orexin levels. And so that opens up the opportunity to treat not only narcolepsy, but diseases that have excessive daytime sleepiness as a component, a comorbidity of their disorders. For example, sleep apnea, depression, neurodegenerative disorders, and the list goes on. So the potential for an orexin agonist to have a huge impact in the field of sleep-wake disorders is incredible. So anticipate in 2024 that we will have healthy volunteer proof of concept data. This data is an important data set for this molecule and this class of agents, because in healthy volunteers, the orexin levels are normal. And being able to show that an orexin agonist can keep healthy volunteers awake is the high bar to achieve with this molecule and this class of drug. So moving on to our third program, which is the LockBody technology platform. So most of us who have spent a lot of time in this cancer space, since 10 years, and it's been over 10 years since PD-1 and CTLA-4 have been approved, there hasn't been much success in the immuno-oncology space. The ideal profile of a cancer drug would be one that can treat durably, cancers that are, resistant or refractory to PD-1. Two, can be given systemically to treat metastatic disease. Three, work as a monotherapy and with a wide therapeutic index. That's the holy grail molecule in immuno-oncology. Unfortunately, that doesn't exist today, but our goal with the LockBody platform is to attempt to try to find such a molecule. And based on this technology, of the LockBody platform, we feel we have a monotherapy-delivered molecule, which in essence, is an IgG1 antibody, but with an extra pair of Fabs. Now, these extra pair of Fabs that are attached to the Fabs of a normal IgG1 molecule are tumor-targeting in nature. So for our first molecule, which is LB101, our tumor-targeting Fabs are PD-L1. These Fabs are linked to Fabs of a normal monoclonal antibody through a hinge, and that hinge is not engineered, but rather derived from nature. That coupling of these two Fabs together with that hinge is what is special about this LockBody platform. It's been known that the Fc Fab hinge that's present in our antibodies is highly labile in areas of high inflammation, and that falls apart in tumors and in joints where the inflammation is high. We borrowed this idea from nature to take this hinge that connects the Fc and the Fab and use that hinge to connect the two Fabs together in a LockBody molecule. Essentially, what we've generated with LB101 is, in the first instance, it's a PD-L1 CD47 antibody. When this antibody is dosed in patients, it essentially stays locked for CD47 activity, which is invisible in circulation and acts like a PD-L1 antibody. The antibody then circulates, and it concentrates in tumors where PD-L1 is expressed on tumor cells, and once it's in tumors, the hinge falls apart. It's highly labile, and the CD47 activity then is released. You have a situation where an antibody that essentially has minimal potential toxicity systemically can have maximal efficacy locally, bringing potent immune effectors into the tumor. Now, in a difficult-to-treat colon cancer model, we were able to achieve monotherapy, significant regressions, and complete tumor responses in most of the animals that we treated, compared to very few with PD-L1 as a control itself. Now, importantly, what we've shown in non-human primates, up to 50 mg/kg, the highest dose that we tested, we did not see any anemia or thrombocytopenia associated with LB101. Now, note that with any other CD47 antibodies that are out there, you would normally see thrombocytopenia or anemia at very low single-dose, single-digit mg/kg levels. So this is very exciting for us because by design of this LockBody platform, we're seeing the safety mechanism non-clinically play out exactly as we would expect. So anticipating 2024, we'll generate additional data, both safety and efficacy, with LB101. So all in all, 2024 is a very exciting year for Centessa. We anticipate many clinical milestones this year, and stay tuned as we update you on these milestones. So thank you so much. And I'm happy to take questions. Yeah. Happy to open it up to any questions. All right, well, I have questions. Sure. First question is, I know you kinda touched on it a little bit, but can you characterize or define, like, how do you characterize or define a best-in-class molecule for narcolepsy? Hi there. Absolutely, great, great question. Mario Accardi here, President of the Orexin program. First of all, best in class orexin agonist, what does that mean, right? It means reducing excessive daytime sleepiness, suppressing cataplexy, addressing disturbed nighttime sleep, and several other clinical features of narcolepsy type 1. Based on the data that we showed at World Sleep back in October, we think that with ORX750, we have a really an incredible shot of being potentially best in class. We've shown we have a molecule that is almost equipotent to the native peptide, so extremely high potency, which means low predicted human doses, minimizing DDI risk and minimizing DDI risk. We have a molecule that activates the orexin-2 receptor in a very similar way as the native peptide in terms of molecular mechanism. We have a molecule that has an optimal predicted human PK profile with an optimal duration of action. And finally, in terms of best in class, where we've seen clinical precedents have shown also tremendous efficacy and transformational efficacy in this space. So it's really about combining both that high efficacy with a favorable adverse event profile, and that's really something that we're very confident we can achieve with ORX750. I have, I have a question, just about the orexin program. We're gonna see some readouts this year from Takeda. We're gonna see some readouts this year from Takeda, potentially Alex as well. What are you guys looking for in that data set, and how do you think you can differentiate from what you see from them? So first of all, we're gonna be showing clinical POC in terms of sleep-deprived healthy volunteers, which Saurabh mentioned earlier. It's really the high bar here. This will de-risk massively the program, because as Saurabh mentioned earlier, it also de-risks Narcolepsy Type 2, Idiopathic Hypersomnia, and expansion into other disorders where there isn't a loss in orexin tone. In terms of what the others are showing, well, first of all, this is not a winner-takes-all situation, right? There are multiple players can coexist here, maybe with, maybe even different PK profiles. And if you just think that 50% of NT1 narcolepsy patients remain undiagnosed and only 25% are on treatment, yet there are some branded sales out there doing $2.2 to $2.3 billion of sales, there is a significant opportunity. We've shown, again, based on the preclinical data, that we can achieve an extremely encouraging profile for ORX750. Any other questions? All right. Well, then I guess this concludes our presentation, and thank you all for joining us.