Morning, everyone, thanks for joining us. My name is Anthony, and I'm an associate here at Oppenheimer. It's my pleasure to introduce Aprea Therapeutics, a precision oncology company focused on targeting the DNA damage response pathway. Their lead program is APRN-1051, a next-gen WEE1 inhibitor. The company is also advancing ATRN-119, a macrocyclic ATR inhibitor. We're pleased to welcome Dr. Oren Gilad and the Aprea team to walk us through the story. Oren, I'll turn it over to you. Thank you, Anthony, for the invitation and for the opportunity to share Aprea with your audience. I'm gonna make some forward-looking statements, so please refer to our10- Qs and 10-Ks for a list of risks. At Aprea, we cannot wait to cure cancer. The way we do it is by building a portfolio of small molecules that are targeting specific enzymes associated with the cell cycle. This is different than chemotherapy. Chemotherapy kills every cell, every dividing cells in the body, and therefore, you see lots of adverse effect. Our approach is to match the drug with the disease, so there's this transition from toxic chemotherapy to potentially safer and precision guided oncology. It's all about the biomarker. Ideally, the ideal outcome is to have patients that are treated on, with our drug, that's gonna have efficacy, so we're gonna see activity, and it's gonna be well tolerated. That's the goal, and that's our focus. We put a slogan here, "One critical pathway, multiple targets." All of our targets, all of our drug, are in the DNA damage and response pathway. We have three clinical programs. We have the ATR that you mentioned, Anthony. We have the WEE1, that's our lead program. We have a p53 reactivator and a preclinical program that we are not gonna be focusing on. The sole focus of the presentation today is the molecule that you mentioned, the WEE1 inhibitor, APR-1051. Now I'm gonna spend all of the presentation just on this program. It's a clinical programs. It's in dose escalation. Starting with the, with the landscape, the competitive landscape and some historical aspect of it, Merck started a WEE1 program. It was the MK-1775. Merck tried to develop it, didn't see much of a therapeutic window, put it on the shelf. AstraZeneca licensed it from Merck, spent a lot of time and money trying to make it work because they showed that the biology works, but the therapeutic window was not up to the standards. It was narrow enough so that they no longer adding patients onto the study. They terminated further clinical development of this molecule. Zentalis made an analog of the AZD-1775. They are now in the development, and the therapeutic window still being defined. Zentalis is treating 5- on, 2- off, so they're taking two days holiday every week. There's another European, private company, Debiopharm, and they have a WEE1 inhibitor that they didn't show single-agent activity. Their liability is associated with QT prolongation. The AstraZeneca and Zentalis, they have GI tox and some hem tox that they have to work on. We went back to the drawing board. We went back to the chemistry, and we designed the molecules that meets our criteria and check the boxes that we put forward. We looked at all of the other programs. We identified some liabilities. We worked on the chemistry. My focus, and the focus today is to share the data and showing you that it was worth taking the time and worth spending the time on developing that molecule. We do see early signs of tumor reductions, without class-limiting tox to date. The drug is seems to be well tolerated. The dose escalation is progressing, and we do see a potential wide therapeutic window. Solving this issue was our main goal, and looks like we may have achieved that. This is the schema of our dose escalation. Starting on the left here, you see that this is not all comers. Patient, again, going back to the biomarker and the matching of the drug with the disease. Patient are eligible to enroll in our study if they carry this mutation, CCNE1, CCNE2, FBXW7, PPP2R1A, KRAS p53, HPV. The focus on, of the presentation today is gonna be on PPP2R1A, FBXW7, and HPV. We're gonna show you some clinical data for these specific mutations that are shown in the clinic. The first response that we saw in the first scan was at the 150 mg, which means that we established 150 as our minimal efficacious dose. We went up to 220 mg, and a second patient, so this showed the same kind of response. Still in the first scan, these two patients are on the study. We're awaiting the second scan to confirm the response. Both of them showed 50% reduction in the target lesion, 90% reduction in the biomarker, and very minimal drug-related adverse effects. It's very well tolerated. We're now enrolling in the 220 mg. The goal is to keep dosing up as high as we can. The higher we go, the wider the therapeutic index is going to be. In the black square here, that's gonna be our focus. Our goal, hopefully we clear the 220 mg, then we enroll the three patients in the 300 mg. Once we complete enrollment of the three patients in the 300 mg, we're gonna add additional patients in the 220 mg, because the idea here is to get higher number of responders. The focus is gonna be enrichment in endometrial, CRC, and HPV-positive patients. We do that because we want to gain confidence in the dose escalation and de-risk the dose optimization. We did financing not long ago with the promise that this is gonna be the goal and the allocation of the financing: to enroll as many patients as we can, to gain as much confidence as we can, to de-risk the next phase of the development, and that is the dose selection optimization. We're gonna spend time and money here to de-risk and gain confidence in our next phase of development. This is the swimmer plot. It's been updated as of last week, and you see that we completed enrollment in the 220 mg, so we are so far, so good. We're waiting for that last patient to complete the DLT period before we go up to the 300 mg. Also interesting is you see a nice dose response. That purple one, the patient that was on the study for 223 days, that's an HPV patient. Again, this is a single agent, daily dosing oral. He was on the drug, on the study for 223 days. We went up to 100 mg, and we saw three stable diseases. From one stable disease at 70 mg up to 100 mg, three stable diseases. At 150 mg, that was the first partial response that we saw in the first scan. Again, this patient is still on the study, waiting for the next scan to hopefully confirm the response. In the 220 mh, same thing. One patient is showing a partial response, and we see how, what the scan is gonna show for that patient. We see a nice dose response with the administration of the drug. That's another differentiation that we have from the other programs, is that this drug is being given daily. Zentalis, for example, is doing 5- on, 2- off, which is important when you target the cell cycle. This is the treatment-related adverse effect, and you can see that it's pretty clean. We don't see the hem tox, we don't see GI. We see nausea, we see fatigue. There was one patient that showed some ALT/AST that was at the 50 mg. He had liver mets. Since then, we enrolled other patients with liver mets, that did not repeat, so looks like it may have been a fluke at the low dose, but pretty much clean here, right? That's, remember, that's the goal. The goal is to have the efficacy with a drug that is well tolerated. I'm gonna walk you through the vignette and the background of the four patients I talked about. The first one is the patient in the 200 mg cohort. That's the patient that showed partial response in the first scan, and she's still on treatment. You can see that she responded pretty well to the second line of therapy, 17 months, but not so great to the first line, third line, or fourth line. So far, so good on treatment. The target lesion at the first scan shrank by 50%, and again, the biomarker, the CA-125, was about 85% reduction and very minimum adverse effect. This is the second patient that showed a partial response in the first scan. That's in the 150 mg cohort, 60 years old female. Same mutation, PPP2R1A. She had four prior lines of therapies, so it's heavily pre-treated. You can see 105 days in the first, 134 days, 79, 55. She's still on treatment, and same response, -50% in the target lesion, and the CA-125 went down 90%. I would like to pause here for just a minute before I move on to the next set of patients because I think that people underestimate the anxiety that cancer patients are going through while waiting for the results, right? They go to the hospital, they do the scan, they do the blood work, and they wait for the results. These are heavily pre-treated patients. They failed prior line of therapies, they don't know what to expect. In the case of these two patients I just shared, that was good news, right? It was tumor target lesion is shrinking, biomarker is going down, patients are not experiencing adverse effects. It's everything that we have been hoping for and waiting for is in these two patients. PPP2R1A, both of them have the same mutation, PPP2R1A. Going back to the enrichment, we are definitely going to enrich for patient with this mutation because we are two for two with this mutation. We want to increase the number and hopefully get more responders with this mutation. Let's not underestimate the anxiety that cancer patients are going through while waiting for the results. This is a patient in the 100, so she was a stable disease, so this is disease stabilization. The 150 mg, 220 mg, we saw a partial response by RECIST, needs to be confirmed. This is stable disease with a pretty decent duration, about six months. You can see that her response was not great to the prior therapies, right? 191 days was for the first line, and then 45, 43, 12, 50, came to us after all of these prior treatments. As single agent, daily administration, oral, the best response was -15%, so it's considered stable disease, but it was a nice duration before she progressed. The last patient I'm gonna show and talk about, that's the HPV patient that was at 70 mg. Remember, 150 mg is the minimum efficacious dose. 100 mg is below that. 70 mg is half of that. That's a 52-year-old male. He had three prior lines, and this is the longest he's ever been on treatment. He was in the first line, 49 days before progressed, 84 days in the second line, progressed, third line, 184, and with our drug, a single agent, 223 days. We are very encouraged, and we're very excited about what we're seeing, and we did do financing, not long ago, to enrich for these patients, to really get a higher number of patients onto the study, gain the confidence, de-risk the next phase of development. That's the goal of the financing that we just did. That's kind of summarizing it. Objective response in the two cohort, 150 mg-220 mg. Hopefully, we'll go higher, so we get a wider therapeutic index. Disease control with CRC, definitely of interest for us. HPV is of interest. We're going to enroll more patients with this indication and mutations. The safety is well tolerated to date, and the therapeutic window is getting wider. That is giving us the confidence to enrich for this biomarker and get more patients onto the study. We do want to expand on the PPP2R1A. Again, two for two, it's very encouraging. We're very excited. The drug seems to be active with this mutation, but again, we want to add another cohort, CRC, HPV, and get more, hopefully, we'll get more responders. We also want to confirm durability, consistency of response, and safety. That's what this is all about, is finding a drug, finding patients that respond and have minimal or no side effects. This is not chemotherapy. This is targeted therapy, specialized medicine. Everything I talked about until now is the single agent, but in oncology, we're also looking at combination. When you have a drug that has that clean of a, that kind of a therapy, you want to combine it. The two graphs on the left, this is data that has been generated at MD Anderson through a collaboration, and this is for HPV cancer. The one on the left is a model that is resistant to the therapy, to APR-1051, but also to cisplatin. You can see the purple line at the bottom that is showing great synergy. The one in the middle, this is a model that is sensitive to PD-1 and to our therapy. Look at the purple line. It's not often that you see that strong of a response in combination with PD-1. These are preclinical mouse model, getting us in preparation for the next phase, combination. When you don't have overlapping toxicities, this drug is very attractive for combination therapy, as shown here. The one on the right, this is data that we generated in-house. This is combination of our ATR with WEE1, and you can see the red line is that when we cut the dose of each by half, and we maintain the efficacy, which means that if in case in the future, we're gonna see some tox, there is room for dosing, and playing with the doses to maintain the efficacy and hopefully eliminate any potential toxicity. To summarize, WEE1 has been clinically validated. It's a good target, it's been clinically validated by us and by others. We did share early clinical proof of concept. We established 150 mg as the minimum efficacious dose. We also see activity in 220 mg, and hopefully we'll keep continuing going higher. There's potentially favorable safety profile at this active dose levels. We're not seeing any tox or drug-related tox, significant drug-related tox. Enrollments continues, additional clinical data expected. This is open label, we have the money to enroll additional patients. We are going to enroll additional patients. What we promise to our investors is what we're gonna be focusing on and delivering on our promise. The clinical team has got stronger. We did announce the addition of Jean-Pierre Bizzari, joining our team. He's already making positive impact on the program and the study. We have the capital in place. We said that we have a cash runway into Q1 of 2027. The additional capital raise was not to extend on the cash runway, but actually to generate data and generate value to our shareholders. Valuation lacks fundamentals, because there is a, an asymmetric opportunity with the data I showed you and the market cap of APRE. That can be a, an opportunity for an investment. The last thing I'm gonna mention here is that all of our three covering analysts are rating APRE as buy at a higher price target. That also gives us a confident to what we do. The competitor programs, still working on the therapeutic window. We're dosing daily, some are dosing five on, two off, and we're excited about this program. We're pushing it forward, and we cannot wait to share additional data as it comes. Thank you so much for walking us through that. Earlier in your presentation, you pointed out dose reductions and dose continuations associated with azenosertib and azacitidine. Is that potentially on target related? Like, what is the bad actor driving those reductions, do you think? I don't think it's on target. Yeah. When I spoke about we went back to the drawing board. Yeah. One thing we identified as liability is the co-inhibition of WEE1 in the PLK family. Yep. I'm not saying that targeting this PLK is not a good approach. What Cardiff is doing and others are doing, I'm not saying it's not. I'm gonna argue that when you co-inhibit, and we have the data, it's on our deck. When you co-inhibit WEE1 and PLK, and we're showing it, that the PLK takes away from the WEE1 activity. In order to achieve the activity of a selective WEE1, you have to dose higher and higher. And that also introducing tox. It's something that we spend a lot of time on, trying to stay away from the PLK, and so far it's been showing that it's working, because we see activity and we don't see much of an adverse effect. We don't see the hem tox, we don't see the QT, so I don't think it's on target, I think it's off target. Eventually, we're gonna see some tox, right? We're gonna dose as high as we can. We're gonna see some tox. We'll see what the tox is going to be, but the PLK doesn't help. The PLK in the co-inhibition, again, I'm talking about co-inhibition, not selective PLK inhibitors, but the PLK co-inhibition with the WEE1 does not help. Have you all disclosed the molecular structure of your WEE1 inhibitor? Mostly asking out of curiosity, 'cause I understand azenosertib and azacitidine are different by, like, an atom. Yeah, well, so yeah. What azeno is, it's a two-carbon change to close the ring of adavo. That's the difference in the chemistry. We did not disclose. We don't want to put our molecule out there and then, you know, have others synthesize it and do whatever they want with it. We kind of not disclosing it at this point. Yeah. What's your take on co-WEE1 and PKMYT1? Do you think those two targets are potentially synergistic? That, that's what Debiopharm is doing. Debiopharm didn't show- Yeah ... single-agent activity with their WEE1 inhibitor, so they're combining with the PKMYT1. Right. I think combination works. The one thing that we stay away from is that the co-inhibitor. If you want to combine, you want to be able to control the doses and not have a fixed dose within the molecule. It could work. They supposed to show data, I think, at ASCO, there's gonna be some key data coming in the field from both Zentalis and Debiopharm, but I hope it would work. The beauty of targeting the DNA damage and response is that, given the mechanism of action, you can combine with other agents. We showed chemotherapy, we showed IO, we showed our own. It's something that it makes sense to combine. When do you think we'll see more data from your escalation cohorts? I understand you're taking it all the way up to 200 mg, right? Yes. Yeah. We are now in the 220 mg, we're waiting for the two patients who have the unconfirmed partial response to get the second scan, hopefully confirmed. It's an open label, so I think that the we will update as the data comes. It can be tomorrow, it can be next month, it can be... It's as data come, we will update. For the expansion cohorts, do you think that data will come sort of year-end or maybe 2027? We're hoping to complete the dose escalation by Q3. That's what we put out. That's where the data-driven comes into play, right? We wanna have additional patients. We want to get the confidence, see who is responding, who is not, what's the rate of respond, the duration. That's what gonna take us to the next phase. Hopefully, we'll complete the dose escalation by the end of Q3 of this year. Great. If we have to go higher, that means that the therapeutic window is wider. I don't think investors are gonna be not satisfied if we get an even wider therapeutic window and safety. Well, I'm not seeing any further questions from the audience, so I wanted to thank you again for taking the time to join us today. Thank you, Anthony, and thank you for the opportunity to share. Absolutely. Take care. Bye. Bye.