Okay, welcome back, everybody. Our second panel of our conference. There'll be a third one tomorrow, doing one per day. We didn't pick the panels randomly. Particularly for oncology, I feel like every conference you go to, there's an oncology panel. Like, it's kind of like it could be anything, right? I think that's a little bit tired. The way we chose this, we chose three companies that are unrelated in terms of what they're doing mechanistically. What they have in common, I think, is that they're in three of the most active spaces in oncology currently. And they're also, from a valuation perspective, I think, I'm gonna use it inappropriately, there's like an arb play here versus peers in the space where they are clinically, the assets they have, the cash that they have, versus what market caps of other companies are in the space. And I think there's a lot of value that could be had there. And with that, our panelists include Oren Gilad, the CEO of Aprea Therapeutics, and they're in the very active synthetic lethality space that includes names like Repare Therapeutics and IDEAYA and Zentalis, and on and on. James Bianco, the CEO of TuHURA Biosciences, that is very close to completing its reverse merger with Kintara, should begin trading, I think, by the end of the week. You know, this company is looking at going into a SPA agreement, first line combination therapy with Keytruda and Merkel cell. They have what could be a really interesting checkpoint inhibitor that comes next, and an anti-VISTA, and a number of other things that we're gonna talk about. Marty Lehr, the CEO of Context Therapeutics. When you look at spaces like ADCs, antibody drug conjugates, and the soaring valuations in M&A in that space, and then look at bispecifics coming up behind them, and that's where Marty's group is currently, as well as with T-cell engagers. There's a lot of value to be had there. So that's the group that we selected. I think there's a lot to talk about. I think, guys, welcome. What would be helpful is if you can give an introduction on yourselves, and your companies, and what you're working on, and I think we'll go from there. Like I said earlier, it's James on my top left here, so that just makes it easy, and maybe we could start with you, James. Sure. Hi. I'm Jim Bianco. I'm the CEO of TuHURA Biosciences. Been in biotech about 30 years, oncologist by training, focused mostly in biology and marrow transplantation, so we are currently a phase three registration stage immuno-oncology company, and we're focused on developing drugs to overcome some of the major limitations to current cancer immunotherapy. Specifically, we're focused on overcoming primary resistance, and where immune therapies fail to work, obviously in the majority of patients, or in the acquired resistance space, where immune therapies like checkpoint inhibitors work, but they ultimately stop working. Our most advanced drug candidate, we call IFx-2.0, and that's designed to overcome primary resistance due to intrinsic factors of the tumor biology, like low neoantigen load or low tumor mutational burden. That drug is scheduled to start a phase 3 accelerated approval study, utilizing the FDA's Project FrontRunner, that's being conducted under an SPA, and it's a randomized trial of IFX with Keytruda or pembrolizumab versus pembrolizumab alone in the front-line treatment of advanced or metastatic Merkel cell carcinoma. The data that we generated in the phase 1b trial show that you can overcome resistance in the relapse setting, in the progression setting, in about 70% of patients, and so the FDA encouraged us to move that into the front-line treatment setting, which we did, and in fact, that trial has a secondary endpoint that, if positive, would satisfy the requirement for a confirmatory trial, so that's kind of a novel set of endpoints in terms of the trial design, and the FDA was very receptive to working with us on that design. We do have another class of technologies, as I mentioned, focused more on the acquired resistance, and that technology's based on a very novel VISTA receptor that's overexpressed on an immune-suppressing group of cells called MDSCs, and we've developed the first group of bifunctional or bispecific antibody or peptide drug conjugates that are really targeting overcoming some of the immunosuppression in the microenvironment that MDSCs contribute to, so not the typical cytotoxic ADC approach, but more an immune-modulating approach for our ADC technologies. As Jason said, we recently raised about $36 million. Takes us through 2025. The phase three study starts up next year, so we should get through its enrollment in 2025. In addition, we should start trading on the NASDAQ under the symbol HURA at the open this Friday. Great. All right, Oren, how about you? Thank you. Thank you, Jason, for the invitation and for sharing A prea with your audience. As you said, we are synthetic lethality, focusing on targeting the DNA damage and response. Our approach is, and our focus is to overcome the toxicities that is associated with chemotherapy. By doing that, this is part of the precision medicine and precision oncology, where we match the drug with the disease. We are a clinical stage company with two drugs in the clinic. First one is the more advanced one, is an ATR inhibitor. You mentioned Repare, as one of the comps there. The second drug is a WEE1 inhibitor that got to the clinic early this year, and we are ahead of schedule with our enrollment. We're gonna share data in the upcoming Triple Conference next week, and then we're gonna do a KOL. Everything is pointing in the right direction. So, patient population, patient selection, biomarker-driven approach is our focus. And by doing that, we try to maximize the therapeutic index, maximize the effect of the drug, and minimize the side effects. Great. How about Context, Marty? Great. Thanks, Jason. Hi, Marty Lehr, CEO of Context Therapeutics. Context is essentially a roll-up of T-cell engaging bispecific antibodies for solid tumors. To achieve that roll-up strategy, we raised $100 million financing in May, led by a half a dozen biotech specialist funds. The specific focus and interest in T-cell engagers is the fact that the primary dose-limiting side effect, cytokine release syndrome, has historically impeded the development of these agents for solid tumors. Essentially, you'd run into CRS before you would get any meaningful therapeutic activity. What has happened over the last couple of years for both TCEs and CAR-Ts is that clinicians have gotten much better at managing that side effect. They do that through pre-medication with a steroid as well as step dosing, and so if you don't have CRS, you can start achieving therapeutic doses. The net result has been fantastic data across, now at this point, over a half a dozen different solid tumor types, some of which are very hard to treat, such as pancreatic cancer or small cell lung cancer, so we built a pipeline of three assets. The targets include Claudin-6, Mesothelin, Nectin-4. These are all targets that are clinically validated through an antibody-drug conjugate, and so, as Jason pointed out earlier, there's a ton of interest, both strategics and investors, in ADCs. Not a whole lot to talk about what you give after an ADC, and that's really where we think a T-cell engager will shine. It's a totally distinct mechanism, mechanism of action, different AE profile, different resistance pathways, and they are typically more potent, and significantly more potent, than an ADC, and so they have the ability to treat low and medium-expressing cells of the particular target. So we're really excited about the pipeline. It's maturing well. The company has very much gone through a metamorphosis over the year. And looking forward to sharing more about the company throughout this conversation. Yeah, I think it's been, if you think back to like CAR-T, and then maybe the ADCs have come along, but it's been really hard, like, what's the hottest thing in oncology, or how do you get above the noise? I'm gonna start with Jim. You know, everybody did combination therapies with Keytruda, right? If you, a couple of years ago, I feel like, you know, like, what combination are you doing now? There's this, and I'm trying to gear this towards, what are investors and pharma looking at now? With patent cliffs approaching for the PD1s, everybody's still looking for what could be the next checkpoint, what's the right combination? And then here you are, and there you're one of only a handful of companies that are going to phase three, first line, looking to move the needle on what Keytruda or PD-1 has already done, with two, you know, a very attractive path to approval, plus the VISTA antibody, right? I, that could be really interesting. Can you talk about, you know, that ability to kind of rise above the noise now? Like, now it seems like it's more of the appropriate time than it was even a couple of years ago. Yeah, thanks, Jason. And I agree. You know, there's been, if you look at the primary reason that checkpoint inhibitors don't work, obviously, is that you don't need an activated T-cell response for it to checkpoint release those activated T-cells. And so if you look at pembrolizumab, overall checkpoint inhibitors fail in about 70% of patients. And in Merkel, it's about 50% get a really good response, and the other half don't. And so the primary objective in this whole cancer immunity cycle is how do you activate a tumor-specific response? And, you know, people have gone after activation of an innate response, particularly using these innate agonists, immune agonists like TLR9 or STING agonists. The technology that we're developing actually really harnesses a natural process of an innate response, right? We use a pDNA that will make a tumor look like a bacterial protein. Specifically, it's a strep protein that gets expressed on the surface of the tumor cell, and that motif, that so-called lipoteichoic acid for gram-positive bacteria, is essentially TLR2 substrate, right? So TLR2 on dendritic cells will engulf the tumor, package all those tumor neoantigens. Now you've initiated that primary epitope spreading, adaptive response, secondary epitope spreading, but importantly, you now have an activated T-cell response that's tumor-specific. So if you rechallenge them with checkpoint inhibitors like we did in the phase one B, we saw, you know, six out of seven patients with advanced disease that progressed through primary checkpoint inhibitor therapy, i.e., PD-1, PD-L1 inhibition, that on rechallenge, you actually have responses lasting some three, three of the six is still ongoing out 33 months. So, as you mentioned, we, you know, we went to the FDA with this, and they suggested putting it in the front-line setting. So if you use this as an adjunct to prevent patients from, quote unquote, progressing through a checkpoint inhibitor, and compare that to Keytruda alone, which is the standard of care in this case for advanced or metastatic Merkel cell carcinoma, you know, that's a major leap forward, right? Because the biology of resistance, the so-called tumor intrinsic biology of not looking foreign, i.e., immune evasion, if you will, is true. It's histology agnostic. So it should work across those tumor types that typically don't respond to checkpoint inhibitors in front-line treatments or first therapies. And there's obviously about 60%-70% of tumors that don't. Sticking with the checkpoint inhibition approach, you know, Kineta was developing a very interesting novel checkpoint called VISTA. VISTA was in development about four or five years ago, but CRS cytokine release syndrome really kind of killed those programs. And what Kineta has for their approach is they really have kind of epitope modified the Fc regions so that you don't get activation, and cytokine release. And the importance of VISTA for us, anyway, from a portfolio fit perspective, you know, we're focused again on, essentially the second aspect of our technology looking at removing the immunosuppression in the tumor microenvironment, so-called tumor microenvironment modulators. VISTA is the only checkpoint that's expressed on quiescent T-cells, resting T-cells. All the other checkpoints are expressed on activated T-cells. And it's becoming clearer that VISTA, especially its expression in the myeloid compartment, we're focused on these myeloid-derived suppressor cells, is an important target. And so from our ADC technology, right, we have a way to not only target a very important immune-suppressing cell called MDSCs, but we can carry with it an anti-VISTA antibody. That's a really novel antibody-drug conjugate, where we're actually using a small molecule as the drug, and the checkpoint inhibitor, in this case, the anti-VISTA, as a release mechanism for essentially removing that immunosuppressive phenotype in the microenvironment. And that will go into a phase two program next year, likely in AML, and in endometrial cancer. Two populations that highly overexpress VISTA as one of their primary resistance phenotypes. And the first line program with Keytruda, like I said, there's Immutep, there's a handful of companies that are there, and then you're looking at these patent expertise for the PD1s, and it seems to be attracting attention. It certainly seems to be attracting investor dollars, but the same applies for precision, more precision oncology, right? For Oren and Marty, you know, you both of your groups did financings this year with quote, unquote, blue chippy biotech investors. What do you think it is that they saw? I mean, there's certainly, in our view, and Chad brought it up earlier, there's a scarcity factor, right, in synthetic lethality. You know, how many assets and good assets and players are really out there? And then the same thing, Marty, for Claudin-6, a mesothelin asset, BiTEs and other T-cell engagers. Maybe you guys could comment on what's attracting dollars into your companies. Marty, you wanna go first or should I? That'll work. Please go ahead. Oh, okay. In the case of Aprea, I think it was really the science what drove the transaction, because at the time when we did the financing early this year, there weren't too many financing going on, especially not with this volume of $16 million upfront, and then another potential $18 million with two half warrants. So the institutions that came in that round really did a good job with their due diligence. They looked under the hood, looked very hard into the science. It's what drove the decision. And the science is really based on cumulative knowledge and understanding of mechanism, understanding normal, understanding transformation, understanding at the time that as normal cell becomes cancer, the changes that are being taking place inside the cell causing reliance on other pathways that cancer cell has to have fully active in order to survive. This is what we are targeting. We're targeting the compensatory pathway that cancer cell cannot live without, and normal cell can live without it. There has also been clinical and commercial validation to this approach, and this is with the PARP inhibitors. PARP inhibitors, for example, olaparib. Olaparib has been in the clinic, on the market for a few years. Annual sales last year were over $2 billion, and it's for one genetic mutation, BRCA loss of function. Now the question is, okay, what's gonna come next? Because the concept is the same concept. Tumors that don't have BRCA functioning there, they're being treated with PARP inhibitors. For ATR, for example, it's likely to be ATM loss of function. We identified that, and we identified other biomarkers. For WEE1, we know that it's gonna be most likely CCNE1 overexpression, and we also have KRAS and p53, not ORR by the way, and p53. So what attracts the investors is really the ability to execute. And one of the things also, one of the other factors is the evaluation. A pre-evaluation is very attractive with two clinical programs. Third one is gonna be disclosed soon, as soon as we file the patent with a platform that resistance has been mentioned here. So we have a platform that can help identify and predict resistance. How does cancer cell become resistant to a drug? Or for in our case, we're also looking at potential biomarkers for patient selection. When you look at the whole package, I think that that was very attractive for investors to come and say, okay, we're gonna back up this company. We like the technology. It makes sense. There is commercial validation of the approach, and let's make sure that they have the capacity and the ability to drive their program forward to success. I guess from our standpoint, T-cell engagers for solid tumors historically have not worked. It's an idea that's been around for a long time. It was first described in a publication in 1964. What we started noticing really two, three years ago, but the data started coming out from a public standpoint over the last year was a series of breadcrumbs leading toward the path that there really had been a breakthrough for T-cell engagers. So you had companies like Amgen, Harpoon, Innovent, Janux, just to name a few, developing T-cell engagers across a range of targets, DLL3, STEAP1, Claudin-18.2, just to name a few. You know, some of these targets were very enriched in tumors. Some were found broadly in the body. Some had low copy number, some had high copy number. So they were very varied in their profiles. But what was consistent across these data sets was the rate of grade three and four CRS was almost nonexistent. And that really had never happened before. And so the question was, was it technology or something the clinicians were doing? And in our view, it it's probably the clinicians. Those approaches I mentioned in tumor types are so varied that the only thing unifying about the approach for all these companies was that for the first two doses, they did step dosing and they pre-medicated with a steroid. And that has just had a profound effect. And so you're starting to see not only robust response rates, but actually really good durability. And in many cases, T-cell engagers actually have better durability than ADCs, 'cause ADCs are susceptible to target-mediated resistance where you're putting clonal pressure on the low and medium expressing cells to propagate. And so that data was all out there, was all public, but really no one had sort of pulled it all together and shared it with investors. And the investors really for the past five or six years had been told that T-cell engagers will never work in solid tumors, that there'll be profound CRS. And so they really weren't keeping an eye on the space. And so it wasn't a reluctance, it was just sort of a lack of awareness. And once we educated the funds, not necessarily on what we were doing, but the overall progress in the field, that lowered their sort of entry bar, so to speak, that they were willing to entertain a company and a concept that maybe now is the time for T-cell engagers. And so that enabled us to start the conversation, and then we had to sell them on the particular targets that we had. And there we needed something that was a clean thesis that was easy for investors to understand. And virtually all of them had made investments in ADCs, and most of them really hadn't thought about what you do after an ADC. And so when we walked through the rationale for TCEs after ADCs, they got it. One of the things that we sold investors on that we had no data to support, but it mechanistically made sense, was that ADCs should be combined with T-cell engagers. What you've seen over the last two months is that is absolutely happening. There have been announcements from Amgen, Merck, and Gilead all doing ADC combinations, ADCs targeting B7-H3, TROP2, just to name a few. The investors now understood, okay, T-cell engagers had fundamentally changed from a risk profile standpoint. There is a clear use case for them, and that got them really excited. The roll-up strategy was attractive. We have been able to acquire these assets very cheaply, and that has everything to do with the market dynamics right now. Venture funds overinvested in 2021, and their LPs have largely pulled back. It's making it hard for small companies to raise money from venture funds. Conversely, large pharma is doing exceedingly well, and they really do not have a need to acquire early stage assets. So there's a real lack of buyers of early stage assets out there right now. And so once we articulate that to investors, they understood it quickly, and were willing to support us in the endeavor. So that's how it all came to be for us. Jim, you can comment on that, I suppose, right? With the VISTA antibody relationship to Kineta. And I have a follow-up, related to your bifunctionals after. Totally agree. Marty, I think, wholesale acquisitions right now, I think when they say last year, coming into the end of the year, there were 100 biotechs trading well below cash. And as you correctly point out, these companies can't get financed. They're either the ultra micro cap, illiquid stocks. So the best thing to do is to go out. And I've done that successfully. I'd say four of the five drugs I got approved, we paid anywhere from $15-$30 million for them. The last one was $15 million, partnered for $180 million, and then got the company sold for $2 billion, just under $2 billion. So it's timing's right to pick the ones that really have the best profile. Like I said, to your point, Jason, Kineta was just sitting there with an asset that probably could have been better positioned to show a signal in phase one. They went the more traditional route, and it's to our benefit, because we think we can close that acquisition probably mid-November. We've already positioned it amongst a bunch of advisory groups, within the GYN malignancy community, within, of course, the community I'm very familiar with in terms of liquid tumors, to put that into a phase two program that is biomarker driven. To your point, Ryan, you have this expression on 80% of a tumor. Why wouldn't you do a study just in tumors that are overexpressing the target? So, and the fact that they were able to tease out the CRS, now even at a thousand milligrams, every two weeks, they finished the phase one cohort. We funded that. So yeah, I think, you're absolutely correct. This is the time to go looking, at assets that fill out a portfolio, certainly risk diversified portfolio. Or, Oren, to Jim's point, you developed your assets, right? Versus the big players in the space that are, I call them now, somewhat fallen angels, you know, from a market cap perspective, Zentalis, Repare, or just a few tried to go another route, analogs, which is successful sometimes, but if it doesn't work, this is what happens. Like we used, we called it the kind of jokingly the garbage in, garbage out, but you know, if you're funded, maybe the funds are seeing what you did from scratch and what are the challenges some of the other companies were having, and it made sense to invest in Aprea. Yes, that was definitely the differentiation was part of it. And what we did, we took a different approach and we looked at the field of both the ATR and the WEE1, as well as the third undisclosed target. And what you see is that pharma and other companies, they make analogs, right? So there's one analog that is the lead analog, and then companies will come, will tweak something. In the case of Zentalis, it's really a two-carbon change to the molecule because analogs work, they do work, and it's a faster path for approval. But as you said, Jason, it's not, doesn't solve the liabilities, not always potentially, right, of the so-called parent, the first analog that everybody is mimicking. So what we did, we did not make an analog at all for the ATR. We made a molecule that is a totally different backbone because one of the things when we looked at the ATR field, and it started with KuDOS that was acquired by AstraZeneca and then Bayer made a toxic analog to that that was not selective. Repare made an analog of the analog, and Artios also have one of the analogs there. And what we saw is that they're all suffering from anemia, neutropenia, that is probably, in our estimation and valuation, due to lack of selectivity. And every field has its own things that you have to be very careful about. In DNA damage response, you have to have a selective molecule. That's my belief. If you wanna do combination of, then combine with others, but don't have a dual molecule and don't have a molecule that is also inhibiting other targets. So to solve that for the ATR, we made a macrocycle. It's conformationally constrained, it's very selective, and we're seeing good translation from the preclinical to the clinic. It's a very safe molecule. We don't see anemia, we do not see neutropenia, which also can have its potential best-in-class, but also preferred molecule for combination therapy. Because when you combine two drugs that have overlapping toxicities, we saw that many times before, it doesn't help. It makes things much worse. Same approach was taken for the WEE1. We looked at the WEE1 field, we had to solve it. So whether it's the lack of selectivity with PLK1, which we believe is the issue and the liabilities associated with one set of molecule, AstraZeneca and Zentalis, or QT prolongation that is associated with another set of molecules like Debiofarm and Impact. So we solved that. And that's what we do. You don't compromise on the science. You take the long way, you spend the time, you spend the money, but you do it right because there's only one chance and you don't, you can't have compromise on the molecule. And that was very attractive for the investors. And that is something that we will continue doing. James, I just wanted to ask you, you know, if you could just talk a little bit more about your bifunctional antibodies, how they work, and could we categorize them as in the ADC space? Even loosely. Yeah. Or, you know. You know, we went after one cell population that four or five years ago, people really kind of just stepped over the myeloid-derived suppressor cells. I think Alan List first correlated them with MDS as being immunomodulatory. If you're not familiar with them, they're normally produced in pregnancy, right? They populate the placenta, they create an immune sanctuary. They do the same thing in malignancy. They're now pretty much under, focused by a number of academic centers and soon to be pharmaceutical companies. The thing that we were focused on, besides the fact that VISTA is overexpressed on myeloid cells, specifically MDSCs, we identified with the group at Moffitt Cancer Center, a delta receptor that's highly expressed on tumor-associated MDSCs. And if you inhibit the receptor with a selective small molecule, you actually change the functionality. You decrease their ability to produce a lot of soluble factors like iNOS, Arg1, COX-2. You prevent their ability to inhibit T-cell proliferation or migration. We then turn around and said, well, what if you, we also have a peptide specific inhibitor? So if you conjugate that to a checkpoint inhibitor, like we did first with the peptide for proof of concept, you change the functionality, you remove that immunosuppressive phenotype, and you allow a checkpoint inhibitor to work significantly better than the checkpoint inhibitor by itself. We really look at this as being an immune modulating class of bispecific and bispecific. In this case, you're targeting a G protein-coupled receptor with a small molecule, and you're targeting a more traditional, in this case, receptor for the VISTA antibody. We can do this with any immune modulator. It could be PD-1, it could be a T-cell activator, it doesn't matter. And if you look at MDSCs being about 60% of the cellular population in and around the tumor that's responsible for that phenotype, you know, we think it's a totally untapped area. We certainly wanna become kind of the leaders in this new class of bispecifics. Is it, Marty, bispecific and it'd be loosely associated with bifunctional? Are these not, I mean, I feel like I'm splitting hairs a little bit. Are they that different? No, you're getting down to the semantics. I think ultimately, you know, it's just what you're using with a protein that combined to two different moieties. Right. So, I guess, James, you're kind of ADC slash bispecific. You're the two hottest spaces in biotech also at the same time. So, how much from an investor perspective was validation of targets before they came in? Even though your modality, your drug category is different, right? For Marty, bispecific versus ADC versus something else. Claudin-6 was starting to become established, right? Mesothelin, people had tried and had trouble. Can you talk a little bit about target validation being a driver for investors looking at Context or any one of your groups? Yeah. So, so within the bispecific context of a T-cell engager, one arm binds to what's referred to as a tumor-associated antigen on the cancer cell. The other arm is an immunostimulatory domain, whether it's CD3, CD28, 4-1BB. Our preference on the immunostimulatory domain is to use a high-affinity CD3. So that is to use an ADC term, a very heavy payload. That is, that is coming in with an absolute hammer with the core thesis that CRS can be again mitigated by step dosing and a steroid. So you'd wanna use the most potent payload possible to maximize the response in the tumor. And that's what we've seen work really well, from products from Harpoon, Amgen, and Janux, with their recent data over the last year. Now, as we thought about what tumor-associated antigens we were most interested in, the funnel again was targets that were clinically validated by ADCs. There's about 20 of them in total. Where we focused from there was what we think are the low hanging fruits. So these are targets that are either fully restricted to the tumor because they're oncofetal in the case of Claudin-6, or generally restricted to the tumor like mesothelin and Nectin-4. We are currently shying away from targets that have very broad expression, things like B7-H3, TROP2, PSMA. We think those are much harder targets, very challenging from a CRS standpoint given the broad expression profile. So in the case of Claudin-6, it's a relatively new target. It was pioneered actually by Ugur Sahin, the CEO of BioNTech. He's the one who discovered it in the late 1990s. And what makes it fascinating is it's only found in tumor cells. There are particular tumor types, ovarian, endometrial, lung, and testicular, where it's heavily enriched, and those are generally underserved markets. So really interesting from that standpoint. In the case of mesothelin, that is an older target. So it was discovered in 1992 at the NCI, and it was always known that it was a cleaved protein. What was not known until 2020 was just how cleaved it was. So it turns out there's not one enzymatic cleavage site, but a multitude of them. And the protein is actually cleaved by six different enzymes, and the cleavage of the protein is incredibly efficient. So what you want to do to avoid all those fragments that are cleaved off is bind as close to the cell surface as possible, which is ideal from bringing the T-cell in close proximity to the cancer cell, but actually pretty hard to do from an antibody screening standpoint. And so we were able to acquire a really nice antibody targeting mesothelin. And then the last program we have, Nectin-4, it's a very well-known ADC target. We really like the target for T-cell engager because really besides keratinocytes and skin follicles, it's generally found in the tumor. And those are side effects that can be mitigated through a variety of strategies. And that target is enriched in a bunch of tumor types that we think are really attractive. Bladder cancer, triple negative breast, but also colorectal cancer, particularly microsatellite stable colorectal, which is an area of great unmet need. Three interesting targets, all clinically validated by ADCs to be used in ADC resistance treatment. Oren, I guess similar, you know, concepts to you in terms of target validation, with the ATR and WEE1 by other groups, that being validating and then them wanting to come, you know, take a look at Aprea and what you guys are doing differently and better, frankly. Yeah. So the target, both targets that you mentioned, the ATR and the WEE1 has been validated in the clinic. The challenges were actually the drugs. The drugs were toxic, and that's what we solved. We're coming with much safer drugs. I mentioned before the ATR, we do not see anemia, we do not see neutropenia. It's actually been very clean. We haven't seen any grade four, no sepsis at all, not even remotely. The WEE1 is the same thing. It's a safe drug. It's still in early stage of development, but we're excited about sharing the data in the upcoming trial and then the KOL event, where we're gonna disclose the initial data from the accelerated titration portion of the study. So in both programs, emphasis on having a clean compound, a safe compound with potential efficacy and reduced toxicity. Jim, I think it's similar in a similar vein. VISTA, Kineta was doing work with their VISTA. They ran into some trouble. But it seems, well, it attracted TuHURA or you, like you could make it better, you know, how to kind of fix what they're doing. There was enough there. Maybe investors are aware there's enough there to do something with Kineta's asset and kind of take it forward. TuHURA ended up funding, right? Reopening that phase one trial, I think it completed enrollment relatively recently. Here you are, right? Is it a similar concept for you guys? It was kind of validated or you knew that there was something there and we can move it forward. Yeah, I mean, the target certainly is novel. The fact that they were able to tease out the cytokine release syndrome that killed Janssen's program and others, et cetera, all the biomarker data, receptor occupancy, the PK, I mean, it's pretty impressive. What wasn't, you know, they didn't get the response signal in their phase one study. And if you look at the population they studied, you wouldn't expect it. You know, there are biomarker panels, you can look at VISTA expression on a tumor, right? And so you can select. Endometrial cancer is a good example. Checkpoint inhibitors are used. They fail in about six months, and it's a population that, you know, if you fail a checkpoint inhibitor, you upregulate VISTA. If you fail a hypomethylating agent, you upregulate VISTA. And so you have. There's two populations, right? MDS treated with hypomethylating agents and endometrial cancer. So that would've been the better substrate perhaps for a phase one study that is really biomarker driven. And I think, like I said, it looks like an asset that we can take forward successfully, as a standalone checkpoint inhibitor, novel checkpoint inhibitor. And then if you think of just the combination, not just on the ADC side of it, but if IFX is priming an innate response and you're removing a negative regulator of activation in the microenvironment, you know, that's a combination we'll look at as well. So it's really a synergistic, not just scientifically, but both from a patient and healthcare user concentration perspective. I, you know, I think it's it will be a great fit and I think we'll, to Marty's point, we'll get it at an attractive price. I think, yeah, that there's. I mean, even we see in research. I mean, we see lots of companies, right? There are definitely assets and shells out there, and we're believers that a lot of times, the trials fail the drugs and not the other way around. And there's, you know, not everything is fundable. Maybe a good segue might be to where each of you are clinically, and also how do you connect that to your peers in the space, right? Like I always characterize your companies as there's a valuation gap here, right? But you're not terribly far behind clinically either. So where are you clinically? Where are your peers and what are those next events, including potentially for outside groups that can really get a tailwind for each of your companies to hear you're not there quite yet Friday, right? And then the tailwind suckers. Yeah. I mean, I could, you know, I could talk a little bit about what, what we did in the phase 1. You know, we went to the FDA and rather than just working with the gene therapy, quote unquote, gene therapy group, we asked the deputy director from the oncology clinical excellence group to get involved. Marc Theoret did a lot of the approvals for checkpoint inhibitors, so we felt he'd be probably the best person to understand. And as I mentioned, you know, he looked at the data in primary progression on, on pembro or avelumab and the fact you were able to overcome that. He was the one who proposed that we do it in the frontline setting as a randomized sequential control trial, with ORR as the primary endpoint for accelerated approval. And he was the one that brought up the concept, well, if you're improving response rates to pembro, those are durable, you might affect a clinically beneficial endpoint like progression-free survival. And so the study is unique and this is dual endpoint, right? You can get accelerated approval. You don't have to have ongoing at the time of your BLA submission a confirmatory trial. The secondary endpoint of progression-free survival is baked into essentially the hierarchical design for the analysis plan. And so 30 months after you get the primary endpoint, you evaluate progression-free survival. And if that is successful, you convert to full approval, right? So it deletes the ability, the requirement to have this second ongoing expensive study, which quite frankly is filled with risk because you wouldn't know the population that you're looking to show either PFS or in the case of full approval, overall survival in other diseases. And just to make sure that nobody changed their mind, and he again, to their credit, that group worked with us on the SPA. So we have a special protocol assessment agreement, that essentially if we hit the primary endpoint of ORR, it'll, it's eligible for accelerated approval and you don't have to have a confirmatory trial ongoing at the time of approval. So that, that's unique. And we went back and looked at accelerated approval and I've done this with three out of five prior drugs, either accelerated or conditional. I felt pretty confident that the signal was there in phase 1, even though people say, well, it's only seven out of 13 patients. You know, seven out of 13 is not a bad number to start with in a relapse setting. The fact the FDA took that as the basis for phase 3 registration trial, a single trial. There are only 54 oncology accelerated approval trials that are ongoing as of the end of last year out of 12,000, more than 12,000 phase 3 oncology trials. The FDA has been pulling back. I think, you know, Biogen didn't do the field any benefits on accelerated approval. You know, it is what it is. So I think, you know, not just mechanistically in the data that was produced, you know, the biomarkers all support about the mechanism, but importantly, I think that's a really good partnership with a group at the FDA that's only been around since 2017, right? I mean, passed to put this together, the OCE group in 2017, and they've been, in our case, very helpful. So it was beneficial to pull 'em into the discussion, changed the total dialogue, changed the total endpoint, and subsequently the design for the program. So from a milestone perspective, we hope to get that started early next year, 118 patients, one-to-one randomization, about 12 months for enrollment. And then of course, so last patient in, you figure six to seven months out for top line data. So 18 months from start to finish. It's only about $15 million for the trial. The most expensive part of this study will be pembro because it's frontline standard of care. That's why physicians were very interested in participating. They're gonna get pembro anyway. So if you can improve the response rate in the other half of patients who don't respond, that receptivity was really much, much more robust than we went into and initially thought. This might be a good discussion to have with Merck with regards to a clinical trial agreement. Clearly it would be the first randomized trial for, in this case, an intralesional immune activator, innate immune activator. Hopefully better than what they're seeing with the individual neoantigen therapy of other companies. And then Oren, if you could just maybe give us, you know, the update on where Aprea is, clinically. Yeah, happy to do so. And I 100% agree that engagement with the FDA is the earlier, the better. And we're also benefiting from their support when we file the IND with the FDA for the ATR program. They came to us and said, you know what, reduce the age to 12 years and older. We've been asking for 18 years and older, and they said, go down to 12 years and older and don't worry about any talks or any additional work. And they have been supportive of both of our programs. On the ATR, we just also announced and shared that we're gonna do BID given the PK and the target engagement and coverage. We wanna explore BID with our ATR program and compared to others. So with Artios should come out with data. We're expecting positive data early next year. And AstraZeneca is doing combination with IO for a specific patient population. So we're playing in an area that there is high interest from pharma on the WEE1. Zentalis, we are in the dose escalation portion of the study where our goal is also to optimize dosing and scheduling now because what we saw from looking at the others, and I use Zentalis as an example, they ran too fast with their single agent activity. And then they realized, oh, we need to go back and now do a five on, two off, dosing and scheduling, which really took them back in their development. So they're not that far in their market cap. But yeah, yeah. So they're not that far ahead of us. But to your point, Jason, yeah, there is a big gap in valuation, especially a company like Aprea where we have the money, we have the science, we have the clinical programs, we have the comps, and that is a potential investment opportunity to the audience here that hopefully will take advantage. Marty, any thoughts? Yeah. So Context is at a fun point a little bit earlier stage than my colleagues here. Our Claudin-6 program, which we refer to as CTIM-76, just entered the clinic. So we have three sites activated and are enrolling patients in the Phase 1a portion of that trial for our mesothelin program, which we refer to as CT-95. That will enter the clinic in Q1. So we're really on the front end of all this and what we've guided to as initial data in the first half of 2026 for those programs. So we're talking about investors and where their interests are, validated targets, valuation gaps and opportunity, and such. But I think investors also will follow kind of what FDA is thinking, what are they more open to these days, right? And so, there's, well, two different things here. One's precision oncology, which more applies, mostly to Aprea and Context, but also, and I'll come back to that. Well, let you guys think about this question. Is FDA more interested? Are Are they becoming more geared towards precision targeted medicines, small, very defined populations, of course with safety, as avenues for getting more therapies approved? And then for Jim, say it's a very similar question 'cause we've seen this theme over this conference with companies we're talking to during this conference is that the discussion around FDA seems to be very interested, from our view, in making therapies that they're already familiar with better, whether it's chemotherapies or whatever PD-1 checkpoints. They've become very familiar now with Keytruda. So when you look at Merkel cell and first line and just putting in IFx-2.0 and you can get people to start responding again, are they more interested in that? Is that an easier path? And that I think investors follow those types of things. Yes. I mean, the first lesson for me, quite frankly, I think, and for the group is don't be afraid to go outside of the division that you're assigned to, right? I mean, there's an overarching group over both biologics and drugs, that we engaged with, and they were very helpful. And I think the direction is to get it out of the relapse setting. You know, it used to be, at least when I started Context way back, you know, the old, you get 30% response rate, it's low hanging fruit. You can get an accelerated approval on ORR. I think their focus now is if you're seeing response in the second line setting, if it makes sense to move it into the frontline setting, right? That's their Project FrontRunner. They launched that a couple of years ago. That's what we did in this setting here. And I think that the FDA is very receptive to unmet medical need populations for sure. But importantly, I don't think the surprise for us was overall survival, right? I mean, PFS in this disease, it's, you know, it's not a validated clinically beneficial endpoint, but they wanna validate it in this disease. And they also wanna see a randomized trial as the contribution of your agent to, if you're doing it as an adjunct, to, you know, to the other approved therapeutic. So in this setting, there's four checkpoint inhibitors, PD-1, PD-L1 inhibitors approved. They're all under accelerated approval. None of 'em had a randomized trial. And so I think you're gonna see more of that where they want more definitive data and endpoint analysis that shows that there's, in fact, you are having a benefit of your talk. I just coming back from ESMO, you look at all the work in ovarian cancer, that is absolutely the case. You wanna put a PARP inhibitor with a checkpoint inhibitor, clearly you're gonna have to define the population specifically. So yes, precision medicine, you now have a number of ways to have patient selection criteria, et cetera. And I think that they're moving towards wanting to see it more in the frontline population, and in populations that are underserved when you talk about pediatric populations that the industry has notoriously stayed away from for all the obvious, you know, legal risk associated with it. Marty, do you look at Claudin-6 or mesothelin or Nectin-4 in a later stage patient, get a little bit of data and then what, like, to Jim's point, do you move, does FDA move you to frontline? Yeah, I think I've always had a pretty sanguine view of the FDA. But I've spent my entire career in oncology and I think that is really, you know, the one bright spot within the agency, right? Of really working hard, and diligently with sponsors to bring creative and better solutions for patients. So I'll give an example. In our world in T cell engagers for solid tumors, there's only been two approvals ever. They've been the last three years, but the most recent was at the end of May. Amgen has a drug, tarlatamab; it's marketed as Imdelltra. It's a DLL3 targeting T cell engager. In its clinical trials, Amgen required 48 hour inpatient monitoring. The drug actually is exceedingly well tolerated. The FDA in the label changed it to one day. That wasn't Amgen's request. The FDA pushed it. They said, your drug looks good. You know, let's try to open the possibilities of more patients being able to get the drug because it will be more accessible. And I think what's also interesting is in its first month of launch in June, it did $12 million. And so I think that speaks to the FDA responding to the desire of clinicians and patients to having not just better drugs, but drugs that are less of a strain on their daily lives, and that better fit within their schedules. So I see the agency of being very supportive and collaborative within oncology. And I think to your point, there certainly are modalities where they're getting more comfortable. T-cell engagers, they absolutely weren't comfortable five years ago, and we've just seen them change over the last 18 months in dramatic fashion where they're very supportive and very prescriptive in what they want. I think that's always a risk for companies that whether the risk is real or perceived that the agency may change their thought on a whim. And what we've seen within T-cell engagers is the agency really streamline their thought process and make it consistent across sponsors. And that's really helpful from a planning standpoint. Oren, any thoughts? I agree 100%. In our case, it's easy because we are a small molecule and the FDA totally get the concept of a biomarker driven, and patient selection, and they care about safety and efficacy, right? So they wanna give the right drug to the right patient. It's not chemotherapy, it's targeted therapy. So from the FDA perspective, if the right drug is given to the right patient population to increase the chance for a safe and well tolerated and efficacious, they're gonna do everything they can to promote and support that. I 100% agree with what was said. Yeah. And we don't have time for this, but I mean, we, some people, you know, on this, on this conference, some of the companies we're talking about, you know, innovators are always ahead of, of regulators, right? And, and regulators start to catch up and, and where things were difficult before, FDA seems to be evolving, and making pathways more, less challenging, for drug developers. But I mean, that's a whole other, that's a whole other discussion and we're out of time. I really appreciate all three of you coming on. And if you didn't catch it earlier, I guess it'll be the ticker HURA, right? Will be Friday. Right. TuHura, well, I'm sorry. Uncertain, correct. Yeah. So TuHura, we'll start trading on Friday, completing its reverse merger with Kintara. Then you have Aprea, CNTX for Context. All three companies, I think there's value to be had there and certainly on the cutting edge of oncology. Really interesting stuff, guys. I appreciate it. Thank you so much. Thanks, guys. Thank you.