Welcome everyone to the State of WEE1 Inhibition in Precision Oncology hosted by Aprea Therapeutics. At this time, all participants are in a listen-only mode, and a replay will be made available on the Aprea website following the conclusion of the event. Before we begin, I would like to remind you that the company will be making forward-looking statements regarding its business, including statements related to the potential and developmental plans for its therapeutic candidates. For further details, please refer to this slide as well as the company's filings with the SEC. With that, I'd now like to turn the call over to your host for today's event, Solomon Wilcots. Please go ahead, Solomon.
All right. Thank you, and welcome everyone to the pre-ESMO webinar. We want to get started by talking about the State of WEE1 Inhibition in Precision Oncology. WEE1 inhibition is emerging as an approach to precision oncology driven by advances in biomarker-defined window. Today, I would like to welcome Dr. Alex Spira, Director of the Thoracic and Phase I Program at the Virginia Cancer Specialists Research Institute, Chief Scientific Officer at NEXT Oncology, and Clinical Assistant Professor at Johns Hopkins, a leader in early-stage oncology drug development. Dr. Alex Spira will share his clinical perspective on the evolving evidence supporting WEE1 inhibition and the unmet need of cancer patients and the potential impact of this therapeutic approach on patient outcomes. Next, Kevin DeGeeter, Managing Director in Equity Research at Ladenburg Thalmann & Co. Inc.
Kevin DeGeeter will provide insights into the broader investment landscape industry interests, as well as the clinical and commercial milestones that could shape the future development of WEE1 inhibition. Also joining us is Dr. Gene Kennedy, Chief Medical Advisor of Aprea Therapeutics. Dr. Gene Kennedy will discuss the specific rationale behind WEE1 inhibition, the importance of biomarker-driven patient selection, and Aprea Therapeutics' approach to developing selective targeted therapies for patients with biomarker-defined cancers. Let's go ahead and get started by talking about the biology, why WEE1 and the DNA damage response truly matter. To set the stage, let's start with the underlying biology, what the DNA damage response is, and why WEE1 has emerged as a compelling target in precision oncology. Dr. Spira, let's start with you. In accessible terms, what is the DNA damage response, and why has it become an attractive source of targets in oncology?
Thanks, Solomon. The easiest way I find to think about this is it's the quality control system of a cell. So every time a cell divides, it has to copy its DNA accurately. If you think about it, even if it's 99.999% accurate, cells replicate hundreds and hundreds and thousands and millions of times a day. Cancer cells are doing it even more. So if there are errors or damage, the cell has to recognize that damage and change it. These are enzymes that are built in, these DNA repair enzymes. So it has to repair it before it continues. Cancer cells are interesting because they have a lot of what we call genomic instability. They're replicating very rapidly, they have inherent defects, and they accumulate DNA damage and replication stress as they grow rapidly. But they also develop ways to survive that stress.
In many cases, they become unusually dependent on these repair pathways. It is a therapeutic opportunity. If we can identify the pathways a particular cancer cell depends on and disrupts them, you can push the cancer cell beyond its ability to recover. Because the cancer cells are replicating far more rapidly than normal cells, you can use this as a therapeutic intervention to take care of the cancer cells but allow the normal cells to grow. We have seen this before, right? This is what PARP inhibitors are. There are other therapies as well, but that is the best example to extrapolate this DNA damage response. WEE1 is also an important part of that strategy. The challenge is not to damage the cancer cells.
It is to identify these biologic vulnerabilities that can exploit this therapeutic ratio where the cancer cells require more than normal cells, and they are more susceptible to it than normal cells.
Dr. Kennedy, let us turn to you. What role does WEE1 play in the DNA damage response, and what makes it a compelling target for cancer therapeutics?
Thanks, Solomon. As Dr. Spira just said, WEE1 is basically one of the edit checks on copying DNA when cells divide as Dr. Spira described, right? These edit checks are designed to make sure things go in a reliable fashion. But, as we just heard, these cancer cells are divided even faster and probably with a little less control than normal cells, primarily because they contain mutations, right? With modern genetic screening, we can look for mutations in these edit checks that exist, so it makes the cells vulnerable. Then if we come through with a drug, like a WEE1 inhibitor, that knocks out an additional edit check, that can tip the cell over from reproducing in a functional way to sort of having a catastrophic collapse and failure when it tries to reproduce, right?
Why is this one particular—and there's multiple of these edit checks you could go after—why do we find that WEE1 is compelling? Well, we benefit from the experience of others, because people have already gone after WEE1 as an approach to fighting cancer cells. Other companies have made some progress in this area, and they've shown that by going after WEE1, you can actually fight cancers and get tumors to shrink.
The challenge thus far has been able to do it with enough of the safety window, this therapeutic window that Dr. Spira was mentioning. Can you make one that's big enough? Can you make the room between shrinking tumors and causing patients to become sick large enough that physicians can actually use this drug for their patients in a reliable and relatively easy fashion? We think it's a great target because we know if you hit it will work, and we think that we can actually work on the toxicity in the future.
Mr. DeGeeter, from a market perspective, why has the WEE1 class captured so much investor and industry attention over the past several years?
Yeah. Thank you. A few things. I think the attitude of investors changed over the last two, three years with regard to precision oncology. The paradigm in precision oncology 1.0 and 2.0 was, for both strategic investors like big pharma and for financial investors was, find new targets that would have very high response rate. If you gave the drug to the patient, 70%, 80%, 90% chance they would have a clinical benefit to, in the evolving paradigm, looking for targets that are important in much larger potential patient populations. The old maxim that if you're going to get a really high response rate, it tends to be for a smaller patient, often holds true in oncology.
The attractive part about WEE1 from a market perspective is the number of patients who potentially benefit from an effective drug in this class is tens of thousands of patients instead of hundreds of thousands of patients that we might have seen in earlier generations of precision oncology. A larger addressable market opportunity is really what is attracting investor interest.
Next, let's have a discussion on where the need is the greatest, patients who have not responded to existing therapies. With that said, with that biology in mind, let's turn to the patients and where WEE1 inhibition may offer the greatest benefit. In cancer patients who have not responded to existing therapies, Dr. Spira, where do WEE1 inhibitors hold the greatest potential? Do you envision using WEE1 inhibitors to overcome antibody drug conjugate resistance?
Lots of stuff to talk about there. One is oncology has been incredibly fruitful over the last couple of years. We made incredible progress with lots of different treatments, immunotherapy, targeted therapy, et cetera. A couple of things. It has not been good enough. I'll use the analogy of pancreatic cancer, right? We've just had these RAS drugs, and everybody's incredibly excited. Yet the median survival in this patient population has gone from 6 - 13 months.
It's still over a year, and that's it. We clearly need to do better. There's still wide open room for tons of drugs. Once a patient has progressed through standard therapy, the options are still limited, and we still struggle to get drugs for our patients that work. There's still other chemotherapy, and for the most part, we still talk about chemotherapy for most of our patients, sometimes immunotherapy, et cetera. But there's still a huge role for many new therapies. Let's specifically talk about where WEE1 has been very important is gynecological cancers, specifically uterine cancer, and as well as ovarian cancer that's platinum-resistant. There's clearly an unmet need here right now. We still do not have a lot of good treatments, and we need to do better. There's still a huge need in all these patient populations, regardless of what you're looking at.
What makes WEE1 inhibition very interesting is that it's completely different. It's a new class. There are no FDA-approved drugs. You're exploiting this DNA damage response that does accumulate over time, and these cells are very susceptible to it. This is not one specific oncogenic driver. You're exploring entire weakness based upon the cells as well. Specifically, we're all very excited because there are some ADCs coming down the pipeline. We've all heard about this. There's a lot in this class, and in drug development, all we talked about for the last two years is another day, another ADC. The fact of the matter is this is actually a really good strategy to overcome resistance for a couple of reasons. Most notably, ADCs are really just chemotherapy.
Chemotherapy causes DNA damage, and as we know, once cancer cells have this DNA damage, they tend to replicate much quicker, and they're setting themselves up. No matter where you look at for these patients, antibody drug conjugates right now are, as I said, chemotherapy on a stick is a nice description for them, but they really are setting the cancer cells up to as a next line of therapy to be susceptible to these WEE1 kinase inhibitors that are really looking at DNA damage.
Really great information. Dr. Kennedy, what types of cancer-associated mutations are emerging as most relevant in terms of identifying patients who might benefit from DDR-targeted approaches?
Well, thanks, Solomon. The key to using drugs in this class really is patient identification. As we were discussing a little bit earlier in the biology section, we talked about cancer cells as having mutations in these pathways that they need to divide and replicate. That differentiates them from normal cells that also divide and replicate, but it's those mutations that make them vulnerable, and then when you come in with a drug like a WEE1 inhibitor, you can kill the cancer cells without harming, to a great extent, the normal cells. You got to find those mutations, as you said. I think for WEE1 specifically, the marker that has the most data behind it is Cyclin E- overexpression. That is a marker that's determined via a specific test, and that's been advanced by a company working in this area called Zentalis.
They have really nice data coming this week at the ESMO Conference in Spain, where they showed that identifying patients with platinum-resistant ovarian cancer and differentiate or dividing them between those who have high Cyclin E- overexpression and those who do not when treated with a WEE1 inhibitor have a difference in survival of about 16 months versus about seven months. That is great progress. Right?
Yeah.
I think based by data right now, you have to put Cyclin E-overexpression sort of at the top of the heap. But we do not think it is the only one. In our hands and in others, as Dr. Spira said, uterine cancer is a great indication for this class of drugs, and there is a subset of uterine cancer called uterine serous carcinoma or USC. These patients are known to have tumors that harbor a lot of mutations that should make them vulnerable to these types of drugs. As I said, in our hands and in others, we have actually seen patients respond with that kind of tumor to this class of drugs. Also on the list are mutations you can identify with genetic sequencing. A little different technique than you would use to identify Cyclin E-overexpression. I do not think the details are important.
The fact is that with standardly available testing, you can identify these patients as well. The three that I sort of put together, because they all sort of feed into the same general pathway as the Cyclin E-overexpression, are mutations called CCNE1, CCNE2, and FBXW7. Then also on our list is another one of these cell cycle mechanism mutations that we have found interesting and actually had a couple of patients respond to, called PPP2R1A. So we think there is different ways of looking at the genetic defects, the mutations in tumor cells. We think there are different pathways and different approaches you can take, and it is just going to take more and more research to decide which patients respond at which rates to the mutations. It is not like one mutation has to win.
Patients with different mutations might potentially all benefit from these drugs, albeit maybe at different rates. Some might benefit more commonly with one than another. But it is up to those of us who are working to develop cancer drugs to figure that all out and bring it forward to patients.
Really good stuff. Dr. DeGeeter, Mr. DeGeeter, excuse me, how significant is the commercial opportunity in these biomarker-defined populations, and what does TheStreet think about market size in precision oncology niches like these?
I'll take the second part of the question first, because I think that's really what the significant part of this audience is focused on. TheStreet, at the end of the day, gives credit to populations where a drug in the class has already shown activity. Dr. Spira and Dr. Kennedy highlighted a number of those populations, primarily in gynecologic cancers. Today, if you add all of those up, at least in our work, that gets you to close to 20,000 patients in the U.S. thinking about WEE1 inhibitors as a monotherapy. If you put a dollar amount on that using reasonably standard pricing, that'll get you to a $3 billion-$5 billion addressable market opportunity. Meaningful from a financial perspective for those looking to invest into the group.
As we explore additional WEE1 inhibitors that appear to have better tolerability profile, are there opportunities to use WEE1 inhibitors, not simply as monotherapy, but in combination with other agents? If that tolerability, the therapeutic window, which we've talked about on this call at length, plays out as additional data sets mature, you could be talking about also being able to benefit patients in other cancer types through combination modalities, and then the addressable market increases significantly from that 20,000 or so that I identified.
So let's move on and talk about some of the central challenges, selectivity and the therapeutic window. One of the historic challenges faced by WEE1 inhibitors has been finding the right balance between efficacy and toxicity. Let's dive into that a little bit deeper. What is TheStreet's read on why earlier efforts in this class struggled, and how much of the current investment theses really do hinge on solving tolerability? Mr. DeGeeter, I'll allow you to begin, and Dr. Kennedy, you can follow up.
Yeah. No, thank you for that. First-generation WEE1 inhibitors demonstrated two side effects that were notable. One being GI adverse events, but really important, particularly for these gynecologic oncology patients, myelosuppression. That really is clinically important, as Dr. Spira already mentioned. These patients see a lot of chemotherapy through their treatment journey, and adding in a new class of drug, or a new drug that had significant myelosuppression really is problematic as you think about the class. One of the things that we think TheStreet tends to do is, when you see some of these adverse events in first generations in the class, it then becomes a bit of a show-me story for other compounds that come later to show how they're different and that those key adverse events, in this case I've identified myelosuppression, are not present in the drugs that come along.
One of the things that has us excited is seeing some phase I work that really does show some reduction in myelosuppression to very tolerable levels in some of the phase I sites of current generation of WEE1 inhibitors. If that's able to be confirmed in additional studies, we think that provides a lot of flexibility in dosing, once again, to run combination studies in this class.
Dr. Kennedy?
Yeah, no, I think just to follow up on what Mr. DeGeeter said. With the first WEE1 inhibitor, two large pharma companies, Merck and AstraZeneca, which are inarguably successful at developing drugs for oncology and for other diseases, worked together on this drug and worked really hard. They did everything they could, and they showed that it works as far as shrinking tumors, but they couldn't solve the toxicity problem. I think that sort of showed everyone else the potential's there. This is a target worth going after if you can do it safely. I just mentioned that Zentalis has data this week coming out at ESMO, and they've been actually able to get that. Merck and AstraZeneca gave up on their program.
They shut down a drug that works because of the toxicity, and that's one of the reasons sometimes a drug doesn't make it from beginning to end, unfortunately. Zentalis is working on the same pathway. They're showing data this week at ESMO. They have a program moving forward. I think it's great for the field, it's encouraging, and they've been able to get the toxicity more under control, as evidenced by the fact they're going forward. But we think the potential is still there to do even more. That maybe someday, Dr. Spira will be giving drugs to people that cures cancer with no side effects. I'm afraid we're not there yet. But if we can actually just keep increasing that window between efficacy and making patients sick, we're doing the right thing, and I think that potential exists with WEE1.
Dr. Spira, why is it so important to ensure that drugs effectively engage WEE1 while avoiding off-target effects? And how has that played a role in the issue of tolerability among first-generation WEE1 inhibitors?
Yeah, and I'm just going to reiterate a lot of what's already been said. But I think my take home message here, there's a therapeutic benefit ratio where you have to come up with a drug that has reasonable side effects that you can give that cause a shrinkage of the tumor. As Gene Kennedy said very eloquently is first generation worked, it was just too toxic. Oncology right now is not just about being first in class, it's about being best in class. So hopefully these newer drugs can take and learn about it. Also is using people's experience.
There's always a desire in oncology to push people to the maximum dose. Maybe we don't have to put people to the maximum dose, and we learned that through good clinical experience that we need to have drugs that work, but we don't necessarily need to be at the maximum dose to cause all these side effects. All it takes is bad side effects in a couple of patients that can really eradicate a good program. We're all very encouraged by some of this data that we've heard, either preliminarily or coming down the pipe, and it's right now to come up with a new generation of drugs that work, expanding on our previous experience.
Let's now move on to Aprea Therapeutics' approach, APR-1051, and a biomarker strategy. That brings us to Aprea's own program and how APR-1051 was designed and some of the key components of the ACESOT-1051 trial. Dr. Kennedy, how was APR-1051 designed, and what was the thinking behind its selectivity profile?
Thanks, Solomon. As I just mentioned, we have the benefit of learning from the progress made by others, having come along behind truly competent organizations like Merck and AstraZeneca. We understood the chemistry that they had in their molecule, and we understood the limitations they had in their toxicity. Zentalis is using the same chemical backbone but made important changes, and they've made further progress. With understanding that, we were able to sort of take a step back and start with, to use a bad analogy, like a clean sheet of paper. We were able to start fresh and try to engineer out some of the problems that were seen with the prior molecules. There's many things you can do when you design a molecule, but there's certain things that you can focus on that are critical. One is potency.
How strong of an inhibitor is it? With the idea being that the more potent it is, the less drug you have to give, and then there's sort of the less opportunity for spillover into side effects if you have a drug that's very, very potent. The other one is how specific it is. We're trying to inhibit a single sort of molecule that does a specific function in a cell. There's many, many molecules that do similar functions, and they all share sort of similarities. The analogy that's often used is a lock and a key. Right?
If that's a lock, if you can develop a key that fits in only that lock and doesn't just sort of at least sort of slide in there and rattle around in some of the other locks without doing sort of the whole thing, you can limit the effects of your drug because some of those effects might be good, but some of those effects might be bad. If you have a molecule that's less specific, again, you can pick up more toxicity. Then the third thing you can sort of engineer is what's called pharmacokinetics, which is how the drug reacts in the body. These drugs are pills. You swallow the pill, you absorb it through your digestive tract, and then the level sort of goes up in your blood and stays there for a certain amount of time, right?
In our opinion, some drugs go up really high and down really quickly. Some drugs go up in sort of a gradual smooth curve. We've tried to engineer something that has sort of this smooth profile of drug in the blood without lots of peaks and lots of valleys, which we think may ultimately be advantageous to patients. Knowing what was done, knowing some of the challenges that others had, gave us this opportunity to take a fresh look at it.
Well, I love the key and the lock analogy. It really does paint a very vivid picture for us. Dr. Spira, as a clinician and investigator who is actively involved with cancer clinical trials, what are some of the key findings that you're watching with APR-1051 that will tell us if the drug is striking the right balance of efficacy and tolerability?
Yeah, so a couple of things. One is you need to understand its safety, evidence of tumor activity and drug exposure. We have to look at all those things. Also use the analogy, it's a marathon, not a sprint. It's important that we come up with drugs that not only can patients take for one cycle, but they can also take for multiple cycles over time. Clearly, it's the phase I study, and then we have to figure out the recommended phase II dosing. Need to understand what these toxicities are and look at the adverse event profile and make a judge. That's using good clinical judgment of the Aprea team, but also with the investigators to strike that balance of what can we give to patients and what will patients tolerate.
Previous generations of drugs had a tough time doing that and maybe tried to push the dose too high. Of course, we have to look at efficacy, very simply, what is the response rate? Of course, then the tumor response. Then looking at all this together with the team there is looking at the PK data, pharmacokinetic data. You can look very quickly, make sure that the drug is engaging its target, looking at that lock and key. Are we actually engaging its target, and how long are we engaging that target for? Again, it's not just looking at a response, it's what are the responses seen at the different dose levels, how high do we have to get, and what can patients tolerate?
I understand the role, and Kevin will tell you in the investment world, everybody wants to know what the response rate is. But it's just not that response rate. A good clinical team, and I think there's one put together here. Obviously, we're involved, so I'll speak of that as well. But it's not just looking at that immediate response. Can the drug be given over a continuous time without having patients drop out because of side effects or patient discretion there? That'll give the idea after a phase I is ongoing, can we expand into other cohorts and see where this goes?
Patient selection. Aprea's strategy involves enrolling patients with a number of different tumor types and genetic alterations. Can you walk us through the rationale of this aspect of the trial design and how these various tumor characteristics all converge on WEE1?
Certainly, Solomon . As I mentioned earlier, there are genetic mutations that we think may predispose people to responding to these types of cancers. A lot of that work comes from science done before you ever take a drug and administer it to a patient. So you want to have that in mind. For drugs that are targeted therapy, aiming at a target, I think, is very important in early trials or else how do you know if it's actually helping people? The first phase of research where Aprea is, called phase I, was classically intended just to see whether or not the drug makes people sick. What are the side effects? In more recent years, a lot of people expect to see, especially with targeted therapies, signs of are you helping people in addition to just making them sick?
If I gave a drug through a clinical trial to unselected patients, I would learn about the making them sick part, but my opportunity to learn about helping them would be very limited. That is why we have this sort of approach here. I said we are going through genetic selection, Cyclin E-overexpression, USC, the other genetic markers, CCNE1, CCNE2, FBXW7, PPP2R1A that I mentioned. Those are key. Then you build this phase I study where you gradually go up in dose, and drug companies do not actually give their drugs to anyone.
For a drug company to actually bring a drug through clinic, a drug company has to partner with experienced investigators like Dr. Spira, who actually sees the patient, who actually looks at what you are doing and says, okay, this passes in my professional judgment as a reasonable thing to actually offer my patients who, when they get to the point of an early stage trial, have no other approved options. If there were drugs that were proven to work, they would be getting those instead of drugs that were not yet proven to work. It seems pretty obvious when you say it out loud, but that is how it works.
Yeah.
There are these sort of checks and balances. Then part of the design is actually to not just write something down, like carve it in stone and say, here is what we are going to do. It is to partner with people who actually see patients every day and then sort of make minor adjustments as you go on, learn what is working, learn what is not working. Then try to sort of, as you go through this process, refine your understanding of who might respond to these therapies. Then sometimes these toxicity studies are very small. Then when you go to the next stage, when you try to figure out does it work more so than is it toxic, you still do not know who actually to offer the drug to.
Lots of companies, including ourselves now, go upward in dose, but sideways in the number of patients, identified by our investigators who are our partners in this. Then by offering the opportunity to participate in the trial to enough patients, you then begin to get the idea of the different ideas we had in our head when they started this trial. Which ones of those were valid? Which ones of those are helping people? And those are the ones we should double down on going forward.
All right, gentlemen, let's look ahead down the road and see what's coming up, maybe even this fall or even beyond that point. We're headed into an unusual data-rich stretch for this field, with several readouts anticipated across the class around ESMO and through early next year. What would be meaningful in terms of clinical validation of WEE1 inhibition, and what would that look like? What would this mean for the field? Dr. Spira, let's start with you.
Yeah. Very quickly, I just want to remind everybody here right now, the goals are very simple. All we're trying to do is establish can we have activity, and can the drug be given? I think it's a very simple concept, but it's very simple. We really need to see reproducible activity with responses that are meaningful and durable. As an investigator on this, I think we're going to get there. Again, this is designed to be best in class, not first in class. The first in class doesn't always win. It's often the second or the third one. I think there's really good take-home messages that the team there has really learned and can design the drug that's better going forward. Secondarily, we have to look at different patient populations.
As you heard from Dr. Kennedy, there's a few different patient populations being looked at. Is it cyclin? Is it CCNE1? Is it FBXW7? Which patients are going to be important here? Is it a little bit agnostic? It'll be very important to help figure that out and get some of this genetic data. Maybe it'll work in everybody, but maybe it work better in a subpopulation, and that's what this early phase I will tell us to generate the data for really the expansion cohort. Very excited about going forward, but I think we should begin to see some data later this fall.
Mr. DeGeeter, how do investors evaluate differentiation and de-risking in a class like this? What does partnership or business development interests tend to signal?
Yeah, no, listen, thanks. I guess I'll build on Dr. Spira's comments and kind of break this into two parts from our perspective. Clinically, data and then address your thoughts on business development. Clinically, there's three inflection points for most of the financial community industry. Responses, do tumor shrink, confirmed responses, it shrank, and we're able to go back and rigorously confirm that the benefits seen on the scans was evaluated to be correct, and then how long is the benefit? Of those three, our view, and I think the view of most people on TheStreet is the cleanest differentiation, particularly in phase I and II work, is on confirmed responses. That's been a little bit of an evolution the last couple of years. Five years ago, I would say investors tended to differentiate a little bit less between response and confirmed response.
Most of our clients today really want to see confirmation that those PRs and CRs are real. The real sort of value question, a little bit of the dark art from the financial community perspective is cross-study comparisons on durability, but you can't really do those, in my view, on phase I and II studies. There's just too much heterogeneity in the patient population. So to really kind of answer the question on how durable is the benefit for patients, I think you really need later stage data on two or more compounds to begin to kind of tease that out. The business development question, I think, is a fascinating one and kind of how that figures into de-risking, because there's really two answers here, right?
If you're developing a drug that's likely to be used as monotherapy, and earlier on I talked about precision oncology 1.0 and 2.0 type drugs, the way we tend to think about them. Most of those drugs were really designed to be used as monotherapy. There, the logic of partnering up with a big pharma before late-stage development, it wasn't particularly compelling. You're evaluating a single drug in defined patient population. Until you're getting closer to commercialization, why not kind of hold on to the full economics? Here, or in opportunities where you may be able to use a drug in combination as well as monotherapy, there the business developing question gets really interesting because there are classes of drugs you may want to partner WEE1 with that another large biotech or big pharma company may have in their development pipeline.
In that context, doing business development to de-risk an asset earlier in development can make a lot of sense. Not only does it bring in some capital and validation, but may allow for some interesting combination studies to be run far sooner than they might otherwise run. What is going to happen in WEE1? Which one of those two paradigms? As you kind of heard our comments in this discussion, we do see an opportunity for combination regimens. We would not be surprised to see some business development in the WEE1 ecosystem potentially sooner than later.
Okay. Dr. Kennedy, Aprea plans to present data from the ACESOT-1051 program later this fall. Without getting ahead of the data, what should the field be looking for based on what the trial was designed to show?
Yeah, thanks, Solomon. About a month from now, there is a major cancer meeting in Europe. We have the opportunity, through one of our investigators, to present an update on the trial. This will not be the final answer for the trial. This is a midstream update. The last time we had a chance to do this was back in June at a big meeting called ASCO, and the data there was from all the work we had done up to May of this year. That is really a six-month interval that has gone by, and this will give us a nice chance to show folks the progress the program has made and hopefully start to show the program the direction the program is going. I cannot really get into the details right now because there are rules about those things.
But I think what people can expect is a meaningful update in the number of patients who had an opportunity to participate in the trial and the experience those patients have had on the trial to date.
All right. Really good stuff. Before we close, gentlemen, I would like to give each of you a moment to share what excites you most about the future of DDR-targeted precision oncology, and what gives you the most optimism about where this field is headed over the next, say, 12 - 24 months. Dr. Spira, we'll start with you, then Mr. DeGeeter, and then Dr. Kennedy, you can close us out.
I've said this a couple of times already, we already know that there's activity with these drugs. We've heard it. We just need to optimize it right now. So getting an opportunity with the best in class or at least newest in class, very excited about. It's validation of what we're doing. We've seen some response rates. We've seen patients respond and benefit. I'm very excited by the fact we're now taking this new drug towards the end of phase I, where we can see the activity and hopefully get it to our patients.
Yeah, I'll build on that from my perspective. One of the things is my job is ultimately about pattern recognition. So we tend to take a view that where there's smoke, there's fire, and we now have multiple WEE1 inhibitors in clinical development. Each of these programs is trying to generate proof of concept data to address specific problems that previously have held back the field in developing drugs for WEE1. I believe two of the obstacles that have held back development in this space have already been largely de-risked. That's patient selection to find who is the likely best responder, and how to mitigate some of the most problematic adverse events that allow for greater dosing flexibility.
The third key question in our mind really is around what do you combine WEE1 inhibitors with in terms of other drug classes, and I think that's a question that there's multiple studies from different sponsors that are going to be kicking off in the coming months. As I think about the collective learning of the field, I think that bodes really well for the opportunity for significant progress in the next 12 - 24 months.
Dr. Kennedy?
Yeah, certainly. No, I think I'd just like to build on what Mr. DeGeeter said about combinations. As we learn more about how well these drugs work and how safely these drugs work, and if we establish, as we hope, that therapeutic window, that difference between toxicity and efficacy that allows them to be used in a reasonable manner, it really opens up the opportunity for combining with other active therapies. There's a ton of laboratory data that shows if you combine these drugs with other established therapies, be they chemotherapy, immunotherapy, or other targeted therapies, you get synergy. The two together are greater than either apart, right? But when you actually go and treat a person, each drug brings its own unique spectrum of side effects.
If one of the ones you're trying to combine is already at the limit of what any reasonable person can tolerate, then you add more to that makes Dr. Spira's job of getting his patients through these therapies probably more challenging than he would care to deal with, right? It's just not going to work. You have to find that right middle point, that balance, right? So what I'm excited about is really seeing if we can get so far with these drugs, and how much further can we get with combining if we can actually crack that tolerability and efficacy window.
Dr. Alex Spira, Kevin DeGeeter, and Dr. Gene Kennedy for sharing their insights and perspectives. If there is one thing that we could take away from today's conversation is that WEE1 inhibition represents an exciting and evolving area of cancer research with the potential to make a meaningful difference for patients who urgently need new treatment options. We've heard how advances in our understanding of cancer biology, combined with precision medicine and biomarker-driven approaches, are creating new opportunities to target vulnerabilities in cancer cells. We've also heard that the future success of WEE1 inhibitors will depend on demonstrating meaningful clinical activity, durable responses, and a manageable safety profile. Perhaps most importantly, it's getting the right treatment to the right patients, ultimately giving more patients reason for hope. With important clinical developments on the horizon, this is certainly a field worth watching.
On behalf of Aprea Therapeutics, I would like to thank our panelists and everyone who has joined us today. Thank you, and we look forward to continuing the conversation as the science and clinical evidence continues to evolve. Thank you, everyone.