On that note, good afternoon, everyone, and welcome to our next session. I'm your moderator, Sara Nik. I'm an Equity Research VP at H.C. Wainwright , and it's my pleasure to introduce our next presenter, Oren Gilad, CEO at Aprea Therapeutics, a biopharmaceutical company developing small molecule inhibitors to exploit genetic mutations in cancer. With that, the floor is yours, Oren.
Thank you. Thank you, Sara, for your ongoing support and for the opportunity to present Aprea Therapeutics, where we can't wait to cure cancer. I'm going to make forward-looking statements, so please refer to our SEC filing for all the risks associated with it. And Aprea Therapeutics is really in the intersection between precision medicine and synthetic lethality. We put the slogan there, "One Clinical Pathway, Multiple Targets," where you can see that the pipeline is very focused. We have an ATR inhibitor.
We have a WEE1 inhibitor, which I'm going to tell you more about. But we also have the legacy p53 reactivator that we're now working on understanding the phase three data. There's also undisclosed targets that we will disclose later in the year. The reason we're not disclosing it is for IP purposes. We want to make sure that we have a very strong IP coverage for all of our programs. The focus of today's talk is our WEE1 inhibitor, the APR-1051. Since 2024, we got the IND filed and cleared. We enrolled the first patient. We completed the dose design. This is an open-label study. The patient is being enrolled.
The study is progressing. We're going to share additional data later in the year, the Triple Conference, the upcoming Triple Conference. With the ATR program, we had the QD in 2024, and then later in the year, we added BID. That's because of the PK property of this molecule. The WEE1 inhibitor has a very long and prolonged half-life. The ATR has a short half-life. It seems like the decision to start to initiate the BID regimen has been paying off for us.
So you can see that at the end of this year and the first half of next year, we're going to be very busy. The management team is very experienced. Some of the team members came from Atrin, and some have joined us later. And you can see that there is experience really in every aspect of drug development. And the board of directors is also very strong, and everybody is involved. So we're going to start with the WEE1 inhibitor. Initially, the MTD was projected to be 150, but then given the positive safety, we went to the FDA and asked them to increase the dose. And we got support for that.
So you can see in addition to the 150, we added 220, 300, and we can go higher, which is really great because it is adding on to the therapeutic index, right? Because it's not affecting the efficacy, but it's giving us a larger safety, which hopefully will translate into a higher therapeutic index. As I said, the study is enrolling and moving forward. What we're showing here is a swimmer plot. You can see even though we are at subtherapeutic levels, we already start to see some signs of early signs of activity at the 70 mg cohort as well as the 100 mg cohorts.
We summarized it in this table here s o can see at the 70 mg, the one patient had two scans. It's the same cut-off date. This is cut-off for July, the end of 21 July . The first scan was minus seven, sorry, minus five. The second scan was plus seven. So it's about the same, right? It's within the standard deviation there. At the 100 mg, we're seeing two patients with stable disease, still not PR, but stable disease. One patient at the first scan was -5%. And the second patient at the first scan was +15%, within the range of stable disease.
So you see that the number of stable diseases is increasing as we're increasing the dose. So the next couple of slides is to show how the preclinical is being translated nicely to the clinical setting. On the left, we're showing a mouse model. This is cyclin OVCAR-3, overexpressing cyclin E, a nd you can see that the treated group is pretty flat. And this is oral administration, daily treatment. On the right, it's a patient that is 86 years old, can be our mother. She's a fighter. She was treated in Next Oncology in Dallas, a nd the mutation that she carries is FBXW7.
When FBXW7 is mutated, it doesn't degrade cyclin E, and therefore, cyclin E is accumulated and overexpressed, so it's a good biomarker for WEE1 inhibition, just like the preclinical model, and you can see that she had five prior lines of treatment, right? The first one, nice response, 191 days, and then in line two, three, four, and five, you're going from 45 before progressing, 43 progressing, 12 days not evaluable, and then in the last line, 50 days before progressed.
As of 21 July , she's on a trial on day 79, so already showing improved response with days compared to line two, three, four, and five, and she was stable disease with a small tumor reduction of -5% and very well tolerated, so that's one biomarker that we are looking at. The second biomarker is HPV-positive head and neck cancer. And for that, we have a very strong ongoing collaboration with MD Anderson. So this is the preclinical data is actually being generated through this collaboration. And you can see that here they treated five on two off and HPV-positive. You can see a nice response as single agent.
The patient on the right also been treated at MD Anderson, HPV-positive. And you can see three prior lines of treatments. First line, 49 days, 84 days in the second line, and 184 days third line. And on our trial as of 21 July , 146 days. Okay? So good translation from the preclinical to the clinic. All of our programs are biomarker-driven, right? This is not chemotherapy. This is personalized medicine. This is targeted therapy. At Aprea, we work hard for matching the disease, the mutation, the indication with the drug, right?
That's where we're expecting to see the highest and the strongest response. These are preclinical model for combination therapy. The two on the left has been generated at MD Anderson. And the one on the left, you can see this is kind of a resistant cell line, right? Because you see the red line, not much of a response, but it also didn't respond to cisplatin. But look at the orange line, the combination, very synergistic, strongly synergistic, and minimum side effects. In the middle, it's the HPV model. And you can see the purple one, very synergistic, right?
Even after we ended the treatment, the tumor and the combination never came back up. It was almost completely gone there. And then on the right, that's the OVCAR-3, where we know it's a sensitive cell line. So what we did there, we cut the doses of our WEE1 and our ATR inhibitor by half. And we maintained the same level of efficacy. So this slide is really showing that there is potential for single agent activity, but also strong for combination therapy. The second program I'm going to share with you is our ATR inhibitor. And it's a very similar story. I mentioned that we added the BID on top of the QD.
And with these are still in dose escalation. So if you look at the BID, we're now in the 400 daily. The 550 daily was not tolerated. And our plan is to go up at 550, five on two off. So what's left to be done here is really fine-tune the dosing and scheduling. But again, we have to choose the right patient population. Why are we excited about the BID? Why we think it was the right decision is in this slide. So if you look at the slide on the left, you see that there are four responders. But really, we saw somewhat tumor shrinkage, minus 10% at the 1300.
But if you look at the BID, the purple on the right, at the 400 mg, one patient, two scans, stable tumor growth, but still stable disease. At the 550, three patients, minus 7%, minus 14%, minus 21%. So what's left to be, again, what's left to be done here is optimizing the dosing and scheduling. Is there good translation just like with the WEE1 from preclinical to the clinic? The answer seems to be yes. And what we are showing here is actually ARID1A. So ARID1A mutation has been shown to be sensitive to ATR inhibition, just like ATM.
This patient here has been diagnosed with the key mutation, ARID1A. He had five prior lines of treatment. You can see the first one, eight months, then four months, six months, one month, and one and a half months. Really not the strong responders. This patient was on our study at a very low dose. This is the 200 mg cohort, 200 mg QD cohort. It lasted. It was on the trial for about six months. We're excited about the programs. We are continuing to progress the programs. Good translation from preclinical to the clinic, still in dose escalation, still have room to increase the exposure.
One of the things, as I mentioned at the beginning, that we do is that we are making sure that our IP is strongly covered. We are covering composition of matter. You can see here, we're covering method of use, so we try to protect our assets as strong as possible for the ATR, for the WEE1, and for the undisclosed one as well. The company has last disclosed $16.5 million in cash. You can see the financial summary and the capitalization here on this slide.
We are traded under the ticker APRE, and we believe that this is a good entry opportunity with a potential upside for investors given the active programs that we have. As mentioned, in the near-term catalysts, so the end of this year and early next year, we're going to be very busy. Hopefully, things would continue to progress, and we're going to see a deeper response and get to the desired PR and RP2D and complete the dose escalation for both our programs.
We will disclose the undisclosed and work on the p53, the APR-246 as well. With that, I want to thank you, Sara, for the opportunity to present and for Wainwright inviting us.
Of course. Thank you, Oren and Aprea. Congrats on the progress. If anyone in the room has questions for Oren, feel free to come up and follow up with him. We'll be here for a few more minutes. Thank you.
Thank you.