Presenting for MAIA is their founder and CEO, Vlad Vitoc. Vlad.
Thank you. Hello, everybody. So it's a pleasure to be here to present an update on MAIA Biotechnology and our telomere targeting immunotherapies for cancer. So at MAIA, we are developing new science for cancer treatment. We are developing agents with a dual mechanism of action: telomere targeting and immunogenicity. Our lead molecule is called THIO. It is in the clinic. It's getting ready for its pivotal trials to start this year. And our second generation of telomere targeting agents are currently in pre-IND stage. So the phase two trial, THIO-101, is the trial that we've been running so far as a dose-finding trial. And now we're expanding it to become a pivotal phase two for accelerated approval in the U.S. This will enroll patients in the course of 2025. We're sequencing THIO with a checkpoint inhibitor, Libtayo, made by Regeneron, and it's targeting non-small cell lung cancer patients.
In this trial, we have seen unprecedented efficacy, in particular in third line. We've seen disease control north of 80%. We've seen response rates very good. We've seen progression-free survival and overall survival that are amazing at this point. Safety profile also extraordinary, far better than any chemotherapy or other drugs that you see now currently as standard of care. We have a clinical supply agreement for this trial with Regeneron, who provided drug Libtayo, and it is tracking for potential accelerated approval in 2026. This is a very significant market opportunity we're talking about here for THIO in several hard-to-treat cancers with high unmet medical need. Certainly, non-small cell lung cancer, the largest tumor type of all, with more than $34 billion in sales last year.
But beyond non-small cell lung cancer, we have also for THIO three FDA orphan drug designations: in liver cancer, hepatocellular carcinoma, in lung cancer, small cell lung cancer, and in brain cancer for malignant gliomas. We also have one rare pediatric disease designation recently received about a month ago for pediatric diffuse high-grade gliomas. So we're developing THIO in these directions as well. And we have announced just a week ago a new clinical supply agreement partnering with BeiGene, under which we would be developing THIO in sequential combination with Tevimbra, tislelizumab for colorectal cancer, liver cancer, and small cell lung cancer. Other solid tumors are under consideration, including brain cancers, gastric cancers, and others. So here's a look at the pipeline as it sits today. So up top, you have the THIO-101 trial, which included non-small cell lung cancer patients in lines of therapy two plus.
This is the one for which we have a clinical supply agreement with Regeneron ongoing. Then THIO-102 is targeting colorectal, HCC, and small cell lung cancer. Most likely, this will become three distinct trials: phase two, designed for signal generation in the first phase, and then for accelerated approval. THIO-103 is a phase two slash three trial that we're planning to start probably in 2026, under which we go for first line of therapy. We'll start with lung cancer, both small cell and non-small cell, and then we go to the other tumor types as well. Now, the second generation of telomere targeting agents is a program that we started in-house about two years ago. In this program, we developed 84 new molecules. They all work with the same mechanism of action: telomere targeting and immunogenic effect.
And seven of them have proven to be at least an order of magnitude superior to the original in certain tumor types. We started the first two. They are now almost completed. They have almost completed their IND enabling studies. We're targeting first patient in phase 1 by the end of this year. And the third one is ready to go. We have four more in reserve. We're developing a franchise of telomere targeting agents. So our mission has always been the same: to treat cancer patients. And our vision is one day we will be curing cancer as well. So THIO is the only direct telomere targeting anti-cancer agent in clinical development. It has a novel dual mechanism of action. First, telomere targeting. Second, immunogenic effect. So here to the left of the slide, you have in blue the representative chromosome that contains our DNA, our genetic information.
And at the end of the chromosome arms, represented in orange, are the telomeres. The telomeres are also made of DNA, and they have a very specific function to protect the integrity of the chromosome in the course of the cell division cycle. They are built and maintained by the enzyme telomerase, which is present in all normal cells in the first year of life. At about age one, telomerase goes away. And at that point, the telomeres have reached their maximum length. And from then on, with each cell division cycle, they lose a little until in the old age, they become critically short. They can no longer protect the chromosome, and mutations begin to appear. And with this, the diseases of the old age, including cancer. But in cancer cells, something extraordinary happens. The enzyme telomerase is reactivated.
And so the cancer cells regain their ability to elongate their telomeres and so reach a state of replicative immortality, meaning they continue to divide and the tumor grows in the otherwise aging body. And this is where THIO comes in. THIO is picked up by telomerase, is placed in the structure of the telomeres, creates an unstable structure. The telomeres collapse, the DNA unwinds, and the cancer cell dies. This process is fast and efficient. It happens in 24 to 72 hours. And THIO directly kills 70%-90% of the cancer cells. Then follows the immunogenic effect. So of the telomeric fragments, THIO builds micronuclei that present these fragments to the immune cells, becoming neoadjuvants in the immune pathways.
They trigger an immune response so efficient that if you follow THIO with an immune therapy such as a checkpoint inhibitor, you get complete response, no recurrence, and anti-tumor immune memory. Cure. We have seen this type of effect in many preclinical models in lung cancer, in colorectal, in liver, in brain, in combination with different checkpoint inhibitors, with Libtayo, with Keytruda, with Tecentriq, and the first go-to-market is with Libtayo of Regeneron for non-small cell lung cancer, and then with Tevimbra also of BeiGene for other tumor types, so this is the test that set up all this. It was a preclinical study conducted in 2019 in lung cancer, and it looked at THIO in sequential combination with Tecentriq, Atezolizumab made by Roche Genentech. Two cycles of therapy were administered here and shaded in light blue.
THIO three consecutive days: Monday, Tuesday, Wednesday, then a day of break, Thursday, for the immunogenic effect to take place, and then Tecentriq on day five. Two cycles, no further therapy after that, so this is what we saw then. In gray, you have the control arm. The tumors grow very fast. It's lung cancer, very aggressive, and in orange, you have Tecentriq, Atezolizumab monotherapy grows just as fast, confirming this is an immunologically cold tumor, doesn't respond to immunotherapy alone. Then THIO as monotherapy, blocking the tumor growth for some time. But if you don't continue to administer THIO, the tumor finds a way, but the combination in dark blue, the sequential combination of THIO and the checkpoint inhibitor with an extraordinary result, 60% complete response. This is, to put things in perspective, in the clinic, Tecentriq or Keytruda or Libtayo have 2%-5% complete response.
This was 60%, so we followed the 60% complete response subjects, and for 70 days, there was no recurrence. 70 days in mice are like seven years in humans. The curative threshold is five. At this point, they were cured, but we went above and beyond and re-challenged with five times more cancer cells with no additional treatment, and there was no cancer taken. Immune memory is now in place because of THIO, so essentially, THIO trained the immune system to respond to cancer without any additional treatment, so with this, we started in non-small cell lung cancer, so our trial, in part, was a dose-finding trial. We tested three different doses of THIO in patients in non-small cell lung cancer that are resistant to checkpoint inhibitors and to chemotherapy.
So we tested three different doses of THIO, 60 milligrams per cycle is the human equivalent of the curative dose in mouse. But we also tested the higher doses just to make sure we don't leave on the table any possible additional efficacy. Safety was great across the doses. Disease control exceptional, over 80%. The dose selection was made on the basis of response rates, which were highest in the 180 milligram dose, the middle dose. Not surprising. In immuno-oncology, this is what happens. You have to take a Goldilocks approach to get to the best dose possible. So this became evident in October about a year ago. And the dose was selected. We then continued enrolling in this dose. Enrollment was completed in February in this part of the trial. And now we are ready to begin the expansion for registration.
And this will focus on third-line therapy, where we have seen the greatest difference between what THIO does and what alternative chemo barely can do. We plan to enroll another 100 to 120, 140 patients at the most. And this is a trial that goes for overall response rates, targeting possible accelerated approval in the United States by the end of 2026. So here's a look at the survival of patients by line of therapy. This is a data cut from September last year. Since then, these patients have traveled very well. So when we'll show this again, it will be far more to the right. Many patients have exceeded a year of therapy here. And especially in third line, as you can see in third line patients, 20 patients here in third line across all doses. The median follow-up survival here was 11.5 months.
The efficacy seen was 85% disease control rates versus 25%-35% with chemotherapy. And in third line, we even saw 88% controls. This group is smaller versus about 30% with chemotherapy, but also response rates of 38% versus 6%-10% what you see with chemotherapy. So this is where the expected efficacy from this trial. We're looking at overall response rates of around 38% for this, progression-free survival of 5.5 months, and overall survival not reached yet, but is tracking well north of 12 months. It's tracking actually at this point even north of 15-16 months. We expect to report a median overall survival at some point in the next month. It took longer than anticipated because the patients are surviving longer. So we're planning our upcoming trials as we speak. This trial, THIO-102, was initially thought as a basket trial with umbrella arms.
We now have a new direction, which means we're going to break it into separate trials. We're going to have phase two trials in colorectal, HCC, and small cell lung cancer. We're going to be testing THIO in sequential combination with Tevimbra in these indications. In colorectal, we have seen our best results. In the beginning, you see here the combination therapy of THIO plus Atezo in preclinical setting with 100% complete response, no recurrence. Even when we re-challenged with 10 times more colorectal cancer cells with no additional treatment, there was no cancer take. Immune memory was in place because of THIO. In small cell lung cancer, very strong results with Pembro in hepatocellular carcinoma with Atezo. These were the two data sets that resulted in the first two orphan drug designations for THIO. The FDA reviewed this. More recently, we had even better results.
This is another HCC model, so we saw THIO as monotherapy with 100% complete response. When we added Libtayo, look at the upper graph in the blue line, THIO plus Libtayo, there was just flat. Even 90 days after treatment. That's like nine years in human time, and when we re-challenged, there was no take, and this time we followed 210 days. That's like 21 years. THIO-103 is a phase 2/3 trial planned for first line of therapy. This will likely start in 2026 when we are closer to commercial, so the investment opportunity here is extraordinary at the moment. From an IP standpoint, we are looking at a new chemical entity marketing exclusivity, which is based off a very large and robust growing patent portfolio. We have more than 30 patents. I believe we're pushing on 40 right now.
The most recently approved is covering THIO as an immunogenic treatment strategy, sequential combination with checkpoint inhibitors. This goes until 2041. Our management team is very experienced. I'm a physician by my first training, businessman by my second training, and have had the privilege and opportunity to work in biotech and oncology roles, commercial and medical, about 50/50 for several different companies and working on the launching of some extraordinary drugs, such as Nexavar, for instance, at Bayer. Nexavar was the first tyrosine kinase inhibitor indicated for renal cell carcinoma and for hepatocellular carcinoma, where we are also going with THIO here. It peaked at $1 billion plus per year. Astellas on Tarceva, Tarceva for first line non-small cell lung cancer, where we are also going with THIO, $3 billion a year. Xtandi for prostate cancer north of five.
Not one of these compounds came to phase 2 or phase 3 pivotal with this type of results we are seeing here with THIO, both in efficacy and in safety. This is the best I've worked on so far. The marketing opportunity here is significant. We're talking billions of dollars across all of the tumor types. The checkpoint inhibitors are the market, $46 billion in 2023 sales, about the same. We're expecting more than $50 billion for 2024 with Keytruda in the lead. THIO can partner with any one of them. We have started our testing in preclinical setting with Keytruda and then Libtayo and then Tecentriq as well. Now in the clinic, we are going beyond that. People ask us, what are some of the comparable companies? There are many ways to look at comparable companies. This is one of them.
We're looking at companies that are in oncology, in lung cancer in particular, and what was their evaluation when they were close to commercial or at commercialization. And you can see they range between $1 billion and $4 billion. Mirati, for instance, had a KRAS inhibitor for non-small cell lung cancer. It was indicated for second line of therapy at the time of acquisition by BMS. So the growth here is absolutely spectacular. So what are we expecting to come? First patient in Part C will be in the first half of 2025. Then we'll report full efficacy in part B about mid-year. Part C efficacy update also will come in the second half. And we expect complete enrollment towards the end of 2025 in the expansion phase. And then filing for U.S. approval with a potential accelerated approval in the U.S. in 2026.
In the THIO-102 program, colorectal, small cell lung cancer, and hepatocellular carcinoma, we expect first patient in to be towards the end of 2025 or beginning of 2026, and then take us to efficacy reporting by end of 2026. THIO-103, we're planning at the moment to start in 2026 once we're closer to market commercialization with THIO-101, so with this, I would like to thank you for your attention and to take any questions.
A question on some of the endpoints.
Question on some of the endpoints and some of the milestones going forward. Could you just reiterate when the THIO-101 data is expected to be released?
From the pivotal part?
Yes. From the pivotal part in 2026.
Okay. Thank you.
Yes. We continue to release data from Part B, and from Part B, we'll probably have median survival at some point in the Q2. Patients are doing much better than expected.