Welcome to Virtual Investor Conferences. On behalf of the Life Sciences Investor Forum and our co-host, Zach Small Cap Research, we are very pleased you have joined us for our quarterly conference. Our next presentation is from Actinium Pharmaceuticals. Please note you may submit questions for the presenter in the box to the left of the slides. You can also view a company's availability for a one-on-one meeting by clicking "Book a Meeting" in the top toolbar. At this point, I'm very pleased to welcome Steve O'Loughlin, Chief Financial Officer of Actinium Pharmaceuticals, which trades on the New York Stock Exchange American under the symbol ATNM. Welcome, Steve.
Thank you, Greg. Pleased to be here, and thank you, everyone, for joining this morning. Before I begin, please note that the presentation may contain forward-looking statements. I would encourage everyone to review our SEC filings, which may be updated and amended from time to time. As an introduction to Actinium Pharmaceuticals, we are a biotechnology company focused on innovation in the field of targeted radiotherapy. Radiation is a validated modality and tool used in the treatment of cancer. It is used in approximately half of all patients who are diagnosed with cancer today. What we do is we link radiation to targeting agents and direct them at various cancer targets. Our clinical and preclinical pipeline is directed across a number of validated cancer targets, and we use a number of different radioisotope payloads, including beta emitters such as iodine-131 and then alpha emitters such as Actinium-225.
We direct these across a broad array of indications in blood cancers, solid tumors, and in targeted conditioning for cell and gene therapy, as well as looking at novel next-generation radiotherapies. Our pipeline is supported by a strong IP portfolio of over 230 patents, and we also have proprietary technology around the manufacturing of the Actinium-225 radioisotope via cyclotron that we are excited about. This is an overview of our pipeline focused on three key disease areas. Hematology or blood cancers, primarily focused on acute myeloid leukemia or AML; solid tumors, where we have two assets that we are advancing; and then targeted conditioning. Our lead clinical program, Actimab-A, is advancing towards a phase II-III trial. We also have several phase I trials that are active or will be advancing this year that I will highlight in more detail later in the presentation.
As we enter 2025 and we looked at our pipeline, we are very excited about the initiatives that we've undertaken and the opportunities that we believe these represent. With Actimab-A, in addition to our own efforts, we have also entered into a cooperative research and development agreement, also what's known as a CRADA, with the NCI , who is co-developing Actimab-A. We've also moved Actimab-A, which is primarily focused on blood cancers historically, into solid tumor indications, looking at combinations with PD-1 checkpoint inhibitors, namely KEYTRUDA and OPDIVO, which are some of the highest-selling oncology drugs today. With our Iomab- ACT program for targeted conditioning, we have initiated two trials, one in the commercial CAR-T setting with the University of Texas Southwestern and the other with Columbia University looking at sickle cell disease.
These are very large market opportunities for us and looking forward to building on very promising preclinical and clinical data to date and looking to generate additional proof of concept data from these two trials. On the R&D side, this year, we announced and unveiled our newest program and our solid tumor program, ATNM-400. This is a first-in-class prostate cancer therapeutic candidate. Prostate cancer is arguably the largest current commercial market for radiotherapy. There is a proof therapy called PLUVICTO that targets PSMA that achieved blockbuster status last year. With ATNM-400, we are focused on addressing potentially large patient population, and we have presented data with ATNM-400 preclinical data that shows that it is more potent than PLUVICTO and works in patients who stop responding to PLUVICTO.
Great excitement for ATNM-400, and we do have in-house R&D capabilities that we will continue to work on in advance to bring potentially more pipeline candidates forward. In addition to our R&D, we are also focused on establishing our in-house manufacturing capability to support future clinical trials and advancement there in the clinic. When we look across the pipeline and look at the disease indications that our pipeline is currently targeting, we have built this out from AML-focused programs now into sickle cell disease and CAR-T for blood cancers such as lymphoma and leukemias, and then advancing into prostate cancer. We have added significant market opportunities to our pipeline, exceeding several 100,000 patients.
With our Actimab-A initiative in combination with the PD-1 checkpoint inhibitors, we are looking at head and neck and non-small cell lung cancer, which is, again, several 100,000 patients, and then looking at other solid tumor opportunities where we think that the Actimab-A combination with PD-1 inhibitors can make an impact. Very excited about the four potential blockbuster opportunities that we have with a pipeline of radiotherapeutic candidates that are first in class. Focusing now on Actimab-A, our lead clinical program, Actimab-A targets a marker expressed on various blood cancer cells called CD33. We label a CD33-targeting antibody with the Actinium-225 radioisotope. Actinium is an alpha emitter. It has very high energy output. That is the mechanism that kills the cancer cells.
However, the energy emission only travels very short distances, only a few cell diameters, which can enable precise cancer cell killing with minimal off-target effect. We licensed Actimab-A from Memorial Sloan Kettering Cancer Center. It has, to date, been studied in approximately 150 patients across six clinical trials. Most recently, we've studied it in combination with a chemotherapy regimen called CLAG-M in patients with relapsed refractory AML, and we are taking that forward into the phase II-III trial that I mentioned earlier, and then also advancing opportunities that have arisen under the CRADA with the NCI. We have aligned with the FDA on a phase II-III study design for Actimab-A plus CLAG-M in the relapsed refractory AML space. Actimab-A represents the first targeted radiotherapy focused on patients with AML.
This builds on our clinical experience, and we will complete a phase II trial that will look at two doses of Actimab-A in combination with the CLAG-M regimen. Based on the results of that, it will determine the dose that is taken forward into the phase III trial, and then that will be compared to CLAG-M alone. Based on the results from our most recently completed Actimab-A plus CLAG-M study, we believe that this combination has high potential, leveraging potential synergy that may exist between chemotherapy and radiation, but now introducing that radiation in a targeted manner directly to these CD33-expressing leukemia cells. In the trial that was conducted that informed the phase II-III trial, we looked at patients with relapsed refractory AML. These were heavily pretreated patients. Many have seen multiple lines of therapy, median being two.
These patients had received prior bone marrow transplant, prior venetoclax therapy. Over half of the patients had a TP53 mutation. All of these are contributing factors that define a patient in this patient population as having high-risk disease, which is typically associated with poor outcomes. We are highly encouraged by the overall response rate that we saw in all patients, but also across the differing kind of patient groups. Patients who have prior venetoclax therapy typically have poor responses and survival outcomes. TP53 is notorious for poor outcomes. However, despite patients having these high-risk features, we saw consistent high overall response rate, over 50% in all groups.
One of the things that this trial looked to evaluate was whether or not the addition of Actimab-A to CLAG-M could produce deeper responses and remissions and put patients into MRD negativity or minimal residual disease negativity, meaning they had no detectable levels of cancer. We were very pleased with the results related to MRD negativity. The patients that did achieve a response, those responses were deep, with, in some patient groups, such as those who had prior venetoclax therapy, all of those patients achieving MRD negativity, and three-quarters of patients across the entire study who achieved a response achieved MRD negativity. The results of this study, including two-year follow-up, have now been published in a peer-reviewed journal. This looked at overall survival of the group going out to two years.
There were some very encouraging survival outcomes that we saw in patients who had previously received one or two lines of therapy. Median overall survival was 18 months. Those who were able to go to a bone marrow transplant, which is a potentially curative treatment option for patients with relapsed refractory AML, those patients had a 24-month median overall survival. Then patients with a TP53 mutation or prior venetoclax therapy, 9.6 and 7.3 months. If you look at the graph on the right, the green bar is the Actimab-A trial, and the red and the purple are other studies that were conducted looking at patients who had either prior venetoclax therapy or TP53 mutation. Typically, those patients have survival of two to four months.
With the figures that we saw from our trial, very encouraging and looking forward to advancing the phase II-III trial now, for which we've aligned with the FDA on. I mentioned our CRADA with the NCI , and earlier this year, we announced the initiation of the first trial under that CRADA. This trial will combine our drug Actimab-A with venetoclax, which is an oral therapy that is used prevalently in the treatment of patients with AML, and combine it with another oral therapy that's been developed by Taiho Oncology, which is a part of Otsuka Group. This is in the frontline AML setting.
These are patients who are newly diagnosed, first diagnosed with the disease, and with this trial being initiated, looking forward to progressing this in 2025 and hoping that by addressing these patients early on in their disease treatment, the addition of targeted radiotherapy can have an impact in their disease progression. When we look at the opportunities in AML across the treatment journey, looking first at relapse refractory, where we'll be with the phase II-III trial, looking at the frontline newly diagnosed patients, and then ultimately patients in the maintenance setting. We're also looking at MDS, or myelodysplastic syndrome, which is a related blood cancer. When we look across that universe, across the treatment journey, there is a potential market opportunity that exceeds 100,000 patients in the U.S. and the top five countries in the United States.
It's important to note that Actimab-A is mutation agnostic, given its Actinium-225 radioisotope payload. So, as we've demonstrated both in the clinic and preclinically, if patients have various mutations, gene mutations, what have you, that are typically seen in AML, Actimab-A has demonstrated cell-killing potency. And then the CD33 marker is expressed ubiquitously across patients with AML. So, we see an opportunity for a backbone therapy for Actimab-A. Very excited to be working with the NCI under the CRADA. We continue to evaluate other trial proposals that come through the NCI network. But then, as I mentioned, we're also starting to look at Actimab-A in the context of solid tumors, which one might not expect, given that CD33 is a blood cancer target.
What our team identified was that there are certain immune cells that also express CD33, particularly one set of immune cells called MDSCs, or myeloid-derived suppressor cells. They have been implicated in outcomes for patients who receive immunotherapy, like the PD-1 checkpoint inhibitors, KEYTRUDA and OPDIVO. Earlier this year, we announced a clinical program that will study Actimab-A in combination with the PD-1 checkpoint inhibitors in head and neck and non-small cell lung cancer. What our team identified was that these MDSCs get recruited into the tumor environment, and they create resistance against the immune response that the PD-1 inhibitors trigger. Our team conducted preclinical work. We also looked at the literature. There was a study published looking at patients with non-small cell lung cancer.
In the patients who had high amounts of MDSCs, they had no response to the PD-1 inhibitors, as depicted here in the graph on the right, or the bar on the right in the graph. They also looked at survival in these patients. I think this is very notable. In the patients who had high MDSCs, they had very poor outcomes compared to the patients who had low MDSCs. The premise for this program is to give patients with solid tumors Actimab-A. Actimab-A will then go in and target and kill the CD33-expressing MDSCs. The PD-1 inhibitors will be administered into the patient, and it will create a more suitable environment for the PD-1 inhibitors to trigger and kill the patient's tumor. We have developed a clinical program that can consist of multiple trials.
We will look at Actimab-A in combination with KEYTRUDA, and we will also look at Actimab-A in combination with OPDIVO, again, across head and neck and non-small cell lung cancer patients. Looking forward to advancing this trial and delivering what we believe will be the first proof-of-concept data, looking at a CD33-targeted radiotherapy for MDSC depletion in combination with PD-1 inhibitors. Then continuing on the solid tumor side, where we've continued to focus, I mentioned earlier we introduced ATNM-400 this year, a next-generation non-PSMA prostate cancer radiotherapy. Prostate cancer will be diagnosed in approximately 300,000 men in 2025. Approximately one in eight men will be diagnosed with this, 1.5 million patients globally. This is a very large disease indication that continues to have high unmet needs despite a significant number of approved therapies.
I mentioned a drug called PLUVICTO, which is developed and marketed and sold by Novartis. PLUVICTO is a radiotherapy that targets PSMA for patients with metastatic prostate cancer. In 2024, it generated sales of approximately $1.4 million. What our preclinical data showed that we presented at the American Association for Cancer Research earlier this year is that ATNM-400 does not, it's not targeted to PSMA. It's another target. It does selectively bind to prostate cancer cells, and it's able to produce a dose-dependent cytotoxicity. In prostate cancer animal models, we showed select uptake into prostate and minimal uptake into normal tissues. We were able to show selective tumor accumulation and clearance from healthy tissues that we think supports a potential safety and efficacy profile. We also presented some efficacy data that showed that ATNM-400 was more potent than PLUVICTO alone in prostate cancer models.
Our team then took tumors that were treated with PLUVICTO. They put those tumors into mouse models and allowed those tumors to grow. These are tumors that are resistant to PLUVICTO. The team then administered ATNM-400. You can see in the graph on the far right, in the line in red, the animals that received the ATNM-400 essentially arrested and halted their tumor growth, speaking to the potential for ATNM-400 to address the need for patients who either do not respond or stop responding to PLUVICTO therapy. Very excited to be building out our solid tumor platform and program and looking forward to delivering proof-of-concept data across these programs. We are also advancing our Iomab- ACT program. This is a CD45 targeting construct. CD45 is expressed on blood cancer cells and immune cells. Here we use the radioisotope iodine-131.
We are developing this in the context of cell and gene therapy. We can essentially use different doses of the radioisotope iodine-131. For CAR-T therapy, for instance, we are looking to deplete lymphocytes. For sickle cell disease, we are looking at reduced-intensity conditioning, so a little bit higher dose. We have studied Iomab-B in a phase III trial that successfully met the primary endpoint, where we used high doses of Iomab-B to destroy the patient's bone marrow, what is called myeloablation. We are now taking Iomab- ACT forward in CAR-T and gene therapy and transplant indications for sickle cell disease. We have presented preclinical data that demonstrates a multimodal mechanism of action for Iomab- ACT. We have done a pilot study with Memorial Sloan Kettering Cancer Center, where we looked at heavily pretreated patients with leukemias and lymphomas.
These patients were given Iomab- ACT conditioning and then administered a novel CD19 CAR-T therapy. We were pleased that there were virtually no cases of CRS or ICANS, which are CAR-T-associated toxicities that in this patient population can occur in about 25%-30% of patients. Despite these patients being heavily pretreated, two of these patients actually achieved a CR. With that data, we forged ahead with our two ongoing trials, which have now been initiated, commercial CAR-T trial at UT Southwestern. This will be the first time Iomab- ACT is studied with a commercial CAR-T. With Columbia in sickle cell disease, we're doing a two-prong study. The first part will look at Iomab- ACT prior to a bone marrow transplant or stem cell transplant for these patients with sickle cell disease.
After an initial safety cohort, if the data is supportive, we can then start looking at Iomab- ACT to condition for gene therapy, for which there are two approved gene therapies for patients with sickle cell disease. One of the things that excites us about this market is CAR-T has grown rapidly in the few years. Following the first approval in 2017, the market has now grown to over $4 billion in annual sales. Across the cell and gene therapy market, there is a forecast for significant growth as new products come to market and become developed, with an estimated potential market opportunity of nearly 100,000 patients by 2030. Looking forward to delivering this data on Iomab- ACT and forging ahead.
As I mentioned, we continue to work in R&D, leveraging our in-house capabilities and our team to look at both blood cancers as well as solid tumor applications. We have presented a significant amount of preclinical data over the last several years that we continue to work on. The other thing that we have developed over the years is know-how and experience working with targeted radiotherapies. We have executed a number of clinical trials at some of the leading comprehensive cancer centers in the United States. We know how to get these therapies to the point of care, working with a cross-functional team. We also have our proprietary Actinium-225 manufacturing technology that we're very excited about. Actinium-225 is a highly sought-after medical isotope. We believe that our proprietary method can produce higher amounts of highly pure Actinium-225 in a cost-effective and efficient manner.
This is something that we have announced that we are actively investing in and looking forward to providing updates there. As we look ahead over the next several months, we have a cash runway into mid-2027. We will be able to execute on a number of milestones across our pipeline. With Actimab-A generating clinical data, both from our own program and trials, as well as trials under our NCI CRADA, including in the solid tumor setting in combination with the PD-1 inhibitors, with Iomab- ACT, moving the two initiated trials forward at UT Southwestern in commercial CAR-T and with gene therapy at sickle cell disease at Columbia. With ATNM-400, advancing that, we expect to present additional clinical data this year supporting ATNM-400, as well as leveraging our in-house R&D capabilities.
Then underpinning our pipeline, moving ahead with our ability to produce radioisotopes ourselves via in-house manufacturing, and exploring partnerships with our Actinium-225 cyclotron technology. In conclusion, we have a balance sheet that will allow us to advance these programs, generate milestones across multiple assets in our pipeline in the targeted radiotherapy space, which continues to be of significant interest. We do have several late-stage pipeline assets and opportunities. We have announced publicly that we would be seeking potential partnerships, such as Actimab-A for the phase II-III trial, the Iomab-B program, and others. Thank you, everyone, for your time. You can always be contacted directly through the Actinium website if there are any follow-up questions. Thank you.