My name is Cabral Happy, and I'm here with TD Cowen. I have the honor of introducing Riccardo Canevari, CEO of Radiopharm Theranostics, who's got years of experience in this space. Without further ado, I'll invite him over to lead the presentation. Thank you.
Thank you very much. Thanks for coming, and thanks, Cowen, for inviting us to be here. Radiopharm Theranostics is a company focused on radiopharmaceutical imaging and therapies. The company was created three and a half years ago in Australia, where it was incorporated. We started at the end of 2021 with listing on the ASX. In reality, the team is U.S. based. We are all on the, I would say, on the East Coast. Last year, in December, we completed the Nasdaq listing. Now we are dual-listed on the ASX and on the Nasdaq . The mandate of the company is really to expand the use of radiopharmaceuticals, particular therapies, in areas where other companies are not yet developing a radiopharmaceutical agent. These are my disclaimers.
In terms of overview, we really used the first three years of the company to complete the preclinical work on four assets that now are in clinical stage. We keep working on additional three molecules. We have seven in total, three molecules that are in late preclinical stage. Let me go to the traditional pipeline chart. Today, we'll focus on the top three assets just for the interest of time. We have some time at the end of the presentation. If there is any specific question on the others, I'm happy to take any of them. The first molecule is a single-domain monoclonal antibody or nanobody. It is targeting PD-L1, so a very well-known pathway in oncology. What we consider interesting is that we are, to our knowledge, the only company that has a PD-L1 radiopharmaceutical.
There is, of course, the checkpoint inhibitor. There is a PD-L1 ADC that is in phase one-two from Pfizer and Seagen in non-small cell lung cancer, but there are no radiopharmaceuticals. We are the first company that is bringing these to clinical stage. It is radiolabeled with Lutetium- 177, and the trial is ongoing in Australia. I will cover more about this molecule in a moment. The second therapeutic molecule that will enter clinical stage now, again, is a nanobody with Lutetium- 177, and it's targeting HER2. We received approval to start the trial in December, and we are screening patients now. Hopefully, we can have the first patient during the month of March. Again, similar, very well-known pathway in oncology, HER2, where there are targeted therapies, monoclonal antibody, ADC.
There are just a couple, two or three HER2 radiopharmaceuticals in development, and they are all at the beginning of their journey. Also, this trial is ongoing in Australia. One of the reasons we do trials in Australia is for the financial advantage of the R&D rebate. You have up to 43% of your investment back when you do trials there. Of course, it's a great way to have non-dilutive funds and to use for clinical development. These are the top two therapeutics. We also have two imaging agents that we carefully select. In our midterm, we would like to be a therapeutic company, but we think that these two imaging agents have really standalone value, and they are worth developing for potential future partnering. The first one is actually our most advanced technology. It's an F-18 pivalate. It's a small molecule that is radiolabeled with Fluorine-18.
It is able to cross the blood-brain barrier, get to the brain, and have a selective uptake for the brain metastases. This is a very large indication. Of course, it's about 300,000 new patients every year, only in the U.S. There is a specific medical need that I will go through in a moment. We completed phase one, phase 2A, and now we got IND approval for the phase 2B. We are screening patients now. Also, in this case, we expect to dose the first patient, hopefully, during the month of March. These are 30 subjects phase 2B trialed. I will focus on these three agents, but a quick overview on the other three molecules that we have. Actually, there are three molecules, four compounds.
You see in the green color that there is an imaging and the therapeutic of the same molecule, the typical theranostic pair. The Gallium-68 integrin alpha- v beta- 6 is in clinical stage. Alpha- v beta- 6, again, is a known pathway in oncology. There is an ADC that is in development now from, again, Seattle Genetics for patients with non-small cell and head and neck cancer . There are no alpha- v beta- 6 in advanced stage as radiopharmaceutical. We are recruiting these patients in the U.S., in New York City. It's a small trial of nine patients only. We think we can conclude the trial in the next couple of quarters. This trial is very important for us because it will inform on the therapeutic molecule, the one that you see at the bottom, the RAD-302. That's the same molecule.
That's why you have the same color code. This is with Lutetium- 177, and it's the therapeutic molecule where we believe there is going to be significantly higher value than the imaging, but it's the typical approach of imaging and therapeutic. Briefly, on the other two, we have two monoclonal antibodies. One of those called RV01 is targeting B7-H3. Again, same logic as we mentioned before. We like to go after biologically validated target, but with the radiopharmaceutical, where the approach has not been developed until today. There are ADC targeting B7-H3. There are a couple of ADC from MacroGenics. There is an ADC from Hansoh Pharma currently in phase three for small cell lung cancer. We are aware that Novartis, the radiopharmaceutical division, has a B7-H3 peptide. They got it from the acquisition of Mariana Oncology, and they are in preclinical stage.
This molecule is coming from MD Anderson. We licensed from them. We are well advanced with the preclinical work. We have already completed a pre-IND meeting with the FDA, and we are targeting IND mid of this year. Our B7-H3 molecule is likely to be in the clinics in the second half. Same timeline for the KLK3. This is a different mechanism of action from prostate cancer. Everybody in prostate cancer, at least in radiopharmaceutical, is using PSMA agent, of course, led by Novartis with the Pluvicto approval. There is Johnson & Johnson with a KLK2, and this is a KLK3. Slightly different, but pretty much similar concept in terms of mechanism of action. It's also a monoclonal antibody. Here, we decided to be a little bit more creative, if you like, in terms of isotope selection.
We are not using Lutetium- 177 like in the other therapeutic trial, but we are using Terbium- 161. This is an emerging isotope. There are more and more data in literature. I think two weeks ago, there was a presentation from Michael Hofman in Australia, a trial called VIOLET using a Terbium- 161 PSMA with very positive results. What is unique about Terbium- 161 compared to other isotopes is a dual emission. You have a beta emission that is similar to Lutetium, but in addition, you also have an Auger effect. Auger is similar to alpha, high energy, short distance. This isotope is likely to emit two types of radiation: one, less energy, longer distance, important for the larger tumor size. The other emission is alpha-like because it's Auger. It helps with smaller size micro-metastasis where you need high energy.
That is the overview of the pipeline, our seven molecules. I will go briefly on the top three. There is the team. I can skip. Maybe before, I can just share again what I mentioned before. From a company point of view, we are now listed on Nasdaq since December 2024. Our market cap is still small, very small. We are $60 million. We made very good progress in June last year. First of all, we have an important shareholder that is Lantheus. Lantheus decided to enter in our capital in June with 7%. In January, a month ago, they added another 5%. Lantheus has 12% of our company, and they are the largest shareholders. Of course, for us, it was an important validation of what we are doing when a pure player in radiopharmaceuticals decided to take a position.
We also have five U.S. institutions, biotech funds that invested in the company in June. Now we are about 65% institution between U.S. and Australia and 35% retail. That is our corporate structure at the moment. Let me go to the top three products, RAD-204. I mentioned this is a single-domain monoclonal antibody. They are small, like 15 kilodalton. They have a behavior similar to peptide, fast in, fast out, excreted by kidney. We radiolabel with Lutetium- 177. We consider this molecule very interesting because, again, it is the first radiopharmaceutical targeting PD-L1 expression. We believe that there is a potential dual effect. The first effect is by killing the cancer cells that express PD-L1 that are expressed on the surface with Lutetium- 177.
The second potential effect is the cascade down, the synergy between radiation and immune system with a potential effect, of course, still to be proven. The fact that immuno checkpoint inhibitors are now not the only way to go after PD-L1, because now there is an ADC in development that is showing positive data. They show 66% overall response rate. It's very promising results of going after PD-L1 with a different mechanism of action that is not only immuno checkpoint inhibitor. In radiopharmaceuticals, what is always a very important advantage is that you can see human data before you start a therapeutic trial. That's what you do with an imaging trial. We have treated already 30 patients with the imaging agent in the past. Data has been published. The value of this data is really to have visible biodistribution. You know where your molecule is going.
You know if you have tumor uptake, and also you know if there is a risk of target toxicity if the molecule is going where it's not supposed to be. The data has been published. We were very much reassured that the compound was able to target the PD-L1 expressing cancer cell. We had very limited activity on target tissue like bone marrow, or spleen, and this gave us the confidence to start the phase one therapeutic. The phase one therapeutic is not starting from scratch, only after animal model, but can rely already on the imaging data. We are looking at patients that are refractory to PD-L1 therapies, usually checkpoint inhibitor plus chemo or triplet approach. We have five indications. We are doing this as a basket trial. I think I have it probably. Yes, here.
We have non- small cell lung cancer, small cell, triple negative, melanoma, head and neck and endometrial. These six cancer types, the patient needs to be PD-L1 positive, more than 1%. What we do, we do not rely only on immunohistochemistry or previous biopsy. What we do in every single patient, we do a low-dose Lutetium. You can see here is 10 millicurie that has the ability of being, again, an imaging agent. We do human dosimetry in every single patient with a low-dose Lutetium. We know where the product goes, if there is tumor uptake. If there is, after two weeks, we start with the dose escalating trial. Higher dose with potential therapeutic effect. We are still at the beginning of the trial. We have done some patients. We are looking to progress to the next dose level.
Until now, we have seen reassuring early results. Of course, it's low dose, so that's what you expect. There was good feedback from the investigator in the centers. We are really excited to go ahead with this program and to see what the higher dose can bring, not only in terms of safety and right dose, that is what you expect from a phase one, but potentially early sign of efficacy. We got approval last year. We treated the first patient. We expanded to six tumor types because we started with non- small cell lung cancer only. We decided to expand. That is what the expectation for 2025 is. The trial is an open-label trial. We do not need to wait at the end of the trial to communicate externally some initial results.
The idea is to have some interim data release around June, July, just to create a sense that the trial is progressing, an early milestone informed the market, and potentially to complete the trial by the end of the year. That is the program for our first molecule. I will go fast for the next two. HER2, again, very well-known target, is almost a copy-paste approach. It is a single-domain monoclonal antibody. We have done an imaging trial before. We have seen what we want to see, and now we are doing a therapeutic dose escalating trial. What I consider very interesting for this molecule is the potential positioning. We know that trastuzumab ADC is a great drug. It works very well in HER2, HER2 low, HER2 ultra low.
Despite it's a great drug, and we have seen some analyst projection of $18 billion-$19 billion by 2028, still all the patients are not cured. There is going to be a total addressable market, very significant, around $8 billion-$9 billion post Enhertu. When the patient progresses on Enhertu or trastuzumab ADC, usually there is only chemo or clinical trials. We believe that post ADC, there might be a very nice space for a radiopharmaceutical. Instead of doing ADC after ADC, you can really sequence post Enhertu with a radiopharmaceutical therapy. We know that the expression of HER2 post trastuzumab ADC is still very high. There is no down regulation. There are plenty of HER2 receptors there. That's where we like to position our product. Again, we know a lot from imaging trials, and now we are doing the therapeutic dose escalation.
It's mainly breast and some gastroesophageal, as you can expect from HER2 expression. These are the data from the phase one imaging, again, confirming the tumor uptake. The molecule goes where it should go, to the target, to the tumor. There is very limited off-target uptake in other organs. This gives us the confidence to do the same approach, dose escalating trial, and to try to go as high as possible with this Lutetium- 177. We got approval in December. We think we can dose the first patient, hopefully this month. In terms of timelines, this trial started about six months after the previous that we saw before. The results consistently are six months later. We want to dose a patient now in the first half and to release some interim data by the end of the year.
We will continue probably by June 2026 with completion of the trial. I like to close with an imaging agent because we think that this is a very interesting business case. There is a very high unmet medical need for this imaging agent. We are talking about a patient with brain metastasis. Usually, MRI works very well to detect brain metastasis. There is no need for an imaging agent. What is the problem? The problem is that a significant amount of those patients, 30%-40%, need treatment. The treatment is SRS or Gamma Knife, stereotactic radiosurgery. After you receive this treatment, MRI does not work well again to show if what is left is tumor or necrosis because, of course, it is very potent energy and creates necrotic cells around the eating area. At that stage, oncologists are in a situation where they are almost blind.
They don't know if what is left is tumor or not, and they don't know if they can treat again with SRS. That's our value proposition that was proven already by the phase 2A data that we presented last year. We decided to take this technology that was from Imperial College London. We transferred to the U.S. We have a center of production now in Michigan, IND approval, and we are recruiting patients now in the phase 2B. That's the journey until now, 24 patients in phase 1, 17 in phase 2A, and we are working on a phase 2B of 30 patients. Again, I explained the trial design. The unmet medical need is really in this patient population. We are working to assess the total addressable market. We believe it's significant because there are 300,000 new patients every year with brain metastases.
Half of them will go with SRS. After SRS, there is a need for a better compound and not only MRI to capture if there is metabolic activity in the cells that are left in the brain. In terms of timeline, again, we think we can dose the first patient of the phase 2B any week now. We are screening them, and we like to report some interim data around mid-year, June, July, and close the trial by the end of the year. That is the overview of the three main programs. I think we still have eight minutes, seven minutes. I am happy to take any question either on those programs or on the rest of the pipeline, or happy to follow up individually with any of you if you would like to reach out.
Yes. If you don't mind, could you kind of describe what the data readout would be like for PD-L1? You mentioned that you'd have two cohorts that are 40 millicurie.
Yes.
Can you disclose what kind of follow-up? In general, would you include efficacy, or is it just biodistribution?
Yeah. The way we structure the trial, we need to have a single dose in each patient to follow the patient for six weeks. That is usually the time where you might have the peak of safety concern in a radiopharmaceutical. The patient is considered to be assessed by DSMC if we can go to the higher dose. After we do the three-patient single dose, in reality, we don't stop working with them. We keep dosing. Even if it's not necessary for the dose escalation, we give multiple doses.
Some patients are likely to receive three, four, or five doses of the compound. It is difficult to say if we will have early efficacy at the first two cohorts because, of course, we started low because it is the first time that there is a PD-L1 radiopharmaceutical. You want to be cautious with the patient. Of course, if there is an early sign of efficacy, it can be stable disease for a very long time or can be maybe a partial response. Of course, we will disclose it. The trial has been designed not only to deliver safety and the right dose for phase two, but potentially to show early sign of efficacy. That is what we think.
The other consideration that we have, based on what we are seeing on the first cohort, we like to discuss at the next DSMC if instead of 40, maybe we can go to 50 or 60 directly with the protocol amendment. If the team assesses that the first human data are showing reassuring safety, maybe we go up faster so that we can have maybe one cohort less or shorten the trial anyhow, doing it in a way that future sign of efficacy potentially might come earlier.
Thank you.
Okay. Thank you very much for being here and happy to follow up. Thank you.