We're joined by the Chief Medical Officer, Dr. Dimitris Voliotis. Radiopharm is developing a world-class platform of innovative radiopharmaceutical products for diagnostic and therapeutic applications in areas of high unmet medical need, and they have a pipeline of six highly differentiated technologies. Once again, just a reminder on questions: if you have one that you'd like to submit during the session, please type it in using the function within Zoom, and we'll get to those at the end. For the slides and the presentation, I'll hand it over to Dr. Voliotis now.
Thank you, Matt. Welcome, everybody. I'm Dimitris Voliotis. I'm the Chief Medical Officer of Radiopharm Theranostics, and I would like to present some of our exciting assets and the pipeline overview. We are a clinical stage company. We have four ongoing trials, two therapeutics, two imaging. We have three very promising therapeutic molecules in late-stage preclinical development. I will go through these projects in more detail. In terms of the financials, I can only say that they're very solid at this point. We have a good number of institutional shareholders. Our partner, Lantheus, owns currently 12%, and our cash runway is mid-2026. This is the pipeline that I was alluding to. The two therapeutic compounds are up top. The first one we call RAD-204, the second RAD-202. The first is a so-called nanobody against PD-L1.
PD-L1 is a checkpoint inhibitor that you are probably familiar with for the antibodies that have been approved and are very successful worldwide in treating various solid tumors. HER2 is a target that is very important not only for breast and gastric cancer, but for a number of other malignancies. We will discuss that a little bit more in detail. These two studies are in phase I, first in human, in Australia. We run both these studies in Australia in a number of different sites. We have two diagnostic studies, both of which are currently run in the U.S. RAD-101 is a study that we use to detect early brain cancer metastases. RAD-301 is an agent that we target for diagnostic assessment of pancreatic cancer and other solid tumors. We have our three preclinical assets. One is called RV01, the next one RAD-402, and then RAD-302.
RV01, or BetaBody, is a novel checkpoint inhibitor, B7-H3. This is a trial that will start this year in the U.S.
RAD-402 is a new asset that we also hope to open the study for in this year. It is directed against an antigen called KLK3 in prostate cancer after approved radiotherapies. RAD-302 is the therapeutic sister compound of RAD-301 against the same target integrin in a number of solid tumors. We will go through these projects in a little more detail. We are currently working with two isotopes. Actually, we are currently working with one therapeutic isotope, lutetium-177. For one of the projects, specifically for the KLK3, we are planning to use terbium, which is a very interesting new—it is not new as an isotope, but it is newly now used in therapeutic applications. It has a number of benefits that make it a very attractive warhead for targeted radiotherapy.
We have a secured supply chain for lutetium as well as for terbium. We are very confident that that is not going to be a problem. There have been in the past some issues with agents like actinium, but we are not using that. We are very confident about the supply for the isotopes. This is the team. Riccardo on the left, he is our CEO. Myself, the CMO, we are both based in the U.S. The rest of the team you see on the right, we are, for the most part, also based in the U.S. We have one person, our preclinical head, in the U.K., and we have a new person that just started in Australia as well to support clinical operations there. We have our board, as you can see here. Our founder is Paul Hopper, who lives in Sydney and is from Sydney.
Very happy to have him as, obviously, our Executive Chairman. Ian Turner is also from Australia, originally from the Sydney area. He's currently based in Miami. Hester is in the U.K., in London. Phillip is our CFO, also based in Sydney. Then Dr. Allan O'Donelly, also based in the U.S. We are listed on the Australian Stock Exchange. RAD is our symbol there. Since December of last year, we have a secondary listing also on the NASDAQ in the United States under RADX. You can see what our current market cap and shares are. We have a number of investor syndicates in the U.S. We have Australian institutions. Our board and management holds approximately 9%. Lantheus, our partner, as earlier mentioned, holds currently 12%. Let's go into the pipeline. Let's start with the PD-L1 targeting nanobody.
When I say nanobody, what I mean is a small-format, so-called single-domain monoclonal antibody. It is much smaller, by a factor of 10, smaller than conventional antibodies. Conventional antibodies are about 150 kilodaltons. This is 15. It is targeting PD-L1, and we're using, as I said earlier, lutetium as the radioactive isotope warhead. The benefits of a small format, in this case of the nanobody, is the specificity of the full-size antibody. However, it binds to different epitopes. It is conceivable that this can be active even in patients who have progressed after PD-L1 or PD-1 targeting monoclonal antibodies. Because of the small format, it has an improved tumor presentation and accumulation, and it also will have a more rapid blood clearance than full monoclonal antibodies. In terms of the therapeutics applications, this is a first-in-class PD-L1 radiotherapy, very strong potential in monotherapy or in combination.
We are the first ones to have a targeted radiotherapy against PD-L1, but there is one antibody drug conjugate in development. We have imaging data demonstrating proof of concept that have been published a few years ago. The results are shown here. On the left-hand side, you can see the excretion pattern. This is one patient. This is a second patient, A and B. What you can see here, basically, is, over the period of time, a very fast renal excretion, which is exactly what we would expect because of the small format. For a monoclonal antibody, we would have expected an accumulation and excretion in the liver. Here, it is through the kidneys, exactly as expected. The time activity curves here show also here the kidney, rapid increase, and then very quickly it goes down and is eliminated through there. On the right-hand side, you see the imaging.
This is with a different isotope, with lutetium. What you can appreciate here very nicely is the inhomogeneous expression. Everything that's green or red and yellow is PD-L1 positive tumor. One of the things that we have, one of the issues that we have many times, is that the histochemistry does not show exactly the results. There is inhomogeneous expression. With the imaging, we get the full picture. We already know from this study here that the antibody or the nanobody delivers its antigen, delivers the target, in this case, the lutetium, to the tumor. When it does that, we already know that it will deliver also the lutetium, and it should be effective there. The study is ongoing. It is a classical phase I dose escalation. We are using a bone design, as we call it. The study has an imaging component here.
Patients receive an imaging with a low dose, and then they go on to the treatment dose. We start with a low 30 millicurie, and then dose escalate further to 40 and higher. This is a typical phase one dose escalation schedule. 202 now, that's the HER2 targeting compound. It's very similar. It's a nanobody again. The only difference, of course, is that we target different tumors. We target cancer cells that express the HER2 antigen. It is a very attractive target for patients, treating physicians, also from a commercial perspective. Because, for example, in breast cancer, there are a number of treatments that are approved worldwide. One of the most recent approvals is a drug called Enhertu. It's an antibody drug conjugate. It has very much increased the number of patients that can be treated because we can also now include patients with a low expression of HER2.
All these patients, unfortunately, though, will relapse, and then they will require some additional treatment option. That's what we can potentially or hopefully provide with our drug. There are a number of patients that will have received HER2-directed antibody therapies, but then will be available to be studied in our study. Again, it's a format with a very high affinity, but it targets different epitopes than the currently approved ones. This is, again, an imaging study. I would like to concentrate you on these images here. This is a brain cancer patient. You can see here these yellow spots are brain metastases. I believe you can appreciate how well we can picture these with our compound. Here on the left-hand side, you can see a patient with different tumors in various parts of their body. What is shown here is the upper part, the thoracic.
You can see here that there is a so-called hot lesion. There is tumor here. This is a standard of care imaging that suggests that there might be also a tumor here, which does not light up. You can see that our antibody is very well in targeting exactly those areas of the body where we could find the tumor cells. This is just a very quick overview showing you, essentially, that in all these tumors, we have various degrees of expression of HER2. When we discuss this asset, this is not just breast cancer, for which the majority of the compounds are approved, or gastric cancer, but all these other tumors: lung, pancreas, colorectal, even prostate, gynecological malignancies, biliary cancer, and so on and so forth.
All these tumors have varying degrees of expression of the HER2 and could be potentially candidates for such a treatment. This is a very similar design. It's a phase one dose escalation with an imaging part here. Patients who are positive then go on to the treatment phase shown here. It is patients who are positive for the antigen as per immunohistochemistry. We confirm the positivity in this imaging part of the study. Both studies have started. We have enrolled patients in 204. We are currently waiting for the first patient in 202, but we are very happy so far with the sites and with the enrollment that we have seen and making good progress on both studies. As I said, both studies are enrolling in Australia. This is the first imaging study. It is for patients, as I said, with suspected brain metastases.
It has a very, very specific, let's say, value proposition, right? Patients with various tumors, such as breast, lung, or colorectal cancer, unfortunately, develop brain metastases. The incidence of brain metastasis is actually increasing a little bit. This is really a very important problem for patients. Many of those patients are candidates for what is called stereotactic radiosurgery or Gamma Knife, but unfortunately, they relapse after that. This is where we can target; this is the target population of patients that we can hopefully include in our study and then provide a solution for their imaging. We are using this small compound called pivalate. It is targeting what we call fatty acid synthase, which is basically a target. It is a substance or an enzyme that tumor cells in the brain are using for their metabolism.
We can target it, disrupt it, and visualize it in imaging. It's not a small indication at all. There's about 300,000 new patients in the U.S. every year, only in the U.S. This is, of course, then including Australia and other parts of the world, much more. There is a very high unmet need. The patients who receive Gamma Knife, unfortunately, will relapse. It is important to be able to diagnose metastases earlier so that the patient can receive another treatment. We also have proof of concept data here. This is from a study that was published from our partner, Imperial College London, that we are working or have been working with in the past.
They were able to show that independent of whether the brain metastasis is from a breast cancer patient or lung cancer or melanoma or colorectal, we can visualize their metastases very, very well. You see here in these upper two graphs, depending on the color, these are all patients with metastases from different tumors. You can see here that they're all at the same level. We are able to detect, independent of the tumor of primary origin, where the metastases are from, we can detect those metastases. Also, it's very important, and this was also shown here in the lower left graph, that independent of whether the patient had pretreatment, had stereotactic radiosurgery or not, in both cases, we can detect those metastases. Remember, what we are trying to do here is really to say, okay, this patient had Gamma Knife.
Does this patient have a metastasis, or is it a necrosis or a pseudoprogression? The standard of care imaging, MRI, is not very good for that. We hope we can improve that very much. We have, as already mentioned, including the study that have been shown, phase one and phase two data. We are currently in phase two in the U.S. It's a relatively small study. We are trying to confirm the results and compare them with standard of care imaging, which is the MRI in patients with the tumors shown here: lung, breast, colon, kidney, and melanoma. Basically, we are trying to show that the imaging with our compound is better than the standard of care in detecting an early relapse.
Once we have the results from this study, we can directly go into a registrational study, a phase three study, to make this drug available to patients. Currently, we are the only company that has such a drug in clinical development or in the clinical study. We would be first to market with this. The other imaging agent, very quickly, RAD-301, it's targeting an antigen called alpha v beta 6, which is heavily expressed in many various tumors. This is another small molecule, also sometimes called cancer integrin. We are trying to target patients with pancreatic cancer here or other malignancies and make sure that we can see if we can improve the validity and the precision of imaging to make sure that we have adequate staging for those patients. The target itself is very interesting, also from a therapeutic perspective.
There's at least one antibody drug conjugate currently in phase three against this same target. Also here, imaging data already available. Very quickly, on the right-hand side, this is the normal scan, a so-called FDG PET, which shows some tumor lesions, but you can see them very well. In contrast to that, on the left side is our agent. I believe you can see very well those dark spots here, here, here, and here. The image quality is much, much better. We're much better able to determine the sites of the disease for this particular patient. These are the compounds that we have in clinical development. Now, very quickly, to the three preclinical compounds. First one is from a collaboration that we have with MD Anderson Cancer Center in the U.S. We call it RV01 or BetaBody.
This collaboration is in the form of a joint venture of which RAD owns 75%. This is our compound. This is the furthest advanced compound from this collaboration. We have also additional data on preclinical compounds for at least three more molecules. This is the most advanced one. It is a modified monoclonal antibody. The target is B7-H3, which is a new checkpoint inhibitor. It has very strong potential to be of use in the tumors shown here. It shows a very strong affinity for the antigen. It is modified in a way that we can have a faster excretion, reduced bone marrow affinity, and shorter half-life, all of which are positive components. You can see here that the B7-H3 antigen is very strongly expressed in a number of tumor cells: prostate, breast, colon, lung, or gastric. It is not expressed. This is the negative control.
It is not expressed in the normal tissues of those organs. It is very important. It is very interesting as a target. We have a number of really great preclinical data. That is my favorite one. Very quickly, on the left side, these are mouse experiments. These are mice who were implanted with a tumor. They receive the treatment. Those that survive, approximately half of these mice survive and are cured. A few days after that, they receive again tumor cells. You would expect that they would develop the tumor again because they did not receive another treatment. That is not what happened. All those mice that were treated with the antibody essentially remain healthy and alive. What you see here, and they do not receive—I am repeating that—they do not receive another antibody. Essentially, they are vaccinated against the tumor. Very exciting.
We will start this study this year. We had a very successful meeting with the U.S. Food and Drug Administration last year. We're going to be on track to start the study this year. The prostate cancer agent, KLK3, we're using a new isotope here, terbium, which is very interesting because it has the additional effect of so-called Auger and conversion electrons. The antigen is very interesting. In the upper row, you can see here that it is only expressed in prostate. Other antigens shown here, including PSMA, are also expressed in other tissues and tumors. This is very, very specific for the prostate. It's a very promising target that we can use after, for example, Pluvicto, which is approved.
This is to show that we're using, after an agent like Pluvicto, which is using another isotope, we're using a different terbium, we're using a different target, and we're using a different format, such as in this case, an antibody. All this means that we have a great chance for this to be effective even in those patients who have a relapse after Pluvicto. This is in preclinical development. We're making great progress, and we'll be able to open this study in the second half of this year, first half of 2026. That study will also be conducted in Australia. Very last, two slides. This is the sister compound of 301, the one that I talked about earlier with pancreas and other tumor imaging. This is the therapeutic compound. We're making also great progress here.
Just as a reminder, there's a very, very strong expression in various tumors. We are currently producing the peptide. We hope that we'll be able to have an ethics committee submission for a small study here in Australia again by the end of this year. That's the end of my presentation. Thank you for your attention. I'm happy to take any questions.
Thanks very much, Dimitris. Once again, if you have a question from the audience, please feel free to type it in on Zoom. We've got about five minutes, so we'll get through as many as we can here. Dimitris, can you speak about the isotopes you require for these technologies and how you manage to secure access to these? Is that difficult to achieve?
No, it's not difficult for us. Let's put it that way.
I showed you earlier that we have partners that we work with. Let me just go there if I can really quickly. Sorry about that. At the very beginning, we have a very close collaboration with a number of suppliers for our antigens. Sorry, for our isotopes, of course. We work with ANSTO, Isotopia, and SHINE for the lutetium-177. We have a collaboration with TerThera for terbium-161. Quite frankly, no, we don't anticipate any issues here. It's going very well. We had no issues whatsoever in the study. This is going to be—we're going to be successful with this in phase one and through the phase two, and hopefully, when we get to that point, also for the phase three. It's also important to realize that there were some initial issues, less with lutetium, but, as I said, with some other isotopes.
That's all being worked on. Obviously, there has been great progress from a clinical perspective. There are many different vendors that are stepping onto the scene now providing isotopes for companies like us and others, of course.
Very good. The next question is, what's the timeframe for the Phase 2 B readout for RAD-101 being your most advanced asset through the pipeline?
Yeah, let's go there really quickly. We think that we will be able to complete the study this year. We will be able to provide interim data from the first approximately 10 patients by mid-year that will demonstrate the value of the compound and the validity of the imaging. We will be able to finish the study by the end of 2025 in such a way that we can then start the Phase 3 next year.
Thank you.
I was going to ask a question about the sector overall, but someone in the audience has submitted a similar one, which is, of all the radiopharmaceutical companies that have been acquired by Big Pharma, which company do you think Radiopharm Theranostics is similar to?
I think we're very unique, to tell you the truth, in the sense that we have a very broad portfolio. If you look at the first wave of radiopharmaceuticals and then also the first waves of buyouts from Big Pharma, clearly, they concentrate on PSMA in prostate and SSTR2 in endocrine tumors. We have, specifically with our pipeline, avoided this very crowded field. We have a very unique and very rich pipeline of very different targets, a very diverse set of targets that you can see again here. Not many companies—I think we're really one of the most diverse.
Also, not just because we have different targets, it's also because we are using different formats, right? So many companies focus on antibodies. Other companies focus on peptides. The jury is still out on which format is better. We are really trying to be very specific and use any formats to our advantage, combine that very well with an isotope that should work well. For example, in prostate in 402, as I've shown here, we deliberately made the decision to use an antibody and terbium as opposed to yet another—and a different target, of course—as opposed to yet another peptide with lutetium against PSMA. I think we're very unique. People are really liking our pipeline, and they're paying attention. We have multiple shots on goal. I think it makes it very exciting for us and for investors.
Very good.
We have got time for one more, which is, what do you see as the main regulatory hurdles for radiopharmaceuticals and your pipeline in particular?
I do not think that the FDA or other agencies necessarily treat them differently than antibody drug conjugates, for example. I mean, at the end of the day, these are also antibody drug conjugates with just a different warhead, right? Conventional ADCs use chemotherapy. We use a radioisotope. There are certain regulations, of course, for the use and safe use and disposal, for example, for isotopes. That is pretty much the only regulatory hurdle, if you will. There is a huge experience with lutetium and, to some extent, also with terbium. Both are isotopes that are easy to handle, essentially. We do not see really any hurdles there from a regulatory perspective.
Excellent. Thank you very much for your presentation today, Dimitris.
Thanks to everyone in the audience for joining. We've got a bit of a break before our next session today. That will be at 11:00 A.M. Eastern Time in Australia. That will be from Syntara. Hope you can join us again then. Thanks again, Dimitris.
Thank you so much. Thanks for your attention. Bye now.