What I want to state here is really that what got us here won't get us there. When we look at the history of Lutathera and Pluvicto, it's been mostly academic endeavors, a lot of compassionate use. And I think between John and Amanda and Matthias, they already made my point that the FDA is unlikely to going to approve a similar drug to Pluvicto, where you don't have dose optimization, where you don't understand the biology as we should for most treatments.
Matthias already showed the classic Gartner Hype Cycle. And I think we're in a similar situation here with the radiopharmaceuticals. When you look at evolution, we had 40 years plus of iodine treatment. Then we had a quick bloop with Bexxar and Zevalin who did not fail for lack of clinical efficacy. They failed for logistical reasons. They failed for financial reasons, but not primarily for lack of efficacy. We had Xofigo come into the game and that ignited some excitement. And then we had Lutathera and Pluvicto and a big hype. And when you look at the investment at the number of deals and the size of deals that we've seen over the last few years, it's really kind of big. But we also realize that the tide is changing.
People are worried about what's coming next after Pluvicto. Where are the new targets that really deliver similar efficacy? Where are the new tracers? Where are the new isotope supplies? And this is what we're facing today. So when you look at the bullseye and you take out all the somatostatin targeting, all the PSMA targeting, there's very little left. There are very few really innovative targets in this picture. And when you then also look at the older tracers that have been around, have been dealt with in clinical trials with academia, with companies, and I don't want to name any specifics here, but I think there are quite a few zombies out there, drugs that have been dragging along and in fairness will never make it to commercial stage.
So what do I expect? What do I wish for? And in a way, it's almost going back to Johannes. I wouldn't call it a bucket list. I would call it a wishlist. Where do we go from here? And what is going to be financed? What are the VCs looking for? What are the big companies looking for?
First, we need to understand the biology. There's still a big debate out there, and Amanda highlighted the AstraZeneca strategy of ligand format. I for myself can say, I'm a big fan of small molecules. When you look at Lutathera and Pluvicto, they have an alpha elimination half life of less than 10 minutes. Everything that tries to improve that by albumin binding or other half-life extensions has failed over the last 30 years.
We will see more bone marrow toxicity with longer circulation half-life, because there is non-specific toxicity from anything that circulates in the blood for extended periods of time. We have to better understand the difference and the synergy between alpha, beta and Auger emitters. There's very exciting data for the Augers, but I think it's not going to be universal. I think it only works for homogenously expressed targets when you can really get to the cell surface. And I don't think it's a DNA effect at all.
In general, I don't think that we should underestimate the non-DNA effects of radioligands. There's a lot of superoxide-related, specific targeting mechanisms that are non-DNA damage related. We talked about, Amanda spoke about, and the discussion was about the decay rate. Can we overwhelm the repair mechanisms of tumors versus healthy tissues with an astatine or a lead where we don't achieve that with a long half-life isotope? We need to understand that biology.
Dose and schedule. We're still driving by our rearview mirrors. We're waiting for the bone marrow to recover before we give the next dose after six weeks, and the FDA is encouraging and propagating that system. We have to get to more aggressive schedules if we want to move out from the slow progressing tumors like NET and prostate cancer. If you want to treat a third line colorectal cancer, you cannot treat every six weeks.
Protect the marrow and the kidney. There are drugs out there that protect the marrow by cell cycle arrest, and we should explore these options to see if we can specifically and differentially protect the sensitive organs, most prominently bone marrow, and then also the kidney with supportive therapy.
And lastly, combination and sequencing. There has been some great data with the combination with PARP, the LuPARP study. I think we need to understand the synergy with immune oncology. Are we helping or are we hurting? Is there benefit in going with lead where the radiation has gone when the immune system invades, or can we work with low dose? Maybe just the 2 megabecquerel of actinium is good enough to trigger immune response. Because as mentioned earlier today, we have not seen any cures from the radioligand therapies, or if so, very few. So eventually, the immune system has to take over and do the rest.
What's the best strategy here? We have to leverage the unique advantages. Find the optimum targets, not necessarily competing with the ADCs and the other methodologies. So high turnover targets where we get internalization and accumulation of the tracer. Extracellular matrix targets that are not necessarily good targets for ADCs and BiTEs. We should look at early translation and low dose biodistribution. Leverage the tactical benefits of the radioligands. Dosimetry based dose adoption, optimization, but then keep it simple in clinical practice. So I don't expect that from an operational perspective, radioligands will be competitive in the hands of the oncologist if every patient has to undergo dosimetry during routine clinical use.
So long-term, we need to move beyond the slowly progressive tumors. We have to establish long-term safety. As we move earlier in the disease, the secondary malignancies will gain importance. We have to prove that we're not trading that off, and we have to find the RLT sweet spot. And my personal prediction is it's going to be in what we don't see. It's going to be in the micrometastatic disease, it's going to be in early adjuvant, and more likely, it's going to be with the alphas than with the betas. But that requires large studies that requires high patient numbers and long-term follow-up, so it's not for the faint of heart. And hopefully, we're going to see fewer zombies, so clean up our portfolios to really be able to convince investors that the radioligands can move beyond PSMA and somatostatin analogs. Thank you very much.