Good morning, everyone. Thank you for joining. I'm Elena Shamsi, and I'm pleased to be hosting Carlos Buesa, CEO of Oryzon Genomics, today. He'll be giving us a presentation before we dive into some Q&A. Over to you, Carlos.
Thank you, Elena. Good morning to everybody, and thank you for being here. I'm going to be explaining to you today about our oncology program. As you will see on our webpage, we have actually another very interesting program in CNS. I think we have a very strong value proposition. Before I start with the catalyst and the programs that we have right now ongoing, I would like to emphasize that we are, of course, a publicly listed company in Europe, and we have a bit of an oddity because we are a company with a strong liquidity. Just as an example, last year we traded more than $1 billion over the whole year.
The company is developing assets, small molecules in epigenetics, in mid, late stage of clinical development in oncology, which is the main presentation today, particularly in AML, but also in some other hematological indications. We have a second program, which is also very promising, I'm not going to talk today about that, in CNS, where we are expecting to have a phase III starting next year in borderline personality disorder, and we have currently an ongoing phase II in schizophrenia. The company expects to be able to deliver on the next quarters a number of catalyst milestone clinical news that we hope will serve as a guide for the investors to see how the programs are proceeding. For those of you who are unfamiliar with the company, this is how the company performed last year in the Madrid Stock Exchange.
The company oscillates between EUR 250 million-EUR 280 million market cap, around $300 million market cap. Just to mention very briefly that we did our financing last year. That was very nicely oversubscribed with a very strong aftermarket. That we secured with different sources last year, $60 million. With these inflows, the company has currently a runway that should go to the second quarter of next year. Let's go to the real fun, to the science. We are working, one of our stellar programs is with iadademstat in oncology, particularly in AML. AML is still a fatal disease. Only the patient that we are able to derive to human stem cell transplantation get a real option to have a definitive cure.
For the rest of them, what we have is different therapeutic approaches to delay the disease, to increase the quality of life of patients. We have an increasing collections of targeted therapies, which are guiding basically the growth of the market, and we have a special asset, iadademstat, iada as a nickname, which we think is a premium asset, and we think, as you will see on the slides later on, that we will be able to capture an important part of this market. How the molecule works. The molecule works basically by decoupling the transcriptional complexes which are blocking the differentiation of cancer blast, leukemic blast, which means that we are able to push this leukemic blast to a situation where they are able to enter in apoptosis. On that regard is basically a pro-apoptotic agent.
There is a second way of working for the molecule, which is that LSD1 activity is really needed for leukemic stem cells to survive. Leukemic stem cells is a small subset of cancer cells which are harder to kill and normally are responsible for the relapse. What we know is that when you suppress LSD1 by inhibiting LSD1 with our molecule, basically what you get is a sort of synthetic lethality on this subset of cells. Third and finally, importantly in leukemia, but also very important in solid tumors, inhibition of LSD1 by iadademstat is able to boost the immune system by overproducing a subset of T cells and avoiding the exhaustion of these T cells when they are attacking the tumor. The asset is a small molecule, oral, daily. It's actually the most potent LSD1 inhibitor under clinical development currently.
We are 100 to 500-fold more potent than any other LSD1 inhibitor being developed in different indications. We have a very good safety profile. I will mention that later. We have treated around 225 patients, a bit more now. We are really seeing that it's a very tolerable agent. Interestingly, we have got orphan drug designation from both FDA and European Medicines Agency. We have reported all this in a number of significant papers, as you see, "Cancer Cell," "Journal of Clinical Oncology," the first-in-man study, and particularly the last one, "The Lancet Haematology," which was describing the data of a clinical trial, ALICE, that we were doing in combination with azacitidine in newly diagnosed AML patients. I will come back to this trial later because it's also part of the narrative moving forward in the clinical development.
In a snapshot, this is our pipeline in oncology, and as you can see, it's very rich. The main question that you might immediately think is, "Well, how these guys are paying for that?" Well, fortunately for us, we were able to set up a number of agreements with the National Cancer Institute here in the U.S. with several academic institutions. Thanks to that, this collaboration started three, four years ago. We are right now seeing a number of clinical outcomes. One of them is the one I am going to tell you today, and that has been done with a very modest or limited financial contribution from the company. As you can see in this pipeline, we have right now currently two trials in newly diagnosed AML patients in combination with venetoclax and azacitidine, VEN/AZA.
We have another trial in MDS, we have another trial in MPN. We have two trials in small cell lung cancer, another very interesting indication where the mechanism of action of LSD1 inhibition is very elegant. One of them is being led by Dr. Rudin's team here in New York at the Memorial Sloan Kettering Cancer Center. The other one has just started now from Yale University. Finally, we have two company-sponsored trials in hematology, one in sickle cell disease and the other in essential thrombocythemia. One of these trials that we were starting with the academia, this investigator-initiated trial, it is going on. It is being led by Dr. Curtis Lachowiez at Oregon Health & Science University. Last ASH, in December, in Florida, we were presenting the data of the first 10 patients.
This trial is in principle aiming to recruit 21 patients with three objectives, three goals. Well, first, safety, of course. Second, to try to find the recommended phase II dose, and third, to have a first glance to the efficacy. As you can see here, the data from the first half of this trial, the first 10 patients, were really amazing. We got 100% of responses, 90% of the responses were CRs, happening very soon, cycle 1, cycle 2. Worth noting that we were able to transfer 70% of the patients to bone marrow transplantation. How do these compare with the backbone alone? Well, what you see here on the right of the slide is the historical data of the VIALE trial that led to the approval of venetoclax as the backbone that we are currently using, VEN/AZA.
As you can see here, for starter, one-third of these patients do not respond to this treatment, while we are having 0% of no responses. Within the responses, the amount of CRs were 50%, whereas we were having, at that moment, 90% of complete responses. Well, you can say, "Well, maybe with these 10 patients, you were lucky enough to have a profile of patients which were very favorable." That was not the case. As you can see in the bottom, we were having 90% of adverse risk patients compared to the 36 adverse risk patients in the VIALE trial. Very promising starting. We are going to present data in one week from now in ASH, but what we released a few days ago was the content of the cutoff with 15 patients that we presented a couple of months ago.
Good news, with these 15 patients, we are still having 100% of responses. Good news, we are having a very high level, a number of high-quality response in 93% of CCRs, 80% of CRs. Some of the CR/CRh are still ongoing. They might evolve to a complete CR. We will see on the following weeks, months. As I said, next week, on the 11th, we are going to present more data that we hope is going to please the medical community and hopefully also to the investment community. Okay, that's very nice. How we can move forward? We can move forward in a smart way, I would say, because first of all, let me tell you that this combination, iadademstat, is market agnostic, which means that we work virtually in all AML patients, all of them.
To go in a faster way to a possible approval, what we have designed is a strategy of selecting patients, those patients which are currently having a poorer response with the current treatment. You can see here on the right, the deconstruction of the VIALE data that was presented by Dr. Amir Fathi at Massachusetts General Hospital. I forgot the name, sorry. He was basically deconstructing the whole 300 patients from VIALE, and they were seeing that there were actually three subpopulations. The subpopulation that have TP53 mutations, they are having very poor prognosis, median overall survival, five months. The population which are TP53 wild type, but they are NRAS or KRAS or FLT3 mutants. Basically, they have 12 months of median overall survival.
Those patients who were lucky to be wild type for those mutations, they were good prognostic patients, and they were having a median overall survival of 27 months. Okay. Good news, in ALICE, the previous study I was mentioning before, we got already a significant hit in TP53 patients, and we were able to double the median overall survival. Next, same story with the NRAS/KRAS patient. What we think is that when we finish this ALICE-2 data trial, which we expect is going to happen by ASH, we will have to recruit it normally the 21 patients. We can go to the FDA and explain them that we would like to do a seamless Phase II/III based on this selection criteria and to get CRs as a possible endpoint for conditional approval and overall survival for full approval.
This is going to need approximately 300 patients, 100 for the cohort of TP53, where we think that we don't need a control cohort because it would be unethical. These patients are basically not responding at all with the current treatment. 100 + 100 patients on the cohort of the intermediate risk NRAS/KRAS. We estimate that we will recruit all these patients in around 24 months since we started trial. We are also hopefully that we can group the CR signals very soon. So far, we are getting the CRs on the first or the second cycle. Is a response happening very quickly? Okay, is this strategy having sense? Is making sense? Are we a bit crazy? Well, we are not inventing the wheel here.
We are following the same clinical designs that the menin inhibitor developers, for instance, Janssen, Kura Oncology, Syndax Pharmaceuticals, have done, and therefore, we don't expect a pushback from the FDA to this design. How are we comparing with those other emerging trials? We think we are comparing quite well. Starting for the thing that told you before, we are able to treat virtually all AML patients, whereas the menin inhibitors, because they are basically targeting NPM1 or KMT2A mutations are basically restricted to one-third of the population. Same story for FLT3 inhibitors. We have this capability to cover a bigger universe of the AML patients, which is important because at the end of the day, which is also important, is the size of the market, as we will discuss later. Okay, in terms of tolerability, and good safety profile, we think that we are better than menin inhibitors.
We don't have the cardiotoxicity issues. We don't have any other issues that the FLT3 inhibitors have, and we are definitely better than any antibody. In terms of the current responses, well, we are so far seeing that we are a bit better. We are going to have 21 patients in December. We are going to have probably 18 patients in a few days. So far we are if not better, we believe we are better, at least equal in terms of responses that all other emerging trials. We think that we have a business case which is interesting. We have compelling data, competitive data. We have a biomarker strategy. We have a meaningful regulatory approach. We think that we are not going to have competition for recruit TP53 patient that we can execute timely.
The question now becomes, well, okay, this is very nice, but how do these translate to the market potential? This is one of the worries, the concerns of some investors in the field. Well, okay. We did with Clarivate, probably you all know this consultant firm, a market analysis, a market study. Typically, you interrogate KOLs, you interrogate payers. What we got from the payers is basically that considering that TP53 right now, they don't have any therapeutic meaningful option that they would be considering as a reasonable price. Between EUR 250,000-EUR 350,000 per patient per year. Also interestingly, they said that they will be not opposing to have this price and accept that other patients which have no TP53 could be treated with this combination.
In Europe, the situation, of course, is very different from the U.S., but still, we are having the same range of prices in Germany, U.K., France, and Italy that the most advanced therapies right now, like gilteritinib or venetoclax are having. Very good news in that regard. If you look now in this slide to the left part, you will see what is the feeling of the KOLs. When we ask the KOLs, "How would you feel about prescribing this combination to patients having a TP53 mutation?" They say unanimously, "We would prescribe that to all of them." When we said, "Well, okay, what about the NRAS, KRAS, FLT3 mutation patients?" They said, "Well, that's interesting. FLT3, maybe yes, maybe not," because they are the gilteritinib approach. We got their estimates that they would basically prescribe that to around 35% of the patients.
Finally, interestingly, when they were requested, "What about the others? The ones that are not having these mutations." They said, "Well, if you are not adding any toxicity," because that's one of the findings of ALICE trial, "If you are not adding any additional toxicity and you have 100% of responses, yes, we will also consider to prescribe this triplet, this combination to these patients." As you see, when you split out all these subpopulation, we can have basically around 5,000 people every year from the different sub-populations being treated with our compound. At the beginning, in 2029, if we are successful, we start commercializing. Of course, the commercial driver would be the P53 population, but as the time goes, the other subpopulation would take also an interesting size, achieving more than $1 billion peak sales only in the U.S.
We think that this is interesting, and this is the story I wanted to tell you today. It's not the whole story of Oryzon. We have a sickle cell disease, we have essential thrombocythemia, and we have another asset, but I think this is the most short-midterm value driver for the company, and that could be interesting for you to hear today. Thank you. Yeah, Elena?
Great. Thank you. Thank you, Carlos. Let's dive into that data that you mentioned for iadademstat. You're going to be presenting the data very soon, on the 11th in Stockholm. We've seen a very strong ORR. We saw 100%. I guess, how durable are the responses that you're seeing so far, and what gives you confidence that this is a real improvement as opposed to patient selection or a smaller sample size?
Well, it's a bit too soon to say that, and we are also having here an interesting effect, that in the first 10 patients, 70% of them were derived to human stem cell transplantation, which, by the way, is the best thing that you could do for a leukemia patient. It has an impact on our capability to really assess, really accurately now the duration of responses. The estimated median overall survival, we have not achieved this calculation yet, but we estimate that 75% of the patients are having more than 12 months, that median overall survival.
Which is already comparing well to the backbone because in ASCO a few days ago, there was a presentation from the MD Anderson with all the trials that they have done with all VEN/AZA regimes. They said that on average, which is one of the best cancer centers of the world, the median overall survival of VEN/AZA is nine months. Yeah, we are there.
Great. Thank you. You touched on it a little bit before, but could you give us some color on how the responses have trended across the subgroups and how you're thinking about looking at all patients again, or would you be looking at a subset, and what's the thought process behind this, and could you maybe quantify it a little bit about the percentage of patients that you think you'd be looking at ahead?
Yes. First of all, we are going to present next week a full panel with the genotypes of all the responses that we have got with the different genetic backgrounds. Second, Clarivate was doing this research for us. Approximately 1/3 of the patients have a TP53 mutation, which when you have a TP53 mutation, that overrides any other mutation you may have. You are no longer an NRAS, a KRAS, or FLT3 because the mutation which is driving the worst prognosis is basically TP53. NRAS, KRAS, FLT3 are on average a bit more than 30%. I think that the label would cover probably around 60% of the whole population.
Great. You also mentioned a little bit about safety versus the menin inhibitors that you've seen. How manageable is the prolonged cytopenia, and how is it comparing to azacitidine plus the backbone?
What we have seen is the contents of Dr. Lachowiez's reports in terms of safety and tolerability. What they say is that they don't see any additional toxicity to the one that you typically observed in a VEN/AZA treatment regime. In terms of thrombocytopenias or neutropenias, first, we have to consider that those patients starting the study normally with grade 3, grade 4 thrombocytopenias or neutropenias. Yet, we are getting CRs in the first cycle, which means that we are able to get them back to normal counts in one month. We have seen also that over time in ALICE we have been able to treat people for more than three years. We have people on compassionate use which are still alive, and they are getting the drug with normal counts.
Okay, fantastic. You're also exploring iadademstat in sickle cell disease, and we'll hopefully be getting some data for that this year. It's an area where we've seen validation in the market before. What sort of level of fetal hemoglobin induction could we expect, or are you hoping to see? If positive, what could the next steps look like here?
Well, this is dictated by the physiology and the pathophysiology. It is a medical common perception that around 20%-25% of fetal hemoglobin, you are able to rescue phenotypically the disease. In monkeys, we have seen that we were able to do this in terms of retics and in ex vivo, in human cell samples, blood samples, we were able to do this. We are starting this trial. Trial, of course, follows the requirement that they follow. Yeah, we shall see if our clinical hypothesis is correct. We shall see an improvement of fetal hemoglobin in the months to come.
Okay, fantastic. If we just pivot quickly to touch on vafidemstat. It's obviously, CNS is a big part of the Oryzon story. What has caused the more near-term focus on iadademstat and how should we be thinking about it?
I think that we are fortunate because we are not a binary company in the sense that for long years we have been developing those assets, which are basically right now getting into an interesting point of clinical maturity. I think that with the data that we have, of course, we could not unsee this data, and the company is now deploying all its efforts to get this clinical development because it can be the fastest route to market and the first molecule potentially approved from the company. Yet, when you go to CNS, the market potentials are another dimension. We estimate that vafidemstat has a market potential in treatment of aggression in BPD and autism and in the treatment of schizophrenia negative symptoms that could surpass EUR 6 billion peak per year. That's, of course, very interesting. Where are we?
We are starting right now a phase exploratory trial in autism in aggression, thanks to a European grant from the European community. We are having a small phase II trial in schizophrenia to see if we can get signals on negative symptoms or cognitive impairment-associated symptoms, which are two domains of the schizophrenia that have not been so far treated. The stellar project, of course, is borderline personality disorder, which is a severe disease where there is nothing approved for patients. These patients are suffering and self-harming, and they have a constant anger that compromise their normal life, their jobs, their romantic life. It's a difficult situation. These patients are right now treated with antipsychotics, which is not really working at all. In the phase II that we did, we got mixed results.
There is no golden standard that has been agreed by the FDA or the community how you measure the improvement on those patients, how you measure the improvement on anger on those patients. We are working now with our new chief medical officer, which is a Harvard-trained psychiatrist and a panel of experts FDA, some of the best academics from the U.S. community. We are right now refining the project of a phase III protocol that we expect to submit to the FDA. If they say yes, we will start next year phase III in borderline personality disorder, which will be the only phase III on the field on a very big commercial interest.