Rigel Pharmaceuticals, Inc. (RIGL) Earnings Call Transcript & Summary

Greetings and welcome to Rigel Pharmaceuticals Fostamatinib in COVID-19 Phase II Trial Results Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce our first speaker, Dolly Vance, who is Rigel's Executive Vice President, Corporate Affairs and General Counsel. Thank you. Ms. Vance, you may begin.

Welcome to our fostamatinib in COVID-19 Phase II top line results conference call. Earlier today, the company issued a press release providing a summary of the top line data, which can be viewed, along with the accompanying slides through this presentation, in the News and Events section of our Investor Relations page on our website at www.rigel.com. As a reminder, during today's call, we may make forward-looking statements regarding our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2020, on file with the SEC. Any forward-looking statements are made only as of today's date, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I'd like to turn the call over to our CEO, Raul Rodriguez.

Thank you, Dolly, and hello, everyone. Thank you for joining us this morning. Also joining me today is our Chief Medical Officer, Wolfgang Dummer; and our Chief Financial Officer, Dean Schorno. Today, we have some very exciting news for you. We will be discussing top line results from the Phase II clinical trial to evaluate the safety of fostamatinib for the treatment of hospitalized COVID patients. We are extremely pleased to report that the trial successfully achieved its primary end point and numerous secondary efficacy end point. Wolfgang will provide an overview of the top line results from the Phase II trial shortly. At the end of the call, we'll open the call up to your questions. But first, a caveat. We can only provide information limited to the top line results released today. A further and more detailed data package and analysis will be provided in a publication in the future. So we just want to be mindful of that. Also to remind you, this study is a result of our partnership with NIH and the National Heart, Lung and Blood Institute and Inova Health Systems and was conducted by NIH, NHLBI in collaboration with Inova Health Systems, and we are delighted to partner with them. Let me start with Slide 5 with our plans to make a difference with fostamatinib for COVID-19. As we have previously mentioned, we have a strong scientific rationale for SYK inhibition in COVID-19 and not just one, but multiple levels of this disease. Fostamatinib can inhibit hyperinflammatory cytokines and, importantly, can reduce hypercoagulation and thrombosis. And finally, fostamatinib can also inhibit NETosis, a very relevant mechanism in COVID disease. Fostamatinib is commercially available under the product name TAVALISSE and has a well-established safety database of approximately 4,800 patients treated in clinical trials. Hence, if the COVID data for our trials look good, it could be rapidly repurposed for the treatment of COVID after regulatory approvals. With that in mind, we launched a comprehensive clinical program for fostamatinib in COVID-19 in a very short time. Fostamatinib is now in 3 clinical trials for COVID-19. We are currently enrolling our own Rigel-sponsored Phase III trial, which we were awarded $16.5 million in support from the Department of Defense. In addition, we have 2 collaborative trials. And today, we will see data from the first one conducted by NIH and Inova. We will get to that shortly. With that, let me turn the call over to Wolfgang. Wolfgang?

Thank you, Raul. On Slide 6, numerous investigations have uncovered 2 receptor systems mediated by SYK, which play a role in the activation of multiple cell types resulting in cytokine release, exuberant inflammation and excessive blood clotting. This can eventually lead to respiratory distress, organ damage and thrombotic complications. On the picture, you see the 2 receptor systems. On the right, there are the C-type lectin receptors, or CLRs, which are engaged by DAMPs and PAMPs that are released during the viral infection. On the left are the Fc receptors, or FcRs, which are engaged by immune complexes consisting of viral particles done by antibodies. Fostamatinib, our oral SYK inhibitor, has the potential to block these processes and their sequelae. Much has been discussed about cytokine storms, but less is known about NETosis and its role in coagulopathy. On Slide 7. Our colleagues at NIH were particularly intrigued by the NETosis angle and set up this fascinating study to test it. First, they induced NETosis by overlaying plasma from severely ill COVID-19 patients on neutrophils. NETs were detected using a green fluorescent probe shown on the right here, the top picture. Each fluorescent dot here is a neutrophil that's making NETs. And then they showed that R406, which is the active component of fostamatinib, profoundly inhibited NETosis, adding to the compelling rationale for moving fostamatinib into COVID-19. You see this on the bottom right with no fluorescent activity. Slide 8. Slide 8 shows you the various patient population coupled with our clinical program. The data you will see today are from NIH in collaboration with Inova, which included patients with a 5, 6 or 7 rating on the widely used 8-point ordinal scale, meaning that included the most severe patients. That has particular interest because these patients are presumably the hardest to treat. The other 2 studies, the Imperial College of London study as well as our Phase III clinical trial, will include mild patients with a score of 3 or 4 and investigate the progression of mild patients to severe disease and the prevention thereof. Slide 9. As Raul pointed out, we are not in a position today to take you through greater detail regarding the data than what is in the press release. But what I will do is try to give you some clinical perspective interpretation on what I believe the data really means. With that, let's move to Slide 10. Slide 10 reminds you of the original study design. Approximately 60 patients were to be randomized 1:1 to either fostamatinib plus standard of care or placebo plus standard of care. The primary end point is safety as measured by the incidence of serious adverse events. In addition, a number of clinical end points typically included in these COVID-19 studies and generally considered clinically meaningful were also analyzed. Moreover, NIH has incorporated very powerful translational research tools that can generate valuable new mechanistic data on fostamatinib in COVID-19. For example, they have already looked at some cytokines as well as a NETosis assay in this study with valuable data coming on the mechanistic effect of fostamatinib on that aspect of the disease. On Slide 11, I'm summarizing baseline characteristics. Some key takeaways. The baseline characteristics and demographics were generally well balanced between treatment groups. That's true for -- we saw similar numbers of patients in both groups had underlying conditions. If anything, more patients in the fostamatinib group had risk factors than in the control group. There was good and balanced representation of patients with a 5, 6 on the ordinal scale in severity. And then importantly, there were 4 patients on mechanical ventilation: 2 in the fostamatinib arm, 2 in the standard-of-care arm. These are the most severe patients with a score of 7 on the 8-point ordinal scale. There is a very high risk of dying for these patients. And also important, all patients in both groups were on remdesivir and dexamethasone as a standard-of-care treatment and about 40% also received convalescent plasma in both groups. All of that means that the results that you are looking at are credible and certainly not skewed by any baseline imbalance. On Slide 12, let me comment on some key clinical results. As you know, the primary end point in the study was safety as measured by the incidence of serious adverse events through the 29 days. In this study, we observed the incidence of serious AEs was approximately half in the fostamatinib plus standard-of-care group compared to the placebo plus standard-of-care group. To put this in perspective, remember, the hypothesis for this trial was that if you add fostamatinib on top of standard of care, that success is if the SAE rate is not higher than with standard of care alone. To cut the SAE rate in half is, in my view, not only establishing the safety of fostamatinib in this patient population, but is also potentially a surrogate for efficacy in COVID-19. Consistent with that notion, there is also a favorable difference in the most frequent and disease-relevant SAE of hypoxemia, which was reported less in the fostamatinib group than in the control group. Number two, with respect to mortality, there were 3 deaths in this trial. All 3 occurred in the standard-of-care alone group. There was no death in the fostamatinib group. It is worth noting that among the 4 patients who had entered the study on mechanical ventilation, that most severe patients, the 2 in the placebo group both deceased while the 2 patients on ventilation in the fostamatinib group survived. That is quite remarkable given the high likelihood of death once a patient needs to be intubated and mechanically ventilated. Number there, there were numerous secondary clinical end points in the study. Let me highlight 2 of them. One is the ordinal scale improvement. During the study, there was a greater improvement in ordinal scale score in the fostamatinib group versus the control group. The time to improvement on fostamatinib was also quite a bit shorter than in the control group. The observed changes in the ordinal scale assessments were quite large. Let me provide an example of ordinal scale improvement. A patient who met criteria for a 6 on the ordinal scale needs invasive ventilation. A 3-point improvement means that, that patient no longer requires intervention and is ready to go home from the hospital. That is definitely a very meaningful improvement in a relatively short time. And number four, looking at the number of days in the ICU, it's clear that patients on fostamatinib spent less days in the ICU compared to standard of care. That treatment effect is not only clinically meaningful, but also very relevant from a pharmacoeconomic standpoint. Slide 13, summary of biomarkers. So the NIH has, I believe, over 7,000 blood samples to analyze for all kinds of biomarkers from the study. And they have already looked at a few important relevant markers from a top line perspective at certain point in time. I can tell you that these markets were all improving faster in the fostamatinib patients than in the standard-of-care patients and clearly corroborated clinical improvement. That is particularly remarkable because remember, all patients were on dexamethasone and remdesivir already, and it was not a given that you can show additional greater improvement on top of those drugs with fostamatinib. But we did show exactly that. And NIH is working on a lot more analysis over the next few weeks with a lot more biomarkers, with a lot more time points, and we'll report more data in the near future. So let me summarize overall on Slide 14. Fostamatinib met the primary end point and appear to be generally well tolerated. So this was the first study in COVID-19 patients, and we are very happy we could establish safety. But moreover, given that we reduced the number of SAEs, like hypoxia -- hypoxemia and others by about half, in my view, this can also be seen as a potential surrogate for efficacy. The key clinical end points, including mortality, favored the fostamatinib group compared to placebo and -- plus standard of care, even in the sickest patients. I am particularly impressed by the 4 subjects on mechanical ventilation with the 2 on fostamatinib improving quickly to extubation while the 2 on standard of care unfortunately passed. And I'm personally really excited about the consistent nature of pretty much all end points pointing in the same direction favoring fostamatinib. These end points are widely used and accepted and considered clinically meaningful. There, I think, gives the data a lot of validity. And as mentioned, all of this was on top of standard of care with remdesivir and dexamethasone in all patients. That should tell you that the treatment effect of fostamatinib appears quite powerful and strong as well as it suggests a different mechanism of action than, for example, a steroid. And finally, the clinical findings are consistent with improvements in inflammatory biomarkers, such as NETosis, CRP, ferritin, D-Dimer, IL-6, all favoring fostamatinib. We see quite beautiful and supporting improvements in these biomarkers that are generally and widely accepted as playing an important role and information in blood clotting in COVID-19 patients. Slide 15. So what's next? NIH and the National Heart, Lung, and Blood Institute will continue to follow all patients out to day 60 and also conduct a lot more biomarker work. There are also some subgroup analysis that could be done and can be done and could be interesting that were not available on top line. And of course, Rigel will discuss the data with the Department of Defense since they provided funding for our Phase III trial as well as the FDA as soon as possible. And we will possibly explore an emergency use authorization or any other path that may be of benefit to patients. With that, I'd like to turn the call back to Raul. Raul?

Thank you, Wolfgang. Well, this is very exciting news, and we are delighted with what we have seen from this trial. Seeing a very broad and consistent benefit of this study is really extraordinary and not just one measure, but all the key measures we've looked at: serious adverse events reduced by half; mortality reduced; improvement in that well-established ordinal scale, that's substantial; and improvement in the days of ICU, that's quite substantial. And -- so that is more than we had hoped -- would have hoped for a trial of this size. I think this is a fantastic outcome. It puts us well positioned to move forward with the other trials in this indication to treat COVID patients and I think make a very good progress in making this available to patients. We think that fostamatinib, because of this trial results, can contribute substantially to the treatment of COVID patients. And we're delighted to contribute to that. So we have a significant opportunity in front of us, and we will move it forward and look forward to that as well. So let me turn the call over to your questions. But just, first, a caveat that we do this -- we fully have the top line data and we do have to stay within the confines of the data presented today in the press release and this presentation. So with that, let us take some of your questions.

[Operator Instructions] And our first question is from the line of Eun Yang with Jefferies.

Good data. Congrats. So I know you have only top line data. But in terms of percentage of patients improving on the ordinal scale, can you actually quantify a percent of patients on TAVALISSE improved compared to placebo?

Yes. As you know, we can make a more general comment, but we can't give the actual percentages right now. What we can say is that the improvement was quite substantial. 3.6 was the mean change for the fostamatinib arm compared to 2.6 for the placebo arm. At day 15, 0.035 and 4.2 and 3.3; and at day 29, 0.12. That's a very substantial improvement, as Wolfgang said. And I'll let him comment as well in terms of that improvement. And also keep in mind, this is relatively quickly. 15 days is a relatively short time. And so -- and that is consistent with what we've seen in terms of the benefit of the product. Wolfgang, any additional comments?

Yes. Maybe just to add, Eun, what's really striking is the improvement in ordinal scale is quicker. It's quite large, as I told you, like minus 3. That's like 3 steps on a pretty growth scale that, that ordinal scale is like pretty big jumps from 1 score to another. And I will also tell you that the range was more narrow in the active group. So that clearly tells you that there's more of the protracted severe causes of the disease were in the standard-of-care group rather than in the fostamatinib group. So in general, the fostamatinib patients improved sooner in larger steps.

Okay. Great. And then -- so there is no death on TAVALISSE, I think there are 3 on placebo. So what percent of the patients on TAVALISSE actually progressed to mechanical ventilation versus the placebo?

Thank you, Eun. I don't recall the numbers in terms of that. How many started not as 7s and progressed to 7s, that I think is your question. But we can come back with that response. Wolfgang may give you that after the call.

Okay. And the last...

Yes. Go ahead, Eun.

Okay. Last -- yes, last question is on Phase III. So can you talk about current enrollment rate and when we may expect the data?

Thank you, Eun. Wolfgang, you want to comment on that?

Yes. I can't tell you definitively when to expect the data, but we are making very good progress in activating sites, and we have started enrollment. And enrollment is so far going well with -- as you know, we are in the U.S. and some countries in Latin America, including Brazil, Argentina, Mexico and others. And we are -- well, we are still in the process in fully activating all the sites and the pandemic is quite active in this area, and we do get patients.

Our next question is from the line of Do Kim with BMO Capital Markets.

This is Ike on for Do. Congrats on the data. Just a couple of questions on my end. Given that some of the end points didn't rate as significant, even the primary end point of itself is a reduction in SAE, can you give us some type of pathway and understanding how the FDA might look at this from a potential EUA standpoint? It seems like generally, they look at duration, time of hospitalization. So if you can give us your thoughts on that, that would be helpful for us.

Sure. Thank you. Just a point on the -- on p values. This is a small trial of 60 patients. And so we weren't expecting to have p values on efficacy that were significant. The primary end point, to remind you, was we were trying to show that there were no increase in SAEs with fostamatinib added on. And we, in fact, reduced that by half, a very substantial improvement, not a p-value 0.05, but that was not the objective of that or any of the others. We did reach statistical significance in a number of different variables. But as Wolfgang also said, all of those went -- all the variables we've looked at went in favor of fostamatinib as we saw it. And so that's a very impressive result. Wolfgang, maybe you want to comment on EUA and plans?

Yes. So the way I see this, again, small sample size, but despite -- I would say, despite the small sample size, we showed definitive benefits for these patients that were very consistent. So it's not just one end point and then the other one is pointing in the wrong direction and things are all over the place. No, that's not the case. So every -- pretty much, every data point points in the right direction. And some of them hitting significant p values, others are being close to this. So if I look at this and look at the totality of the data, you got to conclude that the drug has real benefits. And so what does the FDA -- I can't speak for the FDA because they haven't seen the data yet. We will talk with them in the next couple of weeks. And I'm sure that they will see what I'm seeing, which is that this is a clear and consistent benefit in many regards. Now is that enough for an EUA? Potentially. Because remember, this is not a molecular entity, this is a drug that's out on the market with like close to -- we say, 4,800 patients have been treated in clinical trials. It's being used for ITP patients who take this for months and years and not just for 2 weeks. So it should be very safe. So I would say it's a serious consideration, and we'll see what the sentiment is. Ours is good. So I'm sort of optimistic that this is definitely something to talk about.

Got it. Two quick questions. One, do you have any idea of the number of patients who actually received convalescent plasma, like what the balance between the PBO and treatment group? And then the last question, given the ubiquity of vaccines and the rollout, you're having less severe patients, can you speak a bit about the market dynamics on that front? If this was to receive EUA, how do you see it kind of being adopted within the field?

Yes. Maybe I can take a stab at those and Wolfgang hit as well. In terms of convalescent plasma, there was use of convalescent plasma, and it was balanced between the 2 groups. So that doesn't make much of a difference in terms of the results. That was a good thing about the trial. It was very well balanced throughout. So these results, you can be confident is not driven by an imbalance, which is very good news. In terms of how this product might be used in the market, this is a trial here done in in-patient hospitalized COVID patients on the more serious severe side of the spectrum, 5, 6s and 7s. And we saw a very good benefit in these patients. We think that despite the availability of vaccines that not everyone will avail themselves of them and also that new variance as they come along will make the vaccines maybe less effective over time, causing perhaps the unfortunate continued need hospitalization of patients who contract the virus, and that process will continue and perhaps be with us for some time. We think that this product may be able to contribute substantially to those patients that are infected and do require hospitalization. I think that need is substantial. We also think that it has potential to be enduring over years, not just this calendar year. And that opportunity and, frankly, our ability to contribute here is really very substantial. And I think as you saw from the data here, this product may provide a substantial benefit to these patients. It's not just one measure, as Wolfgang said, that we improved. We really improved every measure we've looked at. There was -- anything there that wasn't improved was not there. Everything was better. And so we're delighted by that, which means that there may be a real role for this product in those patients in COVID-19. Keep in mind also, our objectives with this product in this area is to consider other indications, other acute respiratory disease areas where it might have benefit that is maybe from other viruses, perhaps other etiologies as well. So I think there's a substantial opportunity for treatment of COVID patients in hospital. And I think this opportunity is enduring. I think it will last years, not just this year. And I think there's an opportunity, given that we've demonstrated this mechanism and if things continue to go as we shared today, to treat a wider range of patients beyond COVID patients suffering from hyperimmune response.

Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Congrats on these data and looking forward to reading the future publication with more details. Are you aware of any studies or perhaps have any of your investigators commented on what the mortality rates might be for some of these most severe ordinal scale 6 or 7 patients without treatment intervention versus the 0 cases for fostamatinib and standard of care and the 18% that was reported for placebo and standard of care? And then on that note, could you further break down if there's any thoughts around these percents for those patients who present with mechanical ventilation?

Yes. Wolfgang, maybe you want to comment, I can also add in.

Yes. I'm happy to. Kristen, thanks for your question. So once you are intubated and ventilated, so these patients have a tube down their trachea and/or mechanically ventilated, it's a 7. The 8 on the ordinal scale is death. 7 is shortly before death. You have a very high risk of passing away. Nobody can tell you exactly what the percentage is, but the numbers that are called corridor up to 50%. So the fact that we have 2 patients in the standard-of-care group who are deceasing and the other 2 patients in the fostamatinib group who could be extubated by -- after about a week or less than a week is very striking. And I can tell you that, interestingly, this was also correlated with a very strong improvement in biomarkers. So the 2 patients on fostamatinib had substantial improvement in certain biomarkers and the patients in the standard-of-care group did not. And your other question was the severe patients. Yes. Well, so the fact that we are treating severe patients and get these patients out of the hospital and off of the ventilator that are really at very high risk is a very striking outcome in this result and to show that with only 60 patients is pretty, pretty darn good.

Our next question is coming from the line of Yigal Nochomovitz with Citigroup.

Congrats on the data. Just had a few quick questions. For the 2 patients on mechanical ventilation that received fostamatinib and were extubated, can you just confirm that they were discharged from the hospital? And then for those same 2 patients on mechanical ventilation, am I correct that they received an IV formulation of fostamatinib? And assuming that's right, how did you develop the IV so quickly? And then last question is for your Phase III that you're running for the patients that are hospitalized but not on mechanical ventilation, are they going to receive IV or oral?

Sure. Maybe you want to comment on that as well, Wolfgang?

Yes. So no, it's not an IV formulation. So what we're doing is you mash that pill into a powder, and then you administer it through the gastric feeding tube. So it's not an IV formulation. And I wasn't in the hospital, but I asked how that went. And I was told it's absolutely 0 problem. So you basically -- you make this tablet into tiny little particles, add some water and put it down the feeding tube. And it's the same dose as we use in ITP, 150 milligrams twice a day. And it's -- that will be the same in our Phase III study. But in our Phase III study, remember, we are looking for milder patients, and we're trying to prevent progression to severe disease. So those patients should be able to swallow the pill anyways. I hope that clarifies it.

Yes.

The other question you got, those 2 patients on fostamatinib did come off the ventilator in 7 days and recovered subsequently and were discharged.

Our next question comes from the line of Chris Raymond with Piper Sandler.

Congrats from us as well on the data. Raul, just a question on making this available pre-EUA. I think last time we spoke, you talked about putting in preparatory steps to be able to make this available to docs. My sense with these data being as striking as they are, you're probably going to get more demand. Can you maybe talk about what we should expect on that end, especially pre-EUA?

Thanks, Chris. Appreciate the question. So we are working towards an EUA, and that will happen I hope relatively quickly in terms of getting that discussion with FDA going. And this data, as Wolfgang said, was -- is really very compelling in totality. Prior to that point, there are rules, and we will follow those rules, and we absolutely will be compliant with what we can and cannot do. We will not proactively go and discuss this product in this indication with these clinicians, that would not be appropriate. But we will handle questions as they come to us and, frankly, come to NIH as well, coordinating with them to make information available in a compliantly appropriate manner. And so there might be use of the product in that area. The product, as you know, is available currently. It's on the market. It's available in most hospitals. They have some fostamatinib for their ITP patients. The distribution system is there. And so we have it available and doctors can use the product even prior to an EUA themselves without our encouragement, obviously, or any other action. And so it is there and it will be available. And if they want to use, they certainly can use it relatively easily because its availability. That was one of the reasons that NIH was particularly keen and, frankly, DOD and other partners as well, that it's an approved product, that it's an available product. Its distribution system's in place. None of that has to be created de novo, given if there's utility shown in this area. And so I think we're delighted that, hopefully, that confidence and interest has proven itself.

Okay. And then just a timing question. I'm not sure if this was answered before. But the Imperial College Phase II data, is there an updated expected timing for that trial? And then on your own sponsored Phase III trial, I know on the Q4 call, you were talking about summer fall data. But obviously, you've got pretty high COVID rates in Europe and Latin America. Is there any change to that time line?

Wolfgang, maybe you can comment as well on Imperial and our own timing.

Yes. I don't recall what we told you last time about Imperial. We have about 115 patients enrolled there and growing. I don't know exactly and I can't tell you exactly when that is going to complete enrollment. And with regards to our Phase III, I would say, it's too early to either say we are faster or slower. But as I said earlier, we do get the sites on board. We do enroll patients in -- I mean with this data now in hand and being able to say, look, there is clinical benefit in a NIH-conducted Phase II study. I certainly think that it will help the Phase III trial. But I don't want to give you a definitive time line at this point.

Okay. Fair enough.

Yes. In Brazil, Latin America, the case loads are unfortunately very high. And so that obviously makes more patients available there for fostamatinib.

Our next question is from the line of Joe Pantginis with H.C. Wainwright.

I don't want to belabor the EUA concept, but I think you have an intriguing bit of a push and pull going on here. As you've all commented on thus far, obviously, you have a very broad safety database that you mentioned from an approved drug. But then at the other end, you have the face value of being a relatively small study. So I guess with all your comments in mind that you've already shared, what have your regulatory consultants discussed here? Because you're also going to be talking to 2 different agencies, you said the DOD and the FDA. So it seems like this could be a relatively fast path for you guys. I was just curious what you think the impediments are or the ability for the FDA to come back and basically say we need to wait for your Phase III as well.

Wolfgang, would you like to comment?

Yes. It's very hard for me to speak for the FDA when they haven't seen the data. But I can tell you that we are in contact with them. We have told them we are getting data in April. They are aware. They have asked us to create a draft EUA, which we will have to put in the data story that became available just now. So what does that mean? I don't know exactly what that means. It certainly means that they're interested to see what we have. And then they have to make their judgment call as to what this data that we've seen today means. I can only say, again, in my wildest dreams, I thought if we see some trends, but we see very consistent improvements across the number of end points despite the low sample size. I mean you can go out and look at other papers of trials that have 1,000 patients and show very, very small incremental benefits and they got EUA, emergency use authorization. So now it's up to you to think, well, is it better to have 1,000 patients and the tiny but incremental benefit or is it better to say we have a relatively small study and despite the small sample size, you see pretty large treatment effects? I can't definitively answer that for that and not for the FDA, we will have to talk about it. But again, in my view, the data looks good. And if I think the data looks good, probably other people might think the same way.

No. That's fair. And I'll ask my last two questions at the same time. So first, I was just curious what types of subgroups you will be looking at and will that also include additional earlier drug therapies such as the antibodies. And then secondly, I was hoping to get a little more color because, obviously, you mentioned this earlier, Wolfgang, but really the importance of seeing these biomarker improvements across the board on top of the standard of care and how TAVALISSE's mechanism really comes to play here.

Yes. I -- it's -- I'm so sorry. I've seen the biomarker data and really, I'm looking forward to share that with you whenever we can and whenever the NIH is ready to publish this stuff. But you saw in the press release, these biomarkers, ferritin, D-Dimer, fibrinogen, those are the biomarkers that are representing clotting. They are clearly improved. This whole NETosis, you saw the slides and you saw the publication of [indiscernible] from the NIH, who did this in vitro. He was able to confirm that the drug is inhibiting NETosis in this patient, in this study. It's like it's super exciting. I can't tell you how exciting it is. And what we don't have yet is death by patient by patient. So we know in the fostamatinib group, all these things are pointing in the right direction. And sorry, the other comment that I want to make, and that is on top of remdesivir and dexamethasone. I hope you understand how important that is. Dexamethasone is the most potent steroid that you can possibly give. So the idea was that you are basically hammering everything down with dexamethasone and there's nothing else you can do. No, there is something else you can do. Fostamatinib is better than dexamethasone, this background therapy. And as we told you earlier, everybody was on dexamethasone. So there is no doubt that there is the effect or because people got different standard of care. Now that everybody got dexamethasone and we still have better reduction in those biomarkers that I will tell you. Now what we will do, when you say additional subgroup analysis, we will look at the patient-by-patient number. I already told you the 2 individual patients who were on the ventilator in the 2 groups. The 2 fostamatinib patients came down nicely with their biomarkers, the other 2 patients in the standard-of-care group did not. So that's a very powerful finding, even though it's only in 2 patients. And then, of course, now you can go ahead and look at every single patient and say, okay, that patient improved, what did each individual biomarker do and which ones are the ones that are predictive and prognostic for clinical outcomes? So there's a lot more work to do and a lot more data to come. But the overall picture is already pretty clear.

Our final question comes from the line of Do Kim with BMO Capital Markets.

It's Ike on again guys. So just a follow-up on the biomarker data. Given that we haven't seen the details, but it is promising that you're seeing the reduction with TAVALISSE, I know it's early days, but how has it essentially influenced your thoughts around exploring TAVALISSE and some of these other NETosis-related diseases? I believe, in the past, ARDS has been broadened up as a potential indication to pursue. But again, if you can provide your thoughts on that and maybe potentially when the study can be initiated, that would be helpful.

I appreciate that question. NETosis is such an interesting marker, and there are numerous diseases that -- where it may play a role. This is one of them, obviously. But I think given that results in that exploration, I think we're keen on exploring other areas. We've mentioned other non-COVID viral diseases potentially and then others beyond that. Maybe Wolfgang can also comment.

Yes. No. The question is a good one and the -- and an obvious consequence. I will just say today, looking at this data, this has completely opened a new area of opportunity and approved a concept. This NETosis inhibition, it is real. It is demonstrable in the study. And it's obviously clinically relevant. So there will be subsequent hypothesis and studies to be had in whatever. Today, we're not there yet to predict what exactly, but the data is really good and we will build on that.

At this time, I will turn the floor back to Mr. Raul Rodriguez for closing comments.

Well, thank you. I appreciate your interest and participation on the call. I appreciate that. Let's say -- to say the least, this is a really exciting outcome. And I can't tell you how excited we are by these results, what they mean, our ability to contribute to this disease. And we will drive this forward as best and as fast as we possibly can to make this product available to patients who might benefit from it. So thank you for your support. Appreciate that. Have a good morning.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.