Omeros Corporation (OMER) Earnings Call Transcript & Summary

Good morning, and welcome to today's call for Omeros Corporation. [Operator Instructions] Please be advised that this call is being recorded at the company's request, and a replay will be available on the company's website for one week from today. I'll turn over the call to Jennifer Williams, Investor Relations for Omeros.

Good morning, and thank you for joining today to discuss the final data from our pivotal trial of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy, which we'll refer to today as TA-TMA. The slide presentation accompanying this morning's call are available on our website at www.omeros.com. I'd like to remind you that some of the statements that will be made on today's call will be forward-looking. These forward-looking statements include, without limitation, statements regarding the efficacy, safety and intended utilization of our investigational product, planned regulatory submissions and anticipated regulatory actions and plans for the potential commercialization and future development of our investigational product. You are cautioned to not place undue reliance on these forward-looking statements, which are based on management's beliefs and expectations as of today's date and are subject to change. The company disclaims any obligation to update such statements. All forward-looking statements involve risks and uncertainties that could cause the company's actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings with the Securities and Exchange Commission, including in the Risk Factors section of our most recent annual report on Form 10-K and our subsequent quarterly reports on Form 10-Q. On our call today, we have a team from Omeros, Dr. Greg Demopulos, our Chairman and Chief Executive Officer; Dr. Steve Whitaker, our Chief Medical Officer; Dr. Cathy Melfi, Omeros' Chief Regulatory Officer; and Dan Kirby, our Chief Commercial Officer. Also on the call are 2 international experts in stem cell transplantation, Dr. Alessandro Rambaldi and Dr. Miguel Perales. I will now turn the call over to Dr. Demopulos.

Thank you, Jennifer, and good morning, everyone. We appreciate you joining us. First, I'd like to thank Dr. Perales and Dr. Rambaldi and all of the clinical investigators and site personnel as well as the patients and their families who participated in the pivotal trial. I'd like to welcome this morning, our 2 stem cell transplantation experts, Dr. Rambaldi and Perales. Alessandro and Miguel, would you take a moment please and introduce yourselves?

Sure. Thank you, Greg. My name is Miguel Perales, and I'm the Chief of the Bone Marrow Transplant Program at Memorial Sloan Kettering Cancer Center in New York.

I am Alessandro Rambaldi. I am Professor of Hematology at the University of Milan, and I'm the Head of the Hematology and Oncology Department at the Hospitali Papa Giovanni XXIII Bergamo, Italy.

Thank you. Thank you, both. Before starting the presentation, let me provide a bit of background. Narsoplimab has been granted breakthrough therapy designation in 2 different indications, one of those being hematopoietic stem cell transplant-associated thrombotic microangiopathy, or TA-TMA. We completed the pivotal clinical trial for narsoplimab in TA-TMA and presented earlier this year impressive preliminary results. Following completion of all data collection, database lock and data review, the final trial results are even stronger than we had previously reported. These are the final data that are included in our Biologics License Application, or BLA, the final sections of which are in the publishing phase. With that, I'd like to turn the call over to Dr. Perales, who will speak to the role of stem cell transplantation in the underrecognized and often lethal complication of TA-TMA. And then Dr. Rambaldi will take us through the data. Miguel?

Thank you, Greg. So welcome, everybody, to this webcast. I just want to orient you to the slide. So you should have access to the slides that we're going to review, and we will indicate when we're moving to the next slide, just to to give you the heads up. So I'm going to give a very brief 1-minute introduction to the topic and then will hand over to Professor Rambaldi, who works with the data from the clinical trial. So if you can move to the next slide of the presentation, Slide #2. So we know that TA-TMA is potentially a fatal complication of stem cell transplantation, and this is seen both in patients who undergo autologous and allogeneic transparent. We know that HSCT is associated with marked endothelial injury, and this is driven by a number of factors, including the conditioning regimen that we give the patients to prepare them for the transplant, the immunosuppressive drugs that we use to prevent transplant complications such as graft-versus-host disease as well as infections that patients can develop post-transplant. And there are already a series of endothelial injury syndromes, which are now recognized in the transplant patients. The -- obviously, the primary one being TA-TMA, but we also understand now that other complications of transplant also are associated with endothelial injury syndromes. And these include graft-versus-host disease where the immune system of the donor essentially attacks normal tissue in the patient; diffuse alveolar hemorrhage, a very serious complication where there's bleeding in the lungs, veno-occlusive disease or as it's now known as sinusoidal obstruction syndrome, which is a potentially fatal complication affecting the liver, capillary leak syndrome and idiopathic pneumonia syndrome, which again is a potentially serious and fatal complication involving the lungs. We know that endothelial injury has been shown to activate the lectin pathway complement. And MASP-2 is really a critical enzyme in this pathway and is both proinflammatory and prothrombotic. And you'll see that narsoplimab is the perfect target for this pathway. And one of the issues that we also need to recognize is that HSCT-TMA is under-recognized entity in the transplant patients. And the recent data reported from the group at the Dana-Farber in Boston has shown that it can occur up to 40% in transplantation. So I think this is really an important clinical entity that has a significant impact in terms of morbidity as well as mortality and then really an unmet need as there are currently no approved drugs in this indication. And with that, I'll hand over to Dr. Rambaldi, who will take you through the data of the clinical trial. So if you can move to the next slide.

Okay. Good afternoon. So if we can have a look at Slide #3, it summarizes some key aspects of narsoplimab and its ability to interact with the complement pathway. So narsoplimab is an investigational fully human IgG4 monoclonal antibody against mannan-binding lectin-associated serine protease or MASP-2 and MASP-2 is the effector enzyme of the lectin pathway of complement, which is schematically illustrated in this figure. As you can see in this slide, the activation of the lectin pathway by tissue injury triggers the activation of the common lytic arm of complement. This results in release of anaphylatoxins, optimization of the injured cells and deposition of the C5b-9, the membrane attack complex on the injured cells. This complement activation amplifies the cellular injury and inflammation. So blocking lectin pathway activation could mitigate endothelial injury and thus improve the endothelial injury syndrome. Remarkably, the ability of narsoplimab to interact only with the lectin pathway leaves the classical pathway of complement function fully intact. And this is obviously very important, reserving the ability of complement to interact with pathogens and bacterial infection in particular. So if you can now move to Slide #4. It has been already said by Dr. Demopulos that narsoplimab has received the orphan drug designation from both FDA and EMA. So narsoplimab has been granted breakthrough therapy designation by FDA for transplant-associated tumor microangiopathy and also for IgA nephropathy. Narsoplimab, in addition, is in Phase III clinical trials for the other lectin pathway-associated diseases that include endothelial injury, including IgA nephropathy and aHUS. In Slide #3 (sic) [ #5 ], we can now enter into the pivotal trial design that has been performing in the setting of tumor-associated microangiopathy. This has been a single-arm, open-label study, which was initiated as a Phase II trial. But following the receipt of the breakthrough therapy designation and discussion with FDA, the trial was converted to become a pivotal trial. Protocol specified that patient receive narsoplimab once weekly for at least 4 weeks. Next slide, Slide #6. So the trial enrolled a high-risk population. That was including patient with a very severe condition at study entries and who had not responded to immunosuppression modification, which is some part of the pathogenesis of the disease. Additional inclusion criteria, including the presence of thrombocytopenia, evidence of microangiopathy hemolytic anemia, it has elevated levels of lactate dehydrogenase, decreased haptoglobin and the presence of schistocytes. In addition, patient had evidence of renal failure, represented by the increased creatinine values. Next slide, #7. This slide summarize the objective of this pivotal trial. And the primary objective of this study have been established in collaboration with FDA, and they require both an improvement in TMA laboratory markers, it has an increase of the platelet count and the decrease of the LDH values and also an improvement in clinical status of the patients. We also had to show as a secondary objectives of the study the safety and tolerability of this study drug. In addition, we had secondary objective represented by the survival and the change from baseline in -- of laboratory markers. Next slide, please, Slide #8. Accordingly to this study objectives, the laboratory endpoints of the study were represented by the decrease of the LDH values, less than 1.5 the upper limits of normality and improvement of the platelet counts. In patients with a baseline value below 20,000 per microliter, we had to reach an absolute count above 30,000 and the freedom completely transfusion. Or alternatively, in patient with a baseline value of platelets above 20,000, we had to reach an absolute count of 75,000 or to increase by at least 50%. The next slide. The clinical endpoints of the study were selected to evaluate all the key organs that are usually involved in TA-TMA, so not only blood and kidneys, but also other key organs like the lungs, the GI tract and the central nervous system. We can now move to the main study results we achieved. So the study population was composed by high-risk patients. Large majority had multiple risk factors for poor outcomes, including a median age of 48; the underlying disease, which was always a hematological malignancy for which the transplant was transformed and the concomitant presence of graft-versus-host disease in 78% of cases; a previous history of transplant-related infections, which was present in 86% of the cases; and the multi-organ involvement, which was present in 50% of the cases. So all in all, quite a high-risk patient population. Let's move to Slide #12. Let's summarize the response rate observed in these patients. Among the 28 patients enrolled into the study, a complete response was achieved in 61%. This result is by an intent-to-treat analysis, meaning that it includes patients who received at least 1 dose of the study drug. For the 23 patients who actually received a planned study treatment, at least 4 weeks of dosing, the rate of complete response was 74%. In any case, these results are largely exceeding the 15% FDA-agreed efficacy threshold for the primary endpoint. Next slide, Slide #13. Remarkably, the rate of the response was not affected by age, sex or the presence of concomitant GvHD. No difference in this different patient setting. A previous history of transplant-related infections, the multiplicity of organ involvement or when the transplant graft was obtained by an HLA mismatch donor was similarly not impacting on the response rate observed. Next slide, Slide #15. The complete response was similarly no different in the rate when according to the baseline values of platelet counts, the renal and the pulmonary function. And finally, this was also true according to the presence of neurological dysfunction or GI tract or the transfusion requirement that patient had at study entry. So in Slide #17, we can easily appreciate the rapid improvement of both the platelets on the left part of the slide and the hemoglobin levels observed in the setting -- in this patient population. Quite remarkably, the improvement of the platelet values was rapidly observed early during the treatment with this drug. In Slide 18, you can find the reason of this rapid hematological parameters because the rapid improvement of anemia is fully explained by the rapid change of the hemolytic-related parameters. Thus, for example, the reduction of the LDH values on the left part of this slide and the increase of the haptoglobin level that is a typical marker of resolution of the hemolytic anemia. In Slide #19, you can appreciate the striking clinical and laboratory improvement was associated to a parallel impressive result in terms of 100-day survival, which was 68% in the whole population of 28 patients. And this proportion increased to 83% in patients who actually received the planned dose of 4 weeks of dosing. The overall survival was even much more significant in the group of 17 patients who respond to the study treatment. In Slide #20 [Audio Gap] received the transplant, the survival of this patient has to be considered remarkably good. Next slide, Slide #21, that illustrate the safety and tolerability of narsoplimab in this setting. Narsoplimab was very well tolerated in this very sick population with multiple comorbidities and transplanted for malignant disease. The most commonly reported adverse events were nausea, vomiting, diarrhea, hypokalemia, neutropenia and fever, quite not specific side effects that are usually observed in any transplant patient in this stage of the disease. So in conclusion, the study patients that were enrolled into this pivotal trial with narsoplimab for TA-TMA were surely patients at high risk for poor outcomes. Most narsoplimab-treated patients achieved a complete response with a significant improvement in laboratory markers and in clinical status. The 100-day survival is impressive, but it is also impressive the long-term survival after transplantation of these patients. A response were seen in all patient subgroups defined by baseline characteristic, transplant characteristics and transplant complication. The drug approved, very remarkably safe with no significant side effects to be registered and reported. Data from the compassionate-use program that follows these pivotal trials are highly consistent with the results that I have just shown you. So submitting the license for FDA for this drug is ongoing and similarly is true on the European market with EMA. Thank you for your attention.

Thank you. Thank you, Alessandro. Thank you. That was much appreciated. Miguel, can I ask your thoughts on the data and the potential role of narsoplimab as you see it in TA-TMA?

Sure. So I think you've obviously seen very impressive data presented by Dr. Rambaldi, summarizing the results of the pivotal trial in patients with TA-TMA. And I'd like to make a few points on this. First of all, this is a condition, as I mentioned earlier, which is associated with significant morbidity and mortality, high risk of dying post-transplant. And the patients enrolled on the pivotal trial all had high-risk features, which really illustrates how impressive the data is. I think what struck us in the results of this trial is the fact that the responses were seen very early, as Dr. Rambaldi indicated, with a rapid increase in platelets as well as rapidly changes in other parameters such as haptoglobin and LDH, which sort of speak to the underlying process that's going on in these patients. And the responses were very high, as you saw. The other thing, which is obviously impressive in these patients is to see the 100-day survival as well as the long-term survival, which is also very encouraging. The endpoint for this trial is obviously something new. It's a composite endpoint. And I think it really speaks to the clinical situation that we're dealing with. And it includes both the laboratory findings, which are critical to these patients as well as looking at the different clinical parameters and organ damage. So I think it really captures the dual aspects of the syndrome, which is both changing in lab values, but as well multiple organs being involved. And I think importantly, this endpoint was developed in conjunction with the FDA and was sort of, if you will, baked into the study design in terms of leading to approval process. So where do we stand now? There are actually no drugs approved in patients with TA-TMA? What do we do today in these patients? So we -- most of our care is focused supportive care and trying to address some of the underlying risk factors, removing drugs if we can. And the one drug that is used in this setting is a drug called eculizumab, which is not indicated in the setting but is indicated for atypical aHUS. And so we often label this somewhat incorrect the atypical aHUS so that we can get patients eculizumab. What are the results of eculizumab? Obviously, this has not been formally studied in the setting. I would say that the results from my pediatric colleagues tend to be quite encouraging. But that patient population is somewhat different from what I routinely see in the clinic. And in the adult patient population, I have to say that while we do see responses, what has struck us is the high rate of infections and also the high rates of mortality in these patients. And then our own experience that we've looked at, the patients respond but unfortunately, many of the patients probably die of of complication. And so while you see something working long term, it does not really provide benefit for the patient. So as a result, there's really a significant unmet need in this space. I think the data that you just spoke about narsoplimab is extremely encouraging as a clinician. And obviously, I'm awaiting approval of this drug, so that we can provide it to our patients in this situation. And then the other thing which I'm not sure was mentioned is the fact that this drug is also being studied in patients with COVID. And as you know, we're not anywhere close in the end of the pandemic. And so I think there's also some very early promising in data in those patients as well. Thank you.

Thank you, Miguel. Those are helpful insights. And with that, operator, let's open the call to questions.

[Operator Instructions] Our first question comes from line of Geoff Meacham from Bank of America.

This is Greg Harrison on for Geoff. Congratulations on the data. So it looks like the subgroup analysis showed a pretty consistent response. But were there any characteristics that made patients more likely to be responded? And then also, did you see any meaningful improvement in patients who were not considered complete responders?

Well, as I showed you, the -- we try to identify a subgroup of patients with a different rate of response to narsoplimab, but taking into account several laboratory and clinical factors, we failed to identify patients who might fail this study drug. And so apparently, my interpretation of this finding is related to the specific mechanism of action of the drug that tackles exactly the extrinsic pathway of the lectin -- of the lectin pathway activation. So the overall response rate was exceedingly above what we could expect in such a patient population. So this tells us a lot of about the merit of it.

Steve, do you want to add anything to that?

Sure. Thanks, Greg. We did look at, as you saw, a large number of different parameters. We didn't see -- we saw responses across all the different parameters we observed. There wasn't anything which seemed to identify patients who responded. I think more importantly, there was nothing that would indicate patients who don't respond. So we didn't see anything which would indicate that you -- which would partition these patients and to those who would or wouldn't respond on those you would or wouldn't treat. As far as the partial responders go, we did look at that. We have not made that public yet. This is a public [ webcast ]. I'm just making sure from legal attorneys here since we haven't discussed that. We did see patients who did have partial responses as well, but we haven't gotten the data out yet.

I mean I would just add here that when you have very high response rates, it's hard to tease out in a relatively smaller study who's not responding, you would need many more patients. Obviously, if the response rate was close to 50, then you could get into those discussions. It's -- unfortunately, the response rate is so high that you can't tease out the particular risk factors. But obviously, for our patients, that's a good thing.

Okay. That's helpful. And then just one follow-up. When it comes to the discussions with the FDA, did they give any guidance beyond the 15% complete response rate hurdle on things that they would like to see in the trial?

This is Cathy Melfi.

Well, I think -- can you go ahead and respond to this question?

I think, Cathy?

Yes. This is Cathy Melfi, Regulatory Affairs. And with the breakthrough therapy designation, we've been in close contact with FDA throughout the development of the product. And obviously, the response rate is important. We've talked about the survival endpoint, some of the secondary endpoints that we've seen here. And we have worked very closely with them and are pulling together the -- and have pulled together the information for the BLA that they have requested. And again, we're looking forward to getting the final piece submitted. And again, I think it's the secondary endpoint, the 15% response. And again, the specific data that they requested are all there, and we feel very comfortable with where we are in those discussions.

Our next question comes from the line of Steve Brozak from WBB.

Congrats on these numbers. They were strong before, but they're obviously even more impressive now. So in following through though on the BLA, you mentioned there the last line shows in publication. Can you give as much color as possible on publication? What does that mean? And anything you can tell us would be very much appreciated. And I've got one follow-up after that, please.

Sure. Thanks, Steve. The publishing phase is essentially the procedural stuff that needs to happen once a document or a data set is considered final. And as you know, BLA follows a lot documents and data set. And during the publishing phase, the documents are electronically processed and compiled for integration into what's called the electronic common technical document, the ECTD, which is the structure that's required for all regulatory applications. And the publishing process involves things like conversion documents in the appropriate format, uploading them to the regulatory required publishing system, integrating them into the rest of the BLA, and that includes things like assigning metadata, testing the 10s of thousands of hyper lengths across all the sections of the BLA to make sure that the reviewer can get to the right place with just one click. And so again, that all goes on. The complexity and the amount of time it takes really depends on document size and that sort of thing. Once all of that of the documents are published, the submission then goes through FDA's electronic gateway. And really proud to say that we've had flawless submissions of the nonclinical and the CMC sections of the BLA so far, and we fully intend to make sure that the final parts of the BLA are also successfully submitted. Does that help?

No, thank you. Thank you.

Steve, one comment just on -- just to add to what Cathy said. I believe, Cathy, we're about 70% plus of the BLA has already been published, is it?

Oh, that's a good point, Greg. Actually, the number is higher than 70% right now, last I heard, I've been checking in with our publishing team. But yes, things are going through as we get them, and we're very well on our way to getting this published.

Got it. Let me pivot to one thing. With your indulgence, Dr. Rambaldi is on the line. Obviously, the last conversation you had in describing your results using narsoplimab in Bergamo were impressive and everything you would want. Can you tell us given how topical the long haulers are and the severity of the patients that you've dealt with, have you been monitoring anything going forward with these patients and what happened? And anything you can tell us on that would be greatly appreciated.

Are you talking about the COVID patients?

That's exactly right. The COVID patients.

Okay. As you know, Bergamo was the epicenter of the Europe, and I would say the Western country outbreak of COVID-19 late February this year. And we were so desperate at the very beginning of this outbreak. Very new things and new findings that we have had to face in this disease. And one of the most impressive finding was the vascular problems, the thrombotic events that we -- and in one word, the endothelial damage that we documented very early with the autopsies that we performed at the very beginning of the outbreak. So the damage of the endothelial cell prompt me to ask Dr. Demopulos for having some compression treatment with this drug. And we have been [Audio Gap] quickly. But the most impressive thing is now the late -- the long-term outcome of these patients because all of them have a complete recovery, not only of the clinical condition, but also all the laboratory findings have been normalized. And among these laboratory findings, I'd like to emphasize the normalization of the D-dimer value, which quite often remain significantly elevated for months after the recovery of these patients through the infection. And so I think that this is -- so all of the patients that we have treated responded. It's a limited number of patients, but those patients were severely affected by the disease. And so since the disease is coming back with the second wave here in Europe. I think I would very happy to have the possibility to treat more patient with this drug.

Getting back to that because what we've been monitoring are the symptoms and the signs that these patients that were severely affected have gone through. You specifically seen no brain fog or any of these other things in these patients? Or have you been monitoring for them? Or have you looked at that at all?

Yes. Several patients have long-term sequela, the cardiac and the CNS level. And this is most likely related to the vascular damage that the COVID-19 infection is able to induce.

And have you monitored these patients that you treated with narsoplimab for these sequeli?

They have completely responded. There are no sequeli documented for the time being so.

Steve, just to add to that, and I think Alessandro may have mentioned this where we have a little audio problem in here, so I'm not sure we heard it. But to underscore what Alessandro said, all of the patients that were treated in Bergamo with narsoplimab at 5- to 6-month follow-up are clinically entirely normal. And most interestingly, all of their laboratory are entirely normal, including, as Alessandro said, D-dimer value all have become normal and have remained normal, which given the percentages of patients who are having long-term sequali, which is on the order of 70-plus percent conservatively, those data are quite remarkable. Alessandro, would you agree? Miguel?

Yes. Miguel?

Yes. No, definitely. I think that data is very impressive. And as we know that many of the other drugs that have been touted in this space have not panned out. So I think this does seem to be a drug that seems to have a significant impact in some of our sickest patients with COVID. And I think that's also something, obviously, that people are very interested in pursuing.

And our next question will come from the line of Brandon Folkes from Cantor Fitzgerald.

Congratulations to you getting to this stage. Maybe just curious to following up on an earlier question. When do you expect to complete the publication and/or submissions to the FDA? If you'd only give an exact time line. Should we think of this being measured in weeks or months? Secondly, maybe -- yes, there are 2 additional responders, I believe, in the final data versus the June data. Could you just provide some color on those patients? And then I've got 2 more, but I'll let you answer those just because you do have an audio problem you mentioned. I don't want to ask all 4.

Yes. I mean first, in answer to your first question, Brandon, it's going to be done soon. You're not talking about months. You're talking about a short time frame here. What remains, as I think Cathy laid out, is just procedural stuff. The team has been working hard. The objective has been, as Cathy noted, really has been and remains to submit a high-quality BLA that is thorough, accurate and consistent with the strong efficacy and safety data that we have for narsoplimab. Cutting any corner would be unwise. We've all recently seen really good companies receive refusals to file and complete response letters, which by saving a few days on the front end can cost a very long time in the resolution of those issues. So as you know, we're looking for a rapid priority review with FDA, and we really don't want at this point to have any inadvertent issues that would slow that down. I mean, Cathy, I'll ask you to comment, and then I'll ask Steve to address the question of the additional 2 responders.

Yes. Thanks, Greg. I think you covered it very well there. As I said before, we're very proud of our submission team and the quality of our data and our publication team, and we are taking our time to make sure that we get everything right. And when it is, we'll get it submitted.

And regarding those additional 2 responders, the -- I think as you probably know, the study was originally designed as a certain protocol. And then when it pivoted to -- or was converted to a pivotal trial, we went and did additional data collection that was requested by FDA. As it turns out with the additional data collection, we actually had more responders due to the -- in the data that we collected that they -- from their request, basically.

Thanks, Steve.

Great. And then maybe a question for Dr. Perales. You talked about how you treat patients currently. Do you foresee using narsoplimab on all patients? Or [indiscernible]? And do you think some patients, you would continue to use supportive care or eculizumab?

I mean, I'll be honest with you, I'm not a big fan of eculizumab based on our own experience, and I haven't really continued to use it. I think supportive care obviously is a big part of this. And certainly, when we can withdraw insulting issues, then we welcome that. But at the end of the day, these patients, even if you -- for example, if it's associated with drugs for immune suppression like tacrolimus or cyclosporine, very often, even when you stop the drug, the pus has continued and sometimes gets worst. So these patients definitely need treatment. And based on the data that you've just seen, there really is no reason not to treat these patients. So I would foresee that once approved, I would be using this in these patients.

Great. And one more, if I may. Just [indiscernible]. The EMA application is being prepared. That's another positive. Can you just let us know, have you agreed on the endpoint with the EMA as well? And how should we think about the [ timing ] of that?

Thanks. And yes, we've been in discussions. As you know, we've been assigned a rapporteur in the EMA, and we have discussed with them. In Europe, I think survival is going to be a key endpoint for them. But we have had these discussions. And as we've said previously, once the BLA gets filed in the U.S., and then we're going to turn even more intently on the EMA submission.

Congratulations on getting to this point.

Thanks. Thank you, Brandon.

Our next question comes from the line of Andreas Argyrides from Wedbush.

This is Andreas on for Liana Moussatos. Two questions, maybe 3. Starting with Dr. Perales or Rambaldi. These are definitely impressive absolute median overall survival numbers. But could you put the os data in better context similar to perhaps the 15% complete response threshold?

Yes. I think the -- for me, when I look at the survival curves, what that really speaks to is the fact that those survival curves are what you would expect in these patients without TA-TMA. So you sort of -- you kind of fix the problem, which normally would lead to significant decreased mortality. And most of us estimate that patients with TA-TMA are probably looking at a 20% survival. So you sort of lifted the curve back up to where you would expect survival to be from transplant. I mean these are patients, for the most part, who have underlying hematologic malignancies. And so there is always the risk of relapse and other complications that lead to this type of survival. So those curves, actually, to me are very encouraging even if you may say, well, 15% isn't that great. That's actually in the transplant setting what we expect to see. And I think then the endpoint, 15%, I think is a good place to start. I think the data actually is beyond that, by far. So I think the response rates are really dramatic.

Alessandro, anything you'd like to add?

Yes. I just wish to underline the fact that the proportion of patients who had additional clinical problems and particularly graft-versus-host disease, previous transplant-related infections and the multi-organ involvement makes a reason of an expected high rate of death, so-called transplant-related mortality in these patients. So the Kaplan-Meier curve that I showed you with those results long term illustrates quite well that this drug was able to modify the natural history of this disease in most patient, and this is very impressive to me beyond the result obtained at 100 days after the onset of the disease. So we were dealing with a very compromised patient population as -- and this must be taken into consideration.

Okay. Great. Regarding Slide 19, as you mentioned 100-day survival, could you speak to -- I mean this could be the company or from both of the doctors, the denominator in the complete responders? So why 17? Maybe I missed it during the presentation.

I guess I did not get your question. Sorry. But if you can repeat it.

Absolutely. So if you look at the Slide 19, you have a patient population of 28 patients; you have a per protocol, 23; and for the complete responders, you're at 17. So out of curiosity, the reason for the 17 patients as far as out of the denominator for that one?

17 patients were -- so the difference in the -- between the 28 and 23 was the amount of drug that we were able to deliver to these patients. So the difference between those who were actually in the condition to proceed during the treatment. And the 17 patients were those who achieved a complete response with the treatment. And so...

Yes. So just to add to what Dr. Rambaldi is saying, the complete response is 17 of 28. That's how in the -- I'm sorry, we're now on -- you're asking about the 100-day survival. Those are the 17 responders. So 17 of 28 patients responded. 23 of the 28 patients received the per protocol treatment of 4 weeks of dosing. So I don't know, does that help? That should help.

I can't hear...

We're not hearing a response. Andreas?

Andreas has actually dropped. Our next question will come from the line of Serge Belanger from Needham & Company.

Just a couple questions from me. The first one is for Dr. Perales and Rambaldi. Just a follow-up on the 15% FDA-agreed efficacy threshold for the primary endpoint we mentioned. This was a new endpoint, so what was the prior benchmark used for this indication? And is the 15% -- I guess how did the FDA come up with that number? Is that what you typically see in your practice with the current supportive care for HSCT-TMA?

I mentioned there was no prior benchmark because this is a disease where there hasn't really been an effort to move a drug forward. So this is why I think it was important to develop a clinically meaningful endpoint. And I feel, as I stressed earlier, that this endpoint that includes both laboratory and clinical parameters speaking directly to and organ disease is meaningful. So how do you pick a number in that setting? I think with our supportive care measures, I don't think we hit 15%. But I mean the -- especially, the patients on the better end of the spectrum, if you will, do respond to some supportive care measures, but the patients in this study who were -- or had high risk, I would not expect supportive care measures to significantly change the course. And I think without knowing where to start, you do have to pick a number. And even 15% would be great in these patients who otherwise really have a very poor outcome.

I just like to add that this study for the first time predefines the response criteria and parameters. If you go into the literature, you can see that all the available data are retrospective data describing occasional experience with no predefined endpoint. So for the first time in this effort, we set both clinical and laboratory response criteria. And this is something very new. And I'd just like to underline the fact that the patient population enrolled were severely compromised patient indeed. So.

Okay. And my second question for Greg. What's the current thinking in terms of marketing plans and requiring marketing footprint for this product and its potential launch in around mid-'21?

Sure. Let me ask Dan, our Chief Commercial Officer, to address that.

Sure. When we think about commercialization of narsoplimab in this setting, we are looking at the market itself. And we've seen over the last 1.5 years increased understanding in our market research of both the endothelial injury syndromes, including TMA, as well as the role of the lectin pathway. So we are closely monitoring that to, again, prep our messaging and platforms and campaign. Also to our infrastructure, if you can think of the United States, there are roughly 25 centers that make up almost half of the allogeneic stem cell transplants in the U.S. We are targeting them and working with different parts of Omeros with them already, including Memorial Sloan Kettering that Dr. Miguel Perales is here today. We are also building out our infrastructure. We've hired our sales leadership, our sales leaders in place. We've identified our first layer of management in the sales force. Upon file completion, we will be extending offers to them. And we are already working on building out our sales reps and other infrastructure. Our medical science liaison team is already deployed on the medical affairs side as well. From a coding perspective, we have applied 4 codes for procedural, an ICD-10 procedural code for narsoplimab. And that presentation was in September with CMS held a town hall, and we presented our data there and our case for a code. CMS has preliminarily agreed to that code, but we are -- just finished our comment period. Also, we have applied for a code for an ICD-10 -- sorry, diagnosis code for HSCT-TMA. And that was presented at a meeting that was hosted from the CDC and plenary have support from them for that. We are in comment period right now. I will mention that Dr. Parameswaran Hari, who is the Chief of hem-onc at the Medical College of Wisconsin, a Scientific Director at CIBMTR and Secretary of ASTCT, had presented on behalf of Omeros the need for diagnosis code here and to really identify code and track these patients, which will help the launch. Also, last week, we did complete and file on time our new technology add-on payment application with CMS that has been completed. There will be a meeting in December. And we'll find out next year the ruling on that. So from a coding perspective, we feel very confident that we're preparing the market from infrastructure we are building on appropriately. And we're seeing very good signs in the market regarding understanding the lectin pathway, endothelial injury and specifically HSCT-TMA.

Our next question will come from line of Andreas Argyrides from Wedbush.

All right. Sorry for getting chopped off there. I'll go back and listen to some of the -- the response to the question. And if anything, I can follow up. Just a quick one on OMS906. This is for the company. You guys presented slides earlier in the week. When might we get a first look at that data? And when might we also have that up on clinicaltrials.gov?

I think first, look at the data [Technical Difficulty]

Greg, can you hear us?

All right. Operator, are you able to hear us?

Can you -- can either of you -- can either of you hear us? No?

Yes, I can hear you.

You can? [Technical Difficulty] Okay, I think I'm not sure that you folks are able to hear or not. We're feeling a little... [Technical Difficulty] And like MASP-2, MASP-3 inhibition does not affect the lytic arm of the classical pathway. So like narsoplimab, we expect that OMS906 will not have the infection problems seen with other complement inhibitors. Let me stop there and see if we can hear on our end any questions and if there's anything else that we can run through.

Yes. I have a question from the line of Steve Brozak.

Yes. Again, if -- with your indulgence, I'd like to ask a question to Dr. Rambaldi. Dr. Rambaldi, obviously, you had, had great success in treating patients with COVID. You had mentioned one thing mentioned before everything got cut out, specifically that you're seeing a second wave take place. Have you treated anybody in this second wave? Or are you planning on doing that as well because that is obviously the first question that comes to mind.

Alessandro? Alessandro? I think Alessandro -- Steve, can you hear me?

Yes. Yes, I can.

Okay. Let me see if Alessandro can speak. He's not hearing the question. So again, we have some sort of technical difficulty.

I can hear you there. Actually asked you a question just now.

Okay. Alessandro? Steve, your question was, have we treated anybody else in Bergamo? Was that the question that you asked?

Yes, yes. Anyone else? And are you planning on treating anyone else as well? If not...

Look, I will speak for Alessandro because I think he's not able to hear the question. As Alessandro would tell you, the beast is back in Italy. And we have treated an additional patient. We expect we will be treating more patients. We look to put together a control trial in Bergamo. I know that Alessandro would like that very much. The patient that we just recently treated, I'll give you just a bit of background, this was a 74-year-old obese, diabetic gentleman, a long history of smoking, COPD, status post-surgical treatment for prostate cancer, so obviously, a patient at high risk. And the patient came into the hospital, quickly deteriorated from nasal cannula to mask to CPAP and then intubated. We began treating the patient following intubation. And right around the second dose of narsoplimab, the patient was extubated. Really the most remarkable thing about those data, though, we have the laboratory data on this patient as well. And ALT/AST. AST has been linked, I think as you know, to critically ill COVID patients. LDH, all normalizing quite dramatically. But probably most impressive, the D-dimer values. D-dimer values are returning to normal, again, in this patient. So again, we're talking about small numbers of patients. We are treating others in the U.S. as well. But I think all signals point to the fact that narsoplimab kind of clearly works well in critically ill patients. And we are working hard to make that drug more readily available. That includes manufacturing. We have stepped up our manufacturing on the drug as well. And we think we'll have more to report in the not-too-distant future around the COVID program.

And I'm actually not showing any further questions in the queue at this time.

Okay. Well, first, I'd like to apologize to everyone for the technical difficulties. I'm not sure where those are originating. But we appreciate your patience. I'd also like to thank Professor Rambaldi and Dr. Perales, again, for participating this morning and to all of you for taking the time to listen in. We expect that narsoplimab is going to be an important drug, not only for endothelial injury syndromes like TA-TMA, but really for a wide range of diseases and disorders. And we look forward to its approval in TA-TMA. And then we plan to quickly expand from there. As always, we appreciate your support. Have a good rest of the day. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.