Good afternoon and welcome to the CytoSorbents' Third Quarter 2020 Financial and Operating Results Conference Call. At this time all participants are in a listen-only mode. Following the formal remarks we will open the call for your questions. Please be advised that the call will be recorded at the company's request.

At this time, I would like to turn the call over to our moderator, Jeremy Feffer. Please go ahead..

Thank you, Stacy and good afternoon. Welcome to CytoSorbents' third quarter 2020 financial and operating results conference call Joining me today from the company are Dr. Phillip Chan, Chief Executive Officer; Vincent Capponi, Chief Operating Officer and; Kathleen Bloch, Chief Financial Officer; Dr. Efthymios Deliargyris, Chief Medical Officer; Dr.

Christian Steiner, Senior Vice President of Sales and Marketing and Managing Director of Cytosorbents Europe GMBH; and Christopher Cramer, Vice President of Business Development. Before I turn the call over to Dr.

Chan, I'd like to remind listeners that during the call management's prepared remarks may contain forward-looking statements which are subject to risks and uncertainties. Management may make additional forward-looking statements in response to your questions today.

Therefore, the Company claims protection under Safe Harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Actual results may differ from results discussed today, and therefore, we refer you to a more detailed discussion of these risks and uncertainties in the company's filings with the SEC.

Any projections as to the company's future performance represented by management include estimates today as of November 4, 2020, and we assume no obligation to update these projections in the future as market conditions change.

During today's call, we will have an overview presentation covering the operating and financial highlights for third quarter by Dr. Chan and Ms. Bloch. Following their presentation, we will open the line to your questions, during the live Q&A session with the rest of the management team. At this time, it's my pleasure to turn the call over to Dr.

Phillip Chan.

Phil?.

Thank you very much Jeremy and welcome everyone to the third quarter 2020 earnings call for Cytosorbents Corporation. We had an outstanding third quarter marked by numerous accomplishments. First, third quarter 2020 total revenue grew 73% to $10.5 million and product sales grew 79% to $10.2 million over the third quarter of 2019.

Trailing 12-month product sales were $34.5 million. Secondly, we delivered more than a 110,000 cummalative Cytosorbents today, up 51% from a year ago and up 10,000 from our recently announced milestone of achieving more than 100,000 devices delivered.

We also achieved blended product gross margins of 74% in the third quarter compared to 77% a year ago, but sequentially higher than the 70% in the second quarter of this year due to higher percentage of lower margin distributor sales and higher cost of rents COVID-19 production.

In July, we completed a $57.5 million financing led by Cowen and SVB Leerink with co-manager B. Riley FBR strengthening our cash balance to roughly $88 million at the end of the third quarter. The REFRESH 2 data monitoring committee also recommended resumption of the trial following a favorable review safety data.

In terms of COVID-19 we have now seeking an estimated 2,800 COVID-19 patients in more than 30 countries around the world, including here in the United States, and are working to capture these data in the CTC COVID-19 registry.

We also established collaborations to commercialize CytoSorb in the United States and 25 states with Terumo Cardiovascular, InvoSurg, and Surgical Partners and are working to cover the other states as well currently.

We also hosted a key webinar on the use of CytoSorb for webinar on the use of CytoSorb for Antithrombotic Drug Removal with key opinion leaders and users of CytoSorb for this application in July. We were also awarded a $4.4 million contract from the DoD to complete HemoDefend-Blood Group Antibody pre-clinical development.

And we also expanded distribution to pull 66 countries, including Brazil. With our strong financial performance and solid cash position, coupled with a strong current and anticipated demand for CytoSorb, we are executing a number of key initiatives to drive growth. These are in two major areas. One is commercialization, and sales.

And the second is clinical trials. On the sales growth strategy side, one of our first goals is to maximize the COVID-19 opportunity. We're well positioned in Europe and throughout the world to help in this next wave. We also have established collaboration in the United States, establishing key relationships throughout the country.

Second of all, as COVID-19 fades, which is expected to happen next year with the approval of vaccines for COVID-19, we plan to return to our pre COVID-19 growth strategy. This is detailed very extensively in our press release today.

So I'll only cover this very briefly, but the key tenants of the strategy are the focus on driving both direct and distributor sales, to maximize the Ticagrelor and Rivaroxaban E.U.

approvals, to expand in new applications such as liver disease, and also cardiac surgery, such as endocarditis and other applications, to expand our international team with a focus on commercialization, manufacturing, clinical and R&D.

To expand our plan, to be able to get to the next level of scale, to be able to produce somewhere on the order of $300 million to $400 million in sales of products and thereby helping also to drive expansion of our blended product gross margins, to prepare for us commercialization, which currently involves hiring a new VP of Sales for the United States to help manage COVID-19 sales, but to also prepare for potential feature approved applications in the United States, such as the removal of Ticagrelor and other applications.

And then finally, to streamline our balance sheet and in particular, to come up with a strategy, either refinancing or repayment of recurrent debt and that process is underway. But with that, I'd like to focus more on the clinical program. And with that, I'd like to turn it over to Dr. Efthymios Deliargyris, our Chief Medical Officer.

Makis, if you may be on mute..

Apologies. Thank you, Phil. And good afternoon to everyone on the call. On a personal note, it's been a very exciting for six months for me with the Company. And I'm very pleased today to be able to present to you with the overview of our clinical activities and our clinical plan going forward.

During this last six months, I've had the chance to spend extensive time with my colleagues within CytoSorbents, prioritize our targets and finalize our clinical plans.

During that time, we faced significant challenges for COVID-19 across our clinical programs, but we also encounter significant opportunities, and we'll discuss with you a little later about the COVID-19 related clinical activities.

And finally, as you heard already from Phil, and you're going to hear in more detail from Kathleen later, we have now the available funds to expand on our clinical capabilities and execute an ambitious clinical plan.

As noted on this slide, we will focus on both areas of applications of Cytosorbents that we're seeing practice today in Europe, and that is a critical care, therapeutic area and cardiovascular disease, and specifically cardiac surgery. We have identified six specific priority therapeutic areas that we will target with our clinical programs.

In the critical care space, we will focus on shock reversal, where CytoSorb device can be very effective by removing cytokines and providing rapid hemodynamic civilization.

We will also focus on acute liver failure and liver applications with the removal of liver toxins as a bilirubin or ammonia, coupled with cytokine removal can be extremely effective in reversing the clinical course in this patients.

We will also continue to expand our clinical activities in the COVID-19 space, where again, quenching the cytokine storm with CytoSorb especially in the setting of a combined therapy with ECMO has shown substantial clinical benefits so far.

In the cardiovascular arena, our three targets will focus on antithrombotic removal, known as ATR on the slide, where we have specific bench and a ready clinical evidence, a very efficient removal of these antithrombotic agents by CytoSorb in the operating room.

We will also focus on endocarditis, with cytokine removal and hemodynamic stabilization could lead to substantial clinical benefits in this acutely ill patients faced with high mortality otherwise. And of course, we will continue our clinical program in preventing acute kidney injury in patients undergoing complex cardiac surgery.

We will implement the complimentary approach. Although heavily focused on randomized company sponsored clinical trials, we will also implement innovative other designs to complement data generation, including therapy registries, and single center or single arm prospective trials.

On this next slide, you will note the type table associated with the execution of these programs. Programs like the CTC Registry in COVID-19, The REFRESH 2 trial in acute kidney injury prevention in cardiac surgery, the STAR Registry in antithrombotic removal and the TISORB Study also looking Ticagrelor removal are already on going.

Early into 2021, we plan to initiate three trials in Germany, including the randomized clinical trial in shock reversal process, multicenter trial in Germany. The HepOnFire, single-arm study in patients with acute on-chronic liver failure, again, initiated and executed in Germany.

And finally, our second Ticagrelor removal study called CyTATION is a multicenter PK-PD study also executed in Germany. In the next 12 months after that, we plan to initiate substantial clinical programs in the U.S, including a large randomized shock trial in the U.S. a liver trial in the U.S.

and then the follow-up trials in both novel oral anticoagulant and ticagrelor reversal in multicenter randomized clinical trials in the United States. Next slide. Next slide please. There's a bit of a delay. In addition, we'd like to provide you some specific updates.

Relating to our path to FDA approval, we'll continue to be on a dual path with a REFRESH 2 pivotal trial and the breakthrough designation and ticagrelor removal. During the third quarter, we made progress on both fronts.

Specifically for REFRESH 2, as you already heard, an interim safety analysis was completed with data from the first 152 patients enrolled in the trial that were reviewed by the data monitoring committee and the FDA who both recommended study continuation without major modifications.

The study resumption process has already been initiated and pending COVID-19 related delays, we believe that patient enrollment will commence again in the first quarter of 2021.

In relation to the ticagrelor breakthrough designation, we believe that we have made significant progress in our discussions with the agency during our recent teleconference, and that we are very close to a regulatory path forward that's consistent with breakthrough designation status.

More specifically, we aligned fully on the significant unmet medical need to remove the ticagrelor during urgent and emergent cardiothoracic surgery.

We also reviewed together and discuss additional data that we believe support the very positive benefit risk profile of CytoSorb for this application, including data that will be provided by our studies in the U.K., which is the title of study in Germany, which the CyTATION study.

And finally, despite COVID-19 related resource shortages and challenges at FDA, the review team provided assurances that they will work with us with the necessary speed and urgency consistent with a breakthrough designation for this indications. Moving on to TISORB study, which is a U.K. ticagrelor removal study.

Non COVID-19 related clinical activities continue to be challenged in the U.K, either related to institutional R&D, lockdowns, or prioritization of COVID-19 related vaccine trials. Regardless, our clinical team is working diligently with CytoSorb sites to address these challenges and commence enrollment as soon as feasible.

Moving onto the REMOVE randomized clinical trial. As we already discussed, COVID-19 has been a challenge worldwide. This also applies to this completed 250 patient German government funded investigator sponsored randomized control trial that investigates the use of CytoSorb’s in patients undergoing valve replacement surgery for infective endocarditis.

We remain in close contact with the investigators who are working diligently to have top line data from the study as soon as possible.

Despite suffering COVID-19 related delays in data monitoring and analysis, we believe that the top line results may be available as early as before year's end, and the detailed data and results presented at international scientific meaning and submitted for publication in the first half of 2020. Next slide, please.

On a positive note, COVID-19 has also given us the opportunity to treat critically ill patients with Coronavirus in ICUs in many countries around the world, including the United States under emergency use authorization.

As listed on this slide, we have launched a number of dedicated initiatives to capture data from an estimated 2800 COVID-19 patients who have been treated with CytoSorb worldwide. As we recently announced, the CTC registry is live and actively enrolling patients from U.S. centers with an initial analysis planned for years end.

As a next step, we're expanding the CTC registry to countries with large experienced international. Additional data collection and pooled analysis are in progress to consolidate the experience from smaller countries and from single sites with a large number of patients.

The intent is that all these initiatives will generate high quality data, both on clinical outcomes and best practices for the use of CytoSorb COVID-19 patients and lead to multiple publications. In fact, initial case reports and case series have already been published. And with that, I would like to turn it back to Phil..

Thank you very much, Makis for that overview.

And now I'd like to turn the call over to Kathy for financial overview, Kathy?.

Thank you, Phil. And Greetings, everyone. So for today's call, I'll provide an update regarding our third quarter 2020 financial results. And in addition, I'll talk about our working capital and cash runway. Next slide.

So our CytoSorb product sales for the third quarter of 2020 were $10.2 million, which is an approximately 79% increase over product sales of $6.1 million for Q3 2019.

And this increase was driven by an increase in direct sales of approximately $2.1 million, resulting from sales to both new customers and repeat orders from existing customers, and also an increase in distributor sales of approximately $2.4 million.

Now the Euro to dollar exchange rate increased from an average rate of $1.11 in Q3 2019 to $1 17 in Q3 2020. And this had a positive impact on our third quarter 2020 sales of approximately $428,000.

And though it's difficult to quantify, we did estimate that approximately $2.7 million of total product sales in the third quarter of 2020 were due to the demand for CytoSorb to treat COVID-19 patients.

Our total revenues, which includes both product sales and grant revenue, was approximately $10.5 million for the third quarter of 2020 as compared to $6.1 million for the third quarter of 2019, which represents an increase of approximately 73%.

And importantly, our third quarter 2020 gross profit grew to $7.7 million, which is an increase of 74% or $3.3 million greater than our gross profit for Q3 2019, which was $4.4 million.

Our gross profit margin on product sales were approximately 74% for the third quarter of 2020 as compared to 77% for the third quarter of 2019 primarily due to an increase in the percentage contribution of lower margin distributor sales, as well as due to some additional COVID-19 incentive payments to employees as a result of our continuing efforts to ramp up production.

Next slide. And then turning to our nine months financial results product sales for the first nine months of 2020, were at $27.9 million, which is an increase of 73% over product sales of $16.2 million for the same period in 2019.

Sales to hospitals in the United States under the emergency use authorization, granted by the FDA were approximately $928,000 for the nine months ended September 30 2020.

And once again, we indicate it's difficult to quantitate but we have estimated that approximately $6.9 million of our total product sales in the nine months ended September 30 2020, was due to demand for CytoSorb to treat COVID-19 patients.

We do note that this increase in sales was offset to some extent by decreases in sales related to elective procedures which were avoided or postponed during the COVID-19 pandemic, such as in cardiac surgery where CytoSorb may have otherwise been used. The change in the Euro to U.S.

dollar exchange rate did not have a significant impact on sales for the nine months ended September 30 2020, as compared to the same period in 2019. Next slide.

Looking at our quarter-over-quarter product sales, with the third quarter of 2020 and our product sales of $10.2 million, we achieved another record quarterly product sales growth, with the third quarter of 2020, representing our fourth consecutive quarter-over-quarter growth in product sales.

Sales in 2020 have been positively impacted by demand for CytoSorb to treat COVID-19 patients in the ICU. And given the order of patterns that we are currently experiencing, we expect that the COVID-19 pandemic will continue to have a positive impact on product revenues for the remainder of 2020.

However, this may change in the future should the pandemic be contained. Next, next slide, we look at our trailing 12-months product sales. And as you can see from this chart, overall, our annual product sales growth continues to be very, very strong.

In addition, year-over-year gross margins adjusted for 20 -- in 2020 for the COVID-19 related incentive payments to employees during the ramp up of production continue to rise and they would be 77% if we didn't have those COVID-19 related ramp up costs. And finally, let's take a look at our working capital liquidity and cash flow.

So as previously mentioned, at September 30 2020, we had approximately $88 million in cash, which is the most that we've ever had. And this increase in cash over the prior quarter was a direct result of our July 2020 equity raise, which generated approximately $53.8 million in net proceeds to the company.

We believe, we now benefit from a solid capital foundation, and that the existing cash will provide a runway to beat our operating needs well into the foreseeable future. With regard to our operating strategy, we intend to prioritize our spend around one generating clinical data and obtaining U.S.

FDA approval, two, securing and expanding our production capacity, and three driving worldwide sales, growth and acceptance of CytoSorb as standard-of-care. And I also want to take a minute to mention our current position with regard to our $15 million term loan with Bridge Bank.

We are finalizing a comprehensive analysis of alternatives with regard to the debt financing.

And these alternatives include but are not limited to refinancing the existing debt and extending the interest only period expanding the amount of debt financing available to the company now, and or in the future, repayment of the current debt, as well as repayment of the current debt now, but retaining a commitment for debt availability in the future.

And we have been in extensive discussions with Bridge Bank, our existing bank, as well as other extremely reputable lenders. And with the best interest of our shareholders in mind, we are weighing all of our options and deliberating closely with our board of directors.

And we expect to finalize our decision with regard to the debt in the very near future. Lastly, just turning to our capital structure. As of September 30 2020, we have approximately 48.6 million common shares outstanding on a fully diluted basis. And with that, I'd like to turn the call back to Phil..

Thank you very much, Kathy. And in terms of guidance cytosorbents has now historically given specific financial guidance on quarterly results until the quarter has been completed. However, provided that the current order pattern continues, and notwithstanding uncertainty related to the COVID-19 pandemic.

We expect that the fourth quarter 2020 sales will be one of the company's strongest quarters to date. That concludes our current prepared remarks. Operator, please open up the call for the Q&A session..

Thank you. [Operator Instructions] Our first question comes from Anthony Petrone with Jefferies Please go ahead..

Hi, thanks and congratulations on the good quarter, hope everyone's doing well.

Maybe, hi, how are you? Maybe I can start a little bit with COVID just in light of where the recent case counts are I mentioned 2.7 million in the quarter you do have multiple regulatory clearances, whether it's emergency use authorization or full clearances at this point.

So I'm just wondering how much stocking is there geographically, when we see where case counts are going, where ultimately do you think hospitals will position themselves with having CytoSorb on the shelf to deal with severe cases? And sort of as we go forward on the regulatory front, should we be expecting any additional authorizations and/or clearances? And then I'll have one more follow up..

Yes, so I think that in terms of building inventory ahead of what is expected to be a very difficult and, and severe winter season for COVID-19, and flu, we have seen centers order in the third quarter in advance of the fourth quarter.

However, I think that most of the existing stock that has been taken has been designed for patients who are currently ill and, and so it's a mix of the two. In terms of potential other regulatory approvals or emergencies authorizations throughout the world.

I think at the current moment, we are well positioned again, we have the ability to sell this in 66 countries around the world, for the treatment of cytokine storm. And because of that, we can be used in any country today that we're currently registered in to be able to treat COVID-19. So they're not necessary.

We did get some approvals earlier, some authorizations earlier from Israel, for example, and from India. But again, those are not necessary to be able to use our therapy in COVID-19..

And then maybe the two thoughts, here would be and I'll get back in queue. The first would be just in terms of Germany, this was a ramp here in terms of the sales force, maybe just an update on you know how that process is going.

And really the time you expect it to take the additional sales rep to really, begin contributing the CytoSorb sales in Germany specifically. And then you reference plant expansion, in the U.S. just maybe a little bit on timing as to when you'll begin to actually break ground on plant expansion.

You mentioned to support 300 million to 400 million in sales, but what level of CapEx will be committed to that expansion plan? Thanks..

Sure. Anthony. Two good questions. Let me turn the first one over the Christian Steiner, Dr. Christian Steiner, our Senior VP of Sales and Marketing in Germany. And then the second one, Vince Capponi, our President and Chief Operating Officer if you could take that one. That would be great.

Christian?.

Thank you, Phil. Thank you, Anthony for the question.

Can you hear me right?.

Yes, yes..

Okay, very good. Yet in terms of sales force, in Germany, actually we have finished the build-up of the sales force end of last year beginning of this year. And also the training for all the sales reps was finished in the first quarter.

I think the COVID-19 pandemic has led to the to the case that we also had quite some time to expand the training for the sales reps and bring them on speed on and I think everyone is at the right pace from Q2, still we have restricted access regulations for the sales reps in the hospitals.

But as soon as we can access the hospitals 100% everyone is ready to ready to go. Yes, I think that's for the sales force..

Great, Christian. And, Vince, if you could maybe take that question on manufacturing and CapEx requirements for that, and the time..

Sure. All right. Thanks, Phil. So regarding your question about starting and CapEx expenditure, we are intending to actually zero in on the close of potentially new building here in first quarter of next year, in which case, then it's going to take us roughly 12 months to build that out and actually have it approved and capable producing product.

We expect that that's going to be about with obviously, landlord contributions as well as on around of about $5 million build out to be able to support about a $300 million business.

Did I answer your question?.

Yes. Absolutely. Thank you..

Next question comes from Andrew D'Silva with B. Riley. Please go ahead..

Hey, good afternoon. Thank you very much for taking my questions. Just to follow up on the manufacturing question, as it relates to the current manufacturing facility.

Two parts, one, do you think as you close out the year, you'll be back at that 80% gross margin level? You noted 77% without ramp up the incentive payments, so seems like you're almost there? And then have you reached the ability to, to produce at full capacity near that $80 million annual number?.

So go ahead Phil. Sorry….

No, no, I just pass it on to you Vince..

All right. Thanks, Andrew, for the question. So with respect to the gross margins, as you could, as you Kathy mentioned, we're roughly at the without the incentives, etcetera around the 77%. We expect to be if you take those incentives out, etcetera we'll, expect to be close to the 80% gross margin.

Our efficiencies are improving, as we've now started to come up to for expansion, if you will we're not completely there. And again, we're balancing with demand. So we don't want to go too excessive here. But basically, we are on knocking on the door of that 80% gross margin is, is the bottom line.

Again, I think our efficiencies if approved now, taking out the incentives, etcetera we should be very close to that. With respect to being at the full 80 million capacity if you will, $80 million capacity, we're balancing again, the operation relative to what we see as the orders and Christian’s forecasting.

So certain parts of the operation, we run more, if you will than other parts, but I will say between April of this year, and now we've actually added another production line to help increase, if you will, the velocity of product of which we could put out of the plan.

So that has helped us keep up with Christians demand and be able to supply the market with this, obviously, with this COVID-19 situation. Does that address….

Yes, your two lines now, or are there?.

We're actually at three lines. We're actually three lines now..

Okay, perfect. Thank you for that. And then on the clinical side, you're clearly investing a lot more now on internally funded trials. One notable you stood out in your press release was related to septic shock. That's been historically a fairly challenging bar to hit.

Just curious if you could talk around why you believe now is the right time to pursue that.

And, any differences that you see whether with regulators or from a efficacy standpoint, that gives you confidence to go about that now versus before?.

Oh, yes, Makis, would you like to take that?.

Thank you. Yes. Thank you for the question. The academic community and the thought leaders in Sepsis have for many years suggested that alternative be the measures of randomized clinical trials and that the field should move away from just testing everything against mortality, since that bar is too high to reach.

So in that regard, we recently saw over the last few years, some regulators fall into that line, and recently approved vasopressor based on blood pressure stabilization in people with shock.

So we believe that the ability to now execute clinical trials with innovative endpoints that are clinically meaningful, and now more and more accepted by the regulators makes it an opportunity for us to do to execute clinical studies, especially because the consistent message we're getting from users in the field that one of the most evident benefit they see when they connect CytoSorb to the septic shock patients is this immediate hemodynamic stabilization, with a reduction for the need of a vasopressors with the additional drugs to maintain blood pressure, and the rapid return of the mean arterial pressure, the two levels that are considered to be now stabilized.

And therefore the can improve the other treatment that are necessary for these patients as getting rid of fluids and improving the ventilator setting. So it's twofold.

One, we think the performance of CytoSorb in everyday practice is compelling, and it’s highly for us, it makes us very confident that we can, we can show that in a clinical trial setting.

A second of all is the evolution of both the academic community of regulators into looking into new innovative endpoints that we believe we can we can deliver using such new endpoints in his trials..

Okay, great. And just the last question for me and I get this from clients a lot. It's just related to HemoDefend-RBC, versus HemoDefend-VGA, if you could just discuss where you are, and the development paths for both those. And if there's any other opportunities, you should be thinking about that product line..

So with the HemoDefend red blood cell product, this is a product that is designed to reduce non-infectious contaminants from platelet blood cells, such as cytokines, antibodies, bioactive lipids, potassium, and a wide variety of other contaminants that can cause potential transfusion reactions.

And so this is a program that is subsequently subsidized by National Heart, Lung and Blood Institute. And as we've discussed in the past, this was making its way towards human clinical studies. And then potentially for, we would then apply for approval in the United States.

So, because of COVID-19, it is essentially slowed that program significantly to the point where, because we need to conduct some additional bench studies, and also healthy volunteer studies. This is, has made limited progress over the past several months.

That being said, it is very much still on in our pipeline and very much one of the things that we will be moving forward in a post COVID environment. The second program is the HemoDefend BGA program.

And this is a product that is designed to remove anti-A and anti-B antibodies from plasma as well as whole blood as a way to create a universal plasma product that is not blood type specific.

That can be used off the shelf rapidly and given to trauma patients are critically ill patients or used in plasmapheresis and plasma exchange for example or used actually in a broad, a broad supply chain I guess in the area of plasma processing and production of factors such as albumin and coagulation factors for example, where they do not need to worry about the blood-type specificity of that plasma unit.

So that's the value of universal plasma.

And then, the second application is one in the ability to give whole blood transfusions, which the military believes is a superior alternative to giving rather than giving component in its such as pack red blood cells and platelets and plasma for example, in terms of trying to stop hemorrhaging and bleeding related to combat casualty injuries.

And so this is a program this year, actually that we have received now 8.5 million in funding to complete the preclinical development and advanced this product to human clinical studies and eventually approval. And so, this is a program we are well funded for, and are moving aggressively. It's one of the priorities of the company outside of CytoSorb.

And, and our goal is to, get this to a, out of the pre-clinical realm within the next year and a half or so. So I think that, COVID-19 has, has slowed everything down in terms of, being able to work in the lab, etcetera. So we lost some time there.

But that being said, our R&D folks are now back in the lab and we are continuing to move these programs forward..

Okay, thank you for the color and congrats on all the progress this year. And best of luck closing out 2020..

Thanks a lot, Andy..

Next question comes from Josh Jennings with Cowen & Company. Please go ahead..

Hi, good evening. Secondly, congratulations on the strong results. Hi, Phil, and thanks for all the details on the call. I just wanted to ask about the STAR trials and wanted to see if you had, could help us think about potential primary endpoints or secondary endpoints for this trial, or those two trials.

Just to start with that?.

Sure.

Let me turn it over to Makis just for some additional color, Michael?.

Thank you, Phil, and thanks for the question. So the acronym STAR stands for safe and timely antithrombotic removal. So the idea is that the STAR program will be comprised of a series of studies to look at different important areas for this application. STAR1 is the registry.

As you probably aware, we have CE Mark approval in Europe for removal of ticagrelor and rivaroxaban. So this is happening now in practice. And we have actually now collected, a user's survey that suggests that over 400 cases have already been treated that way.

So the intent of the STAR 1 program will be to capture real world outcomes with its use, and be able to obviously, to publish this data, which we believe will be very compelling and informing other institutions to establish this as a standard-of-care in the approved regions.

The STAR 2 and STAR 3 programs are meant to complement with new information, the STAR 2 specifically looking into drug removal itself. And as per the FDAs own guidance, the gold standard in clinical studies to detect measure removal of drugs, and obviously reversal of the drug effect is by doing PK-PD studies.

So we plan to utilize an extensive program, looking at the PK-PD parameters of using Cytosorbents in patients with every one of the direct oral anticoagulants such as Rivaroxaban, or Apixaban, or dabigatran, and Ticagrelor as we're doing in the CyTATION, and the TISORB trials.

So the start to program is meant to provide a definitive mechanistic PK-PD data of definitive drug removal by CytoSorb.

And then STAR 3 will be the late stage where we're going to show in those randomized clinical trials, the implementation of this approach as a standard-of-care and the associated clinical benefits when it comes to bleeding reductions obviously, those are the most obvious ones, but also substantial economic benefits.

We believe that this application has a tremendous value proposition.

It’s not just a reduction in clinical outcomes, it’s the improvement in the efficiency of care, and the throughput of these patients that today, in today's practice, they're basically sitting around in the hospital waiting for these drugs to wash out before they can have unnecessary operation or intervention.

So the STAR, the STAR platform consists of many programs, all of them designed to provide the full picture of real world use, drug removal, mechanistic evidence, and then of course, clinical outcomes and economic performance data..

Excellent.

And just a follow up on STAR 3, will that include patients on NOACs as well as Ticagrelor?.

Yes, we believe that. Short, we believe that the application has the exact same benefits, including, again, the clinic the reductions in clinical indices of bleeding, and also the increase in efficiency. So, so we plan to invest in generating data on both Ticagrelor and the NOAC class..

Great, thanks for that. And then just had a question on the registries for critically ill COVID-19 patients of the U.S. based registry CTC, 500 patient registry, a bunch of other registries worldwide.

Could you potentially use that data for a submission for a specific CytoSorb to indication in the United States?.

So let me let me turn that over to Phil, or Vince to provide you more of the regulatory side.

So Phil or Vince, do you want to take that one?.

Yes, I think the goal of the registry and COVID-19 is really to generate the clinical data on the treatment of complications of viral Sepsis. So it turns out that COVID-19 as a virus, just like the flu, for example, is causing a viral Sepsis leading to an organ injury, particularly lung injury, shock, and kidney injury.

And these are common complications in a wide variety of different infections, including viral infections, such as influenza and COVID-19. So although the data from the registry we don't believe would be sufficient to drive U.S. regulatory approval, it may be sufficient in other countries, but not in the United States.

We do believe it will provide a key level of data to be able to begin studies in viral Sepsis, particular influenza, which is which is perennial, that happens every year, comes back every year, and there are millions of patients, 10s of millions of patients who get flu every year in the United States, 40, 50 million last year alone, leading to about 25,000 400,000 500,000, hospitalization, and about 25,000 to 30,000 deaths.

And so we think that any progress that we can make with COVID-19, will be potentially leverageable to do a definitive study in flu, for example, that could be a perennial source of revenue for us on an on-going basis..

Now, thanks. That makes sense. Appreciate that. And my last question, just the distributor team or your distributors generated some nice sequential momentum I think 20% sequential revenue growth from that channel.

Can you talk about the drivers? And was it mostly COVID related? Or did you also see demand and/or utilization from the Ticagrelor and rivaroxaban removal indications and -- your thanks for taking the questions guys?.

Sure, Josh, let me turn it over to Christian to give some color on the distributor sales, and where that's coming from? Christian?.

Thank you. Thank you, Josh, for the question. Yes, I think you're, you're right in assuming that COVID plays a role. But that's not the whole story. So I think in that we are currently in more than 60 countries, and takes quite a long time to prepare the markets together as partners. And in many countries, this has been for the last few months and years.

And so the countries or markets were ready at the time when COVID kicked in. And this gave us a kind of head start that we could quickly use the infrastructure in these countries and, and cover the demand. So it's both. It's, on one hand a continuous drove on the on our standard indications, and the kick was really by COVID-19..

Excellent. Thank you..

Does it make sense?.

Yes, I think also, for example, Latin America, which shows you know, we just opened this year. We expected actually, in fact, a much longer ramp to market penetration in many countries within Latin America.

However, the COVID-19 pandemic has really accelerated that usage and adoption, places like Colombia, and many other countries throughout Latin America.

And so I think, that we see as going to have a lasting benefit, even when COVID-19 goes away, that the positive outcomes or the positive outcomes that they've been seeing should help translate into usage and other applications as well..

Great. Thanks for those details..

Next question comes from Danielle Antalffy with SVB Leerink. Please go ahead..

Hey, good afternoon, everyone. Thanks so much for taking the question on my first call, since initiating coverage. I appreciate it.

So just to follow up on Joshua's question, how do we think about the NOAC indication contributing as they come out on the other end of COVID? I mean, it's hope it's limited, the number of elective procedures being done in Europe.

So if we think about a ramp, there like, should we be thinking about it in line with elected procedures ramping? Or hope if you could give us even qualitatively some color there? And I have one follow up..

Sure. Thanks, Danielle. And great to have you on the call. Mikas, do you want to take that in terms of discussing how we feel that the market will develop with Ticagrelor removal, and also the NOAC? Mikas, you may be on mute..

Apologies. Thanks, Daniel, for the question. And this application as it relates both Ticagrelor and all the novel oral anticoagulants, it's an unmet need that's been around for a long time. These drugs have been available anti-thrombotics, for many years and there are Cornerstone now, for most of the cardiac patients over the last couple of decades.

And these new generations, drugs like Ticagrelor, which is considered by many to be best-in-class, and of course, rivaroxaban, apixaban that are replacing coumadin throughout the world are only increasing the penetration among cardiovascular patients.

So frequently, these patients require urgent care, either in the sense of having an accident or requiring an emerging operation. And these doctors, these clinicians are stuck with this management problem and they've been stuck with it for many, many years. So the difference in this market is that you do not need to develop the unmet need.

The unmet need is very clear and there is no solution right now. So we can tell you that the most common response we're getting from physicians when we present the evidence for this application is that this is a no-brainer for them to use.

So we feel now that we have an opportunity for education and communication of our early clinical data and obviously, as we're generating more clinical data even more so, and then we view this as a rapid transition to the standard-of-care for these managers of patients.

We don't see a slow ramp-up, we see a rapid adoption of this as long as we continue to support it with the necessary for clinical information..

Great....

I think....

Thank you for that. Go ahead. Go ahead, Phil. Sorry..

Oh, sorry. I think that we are -- I have mentioned in the press release that sales from our ticagrelor and rivaroxaban approvals that we received earlier this year have been, have not really made major contributions yet.

And I think part of the issue there is the fact that for those who don't know about it, we need to get out there and bring them and educate them as Makis mentioned.

And that's been limited because of COVID-19, in terms of medical conferences, in terms of being able to detail hospitals and talk them about the technology and how it's used, and also in training as well.

And so, I think that once we come out of COVID-19, and are able to now leverage our significant commercial resources to really bring this to clinicians all over the world, I think then, that is when you will see a significant uptick in usage..

Got it..

Those who know about it, really like it a lot, and that's the feedback that we've been getting..

Yes. So just a follow-up on that. So as we think about the upcoming U.S. indication and you're already -- presumably, you're in some centers already given in the COVID EUA, so just curious how to think about the go-to-market strategy, you have a good partner and Terumo. So how quickly should we be thinking about the U.S.

ramp here, is there a way to give us some color on the number of centers that already have this system and have experience? I appreciate it's in the critical care setting versus the cardiac setting, but still gives you an entree presumably into those centers to maybe help even qualitatively, give us some color there..

Yes.

So I think that the exciting thing about COVID-19 is that the patients who are -- it represents an opportunity to actually introduce the technology to cardiac surgery -- surgeons and perfusionist because one of the main modalities of rescuing patients who fail mechanical ventilation is a technology called ECMO, where we've had thousands of uses over the years using CytoSorb with extra-corporal membrane oxygenation, a machine that can oxygenated blood outside of the body when the lungs get so diseased that mechanical ventilation fails.

Typically, these patients will die and ECMO, which was designed in fact by our former Chief Medical Officer, invented by our former Chief Medical Officer, Dr. Robert Bartlett, that's one of the reasons why this is a growing modality in terms of artificial respiratory support throughout the world.

But that being said, we do not market CytoSorb off-label to the centers. However, what they are getting experience with is the concept of the use of CytoSorb to reduce cytokines as a means to improve -- to reduce deadly inflammation and also, how easy it is to hook-up to extra corporal systems.

So we believe that those centers will be prime and ready to go, when we actually look to launch this, if hopefully and when we get U.S. regulatory approval and will be the basis of that commercialization effort.

We also obviously run clinical studies in cardiac surgery here in the United States, REFRESH-2 for example is being done at 25 centers, major centers throughout the country, particularly on the East Coast and they also represent targets for us in the initial commercialization a focus.

One of the things that we are doing and Vince is actually leading this program.

But is we are actually working to begin developing our commercialization efforts here in the United States and maybe with that, Vince, if you want to talk about it or I can keep going or?.

Yes no..

Phil, keep on going. Go ahead, sorry, Daniel..

Okay. Well, so we are actually in the process of hiring a VP of Sales and Marketing for the United States. And that person, the goal of that person is to one, help manage the COVID-19 opportunity while it last. And we believe again that COVID-19 will continue to play a dominant role in U.S. Healthcare through Q4 and also well into Q1.

But because it takes time, we are not a commercialization organization in the United States. We are a -- this is where our headquarter is, this is where we do our manufacturing and all of our quality, our clinical and non-clinical R&D, but we are not a commercialization organization in the U.S. And so, it takes time to build that as you know.

And so, that is going to be one of the goals of coming up with the strategy of rolling out and whether or not it's a direct or partner strategy and then building that infrastructure here in the United States to be able to support that effort. So Vince will be leading that -- is leading that effort right now.

And I guess it will be just a short time now till we can give you a little bit more detail on that strategy..

That's helpful, thanks..

Sure..

Next question comes from Sean Lee with HC Wainwright. Please go ahead..

Good afternoon guys. Congratulations on a great quarter and thanks for taking my questions..

Sure. Hey, Sean..

I have just two quick questions on the clinical programs. So first, could you provide a bit more color on your strategy for tackling the Sepsis? I see that you have both the German study planned and as well as a future U.S. study.

So maybe you can tell us a little more about the design of these studies and what the potential endpoints are and whether there are any differences between the German study and the U.S.

study?.

Sure.

Makis, would you like to take that or I can take it as well?.

Either or Phil, your call..

Sure.

Why don't you go ahead?.

Okay, great. So Sean, thanks for the question. So the process trial is a multi-center trial, that's going to be execute in Germany, targeting Septic shock patients. And the idea here is that we will -- we will attempt to demonstrate shock reversal.

And by shock reversal, that's another term to what I mentioned earlier in the call, which is hemodynamic stabilization, which tends to be the number one treatment goal in these patients when they present themselves in the intensive care units. The first thing you need to do is stabilize the hemodynamic to be able to apply all the other therapies.

So we have implemented a primary endpoint, specifically detecting the time to get these patients stabilized. So it's a time dependent manner, because we know just like in the acute cardiac event, where every minute counts, its a very similar situation in Sepsis.

The longer these organs are hypo procured, the higher the likelihood that will progress to organ failure. So we believe it's a very meaningful endpoint. It's a kind of an innovative endpoint.

But as I presented earlier today on the call, the regulators are believing to -- are starting to believe that this is a kind of endpoints we need to be looking at simply because previous studies that were negative, using mortality have kind of removed the interest of executing clinical studies in the setting. So that's the German trial.

That's meant to have an interim analysis halfway through and we believe that's going to be a very informative initial provided information for us, for the progression of that trial and the next trials. The U.S. trial, we're in the early process of creating the Executive Committee, identifying the PIs of discussing the relevant issues.

We feel based on the experience that we are seeing with the commercial use of CytoSorb in Septic patients and always getting a consistent report of human end stabilization that we would again focus on some similar endpoints.

And we plan to engage with the agency to make sure that whatever endpoints we use, they're considered meaningful by the FDA as well. So we do anticipate this trial to be able to launch before 2021. And we are currently in the early stages of planning it..

Great. Thank you for the additional color. My second question is on the ongoing TISORB and CyTATION studies.

Now, with the flare-up of COVID in Europe, I was wondering what's the impact on those -- on the timeline of those studies and whether you can update on maybe when we can potentially see the results from those?.

Yes, great question. The TISORB, the study was actually activated and enrolled its first patient right before the COVID shutdowns took effect.

So that's an active study and basically the teams both our internal clinical team and the CRO-related team have been working on navigating the COVID-19 related R&D restrictions that have been imposed both in the U.K. and Scotland. We have seen over the last six to eight weeks some easing of these requirements.

And we already have active sites now that are looking to enroll patients in TISORB. Having said that, we are also seeing the second wave now starting to play out throughout Europe including the U.K. So we don't know how exactly this will impact our sites.

But we do expect that there is a possibility of additional restrictions may come in the near future. Regarding CyTATION, CyTATION is about to get started. We recently have made some progress regarding regulatory in IRB approvals in the study. That is being executed as a multi-center study in Germany.

Germany did have a little lighter kind of impact of COVID on the first wave. We don't know exactly how the second wave will impact Germany. But as you know, Germany has a much more, much higher numbers of intensive care beds and much greater capacity to manage a surge in critical cases. So we are progressing both trials.

But at the same time, we're looking carefully at what COVID-19 may impose as the second wave plays out..

Got it. That's all I have. Thanks for taking my questions..

Great, Sean. Thank you..

At this time, I would like to turn it back to management for any additional or closing remarks..

Well, thank you everyone for your participation today. And if you do you have any other questions that we did not answer today, please feel free to reach out to Jeremy Feffer at jeremy@lifescienceadvisors.com and we'll try to reply to your questions where possible. We look forward to the next quarterly call. And thank you everyone very much.

Have a good night..

Thank you. That concludes our conference for today. I like to thank everyone for their participation..