Good afternoon and welcome to the CytoSorbents First Quarter 2021 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'd like to turn the call over to our moderator, Amy Vogel. Please go ahead, Ms. Vogel..

Thank you and good afternoon. Welcome to the CytoSorbents first quarter 2021 financial and operating results conference call. Joining me today from the company are; Dr. Phillip Chan, Chief Executive Officer; Vincent Capponi, President and Chief Operating Officer; Kathleen Bloch, Chief Financial Officer; Dr.

Efthymios Deliargyris, Chief Medical Officer; Dr. Christian Steiner, Executive 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 May 4th, 2021 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 operations - operating and financial highlights for the first quarter by Dr. Chan and Ms. Bloch. Following that 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 now my pleasure to turn the call over to Dr. Phillip Chan..

Thank you very much, Amy and good afternoon, everyone. We had another productive quarter in the first quarter of 2021 with CytoSorb sales of $10.1 million, up 24% from $8.2 million a year ago, with the core underlying non-COVID business accounting for 82% of sales and 27% growth year-over-year. We believe that sales would have been higher. One moment.

We believe that sales would have been even higher, if not for broad restrictions and lockdowns throughout Europe and other countries that impacted sales activities and also rapidly declining new COVID-19 cases globally in the first two months of the quarter.

Blended product gross margins were 77% in the first quarter of 2021 versus 76% in the first quarter of 2020. Excluding non-recurring one-time items in the first quarter of 2021 that Kathy will detail in later on in her presentation. Product gross margins were 81%.

We also ended the quarter with a solid balance sheet with $68.5 million in cash and no long-term debt. During the quarter, we delivered greater than 131,000 cumulative CytoSorb cartridges to date, which is up 49% from 88,000 a year ago, with distribution across 67 countries.

We also treated more than 5,750 COVID-19 patients cumulatively now in more than 30 countries, including here in the United States under FDA Emergency Use Authorization granted in April of 2020.

We also during the quarter entered into a global co-marketing agreement with B Braun Avitum, the third largest dialysis company in the world and a division of B Braun, with EUR 7.5 billion in worldwide sales.

And during the quarter, we also - and just recently we received FDA IDE conditional approval to begin the US STAR-T trial with first patients targeted for the third quarter of this year.

In the first quarter, the Korean Ministry of Food and Drug Safety, KMFDS, also approved CytoSorb for all equivalent EU approved indications in Korea that has a population of 52 million in South Korea, in collaboration with our partner Fresenius Medical Care.

Health Canada also authorized CytoSorb for use in hospitalized COVID-19 patients in Canada, with a population of about 38 million people. During the quarter, we also appointed two industry veterans, with strong medical device backgrounds, that will help us guide future success in the future.

The first is James Komsa, who was appointed as Vice President of US Sales and Marketing was formerly a Vice President of the Restorative Therapies Group and Pain Group at Medtronic and also formerly a Vice President of the North East Cardiac and Vascular Group at Medtronic who knows the cardiac surgery area extremely well. Dr.

David Cox joined us as Vice President of Global Regulatory Affairs. He was formerly the Vice President of Regulatory Affairs for the Tissue and Regenerative Technologies division at Integra Lifesciences.

We also accelerated our clinical marketing of CytoSorb with in-depth webinars in a wide variety of different areas, most notably as a liver dialysis therapy in patients with liver disease and in cardiac surgery applications, particularly anti-thrombotic removal.

And last but not least, we signed our lease for our new Princeton, New Jersey headquarters and began building out our new manufacturing facility that is expected to support sales of roughly $350 million to $400 million in sales. And potential product gross margins in excess of 85%.

During the quarter, we also opened the new CytoSorbents Logistics Hub in Berlin, Germany, an expanded warehouse and distribution facility to accommodate our current and future growth. So let's talk a bit about what COVID-19 doing worldwide and how this relates to our business.

As we presented in our last earnings call, on the upper left-hand side, this was the activity of COVID in March of 2021. We were just starting to see a surge in activity in Latin America, as well as in Europe.

Fast forward that by two months, you can see that the numbers of new cases have grown dramatically in South America, in Europe and middle - the Middle East, as well as we've all heard in India, where they're experiencing roughly 350,000 new cases a day.

On the lower right-hand side, you can see the numbers of new cases of COVID-19 worldwide, within the green bars is the first quarter. And what you can see here is that in the first two quarters, after peaking very early in January, the cases of COVID dropped quite dramatically in the first quarter to roughly 300,000 or so cases a day.

I think that a lot of people had a lot of optimism regarding the availability of vaccines, and did not think that COVID-19 would be much of a problem anymore. But as we cited in the last earnings call, we started to see a plateauing and sure enough, towards the end of the quarter, you can see the rapid rise in new cases of COVID-19 worldwide.

And that has helped serve fuel a strengthening of our CytoSorb business related to COVID-19 across our business areas. So we expect that COVID-19 is expected to contribute to product sales in the second quarter of 2021 and likely for the remainder of the year. But the magnitude may depend on multiple factors, including the rates of vaccination.

In the United States, it's a very different story. As you can see in early March, there was a scattered, low level activity throughout the country. And even in early May, although there were some hotspots like Michigan and Oregon and also Washington State, you can see generally speaking, the rates of COVID-19 new cases have been relatively flat.

And you can see that in the upper right-hand corner in the red graph, where you can see that the numbers of new cases have kind of plateaued. But the rates of hospitalization and death fortunately have dropped dramatically.

And although it may not have been the case previously, it is likely the case now that vaccinations are having finally an impact with 32% of the US population fully vaccinated or 106 million people with 45% or 148 million people with at least one dose, a total of 247 million doses have been administered in the US to date.

And this contrast to even large countries like Germany, one of the leading health care countries in the world, with only 8% of their population fully vaccinated or 6.6 million, with 28% with at least one dose or roughly 23, 24 million people.

And this, the numbers get even worse when you look worldwide are only 3.6% of the world's population are fully vaccinated. And you can see that the United States accounts for more than a third of all of the patients fully vaccinated worldwide. And only 7.8% have at least had one dose or 609 million people.

So, this next slide, coming back to the slide that I presented in the last earnings call, we can safely say that we are not quite in the new normal yet. COVID continues to delay our pre-COVID-19 growth strategy. But that being said, you can see what we have accomplished in the first quarter.

We're certainly not standing still and we're working diligently in the background on making sure that we return to our non-COVID growth - our non-COVID-19 growth business as soon as possible. To give you more color on our clinical activities, let me turn it over now to our Chief Medical Officer, Dr. Makis Deliargyris.

Makis?.

Thank you, Phillip. And good afternoon, everyone. Over the next few minutes, we'll review some of the important updates on our clinical programs. But I'd also like to refer you to the press release we just issued that also has additional information. We are prioritizing the clinical programs that will lead us to US FDA approval.

As we recently disclosed, we have received FDA conditional approval to execute the Investigational Device Exemption study on Ticagrelor removal during cardiac surgery. We're also resuming the REFRESH 2-AKI trial.

And I'm happy to report that in addition to screening activity started in the majority of sites, we also have our first new patient enrolled. We have also made significant progress on the remaining active studies, and those that will be starting in 2021.

CytoSorb Therapy in COVID-19 otherwise known CTC Registry, has now accumulated sufficient data that we are progressing to a publication by the end of this quarter, focusing on critically ill COVID-19 patients requiring extracorporeal mechanical oxygenation [sic - extracorporeal membrane oxygenation] support or otherwise known as ECMO.

The STAR Registry which is meant to capture real world evidence with the use of a device for anti-thrombotic removal in patients undergoing cardiac surgery is getting ready to begin with data entry this summer, the ethics submissions in at least two countries in Europe have been completed.

The two important trials we're launching in Germany, the PROCYSS trial in septic shock, refractory septic shock and the HepOnFire trial in acute and chronic liver failure are making significant progress. Both of these trials have been submitted to ethics.

And we're waiting for their approval, and we're on target for first patient in before the end of this year for both trials. We recently made the decision to close the TISORB study in the UK. This was driven by two main reasons.

First of all, the significant delays that were encountered in the setting of the pandemic in the UK and also with the prioritization of the STAR-T trial, which will now be the primary data and evidence generation study for our FDA submission.

CYTATION on the other hand was able to begin and is actively enrolling patients in three German sites as of the first quarter of this year. Currently we'll remain steadfast on our clinical strategy and our executional plan. We continue to expand our internal clinical capabilities; we've added two 10 new members to the team in the past year.

And we'll continue to expand our teams to ensure that we have cost efficient and timely execution of our clinical plan. We're going to focus on generating data from rigorous, powered, multicenter, company-sponsored trials. And we're going to do that in partnership with a top academic institution and world-renowned investigators.

I will share some more detail later in this presentation about our academic leadership of the STAR-T trial.

And finally, we're going to get this data by using a complementary approach of randomized clinical trials, the registries capture real world outcomes and also health economic analysis to generate the value proposition associated with the use of our device.

In this slide, you will see the progress that we plan to make in 2021 and the milestones that we're anticipating for this year. I guess you could say there's going to be a busy year since all of our programs are targeted to start enrolling patients before the end of 2021.

On top of the lines, the STAR-T study, as we discussed, IDE approval has been obtained. We're right now gearing up our operational readiness and we expect to have the first patient enrolled in the third quarter. REFRESH 2, as I previously stated, we're happy to report that the first patient has been enrolled in the study resumption.

The TISORB study is effectively stopped. The CYTATION trial has begun enrolling early in Q1 and we'll continue to do so throughout the year. And the STAR Registry right now is at the stage of ethics submission and review. And we're gearing up to again enroll, start enrolling data capturing real world evidence in the middle of the summer.

Importantly, in the Critical Care space, the PROCYSS sepsis trial has already been submitted. The protocol is finalized and it has been submitted for review by the ethics committees in Germany. And we anticipate despite the delays associated with COVID-19 that we will still be able to enroll patients towards the end of Q3 or beginning of Q4.

Similar situation applies to our multicenter, single arm, HepOnFire trial, which we again expect to commence enrollment by the end of this year. Relating to the CTC Registry as I stated, we have enough data collected in the US and we plan to submit a publication by the end of this quarter.

And we also plan to expand it now into the CytoSorb Therapy and Critical Care Registry to capture multiple applications in critical care and expand also in the Europe. Next slide, please. Our clear priority is FDA approval and we maintain the dual path with our two studies, the REFRESH 2 and STAR-T study.

Relating to Refresh 2, we now are up to 154 patients enrolled to date. The study resumption as I stated has begun, and we have approximately half of the sites are active and screening and we believe will have the remaining of the sites open and active and enrolling patients by the end of the second quarter.

The next milestone to look forward to is the interim analysis. Regarding the STAR-T study, we received our conditional approval of the IDE in April 2021, which effectively gave us the green light to start the study. The sites that we'll participate have already been identified, and we have begun site initiation activities.

The IRB submission process and the site contracting is currently in progress and we have selected already the study vendors that will assist us in the study including contract research organization.

Most importantly, we'd like to disclose to you today, the academic leaders of the trial, our two investigators are going to be, principal investigators are going to be Dr. Michael Mack, a Cardiac Surgeon from Baylor Scott & White; and Dr. Michael Gibson, an Interventional Cardiologist from Harvard.

The study committees have been established including the data safety monitoring board and the clinical events committee. And as stated previously, we're targeting the first patient to be enrolled in the third quarter of this year. It is important to take a minute to introduce to you in more detail our two principal investigators.

First of all, we're taking the Heart Team approach. He became very obvious during the development programs for the probably the most important innovation in our century in cardiovascular disease and that of the transcatheter valve devices, that a Heart Team approach was necessary.

When cardiovascular patients suffered an acute event, they require a multidisciplinary approach. And in our case, we're targeting acute coronary syndromes, it's a great opportunity to utilize the knowledge and the input from both interventional cardiologists and cardiothoracic surgeons.

As such we have selected two of the most world-renowned investigators in the setting, Dr. Gibson is a Professor of Medicine at Harvard Medical School. He's also the President and CEO of the non-profit Baim Institute, formerly known as Harvard Clinical Research Institute.

And he's also the Founder and Editor-in-Chief of WikiDoc, which is the equivalent of Wikipedia, but for physicians. Dr. Michael Mack is the Chair of the Cardiovascular Service Line at Baylor Scott & White. He's also the President of the Baylor Scott & White Research Institute. However, what's important to note about Dr.

Mack, he's also the Pioneer of the Heart Team and he was part of the leadership of the pivotal trials that brought the first transcatheter valve therapies to FDA approval and to clinical use. Finally, I'd like to introduce to you our key hire on the Clinical Team.

This is Ed Tumaian, the Executive Director of Global Clinical Operations, and he's coming into fill a critical role to lead the Global Clinical teams' operational team in CytoSorbents. He brings with him more than 25 years of experience in clinical development and clinical operations and trial execution optimization.

He has previously held global leadership roles at both CROs such as Quintiles and Parexel, but also very large players in the lifescience industry like Novartis, AstraZeneca and Sanofi.

Ed, throughout his career, he has used technology solutions to drive quality and efficiency, including implementing programs for remote monitoring and risk-based monitoring. He has successfully built and led global teams in clinical operations and portfolio management.

And his activities were critical in driving lifecycle management of blockbuster products like Prilosec, Nexium, Plavix and Gleevec. We think Ed is a key addition to our team and we're very excited about his contribution in the continued progress. Thank you. Back to you, Phillip..

Thank you, Makis for that overview.

Now, Kathy, would you please give the financial overview?.

Certainly. Thank you, Phil and hello, everyone. For today's call, I will be providing an update regarding our March 31st, 2021 financial results, and also an update around our working capital and cash runway. So we'll start with our comparative quarterly revenue results.

Product sales for the first quarter of 2021 was approximately $10.1 million, which is an increase of $2 million or 24% over first quarter 2020 product sales of approximately $8.2 million.

And this increase was primarily driven by an increase in direct sales of approximately $608,000 and also an increase in distributor sales of approximately $1.4 million. Grant revenue for the first quarter of 2021 was $455,000 as compared to $551,000 in the first quarter of 2020.

And total revenues, which includes product sales as well as grant income increased by 22% to $10.6 million for the first quarter of 2021 as compared to $8.7 million for the first quarter of 2020. Our Q1 2021 product gross margins were 77%. Excluding the negative non-recurring impact of 2018, '19 and '20 tariff adjustments of approximately $732,000.

And the offsetting non-recurring positive impact of the employee retention tax credit of $388,000, product gross margins were 81% in Q1 2021. That compares to 76% in the first quarter of 2020. Next slide, please. Now we'll take a look at our quarter-over-quarter product sales. Our first quarter 2021 was our third best quarter in terms of product sales.

And as Phil already mentioned, we believe sales could have been even higher, had it not been for the widespread lockdowns and restrictions throughout Europe, including Germany, Austria, the UK, Italy and others. And for the rapid decline in COVID-19 new cases and hospitalizations for two-thirds of that quarter.

The lockdowns prevented our sales reps and distributors from accessing hospitals and delayed our return to what we're calling the new normal, non-COVID-19 growth strategy that Phil previously discussed.

And though it's difficult to quantitate, we've been trying to do so every quarter, COVID-19 sales were estimated to be approximately $1.8 million in the first quarter of 2021, as compared to approximately $1.6 million in the first quarter of 2020 and lower than the $2.6 million in COVID sales, which we saw in the prior three quarters.

With the resurgence of COVID-19 since March, we have seen a strengthening of COVID-19 related orders of CytoSorb. And just one final note on the first quarter of 2021, if we exclude clinical trial expenses and non-cash stock compensation expenses, our core operations generated a positive EBITDA of approximately $164,000. Next slide, please.

Now we'll take a look at our trailing 12 months product sales and blended gross margins. And as you can see by this chart, we continue to maintain strong year-over-year product sales and gross margin growth.

As of March 31st, 2021, trailing 12 months product sales were $41.4 million, an increase of $15.1 million or 57% over trailing 12 months product sales of $26.3 million one year ago. We also note that our compound annual growth rate or CAGR was 40% over the past three years, and we are continuing to observe a very positive trajectory in this regard.

Year-over-year gross margins also continue to climb with blended gross margins adjusted for non-recurring charges and benefits as I previously discussed of 81% in the first quarter of 2021 compared to approximately 77% for the first quarter of 2020. And lastly, we'll review our working capital position.

As of March 31st, 2021, we had approximately $68.5 million in cash, which is a very healthy cash balance. And we experienced a quarterly burn of less than $3 million in the first quarter of 2021. And that burn by the way, is solely a result of spending associated with our clinical trial activities.

We believe we have sufficient liquidity to provide for the continuing commercialization of CytoSorb as well as to execute on our robust clinical trial strategy. We further believe that we have adequate funding to allow us to continue to operate without the need for any additional capital breakthrough to GAAP breakeven.

And with our 80 plus percentage gross margins, once we reach GAAP breakeven, 40% to 50% of every incremental sales dollar is expected to fall to operating profit. Lastly, as of March 31st, 2021, we had approximately 46 - $48.6 million common shares on a fully diluted basis. Thank you. And at this time, I'd like to turn the call back to Phil.

Phil?.

Thank you very much, Kathy. In terms of guidance CytoSorbents has not historically given specific financial guidance on quarterly results until the quarter has been completed.

However, provided that the current order pattern continues, and not withstanding uncertainty related to the COVID-19 pandemic, we expect that product sales for the second quarter of 2021 will exceed those in the second quarter of 2020.

Because of the recent surge in COVID-19 activity, we expect COVID-19 to positively contribute to sales in the second quarter of 2021 and for the remainder of the year, though the magnitude of these sales will depend on multiple factors, including the rates of vaccination in major markets, as well as globally.

We continue to expect that 2021 will represent another year of growth. So with that, this concludes our current prepared remarks. I would now like to open up the call for a live Q&A session..

Thank you -.

Moderator?.

Thank you. [Operator Instructions] We will take our first question from Anthony Petrone of Jefferies. Please state your question..

Thanks. Hope everyone's well and congratulations, strong start to the year here. You know maybe, Phil and Kathleen, we could dig in a little bit to underlying product sales when we back out COVID sort of - approaching a 26% year-on-year growth level. And sort of just wondering how to sort of think about that in two buckets.

One being, there certainly seems to be some reversal and underlying procedures, one, but also CytoSorb uptake usage triggered by COVID out in non-critical areas you've seen a pickup there as well.

So how do we think about recaptured procedures driving that number versus share gains that were driven by COVID elsewhere and all the surgical procedures? And I'll have a couple of follow-ups..

Yeah. Well, thanks very much, Anthony. I think that in the United States, the rates of non-COVID related procedures has been increasing. But in Europe, I think it's been touch and go because of the various lockdowns that are in countries around Europe, as well as Eastern Europe as well.

So, you know, Christian can probably comment a little bit on what the environment looks like right now. But what we're still continuing to see is, reduced numbers of elective surgeries that were often in the post-operative period. They're using CytoSorb. We're also seeing lower ability of our sales reps to be able to get into hospitals.

And then also, the less effectiveness of conferences, scientific conferences, where that are typically - have been typically poorly attended. But let me turn it over to Christian to give a little bit more color on what he's seeing in Europe.

Christian?.

Yeah. Thank you, Phil and thank you, Anthony for the question. Yeah, as Phillip was pointing out, the COVID situation is still very much impacting our business. And we have two kinds of parts of situation. One is the COVID-related business was significantly lower compared to Q4. You can see this Q4, USD 2.6 million and Q1, USD 1.8 million.

But compared to Q1 2020, it's roughly the same, considering the change of the exchange rate between euro and dollar. So what happened in Q1? The second week ICU patient has declined. So there were less patients, ICU patients in the beginning of Q1. In Latin America, for example, the summer led to less COVID activity.

And as Phil pointed out as well, there were less patients in the US, which led to roughly stable business in the US. On the other hand, the COVID restrictions in our markets, were still there and were the hardest throughout the whole pandemic. So the hospital access for the sales reps and distributors has got even harder.

The doctors and healthcare professionals I have to say are totally exhausted even if they would like to, they have not the time and energy to speak to industry representatives. And most important I have to say, the elective surgery programs are down 40% to 60% all over our markets.

And if you look at the growth, we have shown Q1 to Q1 in 2020 to '21, there is a growth of 27% despite this down of the elective surgery programs, and I think one can imagine that is all the restrictions we would do much better even without the positive impact of COVID-related business.

I could go a little bit more in detail if you want, but timing is sufficient..

That's fine. Two follow-up questions for me, there would be one, one we then consider that elective is still a headwind in key markets.

Was there some stocking in the 27%? And then the last question for me, and I'll hop back in is just on the US STAR-T, you got a little bit more detail on how many sites are expected patients and endpoints to the extent that you can share this at this point? Thanks again..

So if I have understood your question, right, whether there was any stocking in product with the customers or distributors? I can say, no, there was no stocking. It's in and out like the patients get treated. There's no stocking we are aware of..

Yeah. And -.

Thank you..

In terms - yeah in terms of the STAR-T trial, what we've said is that, once we get full approval of the IDE and know exactly what the FDA has agreed to, we'll give more detail on both the primary endpoints, the nature of the trial, the size of the study, the number of sites and all of that other detail..

Thank you again, Phil..

Great. Thank you, Anthony..

Our next question is from Josh Jennings of Cowen. Please state your question..

Hi, good evening. Thanks for taking the questions and I echo Anthony's comments on that. Congratulations on a strong start to the year despite all the challenges. I was hoping to just ask about I know we've probably talked about this before, Phil, but we had an interim quarter call with some [Avimed] [ph] executives.

And they spoke about lobbying for with the FDA to streamline formal approvals of products that have achieved EUA approvals. And I was wondering if there's any discussions that are ongoing between CytoSorbents and the FDA about the CytoSorb EUA for COVID-19.

And whether there could be a potential streamline path for critical care indication?.

Yeah, thanks very much, Josh. It's not something that we can comment on at this time. But we do have an interest, we have actually had considerable amount of experience relative to the overall numbers in ECMO and COVID. And it is to treat acute respiratory distress syndrome.

So but, you know, so we do believe that there is a potential benefit of having CytoSorb approving in the United States for treating ARDS in general, but it's not something that we can comment on at this time..

Great. And just on the CTC COVID-19 registry data, and then on the interim analysis.

I mean, is that - could that be supportive of potential streamline pattern? What do you expect that data set to do? Clearly it could catalyze increased utilization in COVID patients in the US and globally, but then any future ramifications outside of that for the CTC COVID-19 registry data?.

You know, I think that what we've seen is that, the early intervention with CytoSorb and ECMO is potentially a very promising long rest strategy to treat acute respiratory distress syndrome.

We've seen CytoSorb be used with ECMO in a lot of different cases, you know, patients not hyper-inflating patients, where it's being used as kind of a rescue therapy when they've been on mechanical ventilation for weeks and weeks.

And, you know, there, it's hard to have a positive benefit in those patients, but when used earlier and uses more aggressively, I think that and preventing mechanical ventilator-induced lung injury, there may be actually a play here to use ECMO plus CytoSorb as a primary treatment of acute respiratory distress syndrome, which currently today even in a non-COVID environment still has mortality of roughly 30%.

So I think that in order to gain that application, it will require a large - larger scale multicenter study, but it's not - but the, you know, I think the registry data would be supportive of that concept..

Great. Now thanks for taking the questions. And I'll get back in queue..

Yeah, thank you very much..

Our next question is from Danielle Antalffy of SVB Leerink. Please state your question..

Hey, good afternoon, everyone. Thanks so much for taking the questions. Just a question on Europe and I appreciate that there's a lot of moving parts there. COVID is still a big issue in Europe.

But I have to imagine a good portion of your competence in growth this year comes from being able to get back into European centers and really market the ticagrelor and rivaroxaban removal indications.

And so I just wanted to get a little bit more of a sense on sort of, are there centers where you're seeing ramping adoption there yet in Europe? And sort of what gives you the confidence that in the adoption ramp once you guys can actually get back in there? And I have one follow-up..

Sure. Yeah, I think that as we said previously, that we've really invested quite a bit in our infrastructure and sales and marketing, and the commercial team overall in Europe to take advantage of this non-COVID core opportunity in critical care and cardiac surgery.

So the business in sepsis and other critical illness as well as in cardiac surgery is actually quite healthy. And as we mentioned, that core business grew 27% year-over-year. I think that moving forward here, we are looking to try to get back to this non-COVID strategy.

And to tell you a little bit more about what we're doing, I think in, particularly in cardiac surgery, and in the blood thinner application, Christian might be able to provide some additional detail on how we're doing in Germany, for example, as a microcosm of the market.

Christian?.

Yeah. Thank you, Phil and thank you, Danielle for the question. Just to give you a little bit more flavor on what's happening in Europe. I think one has to see the whole development in perspective. As I have said before, the access to hospitals is very much restricted just to reflect us.

Not - nowadays, our sales reps have roughly 10% of the appointments they have normally before the COVID pandemic. And taking this into account, and also the decline of the elective surgery programs by 40% to 60%. The growth of 27% in the core indication, I think is has to be seen in this perspective.

But you also have mentioned our new indication of the antigen body removal fluids. And in this case, I mentioned last earnings call that more than 90% of the heart centers in Germany are our customers. And of those, more than 50% are using CytoSorb in this application.

And we were able, despite the restrictions and also despite almost all heart centers in southern Germany are closed, we could increase this even more. We have now 94% of the heart centers as our customers and those who are using CytoSorb in this new application is more than 60% nowadays.

So you can see, despite all these restrictions, there is a progress. And this progress we see also in other markets outside of Germany, in our direct markets, for example, in Benelux, we had a number of new accounts started in this application. But once we use it also as a door opener once we are in, this is then spreading also to other mutations.

Maybe that is giving you a little bit more insight in the development..

Yeah, no, that's incredibly helpful. Thank you so much, Christian. Appreciate that. And then one quick follow-up on the STAR-T trial. And I mean, congratulations on getting Dr. Michael Mack. I know of him very well and he's very highly regarded. So I think that's a big win for you guys.

I guess what are the sort of gating factors around the enrollment timing for STAR-T? Because that's really going to be, I think the inflection point for the company from a sales perspective is the US approval.

So just want to make sure we're thinking about the enrollment timing and we were appropriately putting our barriers around that sort of bear case and bull case scenarios there. Thanks so much..

Yeah. Thanks, Danielle.

Makis, would you like to take that?.

Yes, thank you, Phil. So yeah, that's a great point, you know, about Dr. Michael Mack, but also, Dr. Mike Gibson has an incredible track record in development, you know, antithrombotics, and it's also very well regarded.

So with their help, and with some additional, you know, network of sites that we had from REFRESH-2 and also from personal connections, we have been now in contact with a very, very large number of US, you know, large US cardiac surgery centers. And we've seen a lot of interest.

So we are, you know, we have a long list of high performing sites that we're slowly going to start bringing them on.

So, we think that's probably the number one factor that can drive enrollment, right, getting the right sites, we vet them all about ticagrelor usage and making sure they're, you know, actively using this drug as a top line agent for acute coronary syndromes. And then obviously, we have the resource capabilities to execute.

But what's really important is the interest we're seeing from the sites. You know, this has been a longstanding unmet need, literally a nightmare in clinical practice for the surgeons to deal with. And they're extremely excited about being part of this study.

So, you know, the kind of momentum we're seeing from the sites that the interest level, the kind of sites we're bringing on board, including a fair amount of a REFRESH-2 sites that want to continue to research with us, gives us you know, a lot of confidence that we will be able to enroll.

Now, having said that, you know, the patients will require urgent or emergency surgery are limited compared to the total number of ACS patients.

So that's why we intend to bring the, you know, the right number of sites on board to support robust enrollment, and like Phil said earlier, you know, a lot of the details around the study, we'll be able to disclose, once we have the full approval from the FDA.

Once our, you know, discussion - our ongoing discussions are completed, we should be very soon. So, we will be disclosing more information then.

Does the help?.

That is helpful. Thank you so much..

Yeah..

Our next question is from Andrew D'Silva of B. Riley Securities. Please state your question..

Hey, good afternoon. Thanks for taking my question. Sorry, if you mentioned any of these, I was jumping between calls. Just to start, as it relates to the uptick in cases, COVID cases in India. Obviously, you've been a longtime strategic partner with Biocon.

I was curious if you're seeing any increased traction in the region there, Biocon did reference CytoSorb, you know, a couple of times in press releases as well as on their conference call. So, it seems like you know, it's being well regarded given current conditions..

Yeah, thanks, Andy. Let me turn it over to Christian to give some color commentary on India and Biocon.

Christian?.

Yeah. Thank you, Phil, Andrew and maybe a little bit more color on India in general.

We are working with Biocon for a long time now, and as you know, over the last years, we also have expanded our fields of application indications, and so we are currently evaluating with Biocon that on how they can represent us in India in all our relevant application segments, and of course, how to grow and speed up the growth in these areas.

So, we have additionally to the partnership, we have installed own manpower in the Indian market to support Biocon and this has led to a number of developments. For example, now that the second wave and the COVID pandemic in India is growing so massively.

We have organized a meeting last Friday, I don't know whether you were aware of this, with all the medical leaders of different specialties involved in the treatment of COVID patients, but also as leaders of big hospital groups like Apollo.

And so our collaboration with this Biocon in this COVID situation is tighter and increasing, and obviously, will also be reflected by several orders from their side. I think that's what we can review..

No, no that was very useful context. So, with that being said, obviously, kind of a transient nature of COVID.

And I know no long-term, this isn't a COVID-19 company, but COVID - I would imagine that at least in some areas, when physicians start using CytoSorb, and then, you know, their amount of COVID-19 related cases drops, they realize that the indication CytoSorb can be utilized for goes far beyond COVID-19.

So I'm kind of curious, has there been any sort of stickiness that you can identify, thanks to the COVID utilization, but outside of COVID? And, you know, the reason I'm asking that is obviously, India is such a large region. I'm curious if you see an analogous situation to that potentially developing as you're utilized there..

So, Phil, Shall I continue with this?.

Yeah, sure. Or I can come in -.

Yeah. Yeah. So maybe India is not the right example for this, because we have worked in India already with - in all the different indications, including cataract surgery, and also including liver disease. But India also is a very specific market as you might know, this a public sector and the private sector.

So even in the public sector, customers or patients in this case, have to pay lots of the treatments privately. So nevertheless, the market is with but I think, between 50 million and 150 million people able to pay healthcare as we know it from the [indiscernible].

But I think your question can be answered much better with territories where we just have started. And we have started in the pandemic, which was the case actually in Latin America last year. So we have added, as you know, 10 countries last year in Latin America, and most of them started with COVID-19 patients.

And based on the successful treatments, they start also to treat other patients, including septic shock patients, including inflammatory shock statuses from other region and but also including patients with liver disease.

So we see absolutely what you were suggesting that based on the experience with COVID that doctors get, let's say, inspired to treat other patients and other clinical pictures..

Okay. Very useful..

Yeah, I think just to add to that. I mean cytokine storm is such - plays such a central role in so many different diseases, not just COVID-19.

Again, CytoSorb used in COVID-19 is not to treat the viral infection, it's to treat the uncontrolled inflammation that gets generated by the infection that then leads to lung failure, kidney failure, shock and all different types of organ injury.

And those are the same complications that we see every day in trauma patients, in patients who were infected with, you know, burst appendix, for example or burned patients or pancreatitis patients or you know complications of cancer immunotherapy and other things.

And so it's a direct, you know, if they see that it helps stabilize shock in COVID-19 patients. It's a very easy translation to think, “Hey, you know, in this patient in this non-COVID patient who's also in shock, let me think about trying to use CytoSorb as well”. Right and that's kind of where we are in a lot of these new markets..

Okay, okay, great. And I just want to make sure I'm understanding our character driving this correctly.

Is it fair to say that during the first quarter, it was still very stringent COVID lockdowns and you know areas such as Germany, where you generate a significant portion of revenue from? However, the types of COVID cases maybe weren't as severe meaning, the amount of critically ill COVID-19 patients likely dropped sequentially or at least relative to, you know, the state that you were seeing for the majority of 2020.

So basically, your legacy business, non-COVID related, you were impacted as a lockdowns, but you didn't get as much of a benefit from treating critically ill COVID-19 patients, because they weren't necessarily as many as a percentage of the total volume of patients that had COVID-19..

Yeah, that's correct. And I think all the numbers support that. If you look at the numbers of hospitalizations, and numbers of deaths, the ICU capacity, utilization, they all dropped when the numbers of cases precipitously dropped in January and February, after having hit that peak in late December and early January.

You know, a lot of countries had instituted lockdowns because of that. But those lockdowns continued even though the cases of COVID-19 worldwide began dropping very rapidly. So it was a little bit of a transition for us as we, you know, look to manage that you know, dropping COVID cases and getting back to business as usual or back to the new normal..

Okay. Yeah, and that makes a lot of sense. I just wanted to make sure I was understanding that correctly. Last question for me.

Any updates on additional candidates, HemoDefend-RBC or BGA? And then, or there was another CytoSorb-XL that you know you referenced previously, I was just curious how the pipeline outside of CytoSorb is developing?.

Yeah. I think that, you know, COVID-19 certainly slowed a little bit of our development work in these various programs.

But last year, as you saw, we received about $8.6 million in government grants from the, mainly from the US Army, to drive the development of HemoDefend-BGA, which has actually been making a very nice progress, particularly very recently.

And so, you know, in terms of these programs, our research and development folks have been back in the lab and, in fact, they're actually at the new facility at the moment in the new labs, with a lot more space and able to stay socially distanced and get their - get the work done.

And so they've been making some really great progress in all of our programs, including the CytoSorb-BGA program, the site to CytoSorb-XL, I mean, the HemoDefend-BGA program, the CytoSorb-XL program. And you know, the HemoDefend-RBC program is slightly delayed, but we are still making some progress on that as well..

Okay, perfect. Thank you very much. Best of luck going forward..

Thanks very much, Andy..

Our next question is from Sean Lee of H.C. Wainwright. Please state your question..

Good afternoon, Phil and thanks for taking my questions. My first question, I think in the prepared remarks, you guys mentioned that you saw quite a bit of growth from distributor sales.

So I was wondering if you could provide a little bit more color on that, for example, which geographies and which distributors are you seeing the biggest growth from and where do you think that's going to go this year? Thanks..

Yeah. I think that as Christian mentioned, COVID-19 has been a catalyst for distributor sales, given how prevalent COVID is around the world. We saw strength in Latin America, for example, we saw strength in the Middle East, certainly, you know, in our - some of our non-direct territories as well in Europe and particularly, Eastern Europe.

And so, you know, we expect that that activity will continue going forward in a COVID or even in a non-COVID environment. There's been a lot of positive responses from those - from physicians from all those territories..

Thanks. And also, it's - on the clinical side, it's great to hear that the REFRESH-2 is resuming.

So I was wondering, have you had to modify or call any of the previous data that you collected? Are you making any changes to the study protocol compared to before? And what's the expected timeline for the study now?.

Let me turn over to Makis to answer some of those questions.

Makis?.

Thank you, Phil and thanks for the question. So, we did not have to make any major modifications to the protocol. If you recall, the voluntary hold on REFRESH-2 was triggered by the quality of the data that was being captured and we greatly improved that and you probably remember the whole saga, we changed the CRO and everything.

So, following the review by the DMC, they suggested we had a couple of additional data points to be collected with the same protocol procedures, meaning, we didn't change at all, how patients are, you know, treated or throughout the trial, study related procedure remained the same we're just capturing some additional data points.

So that was - those were the sole difference in the protocol. But we had to resubmit, obviously, during the resumption process. Regarding timelines, I think what we're looking to do now for the next few months, is, get all the sites up and running and evaluate the rate of enrollment with the study resumption.

We're hoping that the ramp up will be a little faster than usually in the beginning of although the initial start of a trial where sites are not very familiar, because a lot of the sites, you know, probably are familiar with a study based on their previous enrollment.

So I think for us to be able to give you a better idea of the timeline, we'll probably should observe how enrollment is performing over the next quarter or so, and then we should be able to provide better guidance..

Thanks for that. So that's all questions I have..

Great. Thanks, Sean..

We have reached the end of the question-and-answer session. At this time, I would like to turn it back to management for any additional or closing remarks..

Well thank you, everyone for joining us today on today's earnings conference call. We appreciate your participation. If you do have any other questions, please feel free to reach out to Amy Vogel at avogel, A-V-O-G-E-L @cytosorbents.com. And we'll try to reply to your questions where possible.

In the meantime, hopefully you'll join us for our Virtual Annual Meeting on June the 1st. Thank you, everyone very much for joining today. Take care..

Thank you. That concludes our conference for today. I'd like to thank everyone for their participation. Have a great evening..