Cytosorbents Corp. (NASDAQ:CTSO) Q4 2016 Earnings Conference Call March 3, 2017 11:00 AM ET
Amy Phillips - Pascale Communications, IR
Phillip Chan - President & CEO
Kathleen Bloch - CFO
Christian Steiner - VP, Sales & Marketing
Chris Cramer - VP, Business Development
Jason Kolbert - Maxim Group
Andrew D'Silva - B. Riley
Brian Marckx - Zacks Investment Research
Jason Wittes - Aegis Capital
Good day everyone and welcome to the CytoSorbents Fiscal 2016 Financial and Operating Results Conference Call. [Operator Instructions] Today's call is being recorded. And at this time I'd like to turn the conference over to our moderator, Amy Phillips, Please go ahead.
Thank you and good morning. Welcome to CytoSorbents 2016 financial and operating results conference call. Joining me today from the Company are Dr. Phillip Chan, Chief Executive Officer and President; Vince Capponi, Chief Operating Officer; Kathleen Bloch, Chief Financial Officer; Dr. Christian Steiner, VP of Sales and Marketing; and Chris Cramer, VP 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 and 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 March 3, 2017, 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 financial and operating highlights for 2016 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. Chan. Dr. Chan, go ahead.
Thank you very much Amy and good morning and welcome everyone to the call. CytoSorbents is a leader in clinical care immunotherapy, and when we talk about immunotherapy we're really talking about how do you manipulate the immune respond to fight illness.
There are more than $100 billion in sales of immunotherapy type products on the market today and they range from things that are designed to try to stimulate an underactive immune response such as vaccines and cancer immunotherapies including CAR T-cell immunotherapies for example. But on the other end of the spectrum they also include things that are designed to try to quell an overactive immune response and these include drugs and in biologics that are designed to try to treat things like asthma, allergy, anaphylaxis, as well as autoimmune disease. But where there is a major a unmet medical need today in modern medicine is in the treatment of life threatening massive inflammation seen in the intensive care unit and that is exactly where CytoSorb and our company are positioned today. We are leading the prevention or treatment of life threatening inflammation in the ICU and cardiac surgery using our CytoSorb Blood Purification Technology.
Now it's an unfortunate fact that millions of people die every year of uncontrolled deadly inflammation from life threatening illnesses such as sepsis which is the overzealous immune response to a life threatening infection and is one of the top ten killers around the world affecting 30 million people and killing approximately 10 million of them each year. It also includes many other diseases and conditions such as trauma, burn injury, cytokine release syndrome, and cancer immunotherapies, liver failure, surgical complications, pancreatitis, lung injury, complications of influenza, and many other illnesses where inflammation plays a detrimental role. And that is where CytoSorb is designed to come in. CytoSorb removes the fuel to the fire of inflammation and targets a $20 billion opportunity in critical care and cardiac surgery. It is the only specifically approved product in the European Union to reduce cytokines and it is approved for use in any situation where cytokines are elevated.
CytoSorb is particularly good at removing a broad range of inflammatory mediators, not just cytokines including things like free haemoglobin, bacterial toxins, myoglobin and activated complement for example. And very important to our business model is that we are a plug and play cartridge that works with standard dialysis and heart lung machine standard hospitals and operating rooms today. So far CytoSorb has been safe and well-tolerated now in more than 20,000 human treatments which is up from 9,000 a year ago. And our goal is to try to control this deadly inflammation as a way to prevent or treat organ failure; and in doing so hopefully in approved patient outcome and survival while decreasing the cost of ICU in patient care. And in more than 20,000 human treatments that we've seen so far, this has been one of the things that we have observed. And we believe because of that we stand at the edge of becoming a true revolution in critical care medicine.
So with that let me turn it over to Kathy to discuss the financial highlights for the fourth quarter and full fiscal 2016 year. Kathy?
Thank you, Phil and good morning everyone. For today's call I will be providing an update regarding CytoSorbents December 31, 2016 financial results including our product sales progress and an update around our working capital and cash runway.
Turning to our annual financial results; CytoSorbents product sales for the year ended 2016 were $8.2 million, an increase of 103% over 2015 product sales of approximately $4 million. Grant and other income groups 77% from $748,000 in 2015 to $1.3 million in 2016, and our total revenues which includes product sales and grant income increased by 99% to $9.5 million for the year 2016 as compared to $4.8 million for 2015.
Now we'll take a look at our quarter-over-quarter product sales. Our fourth quarter 2016 product sales of approximately $2.6 million represents our best quarterly product sales ever. This was an increase of 22% over the previous quarter and is in fact our seventh consecutive period for which we have reported quarter-over-quarter product sales growth. It is also our sixth consecutive quarter of record sales. And with $2.6 million in quarterly product sales, our annual run rate at the end of 2016 now exceeds $10 million.
With regard to our annual product sales growth, we remain very pleased with the overall trajectory we are experiencing. Our compound annual growth rate, CAGR, was a 115% over the last three years. I also want to note that the drop in the euro in late 2014 had a dampening effect on our 2015 and 2016 reported product sales. If the dollar to euro exchange rate had remained unchanged from 2014 when it was approximately $1.329 to €1, our 2016 reported sales in dollars would have been approximately $9.7 million and the three year CAGR would have been a 127%.
For the past two years we have guided that sales of CytoSorb in Germany represented more than half of our product sales. With our 2016 annual report on Form 10-K; for the first time we are presenting showing a breakdown of our revenues in Germany and then the rest of our territories. Germany's product sales were $545,000 in 2013, our first full year of commercialization. In 2014 direct sales increased by $860,000; then in 2015 direct sales increased by $948,000. In 2016 direct sales in Germany more than doubled, increasing $2.6 million or 112%. And you can see from this chart a clear inflection upward in Germany's product sales that occurred in 2016.
This is because in Germany we've established strong key opinion leader support, we've received recognition and support from the major medical societies, we have established reimbursement, and we have a strong sales and marketing presence. Germany is the market that we've been in the longest and we believe it provides a prototype as to how we might expect our other territories to develop overtime.
And next, we're presenting a summary of our worldwide sales where we've rated [ph] the CytoSorb product sales in the countries outside of Germany, that's the orange area on this chart on top of the sales in Germany which is identical to the chart that we just looked at. Of the 37 countries where we currently have distributors, only about a dozen have been actively commercializing CytoSorb in their territories for two years or longer. These non-German markets in general remain in the early stages of development. As we have seen in Germany, we experienced modest increases in sales in the early years of commercialization and then sales accelerate with more time in the market.
For sales in the territories outside of Germany 2016 sales were $3.2 million which is an increase of $1.5 million or 91% over the prior year. So while these other territories are not as mature as Germany, we expect that overtime these other territories should develop similar growth patterns with sales acceleration that we have seen in Germany. And as we develop these existing markets, remember we are also constantly adding new distribution in new countries.
Let's look at the world map and here we've highlighted the 42 countries where we are selling direct or through distributors. And I just like to mention a few significant drivers of sales for 2017. First, effective January 1, 2017, we've received a dedicated reimbursement code in Germany. And already in Germany one direct sales hospital has more than $1 million in 2016 sales representing 11% of our total revenues. And with more than 400 major university hospitals with more than 400 beds in Germany, you can see the revenue potential for Germany alone as we continue to grow in usage and adoption there.
In addition, with the Fresenius launch in the second quarter of 2016 and Terumo's launch in December 2016, these strategic partners are expected to have a positive impact on sales growth for the future as well. Phil will speak into greater detail about these revenue drivers in a few minutes but lastly, I'd like just to take a look at our working capital position.
As of December 31, 2016 we had approximately $5.2 million in cash which is expected to provide funding for our operations into the second half of 2017. In addition to increased gross margins from higher expected product sales and the additional $5 million in debt that we have available to drawdown from our credit facility with Bridge Bank, we are looking at a number of different strategies to obtain the funding required for our future operations and clinical studies including leveraging the balance sheets of our current and potential strategic partners, additional research and development grants and contracts, non-dilutive sources of capital and traditional equity financing among other mechanisms.
As of December 31, 2016 we have approximately 29.4 million common shares on a fully diluted basis. And now, I'd like to turn the call back to Phil. Phil?
Great, Kathy. Thank you very much. Well, the main message that we want to convey to our investors today is that we believe that we are on the verge of a number of major value creating milestones. And the first major milestone is that we expect to achieve operating profitability within one to two years.
Now it's important to remember that CytoSorbent is a pure-play high margin disposables business where CytoSorb is the high margin razor blade in someone else's razor machine, and these razor machines are like the dialysis or continuous renal replacement therapy machines or echmo machines in the ICU or the heart-lung machines that are found in the operating room. Today we have blended gross margins of 67% that blend higher margin direct sales with lower margin distributor and partner sales. But with economies of scale and manufacturing efficiencies, we expect that we can drive blended gross margins closer to 80%.
Now the average selling prices CytoSorb is approximately a $1,000 per cartridge and depending on the disease state that is being treated one can expect that one to ten cartridges are typically used per patient. So patient undergoing open heart surgery typically uses one to two cartridges, a person undergoing treatment for sepsis typically uses three to five cartridges, and a person with very severe illnesses such as severe acute pancreatitis could be using upto ten cartridges for that patient. But it's important to note that this therapy is actually quite affordable and an entire course of treatment for sepsis is roughly the cost of approximately one day in the intensive care unit compared to the $50,000 to $60,000 for total cost of treatment for a patient with sepsis for example.
And as Kathy mentioned, when we look at this in a microcosm of Germany that is a total addressable market that we estimate to be about a $1 billion to $1.5 billion. There are more than 2,100 acute care hospitals of which 400 hospitals have more than 400 beds; these are the very large public and university hospitals. But each of these hospitals typically see 300 to 600 sepsis patients a year and that three to five cartridges per patient that represents a revenue per patient of about $3,000 to $5,000 per patient. But what that also means is that it represents a potential revenue per hospital of about $1 million to $3 million for sepsis alone. And for the first time, we are able to publicly disclose that we have a number of large accounts that are moving towards this milestone and have already now achieved one of those customers that have had more than $1 million in sales in 2016. So this gives you a glimpse of how large this business could be just with small number of dedicated hospitals.
Now as Kathy mentioning in addition to what we achieved in 2016 we're looking forward to driving growth in 2017 and beyond. And there have been some major milestones that we've hit that will help drive both direct sales as well as indirect distributor and partner sales as well. Now one of the major accomplishments that has happened recently, has been the award of the dedicated reimbursement code for CytoSorb in Germany. Germany is the third largest medical device market in the world and the largest medical device market in the European Union and as you've seen from our results, our most important market. And we were able to achieve this CytoSorb reimbursement code at the initiation and support of major medical societies across major -- across many different medical specialties in Germany today; and we feel that this helps to validate the importance of our therapy to physicians in the country.
So this is a code that took effect in January 2017 and is expected to result in much higher reimbursement compared to the more generic code that we've used in the past that had covered roughly 60% to 100% of the cartridge but do not necessarily cover the cost of the procedure itself. And we believe with now three years of cost [ph], that hospitals are well positioned to achieve both reimbursement of the device as well as the reimbursement for the procedure which would reduce a major impediment for usage and sales. And we expect that this will help catalyze a steady and growing increase in CytoSorb usage and adoption throughout Germany, and we believe that this will also have a positive impact on other countries in terms of reimbursement and usage going forward.
Now in terms of indirect and distributor sales, we have had also a number of significant developments happened recently and one of those major developments is the expansion of our Fresenius partnership. As we discussed before in December of 2014, we had signed with Fresenius to be our exclusive distributor in six countries including France, Poland, Denmark, Norway, Finland and Sweden. And after about a year and a half worth of internal certification and validation, Fresenius and our company helped launch the product in May of 2016. In January of 2017 with just a little more than a month ago we announced an expansion of this mutual partnership where now we have extended the partnership by three years to cover this exclusive distributorship in these six countries.
But importantly, we went from annual minimum payments to maintain exclusivity to now an increased commitment on Fresenius's part to guaranteeing quarterly orders and payments for CytoSorb that is valuable every year and a half. But maybe more importantly, has been the expansion of our agreement to now a co-marketing agreement across all the countries were CytoSorb is sold where possible, and what that has the general effective doing is increasing the "effective" sales force or the people talking about CytoSorb in these countries by 2X to 3X in each of the countries. Fresenius will provide a written endorsement of CytoSorb as a preferred therapy on their multiFiltrate, multiFiltrate PRO platforms and CytoSorb will be again put on the multi-filtrate PRO as an option that technicians can dial into to be able to use the CytoSorb therapy in a very direct manner on the multiFiltrate PRO.
So this is a process that we -- we just signed this agreement in January, we are in the process of developing marketing materials, training and other things and we expect that the impact of this agreement will begin to accelerate into the second half.
Now another major partnership that we announced last year was Terumo Cardiovascular. Terumo Cardiovascular is a division of the Japanese Conglomerate Terumo, and Terumo Cardiovascular is the leading cardiac surgery disposables company in the world and one of the top four cardiac and vascular surgery companies in the world next to companies like Medtronic, LivaNova, as well as Mackay. We entered into a multi-year partnership agreement with them to distribute CytoSorb for cardiac surgery applications in France, Denmark, Norway, Sweden, Finland and Iceland; keeping the ICU separate for Fresenius. And with a lot of hard work on both sides, CytoSorb was launched in these territories in December 2016. And what this is expected to do is be another catalyst for 2017 and beyond sales and it represents strong validation of our technology and opens the door for potential expansion into other countries such as Japan, which is the second largest medical device market in the world, next only to the United States.
And last but not least, Biocon is our partner in India and Sri Lanka currently, and they are the largest biopharmaceutical company in that country. They have combined their critical care antibiotics with our CytoSorb Blood Purification Technology to create one of the most comprehensive treatments for sepsis and critical illness today and last year they reorganized CytoSorb into its own division with its own resources and sales force, and we have seen tremendous progress on that front from Biocon and expect even stronger growth going forward.
But in addition to these strategic partnerships, our existing distributor and independent distributor partners have also been doing very well and collectively it's one of the reasons why X-Y -- sales that do not include Germany have risen 91%. But what this means is that we are driving rapidly towards operating profitability and when you look at this chart, the red line is our fixed operating expenses that exclude clinical trial costs as well as non-cash option expenses. And you can see that we have spent quite a bit in terms of building the infrastructure of our company over the past several years but that our fixed operating expenses have started to plateau and we expect that this trend will continue with less than a 10% increase in operating expenses going forward in this next year.
But meanwhile the revenue of our company and product sales of our company continues to rise very rapidly, that is what you see in the blue line. And the gross margin line is not far behind, and this is one of the reasons why we see that we -- and why we're so confident about reaching operating profitability within the next one to two years at a revenue of top line revenue number of about $20 million in sales. And once we hit that operating profitability and cash flow breakeven point, we expect that $0.40 to $0.50 on every $1 will drop to the bottom line making this a very cash flow rich company which we believe changes the overall profile of our company.
Now the second major milestone that we expect to achieve is to begin the path to U.S. approval later this year with the initiation of a U.S. Cardiac Surgery REFRESH 2 Trial. As many of you know, last year we completed the first of two studies designed to get CytoSorb approved in the United States and that was called our REFRESH 1 Trial also called the Reduction in Free Hemoglobin Trial. Now this was ultimately a 46 patient nine center validating the safety and efficacy of intraoperative use of CytoSorb in a heart-lung machine during complex cardiac surgery where patients were expected to be on heart-lung bypass for more than three hours. And this included a wide range of complex cardiac surgery procedures ranging from aorta re-construction [ph], congenital defect repair, multiple valve replacements and other types of procedures.
And again, we work with major cardiac surgery centers including Columbia Texas Heart, University of Pennsylvania, University of Pittsburgh and many others. And our primary endpoint for the study was safety and the reduction in free hemoglobin. And in this first RCT using CytoSorb in high-risk cardiac surgery patients, and again, there have been a number of smaller RCT studies and actually one larger RCT study in mild-to-moderate risk cardiac surgery patients but in this first RCT and high-risk cardiac surgery patients, we -- one, demonstrated the safety of the therapy; two, we identified surgical procedures that were in this complex cardiac surgery group where patients were identified as having the highest levels of plasma-free hemoglobin and that is very important because that will allow us to enrich the next trial for those at greatest risk of organ injury due to these high levels of plasma-free hemoglobin thereby potentially allowing our trial to be more focused, smaller, less expensive and potentially executed faster. And last but not least, we demonstrated that CytoSorb removes key inflammatory mediators during the treatment period.
And so an abstract of these data have been sent and submitted to the AATS or American Association of Thoracic Surgery Conference that is taking place at the end of April. But meanwhile, we plan to confirm our clinical trial strategy with the FDA and expect to begin a registration trial later this year designed to seek approval for CytoSorb in the U.S. for the application of cardiac surgery. And depending on our discussions with the FDA and depending on the clinical path that they guide us on; approval could happen anywhere in the 2018 to 2020 timeframe. And when we have more detail on be exact path those details will be forthcoming.
So last but not least, you know, this is why we believe that CytoSorb is a very unique company. We believe that it is a "de-risk hybrid" that combines a greater visibility and lower risk of a med-tech company with a razor blade high margin business model and strong technology validation, and you've seen that technology validation in the $8.2 million in 2016 sales; the plus 70% direct margins, the 20,000 human treatments and growing; and the broad adoption in the marketplace particularly amongst our oldest users who have had the most experience with the technology. But it also includes more than $18 million in grants and contract funding as well as validation from major multinational corporations such as Fresenius Medical Care, the largest dialysis company in the world; Terumo, the largest cardiac surgery disposables company in the world; and Biocon, the largest biopharmaceutical company in India.
And it combines it with the upside profile of a biotechnology company with more than a $20 billion worldwide market opportunity in critical care and cardiac surgery. And we can attack that market not by going through multiple phases of clinical trials that you see in a drug and biologics but with a relatively straightforward clinical path of doing a single pivotal registration trial in the United States.
So in 2017 we are expecting a pivotal year, and we plan on continuing to achieve multiple value creating milestones and expect to meet the investment criteria for a wide range of high quality fundamental institutional investors, as well as retail and high net worth investors as well. As of the fourth quarter, we -- as Kathy mentioned, we have already exceeded a $10 million in sales run rate which is a key revenue threshold for many fundamental institutional investors. We expect to achieve operating profitability again with expanding sales and gross margins within the next one to two years which would completely change the investment profile of our company.
And last but not least, following discussions with the FDA we plan to initiate a pivotal registration trial for CytoSorb in the United States putting a timeline for the first time on a potential U.S. approval. With that we expect 2017 to be a major year of visibility and progress for our company to the benefit of all of our shareholders.
So with that we appreciate everyone joining the call in the middle of the morning here. And certainly, if we didn't have a chance to answer your questions please feel free to reach out to us but let's go into the question-and-answer period now. Amy?
Thank you, Dr. Chan. Operator, we are ready to pull for questions.
Thank you. [Operator Instructions] We will take our first question today from Jason Colbert with Maxim. Please go ahead.
Good morning guys. Congratulations, what a great quarter and a greater progress. Can you just talk a little bit about what you think the real potential of Germany is, looking ahead five years; how big could revenues be there? And the reason why I ask the question is because that acts a little bit as a surrogate to me because I think the launch in Germany is a little bit more advanced than the launch in the other countries. And then Phil, could you go back and address a little bit more additional commentary on the steps you're taking to enrich the U.S. trial because I found that's very interesting, both in terms of the time for the market and kind of enriching the trough for success. Thank you.
Sure, thank you Jason. So you know, as we mentioned the market in Germany is as we said, that's the third largest medical device market in the world. They see -- they have about 154,000 severe sepsis and septic patients every year in Germany alone; but that doesn't even account for the other critical illnesses that are seen or the high numbers of cardiac surgeries that are done every single year. This is one of the reasons why we estimate that that total addressable market is approximately $1 billion to $1.5 billion and we believe that within five years we could potentially access potentially 10% of that market or potentially $100 million in sales. You've seen that there has been -- in Germany the foundation laid for broad growth in the country and as you've seen, we've already -- one of our customers has already hit the $1 million mark and there 400 hospitals that are of that size that could approach that number in the future; they are not all of our customers obviously, but you know, we -- that represents the opportunity for us in Germany. But so if we were -- first of all, we expect to be profitable even before we get approval in the United States and that is something very important to note.
And the second thing is that, if we were no further than Germany and we only had focused on Germany and nowhere else in the world, we could be a very profitable and very successful company. But obviously we view this as a much broader opportunity than just Germany because critical illness is killing millions of people worldwide and that is one of the reasons for our broader commercialization strategy.
Now to answer your second question about enriching the trial; so heterogeneity is the death knell of most clinical studies; and what happens is that if you have a strong effect in one population but it is negated by not seeing an effect in other populations then in total if you look at all commerce and the study, you will see no benefit of your therapy despite having this very strong subgroup benefit. Now we know that free hemoglobin is a very deadly toxin, in fact when they had developed free hemoglobin as a blood substitute many years ago; it was actually discontinued because it actually increased mortality and killed patients. The reason why it does this is because iron and free hemoglobin creates oxygen radicals that causes lipid peroxidation, membrane damage and blood vessel injury, and that's bad. But it also is a very potent scavenger of nitric oxide which is your major vasodilator in your body.
Now without this vasodilator helping your blood vessels expand, what happens is that during surgery and immediately after surgery these blood vessels will contract [ph] and create very high resistance for that delicately, surgically -- the post-operative heart, the weakened heart, the very vulnerable heart to need to now pump against. So imagine you've just sod in very delicately to a couple of hard valves and now the heart has to beat against a very high resistance; that high resistance is also decreasing organ perfusion of blood, potentially increasing the risk of intestinal ischemia, kidney failure, brain injury and others. And so this is one of the reasons why free hemoglobin is so dangerous but there are other inflammatory mediators like cytokines activated compliment and others that are contributing to this injury.
Now what is very interesting about our REFRESH 1 Study is that when we have looked at the types of procedures that have been done, what we have seen is that no -- that not all complex cardiac surgery procedures are created equal in terms of generating free hemoglobin which often occurs because of either wrong procedure times on the pump and sheer forces that create hemolysis and a breakdown of blood products releasing blood cells released to free hemoglobin into the plasma. Because there is a lot of bleeding at the heart and you're sucking blood from the field under negative pressure and that causes hemolysis, so the longer you're on doing an operation, the more hemolysis you get and the higher your free hemoglobin levels get.
So this was never characterized before in such a granular level but with our data we now have identified those patient populations that are truly at high risk; these represent more than half of the patients; of all the patients that we've seen more than half of the patients in our clinical study that qualified as in this high-risk subgroup and in that high-risk subgroup we've demonstrated the ability to reduce key inflammatory mediators in a statistically significant way. So there are many studies that show the higher the free hemoglobin, the higher the risk of acute kidney injury, the higher the risk of adverse organ injury. And now having identified this subpopulation that is at highest risk, we believe that we can again enrich the future REFRESH 3 Study with these patients.
Perfect, Phil. Thank you so much.
Thanks very much, Jason.
And we'll go next [indiscernible]. Please go ahead. Please check your line, if your line is muted.
Sorry about that Phil, I apologize. I was on mute. I had few questions. In terms of your relationship with Terumo and Fresenius, obviously it's taken off very well with most [ph]. How do you see this focusing into 2017, especially when there are something in the range of $10 million for the year. The promise of that and you see is going to be an important contributing factor.
I had a little difficulty, there was a connection issue; I had a difficulty hearing the last part of that. But I think I get a general gist of the question; how impactful will these partnerships be in 2017.
I guess, yes. So I think that what we have seen in all of our counts is that it takes time to get out in the market, introduce CytoSorb to keeping the leaders and key accounts, it takes time for them to try the therapy and to get used to the therapy before they move on to higher volume usages and using it in more than just handful of procedures. So as you've seen from our ramp in Germany for example, as Kathy mentioned, that is kind of a prototypic example of how we see sales growing and not just a partner -- strategic partner accounts but other accounts as well. But that said I think there has been -- unlike Germany, when we first started in Germany, we had very little market recognition, very little clinical data and very little -- we had some major key opinion leader support but the numbers were relatively small. Fast forward several years, all that has really changed; where now there is a lot more clinical data in cardiac surgery, for example, for Terumo there been now four randomized control trials in cardiac surgery patients, more than 4,000 open heart surgeries done in critical care; there have been many case reports, case series and even small single-arm prospectively defined studies where the device has been used successfully and that amounts more than 16,000 human uses in critical care.
So I think that we have the ability to accelerate both Fresenius and Terumo and part of the on-boarding process and the training process is to transmit a lot of our experience to them so that they can get up and running as quickly as possible. The nice thing about our therapy is that it is not rocket science, it is just not require a tremendous amount of training and hand-holding, you know, for these respective partners that are leaders in their field in either dialysis and extra corporal blood purification or a heart-lung machine treatment in the OR, this is a very simple. So the first year is always going to be a little slow but I think that this will ramp up very significantly going forward; Fresenius will be finishing their first full year as of this May and Terumo I think has gotten a great start out of the back here, out of the box here and have been very aggressive in getting this to key opinion leaders in key accounts in their respective territories.
So although we can't quantitate what that looks like today, Fresenius of course is committed to quarterly payments that we have not publicly disclosed but Terumo is also expected to be a major contributor as is Biocon. So -- but certainly on a go-forward basis those numbers begin to become very real and very meaningful and again, one of the reasons why we believe we can drive to a $20 million revenue number in one to two years.
Great, Phil. I know I'm one of the guys who have been asking the management [Technical Difficulty]. Staying in that range and now that you have a permanent court from Germany; I'm not sure if this question is already answered. How can you see the impact from the permanent course helping in terms of increased sales from the number that you have seen in 2016? How much of the [Technical Difficulty].
No, we believe that it will have a steadying and growing impact on our direct sales in a positive way going forward. I think what some of the feedback that we've gotten from the field and I can -- I'll let Christian talk a little bit more about his perspective. But I think a lot of the feedback that we've gotten from the field is that there was not a lack of interest to use our therapy more from the clinicians standpoint but because of the suboptimal reimbursement for the hospital administrators, they were forcing I think clinicians to be much more selective about the cases that the USADA Sorbonne [ph]. And I think in follow-up discussions with both hospital administrators and clinicians, they both view -- this view to direct reimbursement code as one significant validation of the technology, again that was supported by major medical societies in the country. And two, a significant potential -- a significant development that would allow the opening up of more uses of CytoSorb. Christian, would you want to comment on -- do you have any more color maybe to add on that?
Yes, sure Phil, thank you. First of all, one has to say that is really a great accomplishment in this relatively short time to achieve such a prominent dedicated reimbursement; so even Baxter, Gambro [ph], and Fresenius and others have not reached this for their product. So actually this new count -- getting -- got defective from January 1. Firstly, trends down thresholds of barriers for the hospitals to buy this product because of course control is a big issue and the controlling department and procurement, they look very much what is getting it and what is getting out. So I think we can assume that they have left resistance from those departments. And secondly, one has to understand the nature of the court to what implications has this for the sales; so the quote is additional reimbursement for the hospital and this can be negotiated every year. And so the hospital can upto negotiate the value of the reimbursement every year. And so this hospital negotiates the budget for the hospital over the year and this negotiation every -- of those procedures get separately negotiated.
So from this perspective I think it is -- one can assume that the very old hospital barrier to the hospital can get for procedures getting up and also -- that is also new each single procedure can be reimbursed so that this -- I think is big advantage and gradually believes to accelerated use of CytoSorb.
Thank you, that's very helpful. And then a question on [Technical Difficulty] and I think I believe in the middle of the year. So where are you in terms of getting products out in this geography and what is your expectation at least for 2017 from these regions?
RK, if you could got just repeat that; you're breaking up there. I think you had mentioned; your question was, what's the prospects for getting CytoSorb in these territories but I couldn't hear which territories you were referring to?
It's Middle East and Russia.
I'm sorry you broke up again, say that one more time please?
Middle East and Russia.
Oh, in Middle East and Russia. I think let me talk to Middle East and let me -- let Christian talk about Russia which I think is very interesting. So you know, the Middle East I think is suffering from the drop in the price of oil and that has had significant reverberating impacts throughout the economies including healthcare. And I think that -- you know, the price of oil had stabilized a little bit but you know, the Middle East is still unclear. We have a number of tenders -- tender orders out there for our product. The Saudi FDA came to audit our facility in person here in New Jersey, and we passed that audit.
And so there is good reason to believe that once the -- and we also have a significant amount of key opinion leader support in Saudi Arabia and countries like Kuwait and Qatar, and others. So I think that there is a good -- there is a very good expectation that when these cost pressures abate and people are hoping that this will abate soon that Middle East will become a significant contributor to our revenue overtime.
So in terms of Russia, Christian maybe you can give a little bit of your thoughts there.
Thank you. First of all, one has to say that Russia I think is a very interesting market for [indiscernible] therapies. So the medical community is in general very open-minded for such therapies, similar to what we see in Italy. So we have got the situation finished in Q2; last year 2016 after more than 2.5 years of registration process. And nevertheless, this was a little bit late for the budget process. In Russia we have budget process for the hospitals which is in spring and summer for the next year, so we missed the 2017 budget negotiations for the hospitals and -- but we are in the middle of the 2018 budget negotiations and the prospective tender. Nevertheless we have seen in the first few quarter of business in Russia that there is a huge interest off the community and beside this relatively rigid mechanisms of tender and budgeting.
We have had already significant sales over there because some hospital, especially [indiscernible] hospitals are very interested in this technology; and so we believe that this market, Russia, is going to be a very big contributor in the future, mainly and substantially contributing from 2018. But nevertheless, 2017 they will also have a relatively steep increase in CS outside results. That's answering your question.
Thank you, Christian.
Thank you. We will go to our next question; we'll go to Andrew D'Silva with B. Riley. Please go ahead.
Good morning guys, thanks for taking my questions. Just to start off; just a couple of quick book-keeping questions; first, related to stocking orders, if there were any larger ones during the fourth quarter, could you let me know otherwise -- it was steady state scenario that'd be pretty good indicator as it going to you -- the first and the second quarter this year. And then the second question, maybe you can answer as well is -- correct me if I'm wrong, but the Fresenius expanded partnership will be implemented in the third or fourth quarter this year, correct? It has not actually begun to impact the P&L yet.
So let me -- Kathy, if you want to talk about the stocking orders; and Chris, if you wanted to talk about expected timing of that program? Kathy?
So Andrew, as we've said before there were no significant stocking orders in the fourth quarter. So it's pretty much steady. So Chris?
Hi Andrew, thanks Kathy. For the co-marketing program, you're correct, you know right now we're actively working with FMC to develop the program itself. I think Bill had mentioned developing joint marketing materials, training and planning for the roll out and you know, the current thinking is that we start with big countries first; we perfect and tweak the model and then roll it out more broadly. So we're tracking towards the second half of 2017 rollout but obviously there is benefit to both parties. I think with co-marketing we benefit from having expanded sales coverage. FMC also benefits by having incremental fall-through on their products. So there is just a natural incentive to get this out in the market as quickly as we can. But right now I think as I look at the program, I'm thinking that we really start to ramp up in second half of this year.
Okay, great. And as far as your distributors go, they've been pretty open to the expanded partnership, obviously in regions where Fresenius doesn't have an exclusive arrangement with you?
Yes, I think that we've made it very clear in the contract that we sell or our distributors or other partners in our territory sell CytoSorb and Fresenius only sells the ancillary disposables associated with that including the hemofilters, the bloodlines, the fluids and other things. But also potentially, even more machines which they are really very interested in doing and view CytoSorb as a way to drive volume of procedures in the intensive care unit. I'm -- so I think that we've made a very delineated or very strong division between those two aspects and for the most part we've have not gotten any negative feedback on this co-marking arrangement. I think everyone sees us as a way to increase the feet-on-the-street, talking about the product and view Fresenius's commitment to introducing their clients and their key opinion leaders in there. Their key accounts to the distributors is very positive thing.
Great, thank you. Great color, Phil. And just moving over to the dedicated reimbursement code in Germany; you obviously touched on this in the prepared remarks in the previous question but maybe provide a little inferential data that you're seeing after the rollout happened or the dedicated reimbursement-co was established. Has it started to resonate with doctors more? Is there a point where it almost becomes negligent that they don't use another, there is a reimbursement code established; are there any data points like that you can point to in your core market?
Yes. Christian, do you want to maybe give some color on sort of physician feedback or hospital administrator feedback about this new code?
Yes, thank you Phil. As I said Phil, the whole process of starting with a new code takes a limit of time. So obviously the users are coding the procedure from January 1 but the up-negotiating, this happens during the negotiations for the hospital budget. Nevertheless, we have a very positive response from the field [ph]. We see for example, that that the doctors who were hesitant in the past are now open to speak again and I think we can approach much more or many more kind of reluctant department now again, and risk to write data. I think this will accelerate the whole issue. U.S. and in your question you have mentioned one thing and this is really true; IFX [ph] appearance two weeks ago at the conference but also first time that actually customers and potential customers mentioned that it might be unethical in the future to not CytoSorb. I mean this is anecdotal, it has happened three-four times but it is the first time and I think it's a great step upwards in quality; how people think about this therapy.
No, that's very positive, definitely, thank you. And then, if we could just briefly move over to your REFRESH 1 trial and the release of the efficacy data; I've been getting this question a lot -- I've had my own response but it would be great to hear it in your own words. Maybe what the rational or what is your rationale for waiting to release the efficacy data at the ATS Conference in April? And then also -- now that you've had time to review the data and compile different sets of it; I'm sure you've looked at items above just reduction in inflammatory mediators. Are there other stats you mean able to compile or should we expect more than just REFRESH 1 efficacy data to be released; maybe pinks [ph] related to clinical benefits such as reduced hospital time or anything like that?
Yes. So if you know, I think again, the genesis of the delay in release in the free hemoglobin data and other inflammatory mediator data really stem from the -- from guidance from our surgical advisory -- Cardiac Surgery Advisory Board and our own internal advisors. And you know, the feeling was essentially this, this was the -- people have known for a long time that free hemoglobin is a toxin that should not be there during or post-cardiac surgery. They have known for a long time about the toxicity of this particular molecule but no one has been able to really eliminate or reduce that molecule before in cardiac surgery. And again, this was going to be the first randomized control trial of CytoSorb at a high-risk cardiac surgery patient population; again, another major milestone.
So this was a U.S. trial done at U.S. sites and the feedback from our U.S. investigators and U.S. cardiac surgery advisors was this is -- we should not be releasing this at a European Cardiothoracic Surgery Conference but really at a American at a U.S. Cardiothoracic Surgery Conference and we should be doing this not in a press release, but in a scientific forum where it would be most impactful and wouldn't be perceived as hype.
And so, I think that we take our advisors guidance very seriously and that is what we elected to do. Now that being said, we have given the market now hence that what we've seen and what we found we fully expect going into the FDA that we still feel very confident about the data that we have and that we feel that it will support moving to a REFRESH 2 Pivotal trial hopefully to start later this year, which is our plan. So we'll see. And as I said before, we'll give the market more feedback on that when we have more visibility. But that being said the second part of your question was, will we have more data to present.
As you can imagine, there's a tremendous amount of data coming out of these studies and many different ways to look at data and so we're absolutely very -- we want to make sure that we do this right and we want to make sure that we get as much information as possible to inform the design of the REFRESH 2 Pivotal trial, which in essence will look very similar to REFRESH 1 but based upon other findings of the data and analysis of the data we have the goal of trying to refine REFRESH 2 to make it easier to conduct to give it a higher chance of success and to select the clinical end-point set that and from economic end-points that would make the study most impactful.
So I guess that is a long way of saying that we are, we are actively looking at our data and have -- and continue to analyze the data and are working to put our best foot forward in front of the FDA when we do meet with them. So, I hope that answers your question.
No, that's great. So thank you, best of luck in '17 as well.
Thank you so much Andy, I really appreciate it.
And we'll go next to Brian Marckx with Zacks Investment Research. Please go ahead.
Good morning. So congratulations on the progress and the results. Relative to REFRESH 1 and sub-population that you've identified I think you mentioned that those patients made up about 50% or more of total enrollment in REFRESH 1. Is that 50% plus proportion also reflective of the broader population of patients that would be candidates for that type of surgery?
Yeah I think that the sub-populations that we've identified are very common in the overall high risk cardiac surgery population overall, not just in our trial program.
Okay. And I think you mentioned that you expected REFRESH 2 to be potentially smaller in cost and in patient enrolment. Number one, did I get that right? And number two, if I did. What are your thoughts today in terms of size of enrollment?
Well, what I said was that the value of enrichment is to reduce the heterogeneity of the trial and to potentially be able to speed up the trial by having fewer patients enrolled because you have a stronger signal, a more focused signal and a more modest patient population. So I think for right now, ahead of an FDA meeting, I guess we'll just say that there is that possibility, but we -- I don't think would commit to anything at the current time.
Okay, fair enough. On to the general guidance that you gave for 17 and beyond, you mentioned operating expense is potentially only up about 10% from 16 numbers. That includes the clinical trial expenses for REFRESH 2 I assume everything is in there. And then, I guess the bigger question I guess had to do with cash versus non-cash that does not just assume cash operating expenses is that correct?
So I'll have Kathy, give a little bit more color on this. But what we're talking about a 10% increase, we're talking about operating expenses which excludes non-cash stock option expenses as well as clinical trial costs. So this is really the fundamental expense line that keeps our business up and running and excludes clinical trial costs.
Kathy, I don't know if you'd like to comment a little more beyond that.
No, no. I think you've got it just right there. We took the clinical trials off because we were looking at operating profitability and that just really swings things out of proportion.
Yeah, understood. Okay.
Yes, appreciate the clarity. Still Japan sounds like it could be a big market, if you could just kind of talk about what you're plans are there? And then, I guess a broader sense what is the regulatory path and what's it like in Japan?
Yes, so to get into the Japanese market it really requires that you have a sponsor, a Japanese company sponsor to get in there. I mean that just makes things a lot easier. And so Terumo as one of the big multinational corporations, but based out of Japan fits that build. There is certainly an interest on both sides to move to Japan. Any kind of regulatory approval in Japan would require that a trial be done in Japan, but you can imagine that if a deal that were struck to do that, then it would not be us that would bear the cost of that trial but one of our for our partner.
But that being said, having a lot of interest from the various partners in cardiac surgery, all of whom know, all of the major ones know of our technology. That provides a potential additional option for us to fund a clinical study here in United States including REFRESH 2. And so, those are all within the realm of possibility and we'll see what happens.
Okay. I'm kind of jumping all over the place here. This is the last one I got. Relative to 21st Century Cures Act, does that potentially applied any way with your current cardiac surgery pathway or any other potential application in terms of an FDA pathway?
So, I think it represents a potential fast track for therapies that can address major unmet medical needs and certainly in the area of critical care as well as in cardiac surgery particularly high risk surgery there is that potential path. So we were actively investigating this as just recently announced, and we're actively assessing our options in that area.
Alright, great. Thanks Phil, appreciate it.
Absolutely Mark, thank you. Good bye. Thank you.
And we will go next to Jason Wittes with Aegis Capital. Please go ahead.
Hi, thank you for taking the question. First off, I noticed SG&A popped up this quarter. I don't know if you could discuss that and also in terms of the SG&A spend for next year, how should we be thinking about it?
Kathy, would you like to take that?
Yes, let me take that. So one of the largest items that was impacting the G&A was a $2.6 million non-cash stock compensation expense. So that was a big driver of that top off.
Okay. So that's not going to repeat. So basically it should go back to kind of what we saw in the other quarters in '17?
Yes, that is correct and it was really the recognition of milestone option awards based on 2016 performance which we typically do once a year.
Okay. And obviously German reimbursements, a catalyst here. Can you give us a sense or an update in terms of reimbursement decisions or progress and some of the other regions in Europe and other countries that are under coverage?
Yeah, I think that we -- so actually this is paid for through either direct reimbursement, through either a DRG, like a lump sum payment, reimbursement with dedicated line item reimbursement as we have in Germany or through tender orders or through self-pay or through other mechanisms or private insurance et cetera. So it varies country to country. And certainly, we've recently brought on a reimbursement expert to basically work on reimbursement in our key territories and either initiate reimbursement or enhance reimbursement in those areas. And so, I think this is an active goal of ours to do and although we can't go into a lot of detail on our progress. We think that we're making good progress.
Okay. I don't want to push it harder since it sounds like there is not a lot of detail you can provide right now, or willing to for competitive reasons. But I guess, also as you mentioned there's no stalking this quarter in the revenue number. How do we -- for quarter to quarter especially in 17 when I think you are going to see a lot more of your partners participating in a revenue line. Should we assume that there is going to be some lumpiness due to stalking throughout the year or how should we be thinking about that?
Kathy, you want to take that.
Yes, let me start on that. So there are some stalking orders generally with new territories coming on. But they are to minimal in terms of everything. So I think what we are now beginning to see and how you should think about modeling it as we are typically receiving at least quarterly orders, sometimes twice in a quarter and sometimes monthly from our distributor. So we are not going to be expecting that irregularity. The only thing that might cause that I can think of would be, if we were to receive some kind of huge tender order from say Saudi Arabia or something like that.
I think of the revenue as more routine and recurring for the year.
Great, thank you. I will jump back in queue.
Great, thank you. Thanks, Jason.
And there are no further questions at this time. I'd like to turn the conference back over to management for any additional or closing remarks.
Well great. Well thank you everyone very much for taking the time this morning to get on this call. And again, if you do have questions that were not answered on today's call, feel free to reach out to Amy Vogel at firstname.lastname@example.org and we'll try to get a response back to you where possible.
Thank you very much everyone and have a wonderful weekend. Take care.
Thank you. That concludes our conference for today. I'd like to thank everyone for their participation. Have a great day.
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